Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro.

PubMed

Nishimoto, Tomoyuki; Amano, Yuichiro; Tozawa, Ryuichi; Ishikawa, Eiichiro; Imura, Yoshimi; Yukimasa, Hidefumi; Sugiyama, Yasuo

2003-07-01

1. Squalene synthase is the enzyme that converts farnesyl pyrophosphate to squalene in the cholesterol biosynthesis pathway. We examined the lipid-lowering properties of 1-[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-acetic acid (TAK-475), a novel squalene synthase inhibitor. 2. TAK-475 inhibited hepatic cholesterol biosynthesis in rats (ED(50), 2.9 mg kg(-1)) and showed lipid-lowering effects in beagle dogs, marmosets, cynomolgus monkeys and Wistar fatty rats. 3. In marmosets, TAK-475 (30, 100 mg kg(-1), p.o., for 4 days) lowered both plasma non-high-density lipoprotein (HDL) cholesterol and triglyceride, but did not affect plasma HDL cholesterol. On the other hand, atorvastatin (10, 30 mg kg(-1), p.o., for 4 days) lowered the levels of all these lipids. A correlation between decrease in triglyceride and increase in HDL cholesterol was observed, and TAK-475 increased HDL cholesterol with a smaller decrease in triglyceride than did atorvastatin. 4. TAK-475 (60 mg kg(-1), p.o., for 15 days) suppressed the rate of triglyceride secretion from the liver in hypertriglyceridemic Wistar fatty rats, which show an enhanced triglyceride secretion rate from the liver compared with their lean littermates. 5. In HepG2 cells, TAK-475 and its pharmacologically active metabolite, T-91485, increased the binding of (125)I-low-density lipoprotein (LDL) to LDL receptors. 6. These results suggest that TAK-475 has clear hypolipidemic effects in animals via inhibition of hepatic triglyceride secretion and upregulation of LDL receptors, and that TAK-475 might increase HDL cholesterol by decreasing triglyceride. Thus, TAK-475 is expected to be useful for the treatment of dyslipidemia.

Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro

PubMed Central

Nishimoto, Tomoyuki; Amano, Yuichiro; Tozawa, Ryuichi; Ishikawa, Eiichiro; Imura, Yoshimi; Yukimasa, Hidefumi; Sugiyama, Yasuo

2003-01-01

Squalene synthase is the enzyme that converts farnesyl pyrophosphate to squalene in the cholesterol biosynthesis pathway. We examined the lipid-lowering properties of 1-[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-acetic acid (TAK-475), a novel squalene synthase inhibitor. TAK-475 inhibited hepatic cholesterol biosynthesis in rats (ED50, 2.9 mg kg−1) and showed lipid-lowering effects in beagle dogs, marmosets, cynomolgus monkeys and Wistar fatty rats. In marmosets, TAK-475 (30, 100 mg kg−1, p.o., for 4 days) lowered both plasma non-high-density lipoprotein (HDL) cholesterol and triglyceride, but did not affect plasma HDL cholesterol. On the other hand, atorvastatin (10, 30 mg kg−1, p.o., for 4 days) lowered the levels of all these lipids. A correlation between decrease in triglyceride and increase in HDL cholesterol was observed, and TAK-475 increased HDL cholesterol with a smaller decrease in triglyceride than did atorvastatin. TAK-475 (60 mg kg−1, p.o., for 15 days) suppressed the rate of triglyceride secretion from the liver in hypertriglyceridemic Wistar fatty rats, which show an enhanced triglyceride secretion rate from the liver compared with their lean littermates. In HepG2 cells, TAK-475 and its pharmacologically active metabolite, T-91485, increased the binding of 125I-low-density lipoprotein (LDL) to LDL receptors. 6 These results suggest that TAK-475 has clear hypolipidemic effects in animals via inhibition of hepatic triglyceride secretion and upregulation of LDL receptors, and that TAK-475 might increase HDL cholesterol by decreasing triglyceride. Thus, TAK-475 is expected to be useful for the treatment of dyslipidemia. PMID:12839864

Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males

PubMed Central

Shi, Hongliang; Faessel, Hélène M.; Saad, Fred

2015-01-01

Context: TAK-385 is a highly selective, oral, nonpeptide GnRH antagonist being investigated as a possible prostate cancer treatment. Objective: The objectives were to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-385 on LH and testosterone. Design, Setting, and Participants: This was a three-part, randomized, double-blind, placebo-controlled, phase 1 dose-escalation study in 176 healthy male UK volunteers. Interventions: Part 1, single doses of TAK-385 (0 [placebo], 80, 120, 180, or 360 mg). Part 2, 14-day TAK-385 (0, 20, 40, 80, or 180 mg) daily. Part 3, 28-day TAK-385 (40 [with loading dose], 60, 80, or 160 mg) or placebo daily. Parts 2 and 3 included men aged 40–75 years. Main Outcome Measures: Main outcome measures included plasma concentrations of TAK-385, LH, and testosterone. Results: Oral TAK-385 was readily absorbed, and steady state was reached in ≤14 days. Food reduced TAK-385 systemic exposure by 47–52%. Mean serum testosterone levels declined ≤6 hours after TAK-385 administration. Loading doses up to 360 mg on day 1 or 360 mg on day 1 followed by 240 mg on day 2 reduced the time to achieve castrate testosterone levels from ≥7 to <3 days. TAK-385 doses ≥80 mg/d achieved sustained medical castration and trough TAK-385 concentrations >4 ng/mL. After discontinuation of TAK-385 on day 28, testosterone levels normalized in most subjects in ≤ 28 days. Common adverse events included bradycardia, headache, and hot flush (all grade ≤2). Conclusions: Oral TAK-385 (40–180 mg/d) was well tolerated and effectively lowered testosterone in healthy men. Planned phase 2 doses in men with hormone-sensitive prostate cancer are 80 and 120 mg/d. PMID:26502357

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

PubMed Central

Ridder, Dirk A.; Wenzel, Jan; Müller, Kristin; Töllner, Kathrin; Tong, Xin-Kang; Assmann, Julian C.; Stroobants, Stijn; Weber, Tobias; Niturad, Cristina; Fischer, Lisanne; Lembrich, Beate; Wolburg, Hartwig; Grand’Maison, Marilyn; Papadopoulos, Panayiota; Korpos, Eva; Truchetet, Francois; Rades, Dirk; Sorokin, Lydia M.; Schmidt-Supprian, Marc; Bedell, Barry J.; Pasparakis, Manolis; Balschun, Detlef; D’Hooge, Rudi; Löscher, Wolfgang; Hamel, Edith

2015-01-01

Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood–brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-κB and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-κB–independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1–NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP. PMID:26347470

Ablation of Tak1 in osteoclast progenitor leads to defects in skeletal growth and bone remodeling in mice.

PubMed

Qi, Bing; Cong, Qian; Li, Ping; Ma, Gang; Guo, Xizhi; Yeh, James; Xie, Min; Schneider, Michael D; Liu, Huijuan; Li, Baojie

2014-11-24

Tak1 is a MAPKKK that can be activated by growth factors and cytokines such as RANKL and BMPs and its downstream pathways include NF-κB and JNK/p38 MAPKs. Tak1 is essential for mouse embryonic development and plays critical roles in tissue homeostasis. Previous studies have shown that Tak1 is a positive regulator of osteoclast maturation, yet its roles in bone growth and remodeling have not been assessed, as mature osteoclast-specific Tak1 deletion with Cstk-Cre resulted in runtedness and postnatal lethality. Here we generated osteoclast progenitor (monocyte)-specific Tak1 knockout mice and found that these mice show normal body weight, limb size and fertility, and osteopetrosis with severity similar to that of RANK or RANKL deficient mice. Mechanistically, Tak1 deficiency altered the signaling of NF-κB, p38MAPK, and Smad1/5/8 and the expression of PU.1, MITF, c-Fos, and NFATc1, suggesting that Tak1 regulates osteoclast differentiation at multiple stages via multiple signaling pathways. Moreover, the Tak1 mutant mice showed defects in skull, articular cartilage, and mesenchymal stromal cells. Ex vivo Tak1-/- monocytes also showed enhanced ability in promoting osteogenic differentiation of mesenchymal stromal cells. These findings indicate that Tak1 functions in osteoclastogenesis in a cell-autonomous manner and in osteoblastogenesis and chondrogenesis in non-cell-autonomous manners.

TAK1 (MAP3K7) inhibition promotes apoptosis in KRAS-dependent colon cancers

PubMed Central

Singh, Anurag; Sweeney, Michael F.; Yu, Min; Burger, Alexa; Greninger, Patricia; Benes, Cyril; Haber, Daniel A.; Settleman, Jeff

2012-01-01

Summary Colon cancers frequently harbor KRAS mutations, yet only a subset of KRAS-mutant colon cancer cell lines are dependent upon KRAS signaling for survival. In a screen for kinases that promote survival of KRAS-dependent colon cancer cells, we found that the TAK1 kinase (MAP3K7) is required for tumor cell viability. The induction of apoptosis by RNAi-mediated depletion or pharmacologic inhibition of TAK1 is linked to its suppression of hyperactivated Wnt signaling, evident in both endogenous and genetically reconstituted cells. In APC-mutant/KRAS-dependent cells, KRAS stimulates BMP-7 secretion and BMP signaling, leading to TAK1 activation and enhancement of Wnt-dependent transcription. An in vitro-derived “TAK1-dependency signature” is enriched in primary human colon cancers with mutations in both APC and KRAS, suggesting potential clinical utility in stratifying patient populations. Together, these findings identify TAK1 inhibition as a potential therapeutic strategy for a treatment-refractory subset of colon cancers exhibiting aberrant KRAS and Wnt pathway activation. PMID:22341439

Ablation of Tak1 in osteoclast progenitor leads to defects in skeletal growth and bone remodeling in mice

PubMed Central

Qi, Bing; Cong, Qian; Li, Ping; Ma, Gang; Guo, Xizhi; Yeh, James; Xie, Min; Schneider, Michael D.; Liu, Huijuan; Li, Baojie

2014-01-01

Tak1 is a MAPKKK that can be activated by growth factors and cytokines such as RANKL and BMPs and its downstream pathways include NF-κB and JNK/p38 MAPKs. Tak1 is essential for mouse embryonic development and plays critical roles in tissue homeostasis. Previous studies have shown that Tak1 is a positive regulator of osteoclast maturation, yet its roles in bone growth and remodeling have not been assessed, as mature osteoclast-specific Tak1 deletion with Cstk-Cre resulted in runtedness and postnatal lethality. Here we generated osteoclast progenitor (monocyte)-specific Tak1 knockout mice and found that these mice show normal body weight, limb size and fertility, and osteopetrosis with severity similar to that of RANK or RANKL deficient mice. Mechanistically, Tak1 deficiency altered the signaling of NF-κB, p38MAPK, and Smad1/5/8 and the expression of PU.1, MITF, c-Fos, and NFATc1, suggesting that Tak1 regulates osteoclast differentiation at multiple stages via multiple signaling pathways. Moreover, the Tak1 mutant mice showed defects in skull, articular cartilage, and mesenchymal stromal cells. Ex vivo Tak1−/− monocytes also showed enhanced ability in promoting osteogenic differentiation of mesenchymal stromal cells. These findings indicate that Tak1 functions in osteoclastogenesis in a cell-autonomous manner and in osteoblastogenesis and chondrogenesis in non-cell-autonomous manners. PMID:25418008

MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling.

PubMed

McNew, Kelsey L; Whipple, William J; Mehta, Anita K; Grant, Trevor J; Ray, Leah; Kenny, Connor; Singh, Anurag

2016-12-01

MEK inhibitors have limited efficacy in treating RAS-RAF-MEK pathway-dependent cancers due to feedback pathway compensation and dose-limiting toxicities. Combining MEK inhibitors with other targeted agents may enhance efficacy. Here, codependencies of MEK, TAK1, and KRAS in colon cancer were investigated. Combined inhibition of MEK and TAK1 potentiates apoptosis in KRAS-dependent cells. Pharmacologic studies and cell-cycle analyses on a large panel of colon cancer cell lines demonstrate that MEK/TAK1 inhibition induces cell death, as assessed by sub-G 1 accumulation, in a distinct subset of cell lines. Furthermore, TAK1 inhibition causes G 2 -M cell-cycle blockade and polyploidy in many of the cell lines. MEK plus TAK1 inhibition causes reduced G 2 -M/polyploid cell numbers and additive cytotoxic effects in KRAS/TAK1-dependent cell lines as well as a subset of BRAF-mutant cells. Mechanistically, sensitivity to MEK/TAK1 inhibition can be conferred by KRAS and BMP receptor activation, which promote expression of NF-κB-dependent proinflammatory cytokines, driving tumor cell survival and proliferation. MEK/TAK1 inhibition causes reduced mTOR, Wnt, and NF-κB signaling in TAK1/MEK-dependent cell lines concomitant with apoptosis. A Wnt/NF-κB transcriptional signature was derived that stratifies primary tumors into three major subtypes: Wnt-high/NF-κB-low, Wnt-low/NF-κB-high and Wnt-high/NF-κB-high, designated W, N, and WN, respectively. These subtypes have distinct characteristics, including enrichment for BRAF mutations with serrated carcinoma histology in the N subtype. Both N and WN subtypes bear molecular hallmarks of MEK and TAK1 dependency seen in cell lines. Therefore, N and WN subtype signatures could be utilized to identify tumors that are most sensitive to anti-MEK/TAK1 therapeutics. This study describes a potential therapeutic strategy for a subset of colon cancers that are dependent on oncogenic KRAS signaling pathways, which are currently difficult to

Deletion of TAK1 in the Myeloid Lineage Results in the Spontaneous Development of Myelomonocytic Leukemia in Mice

PubMed Central

Lamothe, Betty; Lai, YunJu; Hur, Lana; Orozco, Natalia Martin; Wang, Jing; Campos, Alejandro D.; Xie, Min; Schneider, Michael D.; Lockworth, Cynthia R.; Jakacky, Jared; Tran, Diep; Ho, Michael; Dawud, Sity; Dong, Chen; Lin, Hui-Kuan; Hu, Peter; Estrov, Zeev; Bueso-Ramos, Carlos E.; Darnay, Bryant G.

2012-01-01

Previous studies of the conditional ablation of TGF-β activated kinase 1 (TAK1) in mice indicate that TAK1 has an obligatory role in the survival and/or development of hematopoietic stem cells, B cells, T cells, hepatocytes, intestinal epithelial cells, keratinocytes, and various tissues, primarily because of these cells’ increased apoptotic sensitivity, and have implicated TAK1 as a critical regulator of the NF-κB and stress kinase pathways and thus a key intermediary in cellular survival. Contrary to this understanding of TAK1’s role, we report a mouse model in which TAK1 deletion in the myeloid compartment that evoked a clonal myelomonocytic cell expansion, splenomegaly, multi-organ infiltration, genomic instability, and aggressive, fatal myelomonocytic leukemia. Unlike in previous reports, simultaneous deletion of TNF receptor 1 (TNFR1) failed to rescue this severe phenotype. We found that the features of the disease in our mouse model resemble those of human chronic myelomonocytic leukemia (CMML) in its transformation to acute myeloid leukemia (AML). Consequently, we found TAK1 deletion in 13 of 30 AML patients (43%), thus providing direct genetic evidence of TAK1’s role in leukemogenesis. PMID:23251462

Thermal effects on shearing resistance of fractures in Tak granite

NASA Astrophysics Data System (ADS)

Khamrat, S.; Thongprapha, T.; Fuenkajorn, K.

2018-06-01

Triaxial shear tests have been performed on tension-induced fractures and smooth saw-cut surfaces in Tak granite under temperatures up to 773 K. The objective is to gain an understanding of the movement of shallow faults that cause seismic activities in the Tak batholith in the north of Thailand. The results indicate that the peak and residual shear strengths and fracture dilations notably decrease as the temperatures increase. The thermal effect is enhanced under higher confining pressures. The areas of the sheared-off asperities increase with temperature and confining pressure. A power equation can describe the increase of shear strengths with normal stress where the normal stress exponent is a linear function of the temperature. The strain energy principle is applied to incorporate the principal stresses and strains into a strength criterion. A linear relation between the distortional strain energy (Wd) and the mean strain energy (Wm) of the fractures is obtained. The Wd-Wm slope depends on the fracture roughness and strength of the asperities, which can be defined as a function of shear and mean strains and dilation of the fractures. This may allow predicting the peak strength of the shallow faults in the Tak batholith.

Mice with Tak1 deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development.

PubMed

Song, Zhongchen; Liu, Chao; Iwata, Junichi; Gu, Shuping; Suzuki, Akiko; Sun, Cheng; He, Wei; Shu, Rong; Li, Lu; Chai, Yang; Chen, YiPing

2013-04-12

Cleft palate represents one of the most common congenital birth defects in humans. TGFβ signaling, which is mediated by Smad-dependent and Smad-independent pathways, plays a crucial role in regulating craniofacial development and patterning, particularly in palate development. However, it remains largely unknown whether the Smad-independent pathway contributes to TGFβ signaling function during palatogenesis. In this study, we investigated the function of TGFβ activated kinase 1 (Tak1), a key regulator of Smad-independent TGFβ signaling in palate development. We show that Tak1 protein is expressed in both the epithelium and mesenchyme of the developing palatal shelves. Whereas deletion of Tak1 in the palatal epithelium or mesenchyme did not give rise to a cleft palate defect, inactivation of Tak1 in the neural crest lineage using the Wnt1-Cre transgenic allele resulted in failed palate elevation and subsequently the cleft palate formation. The failure in palate elevation in Wnt1-Cre;Tak1(F/F) mice results from a malformed tongue and micrognathia, resembling human Pierre Robin sequence cleft of the secondary palate. We found that the abnormal tongue development is associated with Fgf10 overexpression in the neural crest-derived tongue tissue. The failed palate elevation and cleft palate were recapitulated in an Fgf10-overexpressing mouse model. The repressive effect of the Tak1-mediated noncanonical TGFβ signaling on Fgf10 expression was further confirmed by inhibition of p38, a downstream kinase of Tak1, in the primary cell culture of developing tongue. Tak1 thus functions to regulate tongue development by controlling Fgf10 expression and could represent a candidate gene for mutation in human PRS clefting.

Lipid-lowering effects of TAK-475, a squalene synthase inhibitor, in animal models of familial hypercholesterolemia.

PubMed

Amano, Yuichiro; Nishimoto, Tomoyuki; Tozawa, Ryu ichi; Ishikawa, Eiichiro; Imura, Yoshimi; Sugiyama, Yasuo

2003-04-11

The lipid-lowering effects of 1-[2-[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-1,2,3,5-tetrahydro-2-oxo-5-(2,3-dimethoxyphenyl)-4,1-benzoxazepine-3-yl] acetyl] piperidin-4-acetic acid (TAK-475), a novel squalene synthase inhibitor, were examined in two models of familial hypercholesterolemia, low-density lipoprotein (LDL) receptor knockout mice and Watanabe heritable hyperlipidemic (WHHL) rabbits. Two weeks of treatment with TAK-475 in a diet admixture (0.02% and 0.07%; approximately 30 and 110 mg/kg/day, respectively) significantly lowered plasma non-high-density lipoprotein (HDL) cholesterol levels by 19% and 41%, respectively, in homozygous LDL receptor knockout mice. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, simvastatin and atorvastatin (in 0.02% and 0.07% admixtures), also reduced plasma levels of non-HDL cholesterol. In homozygous WHHL rabbits, 4 weeks of treatment with TAK-475 (0.27%; approximately 100 mg/kg/day) lowered plasma total cholesterol, triglyceride and phospholipid levels by 17%, 52% and 26%, respectively. In Triton WR-1339-treated rabbits, TAK-475 inhibited to the same extent the rate of secretion from the liver of the cholesterol, triglyceride and phospholipid components of very-low-density lipoprotein (VLDL). These results suggest that the lipid-lowering effects of TAK-475 in WHHL rabbits are based partially on the inhibition of secretion of VLDL from the liver. TAK-475 had no effect on plasma aspartate aminotransferase and alanine aminotransferase activities. Thus, the squalene synthase inhibitor TAK-475 revealed lipid-lowering effects in both LDL receptor knockout mice and WHHL rabbits.

Reno-protective effects of TAK-242 on acute kidney injury in a rat model.

PubMed

Mohammad, Bassim I; Raheem, Abdulla K; Hadi, Najah R; Jamil, Dina A; Al-Aubaidy, Hayder A

2018-06-13

Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. Despite the advances in therapeutic techniques, the mortality and morbidity of patients remain high and have not appreciably improved. This study aims to evaluate the potential protective effect of TAK-242 on renal ischemia/reperfusion injury using an animal model. Thirty-five adult male Sprague-dawely rats (weighing 200-300), were assigned randomly into the following experimental groups (n = 7 in each group), Control (I/R), Sham (negative control), TAK-242 (5 mg/kg body weight), TAK-242 (10 mg/kg body weight) and Vehicle (DMSO). Rats were exposed to a 30 min of ischemia then 3 h of reperfusion. At the end of reperfusion phase, rats were sacrificed then plasma, serum and tissue samples were obtained to measure markers of kidney oxidative stress and inflammation. Plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), and tissue levels of interleukin-18 (IL-18) and malondialdehyde (MDA) were significantly lower in TAK-242 pretreated groups than the vehicle group and the control group (p < 0.05). Furthermore; serum levels of urea and creatinine were significantly lower in the TAK-242 pretreated groups as compared to the control group (p < 0.05). We conclude that administration of TAK-242 can be useful preventive method in attenuating the degree of acute kidney injury during ischemic reperfusion process as shown by a significant reduction of urinary inflammatory markers as well as significant reduction of urea and creatinine levels. Copyright © 2018 Elsevier Inc. All rights reserved.

TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice

NASA Technical Reports Server (NTRS)

Zhang, D.; Gaussin, V.; Taffet, G. E.; Belaguli, N. S.; Yamada, M.; Schwartz, R. J.; Michael, L. H.; Overbeek, P. A.; Schneider, M. D.

2000-01-01

The transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.

Bone bonding in bioactive glass ceramics combined with a new synthesized agent TAK-778.

PubMed

Kato, H; Neo, M; Tamura, J; Nakamura, T

2001-11-01

We studied the stimulatory effects of TAK-778, a new synthetic 3-benzothiepin derivative that promotes osteoblast differentiation, in the bonding of bone to bioactive glass ceramic implants in rabbit tibiae. Smooth-surfaced, rectangular plates (15 x 10 x 2 mm) made of apatite-wollastonite-containing glass ceramic were implanted bilaterally into the proximal metaphyses of rabbit tibiae. Sustained-release microcapsules containing TAK-778 were packed into the medullary cavity in one limb and untreated microcapsules were packed into the contralateral limb to serve as a paired control. At 4, 8, and 16 weeks after implantation, bonding at the bone/implant interfaces was evaluated using a detaching test and histological examination of undecalcified specimens. The tensile failure load increased during weeks 4 to 16 in both groups; the tensile failure load in the TAK-778-treated group was significantly greater than that in the control group at each interval after implantation. Histologically, the TAK-778-treated specimens showed greater active new bone formation mainly in the medullary cavity and more extensive bonding between the implant and bone than the untreated specimens. The results of this study suggest that adding the bone formation-promoting TAK-778 to bioactive glass ceramic implants may significantly accelerate bone apposition to the implants and improve the bonding process at the interface. This would help to establish earlier and stronger bonding of orthopedic ceramic implants to the surrounding bone tissue. Copyright 2001 John Wiley & Sons, Inc.

TGF-β Coordinately Activates TAK1/MEK/AKT/NFkB and Smad Pathways to Promote Osteoclast Survival

PubMed Central

Gingery, Anne; Bradley, Elizabeth W.; Pederson, Larry; Ruan, Ming; Horwood, Nikki J.; Oursler, Merry Jo

2008-01-01

To better understand the roles of TGF-β in bone metabolism, we investigated osteoclast survival in response TGF-β and found that TGF-β inhibited apoptosis. We examined the receptors involved in promotion of osteoclast survival and found that the canonical TGF-β receptor complex is involved in the survival response. The upstream MEK kinase TAK1 was rapidly activated following TGF-β treatment. Since osteoclast survival involves MEK, AKT, and NFκB activation, we examined TGF-β effects on activation of these pathways and observed rapid phosphorylation of MEK, AKT, IKK, IκB, and NFκB. The timing of activation coincided with SMAD activation and dominant negative SMAD expression did not inhibit NFκB activation, indicating that kinase pathway activation is independent of SMAD signaling. Inhibition of TAK1, MEK, AKT, NIK, IKK, or NFκB repressed TGF-β-mediated osteoclast survival. Adenoviral-mediated TAK1 or MEK inhibition eliminated TGF-β-mediated kinase pathway activation and constitutively active AKT expression overcame apoptosis induction following MEK inhibition. TAK1/MEK activation induces pro-survival BclXL expression and TAK1/MEK and SMAD pathway activation induces pro-survival Mcl-1 expression. These data show that TGF-β-induced NFκB activation is through TAK1/MEK-mediated AKT activation, which is essential for TGF-β to support of osteoclast survival. PMID:18586026

ETO cloud studies for FIRE 2, part 1

NASA Technical Reports Server (NTRS)

Sassen, Kenneth

1992-01-01

This research program in support of Project FIRE (First ISCCP Regional Experiment) involved two efforts. The results of the first effort, which were in direct support of the Extended Time Observations (ETO) component, are described here. Over the period from June 1990 through May 1991, our remote sensing systems were applied to providing ground-truth cirrus cloud observations for a total of 71 NOAA polar orbiting satellite overpasses. (Chronological tables of this effort are provided.) The primary remote sensor was a dual-polarization ruby (0.694 microns wavelength) lidar, although mid-way through the program we added a number of radiometers to assess the surface radiation budget and cirrus cloud infrared emittance, and some supplemental observations from a Ka-band (8.6 mm) radar were also collected. These studies were conducted from the Facility for Atmospheric Remote Sensing (FARS) at 40 degrees 46 minutes 00 seconds north latitude and 111 degrees 49 minutes 38 seconds east longitude. We also investigated the unusual characteristics of a subset of ETO case studies involving cirrus that generated solar and lunar corona displays. As we reported recently (reprint attached), these cirrus were atypically high and cold in relation to our total midlatitude cloud sample, and were comprised of unexpectedly small ice crystals from 10 to 30 microns in dimension. This finding lends some credence to the so-called cirrus small particle radiative anomaly, but only for very cold (less than -60 C) cirrus clouds. In a supplement, we will describe the design and testing of a prototype cirrus cloud polar nephelometer, which we constructed as part of our second research effort, to allow scattering phase functions to be obtained in future in situ cirrus research.

Procarcinogenic effects of cyclosporine A are mediated through the activation of TAK1/TAB1 signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Jianmin; Walsh, Stephanie B.; Verney, Zoe M.

Research highlights: {yields} Organ transplant recipients are highly susceptible to early skin cancer development. {yields} CsA-mediated TGFB1-dependent TAK1/TAB1 signaling augments invasive tumor growth. {yields} CsA enhances accumulation of upstream kinases, ZMP, AMPK and IRAK to activate TAK1. {yields} TAK1 mediates enhanced proliferation and reduced apoptosis via CsA-dependent NF{kappa}B. -- Abstract: Cyclosporine A (CsA) is an immunosuppressive drug commonly used for maintaining chronic immune suppression in organ transplant recipients. It is known that patients receiving CsA manifest increased growth of aggressive non-melanoma skin cancers. However, the underlying mechanism by which CsA augments tumor growth is not fully understood. Here, we showmore » that CsA augments the growth of A431 epidermoid carcinoma xenograft tumors by activating tumor growth factor {beta}-activated kinase1 (TAK1). The activation of TAK1 by CsA occurs at multiple levels by kinases ZMP, AMPK and IRAK. TAK1 forms heterodimeric complexes with TAK binding protein 1 and 2 (TAB1/TAB2) which in term activate nuclear factor {kappa}B (NF{kappa}B) and p38 MAP kinase. Transcriptional activation of NF{kappa}B is evidenced by IKK{beta}-mediated phosphorylation-dependent degradation of I{kappa}B and consequent nuclear translocation of p65. This also leads to enhancement in the expression of its transcriptional target genes cyclin D1, Bcl2 and COX-2. Similarly, activation of p38 leads to enhanced inflammation-related signaling shown by increased phosphorylation of MAPKAPK2 and which in turn phosphorylates its substrate HSP27. Activation of both NF{kappa}B and p38 MAP kinase provide mitogenic stimuli to augment the growth of SCCs.« less

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Pan; Hongqian, Chu; Qinghe, Meng

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and themore » lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8{sup +} T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. - Highlights: • Lack of TAK1 in DC caused an abolished TCE-induced CHS response. • TAK1 in DCs was essential to maintain the homeostasis of T cells in TCE-induced CHS. • Intact TAK1 in DCs was critical to promote T-cell priming in TCE-induced CHS. • DC-specific TAK1 deficiency abolished the TCE-mediated phosphorylation of Jnk.« less

Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effect on mouse sepsis model

PubMed Central

Takashima, K; Matsunaga, N; Yoshimatsu, M; Hazeki, K; Kaisho, T; Uekata, M; Hazeki, O; Akira, S; Iizawa, Y; Ii, M

2009-01-01

Background and purpose: TAK-242, a novel synthetic small-molecule, suppresses production of multiple cytokines by inhibiting Toll-like receptor (TLR) 4 signalling. In this study, we investigated the target molecule of TAK-242 and examined its therapeutic effect in a mouse sepsis model. Experimental approach: Binding assay with [3H]-TAK-242 and nuclear factor-κB reporter assay were used to identify the target molecule and binding site of TAK-242. Bacillus calmette guerin (BCG)-primed mouse sepsis model using live Escherichia coli was used to estimate the efficacy of TAK-242 in sepsis. Key results: TAK-242 strongly bound to TLR4, but binding to TLR2, 3, 5, 9, TLR-related adaptor molecules and MD-2 was either not observed or marginal. Mutational analysis using TLR4 mutants indicated that TAK-242 inhibits TLR4 signalling by binding to Cys747 in the intracellular domain of TLR4. TAK-242 inhibited MyD88-independent pathway as well as MyD88-dependent pathway and its inhibitory effect was largely unaffected by lipopolysaccharide (LPS) concentration and types of TLR4 ligands. TAK-242 had no effect on the LPS-induced conformational change of TLR4-MD-2 and TLR4 homodimerization. In mouse sepsis model, although TAK-242 alone did not affect bacterial counts in blood, if co-administered with ceftazidime it inhibited the increases in serum cytokine levels and improved survival of mice. Conclusions and implications: TAK-242 suppressed TLR4 signalling by binding directly to a specific amino acid Cys747 in the intracellular domain of TLR4. When co-administered with antibiotics, TAK-242 showed potent therapeutic effects in an E. coli-induced sepsis model using BCG-primed mice. Thus, TAK-242 may be a promising therapeutic agent for sepsis. PMID:19563534

Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling

PubMed Central

Pulikkan, John Anto; Madera, Dmitri; Xue, Liting; Bradley, Paul; Landrette, Sean Francis; Kuo, Ya-Huei; Abbas, Saman; Zhu, Lihua Julie; Valk, Peter

2012-01-01

Oncogenic mutations in components of cytokine signaling pathways elicit ligand-independent activation of downstream signaling, enhancing proliferation and survival in acute myeloid leukemia (AML). The myeloproliferative leukemia virus oncogene, MPL, a homodimeric receptor activated by thrombopoietin (THPO), is mutated in myeloproliferative disorders but rarely in AML. Here we show that wild-type MPL expression is increased in a fraction of human AML samples expressing RUNX1-ETO, a fusion protein created by chromosome translocation t(8;21), and that up-regulation of Mpl expression in mice induces AML when coexpressed with RUNX1-ETO. The leukemic cells are sensitive to THPO, activating survival and proliferative responses. Mpl expression is not regulated by RUNX1-ETO in mouse hematopoietic progenitors or leukemic cells. Moreover, we find that activation of PI3K/AKT but not ERK/MEK pathway is a critical mediator of the MPL-directed antiapoptotic function in leukemic cells. Hence, this study provides evidence that up-regulation of wild-type MPL levels promotes leukemia development and maintenance through activation of the PI3K/AKT axis, and suggests that inhibitors of this axis could be effective for treatment of MPL-positive AML. PMID:22613795

Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling.

PubMed

Pulikkan, John Anto; Madera, Dmitri; Xue, Liting; Bradley, Paul; Landrette, Sean Francis; Kuo, Ya-Huei; Abbas, Saman; Zhu, Lihua Julie; Valk, Peter; Castilla, Lucio Hernán

2012-07-26

Oncogenic mutations in components of cytokine signaling pathways elicit ligand-independent activation of downstream signaling, enhancing proliferation and survival in acute myeloid leukemia (AML). The myeloproliferative leukemia virus oncogene, MPL, a homodimeric receptor activated by thrombopoietin (THPO), is mutated in myeloproliferative disorders but rarely in AML. Here we show that wild-type MPL expression is increased in a fraction of human AML samples expressing RUNX1-ETO, a fusion protein created by chromosome translocation t(8;21), and that up-regulation of Mpl expression in mice induces AML when coexpressed with RUNX1-ETO. The leukemic cells are sensitive to THPO, activating survival and proliferative responses. Mpl expression is not regulated by RUNX1-ETO in mouse hematopoietic progenitors or leukemic cells. Moreover, we find that activation of PI3K/AKT but not ERK/MEK pathway is a critical mediator of the MPL-directed antiapoptotic function in leukemic cells. Hence, this study provides evidence that up-regulation of wild-type MPL levels promotes leukemia development and maintenance through activation of the PI3K/AKT axis, and suggests that inhibitors of this axis could be effective for treatment of MPL-positive AML.

Effect of TAK1 on osteogenic differentiation of mesenchymal stem cells by regulating BMP-2 via Wnt/β-catenin and MAPK pathway.

PubMed

Yang, Hongpeng; Guo, Yue; Wang, Dawei; Yang, Xiaofei; Ha, Chengzhi

2018-01-02

Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts and chondrocytes. In vitro osteogenic differentiation is critical but the molecular mechanism has yet to be further clarified. The role of TGF-β activated kinase 1 (TAK1) in MSCs osteogenesis differentiation has not been reported. By adding si-TAK1 and rhTAK1, the osteogenic differentiation of MSCs was measured. Expression levels of the osteoblastic marker genes during osteogenic differentiation of MSCs were checked. As well as molecules involved in BMP and Wnt/β-catenin signaling pathways. The phosphorylation of p38 and JNK was also checked. TAK1 is essential for mineralization of MSCs at low concentration, but excessive rhTAK1 inhibits mineralization of MSCs. It up regulates the expression levels of bone sialoprotein (BSP), osteocalcin (OSC), Alkaline phosphatase (ALP), and RUNX2 during osteogenic differentiation of MSCs. It can also promote TGF-β/BMP-2 gene expression and β-catenin expression, and down regulate GSK-3β expression. Meanwhile, TAK1 promotes the phosphorylation of p38 and JNK. Additionally, TAK1 up regulates the expression of BMP-2 at all concentration under the inhibition of p38 and JNK. Our results suggested that TAK1 is essential in MSCs osteogenesis differentiation, and functions as a double-edged sword, probably through regulation of β-catenin and p38/JNK.

Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen.

PubMed

Levin, Rebecca S; Hertz, Nicholas T; Burlingame, Alma L; Shokat, Kevan M; Mukherjee, Shaeri

2016-08-16

TGF-β activated kinase 1 (TAK1) is a critical signaling hub responsible for translating antigen binding signals to immune receptors for the activation of the AP-1 and NF-κB master transcriptional programs. Despite its importance, known substrates of TAK1 are limited to kinases of the MAPK and IKK families and include no direct effectors of biochemical processes. Here, we identify over 200 substrates of TAK1 using a chemical genetic kinase strategy. We validate phosphorylation of the dynamic switch II region of GTPase Rab1, a mediator of endoplasmic reticulum to Golgi vesicular transport, at T75 to be regulated by TAK1 in vivo. TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function. Previous studies established that the pathogen Legionella pneumophila is capable of hijacking Rab1 function through posttranslational modifications of the switch II region. Here, we present evidence that Rab1 is regulated by the host in a similar fashion, and that the innate immunity kinase TAK1 and Legionella effectors compete to regulate Rab1 by switch II modifications during infection.

Fasiglifam (TAK-875) Alters Bile Acid Homeostasis in Rats and Dogs: A Potential Cause of Drug Induced Liver Injury

PubMed Central

Zhu, Andy Z. X.; Johnson, Mike; Yu, Shaoxia; Moriya, Yuu; Ebihara, Takuya; Csizmadia, Vilmos; Grieves, Jessica; Paton, Martin; Liao, Mingxiang; Gemski, Christopher; Pan, Liping; Vakilynejad, Majid; Dragan, Yvonne P.; Chowdhury, Swapan K.; Kirby, Patrick J.

2017-01-01

Abstract Fasiglifam (TAK-875), a Free Fatty Acid Receptor 1 (FFAR1) agonist in development for the treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects. A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. TAK-875 was an in vitro inhibitor of multiple influx (NTCP and OATPs) and efflux (BSEP and MRPs) hepatobiliary BA transporters at micromolar concentrations. Repeat dose studies determined that TAK-875 caused a dose-dependent increase in serum total BA in rats and dogs. Additionally, there were dose-dependent increases in both unconjugated and conjugated individual BAs in both species. Rats had an increase in serum markers of liver injury without correlative microscopic signs of tissue damage. Two of 6 dogs that received the highest dose of TAK-875 developed liver injury with clinical pathology changes, and by microscopic analysis had portal granulomatous inflammation with neutrophils around a crystalline deposition. The BA composition of dog bile also significantly changed in a dose-dependent manner following TAK-875 administration. At the highest dose, levels of taurocholic acid were 50% greater than in controls with a corresponding 50% decrease in taurochenodeoxycholic acid. Transporter inhibition by TAK-875 may cause liver injury in dogs through altered bile BA composition characteristics, as evidenced by crystalline deposition, likely composed of test article, in the bile duct. In conclusion, a combination of in vitro and in vivo evidence suggests that BA transporter inhibition could contribute to TAK-875-mediated liver injury in dogs. PMID:28108665

An evolutionarily conserved motif in the TAB1 C-terminal region is necessary for interaction with and activation of TAK1 MAPKKK.

PubMed

Ono, K; Ohtomo, T; Sato, S; Sugamata, Y; Suzuki, M; Hisamoto, N; Ninomiya-Tsuji, J; Tsuchiya, M; Matsumoto, K

2001-06-29

TAK1, a member of the MAPKKK family, is involved in the intracellular signaling pathways mediated by transforming growth factor beta, interleukin 1, and Wnt. TAK1 kinase activity is specifically activated by the TAK1-binding protein TAB1. The C-terminal 68-amino acid sequence of TAB1 (TAB1-C68) is sufficient for TAK1 interaction and activation. Analysis of various truncated versions of TAB1-C68 defined a C-terminal 30-amino acid sequence (TAB1-C30) necessary for TAK1 binding and activation. NMR studies revealed that the TAB1-C30 region has a unique alpha-helical structure. We identified a conserved sequence motif, PYVDXA/TXF, in the C-terminal domain of mammalian TAB1, Xenopus TAB1, and its Caenorhabditis elegans homolog TAP-1, suggesting that this motif constitutes a specific TAK1 docking site. Alanine substitution mutagenesis showed that TAB1 Phe-484, located in the conserved motif, is crucial for TAK1 binding and activation. The C. elegans homolog of TAB1, TAP-1, was able to interact with and activate the C. elegans homolog of TAK1, MOM-4. However, the site in TAP-1 corresponding to Phe-484 of TAB1 is an alanine residue (Ala-364), and changing this residue to Phe abrogates the ability of TAP-1 to interact with and activate MOM-4. These results suggest that the Phe or Ala residue within the conserved motif of the TAB1-related proteins is important for interaction with and activation of specific TAK1 MAPKKK family members in vivo.

TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dey, Nilay; Liu Tianshuang; Garofalo, Roberto P.

2011-09-30

Respiratory syncytial virus (RSV) is the most common cause of epidemic respiratory diseases in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B) and AP-1. In this study, we have investigated the signaling pathway leading to activation of these two transcription factors in response to RSV infection. Our results show that IKK{beta} plays a key role in viral-induced NF-{kappa}B activation, while JNK regulates AP-1-dependent gene transcription, as demonstrated by using kinase inactive proteins and chemical inhibitors of the two kinases.more » Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced RSV-induced NF-{kappa}B and AP-1 nuclear translocation and DNA-binding activity, as well as NF-{kappa}B-dependent gene expression, identifying TAK1 as an important upstream signaling molecule regulating RSV-induced NF-{kappa}B and AP-1 activation. - Highlights: > IKK{beta} is a major kinase involved in RSV-induced NF-{kappa}B activation. > JNK regulates AP-1-dependent gene transcription in RSV infection. > TAK1 is a critical upstream signaling molecule for both pathways in infected cells.« less

Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats.

PubMed

Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki

2010-08-01

Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation. Thrombus formation was initiated by FeCl(3)-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle. TAK-442 (3mg/kg, po), aspirin (100mg/kg, po) or clopidogrel (3mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment. These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings. (c) 2010 Elsevier Ltd. All rights reserved.

Phosphodiesterase 2A Inhibitor TAK-915 Ameliorates Cognitive Impairments and Social Withdrawal in N-Methyl-d-Aspartate Receptor Antagonist-Induced Rat Models of Schizophrenia.

PubMed

Nakashima, Masato; Imada, Haruka; Shiraishi, Eri; Ito, Yuki; Suzuki, Noriko; Miyamoto, Maki; Taniguchi, Takahiko; Iwashita, Hiroki

2018-04-01

The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N -methyl-d-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain-penetrant PDE2A inhibitor, ( N -{(1 S )-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3- b ]pyrazine-4(1 H )-carboxamide) (TAK-915) as a novel treatment of schizophrenia. Oral administration of TAK-915 at 3 and 10 mg/kg significantly increased cGMP levels in the frontal cortex, hippocampus, and striatum of rats. TAK-915 at 10 mg/kg significantly upregulated the phosphorylation of α -amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor subunit GluR1 in the rat hippocampus. TAK-915 at 3 and 10 mg/kg significantly attenuated episodic memory deficits induced by the NMDA receptor antagonist (+)-MK-801 hydrogen maleate (MK-801) in the rat passive avoidance test. TAK-915 at 10 mg/kg significantly attenuated working memory deficits induced by MK-801 in the rat radial arm maze test. Additionally, TAK-915 at 10 mg/kg prevented subchronic phencyclidine-induced social withdrawal in social interaction in rats. In contrast, TAK-915 did not produce antipsychotic-like activity; TAK-915 had little effect on MK-801- or methamphetamine-induced hyperlocomotion in rats. These results suggest that TAK-915 has a potential to ameliorate cognitive impairments and social withdrawal in schizophrenia. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay.

PubMed

Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao

2016-09-15

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. Copyright © 2016 Elsevier Inc. All rights reserved.

A phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-063, a selective PDE10A inhibitor.

PubMed

Tsai, Max; Chrones, Lambros; Xie, Jinhui; Gevorkyan, Hakop; Macek, Thomas A

2016-10-01

Schizophrenia is a complex neuropsychiatric disorder characterized, in part, by impaired dopamine signaling. TAK-063 is a selective inhibitor of phosphodiesterase 10A, a key regulator of intracellular signaling pathways that is highly expressed in the striatum. Safety, tolerability, and pharmacokinetics of TAK-063 were evaluated in a phase 1 study. Healthy Japanese and non-Japanese volunteers were randomized into dose cohorts of 3, 10, 30, 100, 300, and 1000 mg. Each fasting volunteer randomly received a single dose of TAK-063 or placebo. Individuals from the 100-mg cohort also received a post-washout, 100-mg dose under fed conditions. A total of 84 volunteers enrolled (14 per cohort). The most common drug-related adverse events (AEs) were somnolence (33.3 %), orthostatic tachycardia (19.7 %), and orthostatic hypotension (9.1 %). The three severe AEs recorded occurred at the highest doses: orthostatic hypotension (n = 1; 300 mg) and somnolence (n = 2; 1000 mg). There were no deaths, serious AEs, or discontinuations due to AEs. TAK-063 exposure increased in a dose-dependent manner. Median T max was reached 3 to 4 h postdose. Fed conditions slowed absorption (T max =  6 h) and increased oral bioavailability. Renal elimination was negligible. Safety and pharmacokinetic parameters were similar between Japanese and non-Japanese subjects. Impairments in cognitive function consistent with the effects of other sedative or hypnotic agents were detected using a validated, computerized cognition battery, CNS Vital Signs. TAK-063 was safe and well tolerated at doses up to 1000 mg and demonstrated a pharmacokinetic profile supporting once-daily dosing. Further evaluation of the clinical safety and efficacy of TAK-063 is warranted.

TAK-242 treatment ameliorates liver ischemia/reperfusion injury by inhibiting TLR4 signaling pathway in a swine model of Maastricht-category-III cardiac death.

PubMed

Shao, Zigong; Jiao, Baoping; Liu, Tingting; Cheng, Ying; Liu, Hao; Liu, Yongfeng

2016-12-01

This study aims to test the effects of TAK-242 on liver transplant viability in a model of swine Maastricht-category-III cardiac death. A swine DCD Maastricht-III model of cardiac death was established, and TAK-242 was administered prior to the induction of cardiac death. The protein and mRNA level of TLR4 signaling pathway molecules and cytokines that are important in mediating immune and inflammatory responses were assessed at different time points following the induction of cardiac death. After induction of cardiac death, both the mRNA and protein levels of key molecules (TLR4, TRAF6, NF-ϰB, ICAM-1, MCP-1 and MPO), TNF-α and IL-6 increased significantly. Infusion of TAK-242 1h before induction of cardiac death blocked the increase of immune and inflammatory response molecules. However, the increase of TLR4 level was not affected by infusion of TAK-242. Histology study showed that infusion of TAK-242 protect liver tissue from damage during cardiac death. These results indicates that TLR4 signaling pathway may contribute to ischemia/reperfusion injury in the liver grafts, and blocking TLR4 pathway with TAk-242 may reduce TLR4-mediated tissue damage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Efficacy and safety of TAK-085 compared with eicosapentaenoic acid in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized double-blind (ORD) study.

PubMed

Tatsuno, Ichiro; Saito, Yasushi; Kudou, Kentarou; Ootake, Jun

2013-01-01

Hypertriglyceridemia is a risk factor for cardiovascular disease, and clinical practice guidelines advocate treatment to reduce triglyceride (TG) levels. In Japan, an EPA-E (eicosapentaenoic acid-ethyl ester) product has been used clinically for treating dyslipidemia. We investigated the TG-lowering effects of TAK-085 (EPA-E + docosahexaenoic acid-ethyl ester) in comparison with EPA-E in Japanese patients with hypertriglyceridemia (TG ≥150 mg/dL and <750 mg/dL). In this multicenter, 12-week, double-blind study, subjects were stratified for coadministration of a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor then randomized to TAK-085 2 g once daily (n = 205), TAK-085 2 g twice daily (n = 210), or EPA-E 0.6 g three times daily (n = 195). Each one gram of fatty acid in TAK-085 contains approximately 465 mg of EPA plus 375 mg of docosahexaenoic acid-ethyl as ethyl esters. Guidance on lifestyle modifications was provided throughout. The primary end point was the percent change in TG levels (baseline from end of treatment), which was -10.8 ± 22.6, -22.9 ± 23.1, and -11.2 ± 25.7 in the TAK-085 2 g/day, TAK-085 4 g/day, and EPA-E 1.8 g/day groups, respectively. TAK-085 4 g/day produced a significantly greater reduction in TG than EPA-E 1.8 g/day (P < .0001), whereas TAK-085 2 g/day was not inferior to EPA-E 1.8 g/day. Changes in other lipid parameters were relatively modest. There were no notable safety or tolerability differences between the groups. In Japanese patients with modest hypertriglyceridemia who also underwent lifestyle intervention, TAK-085 4 g/day reduced TG more than EPA-E 1.8 g/day. TAK-085 2 g/day had similar effects on TG as EPA-E 1.8 g/day. TAK-085 was well-tolerated. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Altered cerebellar development in nuclear receptor TAK1/ TR4 null mice is associated with deficits in GLAST(+) glia, alterations in social behavior, motor learning, startle reactivity, and microglia.

PubMed

Kim, Yong-Sik; Harry, G Jean; Kang, Hong Soon; Goulding, David; Wine, Rob N; Kissling, Grace E; Liao, Grace; Jetten, Anton M

2010-09-01

Previously, deficiency in the expression of the nuclear orphan receptor TAK1 was found to be associated with delayed cerebellar granule cell migration and Purkinje cell maturation with a permanent deficit in foliation of lobules VI–VII, suggesting a role for TAK1 in cerebellum development. In this study, we confirm that TAK1-deficient (TAK1(−/−)) mice have a smaller cerebellum and exhibit a disruption of lobules VI–VII. We extended these studies and show that at postnatal day 7, TAK1(−/−) mice exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells. The astrocyte-specific glutamate transporter (GLAST) was expressed within Bergmann fibers and internal granule cell layer at significantly lower levels in the cerebellum of TAK1(−/−) mice. At PND21, Golgi-positive Purkinje cells in TAK1(−/−) mice displayed a smaller soma (18%) and shorter distance to first branch point (35%). Neuronal death was not observed in TAK1(−/−) mice at PND21; however, activated microglia were present in the cerebellum, suggestive of earlier cell death. These structural deficits in the cerebellum were not sufficient to alter motor strength, coordination, or activity levels; however, deficits in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Reactions to a novel environment were inhibited in a light/dark chamber, open-field, and home-cage running wheel. TAK1(−/−) mice displayed a plateau in performance on the running wheel, suggesting a deficit in learning to coordinate performance on a motor task. These data indicate that TAK1 is an important transcriptional modulator of cerebellar development and neurodevelopmentally regulated behavior.

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized long-term (ORL) study.

PubMed

Tatsuno, Ichiro; Saito, Yasushi; Kudou, Kentarou; Ootake, Jun

2013-01-01

TAK-085 is an omega-3 preparation that contains eicosapentaenoic acid ethyl-ester (EPA-E) and docosahexaenoic acid-ethyl ester used in the management of hypertriglyceridemia. The aim of the study was to evaluate the long-term safety (adverse events [AEs], laboratory parameters, vital signs, weight, and electrocardiograms) and effects on lipid profiles, especially triglyceride levels, of TAK-085 in Japanese patients with hypertriglyceridemia (triglyceride levels ≥150 mg/dL and <750 mg/dL). In this multicenter, open-label, randomized study, adults with hypertriglyceridemia undergoing lifestyle modification received TAK-085 2 g (2 g once daily; n = 165) or 4 g (2 g twice daily; n = 171), or EPA-E 1.8 g (0.6 g three times daily; n = 167) for 52 weeks. Patients were stratified for co-administration of a statin. TAK-085 was well tolerated throughout the 52-week study. Overall, no substantial differences were found in the tolerability of TAK-085 2 g, TAK-085 4 g, and EPA-E 1.8 g with incidence rates for AEs of 83.6%, 86.0%, and 89.2%, respectively. Most AEs were mild or moderate in severity. Triglyceride levels decreased from baseline in all groups by week 4, and the decreases were maintained throughout the study. At week 52 the reduction in triglycerides with TAK-085 2 g (-13.9%) was similar to that with EPA-E 1.8 g (-12.1%), whereas the reduction seen with TAK-085 4 g (-25.5%) was greater than that with EPA-E 1.8 g, as assessed by point estimates and 95% confidence intervals. TAK-085 was safe and well tolerated for up to 52 weeks of treatment in Japanese patients with hypertriglyceridemia undergoing lifestyle modification. Reductions in triglyceride levels achieved after 4 weeks were maintained at 52 weeks. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Bing, E-mail: wangbin69@yahoo.com; Wang, Xin-bao; Chen, Li-yu

2013-07-19

Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancermore » cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.« less

Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice.

PubMed

Nakata, Daisuke; Masaki, Tsuneo; Tanaka, Akira; Yoshimatsu, Mie; Akinaga, Yumiko; Asada, Mari; Sasada, Reiko; Takeyama, Michiyasu; Miwa, Kazuhiro; Watanabe, Tatsuya; Kusaka, Masami

2014-01-15

TAK-385 (relugolix) is a novel, non-peptide, orally active gonadotropin-releasing hormone (GnRH) antagonist, which builds on previous work with non-peptide GnRH antagonist TAK-013. TAK-385 possesses higher affinity and more potent antagonistic activity for human and monkey GnRH receptors compared with TAK-013. Both TAK-385 and TAK-013 have low affinity for the rat GnRH receptor, making them difficult to evaluate in rodent models. Here we report the human GnRH receptor knock-in mouse as a humanized model to investigate pharmacological properties of these compounds on gonadal function. Twice-daily oral administration of TAK-013 (10mg/kg) for 4 weeks decreased the weights of testes and ventral prostate in male knock-in mice but not in male wild-type mice, demonstrating the validity of this model to evaluate antagonists for the human GnRH receptor. The same dose of TAK-385 also reduced the prostate weight to castrate levels in male knock-in mice. In female knock-in mice, twice-daily oral administration of TAK-385 (100mg/kg) induced constant diestrous phases within the first week, decreased the uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in the pituitary after 4 weeks. Gonadal function of TAK-385-treated knock-in mice began to recover after 5 days and almost completely recovered within 14 days after drug withdrawal in both sexes. Our findings demonstrate that TAK-385 acts as an antagonist for human GnRH receptor in vivo and daily oral administration potently, continuously and reversibly suppresses the hypothalamic-pituitary-gonadal axis. TAK-385 may provide useful therapeutic interventions in hormone-dependent diseases including endometriosis, uterine fibroids and prostate cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

Parental Perceptions of the Effects of the High-Stakes TAKS Test on the Home Lives of At-Risk Fifth Grade Students

ERIC Educational Resources Information Center

Westfall, Dawn M.

2010-01-01

In Texas, fifth grade students are required to pass both the reading and math sections of the Texas Assessment of Knowledge and Skills, or TAKS test, in order to be promoted to the next grade level. The purpose of this study is to describe parents' perceptions of the influence of the high-stakes TAKS test on the family lives of at-risk fifth grade…

AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia.

PubMed

Zhou, Fengbiao; Liu, Yi; Rohde, Christian; Pauli, Cornelius; Gerloff, Dennis; Köhn, Marcel; Misiak, Danny; Bäumer, Nicole; Cui, Chunhong; Göllner, Stefanie; Oellerich, Thomas; Serve, Hubert; Garcia-Cuellar, Maria-Paz; Slany, Robert; Maciejewski, Jaroslaw P; Przychodzen, Bartlomiej; Seliger, Barbara; Klein, Hans-Ulrich; Bartenhagen, Christoph; Berdel, Wolfgang E; Dugas, Martin; Taketo, Makoto Mark; Farouq, Daneyal; Schwartz, Schraga; Regev, Aviv; Hébert, Josée; Sauvageau, Guy; Pabst, Caroline; Hüttelmaier, Stefan; Müller-Tidow, Carsten

2017-07-01

Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential. Genomic deletion of either C/D box snoRNA SNORD14D or SNORD35A suppressed clonogenic potential of leukaemia cells in vitro and delayed leukaemogenesis in vivo. We further showed that AML1-ETO9a, MYC and MLL-AF9 all enhanced snoRNA formation. Expression levels of C/D box snoRNAs in AML patients correlated closely with in vivo frequency of leukaemic stem cells. Collectively, these findings indicate that induction of C/D box snoRNA/RNP function constitutes an important pathway in leukaemogenesis.

HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways

PubMed Central

Berth, Sarah H.; Mesnard-Hoaglin, Nichole; Wang, Bin; Kim, Hajwa; Song, Yuyu; Sapar, Maria; Morfini, Gerardo

2016-01-01

Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a mechanistic basis for these effects, pharmacological experiments revealed an involvement of various phosphotransferases in this toxic effect, including members of mitogen-activated protein kinase pathways (Tak-1, p38, and c-Jun N-terminal Kinase (JNK)), inhibitor of kappa-B-kinase 2 (IKK2), and PP1. Biochemical experiments and axonal outgrowth assays in cell lines and primary cultures extended these findings. Impairments in neurite outgrowth in DRG neurons by gp120 were rescued using a Tak-1 inhibitor, implicating a Tak-1 mitogen-activated protein kinase pathway in gp120 neurotoxicity. Taken together, these observations indicate that kinase-based impairments in FAT represent a novel mechanism underlying gp120 neurotoxicity consistent with the dying-back degeneration seen in DSP. Targeting gp120-based impairments in FAT with specific kinase inhibitors might provide a novel therapeutic strategy to prevent axonal degeneration in DSP. PMID:27872270

TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study

PubMed Central

Bang, Yung-Jue; Takano, Toshimi; Lin, Chia-Chi; Fasanmade, Adedigbo; Yang, Huyuan; Danaee, Hadi; Asato, Takayuki; Kalebic, Thea; Wang, Hui; Doi, Toshihiko

2018-01-01

Purpose This phase 1 dose-escalation portion of the study evaluated the safety, pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC). Materials and Methods Adult patients with advanced GI malignancies expressing GCC (H-score ≥ 10) received TAK-264 on day 1 of 3-week cycles as 30-minute intravenous infusions for up to 1 year or until disease progression or unacceptable toxicity. The primary objectives were to evaluate the safety profile including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum tolerated dose (MTD), and characterize the PK profile of TAK-264. Results Twelve patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8 mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1 to 10). None of the patients experienced a DLT and the MTD was not determined. Ten patients (83%) experienced adverse events (AEs). The most common were neutropenia, anorexia, and nausea (each reported by four patients). Five patients (42%) experienced grade ≥ 3 AEs consisting of tumor hemorrhage and hypertension, ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK-264 increased proportionally with the dose and the median half-life was approximately 5.5-6.6 days. No patients experienced an objective response. Conclusion TAK-264 demonstrated a manageable safety profile with limited antitumor activity consistent with studies conducted in Western patients with advanced GI malignancies. TAK-264 exposure increased proportionally with the dose. PMID:28494535

A Study of the Relationship between Levels of Technology Implementation (LoTi) and Student Performance on Texas Assessment of Knowledge and Skills (TAKS) Scores

ERIC Educational Resources Information Center

Berkeley-Jones, Catherine Spotswood

2012-01-01

The purpose of this study was to examine teacher Levels of Technology Implementation (LoTi) self-ratings and student Texas Assessment of Knowledge and Skills (TAKS) scores. The study assessed the relationship between LoTi ratings and TAKS scores of 6th, 7th, and 8th grade students as reported in student records at Alamo Heights Independent School…

Anti-inflammatory and cytoprotective effects of a squalene synthase inhibitor, TAK-475 active metabolite-I, in immune cells simulating mevalonate kinase deficiency (MKD)-like condition.

PubMed

Suzuki, Nobutaka; Ito, Tatsuo; Matsui, Hisanori; Takizawa, Masayuki

2016-01-01

TAK-475 (lapaquistat acetate) and its active metabolite-I (TAK-475 M-I) inhibit squalene synthase, which catalyzes the conversion of farnesyl diphosphate (FPP) to squalene. FPP is a substrate for synthesis of other mevalonate-derived isoprenoids (MDIs) such as farnesol (FOH), geranlygeranyl diphosphate (GGPP), and geranylgeraniol. In patients with MKD, a rare autosomal recessive disorder, defective activity of mevalonate kinase leads to a shortage of MDIs. MDIs especially GGPP are required for prenylation of proteins, which is a posttranslation modification necessary for proper functioning of proteins like small guanosine triphosphatases. Malfunction of prenylation of proteins results in upregulation of the inflammatory cascade, leading to increased production of proinflammatory cytokines like interleukin-1β (IL-1β), eventually leading to episodic febrile attacks. In vitro, TAK-475 M-I incubation in a concentration dependent manner increased levels of FPP, GGPP, and FOH in human monocytic THP-1 cells. In subsequent experiments, THP-1 cells or human peripheral blood mononuclear cells (PBMCs) were incubated with simvastatin, which inhibits hydroxymethylglutaryl-coenzyme A reductase and thereby decreases levels of the precursors of MDIs, leading to the depletion of MDIs as expected in MKD patients. Increased levels of GGPP and FPP attenuated lipopolysaccharide (LPS)-induced IL-1β production in THP-1 cells and human PBMCs in statin-treated conditions. The MDIs also significantly reduced the damaged cell ratio in this active MKD-like condition. Moreover, TAK-475 M-I directly inhibited LPS-induced IL-1β production from statin-treated THP-1 cells. These results show anti-inflammatory and cytoprotective effects of MDIs via TAK-475 M-I treatment in statin-treated immune cells, suggesting that possible therapeutic effects of TAK-475 treatment in MKD patients.

Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

PubMed Central

2015-01-01

We developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. A 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. PMID:25075558

An Integrated Learning System: Impact on At-Risk Students' Ninth Grade TAKS Mathematics Achievement

ERIC Educational Resources Information Center

Harris, Tina D.

2011-01-01

The purpose of this study was to determine the impact of an integrated learning system on students who were considered at-risk of academic failure on the Texas Assessment of Knowledge and Skills (TAKS) mathematics assessment. Voyager Math (VMath), an integrated learning system had been implemented to address the needs of students at-risk of…

TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipidinduced inflammation and insulin resistance in muscle cells

PubMed Central

Hussey, Sophie E.; Liang, Hanyu; Costford, Sheila R.; Klip, Amira; DeFronzo, Ralph A.; Sanchez-Avila, Alicia; Ely, Brian; Musi, Nicolas

2012-01-01

Emerging evidence suggests that TLR (Toll-like receptor) 4 and downstream pathways [MAPKs (mitogen-activated protein kinases) and NF-κB (nuclear factor κB)] play an important role in the pathogenesis of insulin resistance. LPS (lipopolysaccharide) and saturated NEFA (non-esterified fatty acids) activate TLR4, and plasma concentrations of these TLR4 ligands are elevated in obesity and Type 2 diabetes. Our goals were to define the role of TLR4 on the insulin resistance caused by LPS and saturated NEFA, and to dissect the independent contribution of LPS and NEFA to the activation of TLR4-driven pathways by employing TAK-242, a specific inhibitor of TLR4. LPS caused robust activation of the MAPK and NF-κB pathways in L6 myotubes, along with impaired insulin signalling and glucose transport. TAK-242 completely prevented the inflammatory response (MAPK and NF-κB activation) caused by LPS, and, in turn, improved LPS-induced insulin resistance. Similar to LPS, stearate strongly activated MAPKs, although stimulation of the NF-κB axis was modest. As seen with LPS, the inflammatory response caused by stearate was accompanied by impaired insulin action. TAK-242 also blunted stearate-induced inflammation; yet, the protective effect conferred by TAK-242 was partial and observed only on MAPKs. Consequently, the insulin resistance caused by stearate was only partially improved by TAK-242. In summary, TAK-242 provides complete and partial protection against LPS- and NEFA-induced inflammation and insulin resistance, respectively. Thus, LPS-induced insulin resistance depends entirely on TLR4, whereas NEFA works through TLR4-dependent and -independent mechanisms to impair insulin action. PMID:23050932

Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner.

PubMed

Man, Na; Tan, Yurong; Sun, Xiao-Jian; Liu, Fan; Cheng, Guoyan; Greenblatt, Sarah M; Martinez, Camilo; Karl, Daniel L; Ando, Koji; Sun, Ming; Hou, Dan; Chen, Bingyi; Xu, Mingjiang; Yang, Feng-Chun; Chen, Zhu; Chen, Saijuan; Nimer, Stephen D; Wang, Lan

2017-05-18

AML1-ETO (AE), a fusion oncoprotein generated by t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML. We report here that loss of Caspase-3 triggers a conserved, adaptive mechanism, namely autophagy (or macroautophagy), which acts to limit AE9a-driven leukemia. Furthermore, we identify ULK1 as a novel substrate of Caspase-3 and show that upregulation of ULK1 drives autophagy initiation in leukemia cells and that inhibition of ULK1 can rescue the phenotype induced by Caspase-3 deletion in vitro and in vivo. Collectively, these data highlight Caspase-3 as an important regulator of autophagy in AML and demonstrate that the balance and selectivity between its substrates can dictate the pace of disease. © 2017 by The American Society of Hematology.

Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Li; Nomanbhoy, Tyzoon; Gurbani, Deepak

Here, we developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16more » and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. Lastly, a 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors.« less

Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

DOE PAGES

Tan, Li; Nomanbhoy, Tyzoon; Gurbani, Deepak; ...

2014-07-17

Here, we developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16more » and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. Lastly, a 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors.« less

Shrimp TAB1 interacts with TAK1 and p38 and activates the host innate immune response to bacterial infection.

PubMed

Wang, Sheng; Li, Mengqiao; Yin, Bin; Li, Haoyang; Xiao, Bang; Lǚ, Kai; Huang, Zhijian; Li, Sedong; He, Jianguo; Li, Chaozheng

2017-08-01

Mammalian TAB1 has been previously identified as transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) binding protein, which functions as the activator of TAK1 and p38. This report, for the first time, identified and characterized the homolog of TAB1 in shrimp, to be specific, the homolog gene from Litopenaeus vannamei, containing a 1560-bp open reading frame (ORF) that encoded a putative protein of 519 amino acids with the conserved PP2Cc (Serine/threonine phosphatases, family 2C, catalytic) domain in N-terminal and a TAK1 binding motif in C-terminus, has been cloned and named LvTAB1. LvTAB1 was most abundant in gills and its expression could respond significantly to a series of stimuli, including LPS, Vibrio parahemolyticus and Staphylococcus aureus. Moreover, Co-immunoprecipitation (Co-IP) experiments showed that LvTAB1 could combine with LvTAK1 as well as Lvp38, two members of IMD-NF-κB/MAPK pathway, which meant LvTAB1 could have a role in regulating the activities of these kinases. Over-expression of LvTAB1 in drosophila S2 cells could improve the transcriptional levels of antimicrobial peptide genes (AMPs) such as Diptericin (Dpt), the hallmark of drosophila NF-κB activated genes, indicating its activation effect on NF-κB pathway. Furthermore, suppression of LvTAB1 expression in vivo by RNA-interference increased the sensibility of shrimps to V. parahaemolyticus infection, implying its protective role against bacterial infection. In conclusion, these results provide some insight into the function of LvTAB1 during bacterial infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel cyclohexene derivative, ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242), selectively inhibits toll-like receptor 4-mediated cytokine production through suppression of intracellular signaling.

PubMed

Ii, Masayuki; Matsunaga, Naoko; Hazeki, Kaoru; Nakamura, Kazuyo; Takashima, Katsunori; Seya, Tsukasa; Hazeki, Osamu; Kitazaki, Tomoyuki; Iizawa, Yuji

2006-04-01

Proinflammatory mediators such as cytokines and NO play pivotal roles in various inflammatory diseases. To combat inflammatory diseases successfully, regulation of proinflammatory mediator production would be a critical process. In the present study, we investigated the in vitro effects of ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242), a novel small molecule cytokine production inhibitor, and its mechanism of action. In RAW264.7 cells and mouse peritoneal macrophages, TAK-242 suppressed lipopolysaccharide (LPS)-induced production of NO, tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6, with 50% inhibitory concentration (IC50) of 1.1 to 11 nM. TAK-242 also suppressed the production of these cytokines from LPS-stimulated human peripheral blood mononuclear cells (PBMCs) at IC50 values from 11 to 33 nM. In addition, the inhibitory effects on the LPS-induced IL-6 and IL-12 production were similar in human PBMCs, monocytes, and macrophages. TAK-242 inhibited mRNA expression of IL-6 and TNF-alpha induced by LPS and interferon-gamma in RAW264.7 cells. The phosphorylation of mitogen-activated protein kinases induced by LPS was also inhibited in a concentration-dependent manner. However, TAK-242 did not antagonize the binding of LPS to the cells. It is noteworthy that TAK-242 suppressed the cytokine production induced by Toll-like receptor (TLR) 4 ligands, but not by ligands for TLR2, -3, and -9. In addition, IL-1beta-induced IL-8 production from human PBMCs was not markedly affected by TAK-242. These data suggest that TAK-242 suppresses the production of multiple cytokines by selectively inhibiting TLR4 intracellular signaling. Finally, TAK-242 is a novel small molecule TLR4 signaling inhibitor and could be a promising therapeutic agent for inflammatory diseases, whose pathogenesis involves TLR4.

TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipid-induced inflammation and insulin resistance in muscle cells.

PubMed

Hussey, Sophie E; Liang, Hanyu; Costford, Sheila R; Klip, Amira; DeFronzo, Ralph A; Sanchez-Avila, Alicia; Ely, Brian; Musi, Nicolas

2012-11-30

Emerging evidence suggests that TLR (Toll-like receptor) 4 and downstream pathways [MAPKs (mitogen-activated protein kinases) and NF-κB (nuclear factor κB)] play an important role in the pathogenesis of insulin resistance. LPS (lipopolysaccharide) and saturated NEFA (non-esterified fatty acids) activate TLR4, and plasma concentrations of these TLR4 ligands are elevated in obesity and Type 2 diabetes. Our goals were to define the role of TLR4 on the insulin resistance caused by LPS and saturated NEFA, and to dissect the independent contribution of LPS and NEFA to the activation of TLR4-driven pathways by employing TAK-242, a specific inhibitor of TLR4. LPS caused robust activation of the MAPK and NF-κB pathways in L6 myotubes, along with impaired insulin signalling and glucose transport. TAK-242 completely prevented the inflammatory response (MAPK and NF-κB activation) caused by LPS, and, in turn, improved LPS-induced insulin resistance. Similar to LPS, stearate strongly activated MAPKs, although stimulation of the NF-κB axis was modest. As seen with LPS, the inflammatory response caused by stearate was accompanied by impaired insulin action. TAK-242 also blunted stearate-induced inflammation; yet, the protective effect conferred by TAK-242 was partial and observed only on MAPKs. Consequently, the insulin resistance caused by stearate was only partially improved by TAK-242. In summary, TAK-242 provides complete and partial protection against LPS- and NEFA-induced inflammation and insulin resistance, respectively. Thus, LPS-induced insulin resistance depends entirely on TLR4, whereas NEFA works through TLR4-dependent and -independent mechanisms to impair insulin action.

Characterization of Transporters in the Hepatic Uptake of TAK-475 M-I, a Squalene Synthase Inhibitor, in Rats and Humans.

PubMed

Ebihara, T; Takeuchi, T; Moriya, Y; Tagawa, Y; Kondo, T; Moriwaki, T; Asahi, S

2016-06-01

TAK-475 (lapaquistat acetate) is a squalene synthase inhibitor and M-I is a pharmacologically active metabolite of TAK-475. Preclinical pharmacokinetic studies have demonstrated that most of the dosed TAK-475 was hydrolyzed to M-I during the absorption process and the concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration to rats. In the present study, the mechanism of the hepatic uptake of M-I was investigated.The uptake studies of (14)C-labeled M-I into rat and human hepatocytes indicated that the uptakes of M-I were concentrative, temperature-dependent and saturable in both species with Km values of 4.7 and 2.8 μmol/L, respectively. M-I uptake was also inhibited by cyclosporin A, an inhibitor for hepatic uptake transporters including organic anion transporting polypeptide (OATP). In the human hepatocytes, M-I uptake was hardly inhibited by estrone 3-sulfate as an inhibitor for OATP1B1, and most of the M-I uptake was Na(+)-independent. Uptake studies using human transporter-expressing cells revealed the saturable uptake of M-I for OATP1B3 with a Km of 2.13 μmol/L. No obvious uptake of M-I was observed in the OATP1B1-expressing cells.These results indicated that M-I was taken up into hepatocytes via transporters in both rats and humans. OATP1B3 would be mainly involved in the hepatic uptake of M-I in humans. These findings suggested that hepatic uptake transporters might contribute to the liver-selective inhibition of cholesterol synthesis by TAK-475. This is the first to clarify a carrier-mediated hepatic uptake mechanism for squalene synthase inhibitors. © Georg Thieme Verlag KG Stuttgart · New York.

Repositioning Of Tak-475 In Mevalonate Kinase Disease: Translating Theory Into Practice.

PubMed

Marcuzzi, Annalisa; Loganes, Claudia; Celeghini, Claudio; Kleiner, Giulio

2017-09-11

Mevalonate Kinase Deficiency (MKD, OMIM #610377) is a rare autosomal recessive metabolic and inflammatory disease. In MKD, defective function of the enzyme mevalonate kinase (MK), due to a mutation in the MVK gene, leads to the shortage of mevalonate-derived intermediates, which results in unbalanced prenylation of proteins and altered metabolism of sterols. These defects lead to a complex multisystem inflammatory and metabolic syndrome. Although biologic therapies aimed at blocking the inflammatory cytokine interleukin-1 (IL-1) can significantly reduce inflammation, they cannot completely control the clinical symptoms that affects the nervous system. For this reason, MKD can still be considered an orphan drug disease. Cellular models for MKD can be obtained by biochemical inhibition of mevalonate-derived isoprenoids. Of note, these cells present an exaggerated response to inflammatory stimuli that can be reduced by treatment with zaragozic acid, an inhibitor of squalene synthase (SQS) able to increase the availability of isoprenoids intermediates upstream the enzymatic block. A similar action might be obtained by lapaquistat acetate (TAK-475, Takeda), a drug that underwent extensive clinical trials as a cholesterol lowering agent 10 years ago, with a good safety profile. Here we describe the preclinical evidence supporting the possible repositioning of TAK-475 from its originally intended use to the treatment of MKD and discuss its potential to modulate the mevalonate pathway in inflammatory diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation.

PubMed

Ho, Yik-Khuan; Zhi, Huijun; Bowlin, Tara; Dorjbal, Batsukh; Philip, Subha; Zahoor, Muhammad Atif; Shih, Hsiu-Ming; Semmes, Oliver John; Schaefer, Brian; Glover, J N Mark; Giam, Chou-Zen

2015-08-01

Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells.

HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation

PubMed Central

Ho, Yik-Khuan; Zhi, Huijun; Bowlin, Tara; Dorjbal, Batsukh; Philip, Subha; Zahoor, Muhammad Atif; Shih, Hsiu-Ming; Semmes, Oliver John; Schaefer, Brian; Glover, J. N. Mark; Giam, Chou-Zen

2015-01-01

Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells. PMID:26285145

Computer Modeling of the Instructionally Insensitive Nature of the Texas Assessment of Knowledge and Skills (TAKS) Exam

ERIC Educational Resources Information Center

Pham, Vinh Huy

2009-01-01

Stakeholders of the educational system assume that standardized tests are transparently about the subject content being tested and therefore can be used as a metric to measure achievement in outcome-based educational reform. Both analysis of longitudinal data for the Texas Assessment of Knowledge and Skills (TAKS) exam and agent based computer…

The Effects of CSCOPE on Student Achievement as Measured by Both TAKS and STAAR Test Results

ERIC Educational Resources Information Center

Helm, Maricela Robledo

2013-01-01

The purpose of this study was to examine the effects of CSCOPE curriculum on student achievement. CSCOPE is a curriculum management system used in 750 of the 1,039 school districts in the state of Texas. Student achievement is based on the results acquired from the Texas Assessment of Knowledge and Skills (TAKS) and the new version of the state…

Domain Specificity of MAP3K Family Members, MLK and Tak1, for JNK Signaling in Drosophila

PubMed Central

Stronach, Beth; Lennox, Ashley L.; Garlena, Rebecca A.

2014-01-01

A highly diverse set of protein kinases functions as early responders in the mitogen- and stress-activated protein kinase (MAPK/SAPK) signaling pathways. For instance, humans possess 14 MAPK kinase kinases (MAP3Ks) that activate Jun kinase (JNK) signaling downstream. A major challenge is to decipher the selective and redundant functions of these upstream MAP3Ks. Taking advantage of the relative simplicity of Drosophila melanogaster as a model system, we assessed MAP3K signaling specificity in several JNK-dependent processes during development and stress response. Our approach was to generate molecular chimeras between two MAP3K family members, the mixed lineage kinase, Slpr, and the TGF-β activated kinase, Tak1, which share 32% amino acid identity across the kinase domain but otherwise differ in sequence and domain structure, and then test the contributions of various domains for protein localization, complementation of mutants, and activation of signaling. We found that overexpression of the wild-type kinases stimulated JNK signaling in alternate contexts, so cells were capable of responding to both MAP3Ks, but with distinct outcomes. Relative to wild-type, the catalytic domain swaps compensated weakly or not at all, despite having a shared substrate, the JNK kinase Hep. Tak1 C-terminal domain-containing constructs were inhibitory in Tak1 signaling contexts, including tumor necrosis factor-dependent cell death and innate immune signaling; however, depressing antimicrobial gene expression did not necessarily cause phenotypic susceptibility to infection. These same constructs were neutral in the context of Slpr-dependent developmental signaling, reflecting differential subcellular protein localization and by inference, point of activation. Altogether, our findings suggest that the selective deployment of a particular MAP3K can be attributed in part to its inherent sequence differences, cellular localization, and binding partner availability. PMID:24429281

Barriers to immunization among children of migrant workers from Myanmar living in Tak province, Thailand.

PubMed Central

Plugge, Emma; Suwanjatuporn, Suporn; Sombatrungjaroen, Suteera; Nosten, François

2011-01-01

Abstract Problem Immunization is a cost-effective means of improving child survival but implementation of programmes in low- and middle-income countries is variable. Children of migrants are less likely to be immunized. Approach The qualitative study aimed to identify barriers to the successful implementation of migrant immunization programmes in Tak province, Thailand. We ran a total of 53 focus groups involving 371 participants in three sites. Local setting Tak province in Thailand borders Myanmar and has an estimated 200 000 migrants from Myanmar. Vaccine-preventable diseases are a documented cause of morbidity in this population but there is no systematic or coordinated immunization programme in the area. Relevant changes As a result of the findings, the subsequent immunization campaign targeted children in school to overcome those barriers of distance to immunization services, fear of arrest, not remembering immunization appointments, and the disruption of parental work. The campaigns also included immunization education for both parents and teachers. Lessons learnt Migrant parents identified similar barriers to accessing childhood immunization programmes as migrant populations elsewhere in the world, although a unique barrier identified by parents from Myanmar was “fear of arrest”. The subsequent school-based strategy to overcome these barriers appears to be effective. PMID:21734767

The PPARβ/δ agonist GW501516 attenuates peritonitis in peritoneal fibrosis via inhibition of TAK1-NFκB pathway in rats.

PubMed

Su, Xuesong; Zhou, Guangyu; Wang, Yanqiu; Yang, Xu; Li, Li; Yu, Rui; Li, Detian

2014-06-01

Peritoneal fibrosis is a common consequence of long-term peritoneal dialysis (PD), and peritonitis is a factor in its onset. Agonist-bound peroxisome proliferator-activated receptors (PPARs) function as key regulators of energy metabolism and inflammation. Here, we examined the effects of PPARβ/δ agonist GW501516 on peritonitis in a rat peritoneal fibrosis model. Peritoneal fibrosis secondary to inflammation was induced into uremic rats by daily injection of Dianeal 4.25% PD solutions along with six doses of lipopolysaccharide before commencement of GW501516 treatment. Normal non-uremic rats served as control, and all rats were fed with a control diet or a GW501516-containing diet. Compared to control group, exposure to PD fluids caused peritoneal fibrosis that was accompanied by increased mRNA levels of monocyte chemoattractant protein-1, tumor necrotic factor-α, and interleukin-6 in the uremic rats, and these effects were prevented by GW501516 treatment. Moreover, GW501516 was found to attenuate glucose-stimulated inflammation in cultured rat peritoneal mesothelial cells via inhibition of transforming growth factor-β-activated kinase 1 (TAK1), and nuclear factor kappa B (NFκB) signaling pathway (TAK1-NFκB pathway), a main inflammation regulatory pathway. In conclusion, inhibition of TAK1-NFκB pathway with GW501516 may represent a novel therapeutic approach to ameliorate peritonitis-induced peritoneal fibrosis for patients on PD.

Access to free or low-cost tuberculosis treatment for migrants and refugees along the Thailand-Myanmar border in Tak province, Thailand.

PubMed

Tschirhart, Naomi; Nosten, Francois; Foster, Angel M

2016-07-07

In Tak province, Thailand migrants and refugees from Myanmar navigate a pluralistic healthcare system to seek Tuberculosis (TB) care from a variety of government and non-governmental providers. This multi-methods qualitative study examined access to TB, TB/HIV and multidrug-resistant tuberculosis (MDR-TB) treatment with an emphasis on barriers to care and enabling factors. In the summer and fall of 2014, we conducted 12 key informant interviews with public health officials and TB treatment providers. We also conducted 11 focus group discussions with migrants and refugees who were receiving TB, TB/HIV and MDR-TB treatment in Tak province as well as non-TB patients. We analyzed these data through thematic analysis using both predetermined and emergent codes. As a second step in the qualitative analysis, we explored the barriers and enabling factors separately for migrants and refugees. We found that refugees face fewer barriers to accessing TB treatment than migrants. For both migrants and refugees, legal status plays an important intermediary role in influencing the population's ability to access care and eligibility for treatment. Our results suggest that there is a large geographical catchment area for migrants who seek TB treatment in Tak province that extends beyond provincial boundaries. Migrant participants described their ability to seek care as linked to the financial and non-financial resources required to travel and undergo treatment. Patients identified language of health services, availability of free or low cost services, and psychosocial support as important health system characteristics that affect accessibility. Access to TB treatment for migrants and refugees occurs at the interface of health system accessibility, population ability and legal status. In Tak province, migrant patients draw upon their social networks and financial resources to navigate a pathway to treatment. We revised a conceptual framework for access to healthcare to incorporate

Homoharringtonine combined with aclarubicin and cytarabine synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein.

PubMed

Cao, Jiang; Feng, Hao; Ding, Ning-Ning; Wu, Qing-Yun; Chen, Chong; Niu, Ming-Shan; Chen, Wei; Qiu, Ting-Ting; Zhu, Hong-Hu; Xu, Kai-Lin

2016-11-01

Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML. However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain unclear. In this study, SKNO-1 and Kasumi-1 cells with t(8;21) were used. Compared with individual or pairwise administration of homoharringtonine, aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and induction of apoptosis in SKNO-1 and Kasumi-1 cells. HAA caused cleavage of the AML1-ETO (AE) oncoprotein to form truncated AE (ΔAE). Pretreatment with the caspase-3 inhibitor caspase-3 inhibitor Q-DEVD-OPh (QDO) not only suppressed HAA-induced apoptosis but also abrogated the cleavage of AE and generation of ΔAE. These results suggest that HAA synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein, thus providing direct evidence for the strong activity of HAA toward t(8;21) AML. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Social Marketing in Malaysia: Cognitive, Affective, and Normative Mediators of the TAK NAK Antismoking Advertising Campaign.

PubMed

Lee, Wonkyong Beth; Fong, Geoffrey T; Dewhirst, Timothy; Kennedy, Ryan D; Yong, Hua-Hie; Borland, Ron; Awang, Rahmat; Omar, Maizurah

2015-01-01

Antismoking mass media campaigns are known to be effective as part of comprehensive tobacco control programs in high-income countries, but such campaigns are relatively new in low- and middle-income countries and there is a need for strong evaluation studies from these regions. This study examines Malaysia's first national antismoking campaign, TAK NAK. The data are from the International Tobacco Control Malaysia Survey, which is an ongoing cohort survey of a nationally representative sample of adult smokers (18 years and older; N = 2,006). The outcome variable was quit intentions of adult smokers, and the authors assessed the extent to which quit intentions may have been strengthened by exposure to the antismoking campaign. The authors also tested whether the impact of the campaign on quit intentions was related to cognitive mechanisms (increasing thoughts about the harm of smoking), affective mechanisms (increasing fear from the campaign), and perceived social norms (increasing perceived social disapproval about smoking). Mediational regression analyses revealed that thoughts about the harm of smoking, fear arousal, and social norms against smoking mediated the relation between TAK NAK impact and quit intentions. Effective campaigns should prompt smokers to engage in both cognitive and affective processes and encourage consideration of social norms about smoking in their society.

Momordica charantia Inhibits Inflammatory Responses in Murine Macrophages via Suppression of TAK1.

PubMed

Yang, Woo Seok; Yang, Eunju; Kim, Min-Jeong; Jeong, Deok; Yoon, Deok Hyo; Sung, Gi-Ho; Lee, Seungihm; Yoo, Byong Chul; Yeo, Seung-Gu; Cho, Jae Youl

2018-01-01

Momordica charantia known as bitter melon is a representative medicinal plant reported to exhibit numerous pharmacological activities such as antibacterial, antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic actions. Although this plant has high ethnopharmacological value for treating inflammatory diseases, the molecular mechanisms by which it inhibits the inflammatory response are not fully understood. In this study, we aim to identify the anti-inflammatory mechanism of this plant. To this end, we studied the effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production, mRNA expression of inflammatory genes, luciferase reporter gene activity, and putative molecular targets. Mc-ME blocked NO production in a dose-dependent manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover, the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME decreases the levels of p65 [a nuclear factor (NF)-[Formula: see text]B subunit] and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting assays, luciferase assays, and overexpression experiments suggested that transforming growth factor [Formula: see text]-activated kinase 1 (TAK1) is targeted by Mc-ME, thereby suppressing NF-[Formula: see text]B and AP-1 activity via downregulation of extracellular signal-regulated kinases (ERKs) and AKT. These results strongly suggest that Mc-ME exerts its anti-inflammatory activity by reducing the action of TAK1, which also affects the activation of NF-[Formula: see text]B and AP-1.

Vertical distribution of clouds over Hampton, Virginia observed by lidar under the ECLIPS and FIRE ETO programs

NASA Technical Reports Server (NTRS)

Vaughan, M. A.; Winker, D. M.

1994-01-01

Intensive cloud lidar observations have been made by NASA Langley Research Center during the two observation phases of the ECLIPS project. Less intensive but longer term observations have been conducted as part of the FIRE extended time observation (ETO) program since 1987. We present a preliminary analysis of the vertical distribution of clouds based on these observations. A mean cirrus thickness of just under 1 km has been observed with a mean altitude of about 80 percent of the tropopause height. Based on the lidar data, cirrus coverage was estimated to be just under 20 percent, representing roughly 50 percent of all clouds studied. Cirrus was observed to have less seasonal variation than lower clouds. Mid-level clouds are found to occur primarily in association with frontal activity.

Effects of TGF-β1 on plasminogen activation in human dental pulp cells: Role of ALK5/Smad2, TAK1 and MEK/ERK signalling.

PubMed

Chang, Mei-Chi; Chang, Hsiao-Hua; Lin, Po-Shuan; Huang, Yu-An; Chan, Chiu-Po; Tsai, Yi-Ling; Lee, Shen-Yang; Jeng, Po-Yuan; Kuo, Han-Yueh; Yeung, Sin-Yuet; Jeng, Jiiang-Huei

2018-04-01

Transforming growth factor-β1 (TGF-β1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-β1 on PA system of dental pulp cells and its signalling pathways. Dental pulp cells were treated with different concentrations of TGF-β1. MTT assay, reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-β1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion. The phosphorylation of Smad2 and TAK1 was analysed by Pathscan ELISA or Western blotting. Cells were pretreated with SB431542 (ALK5/Smad2/3 inhibitor), 5z-7-oxozeaenol (TAK1 inhibitor) and U0126 (MEK/ERK inhibitor) for examining the related signalling. TGF-β1 slightly inhibited cell growth that was reversed by SB431542. TGF-β1 upregulated both RNA and protein expression of PAI-1 and uPAR, whereas it downregulated uPA expression. Accordingly, TGF-β1 stimulated PAI-1 and soluble uPAR (suPAR) secretion of pulp cells, whereas uPA secretion was inhibited. TGF-β1 induced the phosphorylation of Smad2 and TAK1. In addition, SB431542, 5z-7-oxozeaenol and U0126 attenuated the TGF-β1-induced secretion of PAI-1 and suPAR. These results indicate that TGF-β1 is possibly involved in the repair/regeneration and inflammatory processes of dental pulp via regulation of PAI-1, uPA and uPAR. These effects of TGF-β1 are related to activation of ALK5/Smad2, TAK1 and MEK/ERK signalling pathways. Clarifying the signal transduction for the effects of TGF-β1 is helpful for pulpo-dentin regeneration and tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Use of psi(alpha)-ETOs in the unified treatment of electronic attraction, electric field and electric field gradient multicenter integrals of screened Coulomb potentials over Slater orbitals.

PubMed

Guseinov, Israfil

2004-02-01

In this study, using complete orthonormal sets of Psi(alpha)-ETOs (where alpha=1, 0, -1, -2, ...) introduced by the author, a large number of series expansion formulae for the multicenter electronic attraction (EA), electric field (EF) and electric field gradient (EFG) integrals of the Yukawa-like screened Coulomb potentials (SCPs) is presented through the new central and noncentral potentials and the overlap integrals with the same screening constants. The final results obtained are valid for arbitrary locations of STOs and their parameters.

AC Power at Power Frequencies: Bilateral comparison between SASO NMCC and TÜBİTAK UME

NASA Astrophysics Data System (ADS)

Çaycı, Hüseyin; Yılmaz, Özlem; AlRobaish, Abdullah M.; AlAnazi, Shafi S.; AlAyali, Ahmed R.; AlRumie, Rashed A.

2018-01-01

A supplementary bilateral comparison measurement on AC Power at 50/60 Hz between SASO NMCC (GULFMET) and TÜBİTAK UME (EURAMET) was performed with the primary power standards of each partner. Measurement methods and setups which are very similar of the participants, measurement results, calculation of differences in the results, evaluation of uncertainties are given within this report. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Characterization of Pressure Fields of Focused Transducers at TÜBİTAK UME

NASA Astrophysics Data System (ADS)

Karaböce, B.; Şahin, A.; İnce, A. T.; Skarlatos, Y.

Field radiated by HIFU (High Intensity Focused Ultrasound) has been investigated by measuring its pressure field and mapping in 2-D and 3-D. A new ultrasound pressure measurement system has been designed and constructed at TÜBİTAK UME (The Scientific and Technological Research Council of Turkey, the National Metrology Institute). System consists of a water tank, positioning system, measurement devices and a controlling program. The hydrophone was attached to a 3-axis, computer-controlled positioning system for alignment with the ultrasound source. The signal was captured and analyzed by the commercially available LabVIEW 8.1 software. The measurements of the ultrasound field were carried out with a needle hydrophone. For each waveform, p, p+ and p-pressures have been calculated. Wave behaviors produced by the KZK model and from experiments look like similar in general. In p, p+, p- the focal point, zero point after the primary peak (focus) and extremum points in the near field well match.

Thyroid hormone activates rat liver adenosine 5,-monophosphate-activated protein kinase: relation to CaMKKb, TAK1 and LKB1 expression and energy status.

PubMed

Vargas, R; Ortega, Y; Bozo, V; Andrade, M; Minuzzi, G; Cornejo, P; Fernandez, V; Videla, L A

2013-01-01

AMP-activated protein kinase (AMPK) is a sensor of energy status supporting cellular energy homeostasis that may represent the metabolic basis for 3,3,,5-triiodo-L-thyronine (T3) liver preconditioning. Functionally transient hyperthyroid state induced by T3 (single dose of 0.1 mg/kg) in fed rats led to upregulation of mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of hepatic AMPK at 8 to 36 h after treatment. AMPK Thr 172 phosphorylation induced by T3 is associated with enhanced mRNA expression of the upstream kinases Ca2+ -calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) and transforming growth-factor-beta-activated kinase-1 (TAK1), with increased protein levels of CaMKKbeta and higher TAK1 phosphorylation, without changes in those of the liver kinase B1 (LKB1) signaling pathway. Liver contents of AMP and ADP were augmented by 291 percent and 44 percent by T3 compared to control values (p less than 0.05), respectively, whereas those of ATP decreased by 64% (p less than 0.05), with no significant changes in the total content of adenine nucleotides (AMP + ADP + ATP) at 24 h after T3 administration. Consequently, hepatic ATP/ADP content ratios exhibited 64 percent diminution (p less than 0.05) and those of AMP/ATP increased by 425 percent (p less than 0.05) in T3-treated rats over controls. It is concluded that in vivoT3 administration triggers liver AMPK upregulation in association with significant enhancements in AMPK mRNA expression, AMPK phosphorylation coupled to CaMKKbeta and TAK1 activation, and in AMP/ATP ratios, which may promote enhanced AMPK activity to support T3-induced energy consuming processes such as those of liver preconditioning.

Myostatin induces interstitial fibrosis in the heart via TAK1 and p38.

PubMed

Biesemann, Nadine; Mendler, Luca; Kostin, Sawa; Wietelmann, Astrid; Borchardt, Thilo; Braun, Thomas

2015-09-01

Myostatin, a member of the TGF-β superfamily of secreted growth factors, is a negative regulator of skeletal muscle growth. In the heart, it is expressed at lower levels compared to skeletal muscle but up-regulated under disease conditions. Cre recombinase-mediated inactivation of myostatin in adult cardiomyocytes leads to heart failure and increased mortality but cardiac function of surviving mice is restored after several weeks probably due to compensatory expression in non-cardiomyocytes. To study long-term effects of increased myostatin expression in the heart and to analyze the putative crosstalk between cardiomyocytes and fibroblasts, we overexpressed myostatin in cardiomyocytes. Increased expression of myostatin in heart muscle cells caused interstitial fibrosis via activation of the TAK-1-MKK3/6-p38 signaling pathway, compromising cardiac function in older mice. Our results uncover a novel role of myostatin in the heart and highlight the necessity for tight regulation of myostatin to maintain normal heart function.

Effect of three fatty acids from the leaf extract of Tiliacora triandra on P-glycoprotein function in multidrug-resistant A549RT-eto cell line.

PubMed

Kaewpiboon, Chutima; Winayanuwattikun, Pakorn; Yongvanich, Tikamporn; Phuwapraisirisan, Preecha; Assavalapsakul, Wanchai

2014-08-01

Cancer cells have the ability to develop resistance to chemotherapy drugs, which then leads to a reduced effectiveness and success of the treatment. Multidrug resistance (MDR) involves the resistance in the same cell/tissue to a diverse range of drugs of different structures. One of the characteristics of MDR is an overexpression of P-glycoprotein (P-gp), which causes the efflux of the accumulated drug out of the cell. The MDR human non-small cell lung carcinoma cell line with a high P-gp expression level (A549RT-eto) was used to investigate the bioactive compounds capable of reversing the etoposide resistance in this cell line. The leaves of Tiliacora triandra were sequentially extracted with hexane, dichloromethane, methanol and water. Only the hexane extract reduced the etoposide resistance of the A549RT-eto cell line, and was further fractionated by column chromatography using the TLC-pattern and the restoration of etoposide sensitivity as the selection criteria. The obtained active fraction (F22) was found by nuclear magnetic resonance and gas chromatography-mass spectroscopy analyses to be comprised of a 49.5:19.6:30.9 (w/w/w) mixture of hexadecanoic: octadecanoic acid: (Z)-6-octadecenoic acids. This stoichiometric mixture was recreated using pure fatty acids (MSFA) and gave a similar sensitization to etoposide and enhanced the relative rate of rhodamine-123 accumulation to a similar extent as F22, supporting the action via reducing P-gp activity. In contrast, the fatty acids alone did not show this effect. This is the first report of the biological activity from the leaves of T. triandra as a potential source of a novel chemosensitizer.

Effect of three fatty acids from the leaf extract of Tiliacora triandra on P-glycoprotein function in multidrug-resistant A549RT-eto cell line

PubMed Central

Kaewpiboon, Chutima; Winayanuwattikun, Pakorn; Yongvanich, Tikamporn; Phuwapraisirisan, Preecha; Assavalapsakul, Wanchai

2014-01-01

Background: Cancer cells have the ability to develop resistance to chemotherapy drugs, which then leads to a reduced effectiveness and success of the treatment. Multidrug resistance (MDR) involves the resistance in the same cell/tissue to a diverse range of drugs of different structures. One of the characteristics of MDR is an overexpression of P-glycoprotein (P-gp), which causes the efflux of the accumulated drug out of the cell. The MDR human non-small cell lung carcinoma cell line with a high P-gp expression level (A549RT-eto) was used to investigate the bioactive compounds capable of reversing the etoposide resistance in this cell line. Materials and Methods: The leaves of Tiliacora triandra were sequentially extracted with hexane, dichloromethane, methanol and water. Only the hexane extract reduced the etoposide resistance of the A549RT-eto cell line, and was further fractionated by column chromatography using the TLC-pattern and the restoration of etoposide sensitivity as the selection criteria. Results: The obtained active fraction (F22) was found by nuclear magnetic resonance and gas chromatography-mass spectroscopy analyses to be comprised of a 49.5:19.6:30.9 (w/w/w) mixture of hexadecanoic: octadecanoic acid: (Z)-6-octadecenoic acids. This stoichiometric mixture was recreated using pure fatty acids (MSFA) and gave a similar sensitization to etoposide and enhanced the relative rate of rhodamine-123 accumulation to a similar extent as F22, supporting the action via reducing P-gp activity. In contrast, the fatty acids alone did not show this effect. Conclusion: This is the first report of the biological activity from the leaves of T. triandra as a potential source of a novel chemosensitizer. PMID:25298673

Computer Modeling of the Instructionally Insensitive Nature of the Texas Assessment of Knowledge and Skills (TAKS) Exam

NASA Astrophysics Data System (ADS)

Pham, Vinh Huy

Stakeholders of the educational system assume that standardized tests are transparently about the subject content being tested and therefore can be used as a metric to measure achievement in outcome-based educational reform. Both analysis of longitudinal data for the Texas Assessment of Knowledge and Skills (TAKS) exam and agent based computer modeling of its underlying theoretical testing framework have yielded results that indicate the exam only rank orders students on a persistent but uncharacterized latent trait across domains tested as well as across years. Such persistent rank ordering of students is indicative of an instructionally insensitive exam. This is problematic in the current atmosphere of high stakes testing which holds teachers, administrators, and school systems accountable for student achievement.

Kinetic Modeling of the Release of Ethylene Oxide from Sterilized Plastic Containers and its Interaction with Monoclonal Antibodies.

PubMed

Yu, Bryan Lei; Han, Jun; Hammond, Matthew; Wang, Xuemei; Zhang, Qingchun; Clausen, Andrew; Forster, Ronald; Eu, Mingda

Ethylene oxide (ETO) is commonly used to sterilize plastic containers, but the effects of residual amounts left after sterilization on protein therapeutics are still not well understood. Here we focus primarily on the factors that influence concentrations of ETO migrating from ETO-treated plastic containers into aqueous solution. A study was designed to investigate the kinetics of this process at various temperatures, and the kinetic data could be fit with a model based on a combination of Fickean diffusion and first-order chemical reaction (to account for observed hydrolysis of ETO). The diffusion and reaction rate constants thus obtained obey Arrhenius-like temperature dependence. These results indicate that for analytical methods involving extraction into water, measurements of residual ETO in a container must account for the effects of ETO hydrolysis. Further, the effects of salt concentration and pH of the fluid in the container on accumulated ETO levels were explored. Finally, interactions of ETO with anti-streptavidin (AntiSA) Immunoglobulin G1 (IgG1) and IgG2 antibodies were studied, with ETO adducts found on all methionine residues when incubated in solutions spiked with ETO at concentrations that could be reached (based on the kinetic studies) in ETO-treated plastic vials. Overall, the likelihood of observable ETO-protein modifications upon storage in ETO-sterilized containers will depend on a complex interplay of protein properties, formulation details, storage conditions, and amount of residual ETO initially in the container. Ethylene oxide (ETO) is commonly used to sterilize plastic containers, but the effects of residual amounts left after sterilization on protein therapeutics are still not well understood. Here we describe experiments exploring the factors that influence concentrations of ETO migrating from ETO-treated plastic containers into aqueous solution over time. Additionally, interactions of ETO with model antibodies were studied, with ETO

Comparison of sum-of-hourly and daily time step standardized ASCE Penman-Monteith reference evapotranspiration

NASA Astrophysics Data System (ADS)

Djaman, Koffi; Irmak, Suat; Sall, Mamadou; Sow, Abdoulaye; Kabenge, Isa

2017-10-01

The objective of this study was to quantify differences associated with using 24-h time step reference evapotranspiration (ETo), as compared with the sum of hourly ETo computations with the standardized ASCE Penman-Monteith (ASCE-PM) model for semi-arid dry conditions at Fanaye and Ndiaye (Senegal) and semiarid humid conditions at Sapu (The Gambia) and Kankan (Guinea). The results showed that there was good agreement between the sum of hourly ETo and daily time step ETo at all four locations. The daily time step overestimated the daily ETo relative to the sum of hourly ETo by 1.3 to 8% for the whole study periods. However, there is location and monthly dependence of the magnitude of ETo values and the ratio of the ETo values estimated by both methods. Sum of hourly ETo tends to give higher ETo during winter time at Fanaye and Sapu, while the daily ETo was higher from March to November at the same weather stations. At Ndiaye and Kankan, daily time step estimates of ETo were high during the year. The simple linear regression slopes between the sum of 24-h ETo and the daily time step ETo at all weather stations varied from 1.02 to 1.08 with high coefficient of determination (R 2 ≥ 0.87). Application of the hourly ETo estimation method might help on accurate ETo estimation to meet irrigation requirement under precision agriculture.

Preparation of Novel Hydrolyzing Urethane Modified Thiol-Ene Networks

DTIC Science & Technology

2011-10-25

EtO EtO EtO Si EtO OEt OEt O OEt Si OEt OEt OEt HO HOEt H H O H H H Si OEt EtO EtO ... EtO H H SiO H H OEt OEt OEt H Polymers 2011, 3 1851 Thiol-ene “click” chemistry, as a means to form polymer networks...Table 3. Analysis of kinetic rates for fluorine modified systems. Sample name a Zero order k r2 First order k r2 Higuchi KH r2

Kinetic Modeling of the Release of Ethylene Oxide from Sterilized Plastic Containers and its Interaction with Monoclonal Antibodies.

PubMed

Yu, Bryan Lei; Han, Jun; Hammond, Matthew; Wang, Xuemei; Zhang, Qingchun; Clausen, Andrew; Forster, Ronald; Eu, Mingda

2016-12-14

Ethylene oxide (ETO) is commonly used to sterilize plastic containers, but the effects of residual amounts left after sterilization on protein therapeutics are still not well understood. Here we focus primarily on the factors that influence concentrations of ETO migrating from ETO-treated plastic containers. A study was designed to investigate the kinetics of this process at various temperatures, and the kinetic data could be fit with a model based on a combination of Fickean diffusion and first order chemical reaction (to account for observed hydrolysis of ETO). The diffusion and reaction rate constants thus obtained obey Arrhenius-like temperature dependence. These results indicate that even with the use of an effective extraction protocol and sensitive analytical method, measurements of residual ETO in a container must account for the effects of ETO hydrolysis. Further, the effects of salt concentration and pH of the fluid in the container on accumulated ETO levels were explored. Finally, interactions of ETO with anti-streptavidin (AntiSA) IgG1 and IgG2 antibodies were studied, with ETO adducts found on all methionine residues when incubated in solutions spiked with ETO at concentrations that could be reached (based on the kinetic studies) in ETO-treated plastic vials. Overall, the likelihood of observable ETO-protein modifications upon storage in ETO-sterilized containers will depend on a complex interplay of protein properties, formulation details, storage conditions, and amount of residual ETO initially in the container. Copyright © 2016, Parenteral Drug Association.

Expanding the geography of evapotranspiration: An improved method to quantify land-to-air water fluxes in tropical and subtropical regions

PubMed Central

Jerszurki, Daniela; Souza, Jorge L. M.; Silva, Lucas C. R.

2017-01-01

The development of new reference evapotranspiration (ETo) methods hold significant promise for improving our quantitative understanding of climatic impacts on water loss from the land to the atmosphere. To address the challenge of estimating ETo in tropical and subtropical regions where direct measurements are scarce we tested a new method based on geographical patterns of extraterrestrial radiation (Ra) and atmospheric water potential (Ψair). Our approach consisted of generating daily estimates of ETo across several climate zones in Brazil–as a model system–which we compared with standard EToPM (Penman-Monteith) estimates. In contrast with EToPM, the simplified method (EToMJS) relies solely on Ψair calculated from widely available air temperature (oC) and relative humidity (%) data, which combined with Ra data resulted in reliable estimates of equivalent evaporation (Ee) and ETo. We used regression analyses of Ψair vs EToPM and Ee vs EToPM to calibrate the EToMJS(Ψair) and EToMJS estimates from 2004 to 2014 and between seasons and climatic zone. Finally, we evaluated the performance of the new method based on the coefficient of determination (R2) and correlation (R), index of agreement “d”, mean absolute error (MAE) and mean reason (MR). This evaluation confirmed the suitability of the EToMJS method for application in tropical and subtropical regions, where the climatic information needed for the standard EToPM calculation is absent. PMID:28658324

Expanding the geography of evapotranspiration: An improved method to quantify land-to-air water fluxes in tropical and subtropical regions.

PubMed

Jerszurki, Daniela; Souza, Jorge L M; Silva, Lucas C R

2017-01-01

The development of new reference evapotranspiration (ETo) methods hold significant promise for improving our quantitative understanding of climatic impacts on water loss from the land to the atmosphere. To address the challenge of estimating ETo in tropical and subtropical regions where direct measurements are scarce we tested a new method based on geographical patterns of extraterrestrial radiation (Ra) and atmospheric water potential (Ψair). Our approach consisted of generating daily estimates of ETo across several climate zones in Brazil-as a model system-which we compared with standard EToPM (Penman-Monteith) estimates. In contrast with EToPM, the simplified method (EToMJS) relies solely on Ψair calculated from widely available air temperature (oC) and relative humidity (%) data, which combined with Ra data resulted in reliable estimates of equivalent evaporation (Ee) and ETo. We used regression analyses of Ψair vs EToPM and Ee vs EToPM to calibrate the EToMJS(Ψair) and EToMJS estimates from 2004 to 2014 and between seasons and climatic zone. Finally, we evaluated the performance of the new method based on the coefficient of determination (R2) and correlation (R), index of agreement "d", mean absolute error (MAE) and mean reason (MR). This evaluation confirmed the suitability of the EToMJS method for application in tropical and subtropical regions, where the climatic information needed for the standard EToPM calculation is absent.

Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model

PubMed Central

Cabezas-Wallscheid, Nina; Eichwald, Victoria; de Graaf, Jos; Löwer, Martin; Lehr, Hans-Anton; Kreft, Andreas; Eshkind, Leonid; Hildebrandt, Andreas; Abassi, Yasmin; Heck, Rosario; Dehof, Anna Katharina; Ohngemach, Svetlana; Sprengel, Rolf; Wörtge, Simone; Schmitt, Steffen; Lotz, Johannes; Meyer, Claudius; Kindler, Thomas; Zhang, Dong-Er; Kaina, Bernd; Castle, John C; Trumpp, Andreas; Sahin, Ugur; Bockamp, Ernesto

2013-01-01

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option. PMID:24124051

TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenström's macroglobulinemia.

PubMed

Ghobrial, Irene M; Siegel, David S; Vij, Ravi; Berdeja, Jesus G; Richardson, Paul G; Neuwirth, Rachel; Patel, Chirag G; Zohren, Fabian; Wolf, Jeffrey L

2016-06-01

The PI3K/AKT/mTOR signaling pathways are frequently dysregulated in multiple human cancers, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Waldenström's macroglobulinemia (WM). This was the first clinical study to evaluate the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and preliminary clinical activity of TAK-228, an oral TORC1/2 inhibitor, in patients with MM, NHL, or WM. Thirty-nine patients received TAK-228 once daily (QD) at 2, 4, 6, or 7 mg, or QD for 3 days on and 4 days off each week (QDx3d QW) at 9 or 12 mg, in 28-day cycles. The overall median age was 61.0 years (range 46-85); 31 patients had MM, four NHL, and four WM. Cycle 1 DLTs occurred in five QD patients (stomatitis, urticaria, blood creatinine elevation, fatigue, and nausea and vomiting) and four QDx3d QW patients (erythematous rash, fatigue, asthenia, mucosal inflammation, and thrombocytopenia). The MTDs were determined to be 4 mg QD and 9 mg QDx3d QW. Thirty-six patients (92%) reported at least one drug-related toxicity; the most common grade ≥3 drug-related toxicities were thrombocytopenia (15%), fatigue (10%), and neutropenia (5%). TAK-228 exhibited a dose-dependent increase in plasma exposure and no appreciable accumulation with repeat dosing; mean plasma elimination half-life was 6-8 hr. Of the 33 response-evaluable patients, one MM patient had a minimal response, one WM patient achieved partial response, one WM patient had a minor response, and 18 patients (14 MM, two NHL, and two WM) had stable disease. These findings encourage further studies including combination strategies. © 2016 Wiley Periodicals, Inc.

Sorption characteristics of cadmium in a clay soil of Mae Ku creek, Tak Province, Thailand

NASA Astrophysics Data System (ADS)

Thunyawatcharakul, P.; Chotpantarat, S.

2018-05-01

Mae Sot is a district in Tak province, the northern part of Thailand where has encountered with cadmium (Cd) contaminated in soils. Exposure of Cd can lead to severe health effect, for examples, bone softening, osteoporosis, renal dysfunction, and Itai-Itai disease. This study aims at elucidating sorption behavior of Cd in the contaminated soil collected from Mae Ku creek, Mae Sot district, Thailand. Batch sorption experiment was conducted in order to investigate sorption characteristics of Cd onto the contaminated soil. The soil sample taken from the study area consists of 26% sand, 16% silt 58% clay, which categorized as a clay soil, based on USDA classification. Soil pH is slightly alkaline (pH∼7.7) and organic matter in the soil is 2.93%. The initial concentration in the batch sorption experiment was in the range from 0- 200 ppm. The result from the batch sorption experiment showed that soil sample can adsorb Cd up to 173.5 ppm and the sorption behavior of the soil sample can be well described by Freundlich isotherm, indicating the multilayer sorption (R2 = 0.9964), with Freundlich constants of 0.312 and 1.760 L g-1 for 1/n and Kf, respectively.

Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

PubMed

Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

2015-02-01

Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Toxic effect of ethylene-oxide-sterilized freeze-dried bone allograft on human gingival fibroblasts.

PubMed

Kudryk, V L; Scheidt, M J; McQuade, M J; Sutherland, D E; VanDyke, T E; Hollinger, J O

1992-11-01

Freeze-dried bone allograft (FDBA) which either had or had not been sterilized by exposure to ethylene oxide (EtO) prior to lyophilization was obtained from two commercial sources. EtO-sterilized FDBA was reexposed to EtO as a positive control. Gas chromatograph assays revealed that three out of four commercially obtained EtO sterilized FDBA had no detectable EtO, with one sample having 0.21 parts per million (PPM). Surprisingly, 0.24 PPM was detected in one sample which had not been sterilized with EtO gas. This was presumed due to contamination from a gas-sterilized rubber stopper. In the cell toxicity study, FDBA and human gingival fibroblasts (HGF) were added simultaneously, incubated for 72 h, and fixed and stained. Samples of FDBA sterilized with EtO which were free of EtO did not alter HGF growth. However, the positive control FDBA which contained 0.72 PPM EtO had a deleterious effect on HGF. FDBA with EtO residuals caused morphologic change in HGF.

Intracellular delivery of etoposide loaded biodegradable nanoparticles: cytotoxicity and cellular uptake studies.

PubMed

Yadav, Khushwant S; Jacob, Sheeba; Sachdeva, Geetanjali; Sawant, Krutika K

2011-08-01

The preferred delivery systems for anticancer drugs would be the one which would have selective and effective destruction of cancer cells. In the present study etoposide (ETO) loaded nanoparticles (NP) were prepared using PLGA (ETO-PLGA NP), PLGA-MPEG block copolymer (ETO-PLGA-MPEG NP) and PLGA-Pluronic copolymer (ETO-PLGA-PLU NP) and they were evaluated for cytotoxicity and cellular uptake studies using two cancer cell lines, L1210 and DU145. The IC50 values for L1210 cells were 18.0, 6.2, 4.8 and 5.4 microM and for DU145 cells the IC50 values were 98.4, 75.1, 60.1 and 71.3 microM for ETO, ETO-PLGA NP, ETO-PLGA-MPEG NP and ETO-PLGA-PLU NP respectively. The increased cytotoxicities were attributed to increased uptake of the NPs by the cells. Moreover the ETO loaded PLGA-MPEG NP and PLGA-Pluronic NP showed a sustained cytotoxic effect till 5 days on both the cell lines. Results of the long term cytotoxicity study concluded that the drug loaded PLGA nanoparticulate formulations were efficient in decreasing the viability of the L1210 cells over a period of three days, whereas the pure drug exerted its maximum efficiency on the day one itself. Z-stack confocal images of NPs showed fluorescence activity in each section of DU 145 and L1210 cells indicating that the nanoparticles were internalized by the cells. The study concluded that ETO loaded PLGA NPs had higher cytotoxicity compared with that of the free drug and ETO-PLGA-MPEG NP and ETO-PLGA-PLU NP had higher cell uptake efficiency compared with that of ETO-PLGA NP. The developed PLGA based NPs shows promise to be used for cancer therapy.

Daily reference crop evapotranspiration in the humid environments of Azores islands using reduced data sets: accuracy of FAO-PM temperature and Hargreaves-Samani methods

NASA Astrophysics Data System (ADS)

Paredes, P.; Fontes, J. C.; Azevedo, E. B.; Pereira, L. S.

2017-11-01

Reference crop evapotranspiration (ETo) estimations using the FAO Penman-Monteith equation (PM-ETo) require several weather variables that are often not available. Then, ETo may be computed with procedures proposed in FAO56, either using the PM-ETo equation with temperature estimates of actual vapor pressure (e a) and solar radiation (R s), and default wind speed values (u 2), the PMT method, or using the Hargreaves-Samani equation (HS). The accuracy of estimates of daily e a, R s, and u 2 is provided in a companion paper (Paredes et al. 2017) applied to data of 20 locations distributed through eight islands of Azores, thus focusing on humid environments. Both estimation procedures using the PMT method (ETo PMT) and the HS equation (ETo HS) were assessed by statistically comparing their results with those obtained for the PM-ETo with data of the same 20 locations. Results show that both approaches provide for accurate ETo estimations, with RMSE for PMT ranging 0.48-0.73 mm day-1 and for HS varying 0.47-0.86 mm day-1. It was observed that ETo PMT is linearly related with PM-ETo, while non-linearity was observed for ETo HS in weather stations located at high elevation. Impacts of wind were not important for HS but required proper adjustments in the case of PMT. Results show that the PMT approach is more accurate than HS. Moreover, PMT allows the use of observed variables together with estimators of the missing ones, which improves the accuracy of the PMT approach. The preference for the PMT method, fully based upon the PM-ETo equation, is therefore obvious.

The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO

PubMed Central

Chou, Fu-Sheng; Griesinger, Andrea; Wunderlich, Mark; Lin, Shan; Link, Kevin A.; Shrestha, Mahesh; Goyama, Susumu; Mizukawa, Benjamin; Shen, Shuhong; Marcucci, Guido

2012-01-01

AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL. PMID:22337712

Investigation on the Reference Evapotranspiration Distribution at Regional Scale By Alternative Methods to Compute the FAO Penman-Monteith Equation

NASA Astrophysics Data System (ADS)

Snyder, R. L.; Mancosu, N.; Spano, D.

2014-12-01

This study derived the summer (June-August) reference evapotranspiration distribution map for Sardinia (Italy) based on weather station data and use of the geographic information system (GIS). A modified daily Penman-Monteith equation from the Food and Agriculture Organization of the United Nations (UN-FAO) and the American Society of Civil Engineers Environmental and Water Resources Institute (ASCE-EWRI) was used to calculate the Standardized Reference Evapotranspiration (ETos) for all weather stations having a "full" set of required data for the calculations. For stations having only temperature data (partial stations), the Hargreaves-Samani equation was used to estimate the reference evapotranspiration for a grass surface (ETo). The ETos and ETo results were different depending on the local climate, so two methods to estimate ETos from the ETo were tested. Substitution of missing solar radiation, wind speed, and humidity data from a nearby station within a similar microclimate was found to give better results than using a calibration factor that related ETos and ETo. Therefore, the substitution method was used to estimate ETos at "partial" stations having only temperature data. The combination of 63 full and partial stations was sufficient to use GIS to map ETos for Sardinia. Three interpolation methods were studied, and the ordinary kriging model fitted the observed data better than a radial basis function or the inverse distance weighting method. Using station data points to create a regional map simplified the zonation of ETos when large scale computations were needed. Making a distinction based on ETos classes allows the simulation of crop water requirements for large areas and it can potentially lead to improved irrigation management and water savings. It also provides a baseline to investigate possible impact of climate change.

Comparison of liquid chemical sterilization with peracetic acid and ethylene oxide sterilization for long narrow lumens.

PubMed

Alfa, M J; DeGagne, P; Olson, N; Hizon, R

1998-10-01

The aim of this study was to determine how well peracetic acid liquid chemical sterilization (LCPAS) killed test organisms in the presence of 10% fetal bovine serum and 0.65% salt challenge (RPMI-S) compared with a 100% ethylene oxide (ETO) sterilizer and an ETO hydrochlorofluorocarbon (ETO-HCFC) sterilization method with long (125 cm), narrow (3-mm internal diameter) flexible lumens as the test carrier. The inoculated lumens were dried overnight before processing. The test organisms included Mycobacterium chelonei, Enterococcus faecalis, and Bacillus subtilis. For all 3 organisms tested, the LCPAS process resulted in a 6 log10 reduction in bacterial load compared with a 2.5 log10 to 6 log10 reduction for the 100% ETO and ETO-HCFC sterilizers. Sterilization was achieved for 100%, 61%, and 67% of the lumen test carriers for the LCPAS, 100% ETO, and ETO-HCFC sterilizers, respectively. The data indicate that of the sterilization methods evaluated, LCPAS was the most effective for sterilizing narrow flexible lumens in the presence of residual inorganic and organic soil. This effectiveness was achieved through a combination of organism wash-off and peracetic acid sterilant killing of organisms. Salt was the major compounding factor for effective ETO gas sterilization, because carriers inoculated with organisms in 10% fetal bovine serum alone all were sterilized by both 100% ETO and ETO-HCFC sterilization methods. Our data support the critical need to ensure adequate precleaning of narrow flexible lumen endoscopes before any sterilization method.

Preliminary study on assessment of lead exposure in Thai children aged between 3-7 years old who live in Umphang district, Tak Province.

PubMed

Neesanan, Naiyana; Kasemsup, Rachada; Ratanachuaeg, Suntree; Kojaranjit, Puangporn; Sakulnoom, Kim; Padungtod, Chantana

2011-08-01

Centers of Disease Control of the United States of America (CDC) informs Ministry of Public Health, Thailand that up to 13% of Burmese refugee children who are transferred to the United States of America during 2007-2009 have elevated blood lead levels (EBLL, Blood Lead Level > or = 10 microg/dl). These are children from a number of refugee camps in Tak Province; two camps are near Umphang but other camps are not. In June 2008, CDC, the result of investigation of Centers for Disease Control/Thailand Ministry of Public Health Collaboration (CDC/TUC) and International Organization for Migration, Thailand indicates that 33 of 64 children aged 6 months to 15 years (5.1%) who live in Mae La, Umpiem and Nupo camps have elevated blood lead level. However, no study on how Thai children who live nearby those camps are exposed to lead. Subsequently, Queen Sirikit National Institute of Child Health, Bangkok, Thailand contacts relevant organizations in Tak Province in order to investigate lead exposure and evaluate health status of Thai children who live close to Burmese refugee camps. 1) Evaluation of lead exposure of Thai children who live nearby Burmese refugee camps; 2) Assessment of risk factors on lead exposure of the children as mentioned above. The present study adopts a retrospective study based on information gathered from health assessment on 213 Thai children aged between 3-7 years old who live nearby Burmese refugee camps. The health assessment was conducted from April 30th, 2010 to May 5th, 2010. The information is from 3 sources. The first source is from blood sampling in order to assess lead level and ferritin level. The next source is from interview of persons who provide primary care in order to identify risk factors on lead exposure of target children. The last source is from physical examination and developmental assessment conducted by pediatricians and special nurses for child development in order to identify health and developmental problems. The

Spatial Interpolation of Reference Evapotranspiration in India: Comparison of IDW and Kriging Methods

NASA Astrophysics Data System (ADS)

Hodam, Sanayanbi; Sarkar, Sajal; Marak, Areor G. R.; Bandyopadhyay, A.; Bhadra, A.

2017-12-01

In the present study, to understand the spatial distribution characteristics of the ETo over India, spatial interpolation was performed on the means of 32 years (1971-2002) monthly data of 131 India Meteorological Department stations uniformly distributed over the country by two methods, namely, inverse distance weighted (IDW) interpolation and kriging. Kriging was found to be better while developing the monthly surfaces during cross-validation. However, in station-wise validation, IDW performed better than kriging in almost all the cases, hence is recommended for spatial interpolation of ETo and its governing meteorological parameters. This study also checked if direct kriging of FAO-56 Penman-Monteith (PM) (Allen et al. in Crop evapotranspiration—guidelines for computing crop water requirements, Irrigation and drainage paper 56, Food and Agriculture Organization of the United Nations (FAO), Rome, 1998) point ETo produced comparable results against ETo estimated with individually kriged weather parameters (indirect kriging). Indirect kriging performed marginally well compared to direct kriging. Point ETo values were extended to areal ETo values by IDW and FAO-56 PM mean ETo maps for India were developed to obtain sufficiently accurate ETo estimates at unknown locations.

Ethylene oxide sterilization: how hospitals can adapt to the changes.

PubMed

1994-12-01

Ethylene oxide (EtO) gas sterilizers have been used by hospitals for over 40 years to sterilize surgical equipment and supplies that are heat sensitive or that cannot tolerate excessive moisture. However, in recent decades, EtO has been recognized as a potential mutagenic, reproductive, neurologic, and fire and explosion hazard to workers, and one agency has reportedly voted to classify EtO as carcinogenic to humans. Strict regulations concerning EtO exposure have been imposed by the Occupational Safety and Health Administration (OSHA), and the use of EtO, along with other toxic pollutants, is also being monitored by the Environmental Protection Agency (EPA) under the Clean Air Act. In addition, the use of chlorofluorocarbons (CFCs) as EtO diluents has focused attention on the EtO-CFC mixtures used in many sterilizers because CFCs have been linked to destruction of the ozone layer. Concerns about restrictive regulations related to these issues have prompted many hospitals to examine their use of EtO sterilization and propagated the misinformation that EtO sterilization is being phased out. In this article, we address some commonly asked questions regarding the use and regulation of EtO mixtures, as well as alternative sterilization agents and methods; provide two case studies illustrating how hospitals can evaluate various sterilization options; and summarize our conclusions and recommendations for hospitals facing decisions about sterilization techniques. For related topics, also see our Evaluation Update on endoscope reprocessors and our Hazard Report on improperly connected EtO-CFC cylinders to EtO sterilizers in this issue.

C-terminal polymorphism of Plasmodium falciparium merozoite surface protein-1 (MSP-1) from Tak Province, Thailand.

PubMed

Viputtigul, Kwanjai; Tungpukdee, Noppadon; Ruangareerate, Toon; Luplertlop, Natthanej; Wilairatana, Polrat; Gaywee, Jariyanart; Krudsood, Srivicha

2013-01-01

This study was undertaken to ascertain the extent of polymorphism in the C-terminal region of Plasmodium falciparum merozoite surface protein (MSP-1) from 119 malaria patients in Tak Province on the western border of Thailand, who were admitted to the Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. P. falciparum infection was confirmed by microscopic examination of peripheral blood smears. Clinical manifestations were categorized into 2 groups: uncomplicated (94 cases) and complicated/severe (25 cases). A 1,040 basepair fragment of P. falciparum MSP-1 gene was compared with MSP-1 of reference strains retrieved from GenBank. The consensus sequences of MSP-1 block 16 showed it belonged to MAD20 genotype, which is the major allele of falciparum malaria from the western border of Thailand. MSP-1 block 16 amino acid fragment could be separated into 2 groups: similar and dissimilar to reference sequence. Four variations in MSP-1 block 16 were -1494K, D1510G, D1556N, and K1696I. MSP-1 block 16 diversity is not significantly associated with clinical manifestation although MAD 20 genotype is the predominant genotype in this area. The genetic data of MSP1 gene of faciparum malaria isolated from western Thai border contribute to the existing genetic database of Thai P. falciparum strain.

Drivers of atmospheric evaporative demand during African droughts

NASA Astrophysics Data System (ADS)

Blakeley, S. L.; Harrison, L.; Hobbins, M.; Dewes, C.; Funk, C. C.; Shukla, S.; Husak, G. J.

2017-12-01

Seeking to advance the practice of famine early warning across sub-Saharan Africa we illuminate past drivers of high-impact droughts to gain a better understanding of the evaporative processes involved in drought dynamics. Atmospheric evaporative demand (ETo) is often used to estimate plant water balance and drought impacts to vegetation, and previously demonstrated linkages between precipitation, temperature, and ETo need to be better understood. This work is timely as new data streams will enable near-real-time monitoring of ETo and incorporation of ETo forecasts into seasonal outlooks for African growing seasons. For historical droughts during major growing seasons in sub-Saharan Africa, we evaluate ETo and identify main drivers for drought cases-identified based on below-normal precipitation during the wettest three months of the growing season-and contrast these with the ETo drivers that dominate in wetter years (we also consider droughts triggered by above normal ETo). Our focus is on regions of Africa where adequate precipitation is important for productive agriculture and pastoral activities and where evaporative demand might exacerbate moisture limitations. It is expected that important ETo drivers are partly connected with precipitation-related processes but that there are variations between regions and events. The goal here is to provide a generalized understanding of what aspects of evaporative demand historically have posed an additional hazard to plant stress and how precipitation outcomes are responsible for the ETo drivers. In addition, we explore whether there have been discernible changes through time in regard to ETo drivers during below-normal precipitation seasons. Upper and lower terciles of CHIRPS precipitation are used to identify anomalous dry and wet cases. The ETo dataset spans the 1980-near present period and is calculated following ASCE's formulation of Penman-Monteith method driven by daily temperature, humidity, wind speed, and solar

A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos inhibits the production of inflammatory mediators and the IRAK-1/TAK1 and TBK1/IRF3 pathways in RAW 264.7 and THP-1 cells.

PubMed

Cheng, Brian Chi Yan; Yu, Hua; Su, Tao; Fu, Xiu-Qiong; Guo, Hui; Li, Ting; Cao, Hui-Hui; Tse, Anfernee Kai-Wing; Kwan, Hiu-Yee; Yu, Zhi-Ling

2015-11-04

As documented in the Chinese Materia Medica Grand Dictionary (), a herbal formula (RL) consisting of Rosae Multiflorae Fructus (multiflora rose hips) and Lonicerae Japonicae Flos (Japanese honeysuckle flowers) has traditionally been used in treating inflammatory disorders. RL was previously reported to inhibit the expression of various inflammatory mediators regulated by NF-κB and MAPKs that are components of the TLR4 signalling pathways. This study aims to provide further justification for clinical application of RL in treating inflammatory disorders by further delineating the involvement of the TLR4 signalling cascades in the effects of RL on inflammatory mediators. RL consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos (in 5:3 ratio) was extracted using absolute ethanol. We investigated the effect of RL on the production of cytokines and chemokines that are regulated by three key transcription factors of the TLR4 signalling pathways AP-1, NF-κB and IRF3 in LPS-stimulated RAW264.7 cells using the multiplex biometric immunoassay. Phosphorylation of AP-1, NF-κB, IRF3, IκB-α, IKKα/β, Akt, TAK1, TBK1, IRAK-1 and IRAK-4 were examined in LPS-stimulated RAW264.7 cells and THP-1 cells using Western blotting. Nuclear localizations of AP-1, NF-κB and IRF3 were also examined using Western blotting. RL reduced the secretion of various pro-inflammatory cytokines and chemokines regulated by transcription factors AP-1, NF-κB and IRF3. Phosphorylation and nuclear protein levels of these transcription factors were decreased by RL treatment. Moreover, RL inhibited the activation/phosphorylation of IκB-α, IKKα/β, TAK1, TBK1 and IRAK-1. Suppression of the IRAK-1/TAK1 and TBK1/IRF3 signalling pathways was associated with the effect of RL on inflammatory mediators in LPS-stimulated RAW264.7 and THP-1 cells. This provides further pharmacological basis for the clinical application of RL in the treatment of inflammatory disorders. Copyright © 2015 Elsevier

Innate immune signaling in Drosophila is regulated by transforming growth factor β (TGFβ)-activated kinase (Tak1)-triggered ubiquitin editing

PubMed Central

Chen, Li; Paquette, Nicholas; Mamoor, Shahan; Rus, Florentina; Nandy, Anubhab; Leszyk, John; Shaffer, Scott A.; Silverman, Neal

2017-01-01

Coordinated regulation of innate immune responses is necessary in all metazoans. In Drosophila the Imd pathway detects Gram-negative bacterial infections through recognition of diaminopimelic acid (DAP)-type peptidoglycan and activation of the NF-κB precursor Relish, which drives robust antimicrobial peptide gene expression. Imd is a receptor-proximal adaptor protein homologous to mammalian RIP1 that is regulated by proteolytic cleavage and Lys-63-polyubiquitination. However, the precise events and molecular mechanisms that control the post-translational modification of Imd remain unclear. Here, we demonstrate that Imd is rapidly Lys-63-polyubiquitinated at lysine residues 137 and 153 by the sequential action of two E2 enzymes, Ubc5 and Ubc13-Uev1a, in conjunction with the E3 ligase Diap2. Lys-63-ubiquitination activates the TGFβ-activated kinase (Tak1), which feeds back to phosphorylate Imd, triggering the removal of Lys-63 chains and the addition of Lys-48 polyubiquitin. This ubiquitin-editing process results in the proteasomal degradation of Imd, which we propose functions to restore homeostasis to the Drosophila immune response. PMID:28377500

CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yiting; Tu, Qunfei; Yan, Wei

Highlights: • CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-induced HepG2 cells. • CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells. • CXC195 regulated TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway in LPS-induced HepG2 cells. - Abstract: CXC195 showed strong protective effects in neuronal apoptosis by exerting its antioxidant activity. However, the anti-cancer effects of CXC195 is still with limited acquaintance. Here, we investigated the role of CXC195 in lipopolysaccharide (LPS)-induced human hepatocellular carcinoma (HCC) cells lines (HepG2) and the possible signaling pathways. CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-inducedmore » HepG2 cells. In addition, CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells, including TNF-α, iNOS, IL-1β, IL-6, CC chemokine ligand (CCL)-2, CCL-22 and epidermal growth factor receptor (EGFR). Moreover, CXC195 inhibited the expressions and interactions of TLR4, MyD88 and TAK1, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of ERK1/2, p38 and JNK. Our results suggested that treatment with CXC195 could attenuate the TLR4-mediated proliferation and inflammatory response in LPS-induced HepG2 cells, thus might be beneficial for the treatment of HCC.« less

Cargo launch vehicles to low earth orbit

NASA Technical Reports Server (NTRS)

Austin, Robert E.

1990-01-01

There are two primary space transportation capabilities required to support both base programs and expanded mission requirements: earth-to-orbit (ETO) transportation systems and space transfer vehicle systems. Existing and new ETO vehicles required to support mission requirements, and planned robotic missions, along with currently planned ETO vehicles are provided. Lunar outposts, Mars' outposts, base and expanded model, ETO vehicles, advanced avionics technologies, expert systems, network architecture and operations systems, and technology transfer are discussed.

NOAA Introduces its First-Generation Reference Evapotranspiration Product

NASA Astrophysics Data System (ADS)

Hobbins, M.; Geli, H. M.; Lewis, C.; Senay, G. B.; Verdin, J. P.

2013-12-01

NOAA is producing daily, gridded operational, long-term, reference evapotranspiration (ETo) data for the National Water Census (NWC). The NWC is a congressional mandate to provide water managers with accurate, up-to-date, scientifically defensible reporting on the national water cycle; as such, it requires a high-quality record of actual ET, which we derive as a fraction of NOAA's land-based ETo a fraction determined by remotely sensed (RS) LST and/or surface reflectance in an operational version of the Simplified Surface Energy Balance (SSEBop). This methodology permits mapping of ET on a routine basis with a high degree of consistency at multiple spatial scales. This presentation addresses the ETo input to this process. NOAA's ETo dataset is generated from the American Society of Civil Engineers Standardized Penman-Monteith equation driven by hourly, 0.125-degree (~12-km) data from the North American Land Data Assimilation System (NLDAS). Coverage is CONUS-wide from Jan 1, 1979, to within five days of the present. The ETo is verified against agro-meteorological stations in western CONUS networks, while a first-order, second-moment uncertainty analysis indicates when, where, and to what extent each driver contributes to ETo variability (and so potentially require the most attention). As the NWC's mandate requires a nationwide coverage, the ETo dataset must also be verified outside of the measure's traditional, agricultural/irrigated areas of application. In this presentation, we summarize the verification of the gridded ETo product and demonstrate the drivers of ETo variability in space and time across CONUS. Beyond its primary use as a component of ET in the NWC, we further explore potential uses of the ETo product as an input to drought models and as a stand-alone index of fast-developing agricultural drought, or 'flash drought.' NOAA's product is the first consistently modeled, daily, continent-wide ETo dataset that is both up-to-date and as temporally

Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats.

PubMed

Balap, Aishwarya; Atre, Bhagyashri; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

2016-05-13

Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats. After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone. The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible

Sources of variability of evapotranspiration in California

USGS Publications Warehouse

Hidalgo, H.G.; Cayan, D.R.; Dettinger, M.D.

2005-01-01

The variability (1990-2002) of potential evapotranspiration estimates (ETo) and related meteorological variables from a set of stations from the California Irrigation Management System (CIMIS) is studied. Data from the National Climatic Data Center (NCDC) and from the Department of Energy from 1950 to 2001 were used to validate the results. The objective is to determine the characteristics of climatological ETo and to identify factors controlling its variability (including associated atmospheric circulations). Daily ETo anomalies are strongly correlated with net radiation (Rn) anomalies, relative humidity (RH), and cloud cover, and less with average daily temperature (Tavg). The highest intraseasonal variability of ETo daily anomalies occurs during the spring, mainly caused by anomalies below the high ETo seasonal values during cloudy days. A characteristic circulation pattern is associated with anomalies of ETo and its driving meteorological inputs, Rn, RH, and Tavg, at daily to seasonal time scales. This circulation pattern is dominated by 700-hPa geopotential height (Z700) anomalies over a region off the west coast of North America, approximately between 32?? and 44?? latitude, referred to as the California Pressure Anomaly (CPA). High cloudiness and lower than normal ETo are associated with the lowheight (pressure) phase of the CPA pattern. Higher than normal ETo anomalies are associated with clear skies maintained through anomalously high Z700 anomalies offshore of the North American coast. Spring CPA, cloudiness, maximum temperature (Tmax), pan evaporation (Epan), and ETo conditions have not trended significantly or consistently during the second half of the twentieth century in California. Because it is not known how cloud cover and humidity will respond to climate change, the response of ETo in California to increased greenhouse-gas concentrations is essentially unknown; however, to retain the levels of ETo in the current climate, a decline of Rn by about 6

A Means Towards Understanding: Reconnaissance and the Practice of Operational Art

DTIC Science & Technology

2011-12-01

Soviet Military Operational Art: In Pursuit of Deep Battle (London: Routledge, 1991), 256-257. 24Matthew K . Green, “Operational Reconnaissance: The...1946), 20-21, app. 3, 4, 5, http://www.cgsc.edu/carl/ eto /eto.asp (accessed 29 August 2011). 103James A. Huston, “Tactical Use of Air Power in World War...Nauheim, GE, 1945-1946), 9-11, http://www.cgsc.edu/carl/ eto /eto.asp (accessed 29 August 2011). 104Stephen E. Ambrose, D-Day June 6, 1944: The

Discovery of a tetrahydropyrimidin-2(1H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor.

PubMed

Fujimoto, Takuya; Imaeda, Yasuhiro; Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki; Textor, Garret P; Aertgeerts, Kathleen; Kubo, Keiji

2010-05-13

Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo[1,5-c]imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. To address this issue, our synthetic efforts were focused on modification of the imidazo[1,5-c]imidazol-3-one moiety of the active metabolite 3a, derived from 1, which resulted in the discovery of the tetrahydropyrimidin-2(1H)-one derivative 5k as a highly potent and selective FXa inhibitor. Compound 5k showed no detectable amide bond cleavage in human liver microsomes, exhibited a good pharmacokinetic profile in monkeys, and had a potent antithrombotic efficacy in a rabbit model without prolongation of bleeding time. Compound 5k is currently under clinical development with the code name TAK-442.

Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

2017-05-01

Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (˜141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

Extended trochanteric osteotomy: current concepts review.

PubMed

Sambandam, Senthil Nathan; Duraisamy, Gopinath; Chandrasekharan, Jayadev; Mounasamy, Varatharaj

2016-04-01

Revision total hip arthroplasty is a technically demanding procedure which has gained importance for more than two decades. It was a nightmare for revision surgeons during its initial years of inception before the advent of extended trochanteric osteotomy (ETO). This technique gains access to the femoral medullary canal without compromising the bone stock and aids removal of primary implant and cement mantle without further damaging the parent bone. Like any other surgery, ETO does have certain limitations and complications as reported by various authors. Though it has been routinely used by revision surgeons, thorough knowledge of technical details of ETO is still lacking. So this review article is aimed at addressing the indications, surgical procedure, fixation technique, implant selection and complication of ETO which has been presented over a period of years by various authors. We searched in the most commonly used portals like MEDLINE (PubMed) and Google scholar using appropriate terminologies for the literature regarding the various preoperative, intraoperative and postoperative clinical scenarios in which revision surgeons utilized ETO. ETO is an important tool in the revision surgeon's armamentarium and can be used in variety of clinical scenarios and for various intraoperative needs and goals. Awareness about biomechanics of ETO, indications, implants selection, fixation techniques and complications is paramount for good intraoperative and postoperative outcome. ETO by posterior approach continues to be a work horse approach for most revision surgeons all over the world.

Climate and ET: Does Plant Water Requirements Increase during Droughts?

NASA Astrophysics Data System (ADS)

Fipps, G.

2015-12-01

Municipalities, engineering consultants and State agencies use reference evapotranspiration (ETo) data (directly and indirectly) for long-term water planning, for designing hydraulic structures, and for establishing regulatory guidance and conservation programs intended to reduce water waste. The use ETo data for agricultural and landscape irrigation scheduling is becoming more common in Texas as ETo-based controllers and automation technologies become more affordable. Until recently, most ETo data has been available as monthly values averaged over many years. Today, automated weather stations and irrigation controllers equipped with specialized instrumentation allow for real-time ETo measurements. With the expected rise in global warming and increased frequency of extreme climate variability in the coming decades, conservation and efficient use of water resources is essential and must make use of the most accurate and representative data available. 2011 marked the driest year on record in the State of Texas. Compounding the lack of rainfall was record heat during the Summer of 2011. An analysis of real time ETo (reference evapotranspiration) data in Texas found that ET was 30 to 50% higher than historic averages during the 2011 Summer. The implications are quite serious, as most current water planning and drought contingency plans do not take into consideration increases in ET during such periods, and irrigation planning and capacity sizing are based on historic averages of consumptive use. This paper examines the relationship between ET and climate during this extreme climatic event. While the solar radiation was near normal levels, temperature and wind was much higher and dew points much lower than norms. The variability and statistical difference between average monthly ETo data and daily, monthly and seasonal ETo measurements (from 2006 to 2014) for selected weather stations of the Texas ET Network. This study will also examine the suitability of using average

Toxic effects of ethylene oxide residues on bovine embryos in vitro.

PubMed

Holyoak, G R; Wang, S; Liu, Y; Bunch, T D

1996-04-15

The potential of ethylene oxide (EtO) residues in exposed plastic tissue culture dishes to adversely affect bovine oocyte maturation, fertilization and subsequent embryonic development was monitored. In experiment 1, the effects of aeration time and aeration combined with washing of EtO-gassed culture dishes on the extent of residual toxicity were investigated. There was no cleavage in any treatment in which oocytes were matured and fertilized in dishes exposed to EtO. EtO residues caused functional degeneration of oocytes even when culture dishes were aerated for more than 12 days post EtO-exposure and repeatedly washed. In experiment 2, the residual toxicity of EtO gas on in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC) were evaluated. Cleavage rate significantly decreased and post-cleavage development was retarded in ova maintained in dishes treated with EtO either during IVM or IVF. EtO residues may be more detrimental to spermatozoa than to oocytes which may have been the primary cause of fertilization failure during IVF.

Industry-wide studies report of an industrial-hygiene survey of Riverside Manor Nursing and Rehabilitation Center, Newcomerstown, Ohio. [Ethylene oxide exposures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ringenburg, V.L.; Molina, D.; Elliott, L.J.

Occupational exposure of workers to ethylene oxide (EtO) was examined. Two of six side-by-side short-term personal breathing-zone (BZ) exposure levels, determined while the sterilizer operator unloaded the EtO sterilizer unit, exceeded NIOSH recommended short term levels of 5 parts per million (ppm) for any 10-minute period per workday. Three of 12 personal BZ exposure levels exceeded the NIOSH recommended standard of less than 0.1ppm for an 8-hour time-weighted average. Measurable levels of EtO, ranging from 0.18 to 14.5ppm were detected in the storage room where the EtO sterilized items were aerated. The authors conclude that EtO exposure potential at themore » nursing and rehabilitation center could be reduced by improving administrative controls, work practices, and engineering controls. Recommended improvements were given.« less

Spatial and temporal trends of reference crop evapotranspiration and its influential variables in Yangtze River Delta, eastern China

NASA Astrophysics Data System (ADS)

Xu, Yu; Xu, Youpeng; Wang, Yuefeng; Wu, Lei; Li, Guang; Song, Song

2017-11-01

Reference crop evapotranspiration (ETo) is one of the most important links in hydrologic circulation and greatly affects regional agricultural production and water resource management. Its variation has drawn more and more attention in the context of global warming. We used the Penman-Monteith method of the Food and Agriculture Organization, based on meteorological factors such as air temperature, sunshine duration, wind speed, and relative humidity to calculate the ETo over 46 meteorological stations located in the Yangtze River Delta, eastern China, from 1957 to 2014. The spatial distributions and temporal trends in ETo were analyzed based on the modified Mann-Kendall trend test and linear regression method, while ArcGIS software was employed to produce the distribution maps. The multiple stepwise regression method was applied in the analysis of the meteorological variable time series to identify the causes of any observed trends in ETo. The results indicated that annual ETo showed an obvious spatial pattern of higher values in the north than in the south. Annual increasing trends were found at 34 meteorological stations (73.91 % of the total), which were mainly located in the southeast. Among them, 12 (26.09 % of the total) stations showed significant trends. We saw a dominance of increasing trends in the monthly ETo except for January, February, and August. The high value zone of monthly ETo appeared in the northwest from February to June, mid-south area from July to August, and southeast coastal area from September to January. The research period was divided into two stages—stage I (1957-1989) and stage II (1990-2014)—to investigate the long-term temporal ETo variation. In stage I, almost 85 % of the total stations experienced decreasing trends, while more than half of the meteorological stations showed significant increasing trends in annual ETo during stage II except in February and September. Relative humidity, wind speed, and sunshine duration were

Contribution of precipitation and reference evapotranspiration to drought indices under different climates

NASA Astrophysics Data System (ADS)

Vicente-Serrano, Sergio M.; Van der Schrier, Gerard; Beguería, Santiago; Azorin-Molina, Cesar; Lopez-Moreno, Juan-I.

2015-07-01

In this study we analyzed the sensitivity of four drought indices to precipitation (P) and reference evapotranspiration (ETo) inputs. The four drought indices are the Palmer Drought Severity Index (PDSI), the Reconnaissance Drought Index (RDI), the Standardized Precipitation Evapotranspiration Index (SPEI) and the Standardized Palmer Drought Index (SPDI). The analysis uses long-term simulated series with varying averages and variances, as well as global observational data to assess the sensitivity to real climatic conditions in different regions of the World. The results show differences in the sensitivity to ETo and P among the four drought indices. The PDSI shows the lowest sensitivity to variation in their climate inputs, probably as a consequence of the standardization procedure of soil water budget anomalies. The RDI is only sensitive to the variance but not to the average of P and ETo. The SPEI shows the largest sensitivity to ETo variation, with clear geographic patterns mainly controlled by aridity. The low sensitivity of the PDSI to ETo makes the PDSI perhaps less apt as the suitable drought index in applications in which the changes in ETo are most relevant. On the contrary, the SPEI shows equal sensitivity to P and ETo. It works as a perfect supply and demand system modulated by the average and standard deviation of each series and combines the sensitivity of the series to changes in magnitude and variance. Our results are a robust assessment of the sensitivity of drought indices to P and ETo variation, and provide advice on the use of drought indices to detect climate change impacts on drought severity under a wide variety of climatic conditions.

Personnel Systems in Europe in Preparation for Operation OVERLORD: How Did They Work?

DTIC Science & Technology

2014-05-01

and processes provided American and Commonwealth nations with the necessary requirements to conduct operations in the ETO . The third section exposed...War Department CARL Combined Arms Research Library CGSC US Army Command and General Staff College EPW Enemy Prisoner of War ETO European Theater...oversight and synchronization of all American and Commonwealth nations operations in the European Theater of Operation ( ETO ).7 From a management of

Spatial pattern of reference evapotranspiration change and its temporal evolution over Southwest China

NASA Astrophysics Data System (ADS)

Sun, Shanlei; Wang, Guojie; Huang, Jin; Mu, Mengyuan; Yan, Guixia; Liu, Chunwei; Gao, Chujie; Li, Xing; Yin, Yixing; Zhang, Fangmin; Zhu, Siguang; Hua, Wenjian

2017-11-01

Due to the close relationship of climate change with reference evapotranspiration (ETo), detecting changes in ETo spatial distribution and its temporal evolution at local and regional levels is favorable to comprehensively understand climate change-induced impacts on hydrology and agriculture. In this study, the objective is to identify whether climate change has caused variation of ETo spatial distribution in different analysis periods [i.e., long- (20-year), medium- (10-year), and short-term (5-year)] and to investigate its temporal evolution (namely, when these changes happened) at annual and monthly scales in Southwest China (SWC). First, we estimated ETo values using the United Nations Food and Agriculture Organization (FAO) Penman-Monteith equation, based on historical climate data measured at 269 weather sites during 1973-2012. The analysis of variance (ANOVA) results indicated that the spatial pattern of annual ETo had significantly changed during the past 40 years, particularly in west SWC for the long-term analysis period, and west and southeast SWC in both medium- and short-term periods, which corresponded to the percent area of significant differences which were 21.9, 58.0, and 48.2 %, respectively. For investigating temporal evolution of spatial patterns of annual ETo, Duncan's multiple range test was used, and we found that the most significant changes appeared during 1988-2002 with the significant area of higher than 25.0 %. In addition, for long-, medium-, and short-term analysis periods, the spatial distribution has significantly changed during March, September, November, and December, especially in the corresponding periods of 1988-1997, 1983-1992, 1973-1977, and 1988-2002. All in all, climate change has resulted in significant ETo changes in SWC since the 1970s. Knowledge of climate change-induced spatial distribution of ETo and its temporal evolution would aid in formulating strategies for water resources and agricultural managements.

Silicon Carbide Emitter Turn-Off Thyristor

DOE PAGES

Wang, Jun; Wang, Gangyao; Li, Jun; ...

2008-01-01

A novel MOS-conmore » trolled SiC thyristor device, the SiC emitter turn-off thyristor (ETO) is a promising technology for future high-voltage switching applications because it integrates the excellent current conduction capability of a SiC thyristor with a simple MOS-control interface. Through unity-gain turn-off, the SiC ETO also achieves excellent Safe Operation Area (SOA) and faster switching speeds than silicon ETOs. The world's first 4.5-kV SiC ETO prototype shows a forward voltage drop of 4.26 V at 26.5  A / cm 2 current density at room and elevated temperatures. Tested in an inductive circuit with a 2.5 kV DC link voltage and a 9.56-A load current, the SiC ETO shows a fast turn-off time of 1.63 microseconds and a low 9.88 mJ turn-off energy. The low switching loss indicates that the SiC ETO could operate at about 4 kHz if 100  W / cm 2 conduction and the 100  W / cm 2 turn-off losses can be removed by the thermal management system. This frequency capability is about 4 times higher than 4.5-kV-class silicon power devices. The preliminary demonstration shows that the SiC ETO is a promising candidate for high-frequency, high-voltage power conversion applications, and additional developments to optimize the device for higher voltage (>5 kV) and higher frequency (10 kHz) are needed.« less

Microbiological evaluation of the mobile biological isolator system

NASA Technical Reports Server (NTRS)

Taylor, D. M.; Morelli, F.; Neiderheiser, W.; Tratz, W. M.

1979-01-01

Evaluations on critical components of the mobile biological isolation system were performed. High efficiency particulate air filter efficiency and suit integrity were found to withstand repeated ethylene oxide (ETO) sterilizations. The minimum ETO sterilization time required to inactivate all contaminant organisms was established at four hours. Two days of aerating at 120 F was found to dissipate all harmful ETO residuals from the suit. Donning and doffing procedures were clarified and written specifically for isolation rooms.

Long-Term Ethylene Oxide Exposure Trends in US Hospitals: Relationship With OSHA Regulatory and Enforcement Actions

PubMed Central

LaMontagne, Anthony D.; Oakes, J. Michael; Lopez Turley, Ruth N.

2004-01-01

Objectives. We assessed long-term trends in ethylene oxide (EtO) worker exposures for the purposes of exposure surveillance and evaluation of the impacts of the Occupational Safety and Health Administration (OSHA) 1984 and 1988 EtO standards. Methods. We obtained exposure data from a large commercial vendor and processor of EtO passive dosimeters. Personal samples (87 582 workshift [8-hr] and 46 097 short-term [15-min] samples) from 2265 US hospitals were analyzed for time trends from 1984 through 2001 and compared with OSHA enforcement data. Results. Exposures declined steadily for the first several years after the OSHA standards were set. Workshift exposures continued to taper off and have remained low and constant through 2001. However, since 1996, the probability of exceeding the short-term excursion limit has increased. This trend coincides with a decline in enforcement of the EtO standard. Conclusions. Results indicate the need for renewed intervention efforts to preserve gains made following the passage and implementation of the 1984 and 1988 EtO standards. PMID:15333324

Interleukin 1 β-induced SMAD2/3 linker modifications are TAK1 dependent and delay TGFβ signaling in primary human mesenchymal stem cells.

PubMed

van den Akker, Guus G; van Beuningen, Henk M; Vitters, Elly L; Koenders, Marije I; van de Loo, Fons A; van Lent, Peter L; Blaney Davidson, Esmeralda N; van der Kraan, Peter M

2017-12-01

was performed to identify kinases involved in SMAD2/3 linker modifications. We identified TAK1 kinase activity as crucial for IL1β-induced SMAD2 linker modifications and CAGA 12 -luciferase activity. TGFβ and IL1β signaling interact at the SMAD2/3 level in human primary MSC. Down-stream TGFβ target genes were repressed by IL1β independent of C-terminal SMAD2 phosphorylation. We demonstrate that SMAD2/3 linker modifications are required for this interplay and identified TAK1 as a crucial mediator of IL1β-induced TGFβ signal modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors affecting delay in seeking treatment among malaria patients along Thailand-Myanmar border in Tak Province, Thailand.

PubMed

Sonkong, Krit; Chaiklieng, Sunisa; Neave, Penny; Suggaravetsiri, Pornnapa

2015-01-07

Malaria is a major health problem in Thailand, especially in areas adjacent to the borders of Myanmar. Delay in seeking treatment is an important factor in the development of severe complications, death and the transmission of the disease. This study aimed to investigate factors affecting delays in seeking treatment of malaria patients. A cross-sectional analytic study was conducted in 456 malaria patients along the Thailand-Myanmar border. Patients were selected by stratified sampling from 11 malaria clinics and five public hospitals in Tak Province, Thailand. Data were collected by the use of a structured interview questionnaire and from patient's medical records. The majority of patients were categorized with an ethnicity of 'hill tribe' (65.8%), followed by Thai (34.2%). Seventy-nine per cent of patients delayed seeking treatment. A simple logistic regression identified significant factors affecting delays in seeking treatment: people of "hill tribe" ethnicity; plasmodium species; self-treatment; visiting sub-district health promotion hospital/malaria post before visiting a malaria clinic or public hospital; and low to medium social support. After being subjected to multivariate analysis, factors significantly associated with the delay were "hill tribe" ethnicity (ORadj = 2.32, 95% CI: 1.34-4.04); infection with P.vivax (ORadj=2.02, 95% CI: 1.19-3.41; self-treatment (ORadj = 1.73, 95% CI: 1.04-2.85); and receiving a low degree of social support (ORadj = 2.58, 95% CI: 1.24-5.35). Emphasis should be placed on need for early diagnosis and treatment in malaria patients as well as on ensuring the first facility for detection and treatment of malaria is a malaria clinic or public hospital, and the promotion of social support. These are especially important issues for the health of hill tribe people.

Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishimoto, Tomoyuki; Ishikawa, Eiichiro; Anayama, Hisashi

2007-08-15

High-dose statin treatment has been recommended as a primary strategy for aggressive reduction of LDL cholesterol levels and protection against coronary artery disease. The effectiveness of high-dose statins may be limited by their potential for myotoxic side effects. There is currently little known about the molecular mechanisms of statin-induced myotoxicity. Previously we showed that T-91485, an active metabolite of the squalene synthase inhibitor lapaquistat acetate (lapaquistat: a previous name is TAK-475), attenuated statin-induced cytotoxicity in human skeletal muscle cells [Nishimoto, T., Tozawa, R., Amano, Y., Wada, T., Imura, Y., Sugiyama, Y., 2003a. Comparing myotoxic effects of squalene synthase inhibitor, T-91485,more » and 3-hydroxy-3-methylglutaryl coenzyme A. Biochem. Pharmacol. 66, 2133-2139]. In the current study, we investigated the effects of lapaquistat administration on statin-induced myotoxicity in vivo. Guinea pigs were treated with either high-dose cerivastatin (1 mg/kg) or cerivastatin together with lapaquistat (30 mg/kg) for 14 days. Treatment with cerivastatin alone decreased plasma cholesterol levels by 45% and increased creatine kinase (CK) levels by more than 10-fold (a marker of myotoxicity). The plasma CK levels positively correlated with the severity of skeletal muscle lesions as assessed by histopathology. Co-administration of lapaquistat almost completely prevented the cerivastatin-induced myotoxicity. Administration of mevalonolactone (100 mg/kg b.i.d.) prevented the cerivastatin-induced myotoxicity, confirming that this effect is directly related to HMG-CoA reductase inhibition. These results strongly suggest that cerivastatin-induced myotoxicity is due to depletion of mevalonate derived isoprenoids. In addition, squalene synthase inhibition could potentially be used clinically to prevent statin-induced myopathy.« less

Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs.

PubMed

Nishimoto, Tomoyuki; Ishikawa, Eiichiro; Anayama, Hisashi; Hamajyo, Hitomi; Nagai, Hirofumi; Hirakata, Masao; Tozawa, Ryuichi

2007-08-15

High-dose statin treatment has been recommended as a primary strategy for aggressive reduction of LDL cholesterol levels and protection against coronary artery disease. The effectiveness of high-dose statins may be limited by their potential for myotoxic side effects. There is currently little known about the molecular mechanisms of statin-induced myotoxicity. Previously we showed that T-91485, an active metabolite of the squalene synthase inhibitor lapaquistat acetate (lapaquistat: a previous name is TAK-475), attenuated statin-induced cytotoxicity in human skeletal muscle cells [Nishimoto, T., Tozawa, R., Amano, Y., Wada, T., Imura, Y., Sugiyama, Y., 2003a. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A. Biochem. Pharmacol. 66, 2133-2139]. In the current study, we investigated the effects of lapaquistat administration on statin-induced myotoxicity in vivo. Guinea pigs were treated with either high-dose cerivastatin (1 mg/kg) or cerivastatin together with lapaquistat (30 mg/kg) for 14 days. Treatment with cerivastatin alone decreased plasma cholesterol levels by 45% and increased creatine kinase (CK) levels by more than 10-fold (a marker of myotoxicity). The plasma CK levels positively correlated with the severity of skeletal muscle lesions as assessed by histopathology. Co-administration of lapaquistat almost completely prevented the cerivastatin-induced myotoxicity. Administration of mevalonolactone (100 mg/kg b.i.d.) prevented the cerivastatin-induced myotoxicity, confirming that this effect is directly related to HMG-CoA reductase inhibition. These results strongly suggest that cerivastatin-induced myotoxicity is due to depletion of mevalonate derived isoprenoids. In addition, squalene synthase inhibition could potentially be used clinically to prevent statin-induced myopathy.

TGF-β–Activated Kinase 1 Is Crucial in Podocyte Differentiation and Glomerular Capillary Formation

PubMed Central

Lee, So-Young; Wang, Zhibo; Ding, Yan; Haque, Nadeem; Zhang, Jiwang; Zhou, Jing

2014-01-01

TGF-β–activated kinase 1 (TAK1) is a key intermediate in signal transduction induced by TGF-β or inflammatory cytokines, such as TNF-α and IL-1, which are potent inducers of podocyte injury responses that lead to proteinuria and glomerulosclerosis. Nevertheless, little is known about the physiologic and pathologic roles of TAK1 in podocytes. To examine the in vivo role of TAK1, we generated podocyte-specific Tak1 knockout mice (Nphs2-Cre+:Tak1fx/fx; Tak1∆/∆). Targeted deletion of Tak1 in podocytes resulted in perinatal lethality, with approximately 50% of animals dying soon after birth and 90% of animals dying within 1 week of birth. Tak1∆/∆ mice developed proteinuria from P1 and exhibited delayed glomerulogenesis and reduced expression of Wilms’ tumor suppressor 1 and nephrin in podocytes. Compared with Tak1fx/fx mice, Tak1∆/∆ mice exhibited impaired formation of podocyte foot processes that caused disruption of the podocyte architecture with prominent foot process effacement. Intriguingly, Tak1∆/∆ mice displayed increased expression of vascular endothelial growth factor within the glomerulus and abnormally enlarged glomerular capillaries. Furthermore, 4- and 7-week-old Tak1∆/∆ mice with proteinuria had increased collagen deposition in the mesangium and the adjacent tubulointerstitial area. Thus, loss of Tak1 in podocytes is associated with the development of proteinuria and glomerulosclerosis. Taken together, our data show that TAK1 regulates the expression of Wilms’ tumor suppressor 1, nephrin, and vascular endothelial growth factor and that TAK1 signaling has a crucial role in podocyte differentiation and attainment of normal glomerular microvasculature during kidney development and glomerular filtration barrier homeostasis. PMID:24652804

Glycyrrhetinic acid-modified TPGS polymeric micelles for hepatocellular carcinoma-targeted therapy.

PubMed

Zhu, Xiumei; Tsend-Ayush, Altansukh; Yuan, Zhongyue; Wen, Jing; Cai, Jiaxin; Luo, Shifu; Yao, Jianxu; Bian, Junxing; Yin, Linfang; Zhou, Jianping; Yao, Jing

2017-08-30

In this study, glycyrrhetinic acid (GA)-modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs) displayed a mean particle size of 133.6±1.2nm with a low poly-dispersity index (0.224±0.013) and negative zeta potential (-16.30mV). The drug loading and entrapment efficiency of ETO-TGA PMs were 10.4% and 79.8%, respectively. ETO-TGA PMs also exhibited faster drug release behavior at pH 5.8 and relatively stable drug release at pH 7.4. Confocal laser scanning microscope (CLSM) observations and in vivo imaging studies revealed that TGA PMs displayed higher cellular uptake and selective accumulation at the tumor site, indicating good tumor targetability. Furthermore, ETO-TGA PMs displayed significant cytotoxicity towards HepG2 cells and higher anti-tumor efficacy (75.96%), compared to the control group. This could be due to TGA-mediated targeted drug delivery to the hepatocytes as well as P-gp inhibition. These findings suggest that TGA PMs have the potential to be used as a targeted drug delivery system for hepatic cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Biocompatibility differences with respect to the dialyzer sterilization method.

PubMed

Müller, T F; Seitz, M; Eckle, I; Lange, H; Kolb, G

1998-01-01

The impact of the method of sterilization (steam vs. ethylene oxide, ETO) on indices of biocompatibility is investigated using polysulfone membranes. Eight patients were treated with a random choice of the high-flux membranes F60S (steam) and F60 (ETO) and the low-flux membrane F6 (ETO). Blood samples were taken prior to and 5, 15, 30, 60, and 180 min after the start of hemodialysis. White blood cell count, platelet count, and plasma concentrations of polymorphonuclear neutrophil elastase, complements C3a and C5a, and beta2-microglobulin were determined. The dialysis procedure was associated with a significant decrease in white blood cell count and beta2-microglobulin level and a significant increase in polymorphonuclear neutrophil elastase and complement C3a and C5a levels. However, the steam-sterilized F60S membrane had a significantly lower impact on the biocompatibility indices than the ETO-sterilized F60 and F6 membranes (p < 0.05 or p < 0.001 for the individual markers). We conclude that using steam instead of ETO for sterilization may improve the biocompatibility of membranes.

Revisited HLA and non-HLA genetics of Takayasu arteritis--where are we?

PubMed

Terao, Chikashi

2016-01-01

Takayasu arteritis (TAK) is an immune-mediated vasculitis affecting large arteries first reported in 1908 from Japan. Case reports of familial onset of TAK from Japan and other countries indicated genetic contribution to TAK onset beyond ethnicity. Genetic studies of TAK have been performed mainly addressing the human leukocyte antigen (HLA) locus. HLA genetic studies of TAK that have previously been reported are reviewed in this manuscript. HLA-B*52:01 is associated with TAK beyond population. Many of the associations other than HLA-B*52:01 can be explained by a haplotype with HLA-B*52:01. HLA-B*67:01 is a novel susceptibility HLA-B allele to TAK confirmed in the Japanese population. Further independent associations are suggested in the HLA locus. Involvement of the 171st and 67th amino acid residues with TAK onset has been indicated. The 67th amino acid may explain the difference in susceptibility effects to TAK and Behçet's disease between HLA-B*52:01 and *51:01. HLA-B*52:01 is associated not only with TAK susceptibility but also with clinical phenotypes. Recent genome-wide association studies of TAK revealed multiple non-HLA susceptibility genes. In particular, the IL12B region seems to have a central role in TAK onset and its progression. Whether TAK and giant cell arteritis (GCA), the other vasculitis affecting large arteries, are the same disease is an interesting question to address in spite of different clinical manifestations between the two diseases. GCA is associated with HLA-DR4, which is not associated with TAK. GCA is not associated with HLA-Bw52. These two diseases seem not to share non-HLA susceptibility loci based on the recent genetic studies.

Identification of TGF-β-activated kinase 1 as a possible novel target for renal cell carcinoma intervention

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, Fandong; Li, Yan; Tian, Xin

Highlights: • Inhibition of TAK1 kinase activity suppresses NF-κB activation and RCC cell survival. • TAK1 inhibitors induces apoptotic cytotoxicity against RCC cells. • RCC cells with TAK1 depletion show reduced cell viability and increased apoptosis. • TAK1 and p-NF-κB are both over-expressed in human RCC tissues. • Inhibition or depletion of TAK1 enhances the activity of vinblastine sulfate. - Abstract: Renal cell carcinoma (RCC) is common renal malignancy within poor prognosis. TGF-β-activated kinase 1 (TAK1) plays vital roles in cell survival, apoptosis-resistance and carcinogenesis through regulating nuclear factor-κB (NF-κB) and other cancer-related pathways. Here we found that TAK1 inhibitorsmore » (LYTAK1, 5Z-7-oxozeanol (5Z) and NG-25) suppressed NF-κB activation and RCC cell (786-O and A489 lines) survival. TAK1 inhibitors induced apoptotic cytotoxicity against RCC cells, which was largely inhibited by the broad or specific caspase inhibitors. Further, shRNA-mediated partial depletion of TAK1 reduced 786-O cell viability whiling activating apoptosis. Significantly, TAK1 was over-expressed in human RCC tissues, and its level was correlated with phosphorylated NF-κB. Finally, kinase inhibition or genetic depletion of TAK1 enhanced the activity of vinblastine sulfate (VLB) in RCC cells. Together, these results suggest that TAK1 may be an important oncogene or an effective target for RCC intervention.« less

Trend analysis and forecast of precipitation, reference evapotranspiration and rainfall deficit in the Blackland Prairie of eastern Mississippi

USDA-ARS?s Scientific Manuscript database

Trend analysis and estimation of monthly and annual precipitation, reference evapotranspiration (ETo) and rainfall deficit are essential for water resources management and cropping system design. Rainfall, ETo, and water deficit patterns and trends in eastern Mississippi USA for a 120-year period (1...

Evaluating OSHA's ethylene oxide standard: employer exposure-monitoring activities in Massachusetts hospitals from 1985 through 1993.

PubMed Central

LaMontagne, A D; Kelsey, K T

1997-01-01

OBJECTIVES: This study characterized exposure-monitoring activities and findings under the Occupational Safety and Health Administration's (OSHA's) 1984 ethylene oxide (EtO) standard. METHODS: In-depth mail and telephone surveys were followed by on-site interviews at all EtO-using hospitals in Massachusetts (n = 92, 96% participation rate). RESULTS: By 1993, most hospitals had performed personal exposure monitoring for OSHA's 8-hour action level (95%) and the excursion limit (87%), although most did not meet the 1985 implementation deadline. In 1993, 66% of hospitals reported the installation of EtO alarms to fulfill the standard's "alert" requirement. Alarm installation also lagged behind the 1985 deadline and peaked following a series of EtO citations by OSHA. From 1990 through 1992, 23% of hospitals reported having exceeded the action level once or more; 24% reported having exceeded the excursion limit; and 33% reported that workers were accidentally exposed to EtO in the absence of personal monitoring. CONCLUSIONS: Almost a decade after passage of the EtO standard, exposure-monitoring requirements were widely, but not completely, implemented. Work-shift exposures had markedly decreased since the mid-1980s, but overexposures continued to occur widely. OSHA enforcement appears to have stimulated implementation. PMID:9240100

Formoxanthone C, isolated from Cratoxylum formosum ssp. pruniflorum, reverses anticancer drug resistance by inducing both apoptosis and autophagy in human A549 lung cancer cells.

PubMed

Kaewpiboon, Chutima; Boonnak, Nawong; Kaowinn, Sirichat; Chung, Young-Hwa

2018-02-15

Multidrug resistance (MDR) cancer toward cancer chemotherapy is one of the obstacles in cancer therapy. Therefore, it is of interested to use formoxanthone C (1,3,5,6-tetraoxygenated xanthone; XanX), a natural compound, which showed cytotoxicity against MDR human A549 lung cancer (A549RT-eto). The treatment with XanX induced not only apoptosis- in A549RT-eto cells, but also autophagy-cell death. Inhibition of apoptosis did not block XanX-induced autophagy in A549RT-eto cells. Furthermore, suppression of autophagy by beclin-1 small interfering RNAs (siRNAs) did not interrupt XanX-induced apoptosis, indicating that XanX can separately induce apoptosis and autophagy. Of interest, XanX treatment reduced levels of histone deacetylase 4 (HDAC4) protein overexpressed in A549RT-etocells. The co-treatment with XanX and HDAC4 siRNA accelerated both autophagy and apoptosis more than that by XanX treatment alone, suggesting survival of HDAC4 in A549RT-eto cells. XanX reverses etoposide resistance in A549RT-eto cells by induction of both autophagy and apoptosis, and confers cytotoxicity through down-regulation of HDAC4. Copyright © 2017. Published by Elsevier Ltd.

Transforming growth factor β-activated kinase 1 transcriptionally suppresses hepatitis B virus replication.

PubMed

Pang, Jinke; Zhang, Geng; Lin, Yong; Xie, Zhanglian; Liu, Hongyan; Tang, Libo; Lu, Mengji; Yan, Ran; Guo, Haitao; Sun, Jian; Hou, Jinlin; Zhang, Xiaoyong

2017-01-03

Hepatitis B Virus (HBV) replication in hepatocytes is restricted by the host innate immune system and related intracellular signaling pathways. Transforming growth factor β-activated kinase 1 (TAK1) is a key mediator of toll-like receptors and pro-inflammatory cytokine signaling pathways. Here, we report that silencing or inhibition of endogenous TAK1 in hepatoma cell lines leads to an upregulation of HBV replication, transcription, and antigen expression. In contrast, overexpression of TAK1 significantly suppresses HBV replication, while an enzymatically inactive form of TAK1 exerts no effect. By screening TAK1-associated signaling pathways with inhibitors and siRNAs, we found that the MAPK-JNK pathway was involved in TAK1-mediated HBV suppression. Moreover, TAK1 knockdown or JNK pathway inhibition induced the expression of farnesoid X receptor α, a transcription factor that upregulates HBV transcription. Finally, ectopic expression of TAK1 in a HBV hydrodynamic injection mouse model resulted in lower levels of HBV DNA and antigens in both liver and serum. In conclusion, our data suggest that TAK1 inhibits HBV primarily at viral transcription level through activation of MAPK-JNK pathway, thus TAK1 represents an intrinsic host restriction factor for HBV replication in hepatocytes.

Recent advances in Takayasu arteritis.

PubMed

Terao, Chikashi; Yoshifuji, Hajime; Mimori, Tsuneyo

2014-03-01

Takayasu arteritis (TAK) is a relatively rare systemic vasculitis mainly affecting the aorta and its large branches. While patients with TAK are more frequently observed in Asian countries, we can find patients with TAK all over the world. This limited number of patients has made it difficult to collect large numbers of patients and perform detailed studies. However, recent progresses have led to the identification of susceptibility genes and novel susceptibility human leukocyte antigen (HLA) alleles as well as accumulation of clues for the pathophysiology of TAK. IL12B was shown to be a susceptibility gene beyond ethnicity. MLX and FCGR2A/3A were shown to be associated with TAK in Japanese and Turkish/American populations, respectively. HLA-B*52:01 and *67:01 are susceptibility alleles to TAK, and the 171st and 67th amino acid residues of HLA-B protein are suggested important for TAK susceptibility. HLA-DQB1/DRB1 is recently reported as an independent susceptibility locus. Although there are no standardized serum markers or composite measures for disease activity of TAK, Japanese and Italian groups showed pentraxin 3 as a novel biomarker for detecting and monitoring patients with TAK. Recently, an Indian group proposed a novel scoring system called ITAS to evaluate disease activity of TAK. Standardization of assessing disease activity would lead to clinical studies with high quality. Several groups reported results of treatment for refractory TAK with biological agents targeting tumor necrosis factor or interleukin-6R. The recent accumulation of research data should improve understanding of the basic pathophysiology of TAK and lead to better management of patients with TAK. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Takayasu arteritis and ulcerative colitis: high rate of co-occurrence and genetic overlap.

PubMed

Terao, Chikashi; Matsumura, Takayoshi; Yoshifuji, Hajime; Kirino, Yohei; Maejima, Yasuhiro; Nakaoka, Yoshikazu; Takahashi, Meiko; Amiya, Eisuke; Tamura, Natsuko; Nakajima, Toshiki; Origuchi, Tomoki; Horita, Tetsuya; Matsukura, Mitsuru; Kochi, Yuta; Ogimoto, Akiyoshi; Yamamoto, Motohisa; Takahashi, Hiroki; Nakayamada, Shingo; Saito, Kazuyoshi; Wada, Yoko; Narita, Ichiei; Kawaguchi, Yasushi; Yamanaka, Hisashi; Ohmura, Koichiro; Atsumi, Tatsuya; Tanemoto, Kazuo; Miyata, Tetsuro; Kuwana, Masataka; Komuro, Issei; Tabara, Yasuharu; Ueda, Atsuhisa; Isobe, Mitsuaki; Mimori, Tsuneyo; Matsuda, Fumihiko

2015-05-01

Takayasu arteritis (TAK) is a systemic vasculitis affecting large arteries and large branches of the aorta. Ulcerative colitis (UC) is a prevalent autoimmune colitis. Since TAK and UC share HLA-B*52:01 and IL12B as genetic determinants, and since there are case reports of the co-occurrence of these diseases, we hypothesized that UC is a common complication of TAK. We undertook this study to perform a large-scale analysis of TAK, both to evaluate the prevalence of concurrent cases of TAK and UC and to identify and estimate susceptibility genes shared between the 2 diseases. We analyzed a total of 470 consecutive patients with TAK from 14 institutions. We characterized patients with TAK and UC by analyzing clinical manifestations and genetic components. Genetic overlapping of TAK and UC was evaluated with the use of UC susceptibility single-nucleotide polymorphisms by comparing risk directions and effect sizes between susceptibility to the 2 diseases. Thirty of 470 patients with TAK had UC (6.4% [95% confidence interval 4.3-9.0]). This percentage was strikingly higher than that expected from the prevalence of UC in Japan. Patients with TAK complicated with UC developed TAK at an earlier stage of life (P = 0.0070) and showed significant enrichment of HLA-B*52:01 compared to TAK patients without UC (P = 1.0 × 10(-5) ) (odds ratio 12.14 [95% confidence interval 2.96-107.23]). The 110 non-HLA markers of susceptibility to UC significantly displayed common risk directions with susceptibility to TAK (P = 0.0054) and showed significant departure of permutation P values from expected P values (P < 1.0 × 10(-10) ). UC is a major complication of TAK. These 2 diseases share a significant proportion of their genetic background, and HLA-B*52:01 may play a central role in their co-occurrence. © 2015, American College of Rheumatology.

Occupational exposure to ethylene oxide--OSHA. Final rule: supplemental statement of reasons.

PubMed

1985-01-02

On June 22, 1984, the Occupational Safety and Health Administration (OSHA) published a final standard for ethylene oxide (EtO) that established a permissible exposure limit of 1 part EtO per million parts of air determined as an 8-hour time--weighted average (TWA) concentration (29 CFR 1910.1047, 49 FR 25734). The standard also includes provisions for methods of exposure control, personal protective equipment, measurement of employee exposure, training, signs, and labels, medical surveillance, regulated areas, emergencies and recordkeeping. The basis for this action was a determination by OSHA, based on human and animal data, that exposure to EtO presents a carcinogenic, mutagenic, genotoxic, reproductive, neurologic, and sensitization hazard to workers. During the rulemaking proceedings that led to the establishment of the 1 ppm TWA, the issue of whether there was a need for a short-term exposure limit (STEL) for workers protection from EtO was raised. OSHA reserved decision on the adoption of a STEL at the conclusion of the rulemaking in order to permit peer review of the available evidence and to review more fully the arguments and pertinent data regarding the STEL issue. Upon receipt of the analyses from most of the peer reviewers, OSHA published a notice to that effect on September 19, 1984 (49 FR 36659) and invited public comment on the pertinent issues addressed in the peer reviews. Based on the entire rulemaking record, including the peer reviews and public comments received since June 22, the Assistant Secretary has determined that adoption of a STEL for EtO is not warranted by the available health evidence, and that a STEL is not reasonably necessary or appropriate for inclusion in the final EtO standard. OSHA has also asked that NIOSH fund certain additional studies related to whether a dose-rate relationship can be established for EtO, and OSHA will review the results of those studies when they become available.

Measuring Evapotranspiration in Urban Irrigated Lawns in Two Kansas Cities

NASA Astrophysics Data System (ADS)

Shonkwiler, K. B.; Bremer, D.; Ham, J. M.

2011-12-01

Conservation of water is becoming increasingly critical in many metropolitan areas. The use of automated irrigation systems for the maintenance of lawns and landscapes is rising and these systems are typically maladjusted to apply more water than necessary, resulting in water wastage. Provision of accurate estimates of actual lawn water use may assist urbanites in conserving water through better adjustment of automatic irrigation systems. Micrometeorological methods may help determine actual lawn water use by measuring evapotranspiration (ET) from urban lawns. From April - August of 2011, four small tripod-mounted weather stations (tripods, five total) were deployed in twelve residential landscapes in the Kansas cities of Manhattan (MHK) and Wichita (ICT) in the USA (six properties in each city). Each tripod was instrumented to estimate reference crop evapotranspiration (ETo) via the FAO-56 method. During tripod deployment in residential lawns, actual evapotranspiration (ETactual) was measured nearby using a stationary, trailer-mounted eddy covariance (EC) station. The EC station sampled well-watered turf at the K-State Rocky Ford Turfgrass Center within 5 km of the study properties in MHK, and was also deployed at a commercial sod farm 15 - 40 km from the study residences in the greater ICT metro area. The fifth tripod was deployed in the source area of the EC station to estimate ETo in conjunction with tripods in the lawns (i.e., to serve as a reference). Data from EC allowed for computation of a so-called lawn coefficient (Kc) by determining the ratio of ETo from the tripods in residential lawns to ETo from the EC station (ETo,EC); hence, Kc = ETo,tripod / ETo,EC. Using this method, ETactual can be estimated for individual tripods within a lawn. Data suggests that it may be more accurate to quantify ET within individual lawns by microclimate (i.e., determine coefficients for "shaded" and "open/unshaded" portions of a lawn). By finding microclimate coefficients

Effective Thinking Outdoors.

ERIC Educational Resources Information Center

Hyde, Rod

1997-01-01

Effective Thinking Outdoors (ETO) is an organization that teaches thinking skills and strategies via significant outdoor experiences. Identifies the three elements of thinking as creativity, play, and persistence; presents a graphic depiction of the problem-solving process and aims; and describes an ETO exercise, determining old routes of travel…

Evaluation of reference crop evapotranspiration methods in arid, semi-arid and humid regions

USDA-ARS?s Scientific Manuscript database

It is necessary to find a simpler method in different climatic regions to calculate reference crop evapotranspiration (ETo) since the application of the FAO-56 Penman-Monteith method is often restricted due to unavailability of a full weather data set. Seven ETo methods, the de facto standard FAO-56...

Sensitivity analysis of monthly reference crop evapotranspiration trends in Iran: a qualitative approach

NASA Astrophysics Data System (ADS)

Mosaedi, Abolfazl; Ghabaei Sough, Mohammad; Sadeghi, Sayed-Hossein; Mooshakhian, Yousof; Bannayan, Mohammad

2017-05-01

The main objective of this study was to analyze the sensitivity of the monthly reference crop evapotranspiration (ETo) trends to key climatic factors (minimum and maximum air temperature ( T max and T min), relative humidity (RH), sunshine hours ( t sun), and wind speed ( U 2)) in Iran by applying a qualitative detrended method, rather than the historical mathematical approach. Meteorological data for the period of 1963-2007 from five synoptic stations with different climatic characteristics, including Mashhad (mountains), Tabriz (mountains), Tehran (semi-desert), Anzali (coastal wet), and Shiraz (semi-mountains) were used to address this objective. The Mann-Kendall test was employed to assess the trends of ETo and the climatic variables. The results indicated a significant increasing trend of the monthly ETo for Mashhad and Tabriz for most part of the year while the opposite conclusion was drawn for Tehran, Anzali, and Shiraz. Based on the detrended method, RH and U 2 were the two main variables enhancing the negative ETo trends in Tehran and Anzali stations whereas U 2 and temperature were responsible for this observation in Shiraz. On the other hand, the main meteorological variables affecting the significant positive trend of ETo were RH and t sun in Tabriz and T min, RH, and U 2 in Mashhad. Although a relative agreement was observed in terms of identifying one of the first two key climatic variables affecting the ETo trend, the qualitative and the quantitative sensitivity analysis solutions did never coincide. Further research is needed to evaluate this interesting finding for other geographic locations, and also to search for the major causes of this discrepancy.

Assessing reference evapotranspiration at regional scale based on remote sensing, weather forecast and GIS tools

NASA Astrophysics Data System (ADS)

Ramírez-Cuesta, J. M.; Cruz-Blanco, M.; Santos, C.; Lorite, I. J.

2017-03-01

Reference evapotranspiration (ETo) is a key component in efficient water management, especially in arid and semi-arid environments. However, accurate ETo assessment at the regional scale is complicated by the limited number of weather stations and the strict requirements in terms of their location and surrounding physical conditions for the collection of valid weather data. In an attempt to overcome this limitation, new approaches based on the use of remote sensing techniques and weather forecast tools have been proposed. Use of the Land Surface Analysis Satellite Application Facility (LSA SAF) tool and Geographic Information Systems (GIS) have allowed the design and development of innovative approaches for ETo assessment, which are especially useful for areas lacking available weather data from weather stations. Thus, by identifying the best-performing interpolation approaches (such as the Thin Plate Splines, TPS) and by developing new approaches (such as the use of data from the most similar weather station, TS, or spatially distributed correction factors, CITS), errors as low as 1.1% were achieved for ETo assessment. Spatial and temporal analyses reveal that the generated errors were smaller during spring and summer as well as in homogenous topographic areas. The proposed approaches not only enabled accurate calculations of seasonal and daily ETo values, but also contributed to the development of a useful methodology for evaluating the optimum number of weather stations to be integrated into a weather station network and the appropriateness of their locations. In addition to ETo, other variables included in weather forecast datasets (such as temperature or rainfall) could be evaluated using the same innovative methodology proposed in this study.

Transforming growth factor β-activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-β/TGFR pathway.

PubMed

Zhang, Liangyu; Fu, Zelong; Li, Xia; Tang, Haitao; Luo, Jiesi; Zhang, Dehui; Zhuang, Yongzhi; Han, Zhiyang; Yin, Mingzhu

2017-09-01

Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies. © 2017 John Wiley & Sons A/S.

Effects of 5,14-HEDGE, a 20-HETE mimetic, on lipopolysaccharide-induced changes in MyD88/TAK1/IKKβ/IκB-α/NF-κB pathway and circulating miR-150, miR-223, and miR-297 levels in a rat model of septic shock

PubMed Central

Sari, A. Nihal; Korkmaz, Belma; Serin, Mehmet Sami; Kacan, Meltem; Unsal, Demet; Buharalioglu, C. Kemal; Firat, Seyhan Sahan; Manhati, Vijay L.; Falck, John R.; Malik, Kafait U.; Tunctan, Bahar

2014-01-01

Objectives We have previously demonstrated that a stable synthetic analog of 20-hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), which mimics the effects of endogenously produced 20-HETE, prevents vascular hyporeactivity, hypotension, tachycardia, inflammation, and mortality in a rodent model of septic shock. The present study was performed to determine whether decreased renal and cardiovascular expression and activity of myeloid differentiation factor 88 (MyD88)/transforming growth factor-activated kinase 1 (TAK1)/inhibitor of κB (IκB) kinase β (IKKβ)/IκB-α/nuclear factor-κB (NF-κB) pathway and reduced circulating microRNA (miR)-150, miR-223, and miR-297 expression levels participate in the protective effect of 5,14-HEDGE against hypotension, tachycardia, and inflammation in response to systemic administration of lipopolysaccharide (LPS). Methods Conscious male Wistar rats received saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. Separate groups of LPS-treated rats were given 5,14-HEDGE (30 mg/kg) 1 h after injection of saline or LPS. The rats were sacrificed 4 h after LPS challenge and blood, kidney, heart, thoracic aorta, and superior mesenteric artery were collected for measurement of the protein expression. Results LPS-induced fall in blood pressure and rise in heart rate were associated with increased MyD88 expression and phosphorylation of TAK1 and IκB-α in cytosolic fractions of the tissues. LPS also caused an increase in both unphosphorylated and phosphorylated NF-κB p65 proteins in the cytosolic and nuclear fractions as well as nuclear translocation of NF-κB p65. In addition, serum miR-150, miR-223, and miR-297 expression levels were increased in LPS-treated rats. These effects of LPS were prevented by 5,14-HEDGE. Conclusions These results suggest that downregulation of MyD88/TAK1/IKKβ/IκB-α/NF-κB pathway as well as

CSTI Earth-to-orbit propulsion research and technology program overview

NASA Technical Reports Server (NTRS)

Gentz, Steven J.

1993-01-01

NASA supports a vigorous Earth-to-orbit (ETO) research and technology program as part of its Civil Space Technology Initiative. The purpose of this program is to provide an up-to-date technology base to support future space transportation needs for a new generation of lower cost, operationally efficient, long-lived and highly reliable ETO propulsion systems by enhancing the knowledge, understanding and design methodology applicable to advanced oxygen/hydrogen and oxygen/hydrocarbon ETO propulsion systems. Program areas of interest include analytical models, advanced component technology, instrumentation, and validation/verification testing. Organizationally, the program is divided between technology acquisition and technology verification as follows: (1) technology acquisition; and (2) technology verification.

21 CFR 880.6100 - Ethylene oxide gas aerator cabinet.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ethylene oxide gas aerator cabinet. 880.6100... Miscellaneous Devices § 880.6100 Ethylene oxide gas aerator cabinet. (a) Identification. An ethyene oxide gas... required to remove residual ethylene oxide (ETO) from wrapped medical devices that have undergone ETO...

GW501516, a PPARδ agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disease via inhibition of TAK1-NFκB pathway in mice.

PubMed

Yang, Xu; Kume, Shinji; Tanaka, Yuki; Isshiki, Keiji; Araki, Shin-ichi; Chin-Kanasaki, Masami; Sugimoto, Toshiro; Koya, Daisuke; Haneda, Masakazu; Sugaya, Takeshi; Li, Detian; Han, Ping; Nishio, Yoshihiko; Kashiwagi, Atsunori; Maegawa, Hiroshi; Uzu, Takashi

2011-01-01

Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family of ligand-inducible transcription factors, which have three different isoforms: PPARα, δ and γ. It has been demonstrated that PPARα and γ agonists have renoprotective effects in proteinuric kidney diseases; however, the role of PPARδ agonists in kidney diseases remains unclear. Thus, we examined the renoprotective effect of GW501516, a PPARδ agonist, in a protein-overload mouse nephropathy model and identified its molecular mechanism. Mice fed with a control diet or GW501516-containing diet were intraperitoneally injected with free fatty acid (FFA)-bound albumin or PBS(-). In the control group, protein overload caused tubular damages, macrophage infiltration and increased mRNA expression of MCP-1 and TNFα. These effects were prevented by GW501516 treatment. In proteinuric kidney diseases, excess exposure of proximal tubular cells to albumin, FFA bound to albumin or cytokines such as TNFα is detrimental. In vitro studies using cultured proximal tubular cells showed that GW501516 attenuated both TNFα- and FFA (palmitate)-induced, but not albumin-induced, MCP-1 expression via direct inhibition of the TGF-β activated kinase 1 (TAK1)-NFκB pathway, a common downstream signaling pathway to TNFα receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases.

GW501516, a PPARδ Agonist, Ameliorates Tubulointerstitial Inflammation in Proteinuric Kidney Disease via Inhibition of TAK1-NFκB Pathway in Mice

PubMed Central

Yang, Xu; Kume, Shinji; Tanaka, Yuki; Isshiki, Keiji; Araki, Shin-ichi; Chin-Kanasaki, Masami; Sugimoto, Toshiro; Koya, Daisuke; Haneda, Masakazu; Sugaya, Takeshi; Li, Detian; Han, Ping; Nishio, Yoshihiko; Kashiwagi, Atsunori; Maegawa, Hiroshi; Uzu, Takashi

2011-01-01

Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family of ligand-inducible transcription factors, which have three different isoforms: PPARα, δ and γ. It has been demonstrated that PPARα and γ agonists have renoprotective effects in proteinuric kidney diseases; however, the role of PPARδ agonists in kidney diseases remains unclear. Thus, we examined the renoprotective effect of GW501516, a PPARδ agonist, in a protein-overload mouse nephropathy model and identified its molecular mechanism. Mice fed with a control diet or GW501516-containing diet were intraperitoneally injected with free fatty acid (FFA)-bound albumin or PBS(−). In the control group, protein overload caused tubular damages, macrophage infiltration and increased mRNA expression of MCP-1 and TNFα. These effects were prevented by GW501516 treatment. In proteinuric kidney diseases, excess exposure of proximal tubular cells to albumin, FFA bound to albumin or cytokines such as TNFα is detrimental. In vitro studies using cultured proximal tubular cells showed that GW501516 attenuated both TNFα- and FFA (palmitate)-induced, but not albumin-induced, MCP-1 expression via direct inhibition of the TGF-β activated kinase 1 (TAK1)-NFκB pathway, a common downstream signaling pathway to TNFα receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases. PMID:21966476

Loss of Par-1a/MARK3/C-TAK1 kinase leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis.

PubMed

Lennerz, Jochen K; Hurov, Jonathan B; White, Lynn S; Lewandowski, Katherine T; Prior, Julie L; Planer, G James; Gereau, Robert W; Piwnica-Worms, David; Schmidt, Robert E; Piwnica-Worms, Helen

2010-11-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a(-/-) but not in control or Par-1b(-/-) mice. The intercrossing of Par-1a(-/-) with Par-1b(-/-) mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a(-/-) mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b(-/-) mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice.

Recent changes and drivers of the atmospheric evaporative demand in the Canary Islands

NASA Astrophysics Data System (ADS)

Vicente-Serrano, Sergio M.; Azorin-Molina, Cesar; Sanchez-Lorenzo, Arturo; El Kenawy, Ahmed; Martín-Hernández, Natalia; Peña-Gallardo, Marina; Beguería, Santiago; Tomas-Burguera, Miquel

2016-08-01

We analysed recent evolution and meteorological drivers of the atmospheric evaporative demand (AED) in the Canary Islands for the period 1961-2013. We employed long and high-quality time series of meteorological variables to analyse current AED changes in this region and found that AED has increased during the investigated period. Overall, the annual ETo, which was estimated by means of the FAO-56 Penman-Monteith equation, increased significantly by 18.2 mm decade-1 on average, with a stronger trend in summer (6.7 mm decade-1). In this study we analysed the contribution of (i) the aerodynamic (related to the water vapour that a parcel of air can store) and (ii) radiative (related to the available energy to evaporate a quantity of water) components to the decadal variability and trends of ETo. More than 90 % of the observed ETo variability at the seasonal and annual scales can be associated with the variability in the aerodynamic component. The variable that recorded more significant changes in the Canary Islands was relative humidity, and among the different meteorological factors used to calculate ETo, relative humidity was the main driver of the observed ETo trends. The observed trend could have negative consequences in a number of water-depending sectors if it continues in the future.

29 CFR 1910.1047 - Ethylene oxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., rupture of containers, or failure of control equipment that is likely to or does result in an unexpected... shall ensure that precautionary labels are affixed to all containers of EtO whose contents are capable... containers of EtO leave the workplace. For the purpose of this paragraph, reaction vessels, storage tanks...

The Influence of E-Learning on Individual and Collective Empowerment in the Public Sector: An Empirical Study of Korean Government Employees

ERIC Educational Resources Information Center

Hur, Mann Hyung; Im, Yeonwook

2013-01-01

Our study explores the influence of e-learning on individual and collective empowerment by using data collected from e-learning class participants of Korea's Cyber-Education Center. For the survey, a questionnaire was sent to each of the 41 central ministries' education and training officers (ETO) via email. The ETOs distributed the questionnaire…

Climate and ET: Does Plant Water Requirements Increase during Droughts?

NASA Astrophysics Data System (ADS)

Fipps, G.; Bonaiti, G.; Swanson, C.

2012-04-01

With the expected rise in global warming and increased frequency of extreme climate variability in the coming decades, conservation and efficient use of water resources is essential and must make use of the most accurate and representative data available. Historically, governmental and private organizations have used estimates of plant water use estimated from a variety of methods for long-term water planning, for designing hydraulic structures, and for establishing regulatory guidance and conservation programs intended to reduce water waste. In recent years, there has been an expansion of agricultural weather station networks which report daily ETo (potential evapotranspiration) and commercial irrigation controllers with instrumentation which calculate real-time ETo from weather parameters. Efforts are underway to use this more precise information for regional water planning and ETo is routinely used for designing and implementing drought response programs. The year 2011 marked the driest year on record in the State of Texas. Compounding the lack of rainfall was record heat during the summer of 2011. In 2011, real-time ETo (reference evapotranspiration) data in Texas was 30 to 50% higher than historic averages. The implications are quite serious, as most current water planning and drought contingency plans do not take into consideration increases in ET during such periods, and irrigation planning and capacity sizing are based on historic averages of consumptive use. This paper examines the relationship between ET and climate during this extreme climatic event. While the solar radiation was near normal levels, temperature and wind was much higher and dew points much lower than norms. The variability and statistical difference between long term average ETo and ETo measurements (from 2006 to 2011) for selected weather stations of the Texas ET Network.

Impact of ethylene oxide gas sterilization of duodenoscopes after a carbapenem-resistant Enterobacteriaceae outbreak.

PubMed

Naryzhny, Igor; Silas, Dean; Chi, Kenneth

2016-08-01

Carbapenem-resistant Enterobacteriaceae (CRE) outbreaks have been implicated at several medical institutions involving gastroenterology laboratories and, specifically, duodenoscopes. Currently, there are no specific guidelines to eradicate or prevent the outbreak of this bacteria. We describe ethylene oxide (ETO) gas sterilizations of duodenoscopes to address this issue. A complete investigation of the gastroenterology laboratory and an evaluation by the Centers for Disease Control and Prevention concluded that no lapses were found in the reprocessing of the equipment. With no deficiencies to address, we began a novel cleaning process using surgical ETO gas sterilizers in addition to standard endoscope reprocessing recommendations and guidelines, all while trying to eradicate the CRE contamination and prevent future recurrences. We also instituted a surveillance system for recurrence of CRE contamination via monthly cultures of the duodenoscopes. Between October 2013 and April 2014, 589 ERCPs were performed with 645 ETO gas sterilizations of 6 duodenoscopes. Given the extra 16 hours needed to sterilize the duodenoscopes, our institution incurred costs resulting from purchasing additional equipment and surveillance cultures. Four duodenoscopes sustained damage during this period; however, this could not be directly attributed to the sterilization process. Furthermore, after an 18-month success period we encountered a positive CRE culture after sterilization, albeit of a different strain than originally detected during the outbreak. The duodenoscope underwent additional ETO gas sterilization, with a negative repeated culture; all potentially exposed individuals screened negative for CRE. Proper use of high-level disinfection alone may not eliminate multidrug-resistant organisms from duodenoscopes. In this single-center study, the addition of ETO sterilization and frequent monitoring with cultures reduced duodenoscope contamination and eliminated clinical infections

Single-particle spectroscopy on large SAPO-34 crystals at work: methanol-to-olefin versus ethanol-to-olefin processes.

PubMed

Qian, Qingyun; Ruiz-Martínez, Javier; Mokhtar, Mohamed; Asiri, Abdullah M; Al-Thabaiti, Shaeel A; Basahel, Suliman N; van der Bij, Hendrik E; Kornatowski, Jan; Weckhuysen, Bert M

2013-08-19

The formation of hydrocarbon pool (HCP) species during methanol-to-olefin (MTO) and ethanol-to-olefin (ETO) processes have been studied on individual micron-sized SAPO-34 crystals with a combination of in situ UV/Vis, confocal fluorescence, and synchrotron-based IR microspectroscopic techniques. With in situ UV/Vis microspectroscopy, the intensity changes of the λ=400 nm absorption band, ascribed to polyalkylated benzene (PAB) carbocations, have been monitored and fitted with a first-order kinetics at low reaction temperatures. The calculated activation energy (Ea ) for MTO, approximately 98 kJ mol(-1) , shows a strong correlation with the theoretical values for the methylation of aromatics. This provides evidence that methylation reactions are the rate-determining steps for the formation of PAB. In contrast for ETO, the Ea value is approximately 60 kJ mol(-1) , which is comparable to the Ea values for the condensation of light olefins into aromatics. Confocal fluorescence microscopy demonstrates that during MTO the formation of the initial HCP species are concentrated in the outer rim of the SAPO-34 crystal when the reaction temperature is at 600 K or lower, whereas larger HCP species are gradually formed inwards the crystal at higher temperatures. In the case of ETO, the observed egg-white distribution of HCP at 509 K suggests that the ETO process is kinetically controlled, whereas the square-shaped HCP distribution at 650 K is indicative of a diffusion-controlled process. Finally, synchrotron-based IR microspectroscopy revealed a higher degree of alkylation for aromatics for MTO as compared to ETO, whereas high reaction temperatures favor dealkylation processes for both the MTO and ETO processes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Soil water sensor-based and evapotranspiration-based irrigation scheduling for soybean production on a Blackland Prairie soil in humid climate

USDA-ARS?s Scientific Manuscript database

In east-central Mississippi, annual rainfall was 1307 mm and reference evapotranspiration (ETo) was 1210 mm for the 120-year period from 1894 to 2014. From May to October, when major crops are typically grown in this area, monthly rainfall ranged from 72 to 118 mm, and monthly ETo from 94 to 146 mm ...

Mouse embryonic stem cells undergo Charontosis, a novel programmed cell death pathway dependent upon cathepsins, p53, and EndoG, in response to etoposide treatment

PubMed Central

Tichy, Elisia D.; Stephan, Zachary A.; Osterburg, Andrew; Noel, Greg; Stambrook, Peter J.

2013-01-01

Embryonic stem cells (ESCs) are hypersensitive to many DNA damaging agents and can rapidly undergo cell death or cell differentiation following exposure. Treatment of mouse ESCs (mESCs) with etoposide (ETO), a topoisomerase II poison, followed by a recovery period resulted in massive cell death with characteristics of a programmed cell death pathway (PCD). While cell death was both caspase- and necroptosis-independent, it was partially dependent on the activity of lysosomal proteases. A role for autophagy in the cell death process was eliminated, suggesting that ETO induces a novel PCD pathway in mESCs. Inhibition of p53 either as a transcription factor by pifithrin α or in its mitochondrial role by pifithrin μ significantly reduced ESC death levels. Finally, EndoG was newly identified as a protease participating in the DNA fragmentation observed during ETO-induced PCD. We coined the term Charontosis after Charon, the ferryman of the dead in Greek mythology, to refer to the PCD signaling events induced by ETO in mESCs. PMID:23500643

Mouse embryonic stem cells undergo charontosis, a novel programmed cell death pathway dependent upon cathepsins, p53, and EndoG, in response to etoposide treatment.

PubMed

Tichy, Elisia D; Stephan, Zachary A; Osterburg, Andrew; Noel, Greg; Stambrook, Peter J

2013-05-01

Embryonic stem cells (ESCs) are hypersensitive to many DNA damaging agents and can rapidly undergo cell death or cell differentiation following exposure. Treatment of mouse ESCs (mESCs) with etoposide (ETO), a topoisomerase II poison, followed by a recovery period resulted in massive cell death with characteristics of a programmed cell death pathway (PCD). While cell death was both caspase- and necroptosis-independent, it was partially dependent on the activity of lysosomal proteases. A role for autophagy in the cell death process was eliminated, suggesting that ETO induces a novel PCD pathway in mESCs. Inhibition of p53 either as a transcription factor by pifithrin α or in its mitochondrial role by pifithrin μ significantly reduced ESC death levels. Finally, EndoG was newly identified as a protease participating in the DNA fragmentation observed during ETO-induced PCD. We coined the term charontosis after Charon, the ferryman of the dead in Greek mythology, to refer to the PCD signaling events induced by ETO in mESCs. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of reference evapotranspiration methods in arid, semiarid, and humid regions

Treesearch

Fei Gao; Gary Feng; Ying Ouyang; Huixiao Wang; Daniel Fisher; Ardeshir Adeli; Johnie Jenkins

2017-01-01

It is often necessary to find a simpler method in different climatic regions to calculate reference crop evapotranspiration (ETo) since the application of the FAO-56 Penman-Monteith method is often restricted due to the unavailability of a comprehensive weather dataset. Seven ETo methods, namely the standard FAO-56 Penman-Monteith, the FAO-24 Radiation, FAO-24 Blaney...

Improving medium-range and seasonal hydroclimate forecasts in the southeast USA

NASA Astrophysics Data System (ADS)

Tian, Di

Accurate hydro-climate forecasts are important for decision making by water managers, agricultural producers, and other stake holders. Numerical weather prediction models and general circulation models may have potential for improving hydro-climate forecasts at different scales. In this study, forecast analogs of the Global Forecast System (GFS) and Global Ensemble Forecast System (GEFS) based on different approaches were evaluated for medium-range reference evapotranspiration (ETo), irrigation scheduling, and urban water demand forecasts in the southeast United States; the Climate Forecast System version 2 (CFSv2) and the North American national multi-model ensemble (NMME) were statistically downscaled for seasonal forecasts of ETo, precipitation (P) and 2-m temperature (T2M) at the regional level. The GFS mean temperature (Tmean), relative humidity, and wind speed (Wind) reforecasts combined with the climatology of Reanalysis 2 solar radiation (Rs) produced higher skill than using the direct GFS output only. Constructed analogs showed slightly higher skill than natural analogs for deterministic forecasts. Both irrigation scheduling driven by the GEFS-based ETo forecasts and GEFS-based ETo forecast skill were generally positive up to one week throughout the year. The GEFS improved ETo forecast skill compared to the GFS. The GEFS-based analog forecasts for the input variables of an operational urban water demand model were skillful when applied in the Tampa Bay area. The modified operational models driven by GEFS analog forecasts showed higher forecast skill than the operational model based on persistence. The results for CFSv2 seasonal forecasts showed maximum temperature (Tmax) and Rs had the greatest influence on ETo. The downscaled Tmax showed the highest predictability, followed by Tmean, Tmin, Rs, and Wind. The CFSv2 model could better predict ETo in cold seasons during El Nino Southern Oscillation (ENSO) events only when the forecast initial condition was in

Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid.

PubMed

Takaoka, Saori; Kamioka, Yuji; Takakura, Kanako; Baba, Ai; Shime, Hiroaki; Seya, Tsukasa; Matsuda, Michiyuki

2016-05-01

Transforming growth factor-β activated kinase 1 (TAK1) has been shown to play a crucial role in cell death, differentiation, and inflammation. Here, we live-imaged robust TAK1 activation in Lewis lung carcinoma 3LL cells implanted into the s.c. tissue of syngeneic C57BL/6 mice and treated with polyinosinic:polycytidylic acid (PolyI:C). First, we developed and characterized a Förster resonance energy transfer-based biosensor for TAK1 activity. The TAK1 biosensor, named Eevee-TAK1, responded to stress-inducing reagents such as anisomycin, tumor necrosis factor-α, and interleukin1-β. The anisomycin-induced increase in Förster resonance energy transfer was abolished by the TAK1 inhibitor (5z)-7-oxozeaenol. Activity of TAK1 in 3LL cells was markedly increased by PolyI:C in the presence of macrophages. 3LL cells expressing Eevee-TAK1 were implanted into mice and observed through imaging window by two-photon excitation microscopy. During the growth of tumor, the 3LL cells at the periphery of the tumor showed higher TAK1 activity than the 3LL cells located at the center of the tumor, suggesting that cells at the periphery of the tumor mass were under stronger stress. Injection of PolyI:C, which is known to induce regression of the implanted tumors, induced marked and homogenous TAK1 activation within the tumor tissues. The effect of PolyI:C faded within 4 days. These observations suggest that Eevee-TAK1 is a versatile tool to monitor cellular stress in cancer tissues. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Past and future spatiotemporal changes in evapotranspiration and effective moisture on the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Yin, Yunhe; Wu, Shaohong; Zhao, Dongsheng

2013-10-01

evaporative demand has decreased worldwide during the past several decades. This trend is also noted on the Tibetan Plateau, a region that is particularly sensitive to climate change. However, patterns and trends of evapotranspiration and their relationship to drought stress on the Tibetan Plateau are complex and poorly understood. Here, we analyze spatiotemporal changes in evapotranspiration and effective moisture (defined as the ratio of actual evapotranspiration (ETa) to reference crop evapotranspiration (ETo)) based on the modified Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ). Climate data from 80 meteorological stations on the Tibetan Plateau were compiled for the period 1981-2010 and future climate projections were generated by a regional climate model through the 21st century. The results show regional trends towards decreasing ETo and statistically significant increases in ETa (p < 0.05) and effective moisture during the period 1981-2010 (p < 0.001). A transition from significant negative to positive ETo occurred in 1997. Additionally, a pronounced increase in effective moisture occurred during the period 1981-1997 because of significant decreased ETo before 1997. In the future, regional ETo and ETa are projected to increase, thus reducing drought stress, because of generally increased effective moisture. Future regional differences are most pronounced in terms of effective moisture, which shows notable increases in the northwestern plateau and decreases in the southeastern plateau. Moreover, the reduced magnitude of effective moisture is likely to intensify in the long term, due mainly to increased evaporative demand.

Acute tier-1 and tier-2 effect assessment approaches in the EFSA Aquatic Guidance Document: are they sufficiently protective for insecticides?

PubMed

van Wijngaarden, René P A; Maltby, Lorraine; Brock, Theo C M

2015-08-01

The objective of this paper is to evaluate whether the acute tier-1 and tier-2 methods as proposed by the Aquatic Guidance Document recently published by the European Food Safety Authority (EFSA) are appropriate for deriving regulatory acceptable concentrations (RACs) for insecticides. The tier-1 and tier-2 RACs were compared with RACs based on threshold concentrations from micro/mesocosm studies (ETO-RAC). A lower-tier RAC was considered as sufficiently protective, if less than the corresponding ETO-RAC. ETO-RACs were calculated for repeated (n = 13) and/or single pulsed applications (n = 17) of 26 insecticides to micro/mesocosms, giving a maximum of 30 insecticide × application combinations (i.e. cases) for comparison. Acute tier-1 RACs (for 24 insecticides) were lower than the corresponding ETO-RACs in 27 out of 29 cases, while tier-2 Geom-RACs (for 23 insecticides) were lower in 24 out of 26 cases. The tier-2 SSD-RAC (for 21 insecticides) using HC5 /3 was lower than the ETO-RAC in 23 out of 27 cases, whereas the tier-2 SSD-RAC using HC5 /6 was protective in 25 out of 27 cases. The tier-1 and tier-2 approaches proposed by EFSA for acute effect assessment are sufficiently protective for the majority of insecticides evaluated. Further evaluation may be needed for insecticides with more novel chemistries (neonicotinoids, biopesticides) and compounds that show delayed effects (insect growth regulators). © 2014 Society of Chemical Industry.

Biological treatments in giant cell arteritis & Takayasu arteritis.

PubMed

Samson, Maxime; Espígol-Frigolé, Georgina; Terrades-García, Nekane; Prieto-González, Sergio; Corbera-Bellalta, Marc; Alba-Rovira, Roser; Hernández-Rodríguez, José; Audia, Sylvain; Bonnotte, Bernard; Cid, Maria C

2018-04-01

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the two main large vessel vasculitides. They share some similarities regarding their clinical, radiological and histological presentations but some pathogenic processes in GCA and TAK are activated differently, thus explaining their different sensitivity to biological therapies. The treatment of GCA and TAK essentially relies on glucocorticoids. However, thanks to major progress in our understanding of their pathogenesis, the role of biological therapies in the treatment of these two vasculitides is expanding, especially in relapsing or refractory diseases. In this review, the efficacy, the safety and the limits of the main biological therapies ever tested in GCA and TAK are discussed. Briefly, anti TNF-α agents appear to be effective in treating TAK but not GCA. Recent randomized placebo-controlled trials have reported on the efficacy and safety of abatacept and mostly tocilizumab in inducing and maintaining remission of GCA. Abatacept was not effective in TAK and robust data are still lacking to draw any conclusions concerning the use of tocilizumab in TAK. Furthermore, ustekinumab appears promising in relapsing/refractory GCA whereas rituximab has been reported to be effective in only a few cases of refractory TAK patients. If a biological therapy is indicated, and in light of the data discussed in this review, the first choice would be tocilizumab in GCA and anti-TNF-α agents (mainly infliximab) in TAK. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

[Susceptibility HLA alleles and amino acids to Takayasu arteritis].

PubMed

Terao, Chikashi; Yoshifuji, Hajime; Mimori, Tsuneyo; Matsuda, Fumihiko

2014-01-01

Takayasu arteritis (TAK) is a systemic vasculitis affecting aorta and its large branches which were firstly reported from Japan. TAK develops mainly in young females and the number of patients with TAK in Japan is estimated about 6,000 to 10,000. This low prevalence has made genetic studies of TAK difficult to elucidate its genetic background. The HLA region, especially HLA-B locus, is the strongest susceptibility locus to TAK. The association between TAK and HLA-B*52:01 has been established beyond ethnicity. Recently, two different Japanese research groups identified HLA-B67:01, a relatively rare allele in East Asian population, as a novel susceptibility allele. At the same time, two amino acid variations, namely, histidine at position 171 and phenylalanine at position 67 were reported as susceptibility and protective variations, respectively. Since these positions of amino acid are in the peptide binding grooves of HLA-B protein, changes of peptide-binding in MHC class I seem to play a critical role on susceptibility to TAK. Furthermore, the importance of these two amino acid variations would explain the lack of susceptibility effect of HLA-B*51:01 to TAK, which shares most of amino acid sequences with HLA-B*52:01 except for two amino acids including the position 67.

The Use of Punishment and Time-Out in a Residential Treatment Program for Emotionally Disturbed Children.

ERIC Educational Resources Information Center

Swartz, Stanley L.; Benjamin, Candice

The use of punishment and time-out with 54 severely emotionally disturbed and behavior disordered children (7-13 years old) in a residential school and treatment program was examined. Both exclusion (E:TO) and isolation (I:TO) varieties of time-out were applied. In E:TO, the student was placed in a portion of the room not being used or in the…

The saline load test of the knee redefined: a test to detect traumatic arthrotomies and rule out periarticular wounds not requiring surgical intervention.

PubMed

Konda, Sanjit R; Howard, Daniel; Davidovitch, Roy I; Egol, Kenneth A

2013-09-01

To describe the use of the saline load test (SLT) using a new definition that more adequately characterizes its use in the emergency department (ED) setting. Retrospective review. Level I trauma center. Fifty consecutive patients who underwent an SLT of the knee in the ED and had a minimum of 14 days follow-up. Saline Load Test. Positive traumatic arthrotomy of the knee (+TAK) defined as operating room (OR) confirmation of an arthrotomy (assumed to develop a septic knee) or -SLT with follow-up revealing a septic knee. Periarticular wound equivalent to no traumatic arthrotomy of the knee [pw = (-TAK)] defined as OR evaluation revealing no arthrotomy (assumed not to develop a septic knee) or -SLT whose follow-up revealed no septic knee. Development of a septic knee was considered the gold standard for determining true positives/negatives and false positives/negatives. The mean wound size was 3.9 ± 4.3 cm and the mean saline load volume was 74.9 ± 28.2 cm. There were 19 +SLTs of which there were 16 +TAK and 3 pw = (-TAK). The 3 pw = (-TAK) in the +SLT group were evaluated in the OR where inspection of the joint capsule revealed the absence of a traumatic arthrotomy. There were 31 -SLTs of which there were 1 +TAK and 30 pw = (-TAK). The SLT has a sensitivity of 94% and a specificity of 91% for detecting +TAKs and ruling out periarticular wounds not requiring surgical intervention [pw = (-TAK)]. The false-positive rate of the SLT to detect +TAK is 9%. Using +TAK and pw = (-TAK) as the newly defined measures of the SLT, we report the sensitivity (94%) and specificity (91%) of the SLT in the ED setting while still maintaining the clinical relevancy of the test. Based on a small sample size, knees with small periarticular wounds and a -SLT and no other radiographic or clinical evidence of an arthrotomy appear to have an infection rate of 0% with nonoperative management. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Comparative assessment of several post-processing methods for correcting evapotranspiration forecasts derived from TIGGE datasets.

NASA Astrophysics Data System (ADS)

Tian, D.; Medina, H.

2017-12-01

Post-processing of medium range reference evapotranspiration (ETo) forecasts based on numerical weather prediction (NWP) models has the potential of improving the quality and utility of these forecasts. This work compares the performance of several post-processing methods for correcting ETo forecasts over the continental U.S. generated from The Observing System Research and Predictability Experiment (THORPEX) Interactive Grand Global Ensemble (TIGGE) database using data from Europe (EC), the United Kingdom (MO), and the United States (NCEP). The pondered post-processing techniques are: simple bias correction, the use of multimodels, the Ensemble Model Output Statistics (EMOS, Gneitting et al., 2005) and the Bayesian Model Averaging (BMA, Raftery et al., 2005). ETo estimates based on quality-controlled U.S. Regional Climate Reference Network measurements, and computed with the FAO 56 Penman Monteith equation, are adopted as baseline. EMOS and BMA are generally the most efficient post-processing techniques of the ETo forecasts. Nevertheless, the simple bias correction of the best model is commonly much more rewarding than using multimodel raw forecasts. Our results demonstrate the potential of different forecasting and post-processing frameworks in operational evapotranspiration and irrigation advisory systems at national scale.

Association of Takayasu arteritis with HLA-B 67:01 and two amino acids in HLA-B protein.

PubMed

Terao, Chikashi; Yoshifuji, Hajime; Ohmura, Koichiro; Murakami, Kosaku; Kawabata, Daisuke; Yurugi, Kimiko; Tazaki, Junichi; Kinoshita, Hideyuki; Kimura, Akinori; Akizuki, Masashi; Kawaguchi, Yasushi; Yamanaka, Hisashi; Miura, Yasuo; Maekawa, Taira; Saji, Hiroo; Mimori, Tsuneyo; Matsuda, Fumihiko

2013-10-01

Takayasu arteritis (TAK) is a rare autoimmune arteritis that affects large arteries. Although the association between TAK and HLA-B 52:01 is established, the other susceptibility HLA-B alleles are not fully known. We performed genetic association studies to determine independent HLA-B susceptibility alleles other than HLA-B 52:01 and to identify important amino acids of HLA-B protein in TAK susceptibility. One hundred patients with TAK and 1000 unrelated healthy controls were genotyped for HLA-B alleles in the first set, followed by a replication set containing 73 patients with TAK and 1000 controls to compare the frequencies of HLA-B alleles. Step-up logistic regression analysis was performed to identify susceptibility amino acids of HLA-B protein. Strong associations of susceptibility to TAK with HLA-B 52:01 and HLA-B 67:01 were observed (P = 1.0 × 10(-16) and 9.5 × 10(-6), respectively). An independent susceptibility effect of HLA-B 67:01 from HLA-B 52:01 was also detected (P = 1.8 × 10(-7)). Amino acid residues of histidine at position 171 and phenylalanine at position 67, both of which are located in antigen binding grooves of the HLA-B protein, were associated with TAK susceptibility (P ≤ 3.8 × 10(-5)) with a significant difference from other amino acid variations (ΔAIC ≥ 9.65). HLA-B 67:01 is associated with TAK independently from HLA-B 52:01. Two amino acids in HLA-B protein are strongly associated with TAK susceptibility.

Protective effects of prescription n-3 fatty acids against impairment of spatial cognitive learning ability in amyloid β-infused rats.

PubMed

Hashimoto, Michio; Tozawa, Ryuichi; Katakura, Masanori; Shahdat, Hossain; Haque, Abdul Md; Tanabe, Yoko; Gamoh, Shuji; Shido, Osamu

2011-07-01

Deposition of amyloid β peptide (Aβ) into the brain causes cognitive impairment. We investigated whether prescription pre-administration of n-3 fatty acids improves cognitive learning ability in young rats and whether it protects against learning ability impairments in an animal model of Alzheimer's disease that was prepared by infusion of Aβ(1-40) into the cerebral ventricles of rats. Pre-administration of TAK-085 (highly purified and concentrated n-3 fatty acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of reference memory errors in an 8-arm radial maze, suggesting that long-term administration of TAK-085 improves cognitive leaning ability in rats. After pre-administration, the control group was divided into the vehicle and Aβ-infused groups, whereas the TAK-085 pre-administration group was divided into the TAK-085 and TAK-085 + Aβ groups (TAK-085-pre-administered Aβ-infused rats). Aβ(1-40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Pre-administration of TAK-085 to the Aβ-infused rats significantly suppressed the number of reference and working memory errors and decreased the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus of Aβ-infused rats, suggesting that TAK-085 increases antioxidative defenses. The present study suggests that long-term administration of TAK-085 is a possible therapeutic agent for protecting against Alzheimer's disease-induced learning deficiencies. This journal is © The Royal Society of Chemistry 2011

Comparison of Adrenal Suppression between Etomidate and Dexmedetomidine in Children with Congenital Heart Disease.

PubMed

Gu, Hongbin; Zhang, Mazhong; Cai, Meihua; Liu, Jinfen

2015-05-29

The aim of this study was to compare plasma cortisol concentration during anesthesia of children with congenital heart disease who received dexmedetomidine (DEX) with those who received etomidate (ETO). We recruited 99 ASA physical status II-III pediatric patients scheduled for congenital heart disease (CHD) corrective surgery and divided into them into 3 groups. Group DEX received an infusion of DEX intravenously with a bolus dose of 0.5 µg·kg-1 within 10 min during anesthesia induction, followed by a maintenance dose of DEX 0.5 µg·kg-1·h-1. Group ETO received ETO intravenously with a bolus dose of 0.3 mg·kg-1 without a maintenance dose. Group CON received routine anesthetics as controls. The preset timepoints were: before anesthesia induction (T0), at the end of induction (T1), 30 min after anesthesia induction (T2), at the time of aortic and inferior vena catheterization (T3), and at 180 min (T4) and 24 h (T5) after anesthesia induction. The cortisol concentration decreased gradually after anesthesia induction in all groups, and returned to baseline values after 24 h. The cortisol concentration was significantly lower in Group ETO children than in Group DEX or group CON at T4. The plasma concentrations of cortisol decreased in CHD children after the operation, but returned to baseline after 24 h of anesthesia induction. The adrenal cortex function inhibition induced by ETO in CHD children is longer and more serious than that induced by DEX (if any) during the preoperative period.

Effect of lithium chloride and antineoplastic drugs on survival and cell cycle of androgen-dependent prostate cancer LNCap cells

PubMed Central

Azimian-Zavareh, Vajihe; Hossein, Ghamartaj; Janzamin, Ehsan

2012-01-01

Objective: Glycogen synthase kinase-3β (GSK-3β) has been reported to be required for androgen receptor (AR) activity. This study sought to determine the usefulness of lithium chloride (LiCl) as a highly selective inhibitor of GSK-3β to increase the sensitivity of LNCap cells to doxorubicin (Dox), etoposide (Eto), and vinblastine (Vin) drugs. Materials and Methods: Thiazolyl Blue Tetrazolium Blue (MTT) assay was used to determine the cytotoxic effect to LiCl alone or in combination with low dose and IC50 doses of drugs. Subsequently, cell cycle analysis was performed by using flow cytometry. Results: LiCl showed cytotoxic effect in a dose- and time-dependent manner (P<0.001). Both Dox (100 or 280 nM) and Vin IC50 (5 nM) doses caused G2/M-phase arrest (P<0.001) compared with control. However, low dose (10 μM) or IC50 (70 μM) Eto doses showed G2/M or S-phase arrests, respectively (P<0.001). Combination of low dose or IC50 dose of Eto with LiCl showed increased apoptosis as revealed by high percent of cells in SubG1 (P<0.05, P<0.01, respectively). Moreover, Eto (10 μM) led to decreased percent of cells in G2/M phase when combined with LiCl (P<0.05). Conclusion: This study showed that LiCl increases apoptosis of (LNCap) Lymph Node Carcinoma of the Prostate cells in the presence of Eto, which is S- and G2-phase-specific drug. PMID:23248400

Daily reference crop evapotranspiration with reduced data sets in the humid environments of Azores islands using estimates of actual vapor pressure, solar radiation, and wind speed

NASA Astrophysics Data System (ADS)

Paredes, P.; Fontes, J. C.; Azevedo, E. B.; Pereira, L. S.

2017-11-01

Reference crop evapotranspiration (ETo) estimations using the FAO Penman-Monteith equation (PM-ETo) require a set of weather data including maximum and minimum air temperatures (T max, T min), actual vapor pressure (e a), solar radiation (R s), and wind speed (u 2). However, those data are often not available, or data sets are incomplete due to missing values. A set of procedures were proposed in FAO56 (Allen et al. 1998) to overcome these limitations, and which accuracy for estimating daily ETo in the humid climate of Azores islands is assessed in this study. Results show that after locally and seasonally calibrating the temperature adjustment factor a d used for dew point temperature (T dew) computation from mean temperature, ETo estimations shown small bias and small RMSE ranging from 0.15 to 0.53 mm day-1. When R s data are missing, their estimation from the temperature difference (T max-T min), using a locally and seasonal calibrated radiation adjustment coefficient (k Rs), yielded highly accurate ETo estimates, with RMSE averaging 0.41 mm day-1 and ranging from 0.33 to 0.58 mm day-1. If wind speed observations are missing, the use of the default u 2 = 2 m s-1, or 3 m s-1 in case of weather measurements over clipped grass in airports, revealed appropriated even for the windy locations (u 2 > 4 m s-1), with RMSE < 0.36 mm day-1. The appropriateness of procedure to estimating the missing values of e a, R s, and u 2 was confirmed.

Loss of Par-1a/MARK3/C-TAK1 Kinase Leads to Reduced Adiposity, Resistance to Hepatic Steatosis, and Defective Gluconeogenesis ▿

PubMed Central

Lennerz, Jochen K.; Hurov, Jonathan B.; White, Lynn S.; Lewandowski, Katherine T.; Prior, Julie L.; Planer, G. James; Gereau, Robert W.; Piwnica-Worms, David; Schmidt, Robert E.; Piwnica-Worms, Helen

2010-01-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a−/− but not in control or Par-1b−/− mice. The intercrossing of Par-1a−/− with Par-1b−/− mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a−/− mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b−/− mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice. PMID:20733003

Synthesis, structural characterization, and electrochemical properties of dinuclear Ni/Mn model complexes for the active site of [NiFe]-hydrogenases.

PubMed

Song, Li-Cheng; Li, Jia-Peng; Xie, Zhao-Jun; Song, Hai-Bin

2013-10-07

Four new dinuclear Ni/Mn model complexes RN(PPh2)2Ni(μ-SEt)2(μ-Cl)Mn(CO)3 (7, R = p-MeC6H4CH2; 8, R = EtO2CCH2) and RN(PPh2)2Ni(μ-SEt)2(μ-Br)Mn(CO)3 (9, R = p-MeC6H4CH2; 10, R = EtO2CCH2) have been prepared via the four separated step-reactions involving six new precursors RN(PPh2)2 (1, R = p-MeC6H4CH2; 2, R = EtO2CCH2), RN(PPh2)2NiCl2 (3, R = p-MeC6H4CH2; 4, R = EtO2CCH2), and RN(PPh2)2Ni(SEt)2 (5, R = p-MeC6H4CH2; 6, R = EtO2CCH2). The Et3N-assisted aminolysis of Ph2PCl with p-MeC6H4CH2NH2 or EtO2CCH2NH2·HCl in CH2Cl2 gave the azadiphosphine ligands 1 and 2 in 38% and 53% yields, whereas the coordination reaction of 1 or 2 with NiCl2·6H2O in CH2Cl2/MeOH afforded the mononuclear Ni dichloride complexes 3 and 4 in 59% and 78% yields, respectively. While thiolysis of 3 or 4 with EtSH under the assistance of Et3N in CH2Cl2 produced the mononuclear Ni dithiolate complexes 5 and 6 in 64% and 68% yields, further treatment of 5 and 6 with Mn(CO)5Cl or Mn(CO)5Br resulted in formation of the dinuclear Ni/Mn model complexes 7-10 in 31-73% yields. All the new compounds 1-10 have been structurally characterized, while model complexes 7 and 9 have been found to be catalysts for HOAc proton reduction to hydrogen under CV conditions.

Dithiolato- and halogenido-bridged nickel-iron complexes related to the active site of [NiFe]-H2ases: preparation, structures, and electrocatalytic H2 production.

PubMed

Song, Li-Cheng; Han, Xiao-Feng; Chen, Wei; Li, Jia-Peng; Wang, Xu-Yong

2017-08-14

A new series of the structural and functional models for the active site of [NiFe]-H 2 ases has been prepared by a simple and convenient synthetic route. Thus, treatment of diphosphines RN(PPh 2 ) 2 (1a, R = p-MeC 6 H 4 CH 2 ; 1b, R = EtO 2 CCH 2 ) with an equimolar NiCl 2 ·6H 2 O, NiBr 2 ·3H 2 O, and NiI 2 in refluxing CH 2 Cl 2 /MeOH or EtOH gave the mononuclear Ni complexes RN(PPh 2 ) 2 NiX 2 (2a, R = p-MeC 6 H 4 CH 2 , X = Cl; 2b, R = EtO 2 CCH 2 , X = Cl; 3a, R = p-MeC 6 H 4 CH 2 , X = Br; 3b, R = EtO 2 CCH 2 , X = Br; 4a, R = p-MeC 6 H 4 CH 2 , X = I; 4b, R = EtO 2 CCH 2 , X = I) in 67-97% yields. Further treatment of complexes 2a,b-4a,b with an equimolar mononuclear Fe complex (dppv)(CO) 2 Fe(pdt) and NaBF 4 resulted in formation of the targeted model complexes [RN(PPh 2 ) 2 Ni(μ-pdt)(μ-X)Fe(CO)(dppv)](BF 4 ) (5a, R = p-MeC 6 H 4 CH 2 , X = Cl; 5b, R = EtO 2 CCH 2 , X = Cl; 6a, R = p-MeC 6 H 4 CH 2 , X = Br; 6b, R = EtO 2 CCH 2 , X = Br; 7a, R = p-MeC 6 H 4 CH 2 , X = I; 7b, R = EtO 2 CCH 2 , X = I) in 60-96% yields. All the new complexes 3a,b-4a,b and 5a,b-7a,b have been characterized by elemental analysis and spectroscopy, and particularly for some of them (3a,b/4a,b and 5b/6b) by X-ray crystallography. More interestingly, the electrochemical and electrocatalytic properties of such halogenido-bridged model complexes are first studied systematically and particularly they have been found to be pre-catalysts for proton reduction to H 2 under CV conditions.

Blocking RhoA/ROCK inhibits the pathogenesis of pemphigus vulgaris by suppressing oxidative stress and apoptosis through TAK1/NOD2-mediated NF-κB pathway.

PubMed

Liang, Junqin; Zeng, Xuewen; Halifu, Yilinuer; Chen, Wenjing; Hu, Fengxia; Wang, Peng; Zhang, Huan; Kang, Xiaojing

2017-12-01

Oxidative stress and apoptosis play critical roles in pemphigus vulgaris (PV). The main aim of the present study was to investigate the effects of RhoA/ROCK signaling on UVB-induced oxidative damage, and to delineate the molecular mechanisms involved in the UVB-mediated inflammatory and apoptotic response. In HaCaT cells, we observed that blockage of RhoA/ROCK signaling with the inhibitor CT04 or Y27632 greatly inhibited the UVB-mediated increase in intracellular reactive oxygen species (ROS). Additionally, inhibition of RhoA/ROCK signaling reduced UVB-induced apoptosis, as exemplified by a reduction in DNA fragmentation, and also elevated anti-apoptotic Bcl-2 protein, concomitant with reduced levels of pro-apoptotic protein Bax, caspase-3 cleavage and decreased PARP-1 protein. The release of inflammatory mediators TNF-α, IL-1β, and IL-6 was also attenuated. Mechanically, we observed that blockage of RhoA/ROCK repressed the TAK1/NOD2-mediated NF-κB pathway in HaCaT cells exposed to UVB. Taken together, these data reveal that RhoA/ROCK signaling is one of the regulators contributing to oxidative damage and apoptosis in human keratinocytes, suggesting that RhoA/ROCK signaling has strong potential to be used as a useful therapeutic target in skin diseases including PV.

Proposed Functional Architecture and Associated Benefits Analysis of a Common Ground Control Station for Unmanned Aircraft Systems

DTIC Science & Technology

2010-03-01

143 Table 12. High Level Analysis of O&S Costs of Different Training Options...Station On station 24/7 ( ETOS 80%) On station 24/7 for 30 consecutive days ( ETOS 95%) Mission Radius ≥ 2,000 nm ≥ 3,000 nm Net Ready-KPP COMMON...Training with As-Is Unique GCS Architectures 143 The results of the analysis for BUQs I-IV are shown in Table 11. The data shows that

Optimal Interpolation scheme to generate reference crop evapotranspiration

NASA Astrophysics Data System (ADS)

Tomas-Burguera, Miquel; Beguería, Santiago; Vicente-Serrano, Sergio; Maneta, Marco

2018-05-01

We used an Optimal Interpolation (OI) scheme to generate a reference crop evapotranspiration (ETo) grid, forcing meteorological variables, and their respective error variance in the Iberian Peninsula for the period 1989-2011. To perform the OI we used observational data from the Spanish Meteorological Agency (AEMET) and outputs from a physically-based climate model. To compute ETo we used five OI schemes to generate grids for the five observed climate variables necessary to compute ETo using the FAO-recommended form of the Penman-Monteith equation (FAO-PM). The granularity of the resulting grids are less sensitive to variations in the density and distribution of the observational network than those generated by other interpolation methods. This is because our implementation of the OI method uses a physically-based climate model as prior background information about the spatial distribution of the climatic variables, which is critical for under-observed regions. This provides temporal consistency in the spatial variability of the climatic fields. We also show that increases in the density and improvements in the distribution of the observational network reduces substantially the uncertainty of the climatic and ETo estimates. Finally, a sensitivity analysis of observational uncertainties and network densification suggests the existence of a trade-off between quantity and quality of observations.

An ionic liquid-in-water microemulsion as a potential carrier for topical delivery of poorly water soluble drug: Development, ex-vivo and in-vivo evaluation.

PubMed

Goindi, Shishu; Kaur, Ramanpreet; Kaur, Randeep

2015-11-30

In this paper, we report an ionic liquid-in-water (IL/w) microemulsion (ME) formulation which is able to solubilize etodolac (ETO), a poorly water soluble drug for topical delivery using BMIMPF6 (1-butyl-3-methylimidazolium hexafluorophosphate) as IL, Tween 80 as surfactant and ethanol as co-surfactant. The prepared ME was characterized for physicochemical parameters, subjected to ex-vivo permeation studies as well as in-vivo pharmacodynamic evaluation. The ex-vivo drug permeation studies through rat skin was performed using Franz-diffusion cell and the IL/w based ME showed maximum mean cumulative percent permeation of 99.030±0.921% in comparison to oil-in-water (o/w) ME (61.548±1.875%) and oily solution (48.830±2.488%) of ETO. In-vivo anti-arthritic and anti-inflammatory activities of the prepared formulations were evaluated using different rodent models and the results revealed that ETO loaded IL/w based ME was found to be more effective in controlling inflammation than oily solution, o/w ME and marketed formulation of ETO. Histopathological studies also demonstrated that IL/w based ME caused no anatomical and pathological changes in the skin. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of trend in long term precipitation and reference evapotranspiration over Narmada river basin (India)

NASA Astrophysics Data System (ADS)

Pandey, Brij Kishor; Khare, Deepak

2018-02-01

Precipitation and reference evapotranspiration are key parameters in hydro-meteorological studies and used for agricultural planning, irrigation system design and management. Precipitation and evaporative demand are expected to be alter under climate change and affect the sustainable development. In this article, spatial variability and temporal trend of precipitation and reference evapotranspiration (ETo) were investigated over Narmada river basin (India), a humid tropical climatic region. In the present study, 12 and 28 observatory stations were selected for precipitation and ETo, respectively of 102-years period (1901-2002). A rigorous analysis for trend detection was carried out using non parametric tests such as Mann-Kendall (MK) and Spearman Rho (SR). Sen's slope estimator was used to analyze the rate of change in long term series. Moreover, all the stations of basin exhibit positive trend for annual ETo, while 8% stations indicate significant negative trend for mean annual precipitation, respectively. Change points of annual precipitation were identified around the year 1962 applying Buishand's and Pettit's test. Annual mean precipitation reduced by 9% in upper part while increased maximum by 5% in lower part of the basin due temporal changes. Although annual mean ETo increase by 4-12% in most of the region. Moreover, results of the study are very helpful in planning and development of agricultural water resources.

Time Series Forecasting of Daily Reference Evapotranspiration by Neural Network Ensemble Learning for Irrigation System

NASA Astrophysics Data System (ADS)

Manikumari, N.; Murugappan, A.; Vinodhini, G.

2017-07-01

Time series forecasting has gained remarkable interest of researchers in the last few decades. Neural networks based time series forecasting have been employed in various application areas. Reference Evapotranspiration (ETO) is one of the most important components of the hydrologic cycle and its precise assessment is vital in water balance and crop yield estimation, water resources system design and management. This work aimed at achieving accurate time series forecast of ETO using a combination of neural network approaches. This work was carried out using data collected in the command area of VEERANAM Tank during the period 2004 - 2014 in India. In this work, the Neural Network (NN) models were combined by ensemble learning in order to improve the accuracy for forecasting Daily ETO (for the year 2015). Bagged Neural Network (Bagged-NN) and Boosted Neural Network (Boosted-NN) ensemble learning were employed. It has been proved that Bagged-NN and Boosted-NN ensemble models are better than individual NN models in terms of accuracy. Among the ensemble models, Boosted-NN reduces the forecasting errors compared to Bagged-NN and individual NNs. Regression co-efficient, Mean Absolute Deviation, Mean Absolute Percentage error and Root Mean Square Error also ascertain that Boosted-NN lead to improved ETO forecasting performance.

An Arabidopsis Soil-Salinity–Tolerance Mutation Confers Ethylene-Mediated Enhancement of Sodium/Potassium Homeostasis[W

PubMed Central

Jiang, Caifu; Belfield, Eric J.; Cao, Yi; Smith, J. Andrew C.; Harberd, Nicholas P.

2013-01-01

High soil Na concentrations damage plants by increasing cellular Na accumulation and K loss. Excess soil Na stimulates ethylene-induced soil-salinity tolerance, the mechanism of which we here define via characterization of an Arabidopsis thaliana mutant displaying transpiration-dependent soil-salinity tolerance. This phenotype is conferred by a loss-of-function allele of ETHYLENE OVERPRODUCER1 (ETO1; mutant alleles of which cause increased production of ethylene). We show that lack of ETO1 function confers soil-salinity tolerance through improved shoot Na/K homeostasis, effected via the ETHYLENE RESISTANT1–CONSTITUTIVE TRIPLE RESPONSE1 ethylene signaling pathway. Under transpiring conditions, lack of ETO1 function reduces root Na influx and both stelar and xylem sap Na concentrations, thereby restricting root-to-shoot delivery of Na. These effects are associated with increased accumulation of RESPIRATORY BURST OXIDASE HOMOLOG F (RBOHF)–dependent reactive oxygen species in the root stele. Additionally, lack of ETO1 function leads to significant enhancement of tissue K status by an RBOHF-independent mechanism associated with elevated HIGH-AFFINITY K+ TRANSPORTER5 transcript levels. We conclude that ethylene promotes soil-salinity tolerance via improved Na/K homeostasis mediated by RBOHF-dependent regulation of Na accumulation and RBOHF-independent regulation of K accumulation. PMID:24064768

Revisiting the susceptibility testing of Mycobacterium tuberculosis to ethionamide in solid culture medium.

PubMed

Lakshmi, Rajagopalan; Ramachandran, Ranjani; Kumar, D Ravi; Sundar, A Syam; Radhika, G; Rahman, Fathima; Selvakumar, N; Kumar, Vanaja

2015-11-01

Increase in the isolation of drug resistant phenotypes of Mycobacterium tuberculosis necessitates accuracy in the testing methodology. Critical concentration defining resistance for ethionamide (ETO), needs re-evaluation in accordance with the current scenario. Thus, re-evaluation of conventional minimum inhibitory concentration (MIC) and proportion sensitivity testing (PST) methods for ETO was done to identify the ideal breakpoint concentration defining resistance. Isolates of M. tuberculosis (n=235) from new and treated patients were subjected to conventional MIC and PST methods for ETO following standard operating procedures. With breakpoint concentration set at 114 and 156 µg/ml, an increase in specificity was observed whereas sensitivity was high with 80 µg/ml as breakpoint concentration. Errors due to false resistant and susceptible isolates were least at 80 µg/ml concentration. Performance parameters at 80 µg/ml breakpoint concentration indicated significant association between PST and MIC methods.

The Use of Fresh Whole Blood Transfusions by the SOF Medic for Hemostatic Resuscitation in the Austere Environment

DTIC Science & Technology

2010-11-24

training and safety measures, WFWB transfu- sions can be that tool. Shipment of whole blood collected from rear echelon troops in the ETO , December 1944...Operations. ( ETO ) WWII. (U.S. AMEDD Office of Medical History) Journal of Special Operations Medicine Volume 10, Edition 3 / Summer 1030 Whole blood...27. 5. Brohi, K ., Singh, J., et al. (2003). Acute traumatic coagulo- pathy. Journal of Trauma; 54:1127-1130. 6. Borgman, M. A., Spinella

Enemies into Allies: American Stability Operations and the Transformation of Japan 1945-1952

DTIC Science & Technology

2011-05-19

on Japanese forces in Manchuria finally shattered the last hopes of Emperor Hirohito and Japan’s governmental leadership.7 Jun Eto suggested that...of Modern Japan (New York: HarperCollins Publishers, 2000), 511. 8 Jun Eto , A Nation Reborn – A Short History of Postwar Japan (Tokyo: International...Modern Japan, trans. Mikiso Hane and John K . Urda (New York: Free Press, 1995), 39. First- 17 Brian J. McVeigh, Nationalisms of Japan – Managing and

Optimization of Return Trajectories for Orbital Transfer Vehicle between Earth and Moon

NASA Technical Reports Server (NTRS)

Funase, Ryu; Tsuda, Yuichi; Kawaguchi, Jun'ichiro

2007-01-01

In this paper, optimum trajectories in Earth Transfer Orbit (ETO) for a lunar transportation system are proposed. This paper aims at improving the payload ratio of the reusable orbital transfer vehicle (OTV), which transports the payload from Low Earth Orbit (LEO) to Lunar Low Orbit (LLO) and returns to LEO. In ETO, we discuss ballistic flight using chemical propulsion, multi-impulse flight using electrical propulsion, and aero-assisted flight using aero-brake. The feasibility of the OTV is considered.

New methods for accelerating the convergence of molecular electronic integrals over exponential type orbitals

NASA Astrophysics Data System (ADS)

Safouhi, Hassan; Hoggan, Philip

2003-01-01

This review on molecular integrals for large electronic systems (MILES) places the problem of analytical integration over exponential-type orbitals (ETOs) in a historical context. After reference to the pioneering work, particularly by Barnett, Shavitt and Yoshimine, it focuses on recent progress towards rapid and accurate analytic solutions of MILES over ETOs. Software such as the hydrogenlike wavefunction package Alchemy by Yoshimine and collaborators is described. The review focuses on convergence acceleration of these highly oscillatory integrals and in particular it highlights suitable nonlinear transformations. Work by Levin and Sidi is described and applied to MILES. A step by step description of progress in the use of nonlinear transformation methods to obtain efficient codes is provided. The recent approach developed by Safouhi is also presented. The current state of the art in this field is summarized to show that ab initio analytical work over ETOs is now a viable option.

Climate change uncertainty and risk assessment in Iran during twenty-first century: evapotranspiration and green water deficit analysis

NASA Astrophysics Data System (ADS)

Karandish, Fatemeh; Mousavi, Seyed-Saeed

2018-01-01

For a 120-year period, the projected effects of climate change on annual, seasonal, and monthly potential evapotranspiration (ETo) and green water deficit (GWD) were analyzed involving the associated uncertainties for five climatic zones of Iran. Analysis was carried out using data obtained from 15 general circulation models (GCMs) under three SRES scenarios of A1B, A2, and B1 which were downscaled using LARS-WG for 52 synoptic stations up to 2100. The majority of GCMs as well as the median of the ensemble for each scenario project a positive change in both ETo and GWD. A total of 5.8-19.8 % increase in annual ETo, drier than normal wet seasons, as well as 2.3-56.4 % increase in ETo during December-March period well represent a probable increase in the hydrological water requirement in Iran under global warming. Regarding GWD, the country will experience more arid years requiring 113.7 × 103-576.8 × 103 Mm3 more water to supply annual atmospheric water demand. Semi-arid and Mediterranean regions, principal agricultural producer areas of Iran, will be the most vulnerable part of the country due to 1-38.6 % increase in annual GWD under climate change. In addition, water scarcity for irrigated agriculture will enhance in all climatic zones due to 0.9-41 % increase GWD in June-August. However, rain-fed agriculture might be less affected in the hyper-humid and Mediterranean regions because of 1.1-105.3 % reduction in GWD during wet season. Nevertheless, uncertainty analysis revealed that given results for monthly timescale as well as those for times and regions with lower ETo will be the most uncertain. Based on the results, suitable adaptation solutions are highly required to be undertaken to relieve the extra pressure on the decreased blue water resources in the future.

Examining the value of global seasonal reference evapotranspiration forecasts tosupport FEWS NET's food insecurity outlooks

NASA Astrophysics Data System (ADS)

Shukla, S.; McEvoy, D.; Hobbins, M.; Husak, G. J.; Huntington, J. L.; Funk, C.; Verdin, J.; Macharia, D.

2017-12-01

The Famine Early Warning Systems Network (FEWS NET) team provides food insecurity outlooks for several developing countries in Africa, Central Asia, and Central America. Thus far in terms of agroclimatic conditions that influence food insecurity, FEWS NET's primary focus has been on the seasonal precipitation forecasts while not adequately accounting for the atmospheric evaporative demand, which is also directly related to agricultural production and hence food insecurity, and is most often estimated by reference evapotranspiration (ETo). This presentation reports on the development of a new global ETo seasonal reforecast and skill evaluation with a particular emphasis on the potential use of this dataset by the FEWS NET to support food insecurity early warning. The ETo reforecasts span the 1982-2009 period and are calculated following ASCE's formulation of Penman-Monteith method driven by seasonal climate forecasts of monthly mean temperature, humidity, wind speed, and solar radiation from NCEP's CFSv2 and NASA's GEOS-5 models. The skill evaluation using deterministic and probabilistic scores focuses on the December-February (DJF), March-May (MAM), June-August (JJA) and September-November (SON) seasons. The results indicate that ETo forecasts are a promising tool for early warning of drought and food insecurity. The FEWS NET regions with promising level of skill (correlation >0.35 at lead times of 3 months) include Northern Sub-Saharan Africa (DJF, dry season), Central America (DJF, dry season), parts of East Africa (JJA, wet Season), Southern Africa (JJA, dry season), and Central Asia (MAM, wet season). A case study over parts of East Africa for the JJA season shows that, in combination with the precipitation forecasts, ETo forecasts could have provided early warning of recent severe drought events (e.g., 2002, 2004, 2009) that contributed to substantial food insecurity in the region.

Poor Linkage to Care Despite Significant Improvement in Access to Early cART in Central Poland - Data from Test and Keep in Care (TAK) Project.

PubMed

Kowalska, Justyna D; Shepherd, Leah; Ankiersztejn-Bartczak, Magdalena; Cybula, Aneta; Czeszko-Paprocka, Hanna; Firląg-Burkacka, Ewa; Mocroft, Amanda; Horban, Andrzej

2016-01-01

The main objective of the TAK project is investigating barriers in accessing HIV care after HIV-diagnosis at the CBVCTs of central Poland. Here we describe factors associated with and changes over time in linkage to care and access to cART. Data collected in 2010-2013 in CBVCTs were linked with HIV clinics records using unique identifiers. Individuals were followed from the day of CBVCTs visit until first clinical visit or 4/06/2014. Cox-proportional hazard models were used to identify factors associated with being linked to care and starting cART. In total 232 persons were diagnosed HIV-positive and 144 (62.1% 95%CI: 55.5-68.3) persons were linked to care. There was no change over time in linkage to care (p = 0.48), while time to starting cART decreased (p = 0.02). Multivariate factors associated with a lower rate of linkage to care were hetero/bisexual sexual orientation, lower education, not having an HIV-positive partner and not using condoms in a stable relationship. Multivariate factors associated with starting cART were lower education, recent year of linked to care, and first HIV RNA and CD4 cell count. Benefits of linkage to care, measured by access to early treatment, steadily improved in recent years. However at least 1 in 3 persons aware of their HIV status in central Poland remained outside professional healthcare. Persons at higher risk of remaining outside care, thus target population for future interventions, are bi/heterosexuals and those with lower levels of education.

Multi-decadal shoreline changes on Takú Atoll, Papua New Guinea: Observational evidence of early reef island recovery after the impact of storm waves

NASA Astrophysics Data System (ADS)

Mann, Thomas; Westphal, Hildegard

2016-03-01

Hurricanes, tropical cyclones and other high-magnitude events are important steering mechanisms in the geomorphic development of coral reef islands. Sandy reef islands located outside the storm belts are strongly sensitive to the impact of occasional high-magnitude events and show abrupt, commonly erosive geomorphic change in response to such events. Based on the interpretation of remote sensing data, it is well known that the process of landform recovery might take several decades or even longer. However, despite the increasing amount of scientific attention towards short- and long-term island dynamics, the lack of data and models often prevent a robust analysis of the timing and nature of recovery initiation. Here we show how natural island recovery starts immediately after the impact of a high-magnitude event. We analyze multi-temporal shoreline changes on Takú Atoll, Papua New Guinea and combine our findings with a unique set of published field observations (Smithers and Hoeke, 2014). Trends of shoreline change since 1943 and changes in planform island area indicate a long-term accretionary mode for most islands. Apparent shoreline instability is detected for the last decade of analysis, however this can be explained by the impact of storm waves in December 2008 that (temporarily?) masked the long-term trend. The transition from negative to positive rates of change in the aftermath of this storm event is indicative of inherent negative feedback processes that counteract short-term changes in energy input and represent the initiation of island recovery. Collectively, our results support the concept of dynamic rather than static reef islands and clearly demonstrate how short-term processes can influence interpretations of medium-term change.

Seasonal evaluation of evapotranspiration fluxes from MODIS satellite and mesoscale model downscaled global reanalysis datasets

NASA Astrophysics Data System (ADS)

Srivastava, Prashant K.; Han, Dawei; Islam, Tanvir; Petropoulos, George P.; Gupta, Manika; Dai, Qiang

2016-04-01

Reference evapotranspiration (ETo) is an important variable in hydrological modeling, which is not always available, especially for ungauged catchments. Satellite data, such as those available from the MODerate Resolution Imaging Spectroradiometer (MODIS), and global datasets via the European Centre for Medium Range Weather Forecasts (ECMWF) reanalysis (ERA) interim and National Centers for Environmental Prediction (NCEP) reanalysis are important sources of information for ETo. This study explored the seasonal performances of MODIS (MOD16) and Weather Research and Forecasting (WRF) model downscaled global reanalysis datasets, such as ERA interim and NCEP-derived ETo, against ground-based datasets. Overall, on the basis of the statistical metrics computed, ETo derived from ERA interim and MODIS were more accurate in comparison to the estimates from NCEP for all the seasons. The pooled datasets also revealed a similar performance to the seasonal assessment with higher agreement for the ERA interim (r = 0.96, RMSE = 2.76 mm/8 days; bias = 0.24 mm/8 days), followed by MODIS (r = 0.95, RMSE = 7.66 mm/8 days; bias = -7.17 mm/8 days) and NCEP (r = 0.76, RMSE = 11.81 mm/8 days; bias = -10.20 mm/8 days). The only limitation with downscaling ERA interim reanalysis datasets using WRF is that it is time-consuming in contrast to the readily available MODIS operational product for use in mesoscale studies and practical applications.

Retrieving air humidity, global solar radiation, and reference evapotranspiration from daily temperatures: development and validation of new methods for Mexico. Part III: reference evapotranspiration

NASA Astrophysics Data System (ADS)

Lobit, P.; Gómez Tagle, A.; Bautista, F.; Lhomme, J. P.

2017-07-01

We evaluated two methods to estimate evapotranspiration (ETo) from minimal weather records (daily maximum and minimum temperatures) in Mexico: a modified reduced set FAO-Penman-Monteith method (Allen et al. 1998, Rome, Italy) and the Hargreaves and Samani (Appl Eng Agric 1(2): 96-99, 1985) method. In the reduced set method, the FAO-Penman-Monteith equation was applied with vapor pressure and radiation estimated from temperature data using two new models (see first and second articles in this series): mean temperature as the average of maximum and minimum temperature corrected for a constant bias and constant wind speed. The Hargreaves-Samani method combines two empirical relationships: one between diurnal temperature range ΔT and shortwave radiation Rs, and another one between average temperature and the ratio ETo/Rs: both relationships were evaluated and calibrated for Mexico. After performing a sensitivity analysis to evaluate the impact of different approximations on the estimation of Rs and ETo, several model combinations were tested to predict ETo from daily maximum and minimum temperature alone. The quality of fit of these models was evaluated on 786 weather stations covering most of the territory of Mexico. The best method was found to be a combination of the FAO-Penman-Monteith reduced set equation with the new radiation estimation and vapor pressure model. As an alternative, a recalibration of the Hargreaves-Samani equation is proposed.

Accuracy assessment of NOAA gridded daily reference evapotranspiration for the Texas High Plains

USGS Publications Warehouse

Moorhead, Jerry; Gowda, Prasanna H.; Hobbins, Michael; Senay, Gabriel; Paul, George; Marek, Thomas; Porter, Dana

2015-01-01

The National Oceanic and Atmospheric Administration (NOAA) provides daily reference evapotranspiration (ETref) maps for the contiguous United States using climatic data from North American Land Data Assimilation System (NLDAS). This data provides large-scale spatial representation of ETref, which is essential for regional scale water resources management. Data used in the development of NOAA daily ETref maps are derived from observations over surfaces that are different from short (grass — ETos) or tall (alfalfa — ETrs) reference crops, often in nonagricultural settings, which carries an unknown discrepancy between assumed and actual conditions. In this study, NOAA daily ETos and ETrs maps were evaluated for accuracy, using observed data from the Texas High Plains Evapotranspiration (TXHPET) network. Daily ETos, ETrs and the climatic data (air temperature, wind speed, and solar radiation) used for calculating ETref were extracted from the NOAA maps for TXHPET locations and compared against ground measurements on reference grass surfaces. NOAA ETrefmaps generally overestimated the TXHPET observations (1.4 and 2.2 mm/day ETos and ETrs, respectively), which may be attributed to errors in the NLDAS modeled air temperature and wind speed, to which reference ETref is most sensitive. Therefore, a bias correction to NLDAS modeled air temperature and wind speed data, or adjustment to the resulting NOAA ETref, may be needed to improve the accuracy of NOAA ETref maps.

Two susceptibility loci to Takayasu arteritis reveal a synergistic role of the IL12B and HLA-B regions in a Japanese population.

PubMed

Terao, Chikashi; Yoshifuji, Hajime; Kimura, Akinori; Matsumura, Takayoshi; Ohmura, Koichiro; Takahashi, Meiko; Shimizu, Masakazu; Kawaguchi, Takahisa; Chen, Zhiyong; Naruse, Taeko K; Sato-Otsubo, Aiko; Ebana, Yusuke; Maejima, Yasuhiro; Kinoshita, Hideyuki; Murakami, Kosaku; Kawabata, Daisuke; Wada, Yoko; Narita, Ichiei; Tazaki, Junichi; Kawaguchi, Yasushi; Yamanaka, Hisashi; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Ogawa, Seishi; Komuro, Issei; Nagai, Ryozo; Yamada, Ryo; Tabara, Yasuharu; Isobe, Mitsuaki; Mimori, Tsuneyo; Matsuda, Fumihiko

2013-08-08

Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 × 10(-13), OR = 1.75, 95% CI 1.42-2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 × 10(-7), OR = 1.50, 95% CI 1.28-1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B*52:01, overall p = 2.8 × 10(-21), OR = 2.44, 95% CI 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p ≤ 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p ≤ 0.027). We also found that rs6871626 showed a significant association with clinical manifestations of TAK, including increased risk and severity of aortic regurgitation, a representative severe complication of TAK. Detection of these susceptibility loci will provide new insights to the basic mechanisms of TAK pathogenesis. Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B(∗)52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Prescription n-3 fatty acids, but not eicosapentaenoic acid alone, improve reference memory-related learning ability by increasing brain-derived neurotrophic factor levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

PubMed

Hashimoto, Michio; Inoue, Takayuki; Katakura, Masanori; Tanabe, Yoko; Hossain, Shahdat; Tsuchikura, Satoru; Shido, Osamu

2013-10-01

Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.

Global fit concept in revision hip arthroplasty for cementless press-fit femoral stems.

PubMed

Canovas, F; LeBeguec, P; Batard, J; Gaillard, F; Dagneaux, L

2017-06-01

A revision stem may be required after a femoral extended trochanteric osteotomy (ETO) is made during revision hip arthroplasty. The two main complications of straight cementless femoral stems are subsidence due to inadequate osteointegration and stress-shielding. We will describe an original revision method with ETO that uses a straight cementless stem. The goal of this method was to achieve the most extensive press-fit possible during stem implantation to improve the transmission of stresses to the bone and to prevent reduction in bone density. The intramedullary preparation was done after closure and fixation of the ETO, which allows impaction of the revision stem with metaphyseal and diaphyseal press-fit. We report encouraging results with preservation of periprosthetic bone stock and good osteointegration of these revision stems at the final follow-up. Pronounced sagittal curvature or large bone defects are contraindications for this technique. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Vitamin D Levels in Takayasu's Arteritis and a Review of the Literature on Vasculitides.

PubMed

Alibaz-Oner, Fatma; Asmaz-Haliloglu, Özlem; Gogas-Yavuz, Dilek; Can, Meryem; Haklar, Goncagul; Direskeneli, Haner

2016-09-01

Takayasu's arteritis (TAK) is a chronic, large-vessel vasculitis. Vitamin D, as a steroidal hormone, has recently been shown to have immunoregulatory and immunosuppressive effects. Low vitamin D levels are demonstrated in various autoimmune disorders. The aim of this study is to investigate vitamin D levels in patients with TAK. A comprehensive review of vitamin D levels in systemic vasculitides (SVs) is also performed. The study included 36 patients with TAK, 28 patients with Behçet's disease (BD) as disease control and 30 sex-matched healthy controls. Plasma 25-hydroxy vitamin D (25(OH) vit D) levels were measured with high-performance liquid chromatography. "Deficiency" was defined as 25(OH) vit D levels below 25 nmol/l and "insufficiency" as below 50 nmol/l. Plasma 25(OH) vit D levels were significantly lower in TAK patients (16.93 ± 10.62 nmol/l) than healthy controls (64.63 ± 21.82 nmol/l). Vitamin D level in BD patients (38.8 ± 20.9 nmol/l) is lower than healthy controls but higher than TAK patients. The frequency of vitamin D deficiency was 83.3% in patients with TAK compared to 3.3% in healthy controls. Plasma 25(OH) vit D levels were same between clinically active and inactive patients. In literature review, very few studies were found to investigate vitamin D in SVs. We observed a high prevalence of vitamin D deficiency in patients with TAK. As various immune effects of vitamin D on mononuclear cells and arterial endothelium is shown, vitamin D deficiency can be a predisposing factor for immune activation in SV. We therefore suggest monitorization and replacement of vitamin D status in all TAK and other SV patients. © 2015 Wiley Periodicals, Inc.

Reconstruction of Mammary Gland Structure Using Three-Dimensional Computer-Based Microscopy

DTIC Science & Technology

2001-08-01

Segmentation of Mammary Gland Ductal Structure Using Geometric Methods. P.l.’s Malladi R . and Ortiz de Solorzano C. Submitted to the LBNL Laboratory...mammary gland biology". Fernandez-Gonzalez, R ., Jones A., Garcia-Rodriguez E., Knowles D., Sudar D. Ortiz de Solorzano, C. Proceedings of Microscopy...the text. 25 3DRcn4rclr FieC4 eto m oosOtosMCUCP suto 5 2 3p4 eto 6 ’lw r 26o W ~Fl. Case Section Area Tools Opt~ons Micoscope

Extended time observations of California marine stratocumulus clouds from GOES for July 1983-1987

NASA Technical Reports Server (NTRS)

Minnis, Patrick; Harrison, Edwin F.; Young, David F.

1990-01-01

One of the goals of the First ISCCP Regional Experiment (FIRE) is to relate the relatively small scale (spatial and temporal) Intensive Field Observations (IFO) to larger time and space domains embodied in the Extended Time Observations (ETO) phase of the experiment. The data analyzed as part of the ETO are to be used to determine some climatological features of the limited area which encompasses the Marine Stratocumulus IFO which took place between 29 June and 19 July 1987 off the coast of southern California.

Cascade of care and factors associated with virological suppression among HIV-positive persons linked to care in the Test and Keep in Care (TAK) project.

PubMed

Kowalska, Justyna D; Ankiersztejn-Bartczak, Magdalena; Shepherd, Leah; Mocroft, Amanda

2018-05-21

Early treatment remains the most effective HIV prevention strategy; poor linkage to care after HIV diagnosis may compromise this benefit. We sought to better understand patient characteristics and their association with virological suppression (VS) following cART initiation. The TAK project collects pre-linkage to care and clinical data on patients diagnosed with HIV in voluntary testing facilities in central Poland. Data collected for persons diagnosed in 2010-2013 were linked with HIV clinic records. Individuals linked to care who commenced cART were followed from until the earliest of first VS (HIV RNA < 50 copies/ml), last visit, death or 6 January 2016. Cox-proportional hazard models were used to identify factors associated with first viral suppression. 232 persons were HIV positive, 144 (62%, 95% CI 55, 68%) linked to care, 116 (81% of those linked to care, 95% CI 73, 87%) started cART during follow up, of which 113 (97%, 95% CI 93, 99%) achieved VS. Non-PI based regimen (for integrase inhibitors aHR: 5.03: 1.90, 13.32) and HLA B5701-positive (aHR: 3.97: 1.33, 11.85) were associated with higher chance of VS. Unknown syphilis status (aHR: 0.27: 0.13, 0.57) and higher HIV RNA (aHR a tenfold increase: 0.56: 0.42, 0.75) remained associated with lower chance of VS. Although a low proportion of persons were linked to care, almost all those linked to care started cART and achieved rapid VS. The high rates of VS were irrespective of prior HIV-associated risk behaviours. Linkage to care remains the highest priority in prevention strategies in central Poland.

OSHA's renewed mandate for regulatory flexibility review: in support of the 1984 ethylene oxide standard.

PubMed

LaMontagne, A D; Kelsey, K T

1998-08-01

The Regulatory Flexibility Act of 1980 requires that all federal agencies consider the impact of regulations on small entities. One of the provisions of the Act requires review of regulations ever 10 years to determine whether such regulations should be continued without changes, rescinded, or amended to make them more effective or less burdensome on businesses. The Small Business Regulatory Enforcement Fairness Act (SBREFA) of 1996 amended and expanded the Regulatory Flexibility Act. Most significantly, SBREFA entitles aggrieved small entities or their representative (e.g., trade associations) to sue OSHA for failure to fulfill Regulatory Flexibility Act requirements. In response to this new political reality, OSHA held the first public meeting of their kind in June of 1997 to gather information on the ethylene oxide and lock-out/tag-out standards for the purposes of Regulatory Flexibility review. This paper presents the development of the Regulatory Flexibility review process and details our analysis of the ethylene oxide standard using OSHA's eight Regulatory Flexibility review criteria. Great progress in ethylene oxide health and safety has been made since the promulgation of the standard in 1984, including a considerable decrease in average workshift exposures. Yet, important concerns remain, such as the lack of safer substitutes for EtO's most common uses, the widespread occurrence of accidental exposures to EtO that are not captured by personal monitoring, and the recent increase in the occurrence of catastrophic EtO explosions. Because of the considerable study that has been devoted to EtO and to the EtO standard, there is a very strong cases for either making the EtO standard more worker protective, or continuing the standard without change while improving outreach and enforcement efforts to address shortcomings. Other valuable standards for which fewer data exist may be inappropriately threatened by the Regulatory Flexibility review process. Importantly

Collaborative Model for Acceleration of Individualized Therapy of Colon Cancer

DTIC Science & Technology

2013-10-01

Methods: The anti-proliferative effects of TAK-960 as a single agent and in combination with irinotecan (SN38) or cetuximab were assessed using an assay...following treatment with TAK-960 alone or in combination with standard agents (irinotecan or cetuximab ). Results: CRC cell lines were quite...sensitive to TAK-960 with IC50 values ranging from 0.007 to 1 umol/L. While no synergy was observed in the KRAS WT CRC cell lines in the cetuximab

Inhibition of autophagy by TAB2 and TAB3

PubMed Central

Criollo, Alfredo; Niso-Santano, Mireia; Malik, Shoaib Ahmad; Michaud, Mickael; Morselli, Eugenia; Mariño, Guillermo; Lachkar, Sylvie; Arkhipenko, Alexander V; Harper, Francis; Pierron, Gérard; Rain, Jean-Christophe; Ninomiya-Tsuji, Jun; Fuentes, José M; Lavandero, Sergio; Galluzzi, Lorenzo; Maiuri, Maria Chiara; Kroemer, Guido

2011-01-01

Autophagic responses are coupled to the activation of the inhibitor of NF-κB kinase (IKK). Here, we report that the essential autophagy mediator Beclin 1 and TGFβ-activated kinase 1 (TAK1)-binding proteins 2 and 3 (TAB2 and TAB3), two upstream activators of the TAK1-IKK signalling axis, constitutively interact with each other via their coiled-coil domains (CCDs). Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. Moreover, overexpression of TAB2 and TAB3 suppresses, while their depletion triggers, autophagy. The expression of the C-terminal domain of TAB2 or TAB3 or that of the CCD of Beclin 1 competitively disrupts the interaction between endogenous Beclin 1, TAB2 and TAB3, hence stimulating autophagy through a pathway that requires endogenous Beclin 1, TAK1 and IKK to be optimally efficient. These results point to the existence of an autophagy-stimulatory ‘switch' whereby TAB2 and TAB3 abandon inhibitory interactions with Beclin 1 to engage in a stimulatory liaison with TAK1. PMID:22081109

Inhibition of autophagy by TAB2 and TAB3.

PubMed

Criollo, Alfredo; Niso-Santano, Mireia; Malik, Shoaib Ahmad; Michaud, Mickael; Morselli, Eugenia; Mariño, Guillermo; Lachkar, Sylvie; Arkhipenko, Alexander V; Harper, Francis; Pierron, Gérard; Rain, Jean-Christophe; Ninomiya-Tsuji, Jun; Fuentes, José M; Lavandero, Sergio; Galluzzi, Lorenzo; Maiuri, Maria Chiara; Kroemer, Guido

2011-11-11

Autophagic responses are coupled to the activation of the inhibitor of NF-κB kinase (IKK). Here, we report that the essential autophagy mediator Beclin 1 and TGFβ-activated kinase 1 (TAK1)-binding proteins 2 and 3 (TAB2 and TAB3), two upstream activators of the TAK1-IKK signalling axis, constitutively interact with each other via their coiled-coil domains (CCDs). Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. Moreover, overexpression of TAB2 and TAB3 suppresses, while their depletion triggers, autophagy. The expression of the C-terminal domain of TAB2 or TAB3 or that of the CCD of Beclin 1 competitively disrupts the interaction between endogenous Beclin 1, TAB2 and TAB3, hence stimulating autophagy through a pathway that requires endogenous Beclin 1, TAK1 and IKK to be optimally efficient. These results point to the existence of an autophagy-stimulatory 'switch' whereby TAB2 and TAB3 abandon inhibitory interactions with Beclin 1 to engage in a stimulatory liaison with TAK1.

Effects of different sterilization methods on the physico-chemical and bioresponsive properties of plasma-treated polycaprolactone films.

PubMed

Ghobeira, Rouba; Philips, Charlot; Declercq, Heidi; Cools, Pieter; De Geyter, Nathalie; Cornelissen, Ria; Morent, Rino

2017-01-24

For most tissue engineering applications, surface modification and sterilization of polymers are critical aspects determining the implant success. The first part of this study is thus dedicated to modifying polycaprolactone (PCL) surfaces via plasma treatment using a medium pressure dielectric barrier discharge, while the second part focuses on the sterilization of plasma-modified PCL. Chemical and physical surface changes are examined making use of water contact angle goniometry (WCA), x-ray photoelectron spectroscopy and atomic force microscopy. Bioresponsive properties are evaluated by performing cell culture tests. The results show that air and argon plasmas decrease the WCA significantly due to the incorporation of oxygen-containing functionalities onto the PCL surface, without modifying its morphology. Extended treatment times lead to PCL degradation, especially in the case of air plasma. In addition to surface modification, the plasma potential to sterilize PCL is studied with appropriate treatment times, but sterility has not been achieved so far. Therefore, plasma-modified films are subjected to UV, H 2 O 2 plasma (HP) and ethylene oxide (EtO) sterilizations. UV exposure of 3 h does not alter the PCL physico-chemical properties. A decreased wettability is observed after EtO sterilization, attributable to the modification of PCL chain ends reacting with EtO molecules. HP sterilization increases the WCA of the plasma-treated samples, presumably due to the scission of the hydrophilic bonds generated during the prior plasma treatments. Moreover, HP modifies the PCL surface morphology. For all the sterilizations, an improved cell adhesion and proliferation is observed on plasma-treated films compared to untreated ones. EtO shows the lowest proliferation rate compared to HP and UV. Overall, of the three sterilizations, UV is the most effective, since the physical alterations provoked by HP might interfere with the structural integrity when it comes to 3D

Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

PubMed

Guzeloglu Kayisli, Ozlem; Kayisli, Umit A; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J

2015-01-01

Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription

Randomized Comparison of 3 High-Level Disinfection and Sterilization Procedures for Duodenoscopes.

PubMed

Snyder, Graham M; Wright, Sharon B; Smithey, Anne; Mizrahi, Meir; Sheppard, Michelle; Hirsch, Elizabeth B; Chuttani, Ram; Heroux, Riley; Yassa, David S; Olafsdottir, Lovisa B; Davis, Roger B; Anastasiou, Jiannis; Bapat, Vijay; Bidari, Kiran; Pleskow, Douglas K; Leffler, Daniel; Lane, Benjamin; Chen, Alice; Gold, Howard S; Bartley, Anthony; King, Aleah D; Sawhney, Mandeep S

2017-10-01

Duodenoscopes have been implicated in the transmission of multidrug-resistant organisms (MDRO). We compared the frequency of duodenoscope contamination with MDRO or any other bacteria after disinfection or sterilization by 3 different methods. We performed a single-center prospective randomized study in which duodenoscopes were randomly reprocessed by standard high-level disinfection (sHLD), double high-level disinfection (dHLD), or standard high-level disinfection followed by ethylene oxide gas sterilization (HLD/ETO). Samples were collected from the elevator mechanism and working channel of each duodenoscope and cultured before use. The primary outcome was the proportion of duodenoscopes with an elevator mechanism or working channel culture showing 1 or more MDRO; secondary outcomes included the frequency of duodenoscope contamination with more than 0 and 10 or more colony-forming units (CFU) of aerobic bacterial growth on either sampling location. After 3 months of enrollment, the study was closed because of the futility; we did not observe sufficient events to evaluate the primary outcome. Among 541 duodenoscope culture events, 516 were included in the final analysis. No duodenoscope culture in any group was positive for MDRO. Bacterial growth of more than 0 CFU was noted in 16.1% duodenoscopes in the sHLD group, 16.0% in the dHLD group, and 22.5% in the HLD/ETO group (P = .21). Bacterial growth or 10 or more CFU was noted in 2.3% of duodenoscopes in the sHLD group, 4.1% in the dHLD group, and 4.2% in the HLD/ETO group (P = .36). MRDOs were cultured from 3.2% of pre-procedure rectal swabs and 2.5% of duodenal aspirates. In a comparison of duodenoscopes reprocessed by sHLD, dHLD, or HLD/ETO, we found no significant differences between groups for MDRO or bacteria contamination. Enhanced disinfection methods (dHLD or HLD/ETO) did not provide additional protection against contamination. However, insufficient events occurred to assess our primary study end

Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.

PubMed

Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E

2015-01-01

To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

The genetics of Takayasu arteritis.

PubMed

Renauer, Paul; Sawalha, Amr H

Takayasu arteritis (TAK) is a rare systemic vasculitis that is characterized by granulomatous inflammation of the aorta and its major branches. The cellular and biochemical processes involved in the pathogenesis of TAK are beginning to be elucidated, and implicate both cell and antibody-mediated autoimmune mechanisms. In addition, the underlying etiology to TAK may be explained, at least in part, by a complex genetic contribution. The most well-recognized genetic susceptibility locus for the disease is the classical HLA allele, HLA-B*52, which has been confirmed in several ethnicities. The genetic susceptibility with HLA-B*52, as well as additional classical alleles and loci, implicate both HLA class I and class II involvement in TAK. Furthermore, genetic associations with genes encoding immune response regulators, pro-inflammatory cytokines and mediators of humoral immunity may directly relate to disease mechanisms. Non-HLA susceptibility loci that have been recently established for TAK with a genome-wide level of significance include FCGR2A/FCGR3A, IL12B, IL6, RPS9/LILRB3, and a locus on chromosome 21 near PSMG1. In this review, we present the complex genetic predisposition to TAK and discuss how recent findings identified potential targets in the pathogenesis and treatment of the disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Bin; Li, Wei; Zheng, Qichang

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negativemore » effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.« less

LYATK1 potently inhibits LPS-mediated pro-inflammatory response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xi, Feng; Liu, Yuan; Wang, Xiujuan

Lipopolysaccharide (LPS)-primed monocytes/macrophages produce pro-inflammatory cytokines, which could lead to endotoxin shock. TGF-β-activated kinase1 (TAK1) activation is involved in the process. In the current study, we studied the potential effect of a selective TAK1 inhibitor, LYTAK1, on LPS-stimulated response both in vitro and in vivo. We demonstrated that LYTAK1 inhibited LPS-induced mRNA expression and production of several pro-inflammatory cytokines [interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)] in RAW 264.7 macrophages. LYTAK1's activity was almost nullified with TAK1 shRNA-knockdown. Meanwhile, in both primary mouse bone marrow derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs), LPS-induced pro-inflammatory cytokine productionmore » was again attenuated with LYTAK1 co-treatment. Molecularly, LYTAK1 dramatically inhibited LPS-induced TAK1-nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (Erk, Jnk and p38) activation in RAW 264.7 cells, mouse BMDMs and human PBMCs. In vivo, oral administration of LYTAK1 inhibited LPS-induced activation of TAK1-NFκB-p38 in ex-vivo cultured PBMCs, and cytokine production and endotoxin shock in mice. Together, these results demonstrate that LYTAK1 inhibits LPS-induced production of several pro-inflammatory cytokines and endotoxin shock probably through blocking TAK1-regulated signalings. - Highlights: • LYTAK1 inhibits LPS-induced pro-inflammatory cytokine production in RAW 264.7 cells. • The effect by LYTAK1 is more potent than other known TAK1 inhibitors. • LYTAK1 inhibits LPS-induced cytokine production in primary macrophages/monocytes. • LYTAK1 inhibits LPS-induced TAK1-NFκB and MAPK activation in macrophages/monocytes. • LYTAK1 gavage inhibits LPS-induced endotoxin shock and cytokine production in mice.« less

Influence of deficit irrigation strategies on fatty acid and tocopherol concentration of almond (Prunus dulcis).

PubMed

Zhu, Ying; Taylor, Cathy; Sommer, Karl; Wilkinson, Kerry; Wirthensohn, Michelle

2015-04-15

The effects of deficit irrigation on almond fatty acid and tocopherol levels were studied in a field trial. Mature almond trees were subjected to three levels of deficit irrigation (85%, 70% and 55% of potential crop evapotranspiration (ETo), as well as control (100% ETo) and over-irrigation (120% ETo) treatments. Two deficit irrigation strategies were employed: regulated deficit irrigation (RDI) and sustained deficit irrigation (SDI). Moderate deficit irrigation (85% RDI and 85% SDI) had no detrimental impact on almond kernel lipid content, but severe and extreme deficiencies (70% and 55%) influenced lipid content. Unsaturated fatty acid (USFA) and saturated fatty acid (SFA) contents fluctuated under these treatments, the oleic/linoleic ratio increased under moderate water deficiency, but decreased under severe and extreme water deficiency. Almond tocopherols concentration was relatively stable under deficit irrigation. The variation between years indicated climate has an effect on almond fruit development. In conclusion it is feasible to irrigate almond trees using less water than the normal requirement, without significant loss of kernel quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

Three decades of reference evapotranspiration estimates for a tropical watershed in the eastern Amazon.

PubMed

Silva, Renato O DA; Souza, Everaldo B DE; Tavares, Alexandra L; Mota, José A; Ferreira, Douglas B S; Souza-Filho, Pedro W M; Rocha, Edson J P DA

2017-01-01

This study estimated the reference evapotranspiration rate (ETo) for the Itacaiúnas River Watershed (IRW), Eastern Amazonia, and measured the accuracy of eight empirical equations: Penman-Monteith (PM), Priestley-Taylor (PT), Hargreaves and Samani (HS), Camargo (CAM), Thornthwaite (TH), Hamon (HM), Kharrufa (KF) and Turc (TC) using monthly data from 1980 to 2013. In addition, it verifies the regional applicability to the IRW using a for the Marabá-PA station. The methods TC and PM (FAO56) presented the best results, which demonstrate that radiation and higher temperatures are the dominant drivers in the Evapotranspiration process, while relative humidity and wind speed have a much smaller impact. The temporal and spatial variability of ETo for IRW show has strong seasonality, increasing during the dry season and decreasing during the rainy season. The statistical analyses at 1% level of significance, indicates that there is no correlation of the residuals between the dry and rainy seasons, and test of the physical parameters such as mean temperature, solar radiation and relative air humidity explains the variations of ETo.

Sensitivity of the reference evapotranspiration to key climatic variables during the growing season in the Ejina oasis northwest China.

PubMed

Hou, Lan-Gong; Zou, Song-Bing; Xiao, Hong-Lang; Yang, Yong-Gang

2013-01-01

The standardized FAO56 Penman-Monteith model, which has been the most reasonable method in both humid and arid climatic conditions, provides reference evapotranspiration (ETo) estimates for planning and efficient use of agricultural water resources. And sensitivity analysis is important in understanding the relative importance of climatic variables to the variation of reference evapotranspiration. In this study, a non-dimensional relative sensitivity coefficient was employed to predict responses of ETo to perturbations of four climatic variables in the Ejina oasis northwest China. A 20-year historical dataset of daily air temperature, wind speed, relative humidity and daily sunshine duration in the Ejina oasis was used in the analysis. Results have shown that daily sensitivity coefficients exhibited large fluctuations during the growing season, and shortwave radiation was the most sensitive variable in general for the Ejina oasis, followed by air temperature, wind speed and relative humidity. According to this study, the response of ETo can be preferably predicted under perturbation of air temperature, wind speed, relative humidity and shortwave radiation by their sensitivity coefficients.

High-resolution global grids of revised Priestley-Taylor and Hargreaves-Samani coefficients for assessing ASCE-standardized reference crop evapotranspiration and solar radiation

NASA Astrophysics Data System (ADS)

Aschonitis, Vassilis G.; Papamichail, Dimitris; Demertzi, Kleoniki; Colombani, Nicolo; Mastrocicco, Micol; Ghirardini, Andrea; Castaldelli, Giuseppe; Fano, Elisa-Anna

2017-08-01

The objective of the study is to provide global grids (0.5°) of revised annual coefficients for the Priestley-Taylor (P-T) and Hargreaves-Samani (H-S) evapotranspiration methods after calibration based on the ASCE (American Society of Civil Engineers)-standardized Penman-Monteith method (the ASCE method includes two reference crops: short-clipped grass and tall alfalfa). The analysis also includes the development of a global grid of revised annual coefficients for solar radiation (Rs) estimations using the respective Rs formula of H-S. The analysis was based on global gridded climatic data of the period 1950-2000. The method for deriving annual coefficients of the P-T and H-S methods was based on partial weighted averages (PWAs) of their mean monthly values. This method estimates the annual values considering the amplitude of the parameter under investigation (ETo and Rs) giving more weight to the monthly coefficients of the months with higher ETo values (or Rs values for the case of the H-S radiation formula). The method also eliminates the effect of unreasonably high or low monthly coefficients that may occur during periods where ETo and Rs fall below a specific threshold. The new coefficients were validated based on data from 140 stations located in various climatic zones of the USA and Australia with expanded observations up to 2016. The validation procedure for ETo estimations of the short reference crop showed that the P-T and H-S methods with the new revised coefficients outperformed the standard methods reducing the estimated root mean square error (RMSE) in ETo values by 40 and 25 %, respectively. The estimations of Rs using the H-S formula with revised coefficients reduced the RMSE by 28 % in comparison to the standard H-S formula. Finally, a raster database was built consisting of (a) global maps for the mean monthly ETo values estimated by ASCE-standardized method for both reference crops, (b) global maps for the revised annual coefficients of the P

Myeloid leukemia factor is a conserved regulator of RUNX transcription factor activity involved in hematopoiesis.

PubMed

Bras, Stéphanie; Martin-Lannerée, Séverine; Gobert, Vanessa; Augé, Benoît; Breig, Osman; Sanial, Matthieu; Yamaguchi, Masamitsu; Haenlin, Marc; Plessis, Anne; Waltzer, Lucas

2012-03-27

Defining the function of the genes that, like RUNX1, are deregulated in blood cell malignancies represents an important challenge. Myeloid leukemia factors (MLFs) constitute a poorly characterized family of conserved proteins whose founding member, MLF1, has been associated with acute myeloid leukemia in humans. To gain insight into the functions of this family, we investigated the role of the Drosophila MLF homolog during blood cell development. Here we report that mlf controls the homeostasis of the Drosophila hematopoietic system. Notably, mlf participates in a positive feedback loop to fine tune the activity of the RUNX transcription factor Lozenge (LZ) during development of the crystal cells, one of the two main blood cell lineages in Drosophila. At the molecular level, our data in cell cultures and in vivo strongly suggest that MLF controls the number of crystal cells by protecting LZ from degradation. Remarkably, it appears that the human MLF1 protein can substitute for MLF in the crystal cell lineage. In addition, MLF stabilizes the human oncogenic fusion protein RUNX1-ETO and is required for RUNX1-ETO-induced blood cell disorders in a Drosophila model of leukemia. Finally, using the human leukemic blood cell line Kasumi-1, we show that MLF1 depletion impairs RUNX1-ETO accumulation and reduces RUNX1-ETO-dependent proliferation. Thus, we propose that the regulation of RUNX protein levels is a conserved feature of MLF family members that could be critical for normal and pathological blood cell development.

Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats

PubMed Central

Zhang, Ning; Liang, Hanyu; Farese, Robert V.; Li, Ji

2015-01-01

Aims To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. Materials and Methods For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Results Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Conclusions Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo. PMID:26196892

Direct molecular interactions between Beclin 1 and the canonical NFκB activation pathway.

PubMed

Niso-Santano, Mireia; Criollo, Alfredo; Malik, Shoaib Ahmad; Michaud, Michael; Morselli, Eugenia; Mariño, Guillermo; Lachkar, Sylvie; Galluzzi, Lorenzo; Maiuri, Maria Chaira; Kroemer, Guido

2012-02-01

General (macro)autophagy and the activation of NFκB constitute prominent responses to a large array of intracellular and extracellular stress conditions. The depletion of any of the three subunits of the inhibitor of NFκB (IκB) kinase (IKKα, IKKβ, IKKγ/NEMO), each of which is essential for the canonical NFκB activation pathway, limits autophagy induction by physiological or pharmacological triggers, while constitutive active IKK subunits suffice to stimulate autophagy. The activation of IKK usually relies on TGFβ-activated kinase 1 (TAK1), which is also necessary for the optimal induction of autophagy in multiple settings. TAK1 interacts with two structurally similar co-activators, TAK1-binding proteins 2 and 3 (TAB2 and TAB3). Importantly, in resting conditions both TAB2 and TAB3 bind the essential autophagic factor Beclin 1, but not TAK1. In response to pro-autophagic stimuli, TAB2 and TAB3 dissociate from Beclin 1 and engage in stimulatory interactions with TAK1. The inhibitory interaction between TABs and Beclin 1 is mediated by their coiled-coil domains (CCDs). Accordingly, the overexpression of either TAB2 or TAB3 CCD stimulates Beclin 1- and TAK1-dependent autophagy. These results point to the existence of a direct molecular crosstalk between the canonical NFκB activation pathway and the autophagic core machinery that guarantees the coordinated induction of these processes in response to stress.

A novel susceptibility locus for Takayasu arteritis in the IL12B region can be a genetic marker of disease severity.

PubMed

Matsumura, Takayoshi; Amiya, Eisuke; Tamura, Natsuko; Maejima, Yasuhiro; Komuro, Issei; Isobe, Mitsuaki

2016-06-01

Takayasu arteritis (TAK) is an acute and chronic vasculitis of unknown etiology. Recently, our group reported that SNP rs6871626 in the IL12B region had significant association with disease susceptibility to TAK. However, association of the SNP with clinical characteristics of TAK has yet to be determined. Therefore, we assessed whether this SNP was associated with TAK disease severity as represented by early onset and/or refractoriness to medical therapy. A total of 90 patients were genotyped for rs6871626 and their clinical charts were reviewed retrospectively. By examining the relationship between genotype and clinical profiles of patients, we found a strong association between the number of risk alleles and the frequency of severe cases as defined by (1) age at onset <20 years old, (2) steroid resistance, and/or (3) a relapse of disease [p = 0.03; odds ratio 3.75 (95 % confidence interval 1.13-13.5)]. Thus, our study points to potential diagnostic use of SNP rs6871626 for predicting disease severity of TAK, with the goal of genotyping-oriented therapy in the near future.

A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development.

PubMed

Zhang, Feng; Yu, Jingwen; Yang, Tao; Xu, Dan; Chi, Zhixia; Xia, Yanheng; Xu, Zhiheng

2016-05-27

Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-β (TGF-β) signaling and microcephaly-associated protein WDR62 are important for neuronal migration during brain development; however, the underlying molecular mechanisms involved remain unclear. We show here that knock-out or knockdown of Tak1 (TGFβ-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knock-out and/or knockdown of Tβr2 (type II TGF-β receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly-associated protein WDR62 and the RAC1-interacting protein POSH (plenty of Src homology). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Detection of heterogeneity and evolution of subclones in t(8;21) AML by QM-FISH].

PubMed

Wang, Ying-chan; Hu, Lin-ping; Lin, Dong; Li, Cheng-wen; Yuan, Tian; Jia, Yu-jiao; Tian, Zheng; Tang, Ke-jing; Wang, Min; Wang, Jian-xiang

2013-10-01

To explore the heterogeneous subclones in acute myeloid leukemia (AML) with t(8;21) by quantitative multicolor- fluorescence in situ hybridization (QM-FISH), and to figure out whether there is putative ancestral relationship among different subclones. Bacterial artificial chromosomes (BAC) clones that contain the targeted genes including AML1, ETO, WT1, p27 and c-kit were searched in the data base UCSC Genome Bioinformatics. Multicolor FISH probes were prepared by linking fluorescein labeled dUTP or dCTP to targeted genes by nick translation. Bone marrow mononuclear cells from t (8;21) AML patients are dropped on to the wet surface of glass slides after hypotonic treatment and fixation. After hybridization, the fluorescence signals were captured by Zeiss fluorescence microscope. The copy number of AML1, ETO, WT1, p27, c- kit and the AML1-ETO fusion gene in AML1-ETO positive cells was counted. The cells with same signals were defined as a subclone. Various subclones were recorded and their proportions were calculated, and their evolutionary relationship was deduced. The subclones in matched primary and relapsed samples were compared, the evolution of dominant clones were figured out and the genomic abnormality that is associated with relapse and drug resistance were speculated. In this study, 36 primary AML with t(8;21) cases and 1 relapsed case paired with the primary case were detected. In these 36 primary cases, 4 cases (11.1%) acquired additional AML1-ETO fusion signal, 3(8.3%) had additional AML1 signal, 4(11.1%) had additional ETO signal, 20(55.6%) had additional WT1 signal, 15(41.7%) had additional p27 signal and 14(38.9%) had additional c-kit signal. In addition, 10(27.8%) displayed AML1 signal deletion, and such an aberration represents statistic significance in male patients. It seems that male patients usually accompany AML1 signal deletion. Of 36 cases, 28(77.8 %) harbored at least 2 subclones (ranged from 2 to 10). According to the genetic signature of

Evaluation of Deterministic Models for Near Surface Soil Moisture Prediction

DTIC Science & Technology

1988-05-01

soil hydrological properties (max of 3) ’ . 30. mean length of segment (hWen) 31. cmax of each layer ( cmax I (k,j), k= kno, j=1,jno) 32. porosity of...kelvin Variable name: tac Subroutines: ’bevapor’ Description: air temperature in celsius • * Variable name: tak Subroutines: ’bevapor’ Description: air...3 C - 1 *’ C GET-TABLE-VALUES assign 9865 to i9930 goto 9930 9865 cloud-yn takc-ta tac-( tak -273.15) ea-6. 108*rh*exp( (ac*tac)/ ( tak -bc)) alphi

Tailored scenarios for streamflow climate change impacts based on the perturbation of precipitation and evapotranspiration

NASA Astrophysics Data System (ADS)

Ntegeka, Victor; Willems, Patrick; Baguis, Pierre; Roulin, Emmanuel

2015-04-01

It is advisable to account for a wide range of uncertainty by including the maximum possible number of climate models and scenarios for future impacts. As this is not always feasible, impact assessments are inevitably performed with a limited set of scenarios. The development of tailored scenarios is a challenge that needs more attention as the number of available climate change simulations grows. Whether these scenarios are representative enough for climate change impacts is a question that needs addressing. This study presents a methodology of constructing tailored scenarios for assessing runoff flows including extreme conditions (peak flows) from an ensemble of future climate change signals of precipitation and potential evapotranspiration (ETo) derived from the climate model simulations. The aim of the tailoring process is to formulate scenarios that can optimally represent the uncertainty spectrum of climate scenarios. These tailored scenarios have the advantage of being few in number as well as having a clear description of the seasonal variation of the climate signals, hence allowing easy interpretation of the implications of future changes. The tailoring process requires an analysis of the hydrological impacts from the likely future change signals from all available climate model simulations in a simplified (computationally less expensive) impact model. Historical precipitation and ETo time series are perturbed with the climate change signals based on a quantile perturbation technique that accounts for the changes in extremes. For precipitation, the change in wetday frequency is taken into account using a markov-chain approach. Resulting hydrological impacts from the perturbed time series are then subdivided into high, mean and low hydrological impacts using a quantile change analysis. From this classification, the corresponding precipitation and ETo change factors are back-tracked on a seasonal basis to determine precipitation-ETo covariation. The

NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

NASA Technical Reports Server (NTRS)

Waters, Eric D.; Creech, Dennis M.; Garcia, Jessica; Threet, Grady E., Jr.; Phillips, Alan

2012-01-01

The Earth-to-Orbit Team (ETO) of the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) is considered the pre-eminent go-to group for pre-phase A and phase A concept definition. Over the past several years the ETO team has evaluated thousands of launch vehicle concept variations for a significant number of studies including agency-wide efforts such as the Exploration Systems Architecture Study (ESAS), Constellation, Heavy Lift Launch Vehicle (HLLV), Augustine Report, Heavy Lift Propulsion Technology (HLPT), Human Exploration Framework Team (HEFT), and Space Launch System (SLS). The ACO ETO Team is called upon to address many needs in NASA s design community; some of these are defining extremely large trade-spaces, evaluating advanced technology concepts which have not been addressed by a large majority of the aerospace community, and the rapid turn-around of highly time critical actions. It is the time critical actions, those often limited by schedule or little advanced warning, that have forced the five member ETO team to develop a design process robust enough to handle their current output level in order to meet their customer s needs. Based on the number of vehicle concepts evaluated over the past year this output level averages to four completed vehicle concepts per day. Each of these completed vehicle concepts includes a full mass breakdown of the vehicle to a tertiary level of subsystem components and a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. A structural analysis of the vehicle to determine flight loads based on the trajectory output, material properties, and geometry of the concept is also performed. Due to working in this fast-paced and sometimes rapidly changing environment, the ETO Team has developed a finely tuned process to maximize their delivery capabilities. The objective of this paper is to describe the interfaces

NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

NASA Technical Reports Server (NTRS)

Waters, Eric D.; Garcia, Jessica; Threet, Grady E., Jr.; Phillips, Alan

2013-01-01

The Earth-to-Orbit Team (ETO) of the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) is considered the pre-eminent "go-to" group for pre-phase A and phase A concept definition. Over the past several years the ETO team has evaluated thousands of launch vehicle concept variations for a significant number of studies including agency-wide efforts such as the Exploration Systems Architecture Study (ESAS), Constellation, Heavy Lift Launch Vehicle (HLLV), Augustine Report, Heavy Lift Propulsion Technology (HLPT), Human Exploration Framework Team (HEFT), and Space Launch System (SLS). The ACO ETO Team is called upon to address many needs in NASA's design community; some of these are defining extremely large trade-spaces, evaluating advanced technology concepts which have not been addressed by a large majority of the aerospace community, and the rapid turn-around of highly time critical actions. It is the time critical actions, those often limited by schedule or little advanced warning, that have forced the five member ETO team to develop a design process robust enough to handle their current output level in order to meet their customer's needs. Based on the number of vehicle concepts evaluated over the past year this output level averages to four completed vehicle concepts per day. Each of these completed vehicle concepts includes a full mass breakdown of the vehicle to a tertiary level of subsystem components and a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. A structural analysis of the vehicle to determine flight loads based on the trajectory output, material properties, and geometry of the concept is also performed. Due to working in this fast-paced and sometimes rapidly changing environment, the ETO Team has developed a finely tuned process to maximize their delivery capabilities. The objective of this paper is to describe the interfaces

A Novel Protocol Obviates Endoscope Sampling for Carbapenem-Resistant Enterobacteriaceae: Experience of a Center with a Prior Outbreak.

PubMed

Smith, Zachary L; Dua, Arshish; Saeian, Kia; Ledeboer, Nathan A; Graham, Mary Beth; Aburajab, Murad; Ballard, Darren D; Khan, Abdul H; Dua, Kulwinder S

2017-11-01

Numerous published outbreaks, including one from our institution, have described endoscope-associated transmission of multidrug-resistant organisms (MDROs). Individual centers have adopted their own protocols to address this issue, including endoscope culture and sequestration. Endoscope culturing has drawbacks and may allow residual bacteria, including MDROs, to go undetected after high-level disinfection. To report the outcome of our novel protocol, which does not utilize endoscope culturing, to address our outbreak. All patients undergoing procedures with elevator-containing endoscopes were asked to permit performance of a rectal swab. All endoscopes underwent high-level disinfection according to updated manufacturer's guidance. Additionally, ethylene oxide (EtO) sterilization was done in the high-risk settings of (1) positive response to a pre-procedure risk stratification questionnaire, (2) positive or indeterminate CRE polymerase chain reaction (PCR) from rectal swab, (3) refusal to consent for PCR or questionnaire, (4) purulent cholangitis or infected pancreatic fluid collections. Two endoscopes per weekend were sterilized on a rotational basis. From September 1, 2015 to April 30, 2016, 556 endoscopy sessions were performed using elevator-containing endoscopes. Prompted EtO sterilization was done on 46 (8.3%) instances, 3 from positive/indeterminate PCR tests out of 530 samples (0.6%). No CRE transmission was observed during the study period. Damage or altered performance of endoscopes related to EtO was not observed. In this pilot study, prompted EtO sterilization in high-risk patients has thus far eliminated endoscope-associated MDRO transmission, although no CRE infections were noted throughout the institution during the study period. Further studies and a larger patient sample will be required to validate these findings.

Examining the value of global seasonal reference evapotranspiration forecasts to support FEWS NET’s food insecurity outlooks

USGS Publications Warehouse

Shukla, Shraddhanand; McEvoy, Daniel; Hobbins, Michael; Husak, Gregory; Huntington, Justin; Funk, Chris; Macharia, Denis; Verdin, James P.

2017-01-01

The Famine Early Warning Systems Network (FEWS NET) team provides food insecurity outlooks for several developing countries in Africa, Central Asia, and Central America. This study describes development of a new global reference evapotranspiration (ETo) seasonal reforecast and skill evaluation with a particular emphasis on the potential use of this dataset by the FEWS NET to support food insecurity early warning. The ETo reforecasts span the 1982-2009 period and are calculated following ASCE’s formulation of Penman-Monteith method driven by seasonal climate forecasts of monthly mean temperature, humidity, wind speed, and solar radiation from NCEP’s CFSv2 and NASA’s GEOS-5 models. The skill evaluation using deterministic and probabilistic scores, focuses on the December-February (DJF), March-May (MAM), June-August (JJA) and September-November (SON) seasons. The results indicate that ETo forecasts are a promising tool for early warning of drought and food insecurity. Globally, the regions where forecasts are most skillful (correlation >0.35 at lead-2) include Western U.S., northern parts of South America, parts of Sahel region and Southern Africa. The FEWS NET regions where forecasts are most skillful (correlation >0.35 at lead-3) include Northern Sub-Saharan Africa (DJF, dry season), Central America (DJF, dry season), parts of East Africa (JJA, wet Season), Southern Africa (JJA, dry season), and Central Asia (MAM, wet season). A case study over parts of East Africa for the JJA season shows that ETo forecasts in combination with the precipitation forecasts could have provided early warning of recent severe drought events (e.g., 2002, 2004, 2009) that contributed to substantial food insecurity in the region.

Physical Limitations of Nuclear Propulsion for Earth to Orbit

NASA Technical Reports Server (NTRS)

Blevins, John A.; Patton, Bruce; Rhys, Noah O.; Schafer, Charles F. (Technical Monitor)

2001-01-01

An assessment of current nuclear propulsion technology for application in Earth to Orbit (ETO) missions has been performed. It can be shown that current nuclear thermal rocket motors are not sufficient to provide single stage performance as has been stated by previous studies. Further, when taking a systems level approach, it can be shown that NTRs do not compete well with chemical engines where thrust to weight ratios of greater than I are necessary, except possibly for the hybrid chemical/nuclear LANTR (LOX Augmented Nuclear Thermal Rocket) engine. Also, the ETO mission requires high power reactors and consequently large shielding weights compared to NTR space missions where shadow shielding can be used. In the assessment, a quick look at the conceptual ASPEN vehicle proposed in 1962 in provided. Optimistic NTR designs are considered in the assessment as well as discussion on other conceptual nuclear propulsion systems that have been proposed for ETO. Also, a quick look at the turbulent, convective heat transfer relationships that restrict the exchange of nuclear energy to thermal energy in the working fluid and consequently drive the reactor mass is included.

Etoxazole resistance in predatory mite Phytoseiulus persimilis A.-H. (Acari: Phytoseiidae): Cross-resistance, inheritance and biochemical resistance mechanisms.

PubMed

Yorulmaz Salman, Sibel; Aydınlı, Fatma; Ay, Recep

2015-07-01

Phytoseiulus persimilis of the family Phytoseiidae is an effective predatory mite species that is used to control pest mites. The LC50 and LC60 values of etoxazole were determined on P. persimilis using a leaf-disc method and spraying tower. A laboratory selection population designated ETO6 was found to have a 111.63-fold resistance to etoxazole following 6 selection cycles. This population developed low cross-resistance to spinosad, spiromesifen, acetamiprid, indoxacarb, chlorantraniliprole, milbemectin and moderate cross-resistance to deltamethrin. PBO, IBP and DEM synergised resistance 3.17-, 2.85- and 3.60-fold respectively. Crossing experiments revealed that etoxazole resistance in the ETO6 population was an intermediately dominant and polygenic. In addition, detoxifying enzyme activities were increased 2.71-fold for esterase, 3.09-fold for glutathione S-transferase (GST) and 2.76-fold for cytochrome P450 monooxygenase (P450) in the ETO6 population. Selection for etoxazole under laboratory conditions resulted in the development of etoxazole resistance in the predatory mite P. persimilis that are resistant to pesticides are considered valuable for use in resistance management programmes within integrated pest control strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

Anatomy of a physics test: Validation of the physics items on the Texas Assessment of Knowledge and Skills

NASA Astrophysics Data System (ADS)

Marshall, Jill A.; Hagedorn, Eric A.; O'Connor, Jerry

2009-06-01

We report the results of an analysis of the Texas Assessment of Knowledge and Skills (TAKS) designed to determine whether the TAKS is a valid indicator of whether students know and can do physics at the level necessary for success in future coursework, STEM careers, and life in a technological society. We categorized science items from the 2003 and 2004 10th and 11th grade TAKS by content area(s) covered, knowledge and skills required to select the correct answer, and overall quality. We also analyzed a 5000 student sample of item-level results from the 2004 11th grade exam, performing full-information factor analysis, calculating classical test indices, and determining each item's response curve using item response theory. Triangulation of our results revealed strengths and weaknesses of the different methods of analysis. The TAKS was found to be only weakly indicative of physics preparation and we make recommendations for increasing the validity of standardized physics testing.

Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey.

PubMed

Sahin, Ziver; Bıcakcıgil, Muge; Aksu, Kenan; Kamali, Sevil; Akar, Servet; Onen, Fatos; Karadag, Omer; Ozbalkan, Zeynep; Ates, Askin; Ozer, Huseyin Te; Yilmaz, Vuslat; Seyahi, Emire; Ozturk, Mehmet A; Cefle, Ayse; Cobankara, Veli; Onat, A Mesut; Tunc, Ercan; Düzgün, Nursen; Aydin, Sibel Z; Yilmaz, Neslihan; Fresko, İzzet; Karaaslan, Yasar; Kiraz, Sedat; Akkoc, Nurullah; Inanc, Murat; Keser, Gokhan; Uyar, F Aytul; Direskeneli, Haner; Saruhan-Direskeneli, Güher

2012-02-06

HLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behçet's disease and HLA-B*52 in Takayasu's arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors. TAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers. We found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78). In this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further.

Evaluation of steam penetration and sterilization of natural latex wraps.

PubMed

Rossanese, Matteo; Gasson, James; Barker, Colin; Bowlt, Kelly

2014-11-01

To evaluate the efficacy of steam and ethylene oxide (EtO) sterilization of Vetrap™ bandages. Prospective experimental study. Vetrap™ bandages (n = 70; 35 as supplied by the manufacturer, 35 unwound and tightly rewound). Vetrap™ bandage rolls (n = 60) marked with a 1 cm square were inoculated with 0.1 mL Geobacillus stearothermophilus spores, packaged in a pouch together with independent sterilization indicators and assigned into 3 sub-groups for sterilizer type: dynamic air removal, gravity displacement, and bench-top pre-vacuum and further sub-divided into 2 sterilization temperatures. Vetrap™ bandages rolls (n = 10) were inoculated with 0.1 mL Bacillus atrophaeus spores in the same manner and underwent EtO sterilization. After sterilization, the 1 cm marked square was aseptically resected to the level of the cardboard tube and enriched in a flask containing 10 mL tryptic soy broth for 24 hours at 60°C for G. stearothermophilus and 37°C for B. atrophaeus. Aliquots were subsequently plated on a Petri dish of tryptic soy agar and incubated at 60°C for G. stearothermophilus and 37°C for B. atrophaeus for 24 hours. Samples were scored positive if colonies of indicator organism were present on the nutrient agar after 24 hours. Three Vetrap™ bandages yielded post-sterilization growth of G. stearothermophilus: 2 from the dynamic air removal sterilizer at 134°C for 3.5 minutes, and 1 from the bench-top pre-vacuum sterilizer at 121°C for 15 minutes. After EtO sterilization, no positive samples were detected. Steam sterilization may be incomplete for Vetrap™ bandages whereas EtO showed complete destruction of resistant bacterial spores. © Copyright 2014 by The American College of Veterinary Surgeons.

Effects of overproduced ethylene on the contents of other phytohormones and expression of their key biosynthetic genes.

PubMed

Li, Weiqiang; Nishiyama, Rie; Watanabe, Yasuko; Van Ha, Chien; Kojima, Mikiko; An, Ping; Tian, Lei; Tian, Chunjie; Sakakibara, Hitoshi; Tran, Lam-Son Phan

2018-05-10

Ethylene is involved in regulation of various aspects of plant growth and development. Physiological and genetic analyses have indicated the existence of crosstalk between ethylene and other phytohormones, including auxin, cytokinin (CK), abscisic acid (ABA), gibberellin (GA), salicylic acid (SA), jasmonic acid (JA), brassinosteroid (BR) and strigolactone (SL) in regulation of different developmental processes. However, the effects of ethylene on the biosynthesis and contents of these hormones are not fully understood. Here, we investigated how overproduction of ethylene may affect the contents of other plant hormones using the ethylene-overproducing mutant ethylene-overproducer 1 (eto1-1). The contents of various hormones and transcript levels of the associated biosynthetic genes in the 10-day-old Arabidopsis eto1-1 mutant and wild-type (WT) plants were determined and compared. Higher levels of CK and ABA, while lower levels of auxin, SA and GA were observed in eto1-1 plants in comparison with WT, which was supported by the up- or down-regulation of their biosynthetic genes. Although we could not quantify the BR and SL contents in Arabidopsis, we observed that the transcript levels of the potential rate-limiting BR and SL biosynthetic genes were increased in the eto1-1 versus WT plants, suggesting that BR and SL levels might be enhanced by ethylene overproduction. JA level was not affected by overproduction of ethylene, which might be explained by unaltered expression level of the proposed rate-limiting JA biosynthetic gene allene oxide synthase. Taken together, our results suggest that ET affects the levels of auxin, CK, ABA, SA and GA, and potentially BR and SL, by influencing the expression of genes involved in the rate-limiting steps of their biosynthesis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Role of TLR4 signaling in the nephrotoxicity of heme and heme proteins.

PubMed

Nath, Karl A; Belcher, John D; Nath, Meryl C; Grande, Joseph P; Croatt, Anthony J; Ackerman, Allan W; Katusic, Zvonimir S; Vercellotti, Gregory M

2018-05-01

Destabilized heme proteins release heme, and free heme is toxic. Heme is now recognized as an agonist for the Toll-like receptor-4 (TLR4) receptor. This study examined whether the TLR4 receptor mediates the nephrotoxicity of heme, specifically, the effects of heme on renal blood flow and inflammatory responses. We blocked TLR4 signaling by the specific antagonist TAK-242. Intravenous administration of heme to mice promptly reduced renal blood flow, an effect attenuated by TAK-242. In vitro, TAK-242 reduced heme-elicited activation of NF-κB and its downstream gene monocyte chemoattractant protein-1(MCP-1); in contrast, TAK-242 failed to reduce heme-induced activation of the anti-inflammatory transcription factor Nrf2 and its downstream gene heme oxygenase-1 (HO-1). TAK-242 did not reduce heme-induced renal MCP-1 upregulation in vivo. TAK-242 did not reduce dysfunction and histological injury in the glycerol model of heme protein-induced acute kidney injury (AKI), findings corroborated by studies in TLR4 +/+ and TLR4 -/- mice. We conclude that 1) acute heme-mediated renal vasoconstriction occurs through TLR4 signaling; 2) proinflammatory effects of heme in renal epithelial cells involve TLR4 signaling, whereas the anti-inflammatory effects of heme do not; 3) TLR4 signaling does not mediate the proinflammatory effects of heme in the kidney; and 4) major mechanisms underlying glycerol-induced, heme protein-mediated AKI do not involve TLR4 signaling. These findings in the glycerol model are in stark contrast with findings in virtually all other AKI models studied to date and emphasize the importance of TLR4-independent pathways of heme protein-mediated injury in this model. Finally, these studies urge caution when using observations derived in vitro to predict what occurs in vivo.

Effect of dietary n-3 fatty acids supplementation on fatty acid metabolism in atorvastatin-administered SHR.Cg-Leprcp/NDmcr rats, a metabolic syndrome model.

PubMed

Al Mamun, Abdullah; Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Tsuchikura, Satoru; Hossain, Shahdat; Shido, Osamu

2017-01-01

The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Lepr cp /NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver. Copyright © 2016 Elsevier Masson

Takayasu Arteritis in Major Rheumatology Centers in Malaysia.

PubMed

Khor, Chiew Gek; Tan, Bee Eng; Kan, Sow Lai; Tsang, Esther Ee Ling; Lim, Ai Lee; Chong, Eleen Yun Yin; Rachel, Thundyil; Teh, Cheng Lay; Loh, Yet Lin; Chʼng, Shereen Suyin; dʼSouza, Beryl Agnes; Mohd Mokhtar, Ainon; Ong, Swee Gaik; Mohd Isa, Liza

2016-06-01

There is paucity of data for Takayasu arteritis (TAK) among South Asians. We aimed to evaluate the clinical features, angiographic findings, as well as treatment and outcome of TAK among Malaysian multiethnic groups. This is a retrospective review of 40 patients with TAK seen in major rheumatology centres in Malaysia between April 2006 and September 2013. Majority were female patients (92.5%), with a female-to-male ratio of 12:1. Median duration of disease from diagnosis was 66 months (interquartile range, 33-177 months). Fifteen (37.5%) were Malays, 9 (22.5%) each were Indians and indigenous from East Malaysia and 7 (17.5%) were Chinese. Indian and indigenous from East Malaysia were overrepresented in this disease. The mean (SD) age of symptom onset and diagnosis were 25.5 (8.1) and 27.4 (8.4), respectively. The 3 most common clinical presentations at diagnosis were diminished or absent pulse, which occurred in 80% of the patients, followed by blood pressure discrepancy (60%) and arterial bruit (52.5%). There was no difference in clinical presentation among ethnic groups. The subclavian artery was the commonest vessel involved (72.5%), followed by the carotid artery (65%) and renal artery (47.5%). Eight patients had coronary artery involvement, and 2 patients had pulmonary artery involvement. Type I arterial involvement was the commonest (80.0%), followed by type IV (35%), present in isolation or mixed type. Glucocorticoid was the main medical treatment (90.0%). Nineteen patients (47.5%) underwent revascularization procedures. Five patients died during the follow-up period. The Malaysian TAK cohort had similarities with and differences from other published TAK cohort. A nationwide TAK registry is needed to determine the prevalence of the disease among different ethnic groups.

Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice.

PubMed

Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D

2010-06-01

The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

Paracentric inversion-associated t(8;21) variant in de novo acute myelogenous leukemia: characteristic patterns of conventional cytogenetics, FISH, and multicolor banding analysis.

PubMed

Park, Tae Sung; Song, Jaewoo; Lee, Kyung-A; Min, Yoo Hong; Lee, Sang-Guk; Park, Yongjung; Kim, Juwon; Lee, Eun Yup; Choi, Jong Rak

2008-05-01

Acute myelogenous leukemia (AML) with t(8;21)(q22;q22) demonstrates unique clinico-pathologic disease entity in patients with hematologic malignancies. The t(8;21), which results in fusion of the AML1 gene on 21q22 and the ETO gene on 8q22 on a molecular level, is one of the most common nonrandom chromosomal changes, and it is found in about 5-12% of patients with AML. Among these cases, complex variants involving chromosomes 8 and 21, as well as a third or fourth chromosome, account for approximately 6-10% of patients with an AML1/ETO chimeric gene, and about 100 variant cases with AML1/ETO fusion transcript have been reported in the literature. Here, we describe a rare case report of reciprocal paracentric inversion-associated t(8;21) variant in a 28-year old male patient with de novo AML. The abnormal results of conventional cytogenetics and interphase fluorescent in situ hybridization in this patient drove us to perform further studies and a literature review. This report emphasizes the value of "conventional" cytogenetics, as well as "newly developed" molecular cytogenetic methods in the diagnosis of rare complex t(8;21) variant in patients with AML. Copyright 2008 Elsevier Inc.

The Relationship between Grade Configuration and Standardized Science Test Scores of Fifth-Grade Students: What School Administrators Should Know

ERIC Educational Resources Information Center

Johnson, Delonda; Jones, Lisa; Simieou, Felix; Matthew, Kathryn; Morgan, Bryan

2013-01-01

This study utilized a causal comparative (ex post facto) design to determine if a consistent relationship existed between fifth-grade students' success on the Science Texas Assessment of Knowledge and Skills (TAKS) at the elementary (K-5) level in comparison to fifth-grade students' success on the science TAKS at the intermediate (5-6) level. The…

Analysis of Texas Achievement Data for Elementary African American and Latino Females

ERIC Educational Resources Information Center

Larke, Patricia J.; Webb-Hasan, Gwendolyn; Jimarez, Teresa; Li, Yeping

2014-01-01

This study provides a critical look at achievement of African American (AA), and Latino (L) females in third and fifth grades on the Texas Assessment of Knowledge and Skills (TAKS) in reading, mathematics and science. Descriptive statistics were used to analyze the 2007 and 2011 TAKS raw data. Data analyses indicate that AAL females had the lowest…

Space Propulsion Synergy Group ETO technology assessments

NASA Astrophysics Data System (ADS)

Bray, James

There exists within the aerospace community a widely recognized need to improve future space launch systems. While these needs have been expressed by many national committees, potential solutions have not achieved consensus nor have they endured. Facing the challenge to remain competitive with limited national resources, the U.S. must improve its strategic planning efforts. A nationally accepted strategic plan for space would enable a focused research & development program. The Space Propulsion Synergy Group (SPSG), chartered to support long range strategic planning, has achieved several breakthroughs. First, using a broad industry/government team, the SPSG evaluated and achieved consensus on the vehicles, propulsion systems, and propulsion technologies that have the best long term potential for achieving desired system attributes. The breakthrough that enabled broad consensus was developing criteria that are measurable a-priori. Second, realizing that systems having the best long term payoffs can loose support when constraints are tight, the SPSG invented a dual prioritization approach that balances long term strategic thrusts with current programmatic constraints. This breakthrough enables individual program managers to make decisions based on both individual project needs and long term strategic needs. Results indicate that a SSTO using an integrated modular engine has the best long term potential for a 20 Klb class vehicle and that health monitoring and control technologies rank among the highest dual priority liquid rocket technologies.

Space Propulsion Synergy Group ETO technology assessments

NASA Astrophysics Data System (ADS)

Bray, James

The Space Propulsion Synergy Group (SPSG), which was chartered to support long-range strategic planning, has, using a broad industry/government team, evaluated and achieved consensus on the vehicles, propulsion systems, and propulsion technologies that have the best long-term potential for achieving desired system attributes. The breakthrough that enabled broad consensus was developing criteria that are measurable a priori. The SPSG invented a dual prioritization approach that balances long-term strategic thrusts with current programmatic constraints. This enables individual program managers to make decisions based on both individual project needs and long-term strategic needs. Results indicate that an SSTO using an integrated modular engine has the best long-term potential for a 20 Klb class vehicle, and that health monitoring and control technologies are among the highest dual priority liquid rocket technologies.

An examination of the association between demographic and educational factors and African American achievement in science

NASA Astrophysics Data System (ADS)

Cottledge, Michael Christopher

Objective of the Study: The objective of this research study was to investigate whether an association exists between teacher demographic factors (years of teaching experience and gender), 2 educational factors (certification type and certification pathway) and the percent passing rate of tenth grade African American male students on the 2010 science TAKS. Answers to the following questions were sought: 1. Is there an association between teacher demographic factors and the percent passing rate of their tenth grade African American male students on the 2010 science TAKS? 2. Is there an association between teacher educational factors and the percent passing rate of their tenth grade African American male students on the 2010 science TAKS? 3. Is there an association between teacher demographic factors, educational factors and the percent passing rate of their tenth grade African American male students on the 2010 science TAKS? Status of the Question: According to the Bureau of Labor Statistics (BLS), science and engineering jobs in the U.S. have increased steadily over recent years and by the year 2016 the number of STEM (Science, Technology, Engineering and Math) jobs will have grown by more than 21 percent. This increase in science and engineering jobs will double the growth rate of all other workforce sectors combined. The BLS also reports that qualified minority applicants needed to fill these positions will be few and far between. African Americans, Latinos, and other minorities constitute 24 percent of the U.S. population but only 13 percent of college graduates and just 10 percent of people with college degrees who work in science and engineering (Education Trust, 2009). Drawing on the above information, I proposed the following hypotheses to the research questions: H01: There will be no significant statistical association between the demographic factors teacher gender and years of teaching experience and the percent passing rate of their tenth grade African

Continuous sterilization of plumbing systems

NASA Technical Reports Server (NTRS)

Bryan, C. J.; Moyers, C. V.; Wright, E. E., Jr.

1979-01-01

Continuous sterilization of plumbing, such as in hospitals, clinics, and biological testing laboratories is possible with ethylene oxide/Freon 12 (ETO/F-12) humidifier developed for sterilization of potable water systems.

Minimum Irrigation Requirements for Cottonwood (Populus fremontii and P. deltoides) and Willow (Salix gooddingii) Grown in a Desert Environment

NASA Astrophysics Data System (ADS)

Glenn, E. P.; Hartwell, S.; Morino, K.; Nagler, P. L.

2009-12-01

Native tree plots have been established in riverine irrigation districts in the western U.S. to provide habitat for threatened and endangered birds. Information is needed on the minimum effective irrigation requirements of the target species. We summarize preliminary (or unpublished) findings of a study or cottonwood (Populus spp.) and willow (Salix gooddingii) trees that were grown for seven years in an outdoor plot in a desert environment in Tucson, Arizona to determine plant water use. Plants were allowed to achieve a nearly complete canopy cover over the first four years, then were subjected to three summer irrigation schedules: 6.2 mm d-1; 8.26 mm d-1 and 15.7 mm d-1. The lowest irrigation rate was sufficient to maintain growth and high leaf area index for cottonwoods over three years, but willows suffered partial die-back on this rate, and required 8.26 mm d-1 to maintain growth. These irrigation rates were required April 15 - September 15, but only 0.88 mm d-1 was required during the dormant periods of the year. Expressed as a fraction of reference crop evapotranspiration (ET/ETo), annual water requirements were 0.83 ETo for cottonwood and 1.01 ETo for willow, which includes irrigation plus precipitation. Current practices tend to over-irrigate restoration plots, and this study can provide guidelines for more efficient water use.

An in-vitro biomechanical study of different fixation techniques for the extended trochanteric osteotomy in revision THA.

PubMed

Zhu, Zhonglin; Ding, Hui; Shao, Hongyi; Zhou, Yixin; Wang, Guangzhi

2013-04-09

The wire fixation and the cable grip fixation have been developed for the extended trochanteric osteotomy (ETO) in the revision of total hip arthroplasty (THA). Many studies reported the postoperative performance of the patients, but with little quantitative biomechanical comparison of the two fixation systems. An in-vitro testing approach was designed to record the loosening between the femoral bed and the greater trochanter after fixations. Ten cadaveric femurs were chosen in this study. Each femur underwent the THA, revision by ETO and fixations. The tension to the greater trochanter was from 0 to 500N in vertical and lateral direction, respectively. The translation and rotation of the greater trochanter with respect to the bony bed were captured by an optical tracking system. In the vertical tension tests, the overall translation of the greater trochanter was observed 0.4 mm in the cable fixations and 7.0 mm in the wire fixations. In the lateral tension tests, the overall motion of the greater trochanter was 2.0 mm and 1.2° in the cable fixations, while it was 6.2 mm and 5.3° in the wire fixations. The result was significantly different between the two fixation systems. The stability of the proximal femur after ETO using different fixations in the revision THA was investigated. The cable grip fixation was significantly more stable than the wire fixation.

Around Marshall

NASA Image and Video Library

2002-05-17

In this photograph, students from all over the country gathered and discussed their Earth-to-Orbit (ETO) Design Challenge project at NASA Marshall Space Flight Center in Huntsville, Alabama. These students who are just "typical teens," have been spending their time tackling some of the same challenges NASA engineers face when designing propulsion systems at MSFC. The ETO Design Challenge is a hands-on educational program, targeted to middle school students, in which students are assigned a project engaging in related design challenges in their classrooms under the supervision of their teachers. The project is valuable because it can be used by any student, and any teacher, even those without technical backgrounds. Student in 12 states: Alabama, Arkansas, California, Colorado, Illinois, Missouri, Montana, New York, Ohio, Ternessee, Virginia, and Washington, are taking part in MSFC's Earth-to-Orbit program. NASA uses such programs to support educational excellence while participating in educational outreach programs through centers around the country. One of the students' teachers, Joanne Fluvog, commented, "the biggest change I've seen is in the students' motivation and their belief in their ability to think." Justin O'Connor and Jeff Alden, students of Lane Middle School in Portland, Oregon, participated in the ETO program and said being involved in a real engineering project has made them realize that "science is cool."

Earth-to-Orbit Education Program 'Makes Science Cool'

NASA Technical Reports Server (NTRS)

2002-01-01

In this photograph, students from all over the country gathered and discussed their Earth-to-Orbit (ETO) Design Challenge project at NASA Marshall Space Flight Center in Huntsville, Alabama. These students who are just 'typical teens,' have been spending their time tackling some of the same challenges NASA engineers face when designing propulsion systems at MSFC. The ETO Design Challenge is a hands-on educational program, targeted to middle school students, in which students are assigned a project engaging in related design challenges in their classrooms under the supervision of their teachers. The project is valuable because it can be used by any student, and any teacher, even those without technical backgrounds. Student in 12 states: Alabama, Arkansas, California, Colorado, Illinois, Missouri, Montana, New York, Ohio, Ternessee, Virginia, and Washington, are taking part in MSFC's Earth-to-Orbit program. NASA uses such programs to support educational excellence while participating in educational outreach programs through centers around the country. One of the students' teachers, Joanne Fluvog, commented, 'the biggest change I've seen is in the students' motivation and their belief in their ability to think.' Justin O'Connor and Jeff Alden, students of Lane Middle School in Portland, Oregon, participated in the ETO program and said being involved in a real engineering project has made them realize that 'science is cool.'

The synthesis of branched TCP chromophores and the research on their electro-optical properties

NASA Astrophysics Data System (ADS)

Bo, Shuhui; Chen, Zhuo; Gao, Wu; Zhen, Zhen; Liu, Xinhou

2012-10-01

In order to minimize the intermolecular electrostatic interactions and effectively translate high value of chromophore into macroscopic electro-optical (EO) coeffcient (r33), the shape-modification of aniline-pyrroline (TCP) chromophore by combining three kinds of dendritic groups respectively to the N atom of pyrroline acceptor produced three kinds of dendritic chromophores. Their spherical structures can minimize intermolecular electrostatic interactions, and thus the poling efficience was higher than the chromophores without dendritic groups when chromophores as a guest in the host polymer APC. A large electro-optical (EO) coefficient was achieved as high as 75 pm/V at 1315 nm with 9% chromophores loading in APC film. On the basis of the above TCP chromophores, two kinds of novel molecular glasses based on self-assembly dendritic chromophores are also designed and synthesized as second-order nonlinear optical (NLO) materials, which named ETO and ETF. The NLO chromophore glasses ETO and ETF showed excellent filmforming ability by themselves. Their glass transition temperatures (Tg) were determined at 41° and 39°, respectively. The in-situ second harmonic generation (SHG) measurement revealed the resonant electro-optical (EO) coefficient (d33) values of 38 and 32 pm/V for the poled films of ETO and ETF, respectively. The results indicate molecular glasses provide a new possible way different from the conventional polymer approach to prepare second-order NLO materials.

Computer-Aided Process and Tools for Mobile Software Acquisition

DTIC Science & Technology

2013-04-01

Software Acquisition Christopher Bonine , Man-Tak Shing, and Thomas W. Otani Naval Postgraduate School Published April 1, 2013 Approved for public...ManTech International Corporation Computer-Aided Process and Tools for Mobile Software Acquisition Christopher Bonine , Man-Tak Shing, and Thomas W. Otani...Mobile Software Acquisition Christopher Bonine — Bonine is a lieutenant in the United States Navy. He is currently assigned to the Navy Cyber Defense

The relationship between vertical teaming in science and student achievement as reported in the Academic Excellence Indicator System (AEIS) at selected public schools in Bexar County, Texas

NASA Astrophysics Data System (ADS)

Arteaga, Veronica Hernandez

The purpose of this study was to examine the relationship between vertical teaming in science and student achievement. This study compared student achievement of campuses implementing vertical teaming with schools that do not practice vertical teaming. In addition, this study explored the relationship between selected demographic variables and vertical teaming using Grade 5 Science TAKS results in the Academic Excellence Indicator System (AEIS). Campus demographic variables such as economically disadvantaged, minority students, English language learners, student mobility, and experienced teachers were researched. A call-out yielded 168 responses. With the exclusion of the 12 campuses, a total of 156 participating campuses from 18 traditional school districts remained. Campuses employing vertical teaming were self-identified on the basis of having implemented the process for two or more years. The gain in percent mastered for Science TAKS scores from 2004 to 2007 was used as the Science TAKS score variable. Results indicated that there was no significant difference in student achievement in science for campuses practicing vertical teaming and campuses that did not. The two-way ANOVA was used to measure the relationship between the independent variables (vertical teaming and campus demographic variables) on the dependent variable (student achievement on Science TAKS). The results suggested that campuses having low percentages of economically disadvantaged students statistically gained more on the Science TAKS than campuses that have high percentages of economically disadvantaged students irrespective of vertical teaming practices. In addition, campuses that have low percentages of minority students statistically gained more on the Science TAKS than campuses that have high percentages of minority students despite vertical teaming participation. Recommendations include districts, state, and federal agencies providing campuses with a high percent of economically

Computed tomography scan to detect traumatic arthrotomies and identify periarticular wounds not requiring surgical intervention: an improvement over the saline load test.

PubMed

Konda, Sanjit R; Davidovitch, Roy I; Egol, Kenneth A

2013-09-01

To report our experience with computed tomography (CT) scans to detect traumatic arthrotomies of the knee (TAK) joint based on the presence of intra-articular air. Retrospective review. Level I trauma center. Sixty-two consecutive patients (63 knees) underwent a CT scan of the knee in the emergency department and had a minimum of 14 days follow-up. Cohort of 37 patients (37 knees) from the original 62 patients who underwent a saline load test (SLT). CT scan and SLT. Positive traumatic arthrotomy of the knee (+TAK) was defined as operating room (OR) confirmation of an arthrotomy or no intra-articular air on CT scan (-iaCT) (and -SLT if performed) with follow-up revealing a septic knee. Periarticular wound equivalent to no traumatic arthrotomy (pw = (-TAK)) was defined as OR evaluation revealing no arthrotomy or -iaCT (and -SLT if performed) with follow-up revealing no septic knee. All 32 knees with intra-articular air on CT scan (+iaCT) had OR confirmation of a TAK and none of these patients had a knee infection at a mean follow-up of 140.0 ± 279.6 days. None of the 31 patients with -iaCT had a knee infection at a mean follow-up of 291.0 ± 548.1 days. Based on these results, the sensitivity and specificity of the CT scan to detect +TAK and pw = (-TAK) was 100%. In a subgroup of 37 patients that received both a CT scan and the conventional SLT, the sensitivity and specificity of the CT scan was 100% compared with 92% for the SLT (P < 0.001). CT scan performs better than the conventional SLT to detect traumatic knee arthrotomies and identify periarticular knee wounds that do not require surgical intervention and should be considered a valid diagnostic test in the appropriate clinical setting. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Appraisal of Weather Research and Forecasting Model Downscaling of Hydro-meteorological Variables and their Applicability for Discharge Prediction: Prognostic Approach for Ungauged Basin

NASA Astrophysics Data System (ADS)

Srivastava, P. K.; Han, D.; Rico-Ramirez, M. A.; Bray, M.; Islam, T.; Petropoulos, G.; Gupta, M.

2015-12-01

Hydro-meteorological variables such as Precipitation and Reference Evapotranspiration (ETo) are the most important variables for discharge prediction. However, it is not always possible to get access to them from ground based measurements, particularly in ungauged catchments. The mesoscale model WRF (Weather Research & Forecasting model) can be used for prediction of hydro-meteorological variables. However, hydro-meteorologists would like to know how well the downscaled global data products are as compared to ground based measurements and whether it is possible to use the downscaled data for ungauged catchments. Even with gauged catchments, most of the stations have only rain and flow gauges installed. Measurements of other weather hydro-meteorological variables such as solar radiation, wind speed, air temperature, and dew point are usually missing and thus complicate the problems. In this study, for downscaling the global datasets, the WRF model is setup over the Brue catchment with three nested domains (D1, D2 and D3) of horizontal grid spacing of 81 km, 27 km and 9 km are used. The hydro-meteorological variables are downscaled using the WRF model from the National Centers for Enviromental Prediction (NCEP) reanalysis datasets and subsequently used for the ETo estimation using the Penman Monteith equation. The analysis of weather variables and precipitation are compared against the ground based datasets, which indicate that the datasets are in agreement with the observed datasets for complete monitoring period as well as during the seasons except precipitation whose performance is poorer in comparison to the measured rainfall. After a comparison, the WRF estimated precipitation and ETo are then used as a input parameter in the Probability Distributed Model (PDM) for discharge prediction. The input data and model parameter sensitivity analysis and uncertainty estimation are also taken into account for the PDM calibration and prediction following the Generalised

Supercritical Wing Preliminary Design Study

DTIC Science & Technology

1975-12-01

SHIN «" NOME« <i./t. TAK t«/C» Ttff MA. TAft 4P) JON*« SO M »<• n y »■« • ii n VT«t 4il rtt-Tin J.l.. .S • T» 4...UPM At 1 54 ;t’ -"fi Vitll TI|K EMS IQH A4 ZEE TAff i>^ /tr TAfE <!•/£► TAK KOMUl CUJT« ■no pl TfJK A« *>1» FT J’ T<»£ 511...N« AMT* Oa/tr I» MB »AIM NO. NO. MATEWAL n «ttr ASSY Ott».!. -1 fio.if 5»»« J («It» TAK , I 1 ftf»6 Sf»* »" Cit/t»T««l

Estimating Evapotranspiration Of Orange Orchards Using Surface Renewal And Remote Sensing Techniques

NASA Astrophysics Data System (ADS)

Consoli, S.; Russo, A.; Snyder, R.

2006-08-01

Surface renewal (SR) analysis was utilized to calculate sensible heat flux density from high frequency temperature measurements above orange orchard canopies during 2005 in eastern Sicily (Italy). The H values were employed to estimate latent heat flux density (LE) using measured net radiation (Rn) and soil heat flux density (G) in the energy balance (EB) equation. Crop coefficients were determined by calculating the ratio Kc=ETa/ETo, with reference ETo derived from the daily Penman-Monteith equation. The estimated daily Kc values showed an average of about 0.75 for canopy covers having about 70% ground shading and 80% of PAR light interception. Remote sensing estimates of Kc and ET fluxes were compared with those measured by SR-EB. IKONOS satellite estimates of Kc and NDVI were linearly correlated for the orchard stands.

Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience.

PubMed

Marcinak, John F; Munsaka, Melvin S; Watkins, Paul B; Ohira, Takashi; Smith, Neila

2018-06-01

Fasiglifam (TAK-875) is a G protein-coupled receptor 40 agonist that was being investigated for treatment of type 2 diabetes mellitus (T2DM). A development program was terminated late in phase III clinical trials due to liver safety concerns. The liver safety of fasiglifam was assessed from data based on six phase II and nine phase III double-blind studies and two open-label studies with emphasis on pooled data from 15 double-blind studies from both global and Japanese development programs. Taking into consideration different daily doses of fasiglifam administered in clinical studies, the primary comparisons were between all patients exposed to fasiglifam (any dose) versus placebo, and, where applicable, versus the two active comparators, sitagliptin or glimepiride. A Liver Safety Evaluation Committee consisting of hepatologists blinded to treatment assignments evaluated hepatic adverse events (AEs) and serious AEs (SAEs) for causal relationship to study drug. The analysis included data from 9139 patients with T2DM in 15 double-blind controlled studies who received either fasiglifam (n = 5359, fasiglifam group), fasiglifam and sitagliptin (n = 123), or a comparator agent (n = 3657, non-exposed group consisting of placebo and other antidiabetic agents). Exposure to treatment for more than 1 year ranged from 249 patients in the placebo arm, to 370 patients in the glimepiride arm and 617 patients in the fasiglifam 50 mg arm. The primary focus of the analysis was on the hepatic safety of fasiglifam. The overall safety profile based on treatment-emergent AEs (TEAEs), SAEs, deaths, and withdrawal due to AEs was similar between fasiglifam and placebo (excluding liver test abnormalities). However, there was an increased incidence rate of serum alanine aminotransferase (ALT) elevations > 3 × upper limit of normal (ULN), 5 × ULN, and 10 × ULN in fasiglifam-treated patients compared with those treated with placebo or active comparators. ALT elevations > 3

The rhizobacterium Variovorax paradoxus 5C-2, containing ACC deaminase, promotes growth and development of Arabidopsis thaliana via an ethylene-dependent pathway

PubMed Central

Dodd, Ian C.

2013-01-01

Many plant-growth-promoting rhizobacteria (PGPR) associated with plant roots contain the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase and can metabolize ACC, the immediate precursor of the plant hormone ethylene, thereby decreasing plant ethylene production and increasing plant growth. However, relatively few studies have explicitly linked ethylene emission and/or action to growth promotion in these plant–microbe interactions. This study examined effects of the PGPR Variovorax paradoxus 5C-2 containing ACC deaminase on the growth and development of Arabidopsis thaliana using wild-type (WT) plants and several ethylene-related mutants (etr1-1, ein2-1, and eto1-1). Soil inoculation with V. paradoxus 5C-2 promoted growth (leaf area and shoot biomass) of WT plants and the ethylene-overproducing mutant eto1-1, and also enhanced floral initiation of WT plants by 2.5 days. However, these effects were not seen in ethylene-insensitive mutants (etr1-1 and ein2-1) even though bacterial colonization of the root system was similar. Furthermore, V. paradoxus 5C-2 decreased ACC concentrations of rosette leaves of WT plants by 59% and foliar ethylene emission of both WT plants and eto1-1 mutants by 42 and 37%, respectively. Taken together, these results demonstrate that a fully functional ethylene signal transduction pathway is required for V. paradoxus 5C-2 to stimulate leaf growth and flowering of A. thaliana. PMID:23404897

The rhizobacterium Variovorax paradoxus 5C-2, containing ACC deaminase, promotes growth and development of Arabidopsis thaliana via an ethylene-dependent pathway.

PubMed

Chen, Lin; Dodd, Ian C; Theobald, Julian C; Belimov, Andrey A; Davies, William J

2013-04-01

Many plant-growth-promoting rhizobacteria (PGPR) associated with plant roots contain the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase and can metabolize ACC, the immediate precursor of the plant hormone ethylene, thereby decreasing plant ethylene production and increasing plant growth. However, relatively few studies have explicitly linked ethylene emission and/or action to growth promotion in these plant-microbe interactions. This study examined effects of the PGPR Variovorax paradoxus 5C-2 containing ACC deaminase on the growth and development of Arabidopsis thaliana using wild-type (WT) plants and several ethylene-related mutants (etr1-1, ein2-1, and eto1-1). Soil inoculation with V. paradoxus 5C-2 promoted growth (leaf area and shoot biomass) of WT plants and the ethylene-overproducing mutant eto1-1, and also enhanced floral initiation of WT plants by 2.5 days. However, these effects were not seen in ethylene-insensitive mutants (etr1-1 and ein2-1) even though bacterial colonization of the root system was similar. Furthermore, V. paradoxus 5C-2 decreased ACC concentrations of rosette leaves of WT plants by 59% and foliar ethylene emission of both WT plants and eto1-1 mutants by 42 and 37%, respectively. Taken together, these results demonstrate that a fully functional ethylene signal transduction pathway is required for V. paradoxus 5C-2 to stimulate leaf growth and flowering of A. thaliana.

Ethylene Regulates Energy-Dependent Non-Photochemical Quenching in Arabidopsis through Repression of the Xanthophyll Cycle.

PubMed

Chen, Zhong; Gallie, Daniel R

2015-01-01

Energy-dependent (qE) non-photochemical quenching (NPQ) thermally dissipates excess absorbed light energy as a protective mechanism to prevent the over reduction of photosystem II and the generation of reactive oxygen species (ROS). The xanthophyll cycle, induced when the level of absorbed light energy exceeds the capacity of photochemistry, contributes to qE. In this work, we show that ethylene regulates the xanthophyll cycle in Arabidopsis. Analysis of eto1-1, exhibiting increased ethylene production, and ctr1-3, exhibiting constitutive ethylene response, revealed defects in NPQ resulting from impaired de-epoxidation of violaxanthin by violaxanthin de-epoxidase (VDE) encoded by NPQ1. Elevated ethylene signaling reduced the level of active VDE through decreased NPQ1 promoter activity and impaired VDE activation resulting from a lower transthylakoid membrane pH gradient. Increasing the concentration of CO2 partially corrected the ethylene-mediated defects in NPQ and photosynthesis, indicating that changes in ethylene signaling affect stromal CO2 solubility. Increasing VDE expression in eto1-1 and ctr1-3 restored light-activated de-epoxidation and qE, reduced superoxide production and reduced photoinhibition. Restoring VDE activity significantly reversed the small growth phenotype of eto1-1 and ctr1-3 without altering ethylene production or ethylene responses. Our results demonstrate that ethylene increases ROS production and photosensitivity in response to high light and the associated reduced plant stature is partially reversed by increasing VDE activity.

Ethylene Regulates Energy-Dependent Non-Photochemical Quenching in Arabidopsis through Repression of the Xanthophyll Cycle

PubMed Central

Chen, Zhong; Gallie, Daniel R.

2015-01-01

Energy-dependent (qE) non-photochemical quenching (NPQ) thermally dissipates excess absorbed light energy as a protective mechanism to prevent the over reduction of photosystem II and the generation of reactive oxygen species (ROS). The xanthophyll cycle, induced when the level of absorbed light energy exceeds the capacity of photochemistry, contributes to qE. In this work, we show that ethylene regulates the xanthophyll cycle in Arabidopsis. Analysis of eto1-1, exhibiting increased ethylene production, and ctr1-3, exhibiting constitutive ethylene response, revealed defects in NPQ resulting from impaired de-epoxidation of violaxanthin by violaxanthin de-epoxidase (VDE) encoded by NPQ1. Elevated ethylene signaling reduced the level of active VDE through decreased NPQ1 promoter activity and impaired VDE activation resulting from a lower transthylakoid membrane pH gradient. Increasing the concentration of CO2 partially corrected the ethylene-mediated defects in NPQ and photosynthesis, indicating that changes in ethylene signaling affect stromal CO2 solubility. Increasing VDE expression in eto1-1 and ctr1-3 restored light-activated de-epoxidation and qE, reduced superoxide production and reduced photoinhibition. Restoring VDE activity significantly reversed the small growth phenotype of eto1-1 and ctr1-3 without altering ethylene production or ethylene responses. Our results demonstrate that ethylene increases ROS production and photosensitivity in response to high light and the associated reduced plant stature is partially reversed by increasing VDE activity. PMID:26630486

Mutagen-induced fetal anomalies and death following treatment of females within hours after mating.

PubMed

Generoso, W M; Rutledge, J C; Cain, K T; Hughes, L A; Downing, D J

1988-05-01

In an earlier study (Generoso et al., 1987), it was observed that the mutagen, ethylene oxide (EtO), produced remarkable increases in the incidence of developmental abnormalities and death of fetuses when early zygotic stages were exposed. This is a major finding in experimental induction of embryopathy, implicating genetic damage to the zygotes as the likely cause. In the subsequent study reported here, 3 other mutagens--ethyl methanesulfonate (EMS), ethyl nitrosourea (ENU), and triethylene melamine (TEM), were studied for embryopathic effects following exposure of dictyate oocytes, prefertilization oviducal eggs and sperm, early pronuclear zygotes, zygotes undergoing pronuclear DNA synthesis, and two-cell embryos. All 4 mutagens produced developmental abnormalities among living fetuses following exposure of early pronuclear zygotes (the only stage studied for this endpoint in this report). With respect to stage specificity and gestational timing of death of conceptuses, EMS and EtO on one hand and ENU and TEM on the other, are very similar to one another. EMS, like EtO, produced a high incidence of midgestation and late fetal deaths only in prefertilization oviducal eggs and sperm and in early pronuclear eggs. In contrast, ENU and TEM produced high losses of conceptuses in all postmating stages studied but death occurred primarily prior to or around the time of implantation. Thus, the frequency of induction and the expression of embryopathy, which ranged from early embryonic preimplantation and late fetal deaths to subtle fetal anomalies, are dependent upon the stage exposed and the mutagen used.

Unidirectional oxide hetero-interface thin-film diode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Youngmin; Lee, Eungkyu; Lee, Jinwon

2015-10-05

The unidirectional thin-film diode based on oxide hetero-interface, which is well compatible with conventional thin-film fabrication process, is presented. With the metal anode/electron-transporting oxide (ETO)/electron-injecting oxide (EIO)/metal cathode structure, it exhibits that electrical currents ohmically flow at the ETO/EIO hetero-interfaces for only positive voltages showing current density (J)-rectifying ratio of ∼10{sup 5} at 5 V. The electrical properties (ex, current levels, and working device yields) of the thin-film diode (TFD) are systematically controlled by changing oxide layer thickness. Moreover, we show that the oxide hetero-interface TFD clearly rectifies an AC input within frequency (f) range of 10{sup 2} Hz < f < 10{sup 6} Hz, providing amore » high feasibility for practical applications.« less

Technology Requirements for Affordable Single-Stage Rocket Launch Vehicles

NASA Technical Reports Server (NTRS)

Stanley, Douglas O.; Piland, William M.

2004-01-01

A number of manned Earth-to-orbit (ETO) vehicle options for replacing or complementing the current Space Transportation System are being examined under the Advanced Manned Launch System (AMLS) study. The introduction of a reusable single-stage vehicle (SSV) into the U.S. launch vehicle fleet early in the next century could greatly reduce ETO launch costs. As a part of the AMLS study, the conceptual design of an SSV using a wide variety of enhancing technologies has recently been completed and is described in this paper. This paper also identifies the major enabling and enhancing technologies for a reusable rocket-powered SSV and provides examples of the mission payoff potential of a variety of important technologies. This paper also discusses the impact of technology advancements on vehicle margins, complexity, and risk, all of which influence the total system cost.

A quantitative comparative analysis of Advancement via Independent Determination (AVID) in Texas middle schools

NASA Astrophysics Data System (ADS)

Reed, Krystal Astra

The "Advancement via Individual Determination (AVID) program was designed to provide resources and strategies that enable underrepresented minority students to attend 4-year colleges" (AVID Center, 2013, p. 2). These students are characterized as the forgotten middle in that they have high test scores, average-to-low grades, minority or low socioeconomic status, and will be first-generation college students (AVID, 2011). Research indicates (Huerta, Watt, & Butcher, 2013) that strict adherence to 11 program components supports success of students enrolled in AVID, and AVID certification depends on districts following those components. Several studies (AVID Center, 2013) have investigated claims about the AVID program through qualitative analyses; however, very few have addressed this program quantitatively. This researcher sought to determine whether differences existed between student achievement and attendance rates between AVID and non-AVID middle schools. To achieve this goal, the researcher compared eighth-grade science and seventh- and eighth-grade mathematics scores from the 2007 to 2011 Texas Assessment of Knowledge and Skills (TAKS) and overall attendance rates in demographically equivalent AVID and non-AVID middle schools. Academic Excellence Indicator System (AEIS) reports from the Texas Education Agency (TEA) were used to obtain 2007 to 2011 TAKS results and attendance information for the selected schools. The results indicated a statistically significant difference between AVID demonstration students and non-AVID students in schools with similar CI. No statistically significant differences were found on any component of the TAKS for AVID economically disadvantaged students. The mean scores indicated an achievement gap between non-AVID and AVID demonstration middle schools. The findings from the other three research questions indicated no statistically significant differences between AVID and non-AVID student passing rates on the seventh- and eighth

Systematic Analysis of Quantitative Logic Model Ensembles Predicts Drug Combination Effects on Cell Signaling Networks

DTIC Science & Technology

2016-08-27

acted to inhibit both TAK1 and MEK. Experimental data for these prediction tests are shown in Figure 4, and comparison between predictions and valida...would decrease did not contain this interaction. The fact that phospho-cJun did decrease in the experimental test of this prediction (Figure 4...pathways primarily through TAK1. Does IL-1 signal through MEKK1 in HepG2 cells? Given the potential importance of MEKK1, we experimentally tested whether IL

Investigation of the Binding Interaction of Fatty Acids with Human G Protein-Coupled Receptor 40 Using a Site-Specific Fluorescence Probe by Flow Cytometry.

PubMed

Ren, Xiao-Min; Cao, Lin-Ying; Zhang, Jing; Qin, Wei-Ping; Yang, Yu; Wan, Bin; Guo, Liang-Hong

2016-04-05

Human G protein-coupled receptor 40 (hGPR40), with medium- and long-chain free fatty acids (FFAs) as its natural ligands, plays an important role in the enhancement of glucose-dependent insulin secretion. To date, information about the direct binding of FFAs to hGPR40 is very limited, and how carbon-chain length affects the activities of FFAs on hGPR40 is not yet understood. In this study, a fluorescein-fasiglifam analogue (F-TAK-875A) conjugate was designed and synthesized as a site-specific fluorescence probe to study the interaction of FFAs with hGPR40. hGPR40 was expressed in human embryonic kidney 293 cells and labeled with F-TAK-875A. By using flow cytometry, competitive binding of FFA and F-TAK-875A to hGPR40-expressed cells was measured. Binding affinities of 18 saturated FFAs, with carbon-chain lengths ranging from C6 to C23, were analyzed. The results showed that the binding potencies of FFAs to hGPR40 were dependent on carbon length. There was a positive correlation between length and binding potency for seven FFAs (C9-C15), with myristic acid (C15) showing the highest potency, 0.2% relative to TAK-875. For FFAs with a length of fewer than C9 or more than C15, they had very weak or no binding. Molecular docking results showed that the binding pocket of TAK-875 in hGPR40 could enclose FFAs with lengths of C15 or fewer. However, for FFAs with lengths longer than C15, part of the alkyl chain extended out of the binding pocket. This study provided insights into the structural dependence of FFAs binding to and activation of hGPR40.

Docosahexaenoic acid, G protein-coupled receptors, and melanoma: is G protein-coupled receptor 40 a potential therapeutic target?

PubMed

Nehra, Deepika; Pan, Amy H; Le, Hau D; Fallon, Erica M; Carlson, Sarah J; Kalish, Brian T; Puder, Mark

2014-05-15

To determine the effect of docosahexaenoic acid (DHA) on the growth of human melanoma in vitro and in vivo and to better understand the potential role of the G protein-coupled receptors (GPRs) in mediating this effect. For in vitro studies, human melanoma and control fibroblast cells were treated with DHA and TAK-875 (selective GPR40 agonist) and a cell viability assay was performed to determine cell counts. A murine subcutaneous xenograft model of human melanoma was used to test the effect of dietary treatment with an omega-3 fatty acid (FA) rich diet compared with an omega-6 FA rich diet on the growth of human melanoma in vivo. A similar animal model was used to test the effect of oral TAK-875 on the growth of established melanoma tumors in vivo. DHA has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals on the omega-3 FA rich diet were 69% smaller in weight (P = 0.005) and 76% smaller in volume compared with tumors from animals on the omega-6 FA rich diet. TAK-875 has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals treated with TAK-875 were 46% smaller in weight (P = 0.07), 62% smaller in volume (P = 0.03), and grew 77% slower (P = 0.04) compared with the placebo group. DHA and TAK-875 have a profound and selective inhibitory effect on the growth of human melanoma both in vitro and in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimization of T-cell Reactivity by Exploiting TCR Chain Centricity for the Purpose of Safe and Effective Antitumor TCR Gene Therapy.

PubMed

Ochi, Toshiki; Nakatsugawa, Munehide; Chamoto, Kenji; Tanaka, Shinya; Yamashita, Yuki; Guo, Tingxi; Fujiwara, Hiroshi; Yasukawa, Masaki; Butler, Marcus O; Hirano, Naoto

2015-09-01

Adoptive transfer of T cells redirected by a high-affinity antitumor T-cell receptor (TCR) is a promising treatment modality for cancer patients. Safety and efficacy depend on the selection of a TCR that induces minimal toxicity and elicits sufficient antitumor reactivity. Many, if not all, TCRs possess cross-reactivity to unrelated MHC molecules in addition to reactivity to target self-MHC/peptide complexes. Some TCRs display chain centricity, in which recognition of MHC/peptide complexes is dominated by one of the TCR hemi-chains. In this study, we comprehensively studied how TCR chain centricity affects reactivity to target self-MHC/peptide complexes and alloreactivity using the TCR, clone TAK1, which is specific for human leukocyte antigen-A*24:02/Wilms tumor 1(235-243) (A24/WT1(235)) and cross-reactive with B*57:01 (B57). The TAK1β, but not the TAK1α, hemi-chain possessed chain centricity. When paired with multiple clonotypic TCRα counter-chains encoding TRAV12-2, 20, 36, or 38-2, the de novo TAK1β-containing TCRs showed enhanced, weakened, or absent reactivity to A24/WT1(235) and/or to B57. T cells reconstituted with these TCRα genes along with TAK1β possessed a very broad range (>3 log orders) of functional and structural avidities. These results suggest that TCR chain centricity can be exploited to enhance desired antitumor TCR reactivity and eliminate unwanted TCR cross-reactivity. TCR reactivity to target MHC/peptide complexes and cross-reactivity to unrelated MHC molecules are not inextricably linked and are separable at the TCR sequence level. However, it is still mandatory to carefully monitor for possible harmful toxicities caused by adoptive transfer of T cells redirected by thymically unselected TCRs. ©2015 American Association for Cancer Research.

Arjunolic acid, a peroxisome proliferator-activated receptor α agonist, regresses cardiac fibrosis by inhibiting non-canonical TGF-β signaling.

PubMed

Bansal, Trisha; Chatterjee, Emeli; Singh, Jasdeep; Ray, Arjun; Kundu, Bishwajit; Thankamani, V; Sengupta, Shantanu; Sarkar, Sagartirtha

2017-10-06

Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant Terminalia arjuna, which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive T. arjuna compound, arjunolic acid (AA), in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target. Our data revealed that AA significantly represses collagen expression and improves cardiac function during hypertrophy. We found that AA binds to and stabilizes the ligand-binding domain of peroxisome proliferator-activated receptor α (PPARα) and increases its expression during cardiac hypertrophy. PPARα knockdown during AA treatment in hypertrophy samples, including angiotensin II-treated adult cardiac fibroblasts and renal artery-ligated rat heart, suggests that AA-driven cardioprotection primarily arises from PPARα agonism. Moreover, AA-induced PPARα up-regulation leads to repression of TGF-β signaling, specifically by inhibiting TGF-β-activated kinase1 (TAK1) phosphorylation. We observed that PPARα directly interacts with TAK1, predominantly via PPARα N-terminal transactivation domain (AF-1) thereby masking the TAK1 kinase domain. The AA-induced PPARα-bound TAK1 level thereby shows inverse correlation with the phosphorylation level of TAK1 and subsequent reduction in p38 MAPK and NF-κBp65 activation, ultimately culminating in amelioration of excess collagen synthesis in cardiac hypertrophy. In conclusion, our findings unravel the mechanism of AA action in regressing hypertrophy-associated cardiac fibrosis by assigning a role of AA as a PPARα agonist that inactivates non-canonical TGF-β signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Modeling The effect of elevated CO2 and climate change on reference evapotranspiration in the semi-arid Great Plains

USDA-ARS?s Scientific Manuscript database

Changes in evapotranspiration demand due to global warming will have profound impact on irrigation water demand and agricultural productivity. In this study, effects of possible future anthropogenic climate change on reference evapotranspiration (ETo) was evaluated. The Penman-Monteith equation was ...

Transdermal Nitroglycerin Delivery Using Acrylic Matrices: Design, Formulation, and In Vitro Characterization

PubMed Central

Ramazani Saadat Abadi, Ahmad

2014-01-01

Nitroglycerin (TNG) transdermal drug delivery systems (TDDSs) with different acrylic pressure-sensitive adhesives (PSAs) and chemical permeation enhancers (CPEs) were prepared. The effects of PSAs and CPEs types and concentrations on skin permeation and in vitro drug release from devices were evaluated using the dissolution method as well as the modified-jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux (J ss) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2516 and Duro-Tak 2054 showed the highest and Duro-Tak 2051 showed the lowest J ss. Among the various CPEs, propylene glycol and cetyl alcohol showed the highest and the lowest enhancement of the skin permeation of TNG, respectively. The adhesion properties of devices such as 180° peel strength and probe tack values were obtained. It was shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA. Moreover, after optimization of the formulation, it was found that the use of 10% PG as a CPE and 25% nitroglycerin loading in Duro-Tak 2054 is an effective monolithic DIAP for the development of a transdermal therapeutic system for nitroglycerin. PMID:24511396

Is It Worth It? - the Economics of Reusable Space Transportation

NASA Technical Reports Server (NTRS)

Webb, Richard

2016-01-01

Over the past several decades billions of dollars have been invested by governments and private companies in the pursuit of lower cost access to space through earth-to-orbit (ETO) space transportation systems. Much of that investment has been focused on the development and operation of various forms of reusable transportation systems. From the Space Shuttle to current efforts by private commercial companies, the overarching belief of those making such investments has been that reusing system elements will be cheaper than utilizing expendable systems that involve throwing away costly engines, avionics, and other hardware with each flight. However, the view that reusable systems are ultimately a "better" approach to providing ETO transportation is not held universally by major stakeholders within the space transportation industry. While the technical feasibility of at least some degree of reusability has been demonstrated, there continues to be a sometimes lively debate over the merits and drawbacks of reusable versus expendable systems from an economic perspective. In summary, is it worth it? Based on our many years of direct involvement with the business aspects of several expendable and reusable transportation systems, it appears to us that much of the discussion surrounding reusability is hindered by a failure to clearly define and understand the financial and other metrics by which the financial "goodness" of a reusable or expandable approach is measured. As stakeholders, the different users and suppliers of space transportation have a varied set of criteria for determining the relative economic viability of alternative strategies, including reusability. Many different metrics have been used to measure the affordability of space transportation, such as dollars per payload pound (kilogram) to orbit, cost per flight, life cycle cost, net present value/internal rate of return, and many others. This paper will examine the key considerations that influence

Preparation and characterization of injectable fibrillar type I collagen and evaluation for pseudoaneurysm treatment in a pig model.

PubMed

Geutjes, Paul J; van der Vliet, J Adam; Faraj, Kaeuis A; de Vries, Noes; van Moerkerk, Herman T B; Wismans, Ronnie G; Hendriks, Thijs; Daamen, Willeke F; van Kuppevelt, Toin H

2010-11-01

Despite the efficacy of collagen in femoral artery pseudoaneurysm treatment, as reported in one patient study, its use has not yet gained wide acceptance in clinical practice. In this particular study, the collagen was not described in detail. To further investigate the potential of collagen preparations, we prepared and characterized highly purified injectable fibrillar type I collagen and evaluated its use for femoral artery pseudoaneurysm (PSA) treatment in vivo using a pig model. Purified fibrillar type I collagen was characterized using electron microscopy. The effect of three different sterilization procedures, ie, hydrogen peroxide gas plasma (H2O2), ethylene oxide gas (EtO), and gamma irradiation, was studied on both SDS-PAGE and platelet aggregation. Different collagen injectables were prepared (3%, 4%, and 5%) and tested using an injection force test applying a 21-gauge needle. To evaluate the network characteristics of the injectable collagen, the collagen was suspended in phosphate buffered saline (PBS) at 37°C and studied both macroscopically and electron microscopically. To determine whether the collagen induced hemostasis in vivo, a pig PSA model was used applying a 4% EtO sterilized collagen injectable, and evaluation by angiography and routine histology. Electron microscopy of the purified type I collagen revealed intact fibrils with a distinct striated pattern and a length<300 μm. Both SDS-PAGE and platelet aggregation analysis of the sterilized collagen indicated no major differences between EtO and H2O2 sterilization, although gamma-irradiated collagen showed degradation products. Both 3% and 4% (w/v) collagen suspensions were acceptable with respect to the force used (<50 N). The 4% suspension was selected as the preferred injectable collagen, which formed a dense network under physiologic conditions. Testing the collagen in vivo (n=5), the angiograms revealed that the PSA partly or completely coagulated. Histology confirmed the network

Global daily reference evapotranspiration modeling and evaluation

USGS Publications Warehouse

Senay, G.B.; Verdin, J.P.; Lietzow, R.; Melesse, Assefa M.

2008-01-01

Accurate and reliable evapotranspiration (ET) datasets are crucial in regional water and energy balance studies. Due to the complex instrumentation requirements, actual ET values are generally estimated from reference ET values by adjustment factors using coefficients for water stress and vegetation conditions, commonly referred to as crop coefficients. Until recently, the modeling of reference ET has been solely based on important weather variables collected from weather stations that are generally located in selected agro-climatic locations. Since 2001, the National Oceanic and Atmospheric Administration’s Global Data Assimilation System (GDAS) has been producing six-hourly climate parameter datasets that are used to calculate daily reference ET for the whole globe at 1-degree spatial resolution. The U.S. Geological Survey Center for Earth Resources Observation and Science has been producing daily reference ET (ETo) since 2001, and it has been used on a variety of operational hydrological models for drought and streamflow monitoring all over the world. With the increasing availability of local station-based reference ET estimates, we evaluated the GDAS-based reference ET estimates using data from the California Irrigation Management Information System (CIMIS). Daily CIMIS reference ET estimates from 85 stations were compared with GDAS-based reference ET at different spatial and temporal scales using five-year daily data from 2002 through 2006. Despite the large difference in spatial scale (point vs. ∼100 km grid cell) between the two datasets, the correlations between station-based ET and GDAS-ET were very high, exceeding 0.97 on a daily basis to more than 0.99 on time scales of more than 10 days. Both the temporal and spatial correspondences in trend/pattern and magnitudes between the two datasets were satisfactory, suggesting the reliability of using GDAS parameter-based reference ET for regional water and energy balance studies in many parts of the world

Inhibition of HIV Fusion with Multivalent Gold Nanoparticles

PubMed Central

Bowman, Mary-Catherine; Ballard, T. Eric; Ackerson, Christopher J.; Feldheim, Daniel L.; Margolis, David M.; Melander, Christian

2010-01-01

The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics. PMID:18473457

75 FR 54387 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

... previously approved collection. Title of Collection: Standard on Ethylene Oxide (29 CFR 1910.1047). OMB... requirements contained in the Standard. The information collection requirements specified in Ethylene Oxide... ethylene oxide. The principal information collection requirements in the EtO Standard include conducting...

Synergistic Combinations of Multiple Chemotherapeutic Agents in High Capacity Poly(2-oxazoline) Micelles

PubMed Central

Han, Yingchao; He, Zhijian; Schulz, Anita; Bronich, Tatiana K.; Jordan, Rainer; Luxenhofer, Robert; Kabanov, Alexander V.

2012-01-01

Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multi-drug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt.% drug per final formulation. Multi-drug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells. PMID:22681126

Industrial-hygiene characterization of ethylene oxide exposures of hospital and nursing-home workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ringenburg, V.L.; Elliott, L.J.; Morelli-Schroth, P.

Industrial-hygiene surveys were conducted at 12 hospitals and one nursing home to determine possible employee exposure to ethylene oxide (EtO). Different types of exposure situations existed at each of the facilities as a result of various engineering controls, administrative controls and work practices. Sampling indicated that the time-weighted averages (TWAs) of exposure over periods of 36 to 724 minutes ranged from below the limit of detection to 6.7 parts per million (ppm). Personal short-term exposure levels covering 2 to 30 minutes ranged from less than the limit of detection to 103.2ppm. Factors found to be responsible for these higher-than-permissible levelsmore » of EtO exposure included improper installation or lack of engineering controls (such as improper placement of the sterilizing operations), unbalanced ventilation systems, and lack of administrative controls resulting in inappropriate work practices.« less

Validation of Physics Standardized Test Items

NASA Astrophysics Data System (ADS)

Marshall, Jill

2008-10-01

The Texas Physics Assessment Team (TPAT) examined the Texas Assessment of Knowledge and Skills (TAKS) to determine whether it is a valid indicator of physics preparation for future course work and employment, and of the knowledge and skills needed to act as an informed citizen in a technological society. We categorized science items from the 2003 and 2004 10th and 11th grade TAKS by content area(s) covered, knowledge and skills required to select the correct answer, and overall quality. We also analyzed a 5000 student sample of item-level results from the 2004 11th grade exam using standard statistical methods employed by test developers (factor analysis and Item Response Theory). Triangulation of our results revealed strengths and weaknesses of the different methods of analysis. The TAKS was found to be only weakly indicative of physics preparation and we make recommendations for increasing the validity of standardized physics testing..

Deficit irrigation of a landscape halophyte for reuse of saline waste water in a desert city

USGS Publications Warehouse

Glenn, E.P.; Mckeon, C.; Gerhart, V.; Nagler, P.L.; Jordan, F.; Artiola, J.

2009-01-01

Saline waste waters from industrial and water treatment processes are an under-utilized resource in desert urban environments. Management practices to safely use these water sources are still in development. We used a deeprooted native halophyte, Atriplex lentiformis (quailbush), to absorb mildly saline effluent (1800 mg l-1 total dissolved solids, mainly sodium sulfate) from a water treatment plant in the desert community of Twentynine Palms, California. We developed a deficit irrigation strategy to avoid discharging water past the root zone to the aquifer. The plants were irrigated at about one-third the rate of reference evapotranspiration (ETo) calculated from meteorological data over five years and soil moisture levels were monitored to a soil depth of 4.7 m at monthly intervals with a neutron hydroprobe. The deficit irrigation schedule maintained the soil below field capacity throughout the study. Water was presented on a more or less constant schedule, so that the application rates were less than ETo in summer and equal to or slightly greater than ETo in winter, but the plants were able to consume water stored in the profile in winter to support summer ET. Sodium salts gradually increased in the soil profile over the study but sulfate levels remained low, due to formation of gypsum in the calcic soil. The high salt tolerance, deep roots, and drought tolerance of desert halophytes such as A. lentiformis lend these plants to use as deficit-irrigated landscape plants for disposal of effluents in urban setting when protection of the aquifer is important. ?? 2008 Elsevier B.V.

Agrometeorological parameters for prediction of the maturation period of Arabica coffee cultivars

NASA Astrophysics Data System (ADS)

Pezzopane, José Ricardo Macedo; Salva, Terezinha de Jesus Garcia; de Lima, Valéria Bittencourt; Fazuoli, Luiz Carlos

2012-09-01

The objective of this study was to determine the harvest period of coffee fruits based on the relationship between agrometeorological parameters and sucrose accumulation in the seeds. Over the crop years 2004/2005 and 2006/2007, from 150 days after flowering (DAF) onwards, samples of 50 fruits of cultivars Mundo Novo IAC 376-4, Obatã IAC 1669-20 and Catuaí Vermelho IAC 144 were collected from coffee trees located in Campinas, Brazil. The endosperm of the fruits was freeze-dried, ground and analyzed for sucrose content by high-performance liquid chromatography. A weather station provided data to calculate the accumulated growing degree-day (GDD) units, and the reference (ETo) and actual (ETr) evapotranspiration rates. The results showed that the highest rates of sucrose accumulation occurred at the transition from the cane-green to the cherry phenological stage. Models for the estimation of sucrose content during maturation based on meteorological variables exhibited similar or better performance than the DAF variable, with better results for the variables GDD and ETo. The Mundo Novo cultivar reached the highest sucrose level in the endosperm after 2,790 GDD, while cultivar Catuaí attained its maximum sucrose concentration after the accumulated evapotranspiration rate has reached a value of 870 mm. As for cultivar Obatã, the maximum sucrose concentration was predicted with the same degree of accuracy using any of the parameters investigated. For the Obatã cultivar, the values of the variables calculated for the maximum sucrose concentration to be reached were 249 DAF, 3,090 GDD, 1,020 ETo and 900 ETr.

Development of outcome measures for large-vessel vasculitis for use in clinical trials: opportunities, challenges, and research agenda.

PubMed

Direskeneli, Haner; Aydin, Sibel Z; Kermani, Tanaz A; Matteson, Eric L; Boers, Maarten; Herlyn, Karen; Luqmani, Raashid A; Neogi, Tuhina; Seo, Philip; Suppiah, Ravi; Tomasson, Gunnar; Merkel, Peter A

2011-07-01

Giant cell (GCA) and Takayasu's arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.

Development of Outcome Measures for Large-vessel Vasculitis for Use in Clinical Trials: Opportunities, Challenges, and Research Agenda

PubMed Central

DIRESKENELI, HANER; AYDIN, SIBEL Z.; KERMANI, TANAZ A.; MATTESON, ERIC L.; BOERS, MAARTEN; HERLYN, KAREN; LUQMANI, RAASHID A.; NEOGI, TUHINA; SEO, PHILIP; SUPPIAH, RAVI; TOMASSON, GUNNAR; MERKEL, PETER A.

2013-01-01

Giant cell (GCA) and Takayasu’s arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development. PMID:21724719

Space transfer concepts and analysis for exploration missions. Implementation plan and element description document. Volume 1: Major trades. Book 2: Draft final

NASA Technical Reports Server (NTRS)

1991-01-01

Topics addressed are: (1) an artificial gravity assessment study; (2) Mars mission transport vehicle (MTV)/Mars excursion vehicle (MEV) mission scenarios; (3) aerobrake issues; (4) equipment life and self-check; (5) earth-to-orbit (ETO) heavy lift launch vehicle (HLLV) definition trades; and (6) risk analysis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Costa, R. C. da; Universidade Federal de Campina Grande, Pombal-PB, 58840-000; Toledo, T. A. de

The effects of the atomic substitution of Pb by Ni in the PbTiO{sub 3} ferroelectric perovskite on the vibrational and structural properties was studied using x-ray diffraction and Raman scattering. It was observed that for Ni concentrations between 0.0 and 0.4, there is the formation of a solid solution with reduction of the Raman wavenumber of the E(TO1) soft mode and the tetragonallity factor, which influence directly the temperature of the tetragonal ferroelectric to cubic paraelectric phase transition, the Curie temperature. For concentrations greater than 0.4, it is observed the formation of a PbTiO{sub 3} and NiTiO{sub 3} composite, denouncedmore » by the recovering of the both, tetragonallity factor and the E(TO1) soft mode wavenumber. The values of the Curie temperatures were estimated by the Raman scattering measurements for temperatures ranging from 300 to 950 K.« less

Discovering Hematopoietic Mechanisms Through Genome-Wide Analysis of GATA Factor Chromatin Occupancy

PubMed Central

Fujiwara, Tohru; O'Geen, Henriette; Keles, Sunduz; Blahnik, Kimberly; Linnemann, Amelia K.; Kang, Yoon-A; Choi, Kyunghee; Farnham, Peggy J.; Bresnick, Emery H.

2009-01-01

SUMMARY GATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction, and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for cross-regulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2 negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis. PMID:19941826

Control of developmentally primed erythroid genes by combinatorial co-repressor actions

PubMed Central

Stadhouders, Ralph; Cico, Alba; Stephen, Tharshana; Thongjuea, Supat; Kolovos, Petros; Baymaz, H. Irem; Yu, Xiao; Demmers, Jeroen; Bezstarosti, Karel; Maas, Alex; Barroca, Vilma; Kockx, Christel; Ozgur, Zeliha; van Ijcken, Wilfred; Arcangeli, Marie-Laure; Andrieu-Soler, Charlotte; Lenhard, Boris; Grosveld, Frank; Soler, Eric

2015-01-01

How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation. PMID:26593974

Periodic mesoporous organosilicas containing interconnected [Si(CH2)]3 rings.

PubMed

Landskron, Kai; Hatton, Benjamin D; Perovic, Doug D; Ozin, Geoffrey A

2003-10-10

A periodic mesoporous organosilica composed of interconnected three-ring [Si(CH2)]3 units built of three SiO2(CH2)2 tetrahedral subunits is reported. It represents the archetype of a previously unknown class of nanocomposite materials in which two bridging organic groups are bound to each silicon atom. It can be obtained with powder and oriented film morphologies. The nanocomposite is self-assembled from the cyclic three-ring silsesquioxane [(EtO)2Si(CH2)]3 precursor and a surfactant mesophase to give a well-ordered mesoporous framework. Low dielectric constants and good mechanical stability of the films were measured, making this material interesting for microelectronic applications. Methylene group reactivity of the three-ring precursor provides entry to a family of nanocomposites, exemplified by the synthesis and self-assembly of [(EtO)2Si(CHR)][(EtO)2Si(CH2)]2 (where R indicates iodine, bromine, or an ethyl group).

Measuring the influence of a mental health training module on the therapeutic optimism of advanced nurse practitioner students in the United Kingdom.

PubMed

Hemingway, Steve; Rogers, Melanie; Elsom, Stephen

2014-03-01

To evaluate the influence of a mental health training module on the therapeutic optimism of advanced nurse practitioner (ANP) students in primary care (family practice). Three cohorts of ANPs who undertook a Mental Health Problems in Primary Care Module as part of their MSc ANP (primary care) run by the University of Huddersfield completed the Elsom Therapeutic Optimism Scale (ETOS), in a pre- and postformat. The ETOS is a 10-item, self-administered scale, which has been used to evaluate therapeutic optimism previously in mental health professionals. All three cohorts who completed the scale showed an improvement in their therapeutic optimism scores. With stigma having such a detrimental effect for people diagnosed with a mental health problem, ANPs who are more mental health literate facilitated by education and training in turn facilitates them to have the skills and confidence to engage and inspire hope for the person diagnosed with mental health problems. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

Effects of Coke Deposits on the Catalytic Performance of Large Zeolite H-ZSM-5 Crystals during Alcohol-to-Hydrocarbon Reactions as Investigated by a Combination of Optical Spectroscopy and Microscopy

PubMed Central

Nordvang, Emily C; Borodina, Elena; Ruiz-Martínez, Javier; Fehrmann, Rasmus; Weckhuysen, Bert M

2015-01-01

The catalytic activity of large zeolite H-ZSM-5 crystals in methanol (MTO) and ethanol-to-olefins (ETO) conversions was investigated and, using operando UV/Vis measurements, the catalytic activity and deactivation was correlated with the formation of coke. These findings were related to in situ single crystal UV/Vis and confocal fluorescence micro-spectroscopy, allowing the observation of the spatiotemporal formation of intermediates and coke species during the MTO and ETO conversions. It was observed that rapid deactivation at elevated temperatures was due to the fast formation of aromatics at the periphery of the H-ZSM-5 crystals, which are transformed into more poly-aromatic coke species at the external surface, preventing the diffusion of reactants and products into and out of the H-ZSM-5 crystal. Furthermore, we were able to correlate the operando UV/Vis spectroscopy results observed during catalytic testing with the single crystal in situ results. PMID:26463581

Inhibition of endogenous heat shock protein 70 attenuates inducible nitric oxide synthase induction via disruption of heat shock protein 70/Na(+) /H(+) exchanger 1-Ca(2+) -calcium-calmodulin-dependent protein kinase II/transforming growth factor β-activated kinase 1-nuclear factor-κB signals in BV-2 microglia.

PubMed

Huang, Chao; Lu, Xu; Wang, Jia; Tong, Lijuan; Jiang, Bo; Zhang, Wei

2015-08-01

Inducible nitric oxide synthase (iNOS) critically contributes to inflammation and host defense. The inhibition of heat shock protein 70 (Hsp70) prevents iNOS induction in lipopolysaccharide (LPS)-stimulated macrophages. However, the role and mechanism of endogenous Hsp70 in iNOS induction in microglia remains unclear. This study addresses this issue in BV-2 microglia, showing that Hsp70 inhibition or knockdown prevents LPS-induced iNOS protein expression and nitric oxide production. Real-time PCR experiments showed that LPS-induced iNOS mRNA transcription was blocked by Hsp70 inhibition. Further studies revealed that the inhibition of Hsp70 attenuated LPS-stimulated nuclear translocation and phosphorylation of nuclear factor (NF)-κB as well as the degradation of inhibitor of κB (IκB)-α and phosphorylation of IκB kinase β (IKKβ). This prevention effect of Hsp70 inhibition on IKKβ-NF-κB activation was found to be dependent on the Ca(2+) /calcium-calmodulin-dependent protein kinase II (CaMKII)/transforming growth factor β-activated kinase 1 (TAK1) signals based on the following observations: 1) chelation of intracellular Ca(2+) or inhibition of CaMKII reduced LPS-induced increases in TAK1 phosphorylation and 2) Hsp70 inhibition reduced LPS-induced increases in CaMKII/TAK1 phosphorylation, intracellular pH value, [Ca(2+) ]i , and CaMKII/TAK1 association. Mechanistic studies showed that Hsp70 inhibition disrupted the association between Hsp70 and Na(+) /H(+) exchanger 1 (NHE1), which is an important exchanger responsible for Ca(2+) influx in LPS-stimulated cells. These studies demonstrate that the inhibition of endogenous Hsp70 attenuates the induction of iNOS, which likely occurs through the disruption of NHE1/Hsp70-Ca(2+) -CaMKII/TAK1-NF-κB signals in BV-2 microglia, providing further insight into the functions of Hsp70 in the CNS. © 2015 Wiley Periodicals, Inc.

Transforming Growth Factor-β-Activated Kinase 1 Is Required for Human FcγRIIIb-Induced Neutrophil Extracellular Trap Formation.

PubMed

Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

2016-01-01

Neutrophils (PMNs) are the most abundant leukocytes in the blood. PMN migrates from the circulation to sites of infection where they are responsible for antimicrobial functions. PMN uses phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. Several stimuli, including bacteria, fungi, and parasites, and some pharmacological compounds, such as Phorbol 12-myristate 13-acetate (PMA), are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. Recently, it was reported that FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. Direct cross-linking of FcγRIIA or integrins did not promote NET formation. FcγRIIIb-induced NET formation presented different kinetics from PMA-induced NET formation, suggesting differences in signaling. Because FcγRIIIb also induces a strong activation of extracellular signal-regulated kinase (ERK) and nuclear factor Elk-1, and the transforming growth factor-β-activated kinase 1 (TAK1) has recently been implicated in ERK signaling, in the present report, we explored the role of TAK1 in the signaling pathway activated by FcγRIIIb leading to NET formation. FcγRIIIb was stimulated by specific monoclonal antibodies, and NET formation was evaluated in the presence or absence of pharmacological inhibitors. The antibiotic LL Z1640-2, a selective inhibitor of TAK1 prevented FcγRIIIb-induced, but not PMA-induced NET formation. Both PMA and FcγRIIIb cross-linking induced phosphorylation of ERK. But, LL Z1640-2 only inhibited the FcγRIIIb-mediated activation of ERK. Also, only FcγRIIIb, similarly to transforming growth factor-β-induced TAK1 phosphorylation. A MEK (ERK kinase)-specific inhibitor was able to prevent ERK phosphorylation induced by both PMA and FcγRIIIb. These data show for the first time that FcγRIIIb cross-linking activates TAK1, and that this kinase is required for triggering the MEK/ERK signaling pathway to NETosis.

Application of a CROPWAT Model to Analyze Crop Yields in Nicaragua

NASA Astrophysics Data System (ADS)

Doria, R.; Byrne, J. M.

2013-12-01

ABSTRACT Changes in climate are likely to influence crop yields due to varying evapotranspiration and precipitation over agricultural regions. In Nicaragua, agriculture is extensive, with new areas of land brought into production as the population increases. Nicaraguan staple food items (maize and beans) are produced mostly by small scale farmers with less than 10 hectares, but they are critical for income generation and food security for rural communities. Given that the majority of these farmers are dependent on rain for crop irrigation, and that maize and beans are sensitive to variations in temperature and rainfall patterns, the present study was undertaken to assess the impact of climate change on these crop yields. Climate data were generated per municipio representing the three major climatic zones of the country: the wet Pacific lowland, the cooler Central highland, and the Caribbean lowland. Historical normal climate data from 1970-2000 (baseline period) were used as input to CROPWAT model to analyze the potential and actual evapotranspiration (ETo and ETa, respectively) that affects crop yields. Further, generated local climatic data of future years (2030-2099) under various scenarios were inputted to the CROPWAT to determine changes in ETo and ETa from the baseline period. Spatial variability maps of both ETo and ETa as well as crop yields were created. Results indicated significant variation in seasonal rainfall depth during the baseline period and predicted decreasing trend in the future years that eventually affects yields. These maps enable us to generate appropriate adaptation measures and best management practices for small scale farmers under future climate change scenarios. KEY WORDS: Climate change, evapotranspiration, CROPWAT, yield, Nicaragua

NASA's Advanced Propulsion Technology Activities for Third Generation Fully Reusable Launch Vehicle Applications

NASA Technical Reports Server (NTRS)

Hueter, Uwe

2000-01-01

NASA's Office of Aeronautics and Space Transportation Technology (OASTT) established the following three major goals, referred to as "The Three Pillars for Success": Global Civil Aviation, Revolutionary Technology Leaps, and Access to Space. The Advanced Space Transportation Program Office (ASTP) at the NASA's Marshall Space Flight Center in Huntsville, Ala. focuses on future space transportation technologies under the "Access to Space" pillar. The Propulsion Projects within ASTP under the investment area of Spaceliner100, focus on the earth-to-orbit (ETO) third generation reusable launch vehicle technologies. The goals of Spaceliner 100 is to reduce cost by a factor of 100 and improve safety by a factor of 10,000 over current conditions. The ETO Propulsion Projects in ASTP, are actively developing combination/combined-cycle propulsion technologies that utilized airbreathing propulsion during a major portion of the trajectory. System integration, components, materials and advanced rocket technologies are also being pursued. Over the last several years, one of the main thrusts has been to develop rocket-based combined cycle (RBCC) technologies. The focus has been on conducting ground tests of several engine designs to establish the RBCC flowpaths performance. Flowpath testing of three different RBCC engine designs is progressing. Additionally, vehicle system studies are being conducted to assess potential operational space access vehicles utilizing combined-cycle propulsion systems. The design, manufacturing, and ground testing of a scale flight-type engine are planned. The first flight demonstration of an airbreathing combined cycle propulsion system is envisioned around 2005. The paper will describe the advanced propulsion technologies that are being being developed under the ETO activities in the ASTP program. Progress, findings, and future activities for the propulsion technologies will be discussed.

Impact of Texas high school science teacher credentials on student performance in high school science

NASA Astrophysics Data System (ADS)

George, Anna Ray Bayless

A study was conducted to determine the relationship between the credentials held by science teachers who taught at a school that administered the Science Texas Assessment on Knowledge and Skills (Science TAKS), the state standardized exam in science, at grade 11 and student performance on a state standardized exam in science administered in grade 11. Years of teaching experience, teacher certification type(s), highest degree level held, teacher and school demographic information, and the percentage of students who met the passing standard on the Science TAKS were obtained through a public records request to the Texas Education Agency (TEA) and the State Board for Educator Certification (SBEC). Analysis was performed through the use of canonical correlation analysis and multiple linear regression analysis. The results of the multiple linear regression analysis indicate that a larger percentage of students met the passing standard on the Science TAKS state attended schools in which a large portion of the high school science teachers held post baccalaureate degrees, elementary and physical science certifications, and had 11-20 years of teaching experience.

A role for NRAGE in NF-κB activation through the non-canonical BMP pathway

PubMed Central

2010-01-01

Background Previous studies have linked neurotrophin receptor-interacting MAGE protein to the bone morphogenic protein signaling pathway and its effect on p38 mediated apoptosis of neural progenitor cells via the XIAP-Tak1-Tab1 complex. Its effect on NF-κB has yet to be explored. Results Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -α/β and subsequent transcriptional activation of the p65 subunit of NF-κB. Ablation of endogenous NRAGE by siRNA inhibited NF-κB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-κB. Finally, cytokine profiling of an NRAGE over-expressing stable line revealed the expression of macrophage migration inhibitory factor. Conclusion Modulation of NRAGE expression revealed novel roles in regulating NF-κB activity in the non-canonical bone morphogenic protein signaling pathway. The expression of macrophage migration inhibitory factor by bone morphogenic protein -4 reveals novel crosstalk between an immune cytokine and a developmental pathway. PMID:20100315

Costunolide ameliorates lipoteichoic acid-induced acute lung injury via attenuating MAPK signaling pathway.

PubMed

Chen, Zhengxu; Zhang, Dan; Li, Man; Wang, Baolong

2018-06-12

Lipoteichoic acid (LTA)-induced acute lung injury (ALI) is an experimental model for mimicking Gram-positive bacteria-induced pneumonia that is a refractory disease with lack of effective medicines. Here, we reported that costunolide, a sesquiterpene lactone, ameliorated LTA-induced ALI. Costunolide treatment reduced LTA-induced neutrophil lung infiltration, cytokine and chemokine production (TNF-α, IL-6 and KC), and pulmonary edema. In response to LTA challenge, treatment with costunolide resulted less iNOS expression and produced less inflammatory cytokines in bone marrow derived macrophages (BMDMs). Pretreatment with costunolide also attenuated the LTA-induced the phosphorylation of p38 MAPK and ERK in BMDMs. Furthermore, costunolide treatment reduced the phosphorylation of TAK1 and inhibited the interaction of TAK1 with Tab1. In conclusion, we have demonstrated that costunolide protects against LTA-induced ALI via inhibiting TAK1-mediated MAPK signaling pathway, and our studies suggest that costunolide is a promising agent for treatment of Gram-positive bacteria-mediated pneumonia. Copyright © 2018 Elsevier B.V. All rights reserved.

Dynamic one-dimensional modeling of secondary settling tanks and design impacts of sizing decisions.

PubMed

Li, Ben; Stenstrom, Michael K

2014-03-01

As one of the most significant components in the activated sludge process (ASP), secondary settling tanks (SSTs) can be investigated with mathematical models to optimize design and operation. This paper takes a new look at the one-dimensional (1-D) SST model by analyzing and considering the impacts of numerical problems, especially the process robustness. An improved SST model with Yee-Roe-Davis technique as the PDE solver is proposed and compared with the widely used Takács model to show its improvement in numerical solution quality. The improved and Takács models are coupled with a bioreactor model to reevaluate ASP design basis and several popular control strategies for economic plausibility, contaminant removal efficiency and system robustness. The time-to-failure due to rising sludge blanket during overloading, as a key robustness indicator, is analyzed to demonstrate the differences caused by numerical issues in SST models. The calculated results indicate that the Takács model significantly underestimates time to failure, thus leading to a conservative design. Copyright © 2013 Elsevier Ltd. All rights reserved.

An Innovative Modeling and Measurement Approach to Improve Rice Water Use Efficiency in California

NASA Astrophysics Data System (ADS)

Montazar, A.; Little, C.; Rejmanek, H.; Tindula, G.; Snyder, R. L.

2014-12-01

California is amongst the top rice producing states in the USA, and more than 95 percent of California's rice is grown in the Sacramento Valley. Based on older literature, the rice water requirement (ETc), ranges between 914 and 1,100 mm. In this study, the actual rice water requirement was measured using the residual of the energy balance method over three paddy rice fields during 2011-2013 seasons in the Sacramento Valley. Net radiation and ground heat flux density were measured, and both eddy covariance (EC) and the surface renewal (SR) technique were employed to determine the sensible heat flux density. The surface renewal method uses high frequency temperature measurements from fine wire thermocouples above the canopy. Mean amplitude and duration of the ramps over half hour periods were determined using a structure function and the characteristics are employed to estimate the direction and magnitude of sensible heat flux using the ratio of the amplitude to the ramp duration as the change in temperature per unit time and the volumetric heat capacity of the air to estimate the magnitude of the heat flux. In the study, 76.2 mm diameter chromel-constantan thermocouples were used to measure high frequency temperature at 10 Hz. The results indicate that there is considerable variability in rice water use both spatially and temporally. The average three-year measured ET of the experimental fields located in Butte County was 734 and 725 mm; and in Colusa County was 771 mm. A typical crop coefficient (Kc) curve was derived from the measured ETc and reference ET (ETo) data. Spatial estimates of monthly climate data from the Sacramento Valley were used to calculate monthly mean ETo, and smooth curve fits of the monthly data gave estimates of typical daily ETo. The daily ETc was calculated as the product of ETo and Kc, and seasonal ETc was calculated by summing the daily ETc values. The results reveal that the seasonal rice ETc was less than earlier estimates. Surface

EPA Prevents the Development of Abdominal Aortic Aneurysms through Gpr-120/Ffar-4.

PubMed

Kamata, Ryo; Bumdelger, Batmunkh; Kokubo, Hiroki; Fujii, Masayuki; Yoshimura, Koichi; Ishida, Takafumi; Ishida, Mari; Yoshizumi, Masao

2016-01-01

Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture with a high mortality rate. Although eicosapentaenoic acid (EPA) has been reported to prevent AAA formation, the mechanism by which EPA works on vascular smooth muscle cells is unknown. This study aimed to investigate the mechanism by which orally-administered EPA prevents the formation of severe AAAs that develop in Osteoprotegerin (Opg) knockout (KO) mice. In the CaCl2-induced AAA model, EPA attenuated the enhanced progression of AAAs in Opg-KO mice, including the increase in aortic diameter with destruction of elastic fibers in the media. Immunohistochemical analyses showed that EPA reduced the phosphorylation of transforming growth factor beta-activated kinase-1/Map3k7 (Tak-1) and c-Jun NH2-terminal kinase (JNK), as well as the expression of Matrix metalloproteinase-9 (Mmp-9) in the media of the aorta. In smooth muscle cell cultures, rh-TRAIL-induced activation of the Tak-1-JNK pathway and increase in Mmp-9 expression were inhibited by EPA. Moreover, GW9508, a specific ligand for G-protein coupled receptor (Gpr)-120/Free fatty acid receptor (Ffar)-4, mimicked the effects of EPA. The effects of EPA were abrogated by knockdown of the Gpr-120/Ffar-4 receptor gene. Our data demonstrate that the Trail-Tak-1-JNK-Mmp-9 pathway is responsible for the enhancement of AAAs in Opg-KO mice, and that EPA inhibits the Tak-1-JNK pathway by activating Gpr-120/Ffar-4, which results in the attenuation of AAA development.

Association of vascular physical examination findings and arteriographic lesions in large vessel vasculitis.

PubMed

Grayson, Peter C; Tomasson, Gunnar; Cuthbertson, David; Carette, Simon; Hoffman, Gary S; Khalidi, Nader A; Langford, Carol A; McAlear, Carol A; Monach, Paul A; Seo, Philip; Warrington, Kenneth J; Ytterberg, Steven R; Merkel, Peter A

2012-02-01

To assess the utility of the vascular physical examination to detect arteriographic lesions in patients with established large vessel vasculitis (LVV), including Takayasu's arteritis (TAK) and giant cell arteritis (GCA). In total, 100 patients (TAK = 68, GCA = 32) underwent standardized physical examination and angiography of the carotid, subclavian, and axillary arteries. Sensitivity and specificity were calculated for the association between findings on physical examination focusing on the vascular system (absent pulse, bruit, and blood pressure difference) and arteriographic lesions defined as stenosis, occlusion, or aneurysm. We found 67% of patients had at least 1 abnormality on physical examination (74% TAK, 53% GCA). Arteriographic lesions were seen in 76% of patients (82% TAK, 63% GCA). Individual physical examination findings had poor sensitivity (range 14%-50%) and good-excellent specificity (range 71%-98%) to detect arteriographic lesions. Even when considering physical examination findings in combination, at least 30% of arteriographic lesions were missed. Specificity improved (range 88%-100%) if individual physical examination findings were compared to a broader region of vessels rather than specific anatomically correlated vessels and if ≥ 1 physical examination findings were combined. In patients with established LVV, physical examination alone is worthwhile to detect arterial disease but does not always localize or reveal the full extent of arteriographic lesions. Abnormal vascular system findings on physical examination are highly associated with the presence of arterial lesions, but normal findings on physical examination do not exclude the possibility of arterial disease. Serial angiographic assessment is advisable to monitor arterial disease in patients with established LVV.

Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts.

PubMed

Fechtner, Sabrina; Singh, Anil; Chourasia, Mukesh; Ahmed, Salahuddin

2017-08-15

In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea. Copyright © 2017. Published by Elsevier Inc.

Migrant and Refugee Patient Perspectives on Travel and Tuberculosis along the Thailand-Myanmar Border: A Qualitative Study.

PubMed

Tschirhart, Naomi; Sein, Tabitha; Nosten, Francois; Foster, Angel M

2016-01-01

The Thailand-Myanmar border separates two very different health systems. The healthcare system in eastern Myanmar remains underdeveloped as a result of decades of instability. Comparatively, Tak province, Thailand has more healthcare resources. In this Thai border province government hospitals and non-governmental organizations provide tuberculosis (TB) treatment to migrants and refugees. Our overall study aimed to explore accessibility of TB treatment, TB surveillance and health system responsiveness specific to migrant and refugee populations in Tak province. In this paper, we focus on the perspectives of migrant and refugee TB patients with respect to travel and treatment in Tak province. In 2014 we conducted focus group discussions with 61 TB, Tuberculosis and Human Immunodeficiency Virus co-infection, and multidrug-resistant TB patients in Tak province. We analyzed the data for content and themes and documented individual travel trajectories. Migrants are travelling with active TB within the country and between Thailand and Myanmar. Migrants primarily travelled to obtain treatment but two participants reported travelling home to seek family care in Myanmar before returning to Thailand for treatment. Travel, while expensive and arduous, is an adaptive strategy that migrants use to access healthcare. Migrant's need for travel points to larger difficulties associated with healthcare access in the border region. Long distance travel with an infectious disease can be seen as an indicator that local healthcare is not available or affordable. These findings suggest that public health officials from both sides of the border should discuss the factors that contribute to travel with active TB and explore potential solutions to mitigate disease transmission in migrant populations.

Air-Cored Linear Induction Motor for Earth-to-Orbit Systems

NASA Technical Reports Server (NTRS)

Zabar, Zivan; Levi, Enrico; Birenbaum, Leo

1996-01-01

The need for lowering the cost of Earth-to-Orbit (ETO) launches has prompted consideration of electromagnetic launchers. A preliminary design based on the experience gained in an advanced type of coilgun and on innovative ideas shows that such a launcher is technically feasible with almost off-the-shelf components.

Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5

PubMed Central

Fizazi, Karim; Jones, Robert; Oudard, Stephane; Efstathiou, Eleni; Saad, Fred; de Wit, Ronald; De Bono, Johann; Cruz, Felipe Melo; Fountzilas, George; Ulys, Albertas; Carcano, Flavio; Agarwal, Neeraj; Agus, David; Bellmunt, Joaquim; Petrylak, Daniel P.; Lee, Shih-Yuan; Webb, Iain J.; Tejura, Bindu; Borgstein, Niels; Dreicer, Robert

2015-01-01

Purpose Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory–Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. Results The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). Conclusion Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity. PMID:25624429

Protein Phosphatase 2A Signaling in Human Prostate Cancer

DTIC Science & Technology

2013-06-01

family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 2001;353:417-39. (6) Eto M, Bennouna J, Hunter OC...phosphatidylinositol 3’-kinase and Akt/protein kinase B. Cancer Res 1999;59:1449-53. (14) Grethe S, Porn -Ares MI. p38 MAPK regulates phosphorylation of Bad

21 CFR 880.6860 - Ethylene oxide gas sterilizer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ethylene oxide gas sterilizer. 880.6860 Section... Miscellaneous Devices § 880.6860 Ethylene oxide gas sterilizer. (a) Identification. An ethylene gas sterilizer is a nonportable device intended for use by a health care provider that uses ethylene oxide (ETO) to...

Petrogenesis of ultramafic rocks and olivine-rich troctolites from the East Taiwan Ophiolite in the Lichi mélange

NASA Astrophysics Data System (ADS)

Morishita, Tomoaki; Ghosh, Biswajit; Soda, Yusuke; Mizukami, Tomoyuki; Tani, Ken-ichiro; Ishizuka, Osamu; Tamura, Akihiro; Komaru, Chihiro; Aari, Shoji; Yang, Hsiao-Chin; Chen, Wen-Shan

2017-12-01

We examine ultramafic and olivine-rich troctolite blocks of the East Taiwan Ophiolite (ETO) in the Lichi Mélange. Although ultramafic rocks are extensively serpentinized, the primary minerals, such as olivine, orthopyroxene, clinopyroxene, spinel and plagioclase can be identified. The ultramafic rocks are classified into harzburgite (± clinopyroxene), dunite, and olivine websterite. Major and trace element compositions of the primary minerals in harzburgites, such as the Cr# [= Cr/(Cr + Al) atomic ratio] of chromian spinel (0.3-0.58) and incompatible elements-depleted trace element patterns of clinopyroxenes, indicate their residue origin after partial melting with less flux components. These compositions are similar to those from mid-ocean ridge peridotites as well as back-arc peridotites from the Philippine Sea Plate. The olivine websterite contains discrete as well as occasional locally concentrated plagioclase grains. Petrological characteristics coupled with similarity in trace element patterns of clinopyroxenes in the harzburgite and olivine websterite samples indicate that the olivine websterite is likely formed by clinopyroxene addition to a lherzolitic/harzburgitic peridotite from a pyroxene-saturated mafic melt. Dunite with medium Cr# spinels indicates cumulus or replacement by melt-peridotite reaction origins. Mineral composition of olivine-rich troctolite cannot be explained by simple crystallization from basaltic magmas, but shows a chemical trend expected for products after melt-peridotite interactions. Mineral compositions of the dunite and olivine-rich troctolite are also within chemical ranges of mid-ocean ridge samples, and are slightly different from back-arc samples from the Philippine Sea Plate. We conclude that peridotites in the ETO are not derived from the northern extension of the Luzon volcanic arc mantle. Further geochronological study is, however, required to constrain the origin of the ETO ophiolite, because peridotites are probably

EPA Prevents the Development of Abdominal Aortic Aneurysms through Gpr-120/Ffar-4

PubMed Central

Kamata, Ryo; Bumdelger, Batmunkh; Kokubo, Hiroki; Fujii, Masayuki; Yoshimura, Koichi; Ishida, Takafumi; Ishida, Mari; Yoshizumi, Masao

2016-01-01

Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture with a high mortality rate. Although eicosapentaenoic acid (EPA) has been reported to prevent AAA formation, the mechanism by which EPA works on vascular smooth muscle cells is unknown. This study aimed to investigate the mechanism by which orally-administered EPA prevents the formation of severe AAAs that develop in Osteoprotegerin (Opg) knockout (KO) mice. In the CaCl2-induced AAA model, EPA attenuated the enhanced progression of AAAs in Opg-KO mice, including the increase in aortic diameter with destruction of elastic fibers in the media. Immunohistochemical analyses showed that EPA reduced the phosphorylation of transforming growth factor beta-activated kinase-1/Map3k7 (Tak-1) and c-Jun NH2-terminal kinase (JNK), as well as the expression of Matrix metalloproteinase-9 (Mmp-9) in the media of the aorta. In smooth muscle cell cultures, rh-TRAIL-induced activation of the Tak-1-JNK pathway and increase in Mmp-9 expression were inhibited by EPA. Moreover, GW9508, a specific ligand for G-protein coupled receptor (Gpr)-120/Free fatty acid receptor (Ffar)-4, mimicked the effects of EPA. The effects of EPA were abrogated by knockdown of the Gpr-120/Ffar-4 receptor gene. Our data demonstrate that the Trail-Tak-1-JNK-Mmp-9 pathway is responsible for the enhancement of AAAs in Opg-KO mice, and that EPA inhibits the Tak-1-JNK pathway by activating Gpr-120/Ffar-4, which results in the attenuation of AAA development. PMID:27764222

Association of Vascular Physical Examination Findings and Arteriographic Lesions in Large Vessel Vasculitis

PubMed Central

GRAYSON, PETER C.; TOMASSON, GUNNAR; CUTHBERTSON, DAVID; CARETTE, SIMON; HOFFMAN, GARY S.; KHALIDI, NADER A.; LANGFORD, CAROL A.; McALEAR, CAROL A.; MONACH, PAUL A.; SEO, PHILIP; WARRINGTON, KENNETH J.; YTTERBERG, STEVEN R.; MERKEL, PETER A.

2013-01-01

Objective To assess the utility of the vascular physical examination to detect arteriographic lesions in patients with established large vessel vasculitis (LVV), including Takayasu’s arteritis (TAK) and giant cell arteritis (GCA). Methods In total, 100 patients (TAK = 68, GCA = 32) underwent standardized physical examination and angiography of the carotid, subclavian, and axillary arteries. Sensitivity and specificity were calculated for the association between findings on physical examination focusing on the vascular system (absent pulse, bruit, and blood pressure difference) and arteriographic lesions defined as stenosis, occlusion, or aneurysm. Results We found 67% of patients had at least 1 abnormality on physical examination (74% TAK, 53% GCA). Arteriographic lesions were seen in 76% of patients (82% TAK, 63% GCA). Individual physical examination findings had poor sensitivity (range 14%–50%) and good-excellent specificity (range 71%–98%) to detect arteriographic lesions. Even when considering physical examination findings in combination, at least 30% of arteriographic lesions were missed. Specificity improved (range 88%–100%) if individual physical examination findings were compared to a broader region of vessels rather than specific anatomically correlated vessels and if ≥ 1 physical examination findings were combined. Conclusion In patients with established LVV, physical examination alone is worthwhile to detect arterial disease but does not always localize or reveal the full extent of arteriographic lesions. Abnormal vascular system findings on physical examination are highly associated with the presence of arterial lesions, but normal findings on physical examination do not exclude the possibility of arterial disease. Serial angiographic assessment is advisable to monitor arterial disease in patients with established LVV. PMID:22174204

Migrant and Refugee Patient Perspectives on Travel and Tuberculosis along the Thailand-Myanmar Border: A Qualitative Study

PubMed Central

Sein, Tabitha; Nosten, Francois; Foster, Angel M.

2016-01-01

Background The Thailand-Myanmar border separates two very different health systems. The healthcare system in eastern Myanmar remains underdeveloped as a result of decades of instability. Comparatively, Tak province, Thailand has more healthcare resources. In this Thai border province government hospitals and non-governmental organizations provide tuberculosis (TB) treatment to migrants and refugees. Objectives Our overall study aimed to explore accessibility of TB treatment, TB surveillance and health system responsiveness specific to migrant and refugee populations in Tak province. In this paper, we focus on the perspectives of migrant and refugee TB patients with respect to travel and treatment in Tak province. Methods In 2014 we conducted focus group discussions with 61 TB, Tuberculosis and Human Immunodeficiency Virus co-infection, and multidrug-resistant TB patients in Tak province. We analyzed the data for content and themes and documented individual travel trajectories. Results and Discussion Migrants are travelling with active TB within the country and between Thailand and Myanmar. Migrants primarily travelled to obtain treatment but two participants reported travelling home to seek family care in Myanmar before returning to Thailand for treatment. Travel, while expensive and arduous, is an adaptive strategy that migrants use to access healthcare. Conclusions Migrant’s need for travel points to larger difficulties associated with healthcare access in the border region. Long distance travel with an infectious disease can be seen as an indicator that local healthcare is not available or affordable. These findings suggest that public health officials from both sides of the border should discuss the factors that contribute to travel with active TB and explore potential solutions to mitigate disease transmission in migrant populations. PMID:27509036

A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations.

PubMed

Ritelli, M; Morlino, S; Giacopuzzi, E; Bernardini, L; Torres, B; Santoro, G; Ravasio, V; Chiarelli, N; D'Angelantonio, D; Novelli, A; Grammatico, P; Colombi, M; Castori, M

2018-01-01

Deletions encompassing TAK1-binding protein 2 (TAB2) associated with isolated and syndromic congenital heart defects. Rare missense variants are found in patients with a similar phenotype as well as in a single individual with frontometaphyseal dysplasia. We describe a family and an additional sporadic patient with polyvalvular heart disease, generalized joint hypermobility and related musculoskeletal complications, soft, velvety and hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism. In the first family, whole-exome sequencing (WES) disclosed the novel TAB2 c.1398dup (p.Thr467Tyrfs*6) variant that eliminates the C-terminal zinc finger domain essential for activation of TAK1 (TGFβ-activated kinase 1)-dependent signaling pathways. The sporadic case carryed a ~2 Mb de novo deletion including 28 genes also comprising TAB2. This study reveal an association between TAB2 mutations and a phenotype resembling Ehlers-Danlos syndrome with severe polyvalvular heart disease and subtle facial dysmorphism. Our findings support the existence of a wider spectrum of clinical phenotypes associated with TAB2 perturbations and emphasize the role of TAK1 signaling network in human development. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Becoming a Minor Teacher

ERIC Educational Resources Information Center

Gorodetsky, Malka; Barak, Judith; Dhaan, Eto

2017-01-01

This article follows one year in the life of one of the authors of this article, Eto--the year she was a graduate student in the M.Ed. program and concurrently was teaching in a second grade elementary school. Addressing her subjective emergence along the intertwining experiences in two different contexts: it explores her conversations with her…

Assessing I-Grid(TM) web-based monitoring for power quality and reliability benchmarking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Divan, Deepak; Brumsickle, William; Eto, Joseph

2003-04-30

This paper presents preliminary findings from DOEs pilot program. The results show how a web-based monitoring system can form the basis for aggregation of data and correlation and benchmarking across broad geographical lines. A longer report describes additional findings from the pilot, including impacts of power quality and reliability on customers operations [Divan, Brumsickle, Eto 2003].

Renovating Organizational Culture: Influencing Your Unit’s Destiny

DTIC Science & Technology

2011-06-01

Thesis Adviser Approved by: Signarure: -~ • H k IL:::. Stepha~eaJar; Committee Member This Page Intentionally Blank 11 iii ABSTRACT The conduct...136 BIBLIOGRAPHY ......................................................................................................... 143 VITA...e>Jn.~ ..- s Of .,..,,.,~ ........... ,~ RNm. - = ,c~-· LITIOri’l""r"’ ’:"n:=" =m- ,...,.. ~ ’~ • ... ~ Stt\\K’MH~ Etos ..... C, 01--nt

29 CFR 1910.1047 - Ethylene oxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (8)-hour time-weighted average. Assistant Secretary means the Assistant Secretary of Labor for... organic compound with chemical formula C2 H4 O. (c) Permissible exposure limits—(1) 8-hour time weighted... in excess of one (1) part EtO per million parts of air (1 ppm) as an 8-hour time-weighted average (8...

29 CFR 1910.1047 - Ethylene oxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (8)-hour time-weighted average. Assistant Secretary means the Assistant Secretary of Labor for... organic compound with chemical formula C2 H4 O. (c) Permissible exposure limits—(1) 8-hour time weighted... in excess of one (1) part EtO per million parts of air (1 ppm) as an 8-hour time-weighted average (8...

29 CFR 1910.1047 - Ethylene oxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (8)-hour time-weighted average. Assistant Secretary means the Assistant Secretary of Labor for... organic compound with chemical formula C2 H4 O. (c) Permissible exposure limits—(1) 8-hour time weighted... in excess of one (1) part EtO per million parts of air (1 ppm) as an 8-hour time-weighted average (8...

Evapotranspiration and water balance of an anthropogenic coastal desert wetland: responses to fire, inflows and salinities

USGS Publications Warehouse

Glenn, Edward P.; Mexicano, Lourdes; Garcia-Hernandez, Jaqueline; Nagler, Pamela L.; Gomez-Sapiens, Martha M.; Tang, Dawei; Lomeli, Marcelo A.; Ramírez-Hernández, Jorge; Zamora-Arroyo, Francisco

2013-01-01

Evapotranspiration (ET) and other water balance components were estimated for Cienega de Santa Clara, an anthropogenic brackish wetland in the delta of the Colorado River in Mexico. The marsh is in the Biosphere Reserve of the Upper Gulf of California and Delta of the Colorado River, and supports a high abundance and diversity of wildlife. Over 95% of its water supply originates as agricultural drain water from the USA, sent for disposal in Mexico. This study was conducted from 2009 to 2011, before, during and after a trial run of the Yuma Desalting Plant in the USA, which will divert water from the wetland and replace it with brine from the desalting operation. The goal was to estimate the main components in the water budget to be used in creating management scenarios for this marsh. We used a remote sensing algorithm to estimate ET from meteorological data and Enhanced Vegetation Index values from the Moderate Resolution Imaging Spectrometer (MODIS) sensors on the Terra satellite. ET estimates from the MODIS method were then compared to results from a mass balance of water and salt inflows and outflows over the study period. By both methods, mean annual ET estimates ranged from 2.6 to 3.0 mm d−1, or 50 to 60% of reference ET (ETo). Water entered at a mean salinity of 2.6 g L−1 TDS and mean salinity in the wetland was 3.73 g L−1 TDS over the 33 month study period. Over an annual cycle, 54% of inflows supported ET while the rest exited the marsh as outflows; however, in winter when ET was low, up to 90% of the inflows exited the marsh. An analysis of ET estimates over the years 2000–2011 showed that annual ET was proportional to the volume of inflows, but was also markedly stimulated by fires. Spring fires in 2006 and 2011 burned off accumulated thatch, resulting in vigorous growth of new leaves and a 30% increase in peak summer ET compared to non-fire years. Following fires, peak summer ET estimates were equal to ETo, while in non-fire years peak ET was

Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

PubMed

Noujima-Harada, Mai; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sakurai, Hiroaki; Igarashi, Kazuhiko; Ito, Etsuro; Nagakita, Keina; Taniguchi, Kohei; Ohnishi, Nobuhiko; Omote, Shizuma; Tabata, Tetsuya; Sato, Yasuharu; Yoshino, Tadashi

2017-05-01

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-β-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis in Mice via a Toll-Like Receptor 4/p21-Activated Kinase 1 Cascade.

PubMed

Wu, Yaxin; Wu, Jiao; Chen, Ting; Li, Qing; Peng, Wei; Li, Huan; Tang, Xiaowei; Fu, Xiangsheng

2018-05-01

The underlying pathogenic mechanism of Fusobacterium nucleatum in the carcinogenesis of colorectal cancer has been poorly understood. Using C57BL/6-Apc Min/+ mice, we investigated gut microbial structures with F. nucleatum, antibiotics, and Toll-like receptor 4 (TLR4) antagonist TAK-242 treatment. In addition, we measured intestinal tumor formation and the expression of TLR4, p21-activated kinase 1 (PAK1), phosphorylated-PAK1 (p-PAK1), phosphorylated-β-catenin S675 (p-β-catenin S675), and cyclin D1 in mice with different treatments. Fusobacterium nucleatum and antibiotics treatment altered gut microbial structures in mice. In addition, F. nucleatum invaded into the intestinal mucosa in large amounts but were less abundant in the feces of F. nucleatum-fed mice. The average number and size of intestinal tumors in F. nucleatum groups was significantly increased compared to control groups in Apc Min/+ mice (P < 0.05). The expression of TLR4, PAK1, p-PAK1, p-β-catenin S675, and cyclin D1 was significantly increased in F. nucleatum groups compared to the control groups (P < 0.05). Moreover, TAK-242 significantly decreased the average number and size of intestinal tumors compared to F. nucleatum groups (P < 0.05). The expression of p-PAK1, p-β-catenin S675, and cyclin D1 was also significantly decreased in the TAK-242-treated group compared to F. nucleatum groups (P < 0.05). Fusobacterium nucleatum potentiates intestinal tumorigenesis in Apc Min/+ mice via a TLR4/p-PAK1/p-β-catenin S675 cascade. Fusobacterium nucleatum-induced intestinal tumorigenesis can be inhibited by TAK-242, implicating TLR4 as a potential target for the prevention and therapy of F. nucleatum-related colorectal cancer.

A Geothermochronologic Investigation of the Coyote Mountains Metamorphic Core Complex (AZ)

NASA Astrophysics Data System (ADS)

Borel, M.; Gottardi, R.; Casale, G.

2017-12-01

The Coyote Mountains metamorphic core complex (CM-MCC) makes up the northern end of the Baboquivari Mountain complex, which is composed of Mesozoic rocks, Tertiary granites, pegmatites, and metasediments. The CM-MCC expose the Pan Tak granite, a 58 Ma intrusive muscovite-biotite-garnet peraluminous granite. The Pan Tak and other intrusions within the Baboquivari Mountains have been interpreted as anatectic melts representing the culmination of a Laramide crustal shortening orogenic event started in the Late Cretaceous ( 70 Ma). Evidence of this magmatic episode includes polysynthetic twinning in plagioclase, myrmekitic texture in alkali feldspars, and garnet, mica and feldspar assemblages. The magmatic fabric is overprinted by a Tertiary tectonic fabric, associated with the exhumation of the CM-MCC along the Ajo road décollement and associated shear zone. In the shear zone, the Pan Tak mylonite display N-dipping foliation defined by gneissic layering and aligned muscovite, and N-trending mineral stretching lineation. Various shear sense indicators are all consistent with a top-to the-N shear sense. Preliminary argon geochronology results suggest that the shear zone was exhumed 29 Ma ago, an age similar to the onset of detachment faulting in other nearby MCCs (Catalina, Rincon, Pinaleño). In the Pan Tak mylonite, quartz grains display regime 2 to 3 microstructures and shows extensive recrystallization by subgrain rotation and grain boundary migration. The recrystallized grain size ranges between 20 and 50 µm in all samples. Quartz crystallographic preferred orientation measured using electron backscatter diffraction (EBSD) shows that recrystallization was accommodated by dominant prism and minor rhomb slip, suggesting deformation temperature ranging from 450°C to 550°C. These preliminary results constrain the timing of uplift and exhumation, and thermomechanical evolution of the CM-MCC, and improve our understanding of recycling of the continental crust in

Genetic diversity of the msp-1, msp-2, and glurp genes of Plasmodium falciparum isolates along the Thai-Myanmar borders.

PubMed

Congpuong, Kanungnit; Sukaram, Rungniran; Prompan, Yuparat; Dornae, Aibteesam

2014-08-01

To study the genetic diversity at the msp-1, msp-2, and glurp genes of Plasmodium falciparum (P. falciparum) isolates from 3 endemic areas in Thailand: Tak, Kanchanaburi and Ranong provinces. A total of 144 P. falciparum isolates collected prior to treatment during January, 2012 to June, 2013 were genotyped. DNA was extracted; allele frequency and diversity of msp-1, msp-2, and glurp genes were investigated by nested polymerase chain reaction. P. falciparum isolates in this study had high rate of multiple genotypes infection (96.5%) with an overall mean multiplicity of infection of 3.21. The distribution of allelic families of msp-1 was significantly different among isolates from Tak, Kanchanaburi, and Ranong but not for the msp-2. K1 and MAD20 were the predominant allelic families at the msp-1 gene, whereas alleles belonging to 3D7 were more frequent at the msp-2 gene. The glurp gene had the least diverse alleles. Population structure of P. falciparum isolates from Tak and Ranong was quite similar as revealed by the presence of similar proportions of MAD20 and K1 alleles at msp-1 loci, 3D7 and FC27 alleles at msp-2 loci as well as comparable mean MOI. Isolates from Kanchanaburi had different structures; the most prevalent alleles were K1 and RO33. The present study shows that P. falciparum isolates from Tak and Ranong provinces had similar allelic pattern of msp-1 and msp-2 and diversity but different from Kanchanaburi isolates. These allelic variant profiles are valuable baseline data for future epidemiological study of malaria transmission and for continued monitoring of polymorphisms associated with antimalarial drug resistance in these areas.

75 FR 31329 - Airworthiness Directives; The Boeing Company Model 757 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... after receipt. FOR FURTHER INFORMATION CONTACT: Tak Kobayashi, Aerospace Engineer, Propulsion Branch..., Aerospace Engineer, Propulsion Branch, ANM- 140S, FAA, Seattle Aircraft Certification Office, 1601 Lind...

Pursuit of the Torch: Influences on Acquisition of USAAF Fighter Aircraft Used in the North African Campaign

DTIC Science & Technology

2010-06-01

138- 143 . 36 advancing bomber versus pursuit technology took on greater significance. The need to establish a balanced force was just one more...54 Watson, 138- 143 . 55 AAF Statistical Digest: World War II, December 1945, Table 79. The percentage...72 William Wolf American Fighter-Bombers in World War II: USAAF Jabos in the MTO and ETO (Atglen, PA: Schiffer

Planning for Action: Campaign Concepts and Tools

DTIC Science & Technology

2012-08-01

142 10-15. Stability Mechanisms – Army .................................... 143 10-16. Stability Mechanisms – Joint...defeat mechanisms, which focus 143 the destructive and coercive capabilities of the force to provide security and public order and safety for...Matthew B. Ridgway. GEN Ridgway successfully led the 82d Airborne Division and XVIII Airborne Corps in the ETO during World War II and Eighth (US

Structural and energetic basis for the molecular recognition of dual synthetic vs. natural inhibitors of EGFR/HER2.

PubMed

Bello, Martiniano; Saldaña-Rivero, Lucia; Correa-Basurto, José; García, Benjamín; Sánchez-Espinosa, Victor Armando

2018-05-01

Activation of EGFR starts by ligand binding at the extracellular domain which results in homo and heterodimerization, leading to phosphorylation, activation of downstream signaling pathways which upregulate expression of genes, proliferation and angiogenesis. Abnormalities in the expression of EGFR play a critical role in the development of different types of cancer. HER2 is the preferred heterodimerization partner for EGFR; this biological characteristic together with the high percentage of structural homology has been exploited in the design of dual synthetic inhibitors against EGFR/HER2. Herein we combined structural data and molecular dynamics (MD) simulations coupled to an MMGBSA approach to provide insight into the binding mechanism between two dual synthetics (lapatinib and TAK-285) and one dual natural inhibitor (EGCG) which target EGFR/HER2. In addition, we proposed some EGCG derivatives which were filtered through in silico screening. Structural analysis demonstrated that the coupling of synthetic, natural or newly designed compounds impacts the conformational space of EGFR and HER2 differently. Energetic analysis points out that lapatinib and TAK-285 have better affinity for inactive EGFR than the active EGFR state or HER2, whereas some EGCG derivatives seem to form binding affinities similar to those observed for lapatinib or TAK-285. Copyright © 2018 Elsevier B.V. All rights reserved.

Neutrino Astrophysics in Slowly Rotating Spacetimes Permeated by Nonlinear Electrodynamics Fields

NASA Astrophysics Data System (ADS)

Mosquera Cuesta, Herman J.

2017-02-01

Many theoretical and astrophysical arguments involve consideration of the effects of super strong electromagnetic fields and the rotation during the late stages of core-collapse supernovae. In what follows, we solve Einstein field equations that are minimally coupled to an arbitrary (current-free) Born-Infeld nonlinear Lagrangian L(F,G) of electrodynamics (NLED) in the slow rotation regime a ≪ r+ (outer horizon size), up to first order in a/r. We cross-check the physical properties of such NLED spacetime w.r.t. against the Maxwell one. A study case on both neutrino flavor ({ν }e\\to {ν }μ ,{ν }τ ) oscillations and flavor+helicity (spin) flip ({ν }e\\to {\\overline{ν }}μ ,τ ) gyroscopic precession proves that in the spacetime of a slowly rotating nonlinear charged black hole (RNCBH), the neutrino dynamics translates into a positive enhancement of the r-process (reduction of the electron fraction Ye < 0.5). Consequently, it guarantees successful hyperluminous core-collapse supernova explosions due to the enlargement of the number and amount of decaying nuclide species. This posits that, as far as the whole luminosity is concerned, hypernovae will be a proof of the formation of astrophysical RNCBH.

Dynamic Processes at the Outer Boundary of the Magnetosphere, Including Coupling to the Ionosphere

DTIC Science & Technology

1994-04-15

numerical simulation, of the stability of laminar flow in the equatorial LLBL in the presence of coupling to the ionosphere and associated nonuniform ...L.C. Laec Theory of inaperfcs eto lhreio s1w dependenceors dependenceon theelecio precpittion associated coupling. GeV*li. Res. Lair ... nonuniform magnetic field, the nonuniformity being created by electic currents that connect the plasma in the layer to two conducting plates which

Stability in the Offense: The Evolution of Civil Affairs During World War II

DTIC Science & Technology

2014-05-22

Department of State ETO European Theater of Operation ETOUSA European Theater United States Army FACT Field Advance Civilian Teams FM Field Manual...monograph. Official histories include Harry L. Cole and Albert K . Weinberg’s Civil Affairs: Soldiers Become Governors, which provides an extensive...US Historical Experience with Civil Affairs: 10Harry L. Coles and Albert K . Weinberg, Civil Affairs: Soldiers Become Governors, CMH Pub 11-5

Evaluating the formulae for integrated lethality in ethylene oxide sterilization using six different endospore forming strains of bacteria, and comparisons of integrated lethality for ethylene oxide and steam systems.

PubMed

Mosley, Gregg A; Gillis, John R; Krushefski, Garrett

2005-01-01

Bacterial endospores from six different species of bacteria were exposed to a spectrum of ethylene oxide (EtO) sterilizing conditions. Temperature was varied from 40 to 60 degrees C and the ethylene oxide concentration was varied from 300 to 750 mg/L. Relative humidity was maintained at 60+/-10% RH. The fraction negative procedure was used to determine the D value for each of the test conditions. Bacterial species tested included Bacillus atrophaeus ATCC # 9372, Bacillus smithii ATCC # 51232, Bacillus subtilis "5230" ATCC # 35021, Bacillus subtilis, DSM # 4181, Bacillus pumilus ATCC # 27142, and Geobacillus stearothermophilus ATCC # 7953. All spore preparations were inoculated on filter paper strips packaged in blue, sterilizable glassine pouches. G. stearothermophilus was the least resistant organism tested. The most resistant organisms tested were B. atrophaeus and B. subtilis "5230". The B. subtilis "5230" strain was slightly more resistant than B. atrophaeus at conditions of 54C and EtO concentrations of 400, 600, and 750 mg/L, as well as at 60C/750mg/L EtO. The other species were between these extremes. This empirical data allowed the application of the recently published formula for converting D values from one set of conditions to another and evaluations of accuracy. The measured D values also allowed the determination of Z values based on temperature variations. These formulae, when applied to process temperatures independent of gas concentration, result in a Z value of approximately 32 degrees C that appears to be similar for all species tested. These data support the application of the previously published formulae 1-6 and allow the same approach to integrated lethality for ethylene oxide processes as is commonly applied to steam sterilization. A review of steam sterilization and related principles was conducted for comparison of integrated lethality for these two methods of sterilization. Errors associated with D values, Z values, extrapolation, and

Dose-rate effects of ethylene oxide exposure on developmental toxicity.

PubMed

Weller, E; Long, N; Smith, A; Williams, P; Ravi, S; Gill, J; Henessey, R; Skornik, W; Brain, J; Kimmel, C; Kimmel, G; Holmes, L; Ryan, L

1999-08-01

In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

Alkali-metal-ion catalysis and inhibition in the nucleophilic displacement reaction of y-substituted phenyl diphenylphosphinates and diphenylphosphinothioates with alkali-metal ethoxides: effect of changing the electrophilic center from P=O to P=S.

PubMed

Um, Ik-Hwan; Shin, Young-Hee; Park, Jee-Eun; Kang, Ji-Sun; Buncel, Erwin

2012-01-16

A kinetic study of the nucleophilic substitution reaction of Y-substituted phenyl diphenylphosphinothioates 2 a-g with alkali-metal ethoxides (MOEt; M = Li, Na, K) in anhydrous ethanol at (25.0±0.1) °C is reported. Plots of pseudo-first-order rate constants (k(obsd)) versus [MOEt], the alkali ethoxide concentration, show distinct upward (KOEt) and downward (LiOEt) curvatures, respectively, pointing to the importance of ion-pairing phenomena and a differential reactivity of dissociated EtO(-) and ion-paired MOEt. Based on ion-pairing treatment of the kinetic data, the k(obsd) values were dissected into k EtO - and k(MOEt), the second-order rate constants for the reaction with the dissociated EtO(-) and ion-paired MOEt, respectively. The reactivity of MOEt toward 2 b (Y = 4-NO(2)) increases in the order LiOEtNaOEt>KOEt>EtO(-). The current study based on Yukawa-Tsuno analysis has revealed that the reactions of 2 a-g (P=S) and Y-substituted phenyl diphenylphosphinates 1 a-g (P=O) with MOEt proceed through the same concerted mechanism, which indicates that the contrasting selectivity patterns are not due to a difference in reaction mechanism. The P=O compounds 1 a-g are approximately 80-fold more reactive than the P=S compounds 2 a-g toward the dissociated EtO(-) (regardless of the electronic nature of substituent Y) but are up to 3.1×10(3)-fold more reactive toward ion-paired LiOEt. The origin of the contrasting selectivity patterns is further discussed on the basis of competing electrostatic effects and solvational requirements as a function of anionic electric field strength and cation size (Eisenman's theory). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Efficacy of preoxygenation using tidal volume breathing: a comparison of Mapleson A, Bain's and Circle system].

PubMed

Arora, Suman; Gupta, Priyanka; Arya, Virender Kumar; Bhatia, Nidhi

Efficacy of preoxygenation depends upon inspired oxygen concentration, its flow rate, breathing system configuration and patient characteristics. We hypothesized that in actual clinical scenario, where breathing circuit is not primed with 100% oxygen, patients may need more time to achieve EtO 2 ≥90%, and this duration may be different among various breathing systems. We thus studied the efficacy of preoxygenation using unprimed Mapleson A, Bain's and Circle system with tidal volume breathing at oxygen flow rates of 5L.min -1 and 10L.min -1 . Patients were randomly allocated into one of the six groups, wherein they were preoxygenated using either Mapleson A, Bain's or Circle system at O 2 flow rate of either 5L.min -1 or 10L.min -1 . The primary outcome measure of our study was the time taken to achieve EtO 2 ≥90% at 5 and 10L.min -1 flow rates. At oxygen flow rate of 5L.min -1 , time to reach EtO 2 ≥90% was significantly longer with Bain's system (3.7±0.67min) than Mapleson A and Circle system (2.9±0.6, 3.3±0.97min, respectively). However at oxygen flow rate of 10L.min -1 this time was significantly shorter and comparable among all the three breathing systems (2.33±0.38min with Mapleson, 2.59±0.50min with Bain's and 2.60±0.47min with Circle system). With spontaneous normal tidal volume breathing at oxygen flow rate of 5L.min -1 , Mapleson A can optimally preoxygenate patients within 3min while Bain's and Circle system require more time. However at O 2 flow rate of 10L.min -1 all the three breathing systems are capable of optimally preoxygenating the patients in less than 3min. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Is the chronic Tier-1 effect assessment approach for insecticides protective for aquatic ecosystems?

PubMed

Brock, Theo Cm; Bhatta, Ranjana; van Wijngaarden, René Pa; Rico, Andreu

2016-10-01

We investigated the appropriateness of several methods, including those recommended in the Aquatic Guidance Document of the European Food Safety Authority (EFSA), for the derivation of chronic Tier-1 regulatory acceptable concentrations (RACs) for insecticides and aquatic organisms. The insecticides represented different chemical classes (organophosphates, pyrethroids, benzoylureas, insect growth regulators, biopesticides, carbamates, neonicotinoids, and miscellaneous). Chronic Tier-1 RACs derived using toxicity data for the standard species Daphnia magna, Chironomus spp., and/or Americamysis bahia, were compared with Tier-3 RACs derived from micro- and mesocosm studies on basis of the ecological threshold option (ETO-RACs). ETO-RACs could be derived for 31 insecticides applied to micro- and mesocosms in single or multiple applications, yielding a total number of 36 cases for comparison. The chronic Tier-1 RACs calculated according to the EFSA approach resulted in a sufficient protection level, except for 1 neonicotinoid (slightly underprotective) and for several pyrethroids if toxicity data for A. bahia were not included. This latter observation can be explained by 1) the fact that A. bahia is the most sensitive standard test species for pyrethroids, 2) the hydrophobic properties of pyrethroids, and 3) the fact that long-term effects observed in (epi) benthic arthropods may be better explained by exposure via the sediment than via overlying water. Besides including toxicity data for A. bahia, the protection level for pyrethroids can be improved by selecting both D. magna and Chironomus spp. as standard test species for chronic Tier-1 derivation. Although protective in the majority of cases, the conservativeness of the recommended chronic Tier-1 RACs appears to be less than an order of magnitude for a relatively large proportion of insecticides when compared with their Tier-3 ETO-RACs. This may leave limited options for refinement of the chronic effect assessment

Shigella flexneri type III secreted effector OspF reveals new crosstalks of proinflammatory signaling pathways during bacterial infection.

PubMed

Reiterer, Veronika; Grossniklaus, Lars; Tschon, Therese; Kasper, Christoph Alexander; Sorg, Isabel; Arrieumerlou, Cécile

2011-07-01

Shigella flexneri type III secreted effector OspF harbors a phosphothreonine lyase activity that irreversibly dephosphorylates MAP kinases (MAPKs) p38 and ERK in infected epithelial cells and thereby, dampens innate immunity. Whereas this activity has been well characterized, the impact of OspF on other host signaling pathways that control inflammation was unknown. Here we report that OspF potentiates the activation of the MAPK JNK and the transcription factor NF-κB during S. flexneri infection. This unexpected effect of OspF was dependent on the phosphothreonine lyase activity of OspF on p38, and resulted from the disruption of a negative feedback loop regulation between p38 and TGF-beta activated kinase 1 (TAK1), mediated via the phosphorylation of TAK1-binding protein 1. Interestingly, potentiated JNK activation was not associated with enhanced c-Jun signaling as OspF also inhibits c-Jun expression at the transcriptional level. Altogether, our data reveal the impact of OspF on the activation of NF-κB, JNK and c-Jun, and demonstrate the existence of a negative feedback loop regulation between p38 and TAK1 during S. flexneri infection. Furthermore, this study validates the use of bacterial effectors as molecular tools to identify the crosstalks that connect important host signaling pathways induced upon bacterial infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

PubMed

Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

2016-06-01

Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH. Copyright © 2016 Elsevier Ltd. All rights reserved.

MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling

PubMed Central

Liu, Wei; Wu, Yuan-Hao; Zhang, Lei; Xue, Bin; Wang, Yi; Liu, Bin; Liu, Xiao-Ya; Zuo, Fang; Yang, Xiao-Yan; Chen, Fu-Yu; Duan, Ran; Cai, Yue; Zhang, Bo; Ji, Yang

2018-01-01

This study investigated whether microRNA-146a (miR-146a) mediating TLR4/NF-κB pathway affected proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes from 12 RA patients (RA-FLSs). FLSs in the logarithmic growth phase were assigned into the control, miR-146a mimic miR-146a inhibitor, Tak-242 (treated with TLR4/NF-κB pathway inhibitor) and mimic + lipopolysaccharide (LPS) groups. Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry. The expression of miR-146a, TLR4/NF-κB pathway-related proteins and cytokines were determined by RT-qPCR, western blotting and ELISA, and the release of NO by Greiss reaction. RA rat models were constructed and the primary cells were classified into the control, negative control (NC), miR-146a mimic, miR-146a inhibitor, Tak-242, mimic + LPS, and TLR4 groups. Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen (PCNA) and intercellular adhesion molecular-1 (ICAM-1). The results showed that miR-146a levels were lower in RA-FLSs than control fibroblasts. miR-146a mimic and Tak-242 decreased RA-FLS proliferation and increased RA-FLS apoptosis, while miR-146a inhibitor had an opposite trend. miR-146a mimic and Tak-242 also decreased expression of TLR4, NF-κB, IL-1β, IL-6, IL-8, IL-17, COX-2, MMP-3, Seprase, and iNOS, as well as reduced NO level in RA-FLSs while miR-146a inhibitor and TLR4 increased them. TLR4 and NF-κB levels and the positive rates of PCNA and ICAM-1 expressions were lower in RA-FLSs from RA rats given miR-146a mimic from control or miR-146a inhibitor-treated rats. These results suggest that miR-146a inhibits the proliferation and inflammatory response of RA-FLSs by down-regulating TLR4/NF-κB pathway.

Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics

DTIC Science & Technology

2006-08-01

bicuspid aortic stenosis . J Am Soc Echocardiogr. 2005 Dec;18(12):1392-8. 44. Eto Y, Yamada H, Shin JH, Agler DA, Tsujino H, Qin JX, Saracino G, Greenberg...nitroprusside in aortic stenosis associated with severe heart failure: pressure- volume loop analysis using a numerical model. Am J Physiol Heart Circ...3D echocardiography, including exercise and intraoperative (epicardial) examinations, with quantitative validation in aneurysmal ventricles,3 aortic

Rocket Based Combined Cycle (RBCC) Propulsion Technology Workshop. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Chojnacki, Kent T.

1992-01-01

The goal of the Rocket-Based Combined Cycle (RBCC) Propulsion Technology Workshop was to assess the RBCC propulsion system's viability for Earth-to-Orbit (ETO) transportation systems. This was accomplished by creating a forum (workshop) in which past work in the field of RBCC propulsion systems was reviewed, current technology status was evaluated, and future technology programs in the field of RBCC propulsion systems were postulated, discussed, and recommended.

Coherent Optical Control of Electronic Excitations in Wide-Band-Gap Semiconductor Structures

DTIC Science & Technology

2015-05-01

ABSTRACT The main objective of this research is to study coherent quantum effects, such as Rabi oscillations in optical spectra of wide- band-gap...field corresponds to the rotation of the B vector about the pseudo field vector, Ω, with components determined by the effective Rabi frequency ( )e...to examine coherent quantum effects, such as Rabi oscillations and quantum entanglement in optical spectra of wide-band-gap materials, and to

SASH1 is a scaffold molecule in endothelial TLR4 signaling.

PubMed

Dauphinee, Shauna M; Clayton, Ashley; Hussainkhel, Angela; Yang, Cindy; Park, Yoo-Jin; Fuller, Megan E; Blonder, Josip; Veenstra, Timothy D; Karsan, Aly

2013-07-15

Recognition of microbial products by TLRs is critical for mediating innate immune responses to invading pathogens. In this study, we identify a novel scaffold protein in TLR4 signaling called SAM and SH3 domain containing protein 1 (SASH1). Sash1 is expressed across all microvascular beds and functions as a scaffold molecule to independently bind TRAF6, TAK1, IκB kinase α, and IκB kinase β. This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-κB, JNK, and p38 activation, culminating in increased production of proinflammatory cytokines and increased LPS-induced endothelial migration. Our findings suggest that SASH1 acts to assemble a signaling complex downstream of TLR4 to activate early endothelial responses to receptor activation.

Optically active antifungal azoles. XII. Synthesis and antifungal activity of the water-soluble prodrugs of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone.

PubMed

Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K

2001-09-01

1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.

TAK228 With Carbo and Taxol in Advanced Malignancies

ClinicalTrials.gov

2018-03-12

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Environment Behavior Models for Real-Time Reactive System Testing Automation

DTIC Science & Technology

2006-09-01

by Muharrem Ugur Aksu September 2006 Co-Advisors: Mikhail Auguston Man-Tak Shing Approved for public release; distribution is......Muharrem Ugur Aksu Naval Postgraduate School Computer Science Department Date: 20 July 2006 File Name: Shuttle.cpp

Improving the performance of the mass transfer-based reference evapotranspiration estimation approaches through a coupled wavelet-random forest methodology

NASA Astrophysics Data System (ADS)

Shiri, Jalal

2018-06-01

Among different reference evapotranspiration (ETo) modeling approaches, mass transfer-based methods have been less studied. These approaches utilize temperature and wind speed records. On the other hand, the empirical equations proposed in this context generally produce weak simulations, except when a local calibration is used for improving their performance. This might be a crucial drawback for those equations in case of local data scarcity for calibration procedure. So, application of heuristic methods can be considered as a substitute for improving the performance accuracy of the mass transfer-based approaches. However, given that the wind speed records have usually higher variation magnitudes than the other meteorological parameters, application of a wavelet transform for coupling with heuristic models would be necessary. In the present paper, a coupled wavelet-random forest (WRF) methodology was proposed for the first time to improve the performance accuracy of the mass transfer-based ETo estimation approaches using cross-validation data management scenarios in both local and cross-station scales. The obtained results revealed that the new coupled WRF model (with the minimum scatter index values of 0.150 and 0.192 for local and external applications, respectively) improved the performance accuracy of the single RF models as well as the empirical equations to great extent.

Psidium guajava Linn confers gastro protective effects on rats.

PubMed

Livingston Raja, N R; Sundar, K

2012-02-01

The best alternatives to synthetic medicines, available, for the treatment of gastric ulcer disorders, are the natural products found in plants. They are known to exhibit a variety of activities. The present study is aimed at the screening of Psidium (P.) guajava Linn for its gastro protective effect. The methanol extracts of the leaves of P. guajava were tested in three different ulcer models viz. aspirin (ASP), pyloric ligation (PL) and ethanol (EtoH) induced ulcer models in rats. The treatment of P. guajava at varying doses (100 mg/kg and 200 mg/kg) significantly (p < 0.001) inhibited the gastric lesions induced by ASP (70.5%), PL (65.07%) and EtoH (70.4%) respectively and the potency was found to be equivalent as compared to the standard drug, omeprazole. Reduction in the gastric secretory volume, acid secretion and increased gastric pH were the factors observed in treated rats. The presence of volatile oil, flavonoids and saponins present in the extracts of P. guajava may be responsible for the anti-ulcer property exhibited. The results further suggest that P. guajava possess gastro protective as well as ulcer healing properties which might also be due to its anti-secretory properties.

JAK inhibitors suppress t(8;21) fusion protein-induced leukemia

PubMed Central

Lo, Miao-Chia; Peterson, Luke F.; Yan, Ming; Cong, Xiuli; Hickman, Justin H.; DeKelver, Russel C.; Niewerth, Denise; Zhang, Dong-Er

2014-01-01

Oncogenic mutations in components of the JAK/STAT pathway, including those in cytokine receptors and JAKs, lead to increased activity of downstream signaling and are frequently found in leukemia and other hematological disorders. Thus, small-molecule inhibitors of this pathway have been the focus of targeted therapy in these hematological diseases. We previously showed that t(8;21) fusion protein AML1-ETO and its alternatively spliced variant AML1-ETO9a (AE9a) enhance the JAK/STAT pathway via down-regulation of CD45, a negative regulator of this pathway. To investigate the therapeutic potential of targeting JAK/STAT in t(8;21) leukemia, we examined the effects of a JAK2-selective inhibitor TG101209 and a JAK1/2-selective inhibitor INCB18424 on t(8;21) leukemia cells. TG101209 and INCB18424 inhibited proliferation and promoted apoptosis of these cells. Furthermore, TG101209 treatment in AE9a leukemia mice reduced tumor burden and significantly prolonged survival. TG101209 also significantly impaired the leukemia-initiating potential of AE9a leukemia cells in secondary recipient mice. These results demonstrate the potential therapeutic efficacy of JAK inhibitors in treating t(8;21) AML. PMID:23812420

Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukemias?

PubMed

Minucci, S; Nervi, C; Lo Coco, F; Pelicci, P G

2001-05-28

Recent discoveries have identified key molecular events in the pathogenesis of acute promyelocytic leukemia (APL), caused by chromosomal rearrangements of the transcription factor RAR (resulting in a fusion protein with the product of other cellular genes, such as PML). Oligomerization of RAR, through a self-association domain present in PML, imposes an altered interaction with transcriptional co-regulators (NCoR/SMRT). NCoR/SMRT are responsible for recruitment of histone deacetylases (HDACs), which is required for transcriptional repression of PML-RAR target genes, and for the transforming potential of the fusion protein. Oligomerization and altered recruitment of HDACs are also responsible for transformation by the fusion protein AML1-ETO, extending these mechanisms to other forms of acute myeloid leukemias (AMLs) and suggesting that HDAC is a common target for myeloid leukemias. Strikingly, AML1-ETO expression blocks retinoic acid (RA) signaling in hematopoietic cells, suggesting that interference with the RA pathway (genetically altered in APL) by HDAC recruitment may be a common theme in AMLs. Treatment of APLs with RA, and of other AMLs with RA plus HDAC inhibitors (HDACi), results in myeloid differentiation. Thus, activation of the RA signaling pathway and inhibition of HDAC activity might represent a general strategy for the differentiation treatment of myeloid leukemias.

Health management and controls for Earth-to-orbit propulsion systems

NASA Astrophysics Data System (ADS)

Bickford, R. L.

1995-03-01

Avionics and health management technologies increase the safety and reliability while decreasing the overall cost for Earth-to-orbit (ETO) propulsion systems. New ETO propulsion systems will depend on highly reliable fault tolerant flight avionics, advanced sensing systems and artificial intelligence aided software to ensure critical control, safety and maintenance requirements are met in a cost effective manner. Propulsion avionics consist of the engine controller, actuators, sensors, software and ground support elements. In addition to control and safety functions, these elements perform system monitoring for health management. Health management is enhanced by advanced sensing systems and algorithms which provide automated fault detection and enable adaptive control and/or maintenance approaches. Aerojet is developing advanced fault tolerant rocket engine controllers which provide very high levels of reliability. Smart sensors and software systems which significantly enhance fault coverage and enable automated operations are also under development. Smart sensing systems, such as flight capable plume spectrometers, have reached maturity in ground-based applications and are suitable for bridging to flight. Software to detect failed sensors has reached similar maturity. This paper will discuss fault detection and isolation for advanced rocket engine controllers as well as examples of advanced sensing systems and software which significantly improve component failure detection for engine system safety and health management.

Nonlinear electrostrictive lattice response of EuTiO3

NASA Astrophysics Data System (ADS)

Pappas, P.; Calamiotou, M.; Köhler, J.; Bussmann-Holder, A.; Liarokapis, E.

2017-07-01

An epitaxial EuTiO3 (ETO) film grown on the SrTiO3 substrate was studied at room temperature with synchrotron XRD and in situ application of an electric field (nominally up to 7.8 kV/cm) in near grazing incidence geometry, in order to monitor the response of the lattice to the field. 2D diffraction images show that apparently misoriented coherently diffracting domains are present close to the surface whereas the film diffracts more as a single crystal towards the interface. Diffraction intensity profiles recorded from the near surface region of the EuTiO3 film showed systematic modifications upon the application of the electric field, indicating that at a critical electric field (nominally above 3.1 kV/cm), there is a clear change in the lattice response to the field, which was much stronger when the field was almost parallel to the diffraction vector. The data suggest that the ETO film, nominally paraelectric at room temperature, transforms under the application of a critical electric field to piezoelectric in agreement with a theoretical analysis based on a double-well potential. In order to exclude effects arising from the substrate, this has been investigated separately and shown not to be affected by the field.

Final Environmental Assessment for Stormwater Drainage Project on F. E. Warren Air Force Base, Wyoming

DTIC Science & Technology

2005-05-01

Colorado Butterfly Habitat on F. E. Warren AFB Stormwater Drainage Project, Final Environmental Assessment April 2005 F. E. Warren AFB iii Figure...A.11 Colorado Butterfly Plant Populations Near Outfall 1 Figure A.12 Preble’s Habitat on F. E. Warren AFB Figure A.13 Preble’s Captures on F. E...to threatened species habitat in the vicinity of the outfalls to Crow Creek, the base will do the following: Colorado butterfly plant: 1

Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells.

PubMed

Benakanakere, Indira; Johnson, Tyler; Sleightholm, Richard; Villeda, Virgilio; Arya, Monika; Bobba, Ravi; Freter, Carl; Huang, Chunfa

2014-01-01

Cholesterol plays an important role in cancer development, drug resistance and chemoimmuno-sensitivity. Statins, cholesterol lowering drugs, can induce apoptosis, but also negatively interfere with CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo immunotherapy of chronic lymphocytic leukemia (CLL). MEC-2 cells, a CLL cell line, and the peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol levels, CD-20 expression and distribution, and cell viability in the presence or absence of fludarabine, rituximab or their combinations. We found that MEC-2 cells treated with cholesterol lowering agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular cholesterol levels, but also significantly promoted CD-20 surface expression. Furthermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced chemoimmuno-sensitivity of the PBMCs from CLL patients. Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20 epitope presentation or its downstream signaling. These results provide a novel strategy which could be applied to CLL treatment.

LESSONS-LEARNED AND SUCCESS STORIES FROM EPA'S REAL-TIME ENVIRONMENTAL MONITORING, DATA DELIVERY, AND PUBLIC OUTREACH PROGRAM

EPA Science Inventory

TTSD has completed a series of technology transfer and risk communication handbooks, case studies, and summary reports for community-based environmental monitoring projects under EPA's Real-Time Environmental Monitoring, Data Delivery, and Public Outreach Program. The Program tak...

76 FR 19710 - Airworthiness Directives; The Boeing Company Model 757 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-08

...: No person may operate an aircraft for which a manufacturer's maintenance manual or instructions for... by latent failures, alterations, repairs, or maintenance actions, which, in combination with... CONTACT: Tak Kobayashi, Aerospace Engineer, Propulsion Branch, ANM-140S, FAA, Seattle Aircraft...

Impacts of Climate Change on Water Requirements of Dry Season Boro Rice: Recent Trends and Future Scenarios

NASA Astrophysics Data System (ADS)

Acharjee, T. K.; Ludwig, F.; Halsema, G. V.; Hellegers, P.; Supit, I.

2017-12-01

The North-West part of Bangladesh is vulnerable to the impacts of climate change, because of dry season water shortage and high water demand for rice cultivation. A study was carried out to understand the impacts of recent climate change (1980-2013) and future consequences (for 2050s and 2080s) on water requirements of Boro rice. The reference crop evapotranspiration (ETo), potential crop water requirement (∑ETC), effective rainfall (ER), potential irrigation requirement for crop evapotranspiration (∑ETC-ER) and net irrigation requirement of Boro rice were estimated in CropWat using observed daily climate data for recent trends and statistically downscaled and bias corrected GCM outputs (five models and two RCPs) for future scenarios. ETo showed a significant decreasing recent trends due to increasing relative humidity and decreasing wind speed and sun shine hours instead of an increase in temperature. However, the strong future increase in temperature will lead to an insignificant increase in ETo. ∑ETC showed a decreasing recent trend and will further decrease in the future because of shortened duration of Boro growth stages as crop's phenological response to increased temperature. The variations in trends of ∑ETC-ER found among different districts, are mainly linked to the variations in trends of changes in effective rainfall. During last three decades, the net irrigation requirement has decreased by 11% at an average rate of -4.4 mm/year, instead of a decreasing effective rainfall, mainly because of high rate of decrease of crop evapotranspiration (-5.9 mm/year). In future, although daily water requirement will increase, the total net irrigation requirement of Boro rice will decrease by 1.6% in 2050s and 7.4% in 2080s for RCP 8.5 scenario on an average for five models and four districts compared to the base period (1980-2013). High variations in projected changes in rainfall bring high uncertainty for future water requirements estimation. Therefore, a

Long-term patterns of air temperatures, daily temperature range, precipitation, grass-reference evapotranspiration and aridity index in the USA great plains: Part II. Temporal trends

NASA Astrophysics Data System (ADS)

Kukal, M.; Irmak, S.

2016-11-01

Detection of long-term changes in climate variables over large spatial scales is a very important prerequisite to the development of effective mitigation and adaptation measures for the future potential climate change and for developing strategies for future hydrologic balance analyses under changing climate. Moreover, there is a need for effective approaches of providing information about these changes to decision makers, water managers and stakeholders to aid in efficient implementation of the developed strategies. This study involves computation, mapping and analyses of long-term (1968-2013) county-specific trends in annual, growing-season (1st May-30th September) and monthly air temperatures [(maximum (Tmax), minimum (Tmin) and average (Tavg)], daily temperature range (DTR), precipitation, grass reference evapotranspiration (ETo) and aridity index (AI) over the USA Great Plains region using datasets from over 800 weather station sites. Positive trends in annual Tavg, Tmax and Tmin, DTR, precipitation, ETo and AI were observed in 71%, 89%, 85%, 31%, 61%, 38% and 66% of the counties in the region, respectively, whereas these proportions were 48%, 89%, 62%, 20%, 57%, 28%, and 63%, respectively, for the growing-season averages of the same variables. On a regional average basis, the positive trends in growing-season Tavg, Tmax and Tmin, DTR, precipitation, ETo and AI were 0.18 °C decade-1, 0.19 °C decade-1, 0.17 °C decade-1, 0.09 °C decade-1, 1.12 mm yr-1, 0.4 mm yr-1 and 0.02 decade-1, respectively, and the negative trends were 0.21 °C decade-1, 0.06 °C decade-1, 0.09 °C decade-1, 0.22 °C decade-1, 1.16 mm yr-1, 0.76 mm yr-1 and 0.02 decade-1, respectively. The temporal trends were highly variable in space and were appropriately represented using monthly, annual and growing-season maps developed using Geographic Information System (GIS) techniques. The long-term and spatial and temporal information and data for a large region provided in this study can be

The Role of the US Army Reserve in Support of the US Army Force 2025 and Beyond: Challenges and Opportunities

DTIC Science & Technology

2015-06-12

waits for no one, and this project was no different. At the conclusion of this research there were many more rabbit holes I wish that I could have...Opportunities 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Major Jacob T. Wilson 5d. PROJECT NUMBER 5e...to incorporate or impact the Army Reserve specifically. Support will also be provided to this research project by incorporating the published works

CUHK Papers in Linguistics, Number 4.

ERIC Educational Resources Information Center

Tang, Gladys, Ed.

1993-01-01

Papers in this issue include the following: "Code-Mixing in Hongkong Cantonese-English Bilinguals: Constraints and Processes" (Brian Chan Hok-shing); "Information on Quantifiers and Argument Structure in English Learner's Dictionaries" (Thomas Hun-tak Lee); "Systematic Variability: In Search of a Linguistic…

Vasculitis Pregnancy Registry

ClinicalTrials.gov

2018-04-30

Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatosis With Polyangiitis (EGPA); Churg-Strauss Syndrome (CSS); Granulomatosis With Polyangiitis (GPA); Wegener's Granulomatosis; IgA Vasculitis; Henoch-Schoenlein Purpura (HSP); Microscopic Polyangiitis (MPA); Polyarteritis Nodosa (PAN); Takayasu Arteritis (TAK); Urticarial Vasculitis; Systemic Vasculitis

A Comparison of Degradable Synthetic Polymer Fibers for Anterior Cruciate Ligament Reconstruction

PubMed Central

Tovar, Nick; Bourke, Sharon; Jaffe, Michael; Murthy, N. Sanjeeva; Kohn, Joachim; Gatt, Charles; Dunn, Michael G.

2009-01-01

We compared mechanical properties, degradation rates, and cellular compatibilities of two synthetic polymer fibers potentially useful as ACL reconstruction scaffolds: poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate)(12,10), p(DTD DD) and poly(L-lactic acid), PLLA. The yield stress of ethylene oxide (ETO) sterilized wet fibers was 150 ± 22 MPa and 87 ± 12 MPa for p(DTD DD) and PLLA, respectively, with moduli of 1.7 ± 0.1 MPa and 4.4 ± 0.43 MPa. Strength and molecular weight retention were determined after incubation under physiological conditions at varying times. After 64 weeks strength decreased to 20 and 37% of the initial sterile fiber values and MW decreased to 41% and 36% of the initial values for p(DTD DD) and PLLA, respectively. ETO sterilization had no significant effect on mechanical properties. Differences in mechanical behavior may be due to the semicrystalline nature of PLLA and the small degree of crystallinity induced by mesogenic ordering in p(DTD DD) suggested by DSC analysis. Fibroblast growth was similar on 50-fiber scaffolds of both polymers through 16 days in vitro. These data suggest that p(DTD DD) fibers, with higher strength, lower stiffness, favorable degradation rate and cellular compatibility, may be a superior alternative to PLLA fibers for development of ACL reconstruction scaffolds. PMID:19623532

Cold cathode emission studies on topographically modified few layer and single layer MoS2 films

NASA Astrophysics Data System (ADS)

Gaur, Anand P. S.; Sahoo, Satyaprakash; Mendoza, Frank; Rivera, Adriana M.; Kumar, Mohit; Dash, Saroj P.; Morell, Gerardo; Katiyar, Ram S.

2016-01-01

Nanostructured materials, such as carbon nanotubes, are excellent cold cathode emitters. Here, we report comparative field emission (FE) studies on topographically tailored few layer MoS2 films consisting of ⟨0001⟩ plane perpendicular (⊥) to c-axis (i.e., edge terminated vertically aligned) along with planar few layer and monolayer (1L) MoS2 films. FE measurements exhibited lower turn-on field Eto (defined as required applied electric field to emit current density of 10 μA/cm2) ˜4.5 V/μm and higher current density ˜1 mA/cm2, for edge terminated vertically aligned (ETVA) MoS2 films. However, Eto magnitude for planar few layer and 1L MoS2 films increased further to 5.7 and 11 V/μm, respectively, with one order decrease in emission current density. The observed differences in emission behavior, particularly for ETVA MoS2 is attributed to the high value of geometrical field enhancement factor (β), found to be ˜1064, resulting from the large confinement of localized electric field at edge exposed nanograins. Emission behavior of planar few layers and 1L MoS2 films are explained under a two step emission mechanism. Our studies suggest that with further tailoring the microstructure of ultra thin ETVA MoS2 films would result in elegant FE properties.

Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge.

PubMed

Skoner, D P; Doyle, W J; Boehm, S; Fireman, P

1991-12-01

Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses.

Around Marshall

NASA Image and Video Library

2002-05-17

In this photograph, Jeff Alden (left) and Justin O'Cornor, two middle school students at Lane Middle School in Portland, Oregon are demonstrating their Earth-to-Orbit (ETO) Design Challenge project at NASA Marshall Space Flight Center (MSFC) in Huntsville, Alabama. Jeff and Justin, who are just a couple of "typical teens," have been spending their time tackling some of the same challenges NASA engineers face when designing propulsion systems at MSFC. The ETO Design Challenge is a hands-on educational program, targeted to middle school students, in which students are assigned a project engaging in related design challenges in their classrooms under the supervision of their teachers. The project is valuable because it can be used by any student and any teacher, even those without technical backgrounds. Students in 12 states: Alabama, Arkansas, California, Colorado, Illinois, Missouri, Montana, New York, Ohio, Tennessee, Virginia, and Washington, are taking part in the MSFC's Earth-to-Orbit program. NASA uses such programs to support educational excellence while participating in educational outreach programs through centers around the country. The Oregon students' teacher, Joanne Fluvog, commented, "the biggest change I've seen is in the students' motivation and their belief in their ability to think." Both Justin and Jeff said being involved in a real engineering project has made them realize that "science is cool."

Earth-to-Orbit Education Program 'Makes Science Cool'

NASA Technical Reports Server (NTRS)

2002-01-01

In this photograph, Jeff Alden (left) and Justin O'Cornor, two middle school students at Lane Middle School in Portland, Oregon are demonstrating their Earth-to-Orbit (ETO) Design Challenge project at NASA Marshall Space Flight Center (MSFC) in Huntsville, Alabama. Jeff and Justin, who are just a couple of 'typical teens,' have been spending their time tackling some of the same challenges NASA engineers face when designing propulsion systems at MSFC. The ETO Design Challenge is a hands-on educational program, targeted to middle school students, in which students are assigned a project engaging in related design challenges in their classrooms under the supervision of their teachers. The project is valuable because it can be used by any student and any teacher, even those without technical backgrounds. Students in 12 states: Alabama, Arkansas, California, Colorado, Illinois, Missouri, Montana, New York, Ohio, Tennessee, Virginia, and Washington, are taking part in the MSFC's Earth-to-Orbit program. NASA uses such programs to support educational excellence while participating in educational outreach programs through centers around the country. The Oregon students' teacher, Joanne Fluvog, commented, 'the biggest change I've seen is in the students' motivation and their belief in their ability to think.' Both Justin and Jeff said being involved in a real engineering project has made them realize that 'science is cool.'

Recent advances in Takayasu’s arteritis

PubMed Central

Alibaz-Öner, Fatma; Aydın, Sibel Zehra; Direskeneli, Haner

2015-01-01

Takayasu’s arteritis (TAK) is a rare, chronic large-vessel vasculitis (LVV) that predominantly affects the aorta, its major branches, and the pulmonary arteries. Recent advances in the diagnosis, clinical course, disease assessment with biomarkers/imaging and new clinical tools, patient-reported outcomes, and new treatment options of TAK are discussed in this review. Conventional angiography, the gold standard method for initial diagnosis, appears to have been replaced with new imaging modalities such as magnetic resonance angiography (MRA) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in recent years. MRA and FDG-PET are also promising for the assessment of disease activity. New tools for disease assessment such as Indian Takayasu’s Arteritis Score 2010 (ITAS2010) and color Doppler ultrasound (CDUS) aim to better characterize and quantify disease activity; however, different imaging modalities in routine follow-up are not incorporated sufficiently in these approaches. Prognosis is possibly getting better, with lower mortality in recent years; however, it is difficult to assess the widely different vascular intervention rates among the clinical series. Leflunomide, tumor necrosis factor (TNF)-α antagonists, and tocilizumab are new options for patients resistant to conventional therapies. There is a clear need to develop a validated set of outcome measures for use in clinical trials of TAK. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group has taken on this task, finished a Delphi exercise with experts, and aims to develop a core set of outcomes for LVV in accordance with OMERACT Filter 2.0. PMID:27708916

Regulatory role of tumor necrosis factor receptor-associated factor 6 in breast cancer by activating the protein kinase B/glycogen synthase kinase 3β signaling pathway.

PubMed

Shen, Hongyu; Li, Liangpeng; Yang, Sujin; Wang, Dandan; Zhou, Siying; Chen, Xiu; Tang, Jinhai

2017-08-01

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an endogenous adaptor of innate and adaptive immune responses, and serves a crucial role in tumor necrosis factor receptor and toll‑like/interleukin‑1 receptor signaling. Although studies have demonstrated that TRAF6 has oncogenic activity, its potential contributions to breast cancer in human remains largely uninvestigated. The present study examined the expression levels and function of TRAF6 in breast carcinoma (n=32) and adjacent healthy (n=25) tissue samples. Compared with adjacent healthy tissues, TRAF6 protein expression levels were significantly upregulated in breast cancer tissues. Reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant upregulation of the cellular proliferative marker Ki‑67 and proliferation cell nuclear antigen expression levels in breast carcinoma specimens. Furthermore, protein expression levels of the accessory molecule, transforming growth factor β‑activated kinase 1 (TAK1), were significantly increased in breast cancer patients, as detected by western blot analysis. As determined by MTT assay, TRAF6 exerted profoundly proliferative effects in the MCF‑7 breast cancer cell line; however, these detrimental effects were ameliorated by TAK1 inhibition. Notably, protein kinase B (AKT)/glycogen synthase kinase (GSK)3β phosphorylation levels were markedly upregulated in breast cancer samples, compared with adjacent healthy tissues. In conclusion, an altered TRAF6‑TAK1 axis and its corresponding downstream AKT/GSK3β signaling molecules may contribute to breast cancer progression. Therefore, TRAF6 may represent a potential therapeutic target for the treatment of breast cancer.

Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells

PubMed Central

2014-01-01

Background Cholesterol plays an important role in cancer development, drug resistance and chemoimmuno-sensitivity. Statins, cholesterol lowering drugs, can induce apoptosis, but also negatively interfere with CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo immunotherapy of chronic lymphocytic leukemia (CLL). Methods MEC-2 cells, a CLL cell line, and the peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol levels, CD-20 expression and distribution, and cell viability in the presence or absence of fludarabine, rituximab or their combinations. Results We found that MEC-2 cells treated with cholesterol lowering agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular cholesterol levels, but also significantly promoted CD-20 surface expression. Furthermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced chemoimmuno-sensitivity of the PBMCs from CLL patients. Conclusion Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20 epitope presentation or its downstream signaling. These results provide a novel strategy which could be applied to CLL treatment. PMID:25401046

In Oregon, the EPA calculates nature's worth now and in the future

EPA Science Inventory

Ecosystem services are the many life-sustaining benefits we receive from nature — clean air and water, food and fiber production, greenhouse gas regulation, maintenance of biodiversity, etc. These ecosystem services are vital to our well-being, yet they are limited and often tak...

Nextgen Navy eLearning Tracking

DTIC Science & Technology

2014-12-01

ELEARNING TRACKING by William E. Miller December 2014 Thesis Advisor: Man-Tak Shing Co-Advisor: Arijit Das THIS PAGE INTENTIONALLY LEFT......Navy’s eLearning (NeL) computer-based learning system relies on a Learning Management System (LMS) for content delivery and tracking learning

The Role of Flushing Dental Waterlines for the Removal of Microbial Contaminants - MCEARD

EPA Science Inventory

Objectives. This study was designed to determine the role of flushing dental water lines for the removal of heterotrophic plate count bacteria, Legionella spp., and free-living protozoa. Methods. Forty dental offices were surveyed in the study. An initial sample and a sample tak...

Long Range Materials Research

DTIC Science & Technology

1976-01-01

the "weight In water -weight In air" method. The compact Is first weighed dry and then weighed while Immersed completely In water . The density was...calculated from the following: (Wdry) ^ compact W. - W dry wet (1) where P^-o ^8 ’^ density of water corrected for temperature. The weight wet...PPh9) ’"NXV 2 (4) ’ X CH20TS + EtO e These bonds are easily cleaved by water and alcohols . Thererore, it should be possible to

Assembly vs. direct launch of transfer vehicles

NASA Technical Reports Server (NTRS)

Katzberg, Stephen J.; Pritchard, E. Brian

1990-01-01

A top level assessment is performed of the relative impacts of on-orbit assembly of the lunar or Mars transfer vehicles versus direct launch. The objective is to identify the major option paths for the Earth-to-orbit, ETO, transportation systems. Heavy lift launch vehicles, if large enough, could reduce or eliminate on-orbit assembly. However, with every new approach, there are always counter-balancing considerations and it is the objective to begin the delineation of the necessary follow-on trade study issues.

Chemical induced behavioral responses in anopheles minimus and Anopheles harrisoni in Thailand

USDA-ARS?s Scientific Manuscript database

Behavioral responses of female mosquitoes representing two species in the Minimus Complex exposed to an operational field dose of bifenthrin or DEET (N,N-diethyl-m-toluamide) were described using an excito-repellency test system. Two test populations of An. minimus, one from the field (Tak Provinc...

Culex (Thaiomyia) Dispectus, A New Subgenus and Species from Thailand (Diptera: Culicidae)

DTIC Science & Technology

1966-06-01

Province; and Doi Sutep, Chiang Mai Province. Biology. Larvae have been collected on four occasions from open bamboo internodes or bamboo stumps in a...primary rain forest en- vironment. The collection from Chiang Mai was from an artificial container. Collections from Tak Province were made at an

A Causal-Comparative Analysis of the Effects of a Student Support Team (SST) Intervention Model at a Secondary School

ERIC Educational Resources Information Center

Johnson, Mid D.

2010-01-01

The purpose of this research was to identify and examine the effectiveness of a "Student Support Team" (SST) intervention model designed to increase the performance of struggling secondary students and to help them achieve prescribed state standards on the mathematics "Texas Assessment of Knowledge and Skills (TAKS)"…

76 FR 12962 - Ocean Transportation Intermediary License Applicants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

...), 17910 Ajax Circle, City of Industry, CA 91748. Officers: Jacky C. Chen, President (Qualifying Individual... Change. J.A. Logistics, Inc. (NVO & OFF), 3905 West Albany Street, McHenry, IL 60050. Officers: Joseph M... Harbour Road, Wanchai, Hong Kong. Officers: Tsang M. Tak, Director/CEO (Qualifying Individual), Joseph P...

Development and Demonstration of Manufacturing Processes for Fabricating Graphite/LARC 160 Polyimide Structural Elements.

DTIC Science & Technology

1981-12-01

microporous mem - brane over the preform bleeder surface and secure in place, wrinkle-free, with pressure sensitive tape on the backside of the mandrel...0 ,1 - a)Q w ( w0O0 aO)W Q)W~ toIt o m 04 0r 0 0 - -0 - -. ’ F0 E-tO 000 F00 H0 OHp oi0 -o 0 0 H *H H H -A P to HH HZ *H HHP o~ 0I 4- m H 044 u It

β-Arrestin Recruitment and Biased Agonism at Free Fatty Acid Receptor 1*

PubMed Central

Mancini, Arturo D.; Bertrand, Gyslaine; Vivot, Kevin; Carpentier, Éric; Tremblay, Caroline; Ghislain, Julien; Bouvier, Michel; Poitout, Vincent

2015-01-01

FFAR1/GPR40 is a seven-transmembrane domain receptor (7TMR) expressed in pancreatic β cells and activated by FFAs. Pharmacological activation of GPR40 is a strategy under consideration to increase insulin secretion in type 2 diabetes. GPR40 is known to signal predominantly via the heterotrimeric G proteins Gq/11. However, 7TMRs can also activate functionally distinct G protein-independent signaling via β-arrestins. Further, G protein- and β-arrestin-based signaling can be differentially modulated by different ligands, thus eliciting ligand-specific responses (“biased agonism”). Whether GPR40 engages β-arrestin-dependent mechanisms and is subject to biased agonism is unknown. Using bioluminescence resonance energy transfer-based biosensors for real-time monitoring of cell signaling in living cells, we detected a ligand-induced GPR40-β-arrestin interaction, with the synthetic GPR40 agonist TAK-875 being more effective than palmitate or oleate in recruiting β-arrestins 1 and 2. Conversely, TAK-875 acted as a partial agonist of Gq/11-dependent GPR40 signaling relative to both FFAs. Pharmacological blockade of Gq activity decreased FFA-induced insulin secretion. In contrast, knockdown or genetic ablation of β-arrestin 2 in an insulin-secreting cell line and mouse pancreatic islets, respectively, uniquely attenuated the insulinotropic activity of TAK-875, thus providing functional validation of the biosensor data. Collectively, these data reveal that in addition to coupling to Gq/11, GPR40 is functionally linked to a β-arrestin 2-mediated insulinotropic signaling axis. These observations expose previously unrecognized complexity for GPR40 signal transduction and may guide the development of biased agonists showing improved clinical profile in type 2 diabetes. PMID:26157145

Polyubiquitination events mediate polymethylmethacrylate (PMMA) particle activation of NF-kappaB pathway.

PubMed

Yamanaka, Yasuhiro; Karuppaiah, Kannan; Abu-Amer, Yousef

2011-07-08

The pathologic response to implant wear-debris constitutes a major component of inflammatory osteolysis and remains under intense investigation. Polymethylmethacrylate (PMMA) particles, which are released during implant wear and loosening, constitute a major culprit by virtue of inducing inflammatory and osteolytic responses by macrophages and osteoclasts, respectively. Recent work by several groups has identified important cellular entities and secreted factors that contribute to inflammatory osteolysis. In previous work, we have shown that PMMA particles contribute to inflammatory osteolysis through stimulation of major pathways in monocytes/macrophages, primarily NF-κB and MAP kinases. The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKKγ/NEMO. We have shown recently that interfering with the NF-κB and MAPK activation pathways, through introduction of inhibitors and decoy molecules, impedes PMMA-induced inflammation and osteolysis in mouse models of experimental calvarial osteolysis and inflammatory arthritis. In this study, we report that PMMA particles activate the upstream transforming growth factor β-activated kinase-1 (TAK1), which is a key regulator of signal transduction cascades leading to activation of NF-κB and AP-1 factors. More importantly, we found that PMMA particles induce TAK1 binding to NEMO and UBC13. In addition, we show that PMMA particles induce TRAF6 and UBC13 binding to NEMO and that lack of TRAF6 significantly attenuates NEMO ubiquitination. Altogether, these observations suggest that PMMA particles induce ubiquitination of NEMO, an event likely mediated by TRAF6, TAK1, and UBC13. Our findings provide important information for better understanding of the mechanisms underlying PMMA particle-induced inflammatory responses.

Peroxiredoxin 5 modulates immune response in Drosophila

PubMed Central

Radyuk, Svetlana N.; Michalak, Katarzyna; Klichko, Vladimir I.; Benes, Judith; Orr, William C.

2010-01-01

Background Peroxiredoxins are redox-sensing enzymes with multiple cellular functions. Previously, we reported on the potent antioxidant function of Drosophila peroxiredoxin 5 (dPrx5). Studies with mammalian and human cells suggest that peroxiredoxins can modulate immune-related signaling. Methods Survivorship studies and bacteriological analysis were used to determine resistance of flies to fungal and bacterial infections. RT-PCR and immunoblot analyses determined expression of dPrx5 and immunity factors in response to bacterial challenge. Double mutants for dprx5 gene and genes comprising the Imd/Relish and dTak1/Basket branches of the immune signaling pathways were used in epistatic analysis. Results The dprx5 mutant flies were more resistant to bacterial infection than controls, while flies overexpressing dPrx5 were more susceptible. The enhanced resistance to bacteria was accompanied by rapid induction of the Imd-dependent antimicrobial peptides, phosphorylation of the JNK kinase Basket and altered transcriptional profiling of the transient response genes, puckered, ets21C and relish, while the opposite effects were observed in flies over-expressing dPrx5. Epistatic analysis of double mutants, using attacin D and Puckered as read outs of activation of the Imd and JNK pathways, implicated dPrx5 function in the control of the dTak1-JNK arm of immune signaling. Conclusions Differential effects on fly survivorship suggested a trade-off between the antioxidant and immune functions of dPrx5. Molecular and epistatic analyses identified dPrx5 as a negative regulator in the dTak1-JNK arm of immune signaling. General significance Our findings suggest that peroxiredoxins play an important modulatory role in the Drosophila immune response. PMID:20600624

The role of hybrid ubiquitin chains in the MyD88 and other innate immune signalling pathways.

PubMed

Cohen, Philip; Strickson, Sam

2017-07-01

The adaptor protein MyD88 is required for signal transmission by toll-like receptors and receptors of the interleukin-1 family of cytokines. MyD88 signalling triggers the formation of Lys63-linked and Met1-linked ubiquitin (K63-Ub, M1-Ub) chains within minutes. The K63-Ub chains, which are formed by the E3 ubiquitin ligases TRAF6, Pellino1 and Pellino2, activate TAK1, the master kinase that switches on mitogen-activated protein (MAP) kinase cascades and initiates activation of the canonical IκB kinase (IKK) complex. The M1-Ub chains, which are formed by the linear ubiquitin chain assembly complex (LUBAC), bind to the NEMO (NF-κB essential modulator) component of the IKK complex and are required for TAK1 to activate IKKs, but not MAP kinases. An essential E3 ligase-independent role of TRAF6 is to recruit LUBAC into the MyD88 signalling complex, where it recognises preformed K63-Ub chains attached to protein components of these complexes, such as IRAK1 (IL-1 receptor-associated kinase), producing ubiquitin chains containing both types of linkage, termed K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids, which is a feature of several innate immune signalling pathways, permits the co-recruitment of proteins that interact with either K63-Ub or M1-Ub chains. Two likely roles for K63/M1-Ub hybrids are to facilitate the TAK1-dependent activation of the IKK complex and to prevent the hyperactivation of these kinases by recruiting A20 and A20-binding inhibitor of NF-κB1 (ABIN1). These proteins restrict activation of the TAK1 and IKK complexes, probably by competing with them for binding to K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids may also regulate the rate at which the ubiquitin linkages in these chains are hydrolysed. The IKK-catalysed phosphorylation of some of its substrates permits their recognition by the E3 ligase SCF βTRCP , leading to their Lys48-linked ubiquitylation and proteasomal degradation. Innate immune signalling is therefore controlled

The role of hybrid ubiquitin chains in the MyD88 and other innate immune signalling pathways

PubMed Central

Cohen, Philip; Strickson, Sam

2017-01-01

The adaptor protein MyD88 is required for signal transmission by toll-like receptors and receptors of the interleukin-1 family of cytokines. MyD88 signalling triggers the formation of Lys63-linked and Met1-linked ubiquitin (K63-Ub, M1-Ub) chains within minutes. The K63-Ub chains, which are formed by the E3 ubiquitin ligases TRAF6, Pellino1 and Pellino2, activate TAK1, the master kinase that switches on mitogen-activated protein (MAP) kinase cascades and initiates activation of the canonical IκB kinase (IKK) complex. The M1-Ub chains, which are formed by the linear ubiquitin chain assembly complex (LUBAC), bind to the NEMO (NF-κB essential modulator) component of the IKK complex and are required for TAK1 to activate IKKs, but not MAP kinases. An essential E3 ligase-independent role of TRAF6 is to recruit LUBAC into the MyD88 signalling complex, where it recognises preformed K63-Ub chains attached to protein components of these complexes, such as IRAK1 (IL-1 receptor-associated kinase), producing ubiquitin chains containing both types of linkage, termed K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids, which is a feature of several innate immune signalling pathways, permits the co-recruitment of proteins that interact with either K63-Ub or M1-Ub chains. Two likely roles for K63/M1-Ub hybrids are to facilitate the TAK1-dependent activation of the IKK complex and to prevent the hyperactivation of these kinases by recruiting A20 and A20-binding inhibitor of NF-κB1 (ABIN1). These proteins restrict activation of the TAK1 and IKK complexes, probably by competing with them for binding to K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids may also regulate the rate at which the ubiquitin linkages in these chains are hydrolysed. The IKK-catalysed phosphorylation of some of its substrates permits their recognition by the E3 ligase SCFβTRCP, leading to their Lys48-linked ubiquitylation and proteasomal degradation. Innate immune signalling is therefore controlled by

A Comparison of Career Technical Education--16 Career Pathway High School Participants with Non-Participants on Academic Achievement, School Engagement, and Development of Technical Skills

ERIC Educational Resources Information Center

Orozco, Edith Aimee

2010-01-01

The objective of this research was to compare Career Technical Education--16 Career Pathway high school participants with non-participants on academic achievement, development of technical skills and school engagement. Academic achievement was measured by Exit Level Math and English Language Arts Texas Assessment of Knowledge and Skills (TAKS)…

The Effects of Elementary School Principals' Leadership Styles and the Preferred Managerial Styles of Teachers on Student Achievement

ERIC Educational Resources Information Center

Pichon, Christopher, Sr.

2010-01-01

The objective of this study is to identify principal leadership styles and teacher preferred principal leadership styles, as well as to examine the independent and combined effects of these variables on the TAKS Mathematics achievement scores of elementary students. School leadership affects every aspect of an institution. Studies reveal that the…

The Effectiveness of Business Leadership Practices among Principals on Student Achievement on Public School Campuses in Texas

ERIC Educational Resources Information Center

Cooper, Kary M.

2009-01-01

The purpose of this descriptive study was to determine if business leadership practices by Texas public school principals have an impact on principals' campus student achievement in mathematics and reading, as measured by TAKS scores. The survey instrument was the Leadership Assessment Instrument (LAI), developed by Warren Bennis in 1989. The…

Processes to Preserve Spice and Herb Quality and Sensory Integrity During Pathogen Inactivation

PubMed Central

Moberg, Kayla; Amin, Kemia N.; Wright, Melissa; Newkirk, Jordan J.; Ponder, Monica A.; Acuff, Gary R.; Dickson, James S.

2017-01-01

Abstract Selected processing methods, demonstrated to be effective at reducing Salmonella, were assessed to determine if spice and herb quality was affected. Black peppercorn, cumin seed, oregano, and onion powder were irradiated to a target dose of 8 kGy. Two additional processes were examined for whole black peppercorns and cumin seeds: ethylene oxide (EtO) fumigation and vacuum assisted‐steam (82.22 °C, 7.5 psia). Treated and untreated spices/herbs were compared (visual, odor) using sensory similarity testing protocols (α = 0.20; β = 0.05; proportion of discriminators: 20%) to determine if processing altered sensory quality. Analytical assessment of quality (color, water activity, and volatile chemistry) was completed. Irradiation did not alter visual or odor sensory quality of black peppercorn, cumin seed, or oregano but created differences in onion powder, which was lighter (higher L *) and more red (higher a*) in color, and resulted in nearly complete loss of measured volatile compounds. EtO processing did not create detectable odor or appearance differences in black peppercorn; however visual and odor sensory quality differences, supported by changes in color (higher b *; lower L *) and increased concentrations of most volatiles, were detected for cumin seeds. Steam processing of black peppercorn resulted in perceptible odor differences, supported by increased concentration of monoterpene volatiles and loss of all sesquiterpenes; only visual differences were noted for cumin seed. An important step in process validation is the verification that no effect is detectable from a sensory perspective. PMID:28407236

PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

PubMed Central

Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

2014-01-01

Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

Comparing Effects of Lake- and Watershed-Scale Influences on Communities of Aquatic Invertebrates in Shallow Lakes

PubMed Central

Hanson, Mark A.; Herwig, Brian R.; Zimmer, Kyle D.; Fieberg, John; Vaughn, Sean R.; Wright, Robert G.; Younk, Jerry A.

2012-01-01

Constraints on lake communities are complex and are usually studied by using limited combinations of variables derived from measurements within or adjacent to study waters. While informative, results often provide limited insight about magnitude of simultaneous influences operating at multiple scales, such as lake- vs. watershed-scale. To formulate comparisons of such contrasting influences, we explored factors controlling the abundance of predominant aquatic invertebrates in 75 shallow lakes in western Minnesota, USA. Using robust regression techniques, we modeled relative abundance of Amphipoda, small and large cladocera, Corixidae, aquatic Diptera, and an aggregate taxon that combined Ephemeroptera-Trichoptera-Odonata (ETO) in response to lake- and watershed-scale characteristics. Predictor variables included fish and submerged plant abundance, linear distance to the nearest wetland or lake, watershed size, and proportion of the watershed in agricultural production. Among-lake variability in invertebrate abundance was more often explained by lake-scale predictors than by variables based on watershed characteristics. For example, we identified significant associations between fish presence and community type and abundance of small and large cladocera, Amphipoda, Diptera, and ETO. Abundance of Amphipoda, Diptera, and Corixidae were also positively correlated with submerged plant abundance. We observed no associations between lake-watershed variables and abundance of our invertebrate taxa. Broadly, our results seem to indicate preeminence of lake-level influences on aquatic invertebrates in shallow lakes, but historical land-use legacies may mask important relationships. PMID:22970275

Interaction of phase variation, host and pressure/gas composition: pneumococcal gene expression of PsaA, SpxB, Ply and LytA in simulated middle ear environments.

PubMed

Li-Korotky, Ha-Sheng; Lo, Chia-Yee; Zeng, Fan-Rui; Lo, David; Banks, Juliane M

2009-10-01

Streptococcus pneumoniae, a leading cause of otitis media (OM), undergoes spontaneous intra-strain variations in colony morphology. Transparent (T) variants are more efficient in colonizing the nasopharynx while opaque (O) variants exhibit greater virulence during systemic infections. This study was intended to delineate the underlying molecular mechanisms by which the predominant S. pneumoniae variant efficiently infects the middle ear (ME) mucosa. Human ME epithelial cells were preconditioned for 24h under one of the three gas/pressure conditions designed to simulate those for (1) normal ME (NME), (2) ME with Eustachian tube obstruction (ETO) and (3) ME with tympanostomy tube placement (TT), and then were incubated with ∼ 10(7)CFU/ml of either T or O variants of S. pneumoniae (6A) for 3h. Relative expression levels of genes encoding virulence factors, PsaA (surface adhesion), SpxB (pyruvate oxidase), Ply (pneumolysin), and LytA (autolysin) were assessed separately in epithelium-attached and supernatant bacteria 3h post infection using real-time PCR. Basal levels of the virulence molecules in inocula were comparable between two variants. However, relative expression levels of the gene transcripts were significantly induced in epithelium-attached T variants 3h after infection. Comparing with NME and TT conditions, ETO environment produced the largest effect on the differential expression of the virulence genes in the infected ME epithelial cells between T (induced) and O (suppressed) phenotypic pneumococci. T variant is a predominant phenotype responsible for the pathogenesis of pneumococcal OM.

Psychological and Physical Performance Factors Associated with Attrition in Explosive Ordnance Disposal Training

DTIC Science & Technology

1984-03-10

S55aI61t;YCSGFICATIO" of "Igs P#.G! (Man VMS. antopao__________ REPOT DOUMETATIN P E AD INSýUCTIOKSREPOR OOCM~l4ATI~4 PAE UgORK COMPLSIT01 PORN 1...public events (rock concerts, sports events) are very exciting. 2. As a child , I was always reading. 3. Happirass Is more important than fame. 4. I e...to talk to people. 21. As a child , school was easy for me. 22. 1 enjoy working crossword puzzles. 23. 1 was a slow learner in school. 24. 1 have a

Differences in Academic Achievement among Texas High School Students as a Function of Music Enrollment

ERIC Educational Resources Information Center

Horton, Robert Wayne

2012-01-01

Purpose: The purpose of this study was to examine the score differences on the Texas Academic Knowledge and Skills (TAKS) Reading and Mathematics measures among students in Grades 10 and 11 as a function of music enrollment. Specifically, gender, ethnicity, socioeconomic status, and enrollment in choir, band, or orchestra or no music enrollment…

The Effect of a Constructivist-Based Approach on Fifth Grade Reading Achievement

ERIC Educational Resources Information Center

Harkness, Lori M.

2016-01-01

The problem investigated in this quantitative study was that schools in a small, rural East Texas town were falling below acceptable ratings in reading on the Texas Assessment of Knowledge and Skills (TAKS) and the State of Texas Assessment of Academic Readiness (STAAR). Researchers have found that constructive-based learning environments (CBLEs)…

Utilizing the Six Realms of Meaning in Improving Campus Standardized Test Scores through Team Teaching and Strategic Planning

ERIC Educational Resources Information Center

Stevenson, Rosnisha D.; Kritsonis, William Allan

2009-01-01

This article will seek to utilize Dr. William Allan Kritsonis' book "Ways of Knowing Through the Realms of Meaning" (2007) as a framework to improve a campus's standardized test scores, more specifically, their TAKS (Texas Assessment of Knowledge and Skills) scores. Many campuses have an improvement plan, also known as a Campus…

Genetics Home Reference: ocular albinism

MedlinePlus

... Available from http://www.ncbi.nlm.nih.gov/books/NBK1343/ Citation on PubMed Oetting WS. New insights into ocular albinism type 1 (OA1): Mutations and polymorphisms of the OA1 gene. Hum Mutat. 2002 Feb;19(2):85-92. Review. Citation on PubMed Tak WJ, Kim MN, Hong ...

Hypoxia preconditioning increases survival and decreases expression of Toll-like receptor 4 in pulmonary artery endothelial cells exposed to lipopolysaccharide.

PubMed

Ali, Irshad; Nanchal, Rahul; Husnain, Fouad; Audi, Said; Konduri, G Ganesh; Densmore, John C; Medhora, Meetha; Jacobs, Elizabeth R

2013-09-01

Abstract Pulmonary or systemic infections and hypoxemic respiratory failure are among the leading causes of admission to intensive care units, and these conditions frequently exist in sequence or in tandem. Inflammatory responses to infections are reproduced by lipopolysaccharide (LPS) engaging Toll-like receptor 4 (TLR4). Apoptosis is a hallmark of lung injury in sepsis. This study was conducted to determine whether preexposure to LPS or hypoxia modulated the survival of pulmonary artery endothelial cells (PAECs). We also investigated the role TLR4 receptor expression plays in apoptosis due to these conditions. Bovine PAECs were cultured in hypoxic or normoxic environments and treated with LPS. TLR4 antagonist TAK-242 was used to probe the role played by TLR4 receptors in cell survival. Cell apoptosis and survival were measured by caspase 3 activity and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) incorporation. TLR4 expression and tumor necrosis factor α (TNF-α) production were also determined. LPS increased caspase 3 activity in a TAK-242-sensitive manner and decreased MTT incorporation. Apoptosis was decreased in PAECs preconditioned with hypoxia prior to LPS exposure. LPS increased TNF-α production, and hypoxic preconditioning blunted it. Hypoxic preconditioning reduced LPS-induced TLR4 messenger RNA and TLR4 protein. TAK-242 decreased to baseline the LPS-stimulated expression of TLR4 messenger RNA regardless of environmental conditions. In contrast, LPS followed by hypoxia substantially increased apoptosis and cell death. In conclusion, protection from LPS-stimulated PAEC apoptosis by hypoxic preconditioning is attributable in part to reduction in TLR4 expression. If these signaling pathways apply to septic patients, they may account for differing sensitivities of individuals to acute lung injury depending on oxygen tensions in PAECs in vivo.

Hypoxia preconditioning increases survival and decreases expression of Toll-like receptor 4 in pulmonary artery endothelial cells exposed to lipopolysaccharide

PubMed Central

Nanchal, Rahul; Audi, Said; Konduri, G. Ganesh; Medhora, Meetha

2013-01-01

Abstract Pulmonary or systemic infections and hypoxemic respiratory failure are among the leading causes of admission to intensive care units, and these conditions frequently exist in sequence or in tandem. Inflammatory responses to infections are reproduced by lipopolysaccharide (LPS) engaging Toll-like receptor 4 (TLR4). Apoptosis is a hallmark of lung injury in sepsis. This study was conducted to determine whether preexposure to LPS or hypoxia modulated the survival of pulmonary artery endothelial cells (PAECs). We also investigated the role TLR4 receptor expression plays in apoptosis due to these conditions. Bovine PAECs were cultured in hypoxic or normoxic environments and treated with LPS. TLR4 antagonist TAK-242 was used to probe the role played by TLR4 receptors in cell survival. Cell apoptosis and survival were measured by caspase 3 activity and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) incorporation. TLR4 expression and tumor necrosis factor α (TNF-α) production were also determined. LPS increased caspase 3 activity in a TAK-242-sensitive manner and decreased MTT incorporation. Apoptosis was decreased in PAECs preconditioned with hypoxia prior to LPS exposure. LPS increased TNF-α production, and hypoxic preconditioning blunted it. Hypoxic preconditioning reduced LPS-induced TLR4 messenger RNA and TLR4 protein. TAK-242 decreased to baseline the LPS-stimulated expression of TLR4 messenger RNA regardless of environmental conditions. In contrast, LPS followed by hypoxia substantially increased apoptosis and cell death. In conclusion, protection from LPS-stimulated PAEC apoptosis by hypoxic preconditioning is attributable in part to reduction in TLR4 expression. If these signaling pathways apply to septic patients, they may account for differing sensitivities of individuals to acute lung injury depending on oxygen tensions in PAECs in vivo. PMID:24618542

What goal is of most worth? The effects of the implementation of the Texas Assessment of Knowledge and Skills on elementary science teaching

NASA Astrophysics Data System (ADS)

Rodgers, Pamela England

This qualitative, narrative study centered on the effects of the implementation of the science portion of the fifth grade Texas Assessment of Knowledge and Skills (TAKS) on the instruction of science at the elementary level, grades one through five. Fourteen teachers and five administrators were interviewed at two elementary schools (kindergarten through grade four) and one middle school (grades five and six). Classroom observations of each of the teachers were also conducted. The study focused on the effect of the implementation of the science TAKS on the amount of time spent on science as well as the instructional methods utilized in the elementary science classroom. Lower grade levels were found to have changed little in these areas unless strong administrative leadership---emphasizing curriculum alignment, providing adequate materials and facilities, and encouraging sustained, content-based professional development in science---was present in the school. At the fifth grade level, however, the amount of time spent on science had increased significantly, although the instructional methods utilized by the teachers were focused more often upon increasing ratings on the test rather than providing the research-based best practice methods of hands-on, inquiry-based science instruction. In addition, the study also explored the teachers' and administrators' perceptions of the state and local mandates concerning science instruction and preparation for the TAKS. Other topics that came to light during the course of the study included the teachers' views on accountability and the effects of the state assessments on children in their classrooms. It was found that most teachers readily accept accountability for themselves, but are opposed to one-shot high-stakes tests which they feel are damaging for their students emotionally and academically---adversely affecting their love of learning science.

The Effects of Airway Microbiome on Corticosteroid Responsiveness in Asthma

PubMed Central

Goleva, Elena; Jackson, Leisa P.; Harris, J. Kirk; Robertson, Charles E.; Sutherland, E. Rand; Hall, Clifton F.; Good, James T.; Gelfand, Erwin W.; Martin, Richard J.

2013-01-01

Rationale: The role of airway microbiome in corticosteroid response in asthma is unknown. Objectives: To examine airway microbiome composition in patients with corticosteroid-resistant (CR) asthma and compare it with patients with corticosteroid-sensitive (CS) asthma and normal control subjects and explore whether bacteria in the airways of subjects with asthma may direct alterations in cellular responses to corticosteroids. Methods: 16S rRNA gene sequencing was performed on bronchoalveolar lavage (BAL) samples of 39 subjects with asthma and 12 healthy control subjects. In subjects with asthma, corticosteroid responsiveness was characterized, BAL macrophages were stimulated with pathogenic versus commensal microorganisms, and analyzed by real-time polymerase chain reaction for the expression of corticosteroid-regulated genes and cellular p38 mitogen-activated protein kinase (MAPK) activation. Measurements and Main Results: Of the 39 subjects with asthma, 29 were CR and 10 were CS. BAL microbiome from subjects with CR and CS asthma did not differ in richness, evenness, diversity, and community composition at the phylum level, but did differ at the genus level, with distinct genus expansions in 14 subjects with CR asthma. Preincubation of asthmatic airway macrophages with Haemophilus parainfluenzae, a uniquely expanded potential pathogen found only in CR asthma airways, resulted in p38 MAPK activation, increased IL-8 (P < 0.01), mitogen-activated kinase phosphatase 1 mRNA (P < 0.01) expression, and inhibition of corticosteroid responses (P < 0.05). This was not observed after exposure to commensal bacterium Prevotella melaninogenica. Inhibition of transforming growth factor-β–associated kinase-1 (TAK1), upstream activator of MAPK, but not p38 MAPK restored cellular sensitivity to corticosteroids. Conclusions: A subset of subjects with CR asthma demonstrates airway expansion of specific gram-negative bacteria, which trigger TAK1/MAPK activation and induce

β-Arrestin Recruitment and Biased Agonism at Free Fatty Acid Receptor 1.

PubMed

Mancini, Arturo D; Bertrand, Gyslaine; Vivot, Kevin; Carpentier, Éric; Tremblay, Caroline; Ghislain, Julien; Bouvier, Michel; Poitout, Vincent

2015-08-21

FFAR1/GPR40 is a seven-transmembrane domain receptor (7TMR) expressed in pancreatic β cells and activated by FFAs. Pharmacological activation of GPR40 is a strategy under consideration to increase insulin secretion in type 2 diabetes. GPR40 is known to signal predominantly via the heterotrimeric G proteins Gq/11. However, 7TMRs can also activate functionally distinct G protein-independent signaling via β-arrestins. Further, G protein- and β-arrestin-based signaling can be differentially modulated by different ligands, thus eliciting ligand-specific responses ("biased agonism"). Whether GPR40 engages β-arrestin-dependent mechanisms and is subject to biased agonism is unknown. Using bioluminescence resonance energy transfer-based biosensors for real-time monitoring of cell signaling in living cells, we detected a ligand-induced GPR40-β-arrestin interaction, with the synthetic GPR40 agonist TAK-875 being more effective than palmitate or oleate in recruiting β-arrestins 1 and 2. Conversely, TAK-875 acted as a partial agonist of Gq/11-dependent GPR40 signaling relative to both FFAs. Pharmacological blockade of Gq activity decreased FFA-induced insulin secretion. In contrast, knockdown or genetic ablation of β-arrestin 2 in an insulin-secreting cell line and mouse pancreatic islets, respectively, uniquely attenuated the insulinotropic activity of TAK-875, thus providing functional validation of the biosensor data. Collectively, these data reveal that in addition to coupling to Gq/11, GPR40 is functionally linked to a β-arrestin 2-mediated insulinotropic signaling axis. These observations expose previously unrecognized complexity for GPR40 signal transduction and may guide the development of biased agonists showing improved clinical profile in type 2 diabetes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Relationship between Computer-Assisted Instruction and Alternative Programs to Enhance Fifth-Grade Mathematics Success on the Annual Texas Assessment of Knowledge and Skills

ERIC Educational Resources Information Center

Tucker, Tommy Howard

2009-01-01

The purpose of this study was to determine the relationship between using computer-assisted instruction (CAI) size and success on the Texas Assessment of Knowledge and Skills (TAKS) mathematics exam with fifth-grade students in Texas compared to the effect of alternative improvement approaches used by a control group. Research explored the use of…

Impact of Texas High School Science Teacher Credentials on Student Performance in High School Science

ERIC Educational Resources Information Center

George, Anna Ray Bayless

2012-01-01

A study was conducted to determine the relationship between the credentials held by science teachers who taught at a school that administered the Science Texas Assessment on Knowledge and Skills (Science TAKS), the state standardized exam in science, at grade 11 and student performance on a state standardized exam in science administered in grade…

Middle School Mathematics: A Study of Three Programs in South Texas

ERIC Educational Resources Information Center

Ellis, Joanetta Dowell

2011-01-01

In 2010, the Texas Assessment of Knowledge and Skills (TAKS) began its seventh year of testing (Texas Education Agency, 2009a). High stakes testing is a reality. This study considered the impact on mathematics achievement based on the mathematics program students were receiving during their middle school years. The purpose of this study was to…

A Comparative Analysis of Texas Grade Five Student Achievement between Year-Round and Traditional School Calendars

ERIC Educational Resources Information Center

Wilmore-Dafonte, Christy N.

2013-01-01

Purpose: The purpose of this dissertation was to determine the extent to which school instructional calendar configuration (i.e., year-round or traditional) influenced Grade 5 student academic performance as reflected on the Texas Assessment of Knowledge and Skills (TAKS) test as a function of student ethnicity (i.e., Hispanic, White, and Black)…

TAB2 Is Essential for Prevention of Apoptosis in Fetal Liver but Not for Interleukin-1 Signaling

PubMed Central

Sanjo, Hideki; Takeda, Kiyoshi; Tsujimura, Tohru; Ninomiya-Tsuji, Jun; Matsumoto, Kunihiro; Akira, Shizuo

2003-01-01

The proinflammatory cytokine interleukin-1 (IL-1) transmits a signal via several critical cytoplasmic proteins such as MyD88, IRAKs and TRAF6. Recently, serine/threonine kinase TAK1 and TAK1 binding protein 1 and 2 (TAB1/2) have been identified as molecules involved in IL-1-induced TRAF6-mediated activation of AP-1 and NF-κB via mitogen-activated protein (MAP) kinases and IκB kinases, respectively. However, their physiological functions remain to be clarified. To elucidate their roles in vivo, we generated TAB2-deficient mice. The TAB2 deficiency was embryonic lethal due to liver degeneration and apoptosis. This phenotype was similar to that of NF-κB p65-, IKKβ-, and NEMO/IKKγ-deficient mice. However, the IL-1-induced activation of NF-κB and MAP kinases was not impaired in TAB2-deficient embryonic fibroblasts. These findings demonstrate that TAB2 is essential for embryonic development through prevention of liver apoptosis but not for the IL-1 receptor-mediated signaling pathway. PMID:12556483

Regulation of the nuclear factor (NF)-kappaB pathway by ISGylation.

PubMed

Minakawa, Miki; Sone, Takayuki; Takeuchi, Tomoharu; Yokosawa, Hideyoshi

2008-12-01

Post-translational modification with ISG15 (interferon-stimulated gene 15 kDa) (ISGylation) is mediated by a sequential reaction similar to ubiquitination, and various target proteins for ISGylation have been identified. We previously reported that ISGylation of the E2 ubiquitin-conjugating enzyme Ubc13 suppresses its E2 activity. Ubc13 forms a heterodimer with Uev1A, a ubiquitin-conjugating enzyme variant, and the Ubc13-Uev1A complex catalyzes the assembly of a Lys63-linked polyubiquitin chain, which plays a non-proteolytic role in the nuclear factor (NF)-kappaB pathway. In this study, we examined the effect of ISGylation on tumor necrosis factor receptor-associated factor (TRAF)-6/transforming growth factor beta-activated kinase (TAK)-1-dependent NF-kappaB activation. We found that expression of the ISGylation system suppresses NF-kappaB activation via TRAF6 and TAK1 and that the level of polyubiquitinated TRAF6 is reduced by expression of the ISGylation system. Taken together, the results suggest that the NF-kappaB pathway is negatively regulated by ISGylation.

The E3 ubiquitin ligase mind bomb-2 (MIB2) protein controls B-cell CLL/lymphoma 10 (BCL10)-dependent NF-κB activation.

PubMed

Stempin, Cinthia C; Chi, Liying; Giraldo-Vela, Juan P; High, Anthony A; Häcker, Hans; Redecke, Vanessa

2011-10-28

B-cell CLL/lymphoma 10 (BCL10) is crucial for the activation of NF-κB in numerous immune receptor signaling pathways, including the T-cell receptor (TCR) and B-cell receptor signaling pathways. However, the molecular mechanisms that lead to signal transduction from BCL10 to downstream NF-κB effector kinases, such as TAK1 and components of the IKK complex, are not entirely understood. Here we used a proteomic approach and identified the E3 ligase MIB2 as a novel component of the activated BCL10 complex. In vitro translation and pulldown assays suggest direct interaction between BCL10 and MIB2. Overexpression experiments show that MIB2 controls BCL10-mediated activation of NF-κB by promoting autoubiquitination and ubiquitination of IKKγ/NEMO, as well as recruitment and activation of TAK1. Knockdown of MIB2 inhibited BCL10-dependent NF-κB activation. Together, our results identify MIB2 as a novel component of the activated BCL10 signaling complex and a missing link in the BCL10-dependent NF-κB signaling pathway.

Strategies for Improving School Performance

ERIC Educational Resources Information Center

Johnson, William L.; Johnson, Annabel M.; Johnson, Jared W.

2014-01-01

The document is from a presentation at the Texas Region VII 2014 Curriculum Conference. The study examined the effects of a three-tiered high school program designed to increase student achievement and Texas end-of-course (EOC) TAKS and STAAR chemistry scores. The student sample (n = 625) consisted 75% high school sophomores and 25% high school…

The Effectiveness of Inclusion in Texas High Schools

ERIC Educational Resources Information Center

Patterson, Steven T.

2013-01-01

The purpose of this study was to employ value-added methodology to determine which placement setting offered the ninth grade 2009 special education high school cohort the most academic growth as measured on the Texas Assessment of Knowledge and Skills (TAKS). This particular cohort was selected because it was the most recent cohort for which 3…

Effects of Year-Round Education on Texas Middle School Student Performance

ERIC Educational Resources Information Center

Coopersmith, Michael

2011-01-01

This study was designed to investigate the effects of the year-round calendar on student performance in Texas middle schools as measured by achievement on the Texas Assessment of Knowledge and Skills (TAKS) test. In the State of Texas, 15 schools served students in grades six through eight using the year-round calendar in 2009-2010. The 15…

Long-Term Implications of the 2013 Future Years Defense Program

DTIC Science & Technology

2012-07-01

difficult for the department to manage because it would need to be achieved in only nine months (between the cut’s tak - ing effect in January 2013 and the...Estimate of DoD’s Funding Under the BCA Caps After Automatic Reductionse 469 472 475 477 480 483 485 487 489 493 d Nominal Dollars 2013 Dollars 2022

The Prediction of Reading Levels between Second and Third Grade Limited English Proficient Students in a Bilingual Program

ERIC Educational Resources Information Center

Moses, Britani Creel

2010-01-01

The purpose of this study was to predict the third grade English reading TAKS scores while considering the same students' native language, Spanish, reading level as assessed by a state-approved reading assessment, the Evaluacion del desarrollo de la lectura (EDL), from the end of the second grade year. In addition, this study was been designed to…

Strategies for Science Student Achievement & Productive School Management

ERIC Educational Resources Information Center

Johnson, William L.

2010-01-01

There is an increasing literature pertaining to student achievement and school productivity. This session will present school and classroom strategies used in high school science classes at Robert E. Lee High School (5A) in Tyler, Texas. This year, 84% of the students at Lee passed the science TAKS test. Lee is also ranked in the top 1500 high…

E-to-E: Spanning Opportunity and Skills Gaps with Education-to-Employment Pathways

ERIC Educational Resources Information Center

Gittell, Ross; Hitchcock, Jeremy

2016-01-01

This article reports on a skills gap problem experienced in New England states where the economy has improved, but economic opportunity and skills gaps contribute to slower growth in employment, income, and social mobility. The article suggests ways to overcome this gap by building stronger bridges between education and employment…

Synthesis of a Novel Polyethoxysilsesquiazane and Thermal Conversion into Ternary Silicon Oxynitride Ceramics with Enhanced Thermal Stability.

PubMed

Iwase, Yoshiaki; Horie, Yoji; Daiko, Yusuke; Honda, Sawao; Iwamoto, Yuji

2017-12-05

A novel polyethoxysilsesquiazane ([EtOSi(NH) 1.5 ] n , EtOSZ) was synthesized by ammonolysis at -78 °C of ethoxytrichlorosilane (EtOSiCl₃), which was isolated by distillation as a reaction product of SiCl₄ and EtOH. Attenuated total reflection-infra red (ATR-IR), 13 C-, and 29 Si-nuclear magnetic resonance (NMR) spectroscopic analyses of the ammonolysis product resulted in the detection of Si-NH-Si linkage and EtO group. The simultaneous thermogravimetric and mass spectrometry analyses of the EtOSZ under helium revealed cleavage of oxygen-carbon bond of the EtO group to evolve ethylene as a main gaseous species formed in-situ, which lead to the formation at 800 °C of quaternary amorphous Si-C-N with an extremely low carbon content (1.1 wt %) when compared to the theoretical EtOSZ (25.1 wt %). Subsequent heat treatment up to 1400 °C in N₂ lead to the formation of X-ray amorphous ternary Si-O-N. Further heating to 1600 °C in N₂ promoted crystallization and phase partitioning to afford Si₂N₂O nanocrystallites identified by the XRD and TEM analyses. The thermal stability up to 1400 °C of the amorphous state achieved for the ternary Si-O-N was further studied by chemical composition analysis, as well as X-ray photoelectron spectroscopy (XPS) and 29 Si-NMR spectroscopic analyses, and the results were discussed aiming to develop a novel polymeric precursor for ternary amorphous Si-O-N ceramics with an enhanced thermal stability.

Processes to Preserve Spice and Herb Quality and Sensory Integrity During Pathogen Inactivation.

PubMed

Duncan, Susan E; Moberg, Kayla; Amin, Kemia N; Wright, Melissa; Newkirk, Jordan J; Ponder, Monica A; Acuff, Gary R; Dickson, James S

2017-05-01

Selected processing methods, demonstrated to be effective at reducing Salmonella, were assessed to determine if spice and herb quality was affected. Black peppercorn, cumin seed, oregano, and onion powder were irradiated to a target dose of 8 kGy. Two additional processes were examined for whole black peppercorns and cumin seeds: ethylene oxide (EtO) fumigation and vacuum assisted-steam (82.22 °C, 7.5 psia). Treated and untreated spices/herbs were compared (visual, odor) using sensory similarity testing protocols (α = 0.20; β = 0.05; proportion of discriminators: 20%) to determine if processing altered sensory quality. Analytical assessment of quality (color, water activity, and volatile chemistry) was completed. Irradiation did not alter visual or odor sensory quality of black peppercorn, cumin seed, or oregano but created differences in onion powder, which was lighter (higher L * ) and more red (higher a * ) in color, and resulted in nearly complete loss of measured volatile compounds. EtO processing did not create detectable odor or appearance differences in black peppercorn; however visual and odor sensory quality differences, supported by changes in color (higher b * ; lower L * ) and increased concentrations of most volatiles, were detected for cumin seeds. Steam processing of black peppercorn resulted in perceptible odor differences, supported by increased concentration of monoterpene volatiles and loss of all sesquiterpenes; only visual differences were noted for cumin seed. An important step in process validation is the verification that no effect is detectable from a sensory perspective. © 2017 The Authors. Journal of Food Science published by Wiley Periodicals, Inc. on behalf of Institute of Food Technologists.

A bio-molecular inspired electronic architecture: bio-based device concepts for enhanced sensing (Invited Paper)

NASA Astrophysics Data System (ADS)

Woolard, Dwight L.; Luo, Ying; Gelmont, Boris L.; Globus, Tatiana; Jensen, James O.

2005-05-01

A biological(bio)-molecular inspired electronic architecture is presented that offers the potential for defining nanoscale sensor platforms with enhanced capabilities for sensing terahertz (THz) frequency bio-signatures. This architecture makes strategic use of integrated biological elements to enable communication and high-level function within densely-packed nanoelectronic systems. In particular, this architecture introduces a new paradigm for establishing hybrid Electro-THz-Optical (ETO) communication channels where the THz-frequency spectral characteristics that are uniquely associated with the embedded bio-molecules are utilized directly. Since the functionality of this architecture is built upon the spectral characteristics of bio-molecules, this immediately allows for defining new methods for enhanced sensing of THz bio-signatures. First, this integrated sensor concept greatly facilitates the collection of THz bio-signatures associated with embedded bio-molecules via interactions with the time-dependent signals propagating through the nanoelectronic circuit. Second, it leads to a new Multi-State Spectral Sensing (MS3) approach where bio-signature information can be collected from multiple metastable state conformations. This paper will also introduce a new class of prototype devices that utilize THz-sensitive bio-molecules to achieve molecular-level sensing and functionality. Here, new simulation results are presented for a class of bio-molecular components that exhibit the prescribed type of ETO characteristics required for realizing integrated sensor platforms. Most noteworthy, this research derives THz spectral bio-signatures for organic molecules that are amenable to photo-induced metastable-state conformations and establishes an initial scientific foundation and design blueprint for an enhanced THz bio-signature sensing capability.

Dissecting the Role of CHITINASE-LIKE1 in Nitrate-Dependent Changes in Root Architecture1[C][W

PubMed Central

Hermans, Christian; Porco, Silvana; Vandenbussche, Filip; Gille, Sascha; De Pessemier, Jérôme; Van Der Straeten, Dominique; Verbruggen, Nathalie; Bush, Daniel R.

2011-01-01

The root phenotype of an Arabidopsis (Arabidopsis thaliana) mutant of CHITINASE-LIKE1 (CTL1), called arm (for anion-related root morphology), was previously shown to be conditional on growth on high nitrate, chloride, or sucrose. Mutants grown under restrictive conditions displayed inhibition of primary root growth, radial swelling, proliferation of lateral roots, and increased root hair density. We found here that the spatial pattern of CTL1 expression was mainly in the root and root tips during seedling development and that the protein localized to the cell wall. Fourier-transform infrared microspectroscopy of mutant root tissues indicated differences in spectra assigned to linkages in cellulose and pectin. Indeed, root cell wall polymer composition analysis revealed that the arm mutant contained less crystalline cellulose and reduced methylesterification of pectins. We also explored the implication of growth regulators on the phenotype of the mutant response to the nitrate supply. Exogenous abscisic acid application inhibited more drastically primary root growth in the arm mutant but failed to repress lateral branching compared with the wild type. Cytokinin levels were higher in the arm root, but there were no changes in mitotic activity, suggesting that cytokinin is not directly involved in the mutant phenotype. Ethylene production was higher in arm but inversely proportional to the nitrate concentration in the medium. Interestingly, eto2 and eto3 ethylene overproduction mutants mimicked some of the conditional root characteristics of the arm mutant on high nitrate. Our data suggest that ethylene may be involved in the arm mutant phenotype, albeit indirectly, rather than functioning as a primary signal. PMID:21949212

Myeloid leukemia factor is a conserved regulator of RUNX transcription factor activity involved in hematopoiesis

PubMed Central

Bras, Stéphanie; Martin-Lannerée, Séverine; Gobert, Vanessa; Augé, Benoît; Breig, Osman; Sanial, Matthieu; Yamaguchi, Masamitsu; Haenlin, Marc; Plessis, Anne; Waltzer, Lucas

2012-01-01

Defining the function of the genes that, like RUNX1, are deregulated in blood cell malignancies represents an important challenge. Myeloid leukemia factors (MLFs) constitute a poorly characterized family of conserved proteins whose founding member, MLF1, has been associated with acute myeloid leukemia in humans. To gain insight into the functions of this family, we investigated the role of the Drosophila MLF homolog during blood cell development. Here we report that mlf controls the homeostasis of the Drosophila hematopoietic system. Notably, mlf participates in a positive feedback loop to fine tune the activity of the RUNX transcription factor Lozenge (LZ) during development of the crystal cells, one of the two main blood cell lineages in Drosophila. At the molecular level, our data in cell cultures and in vivo strongly suggest that MLF controls the number of crystal cells by protecting LZ from degradation. Remarkably, it appears that the human MLF1 protein can substitute for MLF in the crystal cell lineage. In addition, MLF stabilizes the human oncogenic fusion protein RUNX1-ETO and is required for RUNX1-ETO–induced blood cell disorders in a Drosophila model of leukemia. Finally, using the human leukemic blood cell line Kasumi-1, we show that MLF1 depletion impairs RUNX1-ETO accumulation and reduces RUNX1-ETO–dependent proliferation. Thus, we propose that the regulation of RUNX protein levels is a conserved feature of MLF family members that could be critical for normal and pathological blood cell development. PMID:22411814

Transpiration Demand in Southern California Oak Woodlands: Making the Leap from Lab and Individual Tree to Watershed Scale

NASA Astrophysics Data System (ADS)

Weinberger, J. L.; Quinlan, P. T.; Martin, J.; Tartakovsky, D. M.

2013-12-01

Watershed scale estimates of evapotranspiration (ET) have proven difficult to quantify in areas of native vegetation with uncertain or unknown crop coefficients. In this study, we evaluate the water use in Quercus engelmanni and Quercus agrifolia, two species of oak native to Southern California. Thermal dissipation probes (TDPs) were installed at four locations within a 14,500 acre watershed, comprising 770 acres of Q. agrifolia woodland and 2440 acres of Q. engelmanni woodland. Installation duration ranged from 6 weeks to 14 months. The TDPs were calibrated to each species in the laboratory using limbs ranging from 2 to 5 inches in diameter. Dye was run through each limb at the end of the calibration test in order to establish a relationship between active sapwood area and limb diameter. ET measured in the field for each species was 0.15 to 0.3 times that of the reference evapotranspiration (ETo) derived from the Penman-Monteith equation, with the primary variability in the demand related to measured incident solar radiation. The total water demand for each species is estimated using the laboratory determined relationship between the active sapwood area and the diameter of the limb, and a survey of the tree diameter breast height (DBH) of each tree in the watershed. This study provides new insight into the actual water demand of two native tree species in Southern California and has serious implications for conservation plans, which are often developed using watershed models that apply ETo to all vegetation communities, regardless of actual water demand.

NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

NASA Technical Reports Server (NTRS)

Waters, Eric D.; Garcia, Jessica; Beers, Benjamin; Philips, Alan; Holt, James B.; Threet, Grady E., Jr.

2013-01-01

The Earth to Orbit (ETO) Team of the Advanced Concepts Office (ACO) at NASA Marshal Space Flight Center (MSFC) is considered the preeminent group to go to for prephase A and phase A concept definition. The ACO team has been at the forefront of a multitude of launch vehicle studies determining the future direction of the Agency as a whole due, in part, to their rapid turnaround time in analyzing concepts and their ability to cover broad trade spaces of vehicles in that limited timeframe. Each completed vehicle concept includes a full mass breakdown of each vehicle to tertiary subsystem components, along with a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. Additionally, a structural analysis of the vehicle based on material properties and geometries is performed as well as an analysis to determine the flight loads based on the trajectory outputs. As mentioned, the ACO Earth to Orbit Team prides themselves on their rapid turnaround time and often need to fulfill customer requests within limited schedule or little advanced notice. Due to working in this fast paced environment, the ETO team has developed some finely honed skills and methods to maximize the delivery capability to meet their customer needs. This paper will describe the interfaces between the 3 primary disciplines used in the design process; weights and sizing, trajectory, and structural analysis, as well as the approach each discipline employs to streamline their particular piece of the design process.

Development of a Direct Ethanol Fuel Cell System with Anion Exchange Membranes

DTIC Science & Technology

2015-01-15

1 M NaQH + 0., tot EtoH + 1 mM PO(Ae)2 - Relmmel’$eG In ’ W NaQH + 0 .1 M E’ OH E (Voll&) 2S - 1 MNaai +0.5M BCii - 1 M Naa -1 + 0.5 M EtGI + 1 mM...Pb(Ac)2 - ReiiTITIE’J’SE’d in 1 M Naa -1 + o.5 M EtOH I I O.Oo.20AG.6 0.8 E(Volts) - • t.t NacH + , WElOH _ , WNacH + ’ WElOH + 1 mt.tPO(AC)2

Mathematical Model of the Ear’s Response to Weapons Impulses

DTIC Science & Technology

2015-04-01

A-weighted energy, eto .) produce the same ordering of effect. In this paper we will describe the models used for each of the elements in this...of tube. k = 2*PI*f/c , wavenumber of waves in tube. f = frequency in Hz. 139 Fig. 2 shows both a schematic diagram of the ear model along with...u’" ~ -10 M .. 58 ••• • ~ .. • " .. li 15 -29 40 .tK ! K !SK .tK gj -120 48 b ill d ... ~ .. .. E -130 • E 30 ~~ iil • ~ • tal ~-140 20

FAA Aviation Forecasts, Fiscal Years 1981-1992

DTIC Science & Technology

1980-09-01

34" 0 -~~ < ~ -<. .• • • 1at1 Sep;ember 1980 . ; I f’,AA LEV· ~=~~ ~ ~ l~i; n Forecasts Fiscal Years 1981-1992 I!:-, I )r• p ulll\\1𔃻...212. No. of Pages 22. Prie Unclassified ] Unclassified 69 /V 0 Neil E. Goldschmidt, T Secretary, Department of Transportation _ o Langhorne Bond...percentTese lareficraft are poing ar eto above 1979 levels at 2.1 billion miles according toT h e s e la rg e r a irc ra f t a re p ro v in g a tt ra

Effects of Trypanocidal Drugs on the Function of Trypanosomes.

DTIC Science & Technology

1978-09-01

trtod) -Odr__primary results during this past year are: a. 7 tbihdtosriso rpnooabue T rciETO10 n T. brucel 427) in vitro as cultured infective...A 174 .I A -V. A, A’ ~ ~ hA 4 T. brucel 0--a BERENIL TRE:ATEO, 5 mg/kg 0-4 CONTROL 20.0- 10.0: 8.0- 4 .0- 0 I- 1.0 - HOURS Figure 22 t7 d **VI Figure...URIDINE INCORPORATION 14- 12- CONTROL 0 E I- I- ETHIDIUM O BROMIDE 4 6 ANTRYCIDE 2 BERENIL SURAMIN 0 10 20 30 40 50 60 MINUTES Figure 29 T. brucel

Specification, Validation and Verification of Mobile Application Behavior

DTIC Science & Technology

2013-03-01

VALIDATION AND VERIFICATION OF MOBILE APPLICATION BEHAVIOR by Christopher B. Bonine March 2013 Thesis Advisor: Man-Tak Shing Thesis Co...NUMBERS 6. AUTHOR(S) Christopher B. Bonine 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School Monterey, CA 93943–5000 8...VALIDATION AND VERIFICATION OF MOBILE APPLICATION BEHAVIOR Christopher B. Bonine Lieutenant, United States Navy B.S. Southern Polytechnic State

Organizing Chaos: The Tactical Assault Kit Collaborative Mission Planner

DTIC Science & Technology

2018-12-01

choice. Case studies , such as the 2017 Presidential Inauguration Collective Security Event, Operation Flaming Sword 2017, and the counter-ISIS campaign...rallied around the Tactical Assault Kit (TAK) as their mission command tool of choice. Case studies , such as the 2017 Presidential Inauguration...authorities ADA Air Defense Artillery ADM Army Design Methodology ADAPT Advanced Digital Advisor Partner Technologies ATAK Android Tactical Assault Kit

Academic Accountability in Texas Public Schools: 2003-2007

ERIC Educational Resources Information Center

Jaska, Patrick; Hogan, Patrick; Wen, Zhezhu

2009-01-01

This study examines factors affecting test scores in a sample of thirty-seven Texas public high schools from 2003 to 2007 since the implementation of the No Child Left Behind (NCLB) Act of 2001. The schools were chosen based upon similar tax rates and district sizes. The Texas Assessment of Knowledge and Skills (TAKS) test was implemented in 2003…

Sealift and the U.S. Merchant Marine: Vulnerabilities and Implications For Defense

DTIC Science & Technology

1993-12-01

ships with high endurance and enhanced cargo -carrying capacity. As a result of these...gasoline tankers (T-AOG), fleet oilers (T-AO), and multi- purpose cargo ships (T-AK/ AKR ). 2. Maritime Prepositioning Ships Over a decade has passed... cargo carried to Vietnam during this period, twenty-six percent 18 A "system" refers to the method of loading or unloading cargo for a particular ship

Department of Defense Dictionary of Military and Associated Terms

DTIC Science & Technology

2008-05-30

cargo on board a ship for the purpose of accomplishing en route maintenance and security. supersonic — Of or pertaining to speed ...information systems TAK cargo ship T- AKR fast logistics ship TALCE tanker airlift control element Appendix A As Amended Through 30 May 2008...priorities committee — (*) A committee set up to determine the priorities of passengers and cargo . air raid reporting control ship — (*) A

Lagrangian Mixing in an Axisymmetric Hurricane Model

DTIC Science & Technology

2010-07-23

The MMR r is found by tak - ing the log of the time-series 6ρ(t)−A1, where A1 is 90% of the minimum value of6ρ(t), and the slope of the linear func...Advective mixing in a nondivergent barotropic hurricane model, Atmos. Chem. Phys., 10, 475 –497, doi:10.5194/acp-10- 475 -2010, 2010. Salman, H., Ide, K

Transforming growth factor-beta1 transcriptionally activates CD34 and prevents induced differentiation of TF-1 cells in the absence of any cell-cycle effects.

PubMed

Marone, M; Scambia, G; Bonanno, G; Rutella, S; de Ritis, D; Guidi, F; Leone, G; Pierelli, L

2002-01-01

A number of cytokines modulate self-renewal and differentiation of hematopoietic elements. Among these is transforming growth factor beta1 (TGF-beta1), which regulates cell cycle and differentiation of hematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has been previously shown by us and other authors that TGF-beta1 maintains human CD34(+) hematopoietic progenitors in an undifferentiated state, independently of any cell cycle effects, and that depletion of TGF-beta1 triggers differentiation accompanied by a decrease in CD34 antigen expression. In the present work, we show that exogenous TGF-beta1 upregulates the human CD34 antigen in the CD34(+) cell lines TF-1 and KG-1a, but not in the more differentiated CD34(-) cell lines HL-60 and K-562. We further studied this effect in the pluripotent erythroleukemia cell line TF-1. Here, TGF-beta1 did not effect cell growth, but induced transcriptional activation of full-length CD34 and prevented differentiation induced by differentiating agents. This effect was associated with nuclear translocation of Smad-2, activation of TAK-1, and with a dramatic decrease in p38 phosphorylation. In other systems TGF-beta1 has been shown to activate a TGF-beta-activated kinase 1 (TAK1), which in turn, activates p38. The specific inhibitor of p38 phosphorylation, SB202190, also increased CD34 RNA expression, indicating the existence of a link between p-38 inhibition by TGF-beta1 and CD34 overexpression. Our data demonstrate that TGF-beta1 transcriptionally activates CD34 and prevents differentiation of TF-1 cells by acting independently through the Smad, TAK1 and p38 pathways, and thus provide important clues for the understanding of hematopoietic development and a potential tool to modify response of hematopoietic cells to mitogens or differentiating agents.

Angiotensin II increases CTGF expression via MAPKs/TGF-{beta}1/TRAF6 pathway in atrial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, Jun; Liu, Xu, E-mail: xkliuxu@yahoo.cn; Wang, Quan-xing, E-mail: shmywqx@126.com

2012-10-01

The activation of transforming growth factor-{beta}1(TGF-{beta}1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGF{beta}1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGF{beta}-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-{beta}1/non-Smad signaling pathways. In the present study, we explored the role of TGF-{beta}1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1 {mu}M) provoked the activation of P38 mitogen activated proteinmore » kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1 {mu}M) also promoted TGF{beta}1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGF{beta}1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGF{beta}1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis. -- Highlights: Black-Right-Pointing-Pointer MAPKs/TGF{beta}1/TRAF6 participates in AngII-induced CTGF expression in atrial fibroblasts. Black-Right-Pointing-Pointer TGF{beta}1/TRAF6 participates in AngII-induced atrial fibroblasts proliferation. Black-Right-Pointing-Pointer TRAF6 may represent a new target for reversing Ang II-induced atrial fibrosis.« less

A noncanonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia.

PubMed

Shanmugam, Rajasubramaniam; Gade, Padmaja; Wilson-Weekes, Annique; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A; Baghdadi, Tareq Al; Sargent, Katie J; Cripe, Larry D; Kalvakolanu, Dhananjaya V; Boswell, H Scott

2012-01-15

Death-associated protein kinase 1 (DAPK1), a tumor suppressor, is a rate-limiting effector in an endoplasmic reticulum (ER) stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of acute myeloid leukemia (AML) with poor prognosis, which lacked ER stress-induced apoptosis. Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB-and c-Jun-responsive genes, was studied. RNA interference knockdown studies were carried out in an Flt3ITD(+) cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were carried out to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. AMLs characterized by normal karyotype with Flt3ITD were found to have 10- to 100-fold lower DAPK1 transcripts normalized to the expression of c-Jun, a transcriptional activator of DAPK1, as compared with a heterogeneous cytogenetic category. In addition, Meis1, a c-Jun-responsive adverse AML prognostic gene signature was measured as control. These Flt3ITD(+) AMLs overexpress relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter together with histone deacetylase 2 (HDAC2) and HDAC6 in the Flt3ITD(+) human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NF-κB-inducing kinase (NIK), de-repressed DAPK1. DAPK1-repressed primary Flt3ITD(+) AMLs had selective nuclear activation of p52NF-κB. Flt3ITD promotes a noncanonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD(+) AML. ©2011 AACR.

A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

PubMed Central

Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

2014-01-01

Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

Synthesis of a Novel Polyethoxysilsesquiazane and Thermal Conversion into Ternary Silicon Oxynitride Ceramics with Enhanced Thermal Stability

PubMed Central

Iwase, Yoshiaki; Horie, Yoji; Daiko, Yusuke; Honda, Sawao

2017-01-01

A novel polyethoxysilsesquiazane ([EtOSi(NH)1.5]n, EtOSZ) was synthesized by ammonolysis at −78 °C of ethoxytrichlorosilane (EtOSiCl3), which was isolated by distillation as a reaction product of SiCl4 and EtOH. Attenuated total reflection-infra red (ATR-IR), 13C-, and 29Si-nuclear magnetic resonance (NMR) spectroscopic analyses of the ammonolysis product resulted in the detection of Si–NH–Si linkage and EtO group. The simultaneous thermogravimetric and mass spectrometry analyses of the EtOSZ under helium revealed cleavage of oxygen-carbon bond of the EtO group to evolve ethylene as a main gaseous species formed in-situ, which lead to the formation at 800 °C of quaternary amorphous Si–C–N with an extremely low carbon content (1.1 wt %) when compared to the theoretical EtOSZ (25.1 wt %). Subsequent heat treatment up to 1400 °C in N2 lead to the formation of X-ray amorphous ternary Si–O–N. Further heating to 1600 °C in N2 promoted crystallization and phase partitioning to afford Si2N2O nanocrystallites identified by the XRD and TEM analyses. The thermal stability up to 1400 °C of the amorphous state achieved for the ternary Si-O-N was further studied by chemical composition analysis, as well as X-ray photoelectron spectroscopy (XPS) and 29Si-NMR spectroscopic analyses, and the results were discussed aiming to develop a novel polymeric precursor for ternary amorphous Si–O–N ceramics with an enhanced thermal stability. PMID:29206217

Cost-Utility of Competing Strategies to Prevent Endoscopic Transmission of Carbapenem-Resistant Enterobacteriaceae

PubMed Central

Almario, Christopher V.; May, Folasade P.; Shaheen, Nicholas J.; Murthy, Rekha; Gupta, Kapil; Jamil, Laith H.; Lo, Simon K.; Spiegel, Brennan M.R.

2015-01-01

OBJECTIVES Prior reports have linked patient transmission of carbapenem-resistant Enterobacteriaceae (CRE, or “superbug”) to endoscopes used during endoscopic retrograde cholangiopancreatography (ERCP). We performed a decision analysis to measure the cost-effectiveness of four competing strategies for CRE risk management. METHODS We used decision analysis to calculate the cost-effectiveness of four approaches to reduce the risk of CRE transmission among patients presenting to the hospital for symptomatic common bile duct stones. The strategies included: (1) perform ERCP followed by U.S. Food and Drug Administration (FDA)-recommended endoscope reprocessing procedures; (2) perform ERCP followed by “endoscope culture and hold”; (3) perform ERCP followed by ethylene oxide (EtO) sterilization of the endoscope; and (4) stop performing ERCP in lieu of laparoscopic cholecystectomy (LC) with common bile duct exploration (CBDE). Our outcome was incremental cost per quality-adjusted life year (QALY) gained. RESULTS In the base-case scenario, ERCP with FDA-recommended endoscope reprocessing was the most cost-effective strategy. Both the ERCP with culture and hold ($4,228,170/QALY) and ERCP with EtO sterilization ($50,572,348/QALY) strategies had unacceptable incremental costs per QALY gained. LC with CBDE was dominated, being both more costly and marginally less effective versus the alternatives. In sensitivity analysis, ERCP with culture and hold became the most cost-effective approach when the pretest probability of CRE exceeded 24%. CONCLUSIONS In institutions with a low CRE prevalence, ERCP with FDA-recommended reprocessing is the most cost-effective approach for mitigating CRE transmission risk. Only in settings with an extremely high CRE prevalence did ERCP with culture and hold become cost-effective. PMID:26526083

Performance of conducting polymer electrodes for stimulating neuroprosthetics

NASA Astrophysics Data System (ADS)

Green, R. A.; Matteucci, P. B.; Hassarati, R. T.; Giraud, B.; Dodds, C. W. D.; Chen, S.; Byrnes-Preston, P. J.; Suaning, G. J.; Poole-Warren, L. A.; Lovell, N. H.

2013-02-01

Objective. Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. Approach. PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. Main results. It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. Significance. These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

A method to assess the migration properties of cell-derived microparticles within a living tissue.

PubMed

Hoang, Thang Q; Rampon, Christine; Freyssinet, Jean-Marie; Vriz, Sophie; Kerbiriou-Nabias, Danièle

2011-09-01

Cells undergoing activation or apoptosis exhibit plasma membrane changes, leading to the formation of shed vesicles (microparticles, MP). Although their effects on recipient cells in vitro, and their ability to support inflammatory or thrombotic events in the circulation have been studied, the spreading of such vesicles in tissues is still elusive. Our aim was to set up a method to examine the behavior of these vesicles in vivo. We examined the persistence of green-fluorescent microparticles (fMP), prepared after Ca2+ ionophore activation (iono-fMP) or apoptogenic treatment (eto-fMP) of human Jurkat T lymphoblastic or non-hematopoietic embryonic kidney (HEK) cell lines, following injection in zebrafish embryos 2h after egg fertilization. One hour post-injection, iono-fMP issued from both cell types formed a fluorescent dispersal in the intercellular space of embryos. In contrast, eto-fMP or MP deprived of sialic acid at their membrane, gathered together at the site of injection. We propose a method characterizing the abilities of MP to spread in the intercellular space. We showed that MP produced by apoptosis of T cells and those deprived of sialic acid at their membrane do not diffuse within the living cells. On the contrary, MP shed upon calcium induced activation of T and HEK cells, diffuse at a distance and spread in the intercellular space. The fate of injected MP relies on the type of induction rather than the cell species and results provide a model to test the ability of vesicles to interact locally or to spread outside of the site of production. Copyright © 2011 Elsevier B.V. All rights reserved.

Sterilization processes. Meeting the demands of today's health care technology.

PubMed

Crow, S

1993-09-01

Universal Precautions dictate sterilization for all invasive equipment that break the blood barrier; however, current methods of sterilization, such as steam and ethylene oxide gas (ETO), are not compatible with many of the delicate, heat-sensitive surgical instruments used in modern health care. In addition, traditional sterilization methods are often too time consuming for practical use in the operating room. Clearly, new sterilization processes need to be developed. In this article, the criteria modern sterilization processes must meet and how some manufacturers plan to meet this challenge are discussed. In addition, the pros and cons of using peracetic acid (the newest sterilization process currently available) are examined.

Air Emissions Guide for Air Force Mobile Sources: Methods for Estimating Emissions of Air Pollutants for Mobile Sources at U.S. Air Force Installations

DTIC Science & Technology

2013-01-01

Environmental Impact Statement EtO Ethylene Oxide EOD Explosive Ordnance Disposal EPA Environmental Protection Agency EPAct Energy Policy Act EPCRA...5.36 0.53 --- 0.26 0.23 Idle (Taxi) 7% 143 1.83 1.06 183.80 61.52 --- 1.38 1.24 Approach 30% 364 4.59 1.06 20.96 3.24 --- 0.72 0.65 Intermediate 70% 619...2.39 2.15 Flight Idle --- 143 3.08 1.06 30.71 8.65 --- 2.38 2.14 Cruise --- 283 4.90 1.06 2.64 0.18 --- 2.40 2.16 Military --- 412 6.68 1.06 0.75 0.13

Integration of Experience API Into CDET’s E-Learning

DTIC Science & Technology

2016-06-01

based on customers ’ actual usage on a transaction basis. Value-based Penetration Pricing • Market segments where buyers have high price...they need to accomplish the course learning objectives (see Figure 6). This method allows each student to customize their own learning experiences ... EXPERIENCE API INTO CDET’S E- LEARNING by Clayton C. MacAloney June 2016 Thesis Advisor: Man-Tak Shing Co-Advisor: Arijit Das THIS PAGE

Six New Species of the Culex (Lophoceraomyia) Mammilifer Group from Thailand (Diptera: Culicidae)

DTIC Science & Technology

1967-03-01

Distribution. Known only from the following Provinces in Thai- land: Tak, Nakhon Nayok, and Chiang Mai . Eleven individual c Fig. 2, Culer...Distribution. The authors have seen specimens from the following Provinces in Thailand: Trang, Chiang Mai , Sara Buri, Narathiwat, Phatthalung...male with terminalia and antennae slide mounted from Doi Sutep, Chiang Mai Province, Thailand, 7. I. 53, D. C. and E. B. Thurman, deposited in the U

Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beane, Olivia S.; Fonseca, Vera C.; Darling, Eric M., E-mail: Eric_Darling@brown.edu

In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascularmore » fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

Estimating riparian and agricultural evapotranspiration by reference crop evapotranspiration and MODIS Enhanced Vegetation Index

USGS Publications Warehouse

Nagler, Pamela L.; Glenn, Edward P.; Nguyen, Uyen; Scott, Russell; Doody, Tania

2013-01-01

Dryland river basins frequently support both irrigated agriculture and riparian vegetation and remote sensing methods are needed to monitor water use by both crops and natural vegetation in irrigation districts. We developed an algorithm for estimating actual evapotranspiration (ETa) based on the Enhanced Vegetation Index (EVI) from the Moderate Resolution Imaging Spectrometer (MODIS) sensor on the EOS-1 Terra satellite and locally-derived measurements of reference crop ET (ETo). The algorithm was calibrated with five years of ETa data from three eddy covariance flux towers set in riparian plant associations on the upper San Pedro River, Arizona, supplemented with ETa data for alfalfa and cotton from the literature. The algorithm was based on an equation of the form ETa = ETo [a(1 − e−bEVI) − c], where the term (1 − e−bEVI) is derived from the Beer-Lambert Law to express light absorption by a canopy, with EVI replacing leaf area index as an estimate of the density of light-absorbing units. The resulting algorithm capably predicted ETa across riparian plants and crops (r2 = 0.73). It was then tested against water balance data for five irrigation districts and flux tower data for two riparian zones for which season-long or multi-year ETa data were available. Predictions were within 10% of measured results in each case, with a non-significant (P = 0.89) difference between mean measured and modeled ETa of 5.4% over all validation sites. Validation and calibration data sets were combined to present a final predictive equation for application across crops and riparian plant associations for monitoring individual irrigation districts or for conducting global water use assessments of mixed agricultural and riparian biomes.

Evaluation of different methods to estimate daily reference evapotranspiration in ungauged basins in Southern Brazil

NASA Astrophysics Data System (ADS)

Ribeiro Fontoura, Jessica; Allasia, Daniel; Herbstrith Froemming, Gabriel; Freitas Ferreira, Pedro; Tassi, Rutineia

2016-04-01

Evapotranspiration is a key process of hydrological cycle and a sole term that links land surface water balance and land surface energy balance. Due to the higher information requirements of the Penman-Monteith method and the existing data uncertainty, simplified empirical methods for calculating potential and actual evapotranspiration are widely used in hydrological models. This is especially important in Brazil, where the monitoring of meteorological data is precarious. In this study were compared different methods for estimating evapotranspiration for Rio Grande do Sul, the Southernmost State of Brazil, aiming to suggest alternatives to the recommended method (Penman-Monteith-FAO 56) for estimate daily reference evapotranspiration (ETo) when meteorological data is missing or not available. The input dataset included daily and hourly-observed data from conventional and automatic weather stations respectively maintained by the National Weather Institute of Brazil (INMET) from the period of 1 January 2007 to 31 January 2010. Dataset included maximum temperature (Tmax, °C), minimum temperature (Tmin, °C), mean relative humidity (%), wind speed at 2 m height (u2, m s-1), daily solar radiation (Rs, MJ m- 2) and atmospheric pressure (kPa) that were grouped at daily time-step. Was tested the Food and Agriculture Organization of the United Nations (FAO) Penman-Monteith method (PM) at its full form, against PM assuming missing several variables not normally available in Brazil in order to calculate daily reference ETo. Missing variables were estimated as suggested in FAO56 publication or from climatological means. Furthermore, PM was also compared against the following simplified empirical methods: Hargreaves-Samani, Priestley-Taylor, Mccloud, McGuiness-Bordne, Romanenko, Radiation-Temperature, Tanner-Pelton. The statistical analysis indicates that even if just Tmin and Tmax are available, it is better to use PM estimating missing variables from syntetic data than

Monitoring impacts of Tamarix leaf beetles (Diorhabda elongata) on the leaf phenology and water use of Tamarix spp. using ground and remote sensing methods

NASA Astrophysics Data System (ADS)

Nagler, P. L.; Brown, T.; Hultine, K. R.; van Riper, C.; Bean, D. A.; Murray, R.; Pearlstein, S.; Glenn, E. P.

2010-12-01

Tamarix leaf beetles (Diorhabda elongata) have been released in several locations on western U.S. rivers to control the introduced shrub, Tamarix ramosissima and related species. As they are expanding widely throughout the region, information is needed on their impact on Tamarix leaf phenology and water use over multiple cycles of annual defoliation. We used networked digital cameras (phenocams) and ground surveys to monitor the defoliation process from 2008-2010 at multiple sites on the Dolores River, and MODIS satellite imagery from 2000 to 2009 to monitor leaf phenology and evapotranspiration (ET) at beetle release sites on the Dolores, Lower Colorado, Carson, Walker and Bighorn Rivers. Enhanced Vegetation Index (EVI) values for selected MODIS pixels were used to estimate green foliage density before and after beetle releases at each site. EVI values were transformed into estimates of ET using an empirical algorithm relating ET to EVI and potential ET (ETo) at each site. Phenocam and ground observations show that beetle damage is temporary, and plants regenerate new leaves following an eight week defoliation period in summer. The original biocontrol model predicted that Tamarix mortality would reach 75-85% over several years of defoliation due to progressive weakening of the shrubs each year, but over the early stages of leaf beetle-Tamarix interactions studied here (3-8 years), our preliminary findings show actual reductions in EVI and ET of only 13-15% across sites due to the relatively brief period of defoliation and because not all plants at a site were defoliated. Also, baseline ET rates varied across sites but averaged only 329 mm yr-1 (23% of ETo), constraining the possibilities for water salvage through biocontrol of Tamarix. The spatial and temperol resolution of MODIS imagery were too coarse to capture the details of the defoliation process, and high-resolution imagery or expanded phenocam networks are needed for future monitoring programs.

Extensive radioactive characterization of a phosphogypsum stack in SW Spain: 226Ra, 238U, 210Po concentrations and 222Rn exhalation rate.

PubMed

Abril, José-María; García-Tenorio, Rafael; Manjón, Guillermo

2009-05-30

Phosphogypsum (PG) is a by-product of the phosphate fertilizer industries that contains relatively high concentrations of uranium series radionuclides. The US-EPA regulates the agriculture use of PG, attending to its (226)Ra content and to the (222)Rn exhalation rate from inactive stacks. Measurements of (222)Rn exhalation rates in PG stacks typically show a large and still poorly understood spatial and temporal variability, and the published data are scarce. This work studies an inactive PG stack in SW Spain of about 0.5 km(2) from where PG can be extracted for agriculture uses, and an agriculture soil 75 km apart, being representative of the farms to be amended with PG. Activity concentrations of (226)Ra, (238)U and (210)Po have been measured in 30 PG samples (0-90 cm horizon) allowing for the construction of maps with spatial distributions in the PG stack and for the characterization of the associated PG inputs to agriculture soils. Averaged (226)Ra concentrations for the stack were 730+/-60 Bq kg(-1) (d.w.), over the US-EPA limit of 370 Bq kg(-1). (222)Rn exhalation rate has been measured by the charcoal canister method in 49 sampling points with 3 canisters per sampling point. Values in PG stack were under the US-EPA limit of 2600 Bq m(-2)h(-1), but they were one order of magnitude higher than those found in the agriculture soil. Variability in radon emissions has been studied at different spatial scales. Radon exhalation rates were correlated with (226)Ra concentrations and daily potential evapotranspiration (ETo). They increased with ETo in agriculture soils, but showed an opposite behaviour in the PG stack.

A Virtual World for an Autonomous Underwater Vehicle

DTIC Science & Technology

1994-12-01

LEGIBLY ON BLACK AND WHITE MICROFICHE. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704 Public reporting burden for this collection of information is...event simulation. He and Man-Tak Shing also gave v\\aluable advice on the Ph.D. process. Mike Macedonia’s unparalleled understanding of computer...networks helped make an entire field intelligible. Dave Pratt blazed the trail with NPSNET, still the best virtual world around and still gaining on all

U.S. House of Representatives Committee on Armed Services Panel on Roles and Missions: Initial Perspectives

DTIC Science & Technology

2008-01-01

opinions led Alexander Yakovlev, a principal architect of Mikhail Gorbachev’s perestroika, to bemoan his compatriots’ pen- chant for authoritarian rule...isn’t a communist country anymore. It’s got a different sys- tem: meritocratic paternalism . You joke: Imagine the Ivy League tak- ing over the shell of...long as the reforms never chal- lenge the political order). Most of all, you believe, edu- cated paternalism has delivered the goods. China is

The Realistic Job Preview as a Persuasive Communication.

DTIC Science & Technology

1982-02-01

10. PROGRAM ELEMENT, PROJECT. TAK AREA 6 WORK UNIT NUMBERS Michigan State Uiversity NR 170-894 Ii. CONTROLLING OFFICE NAME AND ADDRESS IS. REPORT...RJP research seems to show a stronger preview effect using more intelligent subjects. That is, studies of life insurance agents (Weitz, 1956; Youngberg...University Department of Psychological Sciences west Lafayette, INl 47907 1 Dr. Philip G. Zi±bardo*2 ~ Staniford Uiversity Department of Psychology Stanford, CA 94305 <El

A Sampling of U.S. Naval Humanitarian Operations.

DTIC Science & Technology

1990-11-01

from the evacuation services to survivors of a Naval Auxiliary Air Station, Fallon, volcano eruption on Miyako Island, Nevada, and from the San...February 1974 aircraft from Midway to Hawaii for treatment. On 13 February 1974, TAK-241 Private Francis X. McCraw rescued six Philippine Sea, September...Pacific, July 1989 Western Atlantic, January 1990 DD-965 Kinkaid and Coast Guard While on a training flight on 25 forces from Hawaii rescued a

NASP - Enabling new space launch options

NASA Astrophysics Data System (ADS)

Froning, David; Gaubatz, William; Mathews, George

1990-10-01

Successful NASP developments in the United States are bringing about the possibility of effective, fully reusable vehicles for transport of people and cargo between earth and space. These developments include: extension of airbreathing propulsion to a much higher speed; densification of propellants for greater energy per unit volume of mass; structures with much greater strength-to-weight at high temperatures; computational advancements that enable more optimal design and integration of airframes, engines and controls; and advances in avionics, robotics, artificial intelligence and automation that enable accomplishment of earth-to-orbit (ETO) operations with much less manpower support and cost. This paper describes the relative magnitude of improvement that these developments may provide.

Transparent EuTiO3 films: a possible two-dimensional magneto-optical device

NASA Astrophysics Data System (ADS)

Bussmann-Holder, Annette; Roleder, Krystian; Stuhlhofer, Benjamin; Logvenov, Gennady; Lazar, Iwona; Soszyński, Andrzej; Koperski, Janusz; Simon, Arndt; Köhler, Jürgen

2017-01-01

The magneto-optical activity of high quality transparent thin films of insulating EuTiO3 (ETO) deposited on a thin SrTiO3 (STO) substrate, both being non-magnetic materials, are demonstrated to be a versatile tool for light modulation. The operating temperature is close to room temperature and allows for multiple device engineering. By using small magnetic fields birefringence of the samples can be switched off and on. Similarly, rotation of the sample in the field can modify its birefringence Δn. In addition, Δn can be increased by a factor of 4 in very modest fields with simultaneously enhancing the operating temperature by almost 100 K.

Operability driven space system concept with high leverage technologies

NASA Astrophysics Data System (ADS)

Woo, Henry H.

1997-01-01

One of the common objectives of future launch and space transfer systems is to achieve low-cost and effective operational capability by automating processes from pre-launch to the end of mission. Hierarchical and integrated mission management, system management, autonomous GN&C, and integrated micro-nano avionics technologies are critical to extend or revitalize the exploitation of space. Essential to space transfer, orbital systems, Earth-To-Orbit (ETO), commercial and military aviation, and planetary systems are these high leverage hardware and software technologies. This paper covers the driving issues, goals, and requirements definition supported with typical concepts and utilization of multi-use technologies. The approach and method results in a practical system architecture and lower level design concepts.

One-range addition theorems for derivatives of Slater-type orbitals.

PubMed

Guseinov, Israfil

2004-06-01

Using addition theorems for STOs introduced by the author with the help of complete orthonormal sets of psi(alpha)-ETOs (Guseinov II (2003) J Mol Model 9:190-194), where alpha=1, 0, -1, -2, ..., a large number of one-range addition theorems for first and second derivatives of STOs are established. These addition theorems are especially useful for computation of multicenter-multielectron integrals over STOs that arise in the Hartree-Fock-Roothaan approximation and also in the Hylleraas function method, which play a significant role for the study of electronic structure and electron-nuclei interaction properties of atoms, molecules, and solids. The relationships obtained are valid for arbitrary quantum numbers, screening constants and location of STOs.

FIRE Science Results 1989

NASA Technical Reports Server (NTRS)

Mcdougal, David S. (Editor)

1990-01-01

FIRE (First ISCCP Regional Experiment) is a U.S. cloud-radiation research program formed in 1984 to increase the basic understanding of cirrus and marine stratocumulus cloud systems, to develop realistic parameterizations for these systems, and to validate and improve ISCCP cloud product retrievals. Presentations of results culminating the first 5 years of FIRE research activities were highlighted. The 1986 Cirrus Intensive Field Observations (IFO), the 1987 Marine Stratocumulus IFO, the Extended Time Observations (ETO), and modeling activities are described. Collaborative efforts involving the comparison of multiple data sets, incorporation of data measurements into modeling activities, validation of ISCCP cloud parameters, and development of parameterization schemes for General Circulation Models (GCMs) are described.

Overview of aerothermodynamic loads definition study

NASA Technical Reports Server (NTRS)

Gaugler, Raymond E.

1991-01-01

The objective of the Aerothermodynamic Loads Definition Study is to develop methods of accurately predicting the operating environment in advanced Earth-to-Orbit (ETO) propulsion systems, such as the Space Shuttle Main Engine (SSME) powerhead. Development of time averaged and time dependent three dimensional viscous computer codes as well as experimental verification and engine diagnostic testing are considered to be essential in achieving that objective. Time-averaged, nonsteady, and transient operating loads must all be well defined in order to accurately predict powerhead life. Described here is work in unsteady heat flow analysis, improved modeling of preburner flow, turbulence modeling for turbomachinery, computation of three dimensional flow with heat transfer, and unsteady viscous multi-blade row turbine analysis.

NASP - Enabling new space launch options

NASA Technical Reports Server (NTRS)

Froning, David; Gaubatz, William; Mathews, George

1990-01-01

Successful NASP developments in the United States are bringing about the possibility of effective, fully reusable vehicles for transport of people and cargo between earth and space. These developments include: extension of airbreathing propulsion to a much higher speed; densification of propellants for greater energy per unit volume of mass; structures with much greater strength-to-weight at high temperatures; computational advancements that enable more optimal design and integration of airframes, engines and controls; and advances in avionics, robotics, artificial intelligence and automation that enable accomplishment of earth-to-orbit (ETO) operations with much less manpower support and cost. This paper describes the relative magnitude of improvement that these developments may provide.

The Correlation of Students' Classroom-Assigned Time Social Networking with TAKS Literacy Scores

ERIC Educational Resources Information Center

Bicknell, Angela

2012-01-01

Education has continued to follow a traditional teaching model which may not prepare students with needed workforce skills. Social networking has been viewed as a technology tool useful for enhancing communication at both the business and educational level. The theory of connectivism underscores the need for social group interaction to provide…

Organic Reactions in Aqueous Media (by Chao-Jun Li and Tak-Hang Chan)

NASA Astrophysics Data System (ADS)

Rosan, Reviewed Alan M.

2000-06-01

This concise book joins the series of Wiley Interscience special topic publications. In seven chapters it selectively reviews the burgeoning literature on organic reactions conducted in water or in aqueous media as a reaction cosolvent, nicely complementing another recent book on the subject by Grieco. Following a short introduction there are six chapters that vary in length from 10 to 50 pages; they cover pericyclic reactions, nucleophilic additions and substitutions, metal-mediated reactions, transition metal-catalyzed reactions, oxidation and reduction reactions, and industrial applications. These chapters, each of which is prefaced with a short provocative quotation, also vary in depth, containing from 11 to more than 180 references. The literature is complete through 1996 and commendably includes citations of original papers by Barbier, Faraday, Frankland, Grignard, Kolbe, Lapworth, and Reformatsky as well as references to selected U.S. and foreign patents and the Russian literature. There is a subject index but no author index. This book is timely and effective. From the title, one might expect a broad discussion of the unique properties of water and water-soluble components (salts, surfactants, etc.) that would be thought to bear on organic reactivity. The first chapter opens by noting that water is the most abundant volatile material in comets and briefly describes those properties that suggest its utility as a solvent or cosolvent, summarizing the potential technical, economic, and environmental advantages. Also described are the remarkable changes in density, conductance, heat capacity, dielectric constant, and ionization constant that accompany the transition to the critical point, but the emphasis here is on the effect of water under non-critical conditions. Discussion of the structure of liquid water and the role of hydrogen bonding in mediating molecular recognition events is abbreviated. In fact, the term "hydrogen bond" is surprisingly absent from the index. The text does not explicitly include a discussion of what has come to be broadly termed biphasic reaction conditions. Understandably, enzymatic reactions are beyond the scope of the presentation. This book has a decidedly applied character with an understated environmental theme, and the authors succinctly present the extraordinary effects of water on the kinetics, efficiency, and stereoselectivity of a large number of diverse reactions. In addition to their emphasis on the historically significant aqueous Diels-Alder reaction, discovered in 1980, and the literature regarding reactions of various nucleophilic organometals, the authors are to be commended for gathering together a wide and diverse body of information: it is clear that many of the examples shown are gems buried among larger bodies of work. Thus the book does an excellent job of culling and surveying a vast amount of data. There is, however, less emphasis on organizing the mechanistic bases underlying these often dramatic effects. For example, the apparent lack of generality of the effect of water on rate and selectivity in pericyclic reactions calls for some theoretical foundation. The singularly effective use of aqueous TlOH in the Suzuki reaction is cited without comment. On the other hand, the authors' concept of a mechanistic triad that incorporates to various degrees anion, radical, or covalent character in the carbon-carbon bond-forming step between various organometals and carbonyl substrates is appealing and suggests the need for future sophisticated experimental design. The most interesting sections are those dealing with synthesis and industrial applications. Unfortunately the latter is also the shortest chapter. The synthetic examples are timely and well chosen and include water-promoted Heck, Stille, Suzuki, and aldol reactions. There is an extensive, highly informative listing and survey of the use of water-soluble phosphines (both achiral and chiral) and an excellent discussion of the diastereoselectivity that often accompanies carbonyl attack by indium, tin, and zinc organometals (Barbier-Grignard reaction). The liberal use, on nearly every page, of clear, detailed drawings enhances the text, and substantive errors are few. Inexplicably, water is described as serving as a presumptive weak Lewis acid (pages 54-55) in the aqueous Mukaiyama reaction. Occasional slips of grammar, spelling, and syntax, including confusion over the difference between media and medium, are relatively minor. Some expressions, such as "olefinated", are unfortunate and there are several mysterious changes in font. This is not a textbook and no problems are offered. Many technical advances, some occurring since this book was published, have impacted the economic and environmental advantages of water. However, these more recent findings, involving the use of triphase aqueous-fluorous-organic systems, the discovery of living homogeneous ROMP catalysis in water, the utilization of supercritical water oxidation for toxic cleanup, and the utility of biphasic supercritical carbon dioxide-water emulsions, can be appreciated within the broad scope of reactivity described here. With the emerging wide interest, technical feasibility, and rapid innovative advances and an increasingly vast literature in this area, this book is most useful as a selected compendium rather than a definitive treatise. It is certainly suitable as a reference in a special topics or an advanced course. Rich with well-explicated examples and reactions, it is an invitingly readable and valuable survey of this fascinating area.

The impact of a science-based integrated instructional protocol on the motivation, reading comprehension, and science achievement of fourth and fifth graders

NASA Astrophysics Data System (ADS)

Stephens, Kathy E.

The purpose of this study was to determine the impact of implementing an integrated instructional protocol of science-based informational texts as teacher read alouds, student independent reading, and written journal responses on motivation, reading comprehension, and science achievement of fourth- and fifth-grade students with attention to specific student groups, including gender and ethnicities. A mixed methods research design included a 12-week intervention conducted with 68 fourth and fifth graders and 30 nonintervention fourth and fifth graders. Participating fourth and fifth graders completed the comprehension subtest of the Gates-MacGinitie Reading Test ([GMRT] MacGinitie, MacGinitie, Maria, & Dreyer, 2000) and the Texas Assessment of Knowledge and Skills ([TAKS] Texas Education Agency [TEA], 2005a). The Reading Survey of the Motivation to Read Profile ([MRP], Gambrell, Palmer, Codling, & Mazzoni, 1996) served as another quantitative data source. Qualitative data sources included classroom observations, key informant interviews, and student journal entries. The GMRT results indicated that the intervention fourth graders demonstrated the largest growth in reading comprehension achievement. Significant differences were noted by GMRT results between the intervention and nonintervention fourth graders. A significant difference was found between fourth-grade males and females on the GMRT, with a larger gain posted by the females. No significant differences were found on the GMRT in fifth grade Reading TAKS results indicated a significant difference between intervention fourth-grade Hispanic and African American students, while fifth-grade Science TAKS results indicated no significant differences. The MRP Reading Survey results indicated no significant differences; however, fourth-grade Hispanic and fifth-grade male students demonstrated significant growth. Classroom observations documented the progress of the 12-week intervention; 9 primary instructional and

A Survey of Data-Base Information Systems Relevant to Navy Requirements Planning

DTIC Science & Technology

1983-02-01

SHIPS \\ AK (FEM) T-AK (FEM) AKD/T-AKO _" ’ AKL/T-AKL AKM MULTIPURPOSE CAR 0 SHI’’S AKR VEHICLE CARGO SHIPS . -■, AK3 ANL AO OILER AC • NEW...the most demanding condition of operation for which a ship must be manned. ( a ) At sea in wartime. (b) Capable of performing all offensive... ship , and aircraft) researchers and others could quickly obtain basic information. 3. The Navy currently maintains a number of related

Sub-Saharan Africa Report, No. 2830

DTIC Science & Technology

1983-08-12

proceeds abroad and earn in- come. This scheme would require suffi- cient forex reserves. It would provide a counter revenue which could be set...also as- sisted our credit rating. Forex controls Your Money: Is there a benchmark gold price for the lifting of foreign exchange controls? Dc...first and lest it before tak- ing the next step. Your Money: The lift- ing of forex controls could lead to a vola- tile exchange rate. De Loor

The Nature of Expansion of Paget’s Disease of Bone

DTIC Science & Technology

2013-04-01

SQSTM1 mutant PDB samples. Two exogenous stimulators of the TLR signaling pathway are shown: MV – measles virus and LPS – Lipopolysaccharide. A...stimulation by Interleukins (ILs), LPS or measles , leads to ubiquitination of TRAF6 and binding of the ubiquitinated TRAF6 to the TAB2/TAK1 complex, which... measles virus in the delay of onset of PDB. 11 Conclusion Our laboratory has shown that SQSTM1 mutations also occur in the affected bone of PDB

Aerodynamic Characteristics of Airfoils. Volume 4.

DTIC Science & Technology

1927-01-01

8-6-4 -2 02a46 a 10 12 14 16is 20 2Angie of Attack in Degrees. Angle of Attack in Deprese . I~r xi N . A rxi (𔃺\\I ) M ITTll IK’ FORi AERONAUT~ICS RFM...8217 ~ 86--20a2 46 a10 12 14 163826 D Aogle of Attack in Deprese . Angle of it tak in Deprese . A II~ il A CHC ARACTERIISTICS OF Al RFOILS-i V 205 nzmuRRCS

The effect of curriculum changes and instructional techniques on science-reasoning skills among high school students

NASA Astrophysics Data System (ADS)

Newman, Joan T.

Any change, particularly on a large scale like a sequence change in a district with 75,000 students, is difficult. However, with the advent of the new TAKS science test and the new requirements for high school graduation in the state of Texas, educators and students alike are engaged in innovative educational approaches to meet these requirements. This study investigated a different, non-traditional science sequence to investigate relationships among secondary core-science course sequencing, student science-reasoning performance, and classroom pedagogy. The methodology adopted in the study led to a deeper understanding of the successes and challenges faced by teachers in teaching conceptual physics and chemistry to 8 th and 9th grade students. The qualitative analysis suggested a difference in pedagogy employed by middle and high school science teachers and a need for secondary science teachers to enhance their content knowledge and pedagogical skills, as well as change their underlying attitudes and beliefs about the abilities of students. The study examined scores of 495 randomly chosen students following three different matriculation patterns within one large independent school district. The study indicated that students who follow a sequence with 9th grade IPC generally increase their science-reasoning skills as demonstrated on the 10th grade TAKS science test when these scores are compared with those of students who do not have 9th grade IPC in the science sequence.

Perceptions of leadership and student performance in science from campus leaders in selected high schools

NASA Astrophysics Data System (ADS)

Wilder, Sharon Mae

This naturalistic study focused on the perceptions of leadership and student performance in science from campus leaders in three purposefully selected secondary campuses of ninth through twelfth grades. Each school had experienced an improvement in student passing rates on the science TAKS test that exceeded the state's percent improvement in passing rates for the past three years and had a record of improving science TAKS scores for the period of 2003 to 2008 exceeding fifteen percentage points. The qualitative research technique of multi-case studies design was used. Data was collected through semi-structured, in-depth interviews with four campus leaders from each of the selected schools. These campus leaders included campus administrators, science department chairs, and grade-level team leaders. A framework of transformational leadership was utilized in the analysis of the data generated from the interviews. The perception from the campus leaders was that leadership has a positive impact on student success in science. The findings indicated perceptions of leadership from the campus leaders had certain leadership practices in common. These included (a) clear vision and goals from the campus principal, (b) high performance expectations for teachers and students from administrators and science department leaders, (c) encouragement and support from campus administrators and science department leaders to develop new programs to address problem areas, (d) emphasis on collaborative teams, and (e) open door policy from administrators.

Effect of isopropyl myristate on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserinEffect of isopropyl myristate on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserinretain-->.

PubMed

Zhao, Chunyi; Quan, Peng; Liu, Chao; Li, Qiaoyun; Fang, Liang

2016-11-01

The purpose of this study was to investigate the effect of isopropyl myristate (IPM), a penetration enhancer, on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin. The patches were prepared with DURO-TAK ® 87-2287 as a pressure-sensitive adhesive (PSA) containing 5% ( w / w ) of blonanserin and different concentrations of IPM. An in vitro release experiment was performed and the adhesive performance of the drug-in-adhesive patches with different concentrations of IPM was evaluated by a rolling ball tack test and a shear-adhesion test. The glass transition temperature ( T g ) and rheological parameters of the drug-in-adhesive layers were determined to study the effect of IPM on the mechanical properties of the PSA. The results of the in vitro release experiment showed that the release rate of blonanserin increased with an increasing concentration of IPM. The rolling ball tack test and shear-adhesion test showed decreasing values with increasing IPM concentration. The results were interpreted on the basis of the IPM-induced plasticization of the PSA, as evidenced by a depression of the glass transition temperature and a decrease in the elastic modulus. In conclusion, IPM acted as a plasticizer on DURO-TAK ® 87-2287, and it increased the release of blonanserin and affected the adhesive properties of the PSA.

Investigations on the viscoelastic performance of pressure sensitive adhesives in drug-in-adhesive type transdermal films.

PubMed

Wolff, Hans-Michael; Irsan; Dodou, Kalliopi

2014-08-01

We aimed to investigate the effect of solubility parameter and drug concentration on the rheological behaviour of drug-in-adhesive films intended for transdermal application. Films were prepared over a range of drug concentrations (5%, 10% and 20% w/w) using ibuprofen, benzoic acid, nicotinic acid and lidocaine as model drugs in acrylic (Duro-Tak 87-4287 and Duro-Tak 87900A) or silicone (Bio-PSA 7-4301 and Bio-PSA 7-4302) pressure sensitive adhesives (PSAs). Saturation status of films was determined using light microscopy. Viscoelastic parameters were measured in rheology tests at 32°C. Subsaturated films had lower viscoelastic moduli whereas saturated films had higher moduli than the placebo films and/or a concentration-dependent increase in their modulus. Saturation concentration of each drug in the films was reflected by decreasing/increasing viscoelastic patterns. The viscoelastic windows (VWs) of the adhesive and drug-in-adhesive films clearly depicted the effect of solubility parameter differences, molar concentration of drug in the adhesive film and differences in PSA chemistry. Drug solubility parameters and molar drug concentrations have an impact on rheological patterns and thus on the adhesive performance of tested pressure sensitive adhesives intended for use in transdermal drug delivery systems. Use of the Flory equation in its limiting form was appropriate to predict drug solubility in the tested formulations.

Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an Association.

PubMed

Procop, Gary W; Eng, Charis; Clifford, Alison; Villa-Forte, Alexandra; Calabrese, Leonard H; Roselli, Eric; Svensson, Lars; Johnston, Douglas; Pettersson, Gosta; Soltesz, Edward; Lystad, Lisa; Perry, Julian D; Blandford, Alexander; Wilson, Deborah A; Hoffman, Gary S

2017-01-01

It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen. DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls. Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls.

Investigation of Biological Adhesives and Polyurea Crosslinked Silica-Based Aerogels

NASA Astrophysics Data System (ADS)

Lyons, Laura; Cauble, Meagan; Cole, Judith; Sabri, Firouzeh

2009-11-01

One of the key steps towards developing new technology for nerve repair is to look at the interaction mechanism and strength of biological components with the material under investigation. The existing technology for peripheral nerve repair relies on suturing techniques for attaching and immobilization of the implant. It is also limited to connecting two nerve components only, through a cylindrical-shaped unit which we will refer to as 1-D. The focus of our work is to develop an aerogel-based printed circuit board (PCB) system for precise guidance of multiple (n-D) neuronal components, simultaneously. Here we report on the adhesion strength of sciatic nerve segments removed from cadaver Sprague Dawley rats and the surface of treated and untreated polyurea cross-linked silica-based aerogels. The adhesion strength of the nerve to the aerogel surface was studied under varying environmental conditions as well as surface coating types. The coatings tested were basement membrane extract (BME), Cell Tak, and the combination. Since the mechanism of adhesion to cells and other surfaces is different and non-competing for BME and Cell Tak it is expected that a stronger adhesion should be accomplished by combining these two adhesives. The effect of temperature, nerve elasticity, and ionic concentration on the strength of adhesion was investigated also and will be reported.

Mutagenicity and antimutagenicity of extracts of three spices and a medicinal plant in Thailand.

PubMed

Higashimoto, M; Purintrapiban, J; Kataoka, K; Kinouchi, T; Vinitketkumnuen, U; Akimoto, S; Matsumoto, H; Ohnishi, Y

1993-11-01

Three kinds of spices (caraway, coriander and black pepper seeds) and a medicinal plant called 'tong tak' in Thai (Baliospermum axillar, a species of the spurge family) were fractionated into hot water, methanol and hexane extracts. These extracts were not mutagenic for Salmonella typhimurium strains TA98 and TA100 by the Ames assay. However, when the extracts were treated with nitrite, samples of the water and methanol extracts were mutagenic for strain TA100 without metabolic activation. The mutagenicity of the nitrite-treated methanol and hot water extracts of black pepper was highest (8380 and 22,200 His+ per 0.1 g of spice powder, respectively), and that of the nitrite-treated hot water extracts of caraway and tong tak was moderate. The hot water extracts were examined for their antimutagenic activity against mutagenicity induced by various carcinogens by the Ames assay, using the preincubation technique. The tested samples (equivalent to 1-2 mg of spice powder) reduced the mutagenicity induced by 2.7 nmole (397 ng) of N-methyl-N'-nitro-N-nitrosoguanidine by more than 84%, and that induced by dimethylnitrosamine (1.48 mg) or ICR-170 (10 ng) by 30-60%. However, they did not inhibit the mutagenic activity of 1-nitropyrene, 3-nitrofluoranthene, AF-2, methyl methanesulfonate, N-ethyl-N'-nitro-N-nitrosoguanidine, 2-aminoanthracene, 2-acetylaminofluorene, benzo[a]pyrene or IQ.

Two New Plant-Like Pathways Link Hemoglobin Degradation to Lipid Biogenesis in Falciparum Malaria: Novel Targets for Anti-Malarial Chemotherapy

DTIC Science & Technology

2005-03-01

when the compound was added at 50/uM (Appendix VI, B). Furthermore, clofibric acid , an inhibitor of PtdEtn methylransferases (19), had no effect on Pfpmt...reduced when the compound was added at 50 AM (Fig. 5B). Furthermore, clofibric acid , an inhibitor of PtdEtn B 35 methyltransferases (34), had no...Fig. 5B). Furthermore, clofibric acid , an takDs .Shnmn .Jnsn .Coday n .U~a o inhibitor of PtdEtn methyltransferases, had no effect on Pfpmt helpful

The Defence of Duffer’s Drift

DTIC Science & Technology

1905-01-01

w.arned me that my colour -sergeant was waiting for orders. (See Map 2) After a moment’s consideration, I decided to pitch my small camp on a spot just...recognised as my unhappy camera. Here, I suppose, my mind must have slightly wandered, for I found myself re- peating some Latin lines, once my favourite ...patrols returned shortly with their bag of a few men, women and children . The women indulged in much useless abuse, and refused to obey orders, tak- ing

Advanced Distributed Simulation Technology II (ADST-II) Extended Air Defense Testbed Final Report.

DTIC Science & Technology

1997-12-19

dg1044 IDOIM /CUITN Bldg 044 UITN ATM Switch F/O PATCH Mea 3 (e)To IM 1Mb FI SM Meta VR Slave Alt. 1082 lOMb Link ModSAF 3.0 (Pent) Cisco 7200 Router...MoSF .I(et CiscoModSAF 3.0 (Indy) LightStream 1010 100Mb F/O-MM iuBldgy 082aterI n ae ta(ftin ure) on d 1082 p A HJ 155Mb F/O-MM 155Mb F/O-MM T lg 18...STOW BB L 10/100Mb Cat5 1-12 Rpae B S/S Hb SBE-TMI-I T-Net1 - -- Bldg 1082 alternative to allow access to the 10B2 network. This supports continuity

Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by promoter methylation in myeloid leukemia.

PubMed

Niu, Jihong; Li, Henan; Zhang, Yao; Li, Jinlan; Xie, Min; Li, Lingdi; Qin, Xiaoying; Qin, Yazhen; Guo, Xiaohuan; Jiang, Qian; Liu, Yanrong; Chen, Shanshan; Huang, Xiaojun; Han, Wenling; Ruan, Guorui

2011-06-01

CMTM5 has been shown to exhibit tumor suppressor activities, however, its role in leukemia is unclear. Herein we firstly reported the expression and function of CMTM5 in myeloid leukemia. CMTM5 was down-regulated, or undetectable, in leukemia cell lines and bone marrow cells from leukemia patients with promoter methylation. Ectopic expression of CMTM5-v1 strongly inhibited the proliferation of K562 and MEG-01 cells. In addition, significant negative correlations were observed between CMTM5 and three leukemia-specific fusion genes (AML1-ETO, PML-RARα and BCR/ABL1). CMTM5 expression was up-regulated in patients who had undergone treatment. Therefore, CMTM5 may be involved in the pathomechanism of myeloid leukemias. Copyright © 2010 Elsevier Ltd. All rights reserved.

Advanced transportation system studies technical area 3: Alternate propulsion subsystem concepts, volume 3

NASA Technical Reports Server (NTRS)

Levak, Daniel

1993-01-01

The objective of this contract was to provide definition of alternate propulsion systems for both earth-to-orbit (ETO) and in-space vehicles (upper stages and space transfer vehicles). For such propulsion systems, technical data to describe performance, weight, dimensions, etc. was provided along with programmatic information such as cost, schedule, needed facilities, etc. Advanced technology and advanced development needs were determined and provided. This volume separately presents the various program cost estimates that were generated under three tasks: the F-1A Restart Task, the J-2S Restart Task, and the SSME Upper Stage Use Task. The conclusions, technical results, and the program cost estimates are described in more detail in Volume 1 - Executive Summary and in individual Final Task Reports.

Advanced Transportation System Studies. Technical Area 3: Alternate Propulsion Subsystems Concepts. Volume 3; Program Cost Estimates

NASA Technical Reports Server (NTRS)

Levack, Daniel J. H.

2000-01-01

The objective of this contract was to provide definition of alternate propulsion systems for both earth-to-orbit (ETO) and in-space vehicles (upper stages and space transfer vehicles). For such propulsion systems, technical data to describe performance, weight, dimensions, etc. was provided along with programmatic information such as cost, schedule, needed facilities, etc. Advanced technology and advanced development needs were determined and provided. This volume separately presents the various program cost estimates that were generated under three tasks: the F- IA Restart Task, the J-2S Restart Task, and the SSME Upper Stage Use Task. The conclusions, technical results , and the program cost estimates are described in more detail in Volume I - Executive Summary and in individual Final Task Reports.

Bilateral comparison on electric field measurements between TÜBİTAK UME and SASO NMCC

NASA Astrophysics Data System (ADS)

Aslan, Çağlar; Alrobaish, Abdullah M.; Şen, Osman

2017-01-01

Electromagnetic (EM) probes are widely utilized in the measurement of EM fields for non-ionizing radiation, electromagnetic compatibility (EMC) testing and other applications in the frequency range 5 Hz-60 GHz. They must be calibrated by National Metrology Institutes (NMIs) or accredited calibration laboratories in accordance with international standards such as IEEE 1309. The existing NMIs or emerging NMIs should refer to the international comparison measurements in order to assure the quality of their measurement results. Therefore, the electric field comparison measurements organized by TUBITAK UME were performed between TUBITAK UME and SASO NMCC at the 100 Hz, 1 kHz, 10 MHz, 100 MHz, 1 GHz, 10 GHz and 18 GHz frequencies in order to obtain the correction factors of the electric field probes. The comparison measurements were carried out in accordance with the Technical Protocol prepared by TUBITAK UME. The measurements started in October 2017 and were completed in January 2017. There was good agreement found for the correction factors. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

The Effect of Rician Fading and Partial-Band Interference on Noise- Normalized Fast Frequency-Hopped MFSK Receivers

DTIC Science & Technology

1994-03-01

FSK 16. PmCI coot 17. SECURITY CLASSWsAI1OW IL SICUURW CLA$SIICATION SECURITY CLASSIICATION 20. LIMIATION Of ABSTRACT CW REPOW ? OF TiNS PAU OF ...hop k of a symbol when partial-band interference is present is obtained from (11) and the linear transformation of random variables given by (3) as...from (13) and the transformation of random variables indicated by (9) as [16] fzwjm(zwik) = f cTak!X. (Xmk, = ZmkOkI17) f~(0,kdo . -- (,.U(zk’ )fE2

M/V ELIAS Explosion and Fire at Fort Mifflin, PA., on 9 April 1974 with Loss of Life.

DTIC Science & Technology

1977-09-09

above crude oilin acaro tak my beignted t alowr tepertur tha themeaure flash point of a sample of the same cargo. The reason for this anomaly is as...of 72 hours. William CALAFATY Security Guard 715 E. Allegheny Ave . Philadelphia, Pa. 4. The weather at the time of casualty was overcast with good...recess. Ladder steps on the inside of the Imer boundaries of the recesseswere seveiely wasted to a feather edqe at each sten. BEST AV A1ABIE COPY’ 25 g