Tightly integrated single- and multi-crystal data collection strategy calculation and parallelized data processing in JBluIce beamline control system

PubMed Central

Pothineni, Sudhir Babu; Venugopalan, Nagarajan; Ogata, Craig M.; Hilgart, Mark C.; Stepanov, Sergey; Sanishvili, Ruslan; Becker, Michael; Winter, Graeme; Sauter, Nicholas K.; Smith, Janet L.; Fischetti, Robert F.

2014-01-01

The calculation of single- and multi-crystal data collection strategies and a data processing pipeline have been tightly integrated into the macromolecular crystallographic data acquisition and beamline control software JBluIce. Both tasks employ wrapper scripts around existing crystallographic software. JBluIce executes scripts through a distributed resource management system to make efficient use of all available computing resources through parallel processing. The JBluIce single-crystal data collection strategy feature uses a choice of strategy programs to help users rank sample crystals and collect data. The strategy results can be conveniently exported to a data collection run. The JBluIce multi-crystal strategy feature calculates a collection strategy to optimize coverage of reciprocal space in cases where incomplete data are available from previous samples. The JBluIce data processing runs simultaneously with data collection using a choice of data reduction wrappers for integration and scaling of newly collected data, with an option for merging with pre-existing data. Data are processed separately if collected from multiple sites on a crystal or from multiple crystals, then scaled and merged. Results from all strategy and processing calculations are displayed in relevant tabs of JBluIce. PMID:25484844

Tightly integrated single- and multi-crystal data collection strategy calculation and parallelized data processing in JBluIce beamline control system

DOE PAGES

Pothineni, Sudhir Babu; Venugopalan, Nagarajan; Ogata, Craig M.; ...

2014-11-18

The calculation of single- and multi-crystal data collection strategies and a data processing pipeline have been tightly integrated into the macromolecular crystallographic data acquisition and beamline control software JBluIce. Both tasks employ wrapper scripts around existing crystallographic software. JBluIce executes scripts through a distributed resource management system to make efficient use of all available computing resources through parallel processing. The JBluIce single-crystal data collection strategy feature uses a choice of strategy programs to help users rank sample crystals and collect data. The strategy results can be conveniently exported to a data collection run. The JBluIce multi-crystal strategy feature calculates amore » collection strategy to optimize coverage of reciprocal space in cases where incomplete data are available from previous samples. The JBluIce data processing runs simultaneously with data collection using a choice of data reduction wrappers for integration and scaling of newly collected data, with an option for merging with pre-existing data. Data are processed separately if collected from multiple sites on a crystal or from multiple crystals, then scaled and merged. Results from all strategy and processing calculations are displayed in relevant tabs of JBluIce.« less

Women's views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study).

PubMed

Vidler, Marianne; Magee, Laura A; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E; Menzies, Jennifer; Sanchez, Johanna; Singer, Joel; Gafni, Amiram; Gruslin, Andrée; Helewa, Michael; Hutton, Eileen; Lee, Shoo K; Lee, Terry; Logan, Alexander G; Ganzevoort, Wessel; Welch, Ross; Thornton, Jim G; Moutquin, Jean-Marie

2016-11-01

To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412). Quantitative and qualitative analysis of questionnaire responses. International randomised trial (94 sites, 15 countries). 911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85mmHg) or 'less tight' (target diastolic blood pressure, 100mmHg) who completed questionnaires. A questionnaire was administered at ∼6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views. Satisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend. Among the 533 women in 'tight' (N=265) vs. 'less tight' (N=268) control who provided comments for qualitative analysis, women in 'tight' (vs. 'less tight') control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively; p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively; p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in 'tight' control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in 'less tight' control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p≤0.01), and pre-eclampsia (p<0.001). Women in 'tight' (vs. 'less tight') control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Secondary migration and leakage of methane from a major tight-gas system

NASA Astrophysics Data System (ADS)

Wood, James M.; Sanei, Hamed

2016-11-01

Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere.

Secondary migration and leakage of methane from a major tight-gas system

PubMed Central

Wood, James M.; Sanei, Hamed

2016-01-01

Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere. PMID:27874012

Diabetes management at the end of life: transitioning from tight glycemic control to comfort.

PubMed

Tice, Martha A

2006-05-01

Tight glycemic control has become the standard of care for prevention of the long-term side effects of diabetes mellitus. When individuals with diabetes approach the end of life from advanced cancer or another chronic illness, they often become anorexic. The result is an increased risk for hypoglycemic episodes. It is appropriate to shift the goal of therapy from tight control of blood sugar to maintaining comfort and enhancing quality of life.

Flow behavior of N2 huff and puff process for enhanced oil recovery in tight oil reservoirs.

PubMed

Lu, Teng; Li, Zhaomin; Li, Jian; Hou, Dawei; Zhang, Dingyong

2017-11-16

In the present work, the potential of N 2 huff and puff process to enhance the recovery of tight oil reservoir was evaluated. N 2 huff and puff experiments were performed in micromodels and cores to investigate the flow behaviors of different cycles. The results showed that, in the first cycle, N 2 was dispersed in the oil, forming the foamy oil flow. In the second cycle, the dispersed gas bubbles gradually coalesced into the continuous gas phase. In the third cycle, N 2 was produced in the form of continuous gas phase. The results from the coreflood tests showed that, the primary recovery was only 5.32%, while the recoveries for the three N 2 huff and puff cycles were 15.1%, 8.53% and 3.22%, respectively.The recovery and the pressure gradient in the first cycle were high. With the increase of huff and puff cycles, and the oil recovery and the pressure gradient rapidly decreased. The oil recovery of N 2 huff and puff has been found to increase as the N 2 injection pressure and the soaking time increased. These results showed that, the properly designed and controlled N 2 huff and puff process can lead to enhanced recovery of tight oil reservoirs.

Intensive Insulin Therapy: Tight Blood Sugar Control

MedlinePlus

Intensive insulin therapy: Tight blood sugar control Intensive insulin therapy can help prevent long-term diabetes complications. Consider the benefits — and understand the commitment. By Mayo Clinic Staff If ...

Tight Diabetes Control

MedlinePlus

... results? Here's what they found in the tight-control group as compared with the standard-treatment group: Diabetic ... where you stand. sticky en -- Chef Ronaldo's Sabores de Cuba - 2016-08-book-sabores-de-cuba.html ...

[Influence and mechanism of a tight control of blood glucose by intensive insulin therapy on human sepsis].

PubMed

Yu, Wen-kui; Li, Wei-qin; Wang, Xiao-dong; Yan, Xiao-wen; Qi, Xiao-ping; Li, Ning; Li, Jie-shou

2005-01-01

To investigate the effect of a tight control of blood glucose by intensive insulin therapy on human sepsis, and to explore the potential mechanism of the intensive insulin therapy. Eligible patients were randomized by a blinded pharmacist to receive tight control of blood glucose by intensive insulin therapy (maintenance of blood glucose at a level between 4.4 and 6.1 mmol/L) or to receive conventional treatment (maintenance of glucose at a level between 10.0 and 11.1 mmol/L). The expression of HLA-DR on peripheral monocytes was measured in 54 patients by flow cytometry on 24 h, 3 d, 5 d, 7 d, 10 d and 14 d of intensive care in parallel with serum c-reactive protein (CRP), severity of the disease (APACHE II score, SOFA score) and clinical data collection. Patients receiving intensive insulin therapy were less likely to require prolonged mechanical ventilation. Tight control of blood glucose significantly reduced the number of days during which leukopenia or leukocytosis and the days with hypo- or hyperthermia (P < 0.05). Hypoglycemia occurred in 3 patients (10.7%) in the tight control of blood glucose group. There were no instance of hemodynamic deterioration or convulsions. Compared with the conventional treatment, tight control of blood glucose also increased the HLA-DR expression of peripheral monocytes, and there were significantly difference on 3 d, 5 d and 7 d (P < 0.05). Whereas it suppressed the elevated serum CRP concentrations, there was significantly difference on 7 d (P < 0.05). Tight control of blood glucose by intensive insulin therapy expedited healing of human sepsis, and increased the HLA-DR expression of peripheral and suppressed the elevated serum CRP. So, it is necessary to use insulin to strict control the glucose levels in human sepsis.

Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier.

PubMed

Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim

2016-11-01

The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.

Characteristics of secondary migration driving force of tight oil and its geologic effect: a case study of Jurassic in Central Sichuan Basin

NASA Astrophysics Data System (ADS)

Pang, Zhenglian; Tao, Shizhen; Zhang, Bin; Wu, Songtao; Yang, Jiajing; Chen, Ruiyin

2017-04-01

As the rising of its production, tight oil is becoming more and more important. Much research has been done about it. Some articles mention that buoyancy is ineffective for tight oil secondary migration, and abnormal pressure is the alternative. Others believe that overpressure caused hydrocarbon generation is the very force. Though opinions have been given, there are two inadequacies. Firstly, the points are lack of sufficient evidences. Mostly, they are only one or two sentences in the papers. Secondly, geologic effect of the change of driving force hasn't been discussed. In this context, analog experiments, physical property testing, mercury injection, and oil/source comparison were utilized to study 3 issues: origin and value of tight oil secondary migration resistance, values and effectiveness of different potential driving forces, and geologic effect of tight oil secondary migration driving force. Firstly, resistance values of tight reservoir were detected by analog experiments. The value of tight limestone is 15.8MPa, while tight sandstone is 10.7MPa. Tiny size of pores and throats in tight reservoir is the main reason causing huge resistances. Over 90% of pores and throats in tight reservoir are smaller than 1μm. They form huge capillary force when oil migrating through them. Secondly, maximum of buoyancy in study area was confirmed, 0.09MPa, too small to overcome the resistances. Meanwhile, production data suggests that tight oil distribution pattern is not controlled by buoyancy. Conversely, analog experiment proves that overpressure caused by hydrocarbon generation can reach 38MPa, large enough to be the driving force. This idea is also supported by positive correlation between output and source rock formation pressure. Thirdly, is the geologic effect of tight oil secondary migration resistance and driving force. Tight oil can migrate only as non-darcy flow due to huge resistances according to percolation experiments. It needs to overcome the starting pressure gradient. As a result, it migrated a much shorter distance compared with conventional petroleum, coincident with the result of oil/source comparison. The effect of driving force is that boundary of tight oil profitable area is controlled by source rock. This boundary in the study area is the line of hydrocarbon generating strength of 40×104t/km2. By confirming controlling factors of tight oil formation and their evaluation index, it is of great significance during tight oil exploration.

Meeting critical gate linewidth control needs at the 65 nm node

NASA Astrophysics Data System (ADS)

Mahorowala, Arpan; Halle, Scott; Gabor, Allen; Chu, William; Barberet, Alexandra; Samuels, Donald; Abdo, Amr; Tsou, Len; Yan, Wendy; Iseda, Seiji; Patel, Kaushal; Dirahoui, Bachir; Nomura, Asuka; Ahsan, Ishtiaq; Azam, Faisal; Berg, Gary; Brendler, Andrew; Zimmerman, Jeffrey; Faure, Tom

2006-03-01

With the nominal gate length at the 65 nm node being only 35 nm, controlling the critical dimension (CD) in polysilicon to within a few nanometers is essential to achieve a competitive power-to-performance ratio. Gate linewidths must be controlled, not only at the chip level so that the chip performs as the circuit designers and device engineers had intended, but also at the wafer level so that more chips with the optimum power-to-performance ratio are manufactured. Achieving tight across-chip linewidth variation (ACLV) and chip mean variation (CMV) is possible only if the mask-making, lithography, and etching processes are all controlled to very tight specifications. This paper identifies the various ACLV and CMV components, describes their root causes, and discusses a methodology to quantify them. For example, the site-to-site ACLV component is divided into systematic and random sub-components. The systematic component of the variation is attributed in part to pattern density variation across the field, and variation in exposure dose across the slit. The paper demonstrates our team's success in achieving the tight gate CD tolerances required for 65 nm technology. Certain key challenges faced, and methods employed to overcome them are described. For instance, the use of dose-compensation strategies to correct the small but systematic CD variations measured across the wafer, is described. Finally, the impact of immersion lithography on both ACLV and CMV is briefly discussed.

Control of DNA replication: a new facet of Hox proteins?

PubMed

Miotto, Benoit; Graba, Yacine

2010-09-01

Hox proteins are well-known as developmental transcription factors controlling cell and tissue identity, but recent findings suggest that they are also part of the cell replication machinery. Hox-mediated control of transcription and replication may ensure coordinated control of cell growth and differentiation, two processes that need to be tightly and precisely coordinated to allow proper organ formation and patterning. In this review we summarize the available data linking Hox proteins to the replication machinery and discuss the developmental and pathological implications of this new facet of Hox protein function.

The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial)

PubMed Central

Ahmed, Rashid J.; Gafni, Amiram; Hu, Zheng Jing; Pullenayegum, Eleanor; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E.; Menzies, Jennifer; Sanchez, J. Johanna; Ganzevoort, Wessel; Helewa, Michael; Lee, Shoo K.; Lee, Terry; Logan, Alexander G.; Moutquin, Jean-Marie; Singer, Joel; Thornton, Jim G.; Welch, Ross; Magee, Laura A.

2016-01-01

The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned “less tight” (target diastolic 100 mm Hg) and “tight” (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman–infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus $24 469.06; DM $5723, 95% confidence interval, −$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM $5817; 95% confidence interval, −$385 to $12 349; P=0.0725); or Alberta ($31 510.72 versus $25 510.49; DM $6000.23; 95% confidence interval, −$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412. PMID:27550914

Effect of Extracorporeal Shock Wave Therapy on Hamstring Tightness in Healthy Subjects: A Pilot Study

PubMed Central

Kim, Yong Wook; Chang, Won Hyuk; Kim, Na Young; Kwon, Jun Beom

2017-01-01

Purpose To assess the effect of extracorporeal shock wave therapy (ESWT) for healthy participants with hamstring tightness. Materials and Methods This study was performed at a university rehabilitation hospital. Twenty nine healthy adults with hamstring tightness were enrolled and randomly allocated into four groups (ESWT, stretching exercise, ESWT with stretching exercise, and control). The effects of individual treatments were compared by the finger-to-floor test and popliteal angle. Results The ESWT group, stretching exercise group and ESWT with stretching exercise group had decreased finger-to-floor distances and right popliteal angles immediately after intervention, compared with the control group (p<0.05). At 4 weeks after completion of the interventions, finger-to-floor distances and the right popliteal angle in only the ESWT with stretching exercise group showed a significant improvement, compared with the control group (p=0.008 and 0.023). Conclusion While ESWT and stretching both reduced hamstring tightness immediately after interventions, only ESWT with stretching exercise maintained the significantly improved relief of hamstring tightness significantly after 4 weeks. PMID:28332373

The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression

PubMed Central

Balda, Maria S.; Matter, Karl

2000-01-01

Epithelial tight junctions regulate paracellular diffusion and restrict the intermixing of apical and basolateral plasma membrane components. We now identify a Y-box transcription factor, ZONAB (ZO-1-associated nucleic acid-binding protein), that binds to the SH3 domain of ZO-1, a submembrane protein of tight junctions. ZONAB localizes to the nucleus and at tight junctions, and binds to sequences of specific promoters containing an inverted CCAAT box. In reporter assays, ZONAB and ZO-1 functionally interact in the regulation of the ErbB-2 promoter in a cell density-dependent manner. In stably transfected overexpressing cells, ZO-1 and ZONAB control expression of endogenous ErbB-2 and function in the regulation of paracellular permeability. These data indicate that tight junctions directly participate in the control of gene expression and suggest that they function in the regulation of epithelial cell differentiation. PMID:10790369

Five-Year Plan (FY04-FY-08) for the Manufacturing Technology (ManTech) Program. Supplement to the FY03 - FY07 Plan

DTIC Science & Technology

2003-07-01

magnetorheological (MRF) finishing to reduce surface roughness in half the time of previous processes . Improved image quality directly supports improved...affordably polish the inside surface of small tight free form optics to a finish on the order of 3 angstroms. • Demonstrate cycle time reduction...processes and controls for steel, titanium, and superalloys. FY2007: • Demonstrate an improved superfine finishing for optical components to

Baseline Industrial Hygiene Survey at the Coal Fired Heating Plant, Malmstrom AFB, Montana.

DTIC Science & Technology

1987-12-01

hygiene concern. However, as observed, the flue gas system is fairly tight and seems to control the hazards well. The only exception may be during its...NOX and SO2 are produced during normal 1 operations. Most off-gassing is controlled , such as flue gas , and any gas that does escape, dissipates through...chemical and gas exposures during the desulfurization process, mixing of caustic solutions, and boiler off-gassing. Heat stress and noise exposura

Hepatic immunohistochemical localization of the tight junction protein ZO-1 in rat models of cholestasis.

PubMed Central

Anderson, J. M.; Glade, J. L.; Stevenson, B. R.; Boyer, J. L.; Mooseker, M. S.

1989-01-01

Structural alterations in hepatocyte tight junctions accompanying cholestasis were investigated using immunolocalization of ZO-1, the first known protein component of the tight junction. Disruption in the paracellular barrier function of the tight junction has been proposed to allow reflux of bile into the blood. Cholestasis was induced in 210 to 235 g male Sprague-Dawley rats either by five consecutive daily subcutaneous injections of 17-alpha-ethinyl estradiol (0.5 mg/kg/d in propylene glycol) or ligation of the common bile duct for 72 hours. The structural organization of the tight junction was assessed in each model by indirect immunofluorescent and immunoperoxidase staining for ZO-1 on frozen sections of liver and compared with controls. In control, sham-operated, and estradiol-injected animals, ZO-1 localizes in a uniform continuous manner along the margins of the canaliculi. In contrast, bile duct ligation results in the appearance of numerous discontinuities in ZO-1 staining accompanied by dilation or collapse of the lumenal space. Tissue content of the ZO-1 protein, as determined by quantitative immunoblotting, was unaffected in either cholestatic model compared with controls. These findings indicate that the molecular organization of the tight junction can be assessed from immunostaining patterns of ZO-1 in frozen sections of cholestatic livers. Under these experimental conditions, the organization of the tight junction at the level of the ZO-1 protein is altered by bile duct obstruction but not by ethinyl estradiol. Images Figure 1 Figure 2 PMID:2719075

Tightness Entropic Uncertainty Relation in Quantum Markovian-Davies Environment

NASA Astrophysics Data System (ADS)

Zhang, Jun; Liu, Liang; Han, Yan

2018-05-01

In this paper, we investigate the tightness of entropic uncertainty relation in the absence (presence) of the quantum memory which the memory particle being weakly coupled to a decohering Davies-type Markovian environment. The results show that the tightness of the quantum uncertainty relation can be controlled by the energy relaxation time F, the dephasing time G and the rescaled temperature p, the perfect tightness can be arrived by dephasing and energy relaxation satisfying F = 2G and p = 1/2. In addition, the tightness of the memory-assisted entropic uncertainty relation and the entropic uncertainty relation can be influenced mainly by the purity. While in memory-assisted model, the purity and quantum correlation can also influence the tightness actively while the quantum entanglement can influence the tightness slightly.

Tight junctions and the modulation of barrier function in disease

PubMed Central

2008-01-01

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease. PMID:18415116

Estrogen Modulates Expression of Tight Junction Proteins in Rat Vagina

PubMed Central

Oh, Kyung-Jin; Ahn, Kyuyoun

2016-01-01

Background. The objectives of this study were to investigate the localization of tight junctions and the modulation of zonula occludens- (ZO-) 1, occludin and claudin-1 expression by estrogen in castrated female rat vagina. Female Sprague-Dawley rats (230–240 g, n = 45) were divided into three groups and subjected to a sham operation (control group, n = 15), bilateral ovariectomy (Ovx group, n = 15), or bilateral ovariectomy followed by daily subcutaneous injection of 17β-estradiol (50 μg/kg/day, Ovx + Est group, n = 15). The cellular localization and expression of ZO-1, occludin, and claudin-1 were determined in each group by immunohistochemistry and western blot. Results. Expression of ZO-1 was diffuse in all groups, with the highest intensity in the superficial epithelium in the control group. Occludin was localized in the intermediate and basal epithelium. Claudin-1 was most intense in the superficial layer of the vaginal epithelium in the control group. Expression of ZO-1, occludin, and claudin-1 was significantly decreased after ovariectomy and was restored to the level of the control after estrogen replacement. Conclusions. Tight junctions are distinctly localized in rat vagina, and estrogen modulates the expression of tight junctions. Further researches are needed to clarify the functional role of tight junctions in vaginal lubrication. PMID:27127786

Estrogen Modulates Expression of Tight Junction Proteins in Rat Vagina.

PubMed

Oh, Kyung-Jin; Lee, Hyun-Suk; Ahn, Kyuyoun; Park, Kwangsung

2016-01-01

Background. The objectives of this study were to investigate the localization of tight junctions and the modulation of zonula occludens- (ZO-) 1, occludin and claudin-1 expression by estrogen in castrated female rat vagina. Female Sprague-Dawley rats (230-240 g, n = 45) were divided into three groups and subjected to a sham operation (control group, n = 15), bilateral ovariectomy (Ovx group, n = 15), or bilateral ovariectomy followed by daily subcutaneous injection of 17β-estradiol (50 μg/kg/day, Ovx + Est group, n = 15). The cellular localization and expression of ZO-1, occludin, and claudin-1 were determined in each group by immunohistochemistry and western blot. Results. Expression of ZO-1 was diffuse in all groups, with the highest intensity in the superficial epithelium in the control group. Occludin was localized in the intermediate and basal epithelium. Claudin-1 was most intense in the superficial layer of the vaginal epithelium in the control group. Expression of ZO-1, occludin, and claudin-1 was significantly decreased after ovariectomy and was restored to the level of the control after estrogen replacement. Conclusions. Tight junctions are distinctly localized in rat vagina, and estrogen modulates the expression of tight junctions. Further researches are needed to clarify the functional role of tight junctions in vaginal lubrication.

Intraoperative tight glucose control using hyperinsulinemic normoglycemia increases delirium after cardiac surgery.

PubMed

Saager, Leif; Duncan, Andra E; Yared, Jean-Pierre; Hesler, Brian D; You, Jing; Deogaonkar, Anupa; Sessler, Daniel I; Kurz, Andrea

2015-06-01

Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery. The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, <150 mg/dl). Delirium was assessed using a comprehensive delirium battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness). Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy. Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

General aviation fuel quality control

NASA Technical Reports Server (NTRS)

Poitz, H.

1983-01-01

Quality control measures for aviation gasoline, and some of the differences between quality control on avgas and mogas are discussed. One thing to keep in mind is that with motor gasoline you can always pull off to the side of the road. It's not so easy to do in an airplane. Consequently, there are reasons for having the tight specifications and the tight quality control measures on avgas as compared to motor gasoline.

Preservation of Thermal Control Specular Gold Baffle Surface on the James Webb Space Telescope (JWST) Integrated Science Instrument Module (ISIM) Electronics Compartment (IEC)

NASA Technical Reports Server (NTRS)

MonteedeGarcia, Kristina; Patel, Jignasha; Perry, Radford, III

2010-01-01

Extremely tight thermal control property degradation allowances on the vapor-deposited, gold-coated IEC baffle surface, made necessary by the cryogenic JWST Observatory operations, dictate tight contamination requirements on adjacent surfaces. Theoretical degradation in emittance with contaminant thickness was calculated. Maximum allowable source outgassing rates were calculated using worst case view factors from source to baffle surface. Tight requirements pushed the team to change the design of the adjacent surfaces to minimize the outgassing sources

Preservation of thermal control specular gold baffle surface on the James Webb Space Telescope (JWST) integrated science instrument module (ISIM) electronics compartment (IEC)

NASA Astrophysics Data System (ADS)

Montt de Garcia, Kristina; Patel, Jignasha; Perry, Radford, III

2010-08-01

Extremely tight thermal control property degradation allowances on the vapor-deposited, gold-coated IEC baffle surface, made necessary by the cryogenic JWST Observatory operations, dictate tight contamination requirements on adjacent surfaces. Theoretical degradation in emittance with contaminant thickness was calculated. Maximum allowable source outgassing rates were calculated using worst case view factors from source to baffle surface. Tight requirements pushed the team to change the design of the adjacent surfaces to minimize the outgassing sources.

Study of the effect of soil disturbance on vapor transport through integrated modeling of the atmospheric boundary layer and shallow subsurface

NASA Astrophysics Data System (ADS)

Trautz, A.; Smits, K. M.; Cihan, A.; Wallen, B.

2014-12-01

Soil-water evaporation is one of the governing processes responsible for controlling water and energy exchanges between the land and atmosphere. Despite its wide relevance and application in many natural and manmade environments (e.g. soil tillage practices, wheel-track compaction, fire burn environments, textural layering and buried ordinances), there are very few studies of evaporation from disturbed soil profiles. The purpose of this study was to explore the effect of soil disturbance and capillary coupling on water distribution and fluxes. We modified a theory previously developed by the authors that allows for coupling single-phase (gas), two-component (air and water vapor) transfer in the atmosphere and two-phase (gas, liquid), two-component (air and water vapor) flow in porous media at the REV scale under non-isothermal, non-equilibrium conditions to better account for the hydraulic and thermal interactions within the media. Modeling results were validated and compared using precision data generated in a two-dimensional soil tank consisting of a loosely packed soil surrounded by a tightly packed soil. The soil tank was outfitted with an array of sensors for the measurement of wind velocity, soil and air temperature, relative humidity, soil moisture, and weight. Results demonstrated that, by using this coupling approach, it is possible to predict the different stages of the drying process in heterogeneous soils with good accuracy. Evaporation from a heterogeneous soil consisting of a loose and tight packing condition is larger than the homogeneous equivalent systems. Liquid water is supplied from the loosely packed soil region to the tightly packed soil regions, sustaining a longer Stage I evaporation in the tightly packed regions with overall greater evaporation rate than uniform homogeneous packing. In contrast, lower evaporation rates from the loosely packed regions are observed due to a limited liquid water supply resulting from capillary flow to the tightly packed regions and a shorter stage 1 evaporation period.

Applications of Laser-Induced Breakdown Spectroscopy (LIBS) in Molten Metal Processing

NASA Astrophysics Data System (ADS)

Hudson, Shaymus W.; Craparo, Joseph; De Saro, Robert; Apelian, Diran

2017-10-01

In order for metals to meet the demand for critical applications in the automotive, aerospace, and defense industries, tight control over the composition and cleanliness of the metal must be achieved. The use of laser-induced breakdown spectroscopy (LIBS) for applications in metal processing has generated significant interest for its ability to perform quick analyses in situ. The fundamentals of LIBS, current techniques for deployment on molten metal, demonstrated capabilities, and possible avenues for development are reviewed and discussed.

Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer

PubMed Central

Landy, Jonathan; Ronde, Emma; English, Nick; Clark, Sue K; Hart, Ailsa L; Knight, Stella C; Ciclitira, Paul J; Al-Hassi, Hafid Omar

2016-01-01

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. PMID:27003989

Manipulating membrane lipid profiles to restore T-cell function in autoimmunity.

PubMed

Waddington, Kirsty E; Jury, Elizabeth C

2015-08-01

Plasma membrane lipid rafts are heterogeneous cholesterol and glycosphingolipid (GSL)-enriched microdomains, within which the tight packing of cholesterol with the saturated-acyl chains of GSLs creates a region of liquid-order relative to the surrounding disordered membrane. Thus lipid rafts govern the lateral mobility and interaction of membrane proteins and regulate a plethora of signal transduction events, including T-cell antigen receptor (TCR) signalling. The pathways regulating homoeostasis of membrane cholesterol and GSLs are tightly controlled and alteration of these metabolic processes coincides with immune cell dysfunction as is evident in atherosclerosis, cancer and autoimmunity. Indeed, membrane lipid composition is emerging as an important factor influencing the ability of cells to respond appropriately to microenvironmental stimuli. Consequently, there is increasing interest in targeting membrane lipids or their metabolic control as a novel therapeutic approach to modulate immune cell behaviour and our recent work demonstrates that this is a promising strategy in T-cells from patients with the autoimmune disease systemic lupus erythematosus (SLE). © 2015 Authors; published by Portland Press Limited.

Alignment of the Stanford Linear Collider Arcs: Concepts and results

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

Pitthan, R.; Bell, B.; Friedsam, H.

1987-02-01

The alignment of the Arcs for the Stanford Linear Collider at SLAC has posed problems in accelerator survey and alignment not encountered before. These problems come less from the tight tolerances of 0.1 mm, although reaching such a tight statistically defined accuracy in a controlled manner is difficult enough, but from the absence of a common reference plane for the Arcs. Traditional circular accelerators, including HERA and LEP, have been designed in one plane referenced to local gravity. For the SLC Arcs no such single plane exists. Methods and concepts developed to solve these and other problems, connected with themore » unique design of SLC, range from the first use of satellites for accelerator alignment, use of electronic laser theodolites for placement of components, computer control of the manual adjustment process, complete automation of the data flow incorporating the most advanced concepts of geodesy, strict separation of survey and alignment, to linear principal component analysis for the final statistical smoothing of the mechanical components.« less

Intestinal epithelial barrier function and tight junction proteins with heat and exercise

PubMed Central

Zuhl, Micah N.; Moseley, Pope L.

2015-01-01

A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or “leaky” intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise. PMID:26359485

Intestinal epithelial barrier function and tight junction proteins with heat and exercise.

PubMed

Dokladny, Karol; Zuhl, Micah N; Moseley, Pope L

2016-03-15

A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or "leaky" intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise. Copyright © 2016 the American Physiological Society.

Smooth affine shear tight frames: digitization and applications

NASA Astrophysics Data System (ADS)

Zhuang, Xiaosheng

2015-08-01

In this paper, we mainly discuss one of the recent developed directional multiscale representation systems: smooth affine shear tight frames. A directional wavelet tight frame is generated by isotropic dilations and translations of directional wavelet generators, while an affine shear tight frame is generated by anisotropic dilations, shears, and translations of shearlet generators. These two tight frames are actually connected in the sense that the affine shear tight frame can be obtained from a directional wavelet tight frame through subsampling. Consequently, an affine shear tight frame indeed has an underlying filter bank from the MRA structure of its associated directional wavelet tight frame. We call such filter banks affine shear filter banks, which can be designed completely in the frequency domain. We discuss the digitization of affine shear filter banks and their implementations: the forward and backward digital affine shear transforms. Redundancy rate and computational complexity of digital affine shear transforms are also investigated in this paper. Numerical experiments and comparisons in image/video processing show the advantages of digital affine shear transforms over many other state-of-art directional multiscale representation systems.

Tight versus standard blood pressure control in patients with hypertension with and without cardiovascular disease.

PubMed

Reboldi, Gianpaolo; Angeli, Fabio; de Simone, Giovanni; Staessen, Jan A; Verdecchia, Paolo

2014-03-01

An excessive blood pressure (BP) reduction might be dangerous in high-risk patients with cardiovascular disease. In the Studio Italiano Sugli Effetti CARDIOvascolari del Controllo della Pressione Arteriosa SIStolica (Cardio-Sis), 1111 nondiabetic patients with systolic BP ≥150 mm Hg were randomly assigned to a systolic BP target <140 mm Hg (standard control) or <130 mm Hg (tight control). We stratified patients by absence (n=895) or presence (n=216) of established cardiovascular disease at entry. Antihypertensive treatment was open-label and tailored to each patient's needs. After 2-year follow-up, the primary end point of the study, electrocardiographic left ventricular hypertrophy, occurred less frequently in the tight than in the standard control group in the patients without (10.8% versus 15.2%) and with (14.1% versus 23.5%) established cardiovascular disease (P for interaction=0.82). The main secondary end point, a composite of cardiovascular events and all-cause death, occurred less frequently in the tight than in the standard control group both in patients without (1.47 versus 3.68 patient-years; P=0.016) and with (7.87 versus 11.22 patient-years; P=0.049) previous cardiovascular disease. In a multivariable Cox model, allocation to tight BP control reduced the risk of cardiovascular events to a similar extent in patients with or without overt cardiovascular disease at randomization (P for interaction=0.43). In conclusion, an intensive treatment aimed to lower systolic BP<130 mm Hg reduced left ventricular hypertrophy and improved clinical outcomes to a similar extent in patients with hypertension and without established cardiovascular disease.

Applied metrology in the production of superconducting model magnets for particle accelerators

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

Ferradas Troitino, Jose; Bestmann, Patrick; Bourcey, Nicolas

2017-12-22

The production of superconducting magnets for particle accelerators involves high precision assemblies and tight tolerances, in order to achieve the requirements for their appropriate performance. It is therefore essential to have a strict control and traceability over the geometry of each component of the system, and also to be able to compensate possible inherent deviations coming from the production process.

Russian Political, Economic, and Security Issues and U.S. Interests

DTIC Science & Technology

2007-01-18

polonium 210 from Moscow, through Germany, to London, apparently carried by one of the Russians Litvinenko met November 1. Russian authorities deny...radio under tight state control and virtually eliminated effective political opposition. Federal forces have suppressed large-scale military resistance...Russia’s needs — food and food processing, oil and gas extraction technology, computers, communications, transportation, and investment capital — are

Dynamics of entropic uncertainty for atoms immersed in thermal fluctuating massless scalar field

NASA Astrophysics Data System (ADS)

Huang, Zhiming

2018-04-01

In this article, the dynamics of quantum memory-assisted entropic uncertainty relation for two atoms immersed in a thermal bath of fluctuating massless scalar field is investigated. The master equation that governs the system evolution process is derived. It is found that the mixedness is closely associated with entropic uncertainty. For equilibrium state, the tightness of uncertainty vanishes. For the initial maximum entangled state, the tightness of uncertainty undergoes a slight increase and then declines to zero with evolution time. It is found that temperature can increase the uncertainty, but two-atom separation does not always increase the uncertainty. The uncertainty evolves to different relatively stable values for different temperatures and converges to a fixed value for different two-atom distances with evolution time. Furthermore, weak measurement reversal is employed to control the entropic uncertainty.

Advanced model-based control strategies for the intensification of upstream and downstream processing in mAb production.

PubMed

Papathanasiou, Maria M; Quiroga-Campano, Ana L; Steinebach, Fabian; Elviro, Montaña; Mantalaris, Athanasios; Pistikopoulos, Efstratios N

2017-07-01

Current industrial trends encourage the development of sustainable, environmentally friendly processes with minimal energy and material consumption. In particular, the increasing market demand in biopharmaceutical industry and the tight regulations in product quality necessitate efficient operating procedures that guarantee products of high purity. In this direction, process intensification via continuous operation paves the way for the development of novel, eco-friendly processes, characterized by higher productivity and lower production costs. This work focuses on the development of advanced control strategies for (i) a cell culture system in a bioreactor and (ii) a semicontinuous purification process. More specifically, we consider a fed-batch culture of GS-NS0 cells and the semicontinuous Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) for the purification process. The controllers are designed following the PAROC framework/software platform and their capabilities are assessed in silico, against the process models. It is demonstrated that the proposed controllers efficiently manage to increase the system productivity, returning strategies that can lead to continuous, stable process operation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:966-988, 2017. © 2017 American Institute of Chemical Engineers.

Process control systems: integrated for future process technologies

NASA Astrophysics Data System (ADS)

Botros, Youssry; Hajj, Hazem M.

2003-06-01

Process Control Systems (PCS) are becoming more crucial to the success of Integrated Circuit makers due to their direct impact on product quality, cost, and Fab output. The primary objective of PCS is to minimize variability by detecting and correcting non optimal performance. Current PCS implementations are considered disparate, where each PCS application is designed, deployed and supported separately. Each implementation targets a specific area of control such as equipment performance, wafer manufacturing, and process health monitoring. With Intel entering the nanometer technology era, tighter process specifications are required for higher yields and lower cost. This requires areas of control to be tightly coupled and integrated to achieve the optimal performance. This requirement can be achieved via consistent design and deployment of the integrated PCS. PCS integration will result in several benefits such as leveraging commonalities, avoiding redundancy, and facilitating sharing between implementations. This paper will address PCS implementations and focus on benefits and requirements of the integrated PCS. Intel integrated PCS Architecture will be then presented and its components will be briefly discussed. Finally, industry direction and efforts to standardize PCS interfaces that enable PCS integration will be presented.

Parallel Algorithm for GPU Processing; for use in High Speed Machine Vision Sensing of Cotton Lint Trash.

PubMed

Pelletier, Mathew G

2008-02-08

One of the main hurdles standing in the way of optimal cleaning of cotton lint isthe lack of sensing systems that can react fast enough to provide the control system withreal-time information as to the level of trash contamination of the cotton lint. This researchexamines the use of programmable graphic processing units (GPU) as an alternative to thePC's traditional use of the central processing unit (CPU). The use of the GPU, as analternative computation platform, allowed for the machine vision system to gain asignificant improvement in processing time. By improving the processing time, thisresearch seeks to address the lack of availability of rapid trash sensing systems and thusalleviate a situation in which the current systems view the cotton lint either well before, orafter, the cotton is cleaned. This extended lag/lead time that is currently imposed on thecotton trash cleaning control systems, is what is responsible for system operators utilizing avery large dead-band safety buffer in order to ensure that the cotton lint is not undercleaned.Unfortunately, the utilization of a large dead-band buffer results in the majority ofthe cotton lint being over-cleaned which in turn causes lint fiber-damage as well assignificant losses of the valuable lint due to the excessive use of cleaning machinery. Thisresearch estimates that upwards of a 30% reduction in lint loss could be gained through theuse of a tightly coupled trash sensor to the cleaning machinery control systems. Thisresearch seeks to improve processing times through the development of a new algorithm forcotton trash sensing that allows for implementation on a highly parallel architecture.Additionally, by moving the new parallel algorithm onto an alternative computing platform,the graphic processing unit "GPU", for processing of the cotton trash images, a speed up ofover 6.5 times, over optimized code running on the PC's central processing unit "CPU", wasgained. The new parallel algorithm operating on the GPU was able to process a 1024x1024image in less than 17ms. At this improved speed, the image processing system's performance should now be sufficient to provide a system that would be capable of realtimefeed-back control that is in tight cooperation with the cleaning equipment.

Environmental Regulation of Yersinia Pathophysiology

PubMed Central

Chen, Shiyun; Thompson, Karl M.; Francis, Matthew S.

2016-01-01

Hallmarks of Yersinia pathogenesis include the ability to form biofilms on surfaces, the ability to establish close contact with eukaryotic target cells and the ability to hijack eukaryotic cell signaling and take over control of strategic cellular processes. Many of these virulence traits are already well-described. However, of equal importance is knowledge of both confined and global regulatory networks that collaborate together to dictate spatial and temporal control of virulence gene expression. This review has the purpose to incorporate historical observations with new discoveries to provide molecular insight into how some of these regulatory mechanisms respond rapidly to environmental flux to govern tight control of virulence gene expression by pathogenic Yersinia. PMID:26973818

Energy Metabolism in the Liver

PubMed Central

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

Holding Tight: Cell Junctions and Cancer Spread.

PubMed

Knights, Alexander J; Funnell, Alister P W; Crossley, Merlin; Pearson, Richard C M

2012-01-01

Cell junctions are sites of intercellular adhesion that maintain the integrity of epithelial tissue and regulate signalling between cells. These adhesive junctions are comprised of protein complexes that serve to establish an intercellular cytoskeletal network for anchoring cells, in addition to regulating cell polarity, molecular transport and communication. The expression of cell adhesion molecules is tightly controlled and their downregulation is essential for epithelial-mesenchymal transition (EMT), a process that facilitates the generation of morphologically and functionally diverse cell types during embryogenesis. The characteristics of EMT are a loss of cell adhesion and increased cellular mobility. Hence, in addition to its normal role in development, dysregulated EMT has been linked to cancer progression and metastasis, the process whereby primary tumors migrate to invasive secondary sites in the body. This paper will review the current understanding of cell junctions and their role in cancer, with reference to the abnormal regulation of junction protein genes. The potential use of cell junction molecules as diagnostic and prognostic markers will also be discussed, as well as possible therapies for adhesive dysregulation.

Adaptive tight frame based medical image reconstruction: a proof-of-concept study for computed tomography

NASA Astrophysics Data System (ADS)

Zhou, Weifeng; Cai, Jian-Feng; Gao, Hao

2013-12-01

A popular approach for medical image reconstruction has been through the sparsity regularization, assuming the targeted image can be well approximated by sparse coefficients under some properly designed system. The wavelet tight frame is such a widely used system due to its capability for sparsely approximating piecewise-smooth functions, such as medical images. However, using a fixed system may not always be optimal for reconstructing a variety of diversified images. Recently, the method based on the adaptive over-complete dictionary that is specific to structures of the targeted images has demonstrated its superiority for image processing. This work is to develop the adaptive wavelet tight frame method image reconstruction. The proposed scheme first constructs the adaptive wavelet tight frame that is task specific, and then reconstructs the image of interest by solving an l1-regularized minimization problem using the constructed adaptive tight frame system. The proof-of-concept study is performed for computed tomography (CT), and the simulation results suggest that the adaptive tight frame method improves the reconstructed CT image quality from the traditional tight frame method.

Measurement and Visualization of Tight Rock Exposed to CO2 Using NMR Relaxometry and MRI

PubMed Central

Wang, Haitao; Lun, Zengmin; Lv, Chengyuan; Lang, Dongjiang; Ji, Bingyu; Luo, Ming; Pan, Weiyi; Wang, Rui; Gong, Kai

2017-01-01

Understanding mechanisms of oil mobilization of tight matrix during CO2 injection is crucial for CO2 enhanced oil recovery (EOR) and sequestration engineering design. In this study exposure behavior between CO2 and tight rock of the Ordos Basin has been studied experimentally by using nuclear magnetic resonance transverse relaxation time (NMR T2) spectrum and magnetic resonance imaging (MRI) under the reservoir pressure and temperature. Quantitative analysis of recovery at the pore scale and visualization of oil mobilization are achieved. Effects of CO2 injection, exposure times and pressure on recovery performance have been investigated. The experimental results indicate that oil in all pores can be gradually mobilized to the surface of rock by CO2 injection. Oil mobilization in tight rock is time-consuming while oil on the surface of tight rock can be mobilized easily. CO2 injection can effectively mobilize oil in all pores of tight rock, especially big size pores. This understanding of process of matrix exposed to CO2 could support the CO2 EOR in tight reservoirs. PMID:28281697

p53 on the crossroad between regeneration and cancer.

PubMed

Charni, Meital; Aloni-Grinstein, Ronit; Molchadsky, Alina; Rotter, Varda

2017-01-01

Regeneration and tumorigenesis share common molecular pathways, nevertheless the outcome of regeneration is life, whereas tumorigenesis leads to death. Although the process of regeneration is strictly controlled, malignant transformation is unrestrained. In this review, we discuss the involvement of TP53, the major tumor-suppressor gene, in the regeneration process. We point to the role of p53 as coordinator assuring that regeneration will not shift to carcinogenesis. The fluctuation in p53 activity during the regeneration process permits a tight control. On one hand, its inhibition at the initial stages allows massive proliferation, on the other its induction at advanced steps of regeneration is essential for preservation of robustness and fidelity of the regeneration process. A better understanding of the role of p53 in regulation of regeneration may open new opportunities for implementation of TP53-based therapies, currently available for cancer patients, in regenerative medicine.

Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial.

PubMed

Sadhwani, Anjali; Asaro, Lisa A; Goldberg, Caren; Ware, Janice; Butcher, Jennifer; Gaies, Michael; Smith, Cynthia; Alexander, Jamin L; Wypij, David; Agus, Michael S D

2016-07-01

To assess the association of postoperative tight glycemic control and hypoglycemia in children undergoing cardiac surgery with neurodevelopmental outcomes at 1 year of age. A 2-center, prospective, randomized trial of postoperative tight glycemic control vs standard care was conducted in 980 children undergoing cardiac surgery. Neurodevelopmental outcomes were assessed at nine to 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Adaptive Behavior Assessment System, Second Edition, the Ages and Stages Questionnaire, Third Edition, and the Brief Infant Toddler Social-Emotional Assessment. Neurodevelopmental follow-up was performed on 237 patients with a mean age of 13 months. No significant treatment group differences were found in the Bayley-III and Adaptive Behavior Assessment System, Second Edition composite scores or percentage at risk based on the Ages and Stages Questionnaire, Third Edition and the Brief Infant Toddler Social-Emotional Assessment. Patients who experienced moderate to severe hypoglycemia (n = 8) had lower Bayley-III composite scores compared with patients with no to mild hypoglycemia, even after controlling for factors known to be associated with poorer neurodevelopmental outcomes. For infants undergoing cardiac surgery, tight glycemic control did not impact neurodevelopmental outcomes compared with standard care. These data suggest a possible association between moderate to severe hypoglycemia and poorer neurodevelopmental outcomes at 1 year of age. ClinicalTrials.gov: NCT00443599. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial

PubMed Central

Sadhwani, Anjali; Asaro, Lisa A.; Goldberg, Caren; Ware, Janice; Butcher, Jennifer; Gaies, Michael; Smith, Cynthia; Alexander, Jamin L.; Wypij, David; Agus, Michael S. D.

2016-01-01

Objective To assess the association of postoperative tight glycemic control and hypoglycemia in children undergoing cardiac surgery with neurodevelopmental outcomes at 1 year of age. Study design A 2-center, prospective, randomized trial of postoperative tight glycemic control vs standard care was conducted in 980 children undergoing cardiac surgery. Neurodevelopmental outcomes were assessed at nine to 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Adaptive Behavior Assessment System, Second Edition, the Ages and Stages Questionnaire, Third Edition, and the Brief Infant Toddler Social-Emotional Assessment. Results Neurodevelopmental follow-up was performed on 237 patients with a mean age of 13 months. No significant treatment group differences were found in the Bayley-III and Adaptive Behavior Assessment System, Second Edition composite scores or percentage at risk based on the Ages and Stages Questionnaire, Third Edition and the Brief Infant Toddler Social-Emotional Assessment. Patients who experienced moderate to severe hypoglycemia (n = 8) had lower Bayley-III composite scores compared with patients with no to mild hypoglycemia, even after controlling for factors known to be associated with poorer neurodevelopmental outcomes. Conclusion For infants undergoing cardiac surgery, tight glycemic control did not impact neurodevelopmental outcomes compared with standard care. These data suggest a possible association between moderate to severe hypoglycemia and poorer neurodevelopmental outcomes at 1 year of age. PMID:27112038

RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer.

PubMed

Zihni, Ceniz; Terry, Stephen James

2015-07-01

The establishment and maintenance of epithelial polarity must be correctly controlled for normal development and homeostasis. Tight junctions (TJ) in vertebrates define apical and basolateral membrane domains in polarized epithelia via bi-directional, complex signalling pathways between TJ themselves and the cytoskeleton they are associated with. RhoGTPases are central to these processes and evidence suggests that their regulation is coordinated by interactions between GEFs and GAPs with junctional, cytoplasmic adapter proteins. In this InFocus review we determine that the expression, localization or stability of a variety of these adaptor proteins is altered in various cancers, potentially representing an important mechanistic link between loss of polarity and cancer. We focus here, on two well characterized RhoGTPases Cdc42 and RhoA who's GEFs and GAPs are predominantly localized to TJ via cytoplasmic adaptor proteins. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sequoia: A fault-tolerant tightly coupled multiprocessor for transaction processing

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

Bernstein, P.A.

1988-02-01

The Sequoia computer is a tightly coupled multiprocessor, and thus attains the performance advantages of this style of architecture. It avoids most of the fault-tolerance disadvantages of tight coupling by using a new fault-tolerance design. The Sequoia architecture is similar to other multimicroprocessor architectures, such as those of Encore and Sequent, in that it gives dozens of microprocessors shared access to a large main memory. It resembles the Stratus architecture in its extensive use of hardware fault-detection techniques. It resembles Stratus and Auragen in its ability to quickly recover all processes after a single point failure, transparently to the user.more » However, Sequoia is unique in its combination of a large-scale tightly coupled architecture with a hardware approach to fault tolerance. This article gives an overview of how the hardware architecture and operating systems (OS) work together to provide a high degree of fault tolerance with good system performance.« less

Structural-Diagenetic Controls on Fracture Opening in Tight Gas Sandstone Reservoirs, Alberta Foothills

NASA Astrophysics Data System (ADS)

Ukar, Estibalitz; Eichhubl, Peter; Fall, Andras; Hooker, John

2013-04-01

In tight gas reservoirs, understanding the characteristics, orientation and distribution of natural open fractures, and how these relate to the structural and stratigraphic setting are important for exploration and production. Outcrops provide the opportunity to sample fracture characteristics that would otherwise be unknown due to the limitations of sampling by cores and well logs. However, fractures in exhumed outcrops may not be representative of fractures in the reservoir because of differences in burial and exhumation history. Appropriate outcrop analogs of producing reservoirs with comparable geologic history, structural setting, fracture networks, and diagenetic attributes are desirable but rare. The Jurassic to Lower Cretaceous Nikanassin Formation from the Alberta Foothills produces gas at commercial rates where it contains a network of open fractures. Fractures from outcrops have the same diagenetic attributes as those observed in cores <100 km away, thus offering an ideal opportunity to 1) evaluate the distribution and characteristics of opening mode fractures relative to fold cores, hinges and limbs, 2) compare the distribution and attributes of fractures in outcrop vs. core samples, 3) estimate the timing of fracture formation relative to the evolution of the fold-and-thrust belt, and 4) estimate the degradation of fracture porosity due to postkinematic cementation. Cathodoluminescence images of cemented fractures in both outcrop and core samples reveal several generations of quartz and ankerite cement that is synkinematic and postkinematic relative to fracture opening. Crack-seal textures in synkinematic quartz are ubiquitous, and well-developed cement bridges abundant. Fracture porosity may be preserved in fractures wider than ~100 microns. 1-D scanlines in outcrop and core samples indicate fractures are most abundant within small parasitic folds within larger, tight, mesoscopic folds. Fracture intensity is lower away from parasitic folds; intensity progressively decreases from the faulted cores of mesoscopic folds to their forelimbs, with lowest intensities within relatively undeformed backlimb strata. Fracture apertures locally increase adjacent to reverse faults without an overall increase in fracture frequency. Fluid inclusion analyses of crack-seal quartz cement indicate both aqueous and methane-rich inclusions are present. Homogenization temperatures of two-phase inclusions indicate synkinematic fracture cement precipitation and fracture opening under conditions at or near maximum burial of 190-210°C in core samples, and 120-160°C in outcrop samples. In comparison with the fracture evolution in other, less deformed tight-gas sandstone reservoirs such as the Piceance and East Texas basins where fracture opening is primarily controlled by gas generation, gas charge, and pore fluid pressure, these results suggest a strong control of regional tectonic processes on fracture generation. In conjunction with timing and rate of gas charge, rates of fracture cement growth, and stratigraphic-lithological controls, these processes determine the overall distribution of open fractures in these reservoirs.

Structural-Diagenetic Controls on Fracture Opening in Tight Gas Sandstone Reservoirs, Alberta Foothills

NASA Astrophysics Data System (ADS)

Ukar, E.; Eichhubl, P.; Fall, A.; Hooker, J. N.

2012-12-01

In tight gas reservoirs, understanding the characteristics, orientation and distribution of natural open fractures, and how these relate to the structural and stratigraphic setting are important for exploration and production. Outcrops provide the opportunity to sample fracture characteristics that would otherwise be unknown due to the limitations of sampling by cores and well logs. However, fractures in exhumed outcrops may not be representative of fractures in the reservoir because of differences in burial and exhumation history. Appropriate outcrop analogs of producing reservoirs with comparable geologic history, structural setting, fracture networks, and diagenetic attributes are desirable but rare. The Jurassic to Lower Cretaceous Nikanassin Formation from the Alberta Foothills produces gas at commercial rates where it contains a network of open fractures. Fractures from outcrops have the same diagenetic attributes as those observed in cores <100 km away, thus offering an ideal opportunity to 1) evaluate the distribution and characteristics of opening mode fractures relative to fold cores, hinges and limbs, 2) compare the distribution and attributes of fractures in outcrop vs. core samples, 3) estimate the timing of fracture formation relative to the evolution of the fold-and-thrust belt, and 4) estimate the degradation of fracture porosity due to postkinematic cementation. Cathodoluminescence images of cemented fractures in both outcrop and core samples reveal several generations of quartz and ankerite cement that is synkinematic and postkinematic relative to fracture opening. Crack-seal textures in synkinematic quartz are ubiquitous, and well-developed cement bridges abundant. Fracture porosity may be preserved in fractures wider than ~100 microns. 1-D scanlines in outcrop and core samples indicate fractures are most abundant within small parasitic folds within larger, tight, mesoscopic folds. Fracture intensity is lower away from parasitic folds; intensity progressively decreases from the faulted cores of mesoscopic folds to their forelimbs, with lowest intensities within relatively undeformed backlimb strata. Fracture apertures locally increase adjacent to reverse faults without an overall increase in fracture frequency. Fluid inclusion analyses of crack-seal quartz cement indicate both aqueous and methane-rich inclusions are present. Homogenization temperatures of two-phase inclusions indicate synkinematic fracture cement precipitation and fracture opening under conditions at or near maximum burial of 190-210°C in core samples, and 120-160°C in outcrop samples. In comparison with the fracture evolution in other, less deformed tight-gas sandstone reservoirs such as the Piceance and East Texas basins where fracture opening is primarily controlled by gas generation, gas charge, and pore fluid pressure, these results suggest a strong control of regional tectonic processes on fracture generation. In conjunction with timing and rate of gas charge, rates of fracture cement growth, and stratigraphic-lithological controls, these processes determine the overall distribution of open fractures in these reservoirs.

Moderate Deviation Principles for Stochastic Differential Equations with Jumps

DTIC Science & Technology

2014-01-15

N ŕ’"(dt; dy) and the controls ’" : X [0; T ] ! [0;1) are predictable processes satisfying LT (’") Ma2 (") for some constantM . Here LT denotes...space. Although in the moderate deviations problem one has the stronger bound LT (’") Ma2 (") on the cost of controls, the mere tightness of ’" does not...suitable quadratic form. For " > 0 and M ə, consider the spaces SM+;" : = f’ : X [0; T ]! R+j LT (’) Ma2 (")g (2.5) SM" : = f : X [0; T ]! Rj

Tight glycemic control in the ICU - is the earth flat?

PubMed

Steil, Garry M; Agus, Michael S D

2014-06-27

Tight glycemic control in the ICU has been shown to reduce mortality in some but not all prospective randomized control trials. Confounding the interpretation of these studies are differences in how the control was achieved and underlying incidence of hypoglycemia, which can be expected to be affected by the introduction of continuous glucose monitoring (CGM). In this issue of Critical Care, a consensus panel provides a list of the research priorities they believe are needed for CGM to become routine practice in the ICU. We reflect on these recommendations and consider the implications for using CGM today.

System-wide hybrid MPC-PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction.

PubMed

Singh, Ravendra; Ierapetritou, Marianthi; Ramachandran, Rohit

2013-11-01

The next generation of QbD based pharmaceutical products will be manufactured through continuous processing. This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables, so that the predefined product quality can be achieved consistently. The direct compaction process considered in this study is highly interactive and involves time delays for a number of process variables due to sensor placements, process equipment dimensions, and the flow characteristics of the solid material. A simple feedback regulatory control system (e.g., PI(D)) by itself may not be sufficient to achieve the tight process control that is mandated by regulatory authorities. The process presented herein comprises of coupled dynamics involving slow and fast responses, indicating the requirement of a hybrid control scheme such as a combined MPC-PID control scheme. In this manuscript, an efficient system-wide hybrid control strategy for an integrated continuous pharmaceutical tablet manufacturing process via direct compaction has been designed. The designed control system is a hybrid scheme of MPC-PID control. An effective controller parameter tuning strategy involving an ITAE method coupled with an optimization strategy has been used for tuning of both MPC and PID parameters. The designed hybrid control system has been implemented in a first-principles model-based flowsheet that was simulated in gPROMS (Process System Enterprise). Results demonstrate enhanced performance of critical quality attributes (CQAs) under the hybrid control scheme compared to only PID or MPC control schemes, illustrating the potential of a hybrid control scheme in improving pharmaceutical manufacturing operations. Copyright © 2013 Elsevier B.V. All rights reserved.

Altering wettability to recover more oil from tight formations

DOE PAGES

Brady, Patrick V.; Bryan, Charles R.; Thyne, Geoffrey; ...

2016-06-03

We describe here a method for chemically modifying fracturing fluids and overflushes to chemically increase oil recovery from tight formations. Oil wetting of tight formations is usually controlled by adhesion to illite, kerogen, or both; adhesion to carbonate minerals may also play a role. Oil-illite adhesion is sensitive to salinity, dissolved divalent cation content, and pH. We measure oil-rock adhesion with middle Bakken formation oil and core to verify a surface complexation model of reservoir wettability. The agreement between the model and experiments suggests that wettability trends in tight formations can be quantitatively predicted and that fracturing fluid and overflushmore » compositions can be individually tailored to increase oil recovery.« less

Altering wettability to recover more oil from tight formations

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

Brady, Patrick V.; Bryan, Charles R.; Thyne, Geoffrey

We describe here a method for chemically modifying fracturing fluids and overflushes to chemically increase oil recovery from tight formations. Oil wetting of tight formations is usually controlled by adhesion to illite, kerogen, or both; adhesion to carbonate minerals may also play a role. Oil-illite adhesion is sensitive to salinity, dissolved divalent cation content, and pH. We measure oil-rock adhesion with middle Bakken formation oil and core to verify a surface complexation model of reservoir wettability. The agreement between the model and experiments suggests that wettability trends in tight formations can be quantitatively predicted and that fracturing fluid and overflushmore » compositions can be individually tailored to increase oil recovery.« less

Generation of multicolor vacuum ultraviolet pulses through four-wave sum-frequency mixing in argon

NASA Astrophysics Data System (ADS)

Shi, Liping; Li, Wenxue; Zhou, Hui; Wang, Di; Ding, Liang'en; Zeng, Heping

2013-11-01

We demonstrate efficient generation of multicolor vacuum ultraviolet pulses with excellent mode quality through χ(3)-based four-wave sum-frequency mixing and third-order harmonic generation of 400- and 267-nm femtosecond laser pulses in argon gas. The χ(3)-based nonlinear optical processes were optimized with appropriate control of gas pressure and group velocity delay between the driving pulses. Furthermore, the pulse breakup effects were observed for tightly focused ultraviolet pulses.

Gastrocnemius tightness on joint angle and work of lower extremity during gait.

PubMed

You, Jia-Yuan; Lee, Hsin-Min; Luo, Hong-Ji; Leu, Chwan-Chin; Cheng, Pen-Gang; Wu, Shyi-Kuen

2009-11-01

Muscular tightness is a common clinical musculoskeletal disorder and is regarded as a predisposing factor for muscle injuries. In this study, a two-way mixed design ANOVA was applied to investigate the effects of the gastrocnemius tightness on the joint angle and joint work during walking. Twenty-two patients with muscular tightness of gastrocnemius muscle (<12 degrees of ankle dorsiflexion with knee extended) and 22 age- and gender-matched subjects with normal gastrocnemius flexibility (>15 degrees of ankle dorsiflexion with knee extended) participated in this study. The joint angle and work at hip, knee, and ankle joints during the stance phase were analyzed at two preset cadences of 100 steps/min and 140 steps/min. Significantly greater flexion angles at hip (P=0.025) and knee (P=0.001) were found in the tightness group at the time of maximal ankle dorsiflexion. Significantly less work generation at knee (P=0.034) and greater work absorption at ankle (P=0.024) were detected in the tightness group. The subjects with gastrocnemius tightness revealed a compensatory gait pattern, which included the changes in the joint angles and associated work productions. The potential disturbance of the knee control and strain injuries of plantar flexors might be crucial in the clinical considerations for subjects with gastrocnemius tightness.

Terrestrial tight oil reservoir characteristics and Graded Resource Assessment in China

NASA Astrophysics Data System (ADS)

Wang, Shejiao; Wu, Xiaozhi; Guo, Giulin

2016-04-01

The success of shale/tight plays and the advanced exploitation technology applied in North America have triggered interest in exploring and exploiting tight oil in China. Due to the increased support of exploration and exploitation，great progress has been made in Erdos basin, Songliao basin, Junggar basin, Santanghu basin, Bohai Bay basin, Qaidam Basin, and Sichuan basin currently. China's first tight oil field has been found in Erdos basin in 2015, called xinanbian oil field, with over one hundred million tons oil reserves and one million tons of production scale. Several hundred million tons of tight oil reserve has been found in other basins, showing a great potential in China. Tight oil in China mainly developed in terrestrial sedimentary environment. According to the relations of source rock and reservoir, the source-reservoir combination of tight oil can be divided into three types, which are bottom generating and top storing tight oil,self- generating and self-storing tight oil，top generating and bottom storing tight oil. The self- generating and self-storing tight oil is the main type discovered at present. This type of tight oil has following characteristics:(1) The formation and distribution of tight oil are controlled by high quality source rocks. Terrestrial tight oil source rocks in China are mainly formed in the deep to half deep lacustrine facies. The lithology includes dark mudstone, shale, argillaceous limestone and dolomite. These source rocks with thickness between 20m-150m, kerogen type mostly I-II, and peak oil generation thermal maturity(Ro 0.6-1.4%), have great hydrocarbon generating potential. Most discovered tight oil is distributed in the area of TOC greater than 2 %.( 2) the reservoir with strong heterogeneity is very tight. In these low porosity and permeability reservoir,the resources distribution is controlled by the physical property. Tight sandstone, carbonate and hybrid sedimentary rocks are three main tight reservoir types in China. The porosity is 2-14%(average 5-10%)and the permeability is less than 1mD. The laboratory test and exploration practice confirmed that the oil content was positively related to physical property. The higher the porosity, the better the oil content will have. (3) Source rock and reservoir are superimposed. From the contact relationship of source rock and reservoir, the reservoir developed in the source rock has the advantage of capturing oil and gas, so the oil saturation can be as high as 70-80%. (4) The increased pressure caused by hydrocarbon generation and the connected fracture are the key factors for tight oil accumulation. The Fuyu tight oil formed underling source rock in Songliao Basin is a good example. The fracture system is the key factor for tight oil accumulation. Considering the strong heterogeneity of terrestrial tight oil reservoir in china, we create hierarchical resource abundance analogy, EUR analogy, cell element volumetric methods to evaluate tight oil resource potential. In order to find exploration "sweet spots", establishing tight oil resource classification evaluation standards are key steps to objectively evaluate tight oil resource distribution. The resource classification evaluation standards are established by the relationship analysis between reservoir properties and oil properties, and the correlation analysis between production, resource abundance, and reservoir thickness. The first-grade tight oil resource, which is recently available and can easily be developed, has following main parameters: the porosity is greater than 8%, thickness is over 10m, resource abundance is above 150,000 tons / km2, and pressure coefficient is greater than 1.3; The second-grade tight oil resource is currently unavailable, but with advanced technology can expected to be developed. The main parameters are as following: the porosity is 5% -8%, thickness is less than 5-10m, resource abundance is 50000-150000 tons / km2, the pressure coefficient is 1.0 to 1.3; The third-grade resource has poor quality, need long-term to be effective explored, has following main parameters: porosity is less than 5%, the thickness is less than 5m, resource abundance is less than 50,000 tons / km2, the pressure coefficient is less than 1.0. Using created resource evaluation methods, the tight oil resources has been calculated in china. The first-grade recoverable resource of tight oil is about 610 million tons. The second-grade recoverable resource is 450 million tons. And the third-grade recoverable resource is 400 million tons. The first-grade and second-grade recoverable resources are mainly distributed in the Ordos basin, Bohai Bay basin, Songliao basin, Junggar basin, and Qaidam Basin. The third-grade resources are mainly distributed in Sichuan and Santanghu basin.

MODFLOW–USG version 1: An unstructured grid version of MODFLOW for simulating groundwater flow and tightly coupled processes using a control volume finite-difference formulation

USGS Publications Warehouse

Panday, Sorab; Langevin, Christian D.; Niswonger, Richard G.; Ibaraki, Motomu; Hughes, Joseph D.

2013-01-01

A new version of MODFLOW, called MODFLOW–USG (for UnStructured Grid), was developed to support a wide variety of structured and unstructured grid types, including nested grids and grids based on prismatic triangles, rectangles, hexagons, and other cell shapes. Flexibility in grid design can be used to focus resolution along rivers and around wells, for example, or to subdiscretize individual layers to better represent hydrostratigraphic units. MODFLOW–USG is based on an underlying control volume finite difference (CVFD) formulation in which a cell can be connected to an arbitrary number of adjacent cells. To improve accuracy of the CVFD formulation for irregular grid-cell geometries or nested grids, a generalized Ghost Node Correction (GNC) Package was developed, which uses interpolated heads in the flow calculation between adjacent connected cells. MODFLOW–USG includes a Groundwater Flow (GWF) Process, based on the GWF Process in MODFLOW–2005, as well as a new Connected Linear Network (CLN) Process to simulate the effects of multi-node wells, karst conduits, and tile drains, for example. The CLN Process is tightly coupled with the GWF Process in that the equations from both processes are formulated into one matrix equation and solved simultaneously. This robustness results from using an unstructured grid with unstructured matrix storage and solution schemes. MODFLOW–USG also contains an optional Newton-Raphson formulation, based on the formulation in MODFLOW–NWT, for improving solution convergence and avoiding problems with the drying and rewetting of cells. Because the existing MODFLOW solvers were developed for structured and symmetric matrices, they were replaced with a new Sparse Matrix Solver (SMS) Package developed specifically for MODFLOW–USG. The SMS Package provides several methods for resolving nonlinearities and multiple symmetric and asymmetric linear solution schemes to solve the matrix arising from the flow equations and the Newton-Raphson formulation, respectively.

Processing Impact on Monoclonal Antibody Drug Products: Protein Subvisible Particulate Formation Induced by Grinding Stress.

PubMed

Gikanga, Benson; Eisner, Devon Roshan; Ovadia, Robert; Day, Eric S; Stauch, Oliver B; Maa, Yuh-Fun

2017-01-01

Subvisible particle formation in monoclonal antibody drug product resulting from mixing and filling operations represents a significant processing risk that can lead to filter fouling and thereby lead to process delays or failures. Several previous studies from our lab and others demonstrated the formation of subvisible particulates in mAb formulations resulting from mixing operations using some bottom-mounted mixers or stirrer bars. It was hypothesized that the stress (e.g., shear/cavitation) derived from tight clearance and/or close contact between the impeller and shaft was responsible for protein subvisible particulate generation. These studies, however, could not distinguish between the two surfaces without contact (tight clearance) or between two contacting surfaces (close contact). In the present study we expand on those findings and utilize small-scale mixing models that are able to, for the first time, distinguish between tight clearances and tight contact. In this study we evaluated different mixer types including a top-mounted mixer, several impeller-based bottom-mounted mixers, and a rotary piston pump. The impact of tight clearance/close contact on subvisible particle formation in at-scale mixing platforms was demonstrated in the gap between the impeller and drive unit as well as between the piston and the housing of the pump. Furthermore, small-scale mixing models based on different designs of magnetic stir bars that mimic the tight clearance/close contact of the manufacturing-scale mixers also induced subvisible particles in mAb formulations. Additional small-scale models that feature tight clearance but no close contact (grinding) suggested that it is the repeated grinding/contacting of the moving parts and not the presence of tight clearance in the processing equipment that is the root cause of protein subvisible particulate formation. When multiple mAbs, Fabs (fragment antigen binding), or non-antibody related proteins were mixed in the small-scale mixing model, for molecules investigated, it was observed that mAbs and Fabs appear to be more susceptible to particle formation than non-antibody-related proteins. In the grinding zone, mAb/Fab molecules aggregated into insoluble particles with neither detectable soluble aggregates nor fragmented species. This investigation represents a step closer to the understanding of the underlying stress mechanism leading to mAb subvisible particulate formation as the result of drug product processing. LAY ABSTRACT: Mixing and fill finish are important unit operations in drug product manufacturing for compounding (dilution, pooling, homogenization, etc.) and filling into primary packaging containers (vials, pre-filled syringes, etc.), respectively. The current trend in adopting bottom-mounted mixers as well as low fill-volume filling systems has raised concerns about their impact on drug product quality and process performance. However, investigations into the effects of their use for biopharmaceutical products, particularly monoclonal antibody formulations, are rarely published. The purpose of this study is three-fold: (1) to revisit the impact of bottom-mounted mixer design on monoclonal antibody subvisible particle formation; (2) to identify the root cause for subvisible particle formation; and (3) to fully utilize available particle analysis tools to demonstrate the correlation between particle count in the solution and filter fouling during sterile filtration. The outcomes of this study will benefit scientists and engineers who develop biologic product manufacturing processes by providing a better understanding of drug product process challenges. © PDA, Inc. 2017.

Intelligent laser soldering inspection and process control

NASA Technical Reports Server (NTRS)

Vanzetti, Riccardo

1987-01-01

Component assembly on printed circuitry keeps making giant strides toward denser packaging and smaller dimensions. From a single layer to multilayer, from through holes to surface mounted components and tape applied bonds, unrelenting progress results in new, difficult problems in assembling, soldering, inspecting and controlling the manufacturing process of the new electronics. Among the major problems are the variables introduced by human operators. The small dimensions and the tight assembly tolerances are now successfully met by machines which are faster and more precise than the human hand. The same is true for soldering. But visual inspection of the solder joints is now so severely limited by the ever shrinking area accessible to the human eye that the inspector's diagnosis cannot be trusted any longer. Solutions to correcting these problems are discussed.

Only in dying, life: programmed cell death during plant development.

PubMed

Van Hautegem, Tom; Waters, Andrew J; Goodrich, Justin; Nowack, Moritz K

2015-02-01

Programmed cell death (PCD) is a fundamental process of life. During the evolution of multicellular organisms, the actively controlled demise of cells has been recruited to fulfil a multitude of functions in development, differentiation, tissue homeostasis, and immune systems. In this review we discuss some of the multiple cases of PCD that occur as integral parts of plant development in a remarkable variety of cell types, tissues, and organs. Although research in the last decade has discovered a number of PCD regulators, mediators, and executers, we are still only beginning to understand the mechanistic complexity that tightly controls preparation, initiation, and execution of PCD as a process that is indispensable for successful vegetative and reproductive development of plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Thermal Design, Analysis, and Testing of the Quench Module Insert Bread Board

NASA Technical Reports Server (NTRS)

Breeding Shawn; Khodabandeh, Julia; Turner, Larry D. (Technical Monitor)

2001-01-01

The science requirements for materials processing is to provide the desired PI requirements of thermal gradient, solid/liquid interface front velocity for a given processing temperature desired by the PI. Processing is performed by translating the furnace with the sample in a stationary position to minimize any disturbances to the solid/liquid interface front during steady state processing. Typical sample materials for this metals and alloys furnace are lead-tin alloys, lead-antimony alloys, and aluminum alloys. Samples must be safe to process and therefore typically are contained with hermetically sealed cartridge tubes (gas tight) with inner ceramic liners (liquid tight) to prevent contamination and/or reaction of the sample material with the cartridge tube.

Cost-Effectiveness of Tight Control of Inflammation in Early Psoriatic Arthritis: Economic Analysis of a Multicenter Randomized Controlled Trial.

PubMed

O'Dwyer, John L; Meads, David M; Hulme, Claire T; Mcparland, Lucy; Brown, Sarah; Coates, Laura C; Moverley, Anna R; Emery, Paul; Conaghan, Philip G; Helliwell, Philip S

2018-03-01

Treat-to-target approaches have proved to be effective in rheumatoid arthritis, but have not been studied in psoriatic arthritis (PsA). This study was undertaken to examine the cost-effectiveness of tight control (TC) of inflammation in early PsA compared to standard care. Cost-effectiveness analyses were undertaken alongside a UK-based, open-label, multicenter, randomized controlled trial. Taking the perspective of the health care sector, effectiveness was measured using the 3-level EuroQol 5-domain, which allows for the calculation of quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) are presented, which represent the additional cost per QALY gained over a 48-week time horizon. Sensitivity analyses are presented assessing the impact of variations in the analytical approach and assumptions on the cost-effectiveness estimates. The mean cost and QALYs were higher in the TC group: £4,198 versus £2,000 and 0.602 versus 0.561. These values yielded an ICER of £53,948 per QALY. Bootstrapped uncertainty analysis suggests that the TC has a 0.07 probability of being cost-effective at a £20,000 threshold. Stratified analysis suggests that with certain costs being controlled, an ICER of £24,639 can be calculated for patients with a higher degree of disease severity. A tight control strategy to treat PsA is an effective intervention in the treatment pathway; however, this study does not find tight control to be cost-effective in most analyses. Lower drug prices, targeting polyarthritis patients, or reducing the frequency of rheumatology visits may improve value for money metrics in future studies. © 2017, American College of Rheumatology.

Monolithic optical phased-array transceiver in a standard SOI CMOS process.

PubMed

Abediasl, Hooman; Hashemi, Hossein

2015-03-09

Monolithic microwave phased arrays are turning mainstream in automotive radars and high-speed wireless communications fulfilling Gordon Moores 1965 prophecy to this effect. Optical phased arrays enable imaging, lidar, display, sensing, and holography. Advancements in fabrication technology has led to monolithic nanophotonic phased arrays, albeit without independent phase and amplitude control ability, integration with electronic circuitry, or including receive and transmit functions. We report the first monolithic optical phased array transceiver with independent control of amplitude and phase for each element using electronic circuitry that is tightly integrated with the nanophotonic components on one substrate using a commercial foundry CMOS SOI process. The 8 × 8 phased array chip includes thermo-optical tunable phase shifters and attenuators, nano-photonic antennas, and dedicated control electronics realized using CMOS transistors. The complex chip includes over 300 distinct optical components and over 74,000 distinct electrical components achieving the highest level of integration for any electronic-photonic system.

JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration.

PubMed

Mandicourt, Guillaume; Iden, Sandra; Ebnet, Klaus; Aurrand-Lions, Michel; Imhof, Beat A

2007-01-19

Junctional Adhesion Molecules (JAMs) have been described as major components of tight junctions in endothelial and epithelial cells. Tight junctions are crucial for the establishment and maintenance of cell polarity. During tumor development, they are remodeled, enabling neoplastic cells to escape from constraints imposed by intercellular junctions and to adopt a migratory behavior. Using a carcinoma cell line we tested whether JAM-C could affect tight junctions and migratory properties of tumor cells. We show that transfection of JAM-C improves the tight junctional barrier in tumor cells devoid of JAM-C expression. This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity. More importantly, the same mutation stimulates integrin-mediated cell migration and adhesion via the modulation of beta1 and beta3 integrin activation. These results highlight an unexpected function for JAM-C in controlling epithelial cell conversion from a static, polarized state to a pro-migratory phenotype.

A Randomised, Placebo-Controlled Trial of Neurodynamic Sliders on Hamstring Responses in Footballers with Hamstring Tightness

PubMed Central

Areeudomwong, Pattanasin; Oatyimprai, Ketsarakon; Pathumb, Saranchana

2016-01-01

Background Neurodynamics intervention is known to increase apparent muscle extensibility, but information regarding hamstring responses after a neurodynamic sliders (NS) technique is scarce. The aim of this study was to evaluate the effects of NS on apparent hamstring extensibility and activity in footballers with hamstring tightness. Methods Forty eligible healthy male footballers with hamstring tightness were each randomly allocated to either a 4-week NS technique or a control group (CG) receiving placebo shortwave intervention. Knee extension angles were measured with the passive knee extension test, and maximal voluntary isometric contraction (MVIC) of hamstrings was measured by a surface electromyography at baseline and after intervention sessions. Results The results showed that NS produced a statistically and clinically significant increase in knee extension angle compared to CG (P < 0.001); however, there was no difference between the groups receiving MVIC of hamstrings. Within group comparison, NS also provided a significant increase in knee extension angle (P < 0.001), whereas the control group did not. There was no change in hamstring MVIC in either group after intervention. Conclusions The findings of this study reveal that four weeks of NS technique improved apparent hamstring extensibility but did not change the hamstring activity in footballers with hamstring tightness. PMID:28090180

Second law of thermodynamics and quantum feedback control: Maxwell's demon with weak measurements

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

Jacobs, Kurt

2009-07-15

Recently Sagawa and Ueda [Phys. Rev. Lett. 100, 080403 (2008)] derived a bound on the work that can be extracted from a quantum system with the use of feedback control. For many quantum measurements their bound was not tight. We show that a tight version of this bound follows straightforwardly from recent work on Maxwell's demon by Alicki et al. [Open Syst. Inf. Dyn. 11, 205 (2004)], for both discrete and continuous feedback control. Our analysis also shows that bare, efficient measurements always do non-negative work on a system in equilibrium, but do not add heat.

Flexible distributed architecture for semiconductor process control and experimentation

NASA Astrophysics Data System (ADS)

Gower, Aaron E.; Boning, Duane S.; McIlrath, Michael B.

1997-01-01

Semiconductor fabrication requires an increasingly expensive and integrated set of tightly controlled processes, driving the need for a fabrication facility with fully computerized, networked processing equipment. We describe an integrated, open system architecture enabling distributed experimentation and process control for plasma etching. The system was developed at MIT's Microsystems Technology Laboratories and employs in-situ CCD interferometry based analysis in the sensor-feedback control of an Applied Materials Precision 5000 Plasma Etcher (AME5000). Our system supports accelerated, advanced research involving feedback control algorithms, and includes a distributed interface that utilizes the internet to make these fabrication capabilities available to remote users. The system architecture is both distributed and modular: specific implementation of any one task does not restrict the implementation of another. The low level architectural components include a host controller that communicates with the AME5000 equipment via SECS-II, and a host controller for the acquisition and analysis of the CCD sensor images. A cell controller (CC) manages communications between these equipment and sensor controllers. The CC is also responsible for process control decisions; algorithmic controllers may be integrated locally or via remote communications. Finally, a system server images connections from internet/intranet (web) based clients and uses a direct link with the CC to access the system. Each component communicates via a predefined set of TCP/IP socket based messages. This flexible architecture makes integration easier and more robust, and enables separate software components to run on the same or different computers independent of hardware or software platform.

Permeability and permeability anisotropy in Crab Orchard sandstone: Experimental insights into spatio-temporal effects

NASA Astrophysics Data System (ADS)

Gehne, Stephan; Benson, Philip M.

2017-08-01

Permeability in tight crustal rocks is primarily controlled by the connected porosity, shape and orientation of microcracks, the preferred orientation of cross-bedding, and sedimentary features such as layering. This leads to a significant permeability anisotropy. Less well studied, however, are the effects of time and stress recovery on the evolution of the permeability hysteresis which is becoming increasingly important in areas ranging from fluid migration in ore-forming processes to enhanced resource extraction. Here, we report new data simulating spatio-temporal permeability changes induced using effective pressure, simulating burial depth, on a tight sandstone (Crab Orchard). We find an initially (measured at 5 MPa) anisotropy of 2.5% in P-wave velocity and 180% in permeability anisotropy is significantly affected by the direction of the effective pressure change and cyclicity; anisotropy values decrease to 1% and 10% respectively after 3 cycles to 90 MPa and back. Furthermore, we measure a steadily increasing recovery time (10-20 min) for flow parallel to cross-bedding, and a far slower recovery time (20-50 min) for flow normal to cross-bedding. These data are interpreted via strain anisotropy and accommodation models, similar to the "seasoning" process often used in dynamic reservoir extraction.

Modeling uncertainty in producing natural gas from tight sands

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

Chermak, J.M.; Dahl, C.A.; Patrick, R.H

1995-12-31

Since accurate geologic, petroleum engineering, and economic information are essential ingredients in making profitable production decisions for natural gas, we combine these ingredients in a dynamic framework to model natural gas reservoir production decisions. We begin with the certainty case before proceeding to consider how uncertainty might be incorporated in the decision process. Our production model uses dynamic optimal control to combine economic information with geological constraints to develop optimal production decisions. To incorporate uncertainty into the model, we develop probability distributions on geologic properties for the population of tight gas sand wells and perform a Monte Carlo study tomore » select a sample of wells. Geological production factors, completion factors, and financial information are combined into the hybrid economic-petroleum reservoir engineering model to determine the optimal production profile, initial gas stock, and net present value (NPV) for an individual well. To model the probability of the production abandonment decision, the NPV data is converted to a binary dependent variable. A logit model is used to model this decision as a function of the above geological and economic data to give probability relationships. Additional ways to incorporate uncertainty into the decision process include confidence intervals and utility theory.« less

Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

PubMed

Colombel, Jean-Frederic; Panaccione, Remo; Bossuyt, Peter; Lukas, Milan; Baert, Filip; Vaňásek, Tomas; Danalioglu, Ahmet; Novacek, Gottfried; Armuzzi, Alessandro; Hébuterne, Xavier; Travis, Simon; Danese, Silvio; Reinisch, Walter; Sandborn, William J; Rutgeerts, Paul; Hommes, Daniel; Schreiber, Stefan; Neimark, Ezequiel; Huang, Bidan; Zhou, Qian; Mendez, Paloma; Petersson, Joel; Wallace, Kori; Robinson, Anne M; Thakkar, Roopal B; D'Haens, Geert

2018-12-23

Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week). De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met. The primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers 48 weeks after randomisation. Primary and safety analyses were done in the intention-to-treat population. This trial has been completed, and is registered with ClinicalTrials.gov, number NCT01235689. Between Feb 11, 2011, and Nov 3, 2016, 244 patients (mean disease duration: clinical management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group). 29 (24%) patients in the clinical management group and 32 (26%) patients in the tight control group discontinued the study, mostly because of adverse events. A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 (56 [46%] of 122 patients) than in the clinical management group (37 [30%] of 122 patients), with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1% (95% CI 3·9-28·3; p=0·010). 105 (86%) of 122 patients in the tight control group and 100 (82%) of 122 patients in the clinical management group reported treatment-emergent adverse events; no treatment-related deaths occurred. The most common adverse events were nausea (21 [17%] of 122 patients), nasopharyngitis (18 [15%]), and headache (18 [15%]) in the tight control group, and worsening Crohn's disease (35 [29%] of 122 patients), arthralgia (19 [16%]), and nasopharyngitis (18 [15%]) in the clinical management group. CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone. Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability. AbbVie. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endoribonuclease-Based Two-Component Repressor Systems for Tight Gene Expression Control in Plants

DOE PAGES

Liang, Yan; Richardson, Sarah; Yan, Jingwei; ...

2017-01-17

Tight control and multifactorial regulation of gene expression are important challenges in genetic engineering and are critical for the development of regulatory circuits. In meeting these challenges we will facilitate transgene expression regulation and support the fine-tuning of metabolic pathways to avoid the accumulation of undesired intermediates. By employing the endoribonuclease Csy4 and its recognition sequence from Pseudomonas aeruginosa and manipulating 5'UTR of mRNA, we developed a two-component expression–repression system to tightly control synthesis of transgene products. We demonstrated that this regulatory device was functional in monocotyledonous and dicotyledonous plant species, and showed that it can be used to repressmore » transgene expression by >400-fold and to synchronize transgene repression. In addition to tissue-specific transgene repression, this system offers stimuli-dependent expression control. Here, we identified 54 orthologous systems from various bacteria, using a bioinformatics approach and then validated in planta the activity for a few of those systems, demonstrating the potential diversity of such a two-component repressor system.« less

Endoribonuclease-Based Two-Component Repressor Systems for Tight Gene Expression Control in Plants

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

Liang, Yan; Richardson, Sarah; Yan, Jingwei

Tight control and multifactorial regulation of gene expression are important challenges in genetic engineering and are critical for the development of regulatory circuits. In meeting these challenges we will facilitate transgene expression regulation and support the fine-tuning of metabolic pathways to avoid the accumulation of undesired intermediates. By employing the endoribonuclease Csy4 and its recognition sequence from Pseudomonas aeruginosa and manipulating 5'UTR of mRNA, we developed a two-component expression–repression system to tightly control synthesis of transgene products. We demonstrated that this regulatory device was functional in monocotyledonous and dicotyledonous plant species, and showed that it can be used to repressmore » transgene expression by >400-fold and to synchronize transgene repression. In addition to tissue-specific transgene repression, this system offers stimuli-dependent expression control. Here, we identified 54 orthologous systems from various bacteria, using a bioinformatics approach and then validated in planta the activity for a few of those systems, demonstrating the potential diversity of such a two-component repressor system.« less

The nucleosome: A transparent, slippery, sticky and yet stable DNA-protein complex

NASA Astrophysics Data System (ADS)

Schiessel, H.

2006-03-01

Roughly three quarters of eucaryotic DNA are tightly wrapped onto protein cylinders organized in so-called nucleosomes. Despite this fact, the wrapped DNA cannot be inert since DNA is at the heart of many crucial life processes. We focus here on physical mechanisms that might allow nucleosomes to perform a great deal of such processes, specifically 1) on unwrapping fluctuations that give DNA-binding proteins access to the wrapped DNA portions without disrupting the nucleosome as a whole, 2) on corkscrew sliding along DNA and some implications and on 3) tail-bridging-induced attraction between nucleosomes as a means of controlling higher-order folding.

Boeing CST-100 Starliner Landing Simulation

NASA Image and Video Library

2018-06-05

Boeing, NASA and U.S. Army teams rehearse safely bringing the CST-100 Starliner spacecraft home to Earth on Wed., June 6, 2018, at the U.S. Army's White Sands Missile Range in New Mexico. During the detailed landing simulation, engineers, technicians and spaceflight specialists worked through tight timelines and intense heat running through simulations of the spacecraft's landing and recovery, an operation that will cap each Starliner mission. For flight controllers at Mission Control in Houston, the simulation offered the chance to evaluate their own processes and rehearse everything from undocking the Starliner from the space station to communicating with the recovery teams in the field.

SU-D-201-04: Evaluation of Elekta Agility MLC Performance Using Statistical Process Control

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

Meyers, SM; Balderson, MJ; Letourneau, D

2016-06-15

Purpose: to evaluate the performance and stability of the Elekta Agility MLC model using an automated quality control (QC) test in combination with statistical process control tools. Methods: Leaf positions were collected daily for 11 Elekta units over 5–19 months using the automated QC test, which analyzes 23 MV images to determine the location of MLC leaves relative to the radiation isocenter. The leaf positions are measured at 5 nominal positions, and images are acquired at collimator 0° and 180° to capture all MLC leaves in the field-of-view. Leaf positioning accuracy was assessed using individual and moving range control charts.more » Control limits were recomputed following MLC recalibration (occurred 1–2 times for 4 units). Specification levels of ±0.5, ±1 and ±1.5mm were tested. The mean and range of duration between out-of-control and out-of-specification events were determined. Results: Leaf position varied little over time, as confirmed by very tight individual control limits (mean ±0.19mm, range 0.09–0.44). Mean leaf position error was −0.03mm (range −0.89–0.83). Due to sporadic out-of-control events, the mean in-control duration was 3.3 days (range 1–23). Data stayed within ±1mm specification for 205 days on average (range 3–372) and within ±1.5mm for the entire date range. Measurements stayed within ±0.5mm for 1 day on average (range 0–17); however, our MLC leaves were not calibrated to this level of accuracy. Conclusion: The Elekta Agility MLC model was found to perform with high stability, as evidenced by the tight control limits. The in-specification durations support the current recommendation of monthly MLC QC tests with a ±1mm tolerance. Future work is on-going to determine if Agility performance can be optimized further using high-frequency QC test results to drive recalibration frequency. Factors that can affect leaf positioning accuracy, including beam spot motion, leaf gain calibration, drifting leaves, and image artifacts, are under investigation.« less

Glycemic Control for Patients With Type 2 Diabetes Mellitus: Our Evolving Faith in the Face of Evidence.

PubMed

Rodríguez-Gutiérrez, René; Montori, Victor M

2016-09-01

We sought to determine the concordance between the accumulating evidence about the impact of tight versus less tight glycemic control in patients with type 2 diabetes mellitus since the publication of UKPDS (UK Prospective Diabetes Study) in 1998 until 2015 with the views about that evidence published in journal articles and practice guidelines. We searched in top general medicine and specialty journals for articles referring to glycemic control appearing between 2006 and 2015 and identified the latest practice guidelines. To summarize the evidence, we included all published systematic reviews and meta-analyses of contemporary randomized trials of glycemic control measuring patient-important microvascular and macrovascular outcomes, and completed a meta-analysis of their follow-up extensions. We identified 16 guidelines and 328 statements. The body of evidence produced estimates warranting moderate confidence. This evidence reported no significant impact of tight glycemic control on the risk of dialysis/transplantation/renal death, blindness, or neuropathy. In the past decade, however, most published statements (77%-100%) and guidelines (95%) unequivocally endorsed benefit. There is also no significant effect on all-cause mortality, cardiovascular mortality, or stroke; however, there is a consistent 15% relative-risk reduction of nonfatal myocardial infarction. Between 2006 and 2008, most statements (47%-83%) endorsed the benefit; after 2008 (ACCORD), only a minority (21%-36%) did. Discordance exists between the research evidence and academic and clinical policy statements about the value of tight glycemic control to reduce micro- and macrovascular complications. This discordance may distort priorities in the research and practice agendas designed to improve the lives of patients with type 2 diabetes mellitus. © 2016 American Heart Association, Inc.

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition

PubMed Central

Song, Juhyun; Yoon, So Ra

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor-α), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases. PMID:28680530

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

PubMed

Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

Pore structure characterization of Chang-7 tight sandstone using MICP combined with N2GA techniques and its geological control factors

NASA Astrophysics Data System (ADS)

Cao, Zhe; Liu, Guangdi; Zhan, Hongbin; Li, Chaozheng; You, Yuan; Yang, Chengyu; Jiang, Hang

2016-11-01

Understanding the pore networks of unconventional tight reservoirs such as tight sandstones and shales is crucial for extracting oil/gas from such reservoirs. Mercury injection capillary pressure (MICP) and N2 gas adsorption (N2GA) are performed to evaluate pore structure of Chang-7 tight sandstone. Thin section observation, scanning electron microscope, grain size analysis, mineral composition analysis, and porosity measurement are applied to investigate geological control factors of pore structure. Grain size is positively correlated with detrital mineral content and grain size standard deviation while negatively related to clay content. Detrital mineral content and grain size are positively correlated with porosity, pore throat radius and withdrawal efficiency and negatively related to capillary pressure and pore-to-throat size ratio; while interstitial material is negatively correlated with above mentioned factors. Well sorted sediments with high debris usually possess strong compaction resistance to preserve original pores. Although many inter-crystalline pores are produced in clay minerals, this type of pores is not the most important contributor to porosity. Besides this, pore shape determined by N2GA hysteresis loop is consistent with SEM observation on clay inter-crystalline pores while BJH pore volume is positively related with clay content, suggesting N2GA is suitable for describing clay inter-crystalline pores in tight sandstones.

Pore structure characterization of Chang-7 tight sandstone using MICP combined with N2GA techniques and its geological control factors

PubMed Central

Cao, Zhe; Liu, Guangdi; Zhan, Hongbin; Li, Chaozheng; You, Yuan; Yang, Chengyu; Jiang, Hang

2016-01-01

Understanding the pore networks of unconventional tight reservoirs such as tight sandstones and shales is crucial for extracting oil/gas from such reservoirs. Mercury injection capillary pressure (MICP) and N2 gas adsorption (N2GA) are performed to evaluate pore structure of Chang-7 tight sandstone. Thin section observation, scanning electron microscope, grain size analysis, mineral composition analysis, and porosity measurement are applied to investigate geological control factors of pore structure. Grain size is positively correlated with detrital mineral content and grain size standard deviation while negatively related to clay content. Detrital mineral content and grain size are positively correlated with porosity, pore throat radius and withdrawal efficiency and negatively related to capillary pressure and pore-to-throat size ratio; while interstitial material is negatively correlated with above mentioned factors. Well sorted sediments with high debris usually possess strong compaction resistance to preserve original pores. Although many inter-crystalline pores are produced in clay minerals, this type of pores is not the most important contributor to porosity. Besides this, pore shape determined by N2GA hysteresis loop is consistent with SEM observation on clay inter-crystalline pores while BJH pore volume is positively related with clay content, suggesting N2GA is suitable for describing clay inter-crystalline pores in tight sandstones. PMID:27830731

Saccade Preparation Is Required for Exogenous Attention but Not Endogenous Attention or IOR

ERIC Educational Resources Information Center

Smith, Daniel T.; Schenk, Thomas; Rorden, Chris

2012-01-01

Covert attention is tightly coupled with the control of eye movements, but there is controversy about how tight this coupling is. The premotor theory of attention proposes that activation of the eye movement system is necessary to produce shifts of attention. In this study, we experimentally prevented healthy participants from planning or…

An Objective Measure of Noseband Tightness and Its Measurement Using a Novel Digital Tightness Gauge.

PubMed

Doherty, Orla; Conway, Thomas; Conway, Richard; Murray, Gerard; Casey, Vincent

2017-01-01

Noseband tightness is difficult to assess in horses participating in equestrian sports such as dressage, show jumping and three-day-eventing. There is growing concern that nosebands are commonly tightened to such an extent as to restrict normal equine behaviour and possibly cause injury. In the absence of a clear agreed definition of noseband tightness, a simple model of the equine nose-noseband interface environment was developed in order to guide further studies in this area. The normal force component of the noseband tensile force was identified as the key contributor to sub-noseband tissue compression. The model was used to inform the design of a digital tightness gauge which could reliably measure the normal force component of the noseband tensile force. A digital tightness gauge was developed to measure this parameter under nosebands fitted to bridled horses. Results are presented for field tests using two prototype designs. Prototype version three was used in field trial 1 (n = 15, frontal nasal plane sub-noseband site). Results of this trial were used to develop an ergonomically designed prototype, version 4, which was tested in a second field trial (n = 12, frontal nasal plane and lateral sub-noseband site). Nosebands were set to three tightness settings in each trial as judged by a single rater using an International Society for Equitation Science (ISES) taper gauge. Normal forces in the range 7-95 N were recorded at the frontal nasal plane while a lower range 1-28 N was found at the lateral site for the taper gauge range used in the trials. The digital tightness gauge was found to be simple to use, reliable, and safe and its use did not agitate the animals in any discernable way. A simple six point tightness scale is suggested to aid regulation implementation and the control of noseband tightness using normal force measurement as the objective tightness discriminant.

Systems Proteomics View of the Endogenous Human Claudin Protein Family

PubMed Central

Liu, Fei; Koval, Michael; Ranganathan, Shoba; Fanayan, Susan; Hancock, William S.; Lundberg, Emma K.; Beavis, Ronald C.; Lane, Lydie; Duek, Paula; McQuade, Leon; Kelleher, Neil L.; Baker, Mark S.

2016-01-01

Claudins are the major transmembrane protein components of tight junctions in human endothelia and epithelia. Tissue-specific expression of claudin members suggests that this protein family is not only essential for sustaining the role of tight junctions in cell permeability control but also vital in organizing cell contact signaling by protein–protein interactions. How this protein family is collectively processed and regulated is key to understanding the role of junctional proteins in preserving cell identity and tissue integrity. The focus of this review is to first provide a brief overview of the functional context, on the basis of the extensive body of claudin biology research that has been thoroughly reviewed, for endogenous human claudin members and then ascertain existing and future proteomics techniques that may be applicable to systematically characterizing the chemical forms and interacting protein partners of this protein family in human. The ability to elucidate claudin-based signaling networks may provide new insight into cell development and differentiation programs that are crucial to tissue stability and manipulation. PMID:26680015

Plant TOR signaling components

PubMed Central

John, Florian; Roffler, Stefan; Wicker, Thomas; Ringli, Christoph

2011-01-01

Cell growth is a process that needs to be tightly regulated. Cells must be able to sense environmental factors like nutrient abundance, the energy level or stress signals and coordinate growth accordingly. The Target Of Rapamycin (TOR) pathway is a major controller of growth-related processes in all eukaryotes. If environmental conditions are favorable, the TOR pathway promotes cell and organ growth and restrains catabolic processes like autophagy. Rapamycin is a specific inhibitor of the TOR kinase and acts as a potent inhibitor of TOR signaling. As a consequence, interfering with TOR signaling has a strong impact on plant development. This review summarizes the progress in the understanding of the biological significance and the functional analysis of the TOR pathway in plants. PMID:22057328

Controllable g5p-Protein-Directed Aggregation of ssDNA-Gold Nanoparticles

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

Lee, S.; Maye, M; Zhang, Y

We assembled single-stranded DNA (ssDNA) conjugated nanoparticles using the phage M13 gene 5 protein (g5p) as the molecular glue to bind two antiparallel noncomplementary ssDNA strands. The entire process was controlled tightly by the concentration of the g5p protein and the presence of double-stranded DNA. The g5p-ssDNA aggregate was disintegrated by hybridization with complementary ssDNA (C-ssDNA) that triggers the dissociation of the complex. Polyhistidine-tagged g5p was bound to nickel nitrilotriacetic acid (Ni2+-NTA) conjugated nanoparticles and subsequently used to coassemble the ssDNA-conjugated nanoparticles into multiparticle-type aggregates. Our approach offers great promise for designing biologically functional, controllable protein/nanoparticle composites.

Mold Heating and Cooling Pump Package Operator Interface Controls Upgrade

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

Josh A. Salmond

2009-08-07

The modernization of the Mold Heating and Cooling Pump Package Operator Interface (MHC PP OI) consisted of upgrading the antiquated single board computer with a proprietary operating system to off-the-shelf hardware and off-the-shelf software with customizable software options. The pump package is the machine interface between a central heating and cooling system that pumps heat transfer fluid through an injection or compression mold base on a local plastic molding machine. The operator interface provides the intelligent means of controlling this pumping process. Strict temperature control of a mold allows the production of high quality parts with tight tolerances and lowmore » residual stresses. The products fabricated are used on multiple programs.« less

House Dust Mite Der p 1 Effects on Sinonasal Epithelial Tight Junctions

PubMed Central

Henriquez, Oswaldo A.; Beste, Kyle Den; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma; Wise, Sarah K.

2013-01-01

Background Epithelial permeability is highly dependent upon the integrity of tight junctions, cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Methods Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen versus control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of tight junction proteins was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Results Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1 exposed cultured sinonasal cells versus controls. Conclusion Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. PMID:23592402

Statistical process control charts for attribute data involving very large sample sizes: a review of problems and solutions.

PubMed

Mohammed, Mohammed A; Panesar, Jagdeep S; Laney, David B; Wilson, Richard

2013-04-01

The use of statistical process control (SPC) charts in healthcare is increasing. The primary purpose of SPC is to distinguish between common-cause variation which is attributable to the underlying process, and special-cause variation which is extrinsic to the underlying process. This is important because improvement under common-cause variation requires action on the process, whereas special-cause variation merits an investigation to first find the cause. Nonetheless, when dealing with attribute or count data (eg, number of emergency admissions) involving very large sample sizes, traditional SPC charts often produce tight control limits with most of the data points appearing outside the control limits. This can give a false impression of common and special-cause variation, and potentially misguide the user into taking the wrong actions. Given the growing availability of large datasets from routinely collected databases in healthcare, there is a need to present a review of this problem (which arises because traditional attribute charts only consider within-subgroup variation) and its solutions (which consider within and between-subgroup variation), which involve the use of the well-established measurements chart and the more recently developed attribute charts based on Laney's innovative approach. We close by making some suggestions for practice.

Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes.

PubMed

Vyas, Sheela; Maatouk, Layal

2013-12-01

Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions.

[The effect of 18β-glycyrrhetinic acid on tight junctions of the nasal mucosa epithelial cells in rat models with allergic rhinitis].

PubMed

Ma, Yi; Gui, Yan; Wang, Youhu; Xi, Kehu; Chen, Xiaowan; Zhang, Fuhong; Ma, Chunxia; Hong, Hao; Liu, Xiangyi; Jiang, Ying; Dong, Ming; Yang, Guijun; Zhang, Xiaobing

2014-10-01

To observe 18β-glycyrrhetinic acid (GA) impact on ultrastructure of tight junctions (TJs) of nasal mucosa epithelial cells in rats models of allergic rhinitis (AR). Ninety-six Wistar rats were randomly divided into control group, model group, loratadine group, and 18β-glycyrrhetinic acid group, and each group had 24 rats. Ovalbumin was used to establish a rat AR model. The behavioral changes and the tight junctions of nasal epithelial were observed and compared in different groups after 2,4,6 and 10 weeks intervention. The length of TJs in allergic rhinitis model became shorter, electron-high-density plasma membrane became thicker, number of the integration loci reduced and gap of TJs widened or even ruptured. With the consistent effect of allergens,the changes of TJs in the model group aggravated gradually,and the changes of ultrastructure of TJs in 18β-glycyrrhetinic acid group was relieved apparently compared to model group and even were close to the control model with time. 18β-glycyrrhetinic acid can recover the ultrastructure of the tight junctions of AR rat nasal epithelial cells.

Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature.

PubMed

Chen, Lei; Yokel, Robert A; Hennig, Bernhard; Toborek, Michal

2008-12-01

Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular enrichment with glutathione. In the second series of experiments, rats were infused with nano-alumina at the dose of 29 mg/kg and the brains were stained for expression of tight junction proteins. Treatment with nano-alumina resulted in a marked fragmentation and disruption of integrity of claudin-5 and occludin. These results indicate that cerebral vasculature can be affected by nano-alumina. In addition, our data indicate that alterations of mitochondrial functions may be the underlying mechanism of nano-alumina toxicity.

Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier

PubMed Central

Caron, Tyler J; Scott, Kathleen E; Fox, James G; Hagen, Susan J

2015-01-01

Long-term chronic infection with Helicobacter pylori (H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer, tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach, or dysfunction in the infected stomach, however, are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells, claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules, each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging, because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore, the role of H. pylori virulence factors, such as cytotoxin-associated gene A and vacoulating cytotoxin, in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo, likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study, as well, is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions, normally and in H. pylori infection, and make predictions about the consequences of claudin reorganization during H. pylori infection. PMID:26523106

The ZO-1–associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density

PubMed Central

Balda, Maria S.; Garrett, Michelle D.; Matter, Karl

2003-01-01

Epithelial tight junctions regulate paracellular permeability, restrict apical/basolateral intramembrane diffusion of lipids, and have been proposed to participate in the control of epithelial cell proliferation and differentiation. Previously, we have identified ZO-1–associated nucleic acid binding proteins (ZONAB), a Y-box transcription factor whose nuclear localization and transcriptional activity is regulated by the tight junction–associated candidate tumor suppressor ZO-1. Now, we found that reduction of ZONAB expression using an antisense approach or by RNA interference strongly reduced proliferation of MDCK cells. Transfection of wild-type or ZONAB-binding fragments of ZO-1 reduced proliferation as well as nuclear ZONAB pools, indicating that promotion of proliferation by ZONAB requires its nuclear accumulation. Overexpression of ZONAB resulted in increased cell density in mature monolayers, and depletion of ZONAB or overexpression of ZO-1 reduced cell density. ZONAB was found to associate with cell division kinase (CDK) 4, and reduction of nuclear ZONAB levels resulted in reduced nuclear CDK4. Thus, our data indicate that tight junctions can regulate epithelial cell proliferation and cell density via a ZONAB/ZO-1–based pathway. Although this regulatory process may also involve regulation of transcription by ZONAB, our data suggest that one mechanism by which ZONAB and ZO-1 influence proliferation is by regulating the nuclear accumulation of CDK4. PMID:12566432

The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon

PubMed Central

Cohen, L; Sekler, I; Hershfinkel, M

2014-01-01

The intestinal epithelium is a renewable tissue that requires precise balance between proliferation and differentiation, an essential process for the formation of a tightly sealed barrier. Zinc deficiency impairs the integrity of the intestinal epithelial barrier and is associated with ulcerative and diarrheal pathologies, but the mechanisms underlying the role of Zn2+ are not well understood. Here, we determined a role of the colonocytic Zn2+ sensing receptor, ZnR/GPR39, in mediating Zn2+-dependent signaling and regulating the proliferation and differentiation of colonocytes. Silencing of ZnR/GPR39 expression attenuated Zn2+-dependent activation of ERK1/2 and AKT as well as downstream activation of mTOR/p70S6K, pathways that are linked with proliferation. Consistently, ZnR/GPR39 silencing inhibited HT29 and Caco-2 colonocyte proliferation, while not inducing caspase-3 cleavage. Remarkably, in differentiating HT29 colonocytes, silencing of ZnR/GPR39 expression inhibited alkaline phosphatase activity, a marker of differentiation. Furthermore, Caco-2 colonocytes showed elevated expression of ZnR/GPR39 during differentiation, whereas silencing of ZnR/GPR39 decreased monolayer transepithelial electrical resistance, suggesting compromised barrier formation. Indeed, silencing of ZnR/GPR39 or chelation of Zn2+ by the cell impermeable chelator CaEDTA was followed by impaired expression of the junctional proteins, that is, occludin, zonula-1 (ZO-1) and E-cadherin. Importantly, colon tissues of GPR39 knockout mice also showed a decrease in expression levels of ZO-1 and occludin compared with wildtype mice. Altogether, our results indicate that ZnR/GPR39 has a dual role in promoting proliferation of colonocytes and in controlling their differentiation. The latter is followed by ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. Thus, ZnR/GPR39 may be a therapeutic target for promoting epithelial function and tight junction barrier integrity during ulcerative colon diseases. PMID:24967969

The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon.

PubMed

Cohen, L; Sekler, I; Hershfinkel, M

2014-06-26

The intestinal epithelium is a renewable tissue that requires precise balance between proliferation and differentiation, an essential process for the formation of a tightly sealed barrier. Zinc deficiency impairs the integrity of the intestinal epithelial barrier and is associated with ulcerative and diarrheal pathologies, but the mechanisms underlying the role of Zn(2+) are not well understood. Here, we determined a role of the colonocytic Zn(2+) sensing receptor, ZnR/GPR39, in mediating Zn(2+)-dependent signaling and regulating the proliferation and differentiation of colonocytes. Silencing of ZnR/GPR39 expression attenuated Zn(2+)-dependent activation of ERK1/2 and AKT as well as downstream activation of mTOR/p70S6K, pathways that are linked with proliferation. Consistently, ZnR/GPR39 silencing inhibited HT29 and Caco-2 colonocyte proliferation, while not inducing caspase-3 cleavage. Remarkably, in differentiating HT29 colonocytes, silencing of ZnR/GPR39 expression inhibited alkaline phosphatase activity, a marker of differentiation. Furthermore, Caco-2 colonocytes showed elevated expression of ZnR/GPR39 during differentiation, whereas silencing of ZnR/GPR39 decreased monolayer transepithelial electrical resistance, suggesting compromised barrier formation. Indeed, silencing of ZnR/GPR39 or chelation of Zn(2+) by the cell impermeable chelator CaEDTA was followed by impaired expression of the junctional proteins, that is, occludin, zonula-1 (ZO-1) and E-cadherin. Importantly, colon tissues of GPR39 knockout mice also showed a decrease in expression levels of ZO-1 and occludin compared with wildtype mice. Altogether, our results indicate that ZnR/GPR39 has a dual role in promoting proliferation of colonocytes and in controlling their differentiation. The latter is followed by ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. Thus, ZnR/GPR39 may be a therapeutic target for promoting epithelial function and tight junction barrier integrity during ulcerative colon diseases.

Research on Submarine Pipeline Steel with High Performance

NASA Astrophysics Data System (ADS)

Ren, Yi; Liu, Wenyue; Zhang, Shuai; Wang, Shuang; Gao, Hong

Submarine pipeline steel has largely uniform elongation, low yield ratio and good balance between high strength and high plasticity because of the microstructure with dual phase. In this work, the microstructure and properties of the submarine pipeline steel are studied. The results show that the matrix structure is consisted of ferrite, bainite and martensite -austenite islands. The structure has a tight relationship with the thermal-mechanical controlled process. Fine dual phase shows good plasticity and low yield ratio, which can support the good balance between high strength and high plasticity.

An investigation of low ergonomics risk awareness, among staffs at early product development phase in Malaysia automotive industries

NASA Astrophysics Data System (ADS)

Aziz, Fazilah Abdul; Razali, Noraini; Najmiyah Jaafar, Nur

2016-02-01

Currently there are many automotive companies still unable to effectively prevent consequences of poor ergonomics in their manufacturing processes. This study purpose is to determine the surrounding factors that influence low ergonomics risk awareness among staffs at early product development phase in Malaysia automotive industry. In this study there are four variables, low ergonomic risk awareness, inappropriate method and tools, tight development schedule and lack of management support. The survey data were gathered from 245 respondents of local automotive companies in Malaysia. The data was analysed through multiple regression and moderated regression using the IBM SPSS software. Study results revealed that low ergonomic risk awareness has influenced by inappropriate method and tool, and tight development schedule. There were positive linear relationships between low ergonomic risk awareness and inappropriate method and tools, and tight development schedule. The more inappropriate method and tools applied; the lower their ergonomic risk awareness. The more tight development schedule is the lower ergonomic risk awareness. The relationship between low ergonomic risk awareness and inappropriate method and tools depends on staff's age, and education level. Furthermore the relationship between low ergonomic risk awareness and tight development schedule depends on staff's working experience and number of project involvement. The main contribution of this paper was identified the number of factors of low ergonomics risk awareness and offers better understanding on ergonomics among researchers and automotive manufacturer's employees during product development process.

The loop structure and the RNA helicase p72/DDX17 influence the processing efficiency of the mice miR-132

PubMed Central

Remenyi, Judit; Bajan, Sarah; Fuller-Pace, Frances V.; Arthur, J. Simon C.; Hutvagner, Gyorgy

2016-01-01

miRNAs are small RNAs that are key regulators of gene expression in eukaryotic organisms. The processing of miRNAs is regulated by structural characteristics of the RNA and is also tightly controlled by auxiliary protein factors. Among them, RNA binding proteins play crucial roles to facilitate or inhibit miRNA maturation and can be controlled in a cell, tissue and species-specific manners or in response to environmental stimuli. In this study we dissect the molecular mechanism that promotes the overexpression of miR-132 in mice over its related, co-transcribed and co-regulated miRNA, miR-212. We have shown that the loop structure of miR-132 is a key determinant for its efficient processing in cells. We have also identified a range of RNA binding proteins that recognize the loop of miR-132 and influence both miR-132 and miR-212 processing. The DEAD box helicase p72/DDX17 was identified as a factor that facilitates the specific processing of miR-132. PMID:26947125

Signaling at the Golgi During Mitosis

PubMed Central

Colanzi, Antonino; Sütterlin, Christine

2014-01-01

The Golgi complex of mammalian cells is composed of interconnected stacks of flattened cisternae that form a continuous membrane system in the pericentriolar region of the cell. At the onset of mitosis, this so-called Golgi ribbon is converted into small tubular–vesicular clusters in a tightly regulated fragmentation process, which leads to a temporary loss of the physical Golgi–centrosome proximity. Mitotic Golgi breakdown is required for Golgi partitioning into the two daughter cells, cell cycle progression and may contribute to the dispersal of Golgi-associated signaling molecules. Here, we review our current understanding of the mechanisms that control mitotic Golgi reorganization, its biological significance, and assays that are used to study this process. PMID:24295319

Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma

PubMed Central

Naz, Anam; Obaid, Ayesha; Awan, Faryal M.; Ikram, Aqsa; Ahmad, Jamil; Ali, Amjad

2017-01-01

Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells. PMID:28932213

Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma.

PubMed

Naz, Anam; Obaid, Ayesha; Awan, Faryal M; Ikram, Aqsa; Ahmad, Jamil; Ali, Amjad

2017-01-01

Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.

Short-term outcomes of arthroscopic TightRope® fixation are better than hook plate fixation in acute unstable acromioclavicular joint dislocations.

PubMed

Bin Abd Razak, Hamid Rahmatullah; Yeo, Eng-Meng Nicholas; Yeo, William; Lie, Tijauw-Tjoen Denny

2018-07-01

The aim of this study was to compare the short-term outcomes of arthroscopic TightRope ® fixation with that of hook plate fixation in patients with acute unstable acromioclavicular joint dislocations. We conducted a prospective case-control study of twenty-six patients with an acute ACJ dislocation who underwent surgical repair with either an arthroscopic TightRope ® fixation or a hook plate from 2013 to 2016. Clinical and radiological data were collected prospectively. Clinical outcomes were evaluated using the Constant Score, the University of California at Los Angeles (UCLA) Shoulder Score, Oxford Shoulder Score as well as the visual analogue scale. Radiological outcomes were assessed with the coracoclavicular distance (CCD). Sixteen patients underwent arthroscopic TightRope ® fixation, while 10 patients underwent hook plate fixation. There were no significant differences in the preoperative variables except for the mean UCLA 4b infraspinatus score (TightRope ® 2.8 vs. hook plate 3.8; p = 0.030). Duration of surgery was significantly longer in the TightRope ® group. At 1 year post-operatively, the TightRope ® group had a significantly better Constant Score and CCD with no complications. All patients with hook plate fixation had to undergo a second procedure for removal of implant, and 3 patients had complications. Arthroscopic TightRope ® fixation is a good option for the treatment of acute unstable ACJ dislocations. It has better short-term clinical and radiological outcomes as well as lesser complications when compared to hook plate fixation. Therapeutic, Level III.

Recent clinical advances in diabetic polyneuropathy.

PubMed

Horowitz, Steven H

2006-10-01

Recent dramatic increases in the incidence and prevalence of diabetes make an understanding of chronic symmetric sensorimotor diabetic polyneuropathy, the most common and problematic of chronic diabetic complications, essential for a wide range of medical practitioners. The demonstration of neuropathic dysfunction in patients with prediabetes or impaired glucose tolerance emphasizes the susceptibility of peripheral nerve fibers, especially small A delta fibers and C fibers, to relatively mild, short-duration hyperglycemia. New testing can reveal peripheral nerve dysfunction prior to clinical neuropathic symptoms and signs. In the absence of effective medications to halt or reverse nerve damage or promote nerve regeneration, early diagnosis of diabetic polyneuropathy, followed by tight glycemic control with diet and exercise, offers the best opportunity to prevent progressive symptoms of sensory loss, pain, autonomic dysfunction, ulcerations, and amputations. Some patients with impaired glucose tolerance have a reversal of neuropathic features with tight glycemic control. Nonpharmacologic therapies for neuropathic pain in diabetic polyneuropathy appear promising. Tight glycemic control, especially early in diabetes, is the best approach to minimizing the prevalence and severity of diabetic polyneuropathy and makes research into the deleterious effects of even mild hyperglycemia imperative.

Brains are not just neurons. Comment on “Toward a computational framework for cognitive biology: Unifying approaches from cognitive neuroscience and comparative cognition” by Fitch

NASA Astrophysics Data System (ADS)

Huber, Ludwig

2014-09-01

This comment addresses the first component of Fitch's framework: the computational power of single neurons [3]. Although I agree that traditional models of neural computation have vastly underestimated the computational power of single neurons, I am hesitant to follow him completely. The exclusive focus on neurons is likely to underestimate the importance of other cells in the brain. In the last years, two such cell types have received appropriate attention by neuroscientists: interneurons and glia. Interneurons are small, tightly packed cells involved in the control of information processing in learning and memory. Rather than transmitting externally (like motor or sensory neurons), these neurons process information within internal circuits of the brain (therefore also called 'relay neurons'). Some specialized interneuron subtypes temporally regulate the flow of information in a given cortical circuit during relevant behavioral events [4]. In the human brain approx. 100 billion interneurons control information processing and are implicated in disorders such as epilepsy and Parkinson's.

High-level recombinant protein expression in transgenic plants by using a double-inducible viral vector

PubMed Central

Werner, Stefan; Breus, Oksana; Symonenko, Yuri; Marillonnet, Sylvestre; Gleba, Yuri

2011-01-01

We describe here a unique ethanol-inducible process for expression of recombinant proteins in transgenic plants. The process is based on inducible release of viral RNA replicons from stably integrated DNA proreplicons. A simple treatment with ethanol releases the replicon leading to RNA amplification and high-level protein production. To achieve tight control of replicon activation and spread in the uninduced state, the viral vector has been deconstructed, and its two components, the replicon and the cell-to-cell movement protein, have each been placed separately under the control of an inducible promoter. Transgenic Nicotiana benthamiana plants incorporating this double-inducible system demonstrate negligible background expression, high (over 0.5 × 104-fold) induction multiples, and high absolute levels of protein expression upon induction (up to 4.3 mg/g fresh biomass). The process can be easily scaled up, supports expression of practically important recombinant proteins, and thus can be directly used for industrial manufacturing. PMID:21825158

Global RNA association with the transcriptionally active chromosome of chloroplasts.

PubMed

Lehniger, Marie-Kristin; Finster, Sabrina; Melonek, Joanna; Oetke, Svenja; Krupinska, Karin; Schmitz-Linneweber, Christian

2017-10-01

Processed chloroplast RNAs are co-enriched with preparations of the chloroplast transcriptionally active chromosome. Chloroplast genomes are organized as a polyploid DNA-protein structure called the nucleoid. Transcriptionally active chloroplast DNA together with tightly bound protein factors can be purified by gel filtration as a functional entity called the transcriptionally active chromosome (TAC). Previous proteomics analyses of nucleoids and of TACs demonstrated a considerable overlap in protein composition including RNA binding proteins. Therefore the RNA content of TAC preparations from Nicotiana tabacum was determined using whole genome tiling arrays. A large number of chloroplast RNAs was found to be associated with the TAC. The pattern of RNAs attached to the TAC consists of RNAs produced by different chloroplast RNA polymerases and differs from the pattern of RNA found in input controls. An analysis of RNA splicing and RNA editing of selected RNA species demonstrated that TAC-associated RNAs are processed to a similar extent as the RNA in input controls. Thus, TAC fractions contain a specific subset of the processed chloroplast transcriptome.

The Design and Development of an Omni-Directional Mobile Robot Oriented to an Intelligent Manufacturing System

PubMed Central

Qian, Jun; Zi, Bin; Ma, Yangang; Zhang, Dan

2017-01-01

In order to transport materials flexibly and smoothly in a tight plant environment, an omni-directional mobile robot based on four Mecanum wheels was designed. The mechanical system of the mobile robot is made up of three separable layers so as to simplify its combination and reorganization. Each modularized wheel was installed on a vertical suspension mechanism, which ensures the moving stability and keeps the distances of four wheels invariable. The control system consists of two-level controllers that implement motion control and multi-sensor data processing, respectively. In order to make the mobile robot navigate in an unknown semi-structured indoor environment, the data from a Kinect visual sensor and four wheel encoders were fused to localize the mobile robot using an extended Kalman filter with specific processing. Finally, the mobile robot was integrated in an intelligent manufacturing system for material conveying. Experimental results show that the omni-directional mobile robot can move stably and autonomously in an indoor environment and in industrial fields. PMID:28891964

Biological and physical controls in the Southern Ocean on past millennial-scale atmospheric CO2 changes.

PubMed

Gottschalk, Julia; Skinner, Luke C; Lippold, Jörg; Vogel, Hendrik; Frank, Norbert; Jaccard, Samuel L; Waelbroeck, Claire

2016-05-17

Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean-atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air-sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and (14)C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes.

Biological and physical controls in the Southern Ocean on past millennial-scale atmospheric CO2 changes

PubMed Central

Gottschalk, Julia; Skinner, Luke C.; Lippold, Jörg; Vogel, Hendrik; Frank, Norbert; Jaccard, Samuel L.; Waelbroeck, Claire

2016-01-01

Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean–atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air–sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and 14C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes. PMID:27187527

The Design and Development of an Omni-Directional Mobile Robot Oriented to an Intelligent Manufacturing System.

PubMed

Qian, Jun; Zi, Bin; Wang, Daoming; Ma, Yangang; Zhang, Dan

2017-09-10

In order to transport materials flexibly and smoothly in a tight plant environment, an omni-directional mobile robot based on four Mecanum wheels was designed. The mechanical system of the mobile robot is made up of three separable layers so as to simplify its combination and reorganization. Each modularized wheel was installed on a vertical suspension mechanism, which ensures the moving stability and keeps the distances of four wheels invariable. The control system consists of two-level controllers that implement motion control and multi-sensor data processing, respectively. In order to make the mobile robot navigate in an unknown semi-structured indoor environment, the data from a Kinect visual sensor and four wheel encoders were fused to localize the mobile robot using an extended Kalman filter with specific processing. Finally, the mobile robot was integrated in an intelligent manufacturing system for material conveying. Experimental results show that the omni-directional mobile robot can move stably and autonomously in an indoor environment and in industrial fields.

Epigenetic regulation and chromatin remodeling in learning and memory.

PubMed

Kim, Somi; Kaang, Bong-Kiun

2017-01-13

Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.

A Simplified Baseband Prefilter Model with Adaptive Kalman Filter for Ultra-Tight COMPASS/INS Integration

PubMed Central

Luo, Yong; Wu, Wenqi; Babu, Ravindra; Tang, Kanghua; Luo, Bing

2012-01-01

COMPASS is an indigenously developed Chinese global navigation satellite system and will share many features in common with GPS (Global Positioning System). Since the ultra-tight GPS/INS (Inertial Navigation System) integration shows its advantage over independent GPS receivers in many scenarios, the federated ultra-tight COMPASS/INS integration has been investigated in this paper, particularly, by proposing a simplified prefilter model. Compared with a traditional prefilter model, the state space of this simplified system contains only carrier phase, carrier frequency and carrier frequency rate tracking errors. A two-quadrant arctangent discriminator output is used as a measurement. Since the code tracking error related parameters were excluded from the state space of traditional prefilter models, the code/carrier divergence would destroy the carrier tracking process, and therefore an adaptive Kalman filter algorithm tuning process noise covariance matrix based on state correction sequence was incorporated to compensate for the divergence. The federated ultra-tight COMPASS/INS integration was implemented with a hardware COMPASS intermediate frequency (IF), and INS's accelerometers and gyroscopes signal sampling system. Field and simulation test results showed almost similar tracking and navigation performances for both the traditional prefilter model and the proposed system; however, the latter largely decreased the computational load. PMID:23012564

Effects of soybean agglutinin on intestinal barrier permeability and tight junction protein expression in weaned piglets.

PubMed

Zhao, Yuan; Qin, Guixin; Sun, Zewei; Che, Dongsheng; Bao, Nan; Zhang, Xiaodong

2011-01-01

This study was developed to provide further information on the intestinal barrier permeability and the tight junction protein expression in weaned piglets fed with different levels of soybean agglutinin (SBA). Twenty-five weaned crossbred barrows (Duroc × Landrace × Yorkshire) were selected and randomly allotted to five groups, each group with five replicates. The piglets in the control group were not fed with leguminous products. 0.05, 0.1, 0.15 and 0.2% SBA was added to the control diet to form four experimental diets, respectively. After the experimental period of 7 days (for each group), all the piglets were anesthetized with excess procaine and slaughtered. The d-lactic acid in plasma and the Ileal mucosa diamine oxidase (DAO) was analyzed to observe the change in the intestinal permeability. The tight junction proteins occludin and ZO-1 in the jejunum tissue distribution and relative expression were detected by immunohistochemistry and Western Blot. The results illustrated that a high dose of SBA (0.1-0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no significant affects. The contents of DAO, d-lactic acid, occludin or ZO-1, had a linear relationship with the SBA levels (0-0.2%) in diets. The high dose SBA (0.1-0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no affects.

Propagation of resist heating mask error to wafer level

NASA Astrophysics Data System (ADS)

Babin, S. V.; Karklin, Linard

2006-10-01

As technology is approaching 45 nm and below the IC industry is experiencing a severe product yield hit due to rapidly shrinking process windows and unavoidable manufacturing process variations. Current EDA tools are unable by their nature to deliver optimized and process-centered designs that call for 'post design' localized layout optimization DFM tools. To evaluate the impact of different manufacturing process variations on final product it is important to trace and evaluate all errors through design to manufacturing flow. Photo mask is one of the critical parts of this flow, and special attention should be paid to photo mask manufacturing process and especially to mask tight CD control. Electron beam lithography (EBL) is a major technique which is used for fabrication of high-end photo masks. During the writing process, resist heating is one of the sources for mask CD variations. Electron energy is released in the mask body mainly as heat, leading to significant temperature fluctuations in local areas. The temperature fluctuations cause changes in resist sensitivity, which in turn leads to CD variations. These CD variations depend on mask writing speed, order of exposure, pattern density and its distribution. Recent measurements revealed up to 45 nm CD variation on the mask when using ZEP resist. The resist heating problem with CAR resists is significantly smaller compared to other types of resists. This is partially due to higher resist sensitivity and the lower exposure dose required. However, there is no data yet showing CD errors on the wafer induced by CAR resist heating on the mask. This effect can be amplified by high MEEF values and should be carefully evaluated at 45nm and below technology nodes where tight CD control is required. In this paper, we simulated CD variation on the mask due to resist heating; then a mask pattern with the heating error was transferred onto the wafer. So, a CD error on the wafer was evaluated subject to only one term of the mask error budget - the resist heating CD error. In simulation of exposure using a stepper, variable MEEF was considered.

Transversal Fluctuations of the ASEP, Stochastic Six Vertex Model, and Hall-Littlewood Gibbsian Line Ensembles

NASA Astrophysics Data System (ADS)

Corwin, Ivan; Dimitrov, Evgeni

2018-05-01

We consider the ASEP and the stochastic six vertex model started with step initial data. After a long time, T, it is known that the one-point height function fluctuations for these systems are of order T 1/3. We prove the KPZ prediction of T 2/3 scaling in space. Namely, we prove tightness (and Brownian absolute continuity of all subsequential limits) as T goes to infinity of the height function with spatial coordinate scaled by T 2/3 and fluctuations scaled by T 1/3. The starting point for proving these results is a connection discovered recently by Borodin-Bufetov-Wheeler between the stochastic six vertex height function and the Hall-Littlewood process (a certain measure on plane partitions). Interpreting this process as a line ensemble with a Gibbsian resampling invariance, we show that the one-point tightness of the top curve can be propagated to the tightness of the entire curve.

A CPS Based Optimal Operational Control System for Fused Magnesium Furnace

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

Chai, Tian-you; Wu, Zhi-wei; Wang, Hong

Fused magnesia smelting for fused magnesium furnace (FMF) is an energy intensive process with high temperature and comprehensive complexities. Its operational index namely energy consumption per ton (ECPT) is defined as the consumed electrical energy per ton of acceptable quality and is difficult to measure online. Moreover, the dynamics of ECPT cannot be precisely modelled mathematically. The model parameters of the three-phase currents of the electrodes such as the molten pool level, its variation rate and resistance are uncertain and nonlinear functions of the changes in both the smelting process and the raw materials composition. In this paper, an integratedmore » optimal operational control algorithm proposed is composed of a current set-point control, a current switching control and a self-optimized tuning mechanism. The tight conjoining of and coordination between the computational resources including the integrated optimal operational control, embedded software, industrial cloud, wireless communication and the physical resources of FMF constitutes a cyber-physical system (CPS) based embedded optimal operational control system. Successful application of this system has been made for a production line with ten fused magnesium furnaces in a factory in China, leading to a significant reduced ECPT.« less

Flexible brain network reconfiguration supporting inhibitory control.

PubMed

Spielberg, Jeffrey M; Miller, Gregory A; Heller, Wendy; Banich, Marie T

2015-08-11

The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functional magnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties.

Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells.

PubMed

Nomura, Kazuaki; Obata, Kazufumi; Keira, Takashi; Miyata, Ryo; Hirakawa, Satoshi; Takano, Ken-ichi; Kohno, Takayuki; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

2014-02-18

Pseudomonas aeruginosa causes chronic respiratory disease, and the elastase enzyme that it produces increases the permeability of airway epithelial cells owing to the disruption of tight junctions. P. aeruginosa is also implicated in prolonged chronic rhinosinusitis. However, the effects of P. aeruginosa elastase (PE) against the barrier formed by human nasal epithelial cells (HNECs) remain unknown. To investigate the mechanisms involved in the disruption of tight junctions by PE in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were used. The hTERT-HNECs were pretreated with inhibitors of various signal transduction pathways, PKC, MAPK, p38MAPK, PI3K, JNK, NF-κB, EGF receptor, proteasome, COX1 and COX2 before treatment with PE. Some cells were pretreated with siRNA and agonist of protease activated receptor-2 (PAR-2) before treatment with PE. Expression and structures of tight junctions were determined by Western blotting, real-time PCR, immunostaining and freeze-fracture. Transepithelial electrical resistance (TER) was examined as the epithelial barrier function. PE treatment transiently disrupted the epithelial barrier and downregulated the transmembrane proteins claudin-1 and -4, occludin, and tricellulin, but not the scaffold PDZ-expression proteins ZO-1 and -2 and adherens junction proteins E-cadherin and β-catenin. The transient downregulation of tight junction proteins was controlled via distinct signal transduction pathways such as the PKC, MAPK, PI3K, p38 MAPK, JNK, COX-1 and -2, and NF-κB pathways. Furthermore, treatment with PE transiently decreased PAR-2 expression, which also regulated the expression of the tight junction proteins. Treatment with a PAR-2 agonist prevented the downregulation of the tight junction proteins after PE treatment in HNECs. PE transiently disrupts tight junctions in HNECs and downregulates PAR-2. The transient disruption of tight junctions by PE might occur repeatedly during chronic rhinosinusitis.

Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells

PubMed Central

2014-01-01

Background Pseudomonas aeruginosa causes chronic respiratory disease, and the elastase enzyme that it produces increases the permeability of airway epithelial cells owing to the disruption of tight junctions. P. aeruginosa is also implicated in prolonged chronic rhinosinusitis. However, the effects of P. aeruginosa elastase (PE) against the barrier formed by human nasal epithelial cells (HNECs) remain unknown. Methods To investigate the mechanisms involved in the disruption of tight junctions by PE in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were used. The hTERT-HNECs were pretreated with inhibitors of various signal transduction pathways, PKC, MAPK, p38MAPK, PI3K, JNK, NF-κB, EGF receptor, proteasome, COX1 and COX2 before treatment with PE. Some cells were pretreated with siRNA and agonist of protease activated receptor-2 (PAR-2) before treatment with PE. Expression and structures of tight junctions were determined by Western blotting, real-time PCR, immunostaining and freeze-fracture. Transepithelial electrical resistance (TER) was examined as the epithelial barrier function. Results PE treatment transiently disrupted the epithelial barrier and downregulated the transmembrane proteins claudin-1 and -4, occludin, and tricellulin, but not the scaffold PDZ-expression proteins ZO-1 and -2 and adherens junction proteins E-cadherin and β-catenin. The transient downregulation of tight junction proteins was controlled via distinct signal transduction pathways such as the PKC, MAPK, PI3K, p38 MAPK, JNK, COX-1 and -2, and NF-κB pathways. Furthermore, treatment with PE transiently decreased PAR-2 expression, which also regulated the expression of the tight junction proteins. Treatment with a PAR-2 agonist prevented the downregulation of the tight junction proteins after PE treatment in HNECs. Conclusions PE transiently disrupts tight junctions in HNECs and downregulates PAR-2. The transient disruption of tight junctions by PE might occur repeatedly during chronic rhinosinusitis. PMID:24548792

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

PubMed Central

2018-01-01

Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissue-specific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation but tightly associated with elongating axons of its partner MNs. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool. Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets, including the CM-innervating pool. We identify mesenchyme-derived connective tissue (CT) as a cell type in which Fat1 activity is required for the non–cell-autonomous control of CM muscle progenitor spreading, myogenic differentiation, motor innervation, and for motor pool specification. In parallel, Fat1 is required in MNs to promote their axonal growth and specification, indirectly influencing muscle progenitor progression. These results illustrate how Fat1 coordinates the coupling of muscular and neuronal morphogenesis by playing distinct but complementary actions in several cell types. PMID:29768404

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

PubMed Central

Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

2016-01-01

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology. Trial registration Clinical trials NCT01205854. PMID:27530741

Integration agent-based models and GIS as a virtual urban dynamic laboratory

NASA Astrophysics Data System (ADS)

Chen, Peng; Liu, Miaolong

2007-06-01

Based on the Agent-based Model and spatial data model, a tight-coupling integrating method of GIS and Agent-based Model (ABM) is to be discussed in this paper. The use of object-orientation for both spatial data and spatial process models facilitates their integration, which can allow exploration and explanation of spatial-temporal phenomena such as urban dynamic. In order to better understand how tight coupling might proceed and to evaluate the possible functional and efficiency gains from such a tight coupling, the agent-based model and spatial data model are discussed, and then the relationships affecting spatial data model and agent-based process models interaction. After that, a realistic crowd flow simulation experiment is presented. Using some tools provided by general GIS systems and a few specific programming languages, a new software system integrating GIS and MAS as a virtual laboratory applicable for simulating pedestrian flows in a crowd activity centre has been developed successfully. Under the environment supported by the software system, as an applicable case, a dynamic evolution process of the pedestrian's flows (dispersed process for the spectators) in a crowds' activity center - The Shanghai Stadium has been simulated successfully. At the end of the paper, some new research problems have been pointed out for the future.

Water-tight knee arthrotomy closure: comparison of a novel single bidirectional barbed self-retaining running suture versus conventional interrupted sutures.

PubMed

Nett, Michael; Avelar, Rui; Sheehan, Michael; Cushner, Fred

2011-03-01

Standard medial parapatellar arthrotomies of 10 cadaveric knees were closed with either conventional interrupted absorbable sutures (control group, mean of 19.4 sutures) or a single running knotless bidirectional barbed absorbable suture (experimental group). Water-tightness of the arthrotomy closure was compared by simulating a tense hemarthrosis and measuring arthrotomy leakage over 3 minutes. Mean total leakage was 356 mL and 89 mL in the control and experimental groups, respectively (p = 0.027). Using 8 of the 10 knees (4 closed with control sutures, 4 closed with an experimental suture), a tense hemarthrosis was again created, and iatrogenic suture rupture was performed: a proximal suture was cut at 1 minute; a distal suture was cut at 2 minutes. The impact of suture rupture was compared by measuring total arthrotomy leakage over 3 minutes. Mean total leakage was 601 mL and 174 mL in the control and experimental groups, respectively (p = 0.3). In summary, using a cadaveric model, arthrotomies closed with a single bidirectional barbed running suture were statistically significantly more water-tight than those closed using a standard interrupted technique. The sample size was insufficient to determine whether the two closure techniques differed in leakage volume after suture rupture.

Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.

PubMed

Lechuga, Susana; Ivanov, Andrei I

2017-07-01

The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimizing non-radiative energy transfer in hybrid colloidal-nanocrystal/silicon structures by controlled nanopillar architectures for future photovoltaic cells

NASA Astrophysics Data System (ADS)

Seitz, O.; Caillard, L.; Nguyen, H. M.; Chiles, C.; Chabal, Y. J.; Malko, A. V.

2012-01-01

To optimize colloidal nanocrystals/Si hybrid structures, nanopillars are prepared and organized via microparticle patterning and Si etching. A monolayer of CdSe nanocrystals is then grafted on the passivated oxide-free nanopillar surfaces, functionalized with carboxy-alkyl chain linkers. This process results to a negligible number of non-radiative surface state defects with a tightly controlled separation between the nanocrystals and Si. Steady-state and time-resolved photoluminescence measurements confirm the close-packing nanocrystal arrangement and the dominance of non-radiative energy transfer from nanocrystals to Si. We suggest that radially doped p-n junction devices based on energy transfer offer a viable approach for thin film photovoltaic devices.

New Evidence in the Management of Chronic Hypertension in Pregnancy.

PubMed

Podymow, Tiina; August, Phyllis

2017-07-01

Chronic hypertension complicates 1% to 5% of all pregnancies, but debate continues regarding the benefits of lowering blood pressure in pregnancy as well as the optimal blood pressure targets. Women with chronic hypertension are at significant risk for maternal and fetal morbidity and mortality, yet it remains unclear whether antihypertensive treatment during pregnancy lowers these risks. Severe hypertension (systolic ≥ 160 mm Hg) should be treated, but there is considerable variability in the approach to mild-to-moderate hypertension (140-159/90-109 mm Hg). The recently published CHIPS (Control of Hypertension in Pregnancy Study) trial is an important effort to attempt to determine treatment goals in mild to moderate pregnancy hypertension. The risks and benefits of tight versus less tight control of blood pressure in nonproteinuric hypertensive women, most of whom had pre-existing hypertension, were evaluated. A main finding was an increased risk of severe hypertension (adjusted odds ratio, 1.8) when blood pressure was not tightly controlled. In this review, general management of chronic hypertension in pregnancy is discussed, including changes in treatment that may be appropriate in light of new clinical trial data. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of microtubules in contractile ring function.

PubMed

Conrad, A H; Paulsen, A Q; Conrad, G W

1992-05-01

During cytokinesis, a cortical contractile ring forms around a cell, constricts to a stable tight neck and terminates in separation of the daughter cells. At first cleavage, Ilyanassa obsoleta embryos form two contractile rings simultaneously. The cleavage furrow (CF), in the animal hemisphere between the spindle poles, constricts to a stable tight neck and separates the daughter cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below the spindle, constricts to a transient tight neck, but then relaxes, allowing the polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of PLC-3 formation develop varied numbers of constriction rings in their animal hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At maximum constriction, control embryos display immunolocalization of nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via electron microscopy, many microtubules extending through their CFs, but not through their PLCs. Embryos which form stabilized tightly constricted CFs and PLCs in the presence of taxol display immunolocalization of nonextractable alpha-tubulin in both constrictions and show many polymerized microtubules extending through both CFs and PLCs. These results suggest that the extension of microtubules through a tight contractile ring may be important for stabilizing that constriction and facilitating subsequent cytokinesis.

The role of microtubules in contractile ring function

NASA Technical Reports Server (NTRS)

Conrad, A. H.; Paulsen, A. Q.; Conrad, G. W.; Spooner, B. S. (Principal Investigator)

1992-01-01

During cytokinesis, a cortical contractile ring forms around a cell, constricts to a stable tight neck and terminates in separation of the daughter cells. At first cleavage, Ilyanassa obsoleta embryos form two contractile rings simultaneously. The cleavage furrow (CF), in the animal hemisphere between the spindle poles, constricts to a stable tight neck and separates the daughter cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below the spindle, constricts to a transient tight neck, but then relaxes, allowing the polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of PLC-3 formation develop varied numbers of constriction rings in their animal hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At maximum constriction, control embryos display immunolocalization of nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via electron microscopy, many microtubules extending through their CFs, but not through their PLCs. Embryos which form stabilized tightly constricted CFs and PLCs in the presence of taxol display immunolocalization of nonextractable alpha-tubulin in both constrictions and show many polymerized microtubules extending through both CFs and PLCs. These results suggest that the extension of microtubules through a tight contractile ring may be important for stabilizing that constriction and facilitating subsequent cytokinesis.

Sticking together: building a biofilm the Bacillus subtilis way

PubMed Central

Vlamakis, Hera; Chai, Yunrong; Beauregard, Pascale; Losick, Richard; Kolter, Roberto

2014-01-01

Preface Biofilms are ubiquitous communities of tightly associated bacteria encased in an extracellular matrix. Bacillus subtilis has long-served as a robust model organism to examine the molecular mechanisms of biofilm formation and a number of studies have revealed that this process is subject to a number of integrated regulatory pathways. In this Review, we focus on the molecular mechanisms controlling biofilm assembly and briefly summarize the current state of knowledge regarding their disassembly. We also discuss recent progress that has expanded our understanding of biofilm formation on plant roots, which are a natural habitat for this soil bacterium. PMID:23353768

Investigation of factors affecting the synthesis of nano-cadmium sulfide by pulsed laser ablation in liquid environment

NASA Astrophysics Data System (ADS)

Darwish, Ayman M.; Eisa, Wael H.; Shabaka, Ali A.; Talaat, Mohamed H.

2016-01-01

Pulsed laser ablation in a liquid medium is a promising technique as compared to the other synthetic methods to synthesize different materials in nanoscale form. The laser parameters (e.g., wavelength, pulse width, fluence, and repetition frequency) and liquid medium (e.g., aqueous/nonaqueous liquid or solution with surfactant) were tightly controlled during and after the ablation process. By optimizing these parameters, the particle size and distribution of materials can be adjusted. The UV-vis absorption spectra and weight changes of targets were used for the characterization and comparison of products.

Sticking together: building a biofilm the Bacillus subtilis way.

PubMed

Vlamakis, Hera; Chai, Yunrong; Beauregard, Pascale; Losick, Richard; Kolter, Roberto

2013-03-01

Biofilms are ubiquitous communities of tightly associated bacteria encased in an extracellular matrix. Bacillus subtilis has long served as a robust model organism to examine the molecular mechanisms of biofilm formation, and a number of studies have revealed that this process is regulated by several integrated pathways. In this Review, we focus on the molecular mechanisms that control B. subtilis biofilm assembly, and then briefly summarize the current state of knowledge regarding biofilm disassembly. We also discuss recent progress that has expanded our understanding of B. subtilis biofilm formation on plant roots, which are a natural habitat for this soil bacterium.

The importance of task design and behavioral control for understanding the neural basis of cognitive functions.

PubMed

Fetsch, Christopher R

2016-04-01

The success of systems neuroscience depends on the ability to forge quantitative links between neural activity and behavior. Traditionally, this process has benefited from the rigorous development and testing of hypotheses using tools derived from classical psychophysics and computational motor control. As our capacity for measuring neural activity improves, accompanied by powerful new analysis strategies, it seems prudent to remember what these traditional approaches have to offer. Here I present a perspective on the merits of principled task design and tight behavioral control, along with some words of caution about interpretation in unguided, large-scale neural recording studies. I argue that a judicious combination of new and old approaches is the best way to advance our understanding of higher brain function in health and disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Scratch2 prevents cell cycle re-entry by repressing miR-25 in postmitotic primary neurons.

PubMed

Rodríguez-Aznar, Eva; Barrallo-Gimeno, Alejandro; Nieto, M Angela

2013-03-20

During the development of the nervous system the regulation of cell cycle, differentiation, and survival is tightly interlinked. Newly generated neurons must keep cell cycle components under strict control, as cell cycle re-entry leads to neuronal degeneration and death. However, despite their relevance, the mechanisms controlling this process remain largely unexplored. Here we show that Scratch2 is involved in the control of the cell cycle in neurons in the developing spinal cord of the zebrafish embryo. scratch2 knockdown induces postmitotic neurons to re-enter mitosis. Scratch2 prevents cell cycle re-entry by maintaining high levels of the cycle inhibitor p57 through the downregulation of miR-25. Thus, Scratch2 appears to safeguard the homeostasis of postmitotic primary neurons by preventing cell cycle re-entry.

Dynamic subcellular localization of a respiratory complex controls bacterial respiration

PubMed Central

Alberge, François; Espinosa, Leon; Seduk, Farida; Sylvi, Léa; Toci, René; Walburger, Anne; Magalon, Axel

2015-01-01

Respiration, an essential process for most organisms, has to optimally respond to changes in the metabolic demand or the environmental conditions. The branched character of their respiratory chains allows bacteria to do so by providing a great metabolic and regulatory flexibility. Here, we show that the native localization of the nitrate reductase, a major respiratory complex under anaerobiosis in Escherichia coli, is submitted to tight spatiotemporal regulation in response to metabolic conditions via a mechanism using the transmembrane proton gradient as a cue for polar localization. These dynamics are critical for controlling the activity of nitrate reductase, as the formation of polar assemblies potentiates the electron flux through the complex. Thus, dynamic subcellular localization emerges as a critical factor in the control of respiration in bacteria. DOI: http://dx.doi.org/10.7554/eLife.05357.001 PMID:26077726

The role of JAM-A in inflammatory bowel disease: unrevealing the ties that bind.

PubMed

Vetrano, Stefania; Danese, Silvio

2009-05-01

Tight junctions (TJ) are junctional proteins whose function is to maintain an intact intestinal epithelial barrier and regulate the paracellular movement of water and solutes. Altered TJ structure and epithelial permeability are observed in inflammatory bowel disease and seem to have an important role in the pathogenesis of these diseases. Junctional adhesion molecule-A (JAM-A) is a protein expressed at tight junctions of epithelial and endothelial cells, as well as on circulating leukocytes. Its function at tight junctions appears to be crucial as an extracellular adhesive molecule in the direct regulation of intestinal barrier function. This review focuses on the role of JAM-A in controlling mucosal homeostasis by regulating the integrity and permeability of epithelial barrier function.

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

Decker, A.D.; Kuuskraa, V.A.; Klawitter, A.L.

Recurrent basement faulting is the primary controlling mechanism for aligning and compartmentalizing upper Cretaceous aged tight gas reservoirs of the San Juan and Piceance Basins. Northwest trending structural lineaments that formed in conjunction with the Uncompahgre Highlands have profoundly influenced sedimentation trends and created boundaries for gas migration; sealing and compartmentalizing sedimentary packages in both basins. Fractures which formed over the structural lineaments provide permeability pathways which allowing gas recovery from otherwise tight gas reservoirs. Structural alignments and associated reservoir compartments have been accurately targeted by integrating advanced remote sensing imagery, high resolution aeromagnetics, seismic interpretation, stratigraphic mapping and dynamicmore » structural modelling. This unifying methodology is a powerful tool for exploration geologists and is also a systematic approach to tight gas resource assessment in frontier basins.« less

Scalable Multiprocessor for High-Speed Computing in Space

NASA Technical Reports Server (NTRS)

Lux, James; Lang, Minh; Nishimoto, Kouji; Clark, Douglas; Stosic, Dorothy; Bachmann, Alex; Wilkinson, William; Steffke, Richard

2004-01-01

A report discusses the continuing development of a scalable multiprocessor computing system for hard real-time applications aboard a spacecraft. "Hard realtime applications" signifies applications, like real-time radar signal processing, in which the data to be processed are generated at "hundreds" of pulses per second, each pulse "requiring" millions of arithmetic operations. In these applications, the digital processors must be tightly integrated with analog instrumentation (e.g., radar equipment), and data input/output must be synchronized with analog instrumentation, controlled to within fractions of a microsecond. The scalable multiprocessor is a cluster of identical commercial-off-the-shelf generic DSP (digital-signal-processing) computers plus generic interface circuits, including analog-to-digital converters, all controlled by software. The processors are computers interconnected by high-speed serial links. Performance can be increased by adding hardware modules and correspondingly modifying the software. Work is distributed among the processors in a parallel or pipeline fashion by means of a flexible master/slave control and timing scheme. Each processor operates under its own local clock; synchronization is achieved by broadcasting master time signals to all the processors, which compute offsets between the master clock and their local clocks.

Convergent microRNA actions coordinate neocortical development.

PubMed

Barca-Mayo, Olga; De Pietri Tonelli, Davide

2014-08-01

Neocortical development is a complex process that, at the cellular level, involves tight control of self-renewal, cell fate commitment, survival, differentiation and delamination/migration. These processes require, at the molecular level, the precise regulation of intrinsic signaling pathways and extrinsic factors with coordinated action in a spatially and temporally specific manner. Transcriptional regulation plays an important role during corticogenesis; however, microRNAs (miRNAs) are emerging as important post-transcriptional regulators of various aspects of central nervous system development. miRNAs are a class of small, single-stranded noncoding RNA molecules that control the expression of the majority of protein coding genes (i.e., targets). How do different miRNAs achieve precise control of gene networks during neocortical development? Here, we critically review all the miRNA-target interactions validated in vivo, with relevance to the generation and migration of pyramidal-projection glutamatergic neurons, and for the initial formation of cortical layers in the embryonic development of rodent neocortex. In particular, we focus on convergent miRNA actions, which are still a poorly understood layer of complexity in miRNA signaling, but potentially one of the keys to disclosing how miRNAs achieve the precise coordination of complex biological processes such as neocortical development.

Acceleration of fusion in mouse palates by in vitro exposure to excess G

NASA Technical Reports Server (NTRS)

Duke, J.; Janer, L.; Campbell, M.

1984-01-01

Palatal shelves from 13- and 14-day mouse embryos were excised and cultured in contiguous pairs. Experimental cultures were exposed to 2.6 G in a culture centrifuge; controls were in the same incubator. After 24 hours, palates were prepared for light or electron microscopy. Scoring of paraffin sections according to the stage of fusion seen in the medial epithelial edges (MEE) showed that palates exposed to excess G were in more advanced stages of fusion than were controls. Ultrastructurally, control MEE had tightly apposed cell membranes and numerous desmosomes; in centrifuged MEE, desmosomes had been removed and there was much intercellular space. Nuclear membranes were intact in control MEE, but showed marked deterioration in MEE of centrifuged palates. Few lysosomes and no necrosis were seen in control MEE; centrifuged MEE had numerous lysosomes as well as necrotic cells. Basal lamina were intact in controls, but interrupted in centrifuged palates. The results confirm the hypothesis that gravitational increases speed up the differentiative process.

Design and Evaluation of a Robust PID Controller for a Fully Implantable Artificial Pancreas

PubMed Central

2015-01-01

Treatment of type 1 diabetes mellitus could be greatly improved by applying a closed-loop control strategy to insulin delivery, also known as an artificial pancreas (AP). In this work, we outline the design of a fully implantable AP using intraperitoneal (IP) insulin delivery and glucose sensing. The design process utilizes the rapid glucose sensing and insulin action offered by the IP space to tune a PID controller with insulin feedback to provide safe and effective insulin delivery. The controller was tuned to meet robust performance and stability specifications. An anti-reset windup strategy was introduced to prevent dangerous undershoot toward hypoglycemia after a large meal disturbance. The final controller design achieved 78% of time within the tight glycemic range of 80–140 mg/dL, with no time spent in hypoglycemia. The next step is to test this controller design in an animal model to evaluate the in vivo performance. PMID:26538805

Effects of Soybean Agglutinin on Intestinal Barrier Permeability and Tight Junction Protein Expression in Weaned Piglets

PubMed Central

Zhao, Yuan; Qin, Guixin; Sun, Zewei; Che, Dongsheng; Bao, Nan; Zhang, Xiaodong

2011-01-01

This study was developed to provide further information on the intestinal barrier permeability and the tight junction protein expression in weaned piglets fed with different levels of soybean agglutinin (SBA). Twenty-five weaned crossbred barrows (Duroc × Landrace × Yorkshire) were selected and randomly allotted to five groups, each group with five replicates. The piglets in the control group were not fed with leguminous products. 0.05, 0.1, 0.15 and 0.2% SBA was added to the control diet to form four experimental diets, respectively. After the experimental period of 7 days (for each group), all the piglets were anesthetized with excess procaine and slaughtered. The d-lactic acid in plasma and the Ileal mucosa diamine oxidase (DAO) was analyzed to observe the change in the intestinal permeability. The tight junction proteins occludin and ZO-1 in the jejunum tissue distribution and relative expression were detected by immunohistochemistry and Western Blot. The results illustrated that a high dose of SBA (0.1–0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no significant affects. The contents of DAO, d-lactic acid, occludin or ZO-1, had a linear relationship with the SBA levels (0–0.2%) in diets. The high dose SBA (0.1–0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no affects. PMID:22272087

Tight coupling of Na+/K+-ATPase with glycolysis demonstrated in permeabilized rat cardiomyocytes.

PubMed

Sepp, Mervi; Sokolova, Niina; Jugai, Svetlana; Mandel, Merle; Peterson, Pearu; Vendelin, Marko

2014-01-01

The effective integrated organization of processes in cardiac cells is achieved, in part, by the functional compartmentation of energy transfer processes. Earlier, using permeabilized cardiomyocytes, we demonstrated the existence of tight coupling between some of cardiomyocyte ATPases and glycolysis in rat. In this work, we studied contribution of two membrane ATPases and whether they are coupled to glycolysis--sarcoplasmic reticulum Ca2+ ATPase (SERCA) and plasmalemma Na+/K+-ATPase (NKA). While SERCA activity was minor in this preparation in the absence of calcium, major role of NKA was revealed accounting to ∼30% of the total ATPase activity which demonstrates that permeabilized cell preparation can be used to study this pump. To elucidate the contribution of NKA in the pool of ATPases, a series of kinetic measurements was performed in cells where NKA had been inhibited by 2 mM ouabain. In these cells, we recorded: ADP- and ATP-kinetics of respiration, competition for ADP between mitochondria and pyruvate kinase (PK), ADP-kinetics of endogenous PK, and ATP-kinetics of total ATPases. The experimental data was analyzed using a series of mathematical models with varying compartmentation levels. The results show that NKA is tightly coupled to glycolysis with undetectable flux of ATP between mitochondria and NKA. Such tight coupling of NKA to PK is in line with its increased importance in the pathological states of the heart when the substrate preference shifts to glucose.

Effect of ceramide-1-phosphate transfer protein on intestinal bacterial translocation in severe acute pancreatitis.

PubMed

Wang, Jiang; Li, Chang; Jiang, Yingjian; Zheng, Hongmei; Li, Dehui; Liang, Yibo; Deng, Wensheng; Zhang, Dianliang

2017-02-01

The aim of the study was to investigate the effects of ceramide-1-phosphate transfer protein (CPTP) on the intestinal epithelial tight junction proteins in patients with severe acute pancreatitis (SAP). Fifty patients with SAP were classified into two groups according to the presence of bacterial translocation (BT) in the blood. Thirty healthy individuals were included in the control group. The presence of BT was analyzed by polymerase chain reaction. The expression of tight junction proteins and CPTP was determined using immunohistochemistry and western blotting. Bacterial DNA was detected in the peripheral blood of 62.0% of the patients with SAP. The expression of CPTP and tight junction proteins in SAP patients was lower than that in healthy controls. Among the patients with SAP, those positive for BT(+) showed a lower level of CPTP and occluding (OC) and zonula occludens-1 (ZO-1) expression and a higher level of IVA cPLA2 expression than BT(-) patients. Moreover, the expression of CPTP was significantly associated with ZO-1 and showed a negative correlation with expression of IVA cPLA2 in SAP-BT(+) patients. CPTP affects the expression of tight junction proteins and may protects the intestinal epithelial barrier by downregulating the expression of IVA cPLA2. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Multiscale Pore Throat Network Reconstruction of Tight Porous Media Constrained by Mercury Intrusion Capillary Pressure and Nuclear Magnetic Resonance Measurements

NASA Astrophysics Data System (ADS)

Xu, R.; Prodanovic, M.

2017-12-01

Due to the low porosity and permeability of tight porous media, hydrocarbon productivity strongly depends on the pore structure. Effective characterization of pore/throat sizes and reconstruction of their connectivity in tight porous media remains challenging. Having a representative pore throat network, however, is valuable for calculation of other petrophysical properties such as permeability, which is time-consuming and costly to obtain by experimental measurements. Due to a wide range of length scales encountered, a combination of experimental methods is usually required to obtain a comprehensive picture of the pore-body and pore-throat size distributions. In this work, we combine mercury intrusion capillary pressure (MICP) and nuclear magnetic resonance (NMR) measurements by percolation theory to derive pore-body size distribution, following the work by Daigle et al. (2015). However, in their work, the actual pore-throat sizes and the distribution of coordination numbers are not well-defined. To compensate for that, we build a 3D unstructured two-scale pore throat network model initialized by the measured porosity and the calculated pore-body size distributions, with a tunable pore-throat size and coordination number distribution, which we further determine by matching the capillary pressure vs. saturation curve from MICP measurement, based on the fact that the mercury intrusion process is controlled by both the pore/throat size distributions and the connectivity of the pore system. We validate our model by characterizing several core samples from tight Middle East carbonate, and use the network model to predict the apparent permeability of the samples under single phase fluid flow condition. Results show that the permeability we get is in reasonable agreement with the Coreval experimental measurements. The pore throat network we get can be used to further calculate relative permeability curves and simulate multiphase flow behavior, which will provide valuable insights into the production optimization and enhanced oil recovery design.

A comparison of a novel robust decentralised control strategy and MPC for industrial high purity, high recovery, multicomponent distillation.

PubMed

Udugama, Isuru A; Wolfenstetter, Florian; Kirkpatrick, Robert; Yu, Wei; Young, Brent R

2017-07-01

In this work we have developed a novel, robust practical control structure to regulate an industrial methanol distillation column. This proposed control scheme is based on a override control framework and can manage a non-key trace ethanol product impurity specification while maintaining high product recovery. For comparison purposes, a MPC with a discrete process model (based on step tests) was also developed and tested. The results from process disturbance testing shows that, both the MPC and the proposed controller were capable of maintaining both the trace level ethanol specification in the distillate (X D ) and high product recovery (β). Closer analysis revealed that the MPC controller has a tighter X D control, while the proposed controller was tighter in β control. The tight X D control allowed the MPC to operate at a higher X D set point (closer to the 10ppm AA grade methanol standard), allowing for savings in energy usage. Despite the energy savings of the MPC, the proposed control scheme has lower installation and running costs. An economic analysis revealed a multitude of other external economic and plant design factors, that should be considered when making a decision between the two controllers. In general, we found relatively high energy costs favour MPC. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Importance of bicarbonate transport in pH control during amelogenesis - need for functional studies.

PubMed

Varga, G; DenBesten, P; Rácz, R; Zsembery, Á

2017-08-18

Dental enamel, the hardest mammalian tissue, is produced by ameloblasts. Ameloblasts show many similarities to other transporting epithelia although their secretory product, the enamel matrix, is quite different. Ameloblasts direct the formation of hydroxyapatite crystals, which liberate large quantities of protons that then need to be buffered to allow mineralization to proceed. Buffering requires a tight pH regulation and secretion of bicarbonate by ameloblasts. Many investigations have used immunohistochemical and knockout studies to determine the effects of these genes on enamel formation, but up till recently very little functional data were available for mineral ion transport. To address this, we developed a novel 2D in vitro model using HAT-7 ameloblast cells. HAT-7 cells can be polarized and develop functional tight junctions. Furthermore, they are able to accumulate bicarbonate ions from the basolateral to the apical fluid spaces. We propose that in the future, the HAT-7 2D system along with similar cellular models will be useful to functionally model ion transport processes during amelogenesis. Additionally, we also suggest that similar approaches will allow a better understanding of the regulation of the cycling process in maturation-stage ameloblasts, and the pH sensory mechanisms, which are required to develop sound, healthy enamel. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus

PubMed Central

Chen, Xiaodi; Threlkeld, Steven W.; Cummings, Erin E.; Juan, Ilona; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Sadowska, Grazyna B.; Stonestreet, Barbara S.

2012-01-01

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days-of-gestation without ischemia, and 4-, 24-, or 48-h after ischemia. The largest increase in Ki (P<0.05) was 4-h after ischemia. Occludin and claudin-5 expressions decreased at 4-h, but returned toward control levels 24- and 48-h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4-h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24- and 48- than 4-h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. PMID:22986172

Wormholes, baby universes, and causality

NASA Astrophysics Data System (ADS)

Visser, Matt

1990-02-01

In this paper wormholes defined on a Minkowski signature manifold are considered, both at the classical and quantum levels. It is argued that causality in quantum gravity may best be imposed by restricting the functional integral to include only causal Lorentzian spacetimes. Subject to this assumption, one can put very tight constraints on the quantum behavior of wormholes, their cousins the baby universes, and topology-changing processes in general. Even though topology-changing processes are tightly constrained, this still allows very interesting geometrical (rather than topological) effects. In particular, the laboratory construction of baby universes is not prohibited provided that the ``umbilical cord'' is never cut. Methods for relaxing these causality constraints are also discussed.

Differential roles of NADPH oxidases in vascular physiology and pathophysiology

PubMed Central

Amanso, Angelica M.; Griendling, Kathy K.

2012-01-01

Reactive oxygen species (ROS) are produced by all vascular cells and regulate the major physiological functions of the vasculature. Production and removal of ROS are tightly controlled and occur in discrete subcellular locations, allowing for specific, compartmentalized signaling. Among the many sources of ROS in the vessel wall, NADPH oxidases are implicated in physiological functions such as control of vasomotor tone, regulation of extracellular matrix and phenotypic modulation of vascular smooth muscle cells. They are involved in the response to injury, whether as an oxygen sensor during hypoxia, as a regulator of protein processing, as an angiogenic stimulus, or as a mechanism of wound healing. These enzymes have also been linked to processes leading to disease development, including migration, proliferation, hypertrophy, apoptosis and autophagy. As a result, NADPH oxidases participate in atherogenesis, systemic and pulmonary hypertension and diabetic vascular disease. The role of ROS in each of these processes and diseases is complex, and a more full understanding of the sources, targets, cell-specific responses and counterbalancing mechanisms is critical for the rational development of future therapeutics. PMID:22202108

In situ post-weld heat treatment on martensitic stainless steel turbine runners using a robotic induction heating process to control temperature distribution

NASA Astrophysics Data System (ADS)

Boudreault, E.; Hazel, B.; Côté, J.; Godin, S.

2014-03-01

A new robotic heat treatment process is developed. Using this solution it is now possible to perform local heat treatment on large steel components. Crack, cavitation and erosion repairs on turbine blades and Pelton buckets are among the applications of this technique. The proof of concept is made on a 13Cr-4Ni stainless steel designated "CA6NM". This alloy is widely used in the power industry for modern system components. Given the very tight temperature tolerance (600 to 630 °C) for post-weld heat treatment on this alloy, 13Cr-4Ni stainless steel is very well suited for demonstrating the possibilities of this process. To achieve heat treatment requirements, an induction heating system is mounted on a compact manipulator named "Scompi". This robot moves a pancake coil in order to control the temperature distribution. A simulator using thermal finite element analysis is first used for path planning. A feedback loop adjusts parameters in function of environmental conditions.

Multi-Objective Hybrid Optimal Control for Interplanetary Mission Planning

NASA Technical Reports Server (NTRS)

Englander, Jacob

2015-01-01

Preliminary design of low-thrust interplanetary missions is a highly complex process. The mission designer must choose discrete parameters such as the number of flybys, the bodies at which those flybys are performed, and in some cases the final destination. Because low-thrust trajectory design is tightly coupled with systems design, power and propulsion characteristics must be chosen as well. In addition, a time-history of control variables must be chosen which defines the trajectory. There are often many thousands, if not millions, of possible trajectories to be evaluated. The customer who commissions a trajectory design is not usually interested in a point solution, but rather the exploration of the trade space of trajectories between several different objective functions. This can be very expensive process in terms of the number of human analyst hours required. An automated approach is therefore very desirable. This work presents such an approach by posing the mission design problem as a multi-objective hybrid optimal control problem. The methods is demonstrated on hypothetical mission to the main asteroid belt and to Deimos.

Multi-Objective Hybrid Optimal Control for Interplanetary Mission Planning

NASA Technical Reports Server (NTRS)

Englander, Jacob A.

2014-01-01

Preliminary design of low-thrust interplanetary missions is a highly complex process. The mission designer must choose discrete parameters such as the number of flybys, the bodies at which those flybys are performed, and in some cases the final destination. Because low-thrust trajectory design is tightly coupled with systems design, power and propulsion characteristics must be chosen as well. In addition, a time-history of control variables must be chosen which defines the trajectory. There are often may thousands, if not millions, of possible trajectories to be evaluated. The customer who commissions a trajectory design is not usually interested in a point solution, but rather the exploration of the trade space of trajectories between several different objective functions. This can be a very expensive process in terms of the number of human analyst hours required. An automated approach is therefore very desirable. This work presents such an approach by posing the mission design problem as a multi-objective hybrid optimal control problem. The method is demonstrated on hypothetical mission to the main asteroid belt and to Deimos.

Event-Driven Random-Access-Windowing CCD Imaging System

NASA Technical Reports Server (NTRS)

Monacos, Steve; Portillo, Angel; Ortiz, Gerardo; Alexander, James; Lam, Raymond; Liu, William

2004-01-01

A charge-coupled-device (CCD) based high-speed imaging system, called a realtime, event-driven (RARE) camera, is undergoing development. This camera is capable of readout from multiple subwindows [also known as regions of interest (ROIs)] within the CCD field of view. Both the sizes and the locations of the ROIs can be controlled in real time and can be changed at the camera frame rate. The predecessor of this camera was described in High-Frame-Rate CCD Camera Having Subwindow Capability (NPO- 30564) NASA Tech Briefs, Vol. 26, No. 12 (December 2002), page 26. The architecture of the prior camera requires tight coupling between camera control logic and an external host computer that provides commands for camera operation and processes pixels from the camera. This tight coupling limits the attainable frame rate and functionality of the camera. The design of the present camera loosens this coupling to increase the achievable frame rate and functionality. From a host computer perspective, the readout operation in the prior camera was defined on a per-line basis; in this camera, it is defined on a per-ROI basis. In addition, the camera includes internal timing circuitry. This combination of features enables real-time, event-driven operation for adaptive control of the camera. Hence, this camera is well suited for applications requiring autonomous control of multiple ROIs to track multiple targets moving throughout the CCD field of view. Additionally, by eliminating the need for control intervention by the host computer during the pixel readout, the present design reduces ROI-readout times to attain higher frame rates. This camera (see figure) includes an imager card consisting of a commercial CCD imager and two signal-processor chips. The imager card converts transistor/ transistor-logic (TTL)-level signals from a field programmable gate array (FPGA) controller card. These signals are transmitted to the imager card via a low-voltage differential signaling (LVDS) cable assembly. The FPGA controller card is connected to the host computer via a standard peripheral component interface (PCI).

Controlled energy deposition and void-like modification inside transparent solids by two-color tightly focused femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Potemkin, Fedor; Mareev, Evgeniy; Bezsudnova, Yulia; Platonenko, Victor; Bravy, Boris; Gordienko, Vyacheslav

2017-04-01

We report a bulk void-like micromodification of fused silica using two-color μJ-energy level tightly focused (NA = 0.5) co-propagating seeding (visible, 0.62 μm) and heating (near-IR, 1.24 μm) femtosecond laser pulses with online third harmonic diagnostics of created microplasmas as well as subsequent laser-induced void-like defects. It has been shown experimentally and theoretically that production of seeding electrons through multiphoton ionization by visible laser pulses paves the way for controllability of the energy deposition and laser-induced micromodification via carrier heating by delayed infrared laser pulses inside the material. Experimental results demonstrate wide possibilities to increase the density of energy deposited up to 6 kJ cm-3 inside the dielectric by tight focusing of two color fs-laser pulses and elliptical polarization for infrared heating fs-laser pulses. The developed theoretical approach predicts the enhancement of deposited energy density up to 9 kJ cm-3 using longer (mid-IR) wavelengths for heating laser pulses.

Planetary nebula progenitors that swallow binary systems

NASA Astrophysics Data System (ADS)

Soker, Noam

2016-01-01

I propose that some irregular messy planetary nebulae (PNe) owe their morphologies to triple-stellar evolution where tight binary systems evolve inside and/or on the outskirts of the envelope of asymptotic giant branch (AGB) stars. In some cases, the tight binary system can survive, in others, it is destroyed. The tight binary system might break up with one star leaving the system. In an alternative evolution, one of the stars of the broken-up tight binary system falls towards the AGB envelope with low specific angular momentum, and drowns in the envelope. In a different type of destruction process, the drag inside the AGB envelope causes the tight binary system to merge. This releases gravitational energy within the AGB envelope, leading to a very asymmetrical envelope ejection, with an irregular and messy PN as a descendant. The evolution of the triple-stellar system can be in a full common envelope evolution or in a grazing envelope evolution. Both before and after destruction (if destruction takes place), the system might launch pairs of opposite jets. One pronounced signature of triple-stellar evolution might be a large departure from axisymmetrical morphology of the descendant PN. I estimate that about one in eight non-spherical PNe is shaped by one of these triple-stellar evolutionary routes.

Tightly coupled integration of ionosphere-constrained precise point positioning and inertial navigation systems.

PubMed

Gao, Zhouzheng; Zhang, Hongping; Ge, Maorong; Niu, Xiaoji; Shen, Wenbin; Wickert, Jens; Schuh, Harald

2015-03-10

The continuity and reliability of precise GNSS positioning can be seriously limited by severe user observation environments. The Inertial Navigation System (INS) can overcome such drawbacks, but its performance is clearly restricted by INS sensor errors over time. Accordingly, the tightly coupled integration of GPS and INS can overcome the disadvantages of each individual system and together form a new navigation system with a higher accuracy, reliability and availability. Recently, ionosphere-constrained (IC) precise point positioning (PPP) utilizing raw GPS observations was proven able to improve both the convergence and positioning accuracy of the conventional PPP using ionosphere-free combined observations (LC-PPP). In this paper, a new mode of tightly coupled integration, in which the IC-PPP instead of LC-PPP is employed, is implemented to further improve the performance of the coupled system. We present the detailed mathematical model and the related algorithm of the new integration of IC-PPP and INS. To evaluate the performance of the new tightly coupled integration, data of both airborne and vehicle experiments with a geodetic GPS receiver and tactical grade inertial measurement unit are processed and the results are analyzed. The statistics show that the new approach can further improve the positioning accuracy compared with both IC-PPP and the tightly coupled integration of the conventional PPP and INS.

Tight junctions in cancer metastasis.

PubMed

Martin, Tracey A; Mason, Malcolm D; Jiang, Wen G

2011-01-01

Tight Junctions (TJ) are well known to function as a control for the paracellular diffusion of ions and certain molecules, it has however, become evident that the TJ has a vital role in maintaining cell to cell integrity. Loss of cohesion of the TJ structure can lead to invasion and ultimately to the metastasis of cancer cells. This review will discuss how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the progression of cancer and progression of metastasis.

SMG-1 and mTORC1 Act Antagonistically to Regulate Response to Injury and Growth in Planarians

PubMed Central

González-Estévez, Cristina; Felix, Daniel A.; Smith, Matthew D.; Paps, Jordi; Morley, Simon J.; James, Victoria; Sharp, Tyson V.; Aboobaker, A. Aziz

2012-01-01

Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth and the formation of regenerative blastemas that remain undifferentiated and that lead to lethal ectopic outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and differentiation defects are hallmarks of this uncontrolled growth. These data imply a previously unappreciated and novel physiological function for this PIKK family member. In contrast we found that planarian members of the mTOR complex 1, tor and raptor, are required for the initial response to injury and blastema formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal growth requires mTOR signalling. We also found that the macrolide rapamycin, a natural compound inhibitor of mTORC1, is able to increase the survival rate of smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model where Smg-1 acts as a novel regulator of both the response to injury and growth control mechanisms. Our data suggest the possibility that this may be by suppressing mTOR signalling. Characterisation of both the planarian mTORC1 signalling components and another PIKK family member as key regulators of regeneration and growth will influence future work on regeneration, growth control, and the development of anti-cancer therapies that target mTOR signalling. PMID:22479207

The Reproductive System.

PubMed

Pask, Andrew

2016-01-01

Correct sexual development is arguably the most important trait in an organism's life history since it is directly related to its genetic fitness. The developing gonad houses the germ cells, the only legacy we pass on to subsequent generations. Given the pivotal importance of correct reproductive function, it is confounding that disorders of sex development (DSDs) are among the most common congenital abnormalities in humans (Lee et al. J Pediatr Urol 8(6):611-615, 2012). Urogenital development is a highly complex process involving coordinated interactions between molecular and hormonal pathways in a tightly regulated order. The controls that regulate some of the key events in this process are beginning to be unraveled. This chapter provides an overview of our understanding of urogenital development from the gonads to the urogenital ducts and external genitalia.

Distinct functions of human RecQ helicases during DNA replication.

PubMed

Urban, Vaclav; Dobrovolna, Jana; Janscak, Pavel

2017-06-01

DNA replication is the most vulnerable process of DNA metabolism in proliferating cells and therefore it is tightly controlled and coordinated with processes that maintain genomic stability. Human RecQ helicases are among the most important factors involved in the maintenance of replication fork integrity, especially under conditions of replication stress. RecQ helicases promote recovery of replication forks being stalled due to different replication roadblocks of either exogenous or endogenous source. They prevent generation of aberrant replication fork structures and replication fork collapse, and are involved in proper checkpoint signaling. The essential role of human RecQ helicases in the genome maintenance during DNA replication is underlined by association of defects in their function with cancer predisposition. Copyright © 2016 Elsevier B.V. All rights reserved.

[Mg2+, ATP-dependent plasma membrane calcium pump of smooth muscle cells. I. Structural organization and properties].

PubMed

Veklich, T O; Mazur, Iu Iu; Kosterin, S O

2015-01-01

Tight control of cytoplasm Ca2+ concentration is essential in cell functioning. Changing of Ca2+ concentration is thorough in smooth muscle cells, because it determines relaxation/constraint process. One of key proteins which control Ca2+ concentration in cytoplasm is Mg2+, ATP-dependent plasma membrane calcium pump. Thus, it is important to find compoumds which allowed one to change Mg2+, ATP-dependent plasma membrane calcium pump activity, as long as this topic is of current interest in biochemical research which regards energy and pharmacomechanical coupling mechanism of muscle excitation and contraction. In this article we generalized literatute and own data about properties of smooth muscle cell plasma membrane Ca(2+)-pump. Stuctural oganization, kinetical properties and molecular biology are considered.

Communication Dynamics in Finite Capacity Social Networks

NASA Astrophysics Data System (ADS)

Haerter, Jan O.; Jamtveit, Bjørn; Mathiesen, Joachim

2012-10-01

In communication networks, structure and dynamics are tightly coupled. The structure controls the flow of information and is itself shaped by the dynamical process of information exchanged between nodes. In order to reconcile structure and dynamics, a generic model, based on the local interaction between nodes, is considered for the communication in large social networks. In agreement with data from a large human organization, we show that the flow is non-Markovian and controlled by the temporal limitations of individuals. We confirm the versatility of our model by predicting simultaneously the degree-dependent node activity, the balance between information input and output of nodes, and the degree distribution. Finally, we quantify the limitations to network analysis when it is based on data sampled over a finite period of time.

Density control in ITER: an iterative learning control and robust control approach

NASA Astrophysics Data System (ADS)

Ravensbergen, T.; de Vries, P. C.; Felici, F.; Blanken, T. C.; Nouailletas, R.; Zabeo, L.

2018-01-01

Plasma density control for next generation tokamaks, such as ITER, is challenging because of multiple reasons. The response of the usual gas valve actuators in future, larger fusion devices, might be too slow for feedback control. Both pellet fuelling and the use of feedforward-based control may help to solve this problem. Also, tight density limits arise during ramp-up, due to operational limits related to divertor detachment and radiative collapses. As the number of shots available for controller tuning will be limited in ITER, in this paper, iterative learning control (ILC) is proposed to determine optimal feedforward actuator inputs based on tracking errors, obtained in previous shots. This control method can take the actuator and density limits into account and can deal with large actuator delays. However, a purely feedforward-based density control may not be sufficient due to the presence of disturbances and shot-to-shot differences. Therefore, robust control synthesis is used to construct a robustly stabilizing feedback controller. In simulations, it is shown that this combined controller strategy is able to achieve good tracking performance in the presence of shot-to-shot differences, tight constraints, and model mismatches.

Effects of Gravity on Cells, Tissues, and Organisms: Their Implications on Habitat and Human Support in Microgravity

NASA Technical Reports Server (NTRS)

Kizito, John

2004-01-01

This presentation will demonstrate that gravity plays a major role in advanced human life support in a closed habitat. The examples include, but are not limited to, control of purity in drinking water supplies (application of biocides), control of urine in space rodent habitats and operation of space septic tanks (waste management). Our goal is to understand and determine possible mechanisms that describe the process by which cells anchor to a substrate to form dynamic, vibrant communities of cells which influence human health in absence of gravity. The balance of all forces (mechanotransduction) acting on a cell will determine whether a cell thrives and multiplies or dies in a process called apoptosis and/or necrosis. The balance of forces are tightly coupled to the transport of nutrients and metabolic products (biochemotransduction) to and from the cell interface. We will highlight our effort to improve astronaut health by showing that microgravity life support systems have to be designed differently from those on Earth.

Dynamic DNA-controlled "stop-and-go" assembly of well-defined protein domains on RNA-scaffolded TMV-like nanotubes.

PubMed

Schneider, Angela; Eber, Fabian J; Wenz, Nana L; Altintoprak, Klara; Jeske, Holger; Eiben, Sabine; Wege, Christina

2016-12-01

A DNA-based approach allows external control over the self-assembly process of tobacco mosaic virus (TMV)-like ribonucleoprotein nanotubes: their growth from viral coat protein (CP) subunits on five distinct RNA scaffolds containing the TMV origin of assembly (OAs) could be temporarily blocked by a stopper DNA oligomer hybridized downstream (3') of the OAs. At two upstream (5') sites tested, simple hybridization was not sufficient for stable stalling, which correlates with previous findings on a non-symmetric assembly of TMV. The growth of DNA-arrested particles could be restarted efficiently by displacement of the stopper via its toehold by using a release DNA oligomer, even after storage for twelve days. This novel strategy for growing proteinaceous tubes under tight kinetic and spatial control combines RNA guidance and its site-specific but reversible interruption by DNA blocking elements. As three of the RNA scaffolds contained long heterologous non-TMV sequence portions that included the stopping sites, this method is applicable to all RNAs amenable to TMV CP encapsidation, albeit with variable efficiency most likely depending on the scaffolds' secondary structures. The use of two distinct, selectively addressable CP variants during the serial assembly stages finally enabled an externally configured fabrication of nanotubes with highly defined subdomains. The "stop-and-go" strategy thus might pave the way towards production routines of TMV-like particles with variable aspect ratios from a single RNA scaffold, and of nanotubes with two or even more adjacent protein domains of tightly pre-defined lengths.

Toward an injectable continuous osmotic glucose sensor.

PubMed

Johannessen, Erik; Krushinitskaya, Olga; Sokolov, Andrey; Philipp, Häfliger; Hoogerwerf, Arno; Hinderling, Christian; Kautio, Kari; Lenkkeri, Jaakko; Strömmer, Esko; Kondratyev, Vasily; Tønnessen, Tor Inge; Mollnes, Tom Eirik; Jakobsen, Henrik; Zimmer, Even; Akselsen, Bengt

2010-07-01

The growing pandemic of diabetes mellitus places a stringent social and economic burden on the society. A tight glycemic control circumvents the detrimental effects, but the prerogative is the development of new more effective tools capable of longterm tracking of blood glucose (BG) in vivo. Such discontinuous sensor technologies will benefit from an unprecedented marked potential as well as reducing the current life expectancy gap of eight years as part of a therapeutic regime. A sensor technology based on osmotic pressure incorporates a reversible competitive affinity assay performing glucose-specific recognition. An absolute change in particles generates a pressure that is proportional to the glucose concentration. An integrated pressure transducer and components developed from the silicon micro- and nanofabrication industry translate this pressure into BG data. An in vitro model based on a 3.6 x 8.7 mm large pill-shaped implant is equipped with a nanoporous membrane holding 4-6 nm large pores. The affinity assay offers a dynamic range of 36-720 mg/dl with a resolution of +/-16 mg/dl. An integrated 1 x 1 mm(2) large control chip samples the sensor signals for data processing and transmission back to the reader at a total power consumption of 76 microW. Current studies have demonstrated the design, layout, and performance of a prototype osmotic sensor in vitro using an affinity assay solution for up to four weeks. The small physical size conforms to an injectable device, forming the basis of a conceptual monitor that offers a tight glycemic control of BG. 2010 Diabetes Technology Society.

Analysis of cholesterol trafficking with fluorescent probes

PubMed Central

Maxfield, Frederick R.; Wüstner, Daniel

2013-01-01

Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport processes are not well understood. Fluorescence microscopy is a valuable tool for studying intracellular transport processes, but this method can be challenging for lipid molecules because addition of a fluorophore may alter the properties of the molecule greatly. We discuss the use of fluorescent molecules that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy and by multiphoton microscopy are described. Some label-free methods for imaging cholesterol itself are also discussed briefly. PMID:22325611

Assessment of respiratory symptoms and lung function values among the brick field workers of West Bengal, India.

PubMed

Das, Banibrata

2016-07-03

Brick manufacturing process releases large amounts of silica dust into the work environment due to the use of silica-containing materials. The main aim of the study was to investigate the impairment of lung function and prevalence of respiratory symptoms among the different groups of brick field workers in comparison with control subjects. A total of 250 brick field workers and 130 unexposed control subjects were randomly selected in which demographic characteristics, respiratory symptoms, and lung function values were recorded. The result showed significantly lower p value (<.001) in lung function and respiratory symptoms among brick field workers when compared with control group. The prevalence of respiratory symptoms was dyspnea (46.8%), phlegm (39.2%), and chest tightness (27.6%). Dust exposure in working environment affected the lung function values and increased the respiratory symptoms among the brick field workers.

Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

PubMed

Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

2015-04-20

Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

Optical diagnostics in gas turbine combustors

NASA Astrophysics Data System (ADS)

Woodruff, Steven D.

1999-01-01

Deregulation of the power industry and increasingly tight emission controls are pushing gas turbine manufacturers to develop engines operating at high pressure for efficiency and lean fuel mixtures to control NOx. This combination also gives rise to combustion instabilities which threaten engine integrity through acoustic pressure oscillations and flashback. High speed imaging and OH emission sensors have been demonstrated to be invaluable tools in characterizing and monitoring unstable combustion processes. Asynchronous imaging technique permit detailed viewing of cyclic flame structure in an acoustic environment which may be modeled or utilized in burner design . The response of the flame front to the acoustic pressure cycle may be tracked with an OH emission monitor using a sapphire light pipe for optical access. The OH optical emission can be correlated to pressure sensor data for better understanding of the acoustical coupling of the flame. Active control f the combustion cycle can be implemented using an OH emission sensor for feedback.

Neural network evaluation of reflectometry density profiles for control purposes

NASA Astrophysics Data System (ADS)

Santos, J.; Nunes, F.; Manso, M.; Nunes, I.

1999-01-01

Broadband reflectometry is a diagnostic that is able to measure the density profile with high spatial and temporal resolutions, therefore it can be used to improve the performance of advanced tokamak operation modes and to supplement or correct the magnetics for plasma position control. To perform these tasks real-time processing is needed. Here we present a method that uses a neural network to make a fast evaluation of radial positions for selected density layers. Typical ASDEX Upgrade density profiles were used to generate the simulated network training and test sets. It is shown that the method has the potential to meet the tight timing requirements of control applications with the required accuracy. The network is also able to provide an accurate estimation of the position of density layers below the first density layer which is probed by an O-mode reflectometer, provided that it is trained with a realistic density profile model.

Application of Reservoir Flow Simulation Integrated with Geomechanics in Unconventional Tight Play

NASA Astrophysics Data System (ADS)

Lin, Menglu; Chen, Shengnan; Mbia, Ernest; Chen, Zhangxing

2018-01-01

Multistage hydraulic fracturing techniques, combined with horizontal drilling, have enabled commercial production from the vast reserves of unconventional tight formations. During hydraulic fracturing, fracturing fluid and proppants are pumped into the reservoir matrix to create the hydraulic fractures. Understanding the propagation mechanism of hydraulic fractures is essential to estimate their properties, such as half-length. In addition, natural fractures are often present in tight formations, which might be activated during the fracturing process and contribute to the post-stimulation well production rates. In this study, reservoir simulation is integrated with rock geomechanics to predict the well post-stimulation productivities. Firstly, a reservoir geological model is built based on the field data collected from the Montney formation in the Western Canadian Sedimentary Basin. The hydraulic fracturing process is then simulated through an integrated approach of fracturing fluid injection, rock geomechanics, and tensile failure criteria. In such a process, the reservoir pore pressure increases with a continuous injection of the fracturing fluid and proppants, decreasing the effective stress exerted on the rock matrix accordingly as the overburden pressure remains constant. Once the effective stress drops to a threshold value, tensile failure of the reservoir rock occurs, creating hydraulic fractures in the formation. The early production history of the stimulated well is history-matched to validate the predicted fracture geometries (e.g., half-length) generated from the fracturing simulation process. The effects of the natural fracture properties and well bottom-hole pressures on well productivity are also studied. It has been found that nearly 40% of hydraulic fractures propagate in the beginning stage (the pad step) of the fracturing schedule. In addition, well post-stimulation productivity will increase significantly if the natural fractures are propped or partially propped by the proppants. This paper provides insights on fracture propagation and can be a reference for fracturing treatments in unconventional tight reservoirs.

How a "Top-Performing" Asian School System Formulates and Implements Policy: The Case of Singapore

ERIC Educational Resources Information Center

Tan, Cheng Yong; Dimmock, Clive

2014-01-01

This article analyses the paradox inherent in the "top-performing" yet tightly controlled Singapore education system. As government controls have increased in complexity, existing policymaking conceptual heuristics in accounting for centre-periphery relationships appear inadequate. It argues that more direct government control is being…

A Comprehensive Computer Package for Ambulatory Surgical Facilities

PubMed Central

Kessler, Robert R.

1980-01-01

Ambulatory surgical centers are a cost effective alternative to hospital surgery. Their increasing popularity has contributed to heavy case loads, an accumulation of vast amounts of medical and financial data and economic pressures to maintain a tight control over “cash flow”. Computerization is now a necessity to aid ambulatory surgical centers to maintain their competitive edge. An on-line system is especially necessary as it allows interactive scheduling of surgical cases, immediate access to financial data and rapid gathering of medical and statistical information. This paper describes the significant features of the computer package in use at the Salt Lake Surgical Center, which processes 500 cases per month.

Improvement of energy efficiency: the use of thermography and air-tightness test in verification of thermal performance of school buildings

NASA Astrophysics Data System (ADS)

Kauppinen, Timo; Siikanen, Sami

2011-05-01

The improvement of energy efficiency is the key issue after the energy performance of buildings directive came into the force in European Union countries. The city of Kuopio participate a project, in which different tools will be used, generated and tested to improve the energy efficiency of public buildings. In this project there are 2 schools, the other consuming much more heating energy than the other same type of school. In this paper the results of the thermography in normal conditions and under 50 Pa pressure drop will be presented; as well as the results of remote controlled air tightness test of the buildings. Thermography combined with air tightness test showed clearly the reasons of specific consumption differences of heating energy - also in the other hand, the measurements showed the problems in the performance of ventilation system. Thermography, air tightness test and other supporting measurements can be used together to solve energy loss problems - if these measurements will be carried out by proper way.

40 CFR 65.85 - Procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... permit limit applicable to the process vent. (4) Design analysis based on accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or properties. (5) All data... tested for vapor tightness. (b) Engineering assessment. Engineering assessment to determine if a vent...

40 CFR 65.85 - Procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... permit limit applicable to the process vent. (4) Design analysis based on accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or properties. (5) All data... tested for vapor tightness. (b) Engineering assessment. Engineering assessment to determine if a vent...

40 CFR 65.85 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... permit limit applicable to the process vent. (4) Design analysis based on accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or properties. (5) All data... tested for vapor tightness. (b) Engineering assessment. Engineering assessment to determine if a vent...

40 CFR 65.85 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... permit limit applicable to the process vent. (4) Design analysis based on accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or properties. (5) All data... tested for vapor tightness. (b) Engineering assessment. Engineering assessment to determine if a vent...

40 CFR 65.85 - Procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... permit limit applicable to the process vent. (4) Design analysis based on accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or properties. (5) All data... tested for vapor tightness. (b) Engineering assessment. Engineering assessment to determine if a vent...

Trans-methylation reactions in plants: focus on the activated methyl cycle.

PubMed

Rahikainen, Moona; Alegre, Sara; Trotta, Andrea; Pascual, Jesús; Kangasjärvi, Saijaliisa

2018-02-01

Trans-methylation reactions are vital in basic metabolism, epigenetic regulation, RNA metabolism, and posttranslational control of protein function and therefore fundamental in determining the physiological processes in all living organisms. The plant kingdom is additionally characterized by the production of secondary metabolites that undergo specific hydroxylation, oxidation and methylation reactions to obtain a wide array of different chemical structures. Increasing research efforts have started to reveal the enzymatic pathways underlying the biosynthesis of complex metabolites in plants. Further engineering of these enzymatic machineries offers significant possibilities in the development of bio-based technologies, but necessitates deep understanding of their potential metabolic and regulatory interactions. Trans-methylation reactions are tightly coupled with the so-called activated methyl cycle (AMC), an essential metabolic circuit that maintains the trans-methylation capacity in all living cells. Tight regulation of the AMC is crucial in ensuring accurate trans-methylation reactions in different subcellular compartments, cell types, developmental stages and environmental conditions. This review addresses the organization and posttranslational regulation of the AMC and elaborates its critical role in determining metabolic regulation through modulation of methyl utilization in stress-exposed plants. © 2017 Scandinavian Plant Physiology Society.

CAVEOLIN-1 REGULATES HIV-1 TAT-INDUCED ALTERATIONS OF TIGHT JUNCTION PROTEIN EXPRESSION VIA MODULATION OF THE RAS SIGNALING

PubMed Central

Zhong, Yu; Smart, Eric J.; Weksler, Babette; Couraud, Pierre-Olivier; Hennig, Bernhard; Toborek, Michal

2009-01-01

The blood-brain barrier (BBB) is the critical structure for preventing HIV trafficking into the brain. Specific HIV proteins, such as Tat protein, can contribute to the dysfunction of tight junctions at the BBB and HIV entry into the brain. Tat is released by HIV-1 infected cells and can interact with a variety of cell surface receptors activating several signal transduction pathways, including those localized in caveolae. The present study focused on the mechanisms of Tat-induced caveolae-associated Ras signaling at the level of the BBB. Treatment with Tat activated the Ras pathway in human brain microvascular endothelial cells (HBMEC). However, caveolin-1 silencing markedly attenuated these effects. Because the integrity of the brain endothelium is regulated by intercellular tight junctions, these structural elements of the BBB were also evaluated in the present study. Exposure to Tat diminished the expression of several tight junction proteins, namely, occludin, zonula occludens (ZO)-1, and ZO-2 in the caveolar fraction of HBMEC. These effects were effectively protected by pharmacological inhibition of the Ras signaling and by silencing of caveolin-1. The present data indicate the importance of caveolae-associated signaling in the disruption of tight junctions upon Tat exposure. They also demonstrate that caveolin-1 may constitute an early and critical modulator that controls signaling pathways leading to the disruption of tight junction proteins. Thus, caveolin-1 may provide an effective target to protect against Tat-induced HBMEC dysfunction and the disruption of the BBB in HIV-1-infected patients. PMID:18667611

Comparison of the effects of local cryotherapy and passive cross-body stretch on extensibility in subjects with posterior shoulder tightness.

PubMed

Park, Kyue-Nam; Kwon, Oh-Yun; Weon, Jong-Hyuck; Choung, Sung-Dae; Kim, Si-Hyun

2014-01-01

The objective was to compare the immediate effects of local cryotherapy (LC) and passive cross-body stretch on the extensibility of the posterior shoulder muscle in individuals with posterior shoulder tightness. Eighty-seven healthy subjects with a between-shoulder difference in internal rotation (IR) range of motion (ROM) greater than 10° were randomly divided into three groups: LC group, stretching group, and control group (n = 29 in each group). Subjects in the LC group received LC on infraspinatus and posterior deltoid muscles and subjects in the stretching group performed passive cross-body stretch. Stretch sensation was measured at the end range of passive IR and horizontal adduction (HA) using numerical rating scale, and the pressure pain threshold (PPT) at the infraspinatus and posterior deltoid muscles was measured using pressure algometry. Passive and active ROM of IR and HA of the glenohumeral joint were measured using an inclinometer. All measurements were performed at pre-intervention, post- intervention, and 10-min follow-up. Stretch sensation was significantly decreased and PPT was significantly increased in the LC and stretching groups at post-intervention, and these effects were maintained at 10-min follow-up, compared to the control group. Both the LC group and stretching group had a significantly greater increase in passive and active ROM of IR and HA, compared to the control group at post-intervention and 10-min follow-up. However, there were no significant differences in stretch sensation, PPT, or ROM of IR and HA between the LC group and stretching group. LC can be used to decrease the stretch sensation and increase PPT and ROM of IR and HA as much as a stretching exercise. LC could be an alternative method for increasing the restricted ROM of glenohumeral IR and HA for individuals with posterior shoulder tightness, especially for patients and sports players who have severe stretching discomfort. Key PointsLocal cryotherapy (LC) decreased the uncomfortable stretch sensation, and increased the pressure pain threshold (PPT) of infraspinatus and posterior deltoid muscles in subjects with posterior shoulder tightness.Decreased stretch sensation by LC without passive stretching could improve the passive and active ROM of internal rotation and horizontal adduction in subjects with posterior shoulder tightness, similar to cross-body stretch.LC can be an alternative method to increase extensibility when individuals with posterior shoulder tightness have high stretch sensitivity and low PPT in the infraspinatus and posterior deltoid muscles.

Comparison of the Effects of Local Cryotherapy and Passive Cross-Body Stretch on Extensibility in Subjects with Posterior Shoulder Tightness

PubMed Central

Park, Kyue-nam; Kwon, Oh-yun; Weon, Jong-hyuck; Choung, Sung-dae; Kim, Si-hyun

2014-01-01

The objective was to compare the immediate effects of local cryotherapy (LC) and passive cross-body stretch on the extensibility of the posterior shoulder muscle in individuals with posterior shoulder tightness. Eighty-seven healthy subjects with a between-shoulder difference in internal rotation (IR) range of motion (ROM) greater than 10° were randomly divided into three groups: LC group, stretching group, and control group (n = 29 in each group). Subjects in the LC group received LC on infraspinatus and posterior deltoid muscles and subjects in the stretching group performed passive cross-body stretch. Stretch sensation was measured at the end range of passive IR and horizontal adduction (HA) using numerical rating scale, and the pressure pain threshold (PPT) at the infraspinatus and posterior deltoid muscles was measured using pressure algometry. Passive and active ROM of IR and HA of the glenohumeral joint were measured using an inclinometer. All measurements were performed at pre-intervention, post- intervention, and 10-min follow-up. Stretch sensation was significantly decreased and PPT was significantly increased in the LC and stretching groups at post-intervention, and these effects were maintained at 10-min follow-up, compared to the control group. Both the LC group and stretching group had a significantly greater increase in passive and active ROM of IR and HA, compared to the control group at post-intervention and 10-min follow-up. However, there were no significant differences in stretch sensation, PPT, or ROM of IR and HA between the LC group and stretching group. LC can be used to decrease the stretch sensation and increase PPT and ROM of IR and HA as much as a stretching exercise. LC could be an alternative method for increasing the restricted ROM of glenohumeral IR and HA for individuals with posterior shoulder tightness, especially for patients and sports players who have severe stretching discomfort. Key Points Local cryotherapy (LC) decreased the uncomfortable stretch sensation, and increased the pressure pain threshold (PPT) of infraspinatus and posterior deltoid muscles in subjects with posterior shoulder tightness. Decreased stretch sensation by LC without passive stretching could improve the passive and active ROM of internal rotation and horizontal adduction in subjects with posterior shoulder tightness, similar to cross-body stretch. LC can be an alternative method to increase extensibility when individuals with posterior shoulder tightness have high stretch sensitivity and low PPT in the infraspinatus and posterior deltoid muscles. PMID:24570610

Total-energy Assisted Tight-binding Method Based on Local Density Approximation of Density Functional Theory

NASA Astrophysics Data System (ADS)

Fujiwara, Takeo; Nishino, Shinya; Yamamoto, Susumu; Suzuki, Takashi; Ikeda, Minoru; Ohtani, Yasuaki

2018-06-01

A novel tight-binding method is developed, based on the extended Hückel approximation and charge self-consistency, with referring the band structure and the total energy of the local density approximation of the density functional theory. The parameters are so adjusted by computer that the result reproduces the band structure and the total energy, and the algorithm for determining parameters is established. The set of determined parameters is applicable to a variety of crystalline compounds and change of lattice constants, and, in other words, it is transferable. Examples are demonstrated for Si crystals of several crystalline structures varying lattice constants. Since the set of parameters is transferable, the present tight-binding method may be applicable also to molecular dynamics simulations of large-scale systems and long-time dynamical processes.

Machine learning and predictive data analytics enabling metrology and process control in IC fabrication

NASA Astrophysics Data System (ADS)

Rana, Narender; Zhang, Yunlin; Wall, Donald; Dirahoui, Bachir; Bailey, Todd C.

2015-03-01

Integrate circuit (IC) technology is going through multiple changes in terms of patterning techniques (multiple patterning, EUV and DSA), device architectures (FinFET, nanowire, graphene) and patterning scale (few nanometers). These changes require tight controls on processes and measurements to achieve the required device performance, and challenge the metrology and process control in terms of capability and quality. Multivariate data with complex nonlinear trends and correlations generally cannot be described well by mathematical or parametric models but can be relatively easily learned by computing machines and used to predict or extrapolate. This paper introduces the predictive metrology approach which has been applied to three different applications. Machine learning and predictive analytics have been leveraged to accurately predict dimensions of EUV resist patterns down to 18 nm half pitch leveraging resist shrinkage patterns. These patterns could not be directly and accurately measured due to metrology tool limitations. Machine learning has also been applied to predict the electrical performance early in the process pipeline for deep trench capacitance and metal line resistance. As the wafer goes through various processes its associated cost multiplies. It may take days to weeks to get the electrical performance readout. Predicting the electrical performance early on can be very valuable in enabling timely actionable decision such as rework, scrap, feedforward, feedback predicted information or information derived from prediction to improve or monitor processes. This paper provides a general overview of machine learning and advanced analytics application in the advanced semiconductor development and manufacturing.

Systems-oriented survey of noncontact temperature measurement techniques for rapid thermal processing

NASA Astrophysics Data System (ADS)

Peyton, David; Kinoshita, Hiroyuki; Lo, G. Q.; Kwong, Dim-Lee

1991-04-01

Rapid Thermal Processing (RTP) is becoming a popular approach for future ULSI manufacturing due to its unique low thermal budget and process flexibility. Furthermore when RTP is combined with Chemical Vapor Deposition (CVD) the so-called RTP-CVD technology it can be used to deposit ultrathin films with extremely sharp interfaces and excellent material qualities. One major consequence of this type of processing however is the need for extremely tight control of wafer temperature both to obtain reproducible results for process control and to minimize slip and warpage arising from nonuniformities in temperature. Specifically temperature measurement systems suitable for RiP must have both high precision--within 1-2 degrees--and a short response time--to output an accurate reading on the order of milliseconds for closedloop control. Any such in-situ measurement technique must be non-contact since thermocouples cannot meet the response time requirements and have problems with conductive heat flow in the wafer. To date optical pyrometry has been the most widely used technique for RiP systems although a number of other techniques are being considered and researched. This article examines several such techniques from a systems perspective: optical pyrometry both conventional and a new approach using ellipsometric techniques for concurrent emissivity measurement Raman scattering infrared laser thermometry optical diffraction thermometry and photoacoustic thermometry. Each approach is evaluated in terms of its actual or estimated manufacturing cost remote sensing capability precision repeatability dependence on processing history range

Target Organ Damage and Target Systolic Blood Pressure in Clinical Practice: The Campania Salute Network.

PubMed

D'Amato, Andrea; Mancusi, Costantino; Losi, Maria Angela; Izzo, Raffaele; Arnone, Maria Immacolata; Canciello, Grazia; Senese, Salvatore; De Luca, Nicola; de Simone, Giovanni; Trimarco, Bruno

2018-05-07

Lowering systolic blood pressure (SBP) below the conventional threshold (140 mm Hg) reduces left ventricular (LV) hypertrophy and incident cardiovascular (CV) events. We assessed whether different thresholds of SBP as the average value during follow-up (FU) have different impact on changes in target organ damage (TOD). From the Campania Salute Network registry, we selected 4,148 hypertensive patients with average SBP-FU <140 mm Hg, and without history of prevalent CV or chronic kidney disease (i.e.,

Industrial hygiene walk-through survey report of E. I. Dupont de Nemours and Company, Inc. , Chocolate Bayou Plant, Alvin, Texas

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

Fajen, J.M.

1985-05-01

A walkthrough survey of EI duPont deNemours and Company, Incorporated, Alvin, Texas was conducted in November, 1984. The purpose of the survey was to obtain information on the 1,3-butadiene monomer manufacturing process and the potential for exposure. The facility manufactured a crude product stream containing 1,3-butadiene as a coproduct of its ethylene process. The crude was refined to a 99.5% 1,3-butadiene product. The refining process occurred in a closed system, tightly maintained for economic, fire, and health-hazard reasons. The product was transferred by way of a pipeline to storage spheres for later transport off site. The facility used an open-loopmore » cylinder (bomb) technique for quality control sampling. All pumps were equipped with single mechanical seals, which were in the process of being replaced by tandem seals. Since 1962, the facility had experienced process changes and three changes of ownership. Because of these changes, records from previous owners of industrial hygiene monitoring were not available. Job titles identified as having potential exposure were processors, wage employee supervisors, production engineers, and laboratory technicians. The author concludes that a closed-loop manual quality-control sampling system should be installed to reduce exposure from this source.« less

Numerical modelling of heat transfer in a cavity due to liquid jet impingement for liquid supported stretch blow moulding

NASA Astrophysics Data System (ADS)

Smyth, Trevor; Menary, Gary; Geron, Marco

2018-05-01

Impingement of a liquid jet in a polymer cavity has been modelled numerically in this study. Liquid supported stretch blow moulding is a nascent polymer forming process using liquid as the forming medium to produce plastic bottles. The process derives from the conventional stretch blow moulding process which uses compressed air to deform the preform. Heat transfer away from the preform greatly increases when a liquid instead of a gas is flowing over a solid; in the blow moulding process the temperature of the preform is tightly controlled to achieve optimum forming conditions. A model was developed with Computational Fluid Dynamics code ANSYS Fluent which allows the extent of heat transfer between the incoming liquid and the solid preform to be determined in the initial transient stage, where a liquid jet enters an air filled preform. With this data, an approximation of the extent of cooling through the preform wall can be determined.

Tightly Coupled Integration of Ionosphere-Constrained Precise Point Positioning and Inertial Navigation Systems

PubMed Central

Gao, Zhouzheng; Zhang, Hongping; Ge, Maorong; Niu, Xiaoji; Shen, Wenbin; Wickert, Jens; Schuh, Harald

2015-01-01

The continuity and reliability of precise GNSS positioning can be seriously limited by severe user observation environments. The Inertial Navigation System (INS) can overcome such drawbacks, but its performance is clearly restricted by INS sensor errors over time. Accordingly, the tightly coupled integration of GPS and INS can overcome the disadvantages of each individual system and together form a new navigation system with a higher accuracy, reliability and availability. Recently, ionosphere-constrained (IC) precise point positioning (PPP) utilizing raw GPS observations was proven able to improve both the convergence and positioning accuracy of the conventional PPP using ionosphere-free combined observations (LC-PPP). In this paper, a new mode of tightly coupled integration, in which the IC-PPP instead of LC-PPP is employed, is implemented to further improve the performance of the coupled system. We present the detailed mathematical model and the related algorithm of the new integration of IC-PPP and INS. To evaluate the performance of the new tightly coupled integration, data of both airborne and vehicle experiments with a geodetic GPS receiver and tactical grade inertial measurement unit are processed and the results are analyzed. The statistics show that the new approach can further improve the positioning accuracy compared with both IC-PPP and the tightly coupled integration of the conventional PPP and INS. PMID:25763647

Simple and tight monogamy relations for a class of Bell inequalities

NASA Astrophysics Data System (ADS)

Augusiak, Remigiusz

2017-01-01

Physical principles constrain the way nonlocal correlations can be distributed among distant parties in a Bell-type experiment. These constraints are usually expressed by monogamy relations that bound the amount of Bell inequality violation observed by a set of parties by the violation observed by a different set of parties. Here we show that the no-signaling principle yields simple and tight monogamy relations for an important class of bipartite and multipartite Bell inequalities. We also link these trade-offs to the guessing probability—a key quantity in device-independent information processing.

OLIFE: Tight Binding Code for Transmission Coefficient Calculation

NASA Astrophysics Data System (ADS)

Mijbil, Zainelabideen Yousif

2018-05-01

A new and human friendly transport calculation code has been developed. It requires a simple tight binding Hamiltonian as the only input file and uses a convenient graphical user interface to control calculations. The effect of magnetic field on junction has also been included. Furthermore the transmission coefficient can be calculated between any two points on the scatterer which ensures high flexibility to check the system. Therefore Olife can highly be recommended as an essential tool for pretesting studying and teaching electron transport in molecular devices that saves a lot of time and effort.

Dual leakoff beehavior in hydraulic fracturing of tight, lenticular gas sands

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

Warpinski, N.R.

Stimulation experiments conducted in anisotropic, naturally fractured, tight, lenticular, gas sandstones have shown the existence of a dual leakoff phenomenon. Below a threshold, leakoff increases by a factor of 50, slurries dehydrate rapidly, and screenouts occur in minutes. The leakoff has been shown to be controllable to some extent with 100-mesh sand. Results of three stimulation experiments are presented; three include a treatment that screened out, a minifrac experiment that showed the effectiveness of 100-mesh sand, and a final successful stimulation. 30 refs., 14 figs., 6 tabs.

Using a theory-driven conceptual framework in qualitative health research.

PubMed

Macfarlane, Anne; O'Reilly-de Brún, Mary

2012-05-01

The role and merits of highly inductive research designs in qualitative health research are well established, and there has been a powerful proliferation of grounded theory method in the field. However, tight qualitative research designs informed by social theory can be useful to sensitize researchers to concepts and processes that they might not necessarily identify through inductive processes. In this article, we provide a reflexive account of our experience of using a theory-driven conceptual framework, the Normalization Process Model, in a qualitative evaluation of general practitioners' uptake of a free, pilot, language interpreting service in the Republic of Ireland. We reflect on our decisions about whether or not to use the Model, and describe our actual use of it to inform research questions, sampling, coding, and data analysis. We conclude with reflections on the added value that the Model and tight design brought to our research.

Context-aware access control for pervasive access to process-based healthcare systems.

PubMed

Koufi, Vassiliki; Vassilacopoulos, George

2008-01-01

Healthcare is an increasingly collaborative enterprise involving a broad range of healthcare services provided by many individuals and organizations. Grid technology has been widely recognized as a means for integrating disparate computing resources in the healthcare field. Moreover, Grid portal applications can be developed on a wireless and mobile infrastructure to execute healthcare processes which, in turn, can provide remote access to Grid database services. Such an environment provides ubiquitous and pervasive access to integrated healthcare services at the point of care, thus improving healthcare quality. In such environments, the ability to provide an effective access control mechanism that meets the requirement of the least privilege principle is essential. Adherence to the least privilege principle requires continuous adjustments of user permissions in order to adapt to the current situation. This paper presents a context-aware access control mechanism for HDGPortal, a Grid portal application which provides access to workflow-based healthcare processes using wireless Personal Digital Assistants. The proposed mechanism builds upon and enhances security mechanisms provided by the Grid Security Infrastructure. It provides tight, just-in-time permissions so that authorized users get access to specific objects according to the current context. These permissions are subject to continuous adjustments triggered by the changing context. Thus, the risk of compromising information integrity during task executions is reduced.

Approaches of multilayer overlay process control for 28nm FD-SOI derivative applications

NASA Astrophysics Data System (ADS)

Duclaux, Benjamin; De Caunes, Jean; Perrier, Robin; Gatefait, Maxime; Le Gratiet, Bertrand; Chapon, Jean-Damien; Monget, Cédric

2018-03-01

Derivative technology like embedded Non-Volatile Memories (eNVM) is raising new types of challenges on the "more than Moore" path. By its construction: overlay is critical across multiple layers, by its running mode: usage of high voltage are stressing leakages and breakdown, and finally with its targeted market: Automotive, Industry automation, secure transactions… which are all requesting high device reliability (typically below 1ppm level). As a consequence, overlay specifications are tights, not only between one layer and its reference, but also among the critical layers sharing the same reference. This work describes a broad picture of the key points for multilayer overlay process control in the case of a 28nm FD-SOI technology and its derivative flows. First, the alignment trees of the different flow options have been optimized using a realistic process assumptions calculation for indirect overlay. Then, in the case of a complex alignment tree involving heterogeneous scanner toolset, criticality of tool matching between reference layer and critical layers of the flow has been highlighted. Improving the APC control loops of these multilayer dependencies has been studied with simulations of feed-forward as well as implementing new rework algorithm based on multi-measures. Finally, the management of these measurement steps raises some issues for inline support and using calculations or "virtual overlay" could help to gain some tool capability. A first step towards multilayer overlay process control has been taken.

Endothelial cell culture in microfluidic devices for investigating microvascular processes.

PubMed

Mannino, Robert G; Qiu, Yongzhi; Lam, Wilbur A

2018-07-01

Numerous conditions and disease states such as sickle cell disease, malaria, thrombotic microangiopathy, and stroke significantly impact the microvasculature function and its role in disease progression. Understanding the role of cellular interactions and microvascular hemodynamic forces in the context of disease is crucial to understanding disease pathophysiology. In vivo models of microvascular disease using animal models often coupled with intravital microscopy have long been utilized to investigate microvascular phenomena. However, these methods suffer from some major drawbacks, including the inability to tightly and quantitatively control experimental conditions, the difficulty of imaging multiple microvascular beds within a living organism, and the inability to isolate specific microvascular geometries such as bifurcations. Thus, there exists a need for in vitro microvascular models that can mitigate the drawbacks associated with in vivo systems. To that end, microfluidics has been widely used to develop such models, as it allows for tight control of system inputs, facile imaging, and the ability to develop robust and repeatable systems with well-defined geometries. Incorporating endothelial cells to branching microfluidic models allows for the development of "endothelialized" systems that accurately recapitulate physiological microvessels. In this review, we summarize the field of endothelialized microfluidics, specifically focusing on fabrication methods, limitations, and applications of these systems. We then speculate on future directions and applications of these cutting edge technologies. We believe that this review of the field is of importance to vascular biologists and bioengineers who aim to utilize microfluidic technologies to solve vascular problems.

Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation

PubMed Central

Zihni, Ceniz; Munro, Peter M.G.; Elbediwy, Ahmed; Keep, Nicholas H.; Terry, Stephen J.; Harris, John

2014-01-01

Epithelial cells develop morphologically characteristic apical domains that are bordered by tight junctions, the apical–lateral border. Cdc42 and its effector complex Par6–atypical protein kinase c (aPKC) regulate multiple steps during epithelial differentiation, but the mechanisms that mediate process-specific activation of Cdc42 to drive apical morphogenesis and activate the transition from junction formation to apical differentiation are poorly understood. Using a small interfering RNA screen, we identify Dbl3 as a guanine nucleotide exchange factor that is recruited by ezrin to the apical membrane, that is enriched at a marginal zone apical to tight junctions, and that drives spatially restricted Cdc42 activation, promoting apical differentiation. Dbl3 depletion did not affect junction formation but did affect epithelial morphogenesis and brush border formation. Conversely, expression of active Dbl3 drove process-specific activation of the Par6–aPKC pathway, stimulating the transition from junction formation to apical differentiation and domain expansion, as well as the positioning of tight junctions. Thus, Dbl3 drives Cdc42 signaling at the apical margin to regulate morphogenesis, apical–lateral border positioning, and apical differentiation. PMID:24379416

Improved Characterization and Modeling of Tight Oil Formations for CO 2 Enhanced Oil Recovery Potential and Storage Capacity Estimation

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

Sorensen, James; Smith, Steven; Kurz, Bethany

Tight oil formations such as those in the Bakken petroleum system are known to hold hundreds of billions of barrels of oil in place; however, the primary recovery factor for these plays is typically less than 10%. Tight oil formations, including the Bakken Formation, therefore, may be attractive candidates for enhanced oil recovery (EOR) using CO 2. Multiphase fluid behavior and flow in fluid-rich shales can vary substantially depending on the size of pore throats, and properties such as fluid viscosity and density are much different in nanoscale pores than in macroscale pores. Thus it is critical to understand themore » nature and distribution of nano-, micro-, and macroscale pores and fracture networks. To address these issues, the Energy & Environmental Research Center (EERC) has been conducting a research program entitled “Improved Characterization and Modeling of Tight Oil Formations for CO 2 Enhanced Oil Recovery Potential and Storage Capacity Estimation.” The objectives of the project are 1) the use of advanced characterization methods to better understand and quantify the petrophysical and geomechanical factors that control CO 2 and oil mobility within tight oil formation samples, 2) the determination of CO 2 permeation and oil extraction rates in tight reservoir rocks and organic-rich shales of the Bakken, and 3) the integration of the laboratory-based CO 2 permeation and oil extraction data and the characterization data into geologic models and dynamic simulations to develop predictions of CO 2 storage resource and EOR in the Bakken tight oil formation. A combination of standard and advanced petrophysical characterization techniques were applied to characterize samples of Bakken Formation tight reservoir rock and shales from multiple wells. Techniques included advanced computer tomography (CT) imaging, scanning electron microscopy (SEM) techniques, whole-core and micro x-ray CT imaging, field emission (FE) SEM, and focused ion beam (FIB) SEM. Selected samples were also analyzed for geomechanical properties. X-ray CT imaging yielded information on the occurrence of fractures, bedding planes, fossils, and bioturbation in core, as well as data on bulk density and photoelectric factor logs, which were used to interpret porosity, organic content, and mineralogy. FESEM was used for characterization of nano- and microscale features, including nanoscale pore visualization and micropore and pore throat mineralogy. FIBSEM yielded micro- to nanoscale visualization of fracture networks, porosity and pore-size distribution, connected versus isolated porosity, and distribution of organics. Results from the characterization activities provide insight on nanoscale fracture properties, pore throat mineralogy and connectivity, rock matrix characteristics, mineralogy, and organic content. Laboratory experiments demonstrated that CO 2 can permeate the tight matrix of Bakken shale and nonshale reservoir samples and mobilize oil from those samples. Geologic models were created at scales ranging from the core plug to the reservoir, and dynamic simulations were conducted. The data from the characterization and laboratory-based activities were integrated into modeling research activities to determine the fundamental mechanisms controlling fluid transport in the Bakken, which support EOR scheme design and estimation of CO 2 storage potential in tight oil formations. Simulation results suggest a CO 2 storage resource estimate range of 169 million to 1.5 billion tonnes for the Bakken in North Dakota, possibly resulting in 1.8 billion to 16 billion barrels of incremental oil.« less

H+- and Na+- elicited rapid changes of the microtubule cytoskeleton in the biflagellated green alga Chlamydomonas

PubMed Central

Liu, Yi; Visetsouk, Mike; Mynlieff, Michelle; Qin, Hongmin; Lechtreck, Karl F

2017-01-01

Although microtubules are known for dynamic instability, the dynamicity is considered to be tightly controlled to support a variety of cellular processes. Yet diverse evidence suggests that this is not applicable to Chlamydomonas, a biflagellate fresh water green alga, but intense autofluorescence from photosynthesis pigments has hindered the investigation. By expressing a bright fluorescent reporter protein at the endogenous level, we demonstrate in real time discreet sweeping changes in algal microtubules elicited by rises of intracellular H+ and Na+. These results from this model organism with characteristics of animal and plant cells provide novel explanations regarding how pH may drive cellular processes; how plants may respond to, and perhaps sense stresses; and how organisms with a similar sensitive cytoskeleton may be susceptible to environmental changes. PMID:28875932

Vascular Glucose Sensor Symposium: Continuous Glucose Monitoring Systems (CGMS) for Hospitalized and Ambulatory Patients at Risk for Hyperglycemia, Hypoglycemia, and Glycemic Variability.

PubMed

Joseph, Jeffrey I; Torjman, Marc C; Strasma, Paul J

2015-07-01

Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, length of stay, and cost in a variety of critical care and non-critical care patient populations in the hospital. The results from prospective randomized clinical trials designed to determine the risks and benefits of intensive insulin therapy and tight glycemic control have been confusing; and at times conflicting. The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the great clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes. Automation and standardization of the glucose measurement process have the potential to significantly improve BG control, clinical outcome, safety and cost. © 2015 Diabetes Technology Society.

Edge usage, motifs, and regulatory logic for cell cycling genetic networks

NASA Astrophysics Data System (ADS)

Zagorski, M.; Krzywicki, A.; Martin, O. C.

2013-01-01

The cell cycle is a tightly controlled process, yet it shows marked differences across species. Which of its structural features follow solely from the ability to control gene expression? We tackle this question in silico by examining the ensemble of all regulatory networks which satisfy the constraint of producing a given sequence of gene expressions. We focus on three cell cycle profiles coming from baker's yeast, fission yeast, and mammals. First, we show that the networks in each of the ensembles use just a few interactions that are repeatedly reused as building blocks. Second, we find an enrichment in network motifs that is similar in the two yeast cell cycle systems investigated. These motifs do not have autonomous functions, yet they reveal a regulatory logic for cell cycling based on a feed-forward cascade of activating interactions.

Differential roles of right temporal cortex and Broca's area in pitch processing: evidence from music and Mandarin.

PubMed

Nan, Yun; Friederici, Angela D

2013-09-01

Superior temporal and inferior frontal cortices are involved in the processing of pitch information in the domain of language and music. Here, we used fMRI to test the particular roles of these brain regions in the neural implementation of pitch in music and in tone language (Mandarin) with a group of Mandarin speaking musicians whose pertaining experiences in pitch are similar across domains. Our findings demonstrate that the neural network for pitch processing includes the pars triangularis of Broca's area and the right superior temporal gyrus (STG) across domains. Within this network, pitch sensitive activation in Broca's area is tightly linked to the behavioral performance of pitch congruity judgment, thereby reflecting controlled processes. Activation in the right STG is independent of performance and more sensitive to pitch congruity in music than in tone language, suggesting a domain-specific modulation of the perceptual processes. These observations provide a first glimpse at the cortical pitch processing network shared across domains. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease.

PubMed

Gweon, Tae-Geun; Park, Jong-Hyung; Kim, Byung-Wook; Choi, Yang Kyu; Kim, Joon Sung; Park, Sung Min; Kim, Chang Whan; Kim, Hyung-Gil; Chung, Jun-Won

2018-01-15

The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.

House dust mite allergen Der p 1 effects on sinonasal epithelial tight junctions.

PubMed

Henriquez, Oswaldo A; Den Beste, Kyle; Hoddeson, Elizabeth K; Parkos, Charles A; Nusrat, Asma; Wise, Sarah K

2013-08-01

Epithelial permeability is highly dependent upon the integrity of tight junctions, which are cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen vs control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of TJPs was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1-exposed cultured sinonasal cells vs controls. Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. © 2013 ARS-AAOA, LLC.

DISTRIBUTED CONTROL AND DA FOR ATLAS

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

D. SCUDDER; ET AL

1999-05-01

The control system for the Atlas pulsed power generator being built at Los Alamos National Laboratory will utilize a significant level of distributed control. Other principal design characteristics include noise immunity, modularity and use of commercial products wherever possible. The data acquisition system is tightly coordinated with the control system. Both share a common database server and a fiber-optic ethernet communications backbone.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.

PubMed

Chen, X; Threlkeld, S W; Cummings, E E; Juan, I; Makeyev, O; Besio, W G; Gaitanis, J; Banks, W A; Sadowska, G B; Stonestreet, B S

2012-12-13

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between K(i) and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K(i)) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Visualisation of Multiple Tight Junctional Complexes in Human Airway Epithelial Cells.

PubMed

Buckley, Alysia G; Looi, Kevin; Iosifidis, Thomas; Ling, Kak-Ming; Sutanto, Erika N; Martinovich, Kelly M; Kicic-Starcevich, Elizabeth; Garratt, Luke W; Shaw, Nicole C; Lannigan, Francis J; Larcombe, Alexander N; Zosky, Graeme; Knight, Darryl A; Rigby, Paul J; Kicic, Anthony; Stick, Stephen M

2018-01-01

Apically located tight junctions in airway epithelium perform a fundamental role in controlling macromolecule migration through paracellular spaces. Alterations in their expression may lead to disruptions in barrier integrity, which subsequently facilitates entry of potential bacterial and other pathogens into the host. Furthermore, there is emerging evidence that the barrier integrity of the airway in certain airway inflammatory diseases may be altered. However, there is little consensus on the way this is assessed and measured and the type of cells used to achieve this. Here, we assessed four fixation methods including; (i) 4% ( v /v) paraformaldehyde; (ii) 100% methanol; (iii) acetone or; (iv) 1:1 methanol: acetone. Pre-extraction with Triton X-100 was also performed and assessed on cells prior to fixation with either methanol or paraformaldehyde. Cells were also permeabilized with 0.1% (v/v) Saponin in 1× TBS following fixation and subsequently stained for tight junction proteins. Confocal microscopy was then used to visualise, compare and evaluate staining intensity of the tight junctional complexes in order to determine a standardised workflow of reproducible staining. Positive staining was observed following methanol fixation for claudin-1 and ZO-1 tight junction proteins but no staining was detected for occludin in 16HBE14o- cells. Combinatorial fixation with methanol and acetone also produced consistent positive staining for both occludin and ZO-1 tight junction proteins in these cells. When assessed using primary cells cultured at air-liquid interface, similar positive staining for claudin-1 and ZO-1 was observed following methanol fixation, while similar positive staining for occludin and ZO-1 was observed following the same combinatorial fixation with methanol and acetone. The present study demonstrates the importance of a personalised approach to optimise staining for the visualisation of different tight junction proteins. Of significance, the workflow, once optimised, can readily be translated into primary airway epithelial cell air-liquid interface cultures where it can be used to assess barrier integrity in chronic lung diseases.

Tight ceramic UF membrane as RO pre-treatment: the role of electrostatic interactions on phosphate rejection.

PubMed

Shang, Ran; Verliefde, Arne R D; Hu, Jingyi; Zeng, Zheyi; Lu, Jie; Kemperman, Antoine J B; Deng, Huiping; Nijmeijer, Kitty; Heijman, Sebastiaan G J; Rietveld, Luuk C

2014-01-01

Phosphate limitation has been reported as an effective approach to inhibit biofouling in reverse osmosis (RO) systems for water purification. The rejection of dissolved phosphate by negatively charged TiO2 tight ultrafiltration (UF) membranes (1 kDa and 3 kDa) was observed. These membranes can potentially be adopted as an effective process for RO pre-treatment in order to constrain biofouling by phosphate limitation. This paper focuses on electrostatic interactions during tight UF filtration. Despite the larger pore size, the 3 kDa ceramic membrane exhibited greater phosphate rejection than the 1 kDa membrane, because the 3 kDa membrane has a greater negative surface charge and thus greater electrostatic repulsion against phosphate. The increase of pH from 6 to 8.5 led to a substantial increase in phosphate rejection by both membranes due to increased electrostatic repulsion. At pH 8.5, the maximum phosphate rejections achieved by the 1 kDa and 3 kDa membrane were 75% and 86%, respectively. A Debye ratio (ratio of the Debye length to the pore radius) is introduced in order to evaluate double layer overlapping in tight UF membranes. Threshold Debye ratios were determined as 2 and 1 for the 1 kDa and 3 kDa membranes, respectively. A Debye ratio below the threshold Debye ratio leads to dramatically decreased phosphate rejection by tight UF membranes. The phosphate rejection by the tight UF, in combination with chemical phosphate removal by coagulation, might accomplish phosphate-limited conditions for biological growth and thus prevent biofouling in the RO systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Blufensin1 Negatively Impacts Basal Defense in Response to Barley Powdery Mildew

USDA-ARS?s Scientific Manuscript database

Plants have evolved complex regulatory mechanisms to control the defense response against microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSIN1 (BLN1), a small peptide ...

Cell-cell interactions of isolated and cultured oligodendrocytes: formation of linear occluding junctions and expression of peculiar intramembrane particles.

PubMed

Massa, P T; Szuchet, S; Mugnaini, E

1984-12-01

Oligodendrocytes were isolated from lamb brain. Freshly isolated cells and cultured cells, either 1- to 4-day-old unattached or 1- to 5-week-old attached, were examined by thin section and freeze-fracture electron microscopy. Freeze-fracture of freshly isolated oligodendrocytes showed globular and elongated intramembrane particles similar to those previously described in oligodendrocytes in situ. Enrichment of these particles was seen at sites of inter-oligodendrocyte contact. Numerous gap junctions and scattered linear tight junctional arrays were apparent. Gap junctions were connected to blebs of astrocytic plasma membrane sheared off during isolation, whereas tight junctions were facing extracellular space or blebs of oligodendrocytic plasma membrane. Thin sections of cultured, unattached oligodendrocytes showed rounded cell bodies touching one another at points without forming specialized cell junctions. Cells plated on polylysine-coated aclar dishes attached, emanated numerous, pleomorphic processes, and expressed galactocerebroside and myelin basic protein, characteristic markers for oligodendrocytes. Thin sections showed typical oligodendrocyte ultrastructure but also intermediate filaments not present in unattached cultures. Freeze-fracture showed intramembrane particles similar to but more numerous, and with a different fracture face repartition, than those seen in oligodendrocytes, freshly isolated or in situ. Gap junctions were small and rare. Apposed oligodendrocyte plasma membrane formed linear tight junctions which became more numerous with time in culture. Thus, cultured oligodendrocytes isolated from ovine brains develop and maintain features characteristic of mature oligodendrocytes in situ and can be used to explore formation and maintenance of tight junctions and possibly other classes of cell-cell interactions important in the process of myelination.

Neural oscillatory deficits in schizophrenia predict behavioral and neurocognitive impairments

PubMed Central

Martínez, Antígona; Gaspar, Pablo A.; Hillyard, Steven A.; Bickel, Stephan; Lakatos, Peter; Dias, Elisa C.; Javitt, Daniel C.

2015-01-01

Paying attention to visual stimuli is typically accompanied by event-related desynchronizations (ERD) of ongoing alpha (7–14 Hz) activity in visual cortex. The present study used time-frequency based analyses to investigate the role of impaired alpha ERD in visual processing deficits in schizophrenia (Sz). Subjects viewed sinusoidal gratings of high (HSF) and low (LSF) spatial frequency (SF) designed to test functioning of the parvo- vs. magnocellular pathways, respectively. Patients with Sz and healthy controls paid attention selectively to either the LSF or HSF gratings which were presented in random order. Event-related brain potentials (ERPs) were recorded to all stimuli. As in our previous study, it was found that Sz patients were selectively impaired at detecting LSF target stimuli and that ERP amplitudes to LSF stimuli were diminished, both for the early sensory-evoked components and for the attend minus unattend difference component (the Selection Negativity), which is generally regarded as a specific index of feature-selective attention. In the time-frequency domain, the differential ERP deficits to LSF stimuli were echoed in a virtually absent theta-band phase locked response to both unattended and attended LSF stimuli (along with relatively intact theta-band activity for HSF stimuli). In contrast to the theta-band evoked responses which were tightly stimulus locked, stimulus-induced desynchronizations of ongoing alpha activity were not tightly stimulus locked and were apparent only in induced power analyses. Sz patients were significantly impaired in the attention-related modulation of ongoing alpha activity for both HSF and LSF stimuli. These deficits correlated with patients’ behavioral deficits in visual information processing as well as with visually based neurocognitive deficits. These findings suggest an additional, pathway-independent, mechanism by which deficits in early visual processing contribute to overall cognitive impairment in Sz. PMID:26190988

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

NASA Astrophysics Data System (ADS)

Coffey, Aaron M.; Shchepin, Roman V.; Feng, Bibo; Colon, Raul D.; Wilkens, Ken; Waddell, Kevin W.; Chekmenev, Eduard Y.

2017-11-01

Applications of parahydrogen induced polarization (PHIP) often warrant conversion of the chemically-synthesized singlet-state spin order into net heteronuclear magnetization. In order to obtain optimal yields from the overall hyperpolarization process, catalytic hydrogenation must be tightly synchronized to subsequent radiofrequency (RF) transformations of spin order. Commercial NMR consoles are designed to synchronize applied waves on multiple channels and consequently are well-suited as controllers for these types of hyperpolarization experiments that require tight coordination of RF and non-RF events. Described here is a PHIP instrument interfaced to a portable NMR console operating with a static field electromagnet in the milliTesla regime. In addition to providing comprehensive control over chemistry and RF events, this setup condenses the PHIP protocol into a pulse-program that in turn can be readily shared in the manner of traditional pulse sequences. In this device, a TTL multiplexer was constructed to convert spectrometer TTL outputs into 24 VDC signals. These signals then activated solenoid valves to control chemical shuttling and reactivity in PHIP experiments. Consolidating these steps in a pulse-programming environment speeded calibration and improved quality assurance by enabling the B0/B1 fields to be tuned based on the direct acquisition of thermally polarized and hyperpolarized NMR signals. Performance was tested on the parahydrogen addition product of 2-hydroxyethyl propionate-1-13C-d3, where the 13C polarization was estimated to be P13C = 20 ± 2.5% corresponding to 13C signal enhancement approximately 25 million-fold at 9.1 mT or approximately 77,000-fold 13C enhancement at 3 T with respect to thermally induced polarization at room temperature.

Barley malt increases hindgut and portal butyric acid, modulates gene expression of gut tight junction proteins and Toll-like receptors in rats fed high-fat diets, but high advanced glycation end-products partially attenuate the effects.

PubMed

Zhong, Yadong; Teixeira, Cristina; Marungruang, Nittaya; Sae-Lim, Watina; Tareke, Eden; Andersson, Roger; Fåk, Frida; Nyman, Margareta

2015-09-01

Barley malt, a product of controlled germination, has been shown to produce high levels of butyric acid in the cecum and portal serum of rats and may therefore have anti-inflammatory effects. The aim of the study was to investigate how four barley malts, caramelized and colored malts, 50-malt and 350-malt, differing in functional characteristics concerning beta-glucan content and color, affect short-chain fatty acids (SCFA), barrier function and inflammation in the hindgut of rats fed high-fat diets. Male Wistar rats were given malt-supplemented high-fat diets for four weeks. Low and high-fat diets containing microcrystalline cellulose were incorporated as controls. All diets contained 70 g kg(-1) dietary fiber. The malt-fed groups were found to have had induced higher amounts of butyric and propionic acids in the hindgut and portal serum compared with controls, while cecal succinic acid only increased to a small extent. Fat increased the mRNA expression of tight junction proteins and Toll-like receptors (TLR) in the small intestine and distal colon of the rats, as well as the concentration of some amino acids in the portal plasma, but malt seemed to counteract these adverse effects to some extent. However, the high content of advanced glycation end-products (AGE) in caramelized malt tended to prohibit the positive effects on occludin in the small intestine and plasma amino acids seen with the other malt products. In conclusion, malting seems to be an interesting process for producing foods with positive health effects, but part of these effects may be destroyed if the malt contains a high content of AGE.

Language processing is not a race against time.

PubMed

Baggio, Giosuè; Vicario, Carmelo M

2016-01-01

We agree with Christiansen & Chater (C&C) that language processing and acquisition are tightly constrained by the limits of sensory and memory systems. However, the human brain supports a range of cognitive functions that mitigate the effects of information processing bottlenecks. The language system is partly organised around these moderating factors, not just around restrictions on storage and computation.

Micro-structure and Air-tightness of Squeeze Casting Motor housing for New Energy Vehicle

NASA Astrophysics Data System (ADS)

Jiang, Y. F.; Kang, Z. Q.; Jiang, W. F.; Wang, K. W.; Sha, D. L.; Li, M. L.; Sun, J.

2018-05-01

In order to improve the performance of automobile parts, the influence of squeeze casting process parameters on casting defects, material structure and air-tightness of aluminum alloy motor housing for new energy vehicle was studied. The results show that the density of the castings increases with the increase in pressure and mold temperature. With increase in pouring temperature, it increases first and then decreases. Pressure has the greatest influence on the density of the castings. Under a certain pressure, with moderate increase in casting temperature and mold temperature, the grain growth begins to increase; the dendrites become less, the new α - Al grains are spherical and granular, the micro-structure is uniform. Also, with increase in pressure, this effect is more pronounced, the air-tightness of castings improve. In conclusion, when the pressure is 110MPa, pouring temperature is 680° C, mold temperature is 280° C, pressure holding for 30s, and punch speed of 0.1m/s, there is no clear shrinkage in the casting, the structure is uniform, the qualified rate of air-tightness of production reaches 86%, and the performance is excellent.

Let it grow-the open market solution to marijuana control.

PubMed

Gettman, Jon; Kennedy, Michael

2014-11-18

This commentary evaluates regulatory frameworks for the legalized production, sale, and use of marijuana. Specifically, we argue that the primary goal of legalization should be the elimination of the illicit trade in marijuana and that maximizing market participation through open markets and personal cultivation is the best approach to achieving this goal. This argument is based on the assertion that regulatory models based on a tightly controlled government market will fail because they replicate the fatal flaws of the prohibition model. This commentary argues that an examination of the reasons for prohibition's failure-to wit, the inability of government to control the production of marijuana-completely undercuts the basic premise of a tightly controlled market, which depends on the ability of the government to control production. The public interest would be better served by an effective regulatory framework which recognizes and takes advantage of competitive market forces. This analysis argues that reducing teenage access to marijuana requires the elimination of an overcapitalized illicit market. Further, it asserts that this goal and maximization of tax revenue from a legal marijuana market are mutually exclusive objectives.

Cranes, Crops and Conservation: Understanding Human Perceptions of Biodiversity Conservation in South Korea's Civilian Control Zone

NASA Astrophysics Data System (ADS)

Kim, Jin-Oh; Steiner, Frederick; Mueller, Elizabeth

2011-01-01

South Korea's Civilian Control Zone (CCZ), a relatively untouched area due to tight military oversight since the end of Korean War, has received considerable attention nationally and internationally for its rich biodiversity. However, the exclusion of local communities from the process of defining problems and goals and of setting priorities for biodiversity conservation has halted a series of biodiversity conservation efforts. Through qualitative research, we explored CCZ farmers' views of key problems and issues and also the sources of their opposition to the government-initiated conservation approaches. Key findings include the farmers' concerns about the impact of conservation restrictions on their access to necessary resources needed to farm, wildlife impacts on the value of rice and other agricultural goods they produce, and farmers' strong distrust of government, the military, and planners, based on their experiences with past conservation processes. The findings regarding farmers' perceptions should prove useful for the design of future participatory planning processes for biodiversity conservation in the CCZ. This case highlights how conservative measures, perceived to be imposed from above—however scientifically valuable—can be undermined and suggests the value that must be placed on communication among planners and stakeholders.

Cranes, crops and conservation: understanding human perceptions of biodiversity conservation in South Korea's Civilian Control Zone.

PubMed

Kim, Jin-Oh; Steiner, Frederick; Mueller, Elizabeth

2011-01-01

South Korea's Civilian Control Zone (CCZ), a relatively untouched area due to tight military oversight since the end of Korean War, has received considerable attention nationally and internationally for its rich biodiversity. However, the exclusion of local communities from the process of defining problems and goals and of setting priorities for biodiversity conservation has halted a series of biodiversity conservation efforts. Through qualitative research, we explored CCZ farmers' views of key problems and issues and also the sources of their opposition to the government-initiated conservation approaches. Key findings include the farmers' concerns about the impact of conservation restrictions on their access to necessary resources needed to farm, wildlife impacts on the value of rice and other agricultural goods they produce, and farmers' strong distrust of government, the military, and planners, based on their experiences with past conservation processes. The findings regarding farmers' perceptions should prove useful for the design of future participatory planning processes for biodiversity conservation in the CCZ. This case highlights how conservative measures, perceived to be imposed from above--however scientifically valuable--can be undermined and suggests the value that must be placed on communication among planners and stakeholders.

The Influence of Endogenous and Exogenous Spatial Attention on Decision Confidence.

PubMed

Kurtz, Phillipp; Shapcott, Katharine A; Kaiser, Jochen; Schmiedt, Joscha T; Schmid, Michael C

2017-07-25

Spatial attention allows us to make more accurate decisions about events in our environment. Decision confidence is thought to be intimately linked to the decision making process as confidence ratings are tightly coupled to decision accuracy. While both spatial attention and decision confidence have been subjected to extensive research, surprisingly little is known about the interaction between these two processes. Since attention increases performance it might be expected that confidence would also increase. However, two studies investigating the effects of endogenous attention on decision confidence found contradictory results. Here we investigated the effects of two distinct forms of spatial attention on decision confidence; endogenous attention and exogenous attention. We used an orientation-matching task, comparing the two attention conditions (endogenous and exogenous) to a control condition without directed attention. Participants performed better under both attention conditions than in the control condition. Higher confidence ratings than the control condition were found under endogenous attention but not under exogenous attention. This finding suggests that while attention can increase confidence ratings, it must be voluntarily deployed for this increase to take place. We discuss possible implications of this relative overconfidence found only during endogenous attention with respect to the theoretical background of decision confidence.

Automated aerial image based CD metrology initiated by pattern marking with photomask layout data

NASA Astrophysics Data System (ADS)

Davis, Grant; Choi, Sun Young; Jung, Eui Hee; Seyfarth, Arne; van Doornmalen, Hans; Poortinga, Eric

2007-05-01

The photomask is a critical element in the lithographic image transfer process from the drawn layout to the final structures on the wafer. The non-linearity of the imaging process and the related MEEF impose a tight control requirement on the photomask critical dimensions. Critical dimensions can be measured in aerial images with hardware emulation. This is a more recent complement to the standard scanning electron microscope measurement of wafers and photomasks. Aerial image measurement includes non-linear, 3-dimensional, and materials effects on imaging that cannot be observed directly by SEM measurement of the mask. Aerial image measurement excludes the processing effects of printing and etching on the wafer. This presents a unique contribution to the difficult process control and modeling tasks in mask making. In the past, aerial image measurements have been used mainly to characterize the printability of mask repair sites. Development of photomask CD characterization with the AIMS TM tool was motivated by the benefit of MEEF sensitivity and the shorter feedback loop compared to wafer exposures. This paper describes a new application that includes: an improved interface for the selection of meaningful locations using the photomask and design layout data with the Calibre TM Metrology Interface, an automated recipe generation process, an automated measurement process, and automated analysis and result reporting on a Carl Zeiss AIMS TM system.

GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

NASA Technical Reports Server (NTRS)

Cross, James H., II

1990-01-01

The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

STEPS: Modeling and Simulating Complex Reaction-Diffusion Systems with Python

PubMed Central

Wils, Stefan; Schutter, Erik De

2008-01-01

We describe how the use of the Python language improved the user interface of the program STEPS. STEPS is a simulation platform for modeling and stochastic simulation of coupled reaction-diffusion systems with complex 3-dimensional boundary conditions. Setting up such models is a complicated process that consists of many phases. Initial versions of STEPS relied on a static input format that did not cleanly separate these phases, limiting modelers in how they could control the simulation and becoming increasingly complex as new features and new simulation algorithms were added. We solved all of these problems by tightly integrating STEPS with Python, using SWIG to expose our existing simulation code. PMID:19623245

Strategies for immortalization of primary hepatocytes

PubMed Central

Eva, Ramboer; Bram, De Craene; Joery, De Kock; Tamara, Vanhaecke; Geert, Berx; Vera, Rogiers; Mathieu, Vinken

2014-01-01

The liver has the unique capacity to regenerate in response to a damaging event. Liver regeneration is hereby largely driven by hepatocyte proliferation, which in turn relies on cell cycling. The hepatocyte cell cycle is a complex process that is tightly regulated by several well-established mechanisms. In vitro, isolated hepatocytes do not longer retain this proliferative capacity. However, in vitro cell growth can be boosted by immortalization of hepatocytes. Well-defined immortalization genes can be artificially overexpressed in hepatocytes or the cells can be conditionally immortalized leading to controlled cell proliferation. This paper discusses the current immortalization techniques and provides a state-of-the-art overview of the actually available immortalized hepatocyte-derived cell lines and their applications. PMID:24911463

BIOGEOCHEMICAL STUDIES OF PHOTOSYNTHETIC MICROBIAL MATS AND THEIR BIOTA

NASA Technical Reports Server (NTRS)

DesMarais, David; Discipulo, M.; Turk, K.; Londry, K. L.

2005-01-01

Photosynthetic microbial mats offer an opportunity to define holistic functionality at the millimeter scale. At the same time. their biogeochemistry contributes to environmental processes on a planetary scale. These mats are possibly direct descendents of the most ancient biological communities; communities in which oxygenic photosynthesis might have been invented. Mats provide one of the best natural systems to study how microbial populations associate to control dynamic biogeochemical gradients. These are self- sustaining, complete ecosystems in which light energy absorbed over a dial (24 hour) cycle drives the synthesis of spatially-organized, diverse biomass. Tightly-coupled microorganisms in the mat have specialized metabolisms that catalyze transformations of carbon, nitrogen, sulfur, and a host of other elements.

Mutations, kataegis, and translocations in B lymphocytes: towards a mechanistic understanding of AID promiscuous activity

PubMed Central

Casellas, Rafael; Basu, Uttiya; Yewdell, William T.; Chaudhuri, Jayanta; Robbiani, Davide F.; Di Noia, Javier M.

2016-01-01

As B cells engage in the immune response they express the deaminase AID to initiate the hypermutation and recombination of immunoglobulin genes, which are crucial processes for the efficient recognition and disposal of pathogens, However, AID must be tightly controlled in B cells to minimize off-targeting mutations, which can drive chromosomal translocations and the development of B cell malignancies, such as lymphomas. Recent genomic and biochemical analyses have begun to unravel the crucial question of how AID-mediated deamination is targeted outside immunoglobulin genes. Here, we discuss the transcriptional and topological features that are emerging as key drivers of AID promiscuous activity. PMID:26898111

Controlling the Transport of an Ion: Classical and Quantum Mechanical Solutions

DTIC Science & Technology

2014-07-09

quantum systems: tools, achievements, and limitations Christiane P Koch Shortcuts to adiabaticity for an ion in a rotating radially- tight trap M Palmero...Keywords: coherent control, ion traps, quantum information, optimal control theory 1. Introduction Control methods are key enabling techniques in many...figure 6. 3.4. Feasibility analysis of quantum optimal control Numerical optimization of the wavepacket motion is expected to become necessary once

Blood-brain Barrier Disruption Leads to Postoperative Cognitive Dysfunction.

PubMed

Wang, Bin; Li, Siyuan; Cao, Xipeng; Dou, Xinghui; Li, Jingzhu; Wang, Ling; Wang, Mingshan; Bi, Yanlin

2017-01-01

Postoperative Cognitive Dysfunction (POCD) has received considerable attention as one of the main postoperative complications. The underlying mechanism of POCD in elderly subjects has not been fully elucidated to date. The Central Nervous System (CNS) is isolated from the bloodstream by the Blood Brain Barrier (BBB) that consists of endothelial cells, capillary blood vessels and tight junctions. The tight junctions carry out significant biological functions that are associated with the CNS and blood circulation. In this review, I present a hypothesis that blood-brain barrier disruption leads to postoperative cognitive dysfunction. A total of 81 healthy male Wistar rats were used for the present study. All the experimental animals were randomly divided into 3 groups: normal control group, isoflurane group and splenectomy group. The control group was not subjected to any form of treatment. The rats in isoflurane group were given 1.5-2% isoflurane under intubation and mechanical ventilation. The rats in splenectomy group underwent splenectomy under the same anesthesia as the isoflurane group. The Morris water maze was used to examine the learning and memory ability of the animals. The expression of the Tight Junctions Proteins (TJPs) in the hippocampus was analyzed using Western blotting. The concentration of Evans Blue (EB) in the supernatant was analyzed using UV spectroscopy. Ultrastructure changes in the basal laminas, the Tight Junctions (TJs), mitochondria and the endoplasmic reticulum surrounding the capillaries were assessed by Transmission Electron Microscopy (TEM). Following splenectomy, the rats displayed concomitant significant cognitive deficits in the Morris water maze test. Taken together, the results indicate that the expression levels of occludin (65KD) following splenectomy were reduced on days one and three in aged rats. No significant difference was noted in the expression levels of claudin-5, except for a reduction after surgery on day one. The leakage of EB was higher following splenectomy than control group and isoflurane group. The ultrastructure of the neurovascular unit was monitored on the day prior to surgery and on the 1st, 3rd and 7th day following surgery using a transmission electronmicroscope. The alterations in the levels of tight junction proteins following splenectomy may contribute to the BBB permeability increase, which in turn will induce postoperative cognitive dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Assessment Relationships in Higher Education: The Tension of Process and Practice

ERIC Educational Resources Information Center

Crook, Charles; Gross, Harriet; Dymott, Roy

2006-01-01

It is argued that the auditing demands of quality assurance have encouraged a greater proceduralisation of university coursework assessment. Interviews with academics from a cross-section of Psychology departments illustrated how assessment had acquired the tightly scripted character of an organisational process. Yet undergraduate focus group…

An Access Control and Trust Management Framework for Loosely-Coupled Multidomain Environments

ERIC Educational Resources Information Center

Zhang, Yue

2010-01-01

Multidomain environments where multiple organizations interoperate with each other are becoming a reality as can be seen in emerging Internet-based enterprise applications. Access control to ensure secure interoperation in such an environment is a crucial challenge. A multidomain environment can be categorized as "tightly-coupled" and…

40 CFR 63.421 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Administrator and any other person. Controlled loading rack, for the purposes of § 63.420, means a loading rack... heat air pollutants to combustion temperatures. Uncontrolled loading rack means a loading rack used to load gasoline cargo tanks that is not a controlled loading rack. Vapor-tight gasoline cargo tank means...

Seizing Workplace Learning Affordances in High-Pressure Work Environments

ERIC Educational Resources Information Center

Gnaur, Dorina

2010-01-01

Work in call centres is often presented as a form of unskilled labour characterized by routinization, technological surveillance and tight management control aimed at reaching intensive performance targets. Beyond delivering business objectives, this control and efficiency strategy is often held to produce counterproductive effects with regard to…

Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

PubMed Central

Chiu, Chun-Ching; Shi, Ya-Fang; Yang, Jiann-Jou; Hsiao, Yuan-Chao; Tzang, Bor-Show; Hsu, Tsai-Ching

2014-01-01

As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-α (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-α or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-α, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity. PMID:25268969

Influence of Hamstring Tightness in Pelvic, Lumbar and Trunk Range of Motion in Low Back Pain and Asymptomatic Volunteers during Forward Bending

PubMed Central

Macedo, Adriana Ribeiro

2015-01-01

Study Design Cross-sectional study. Purpose To verify the association of hamstring tightness and range of motion in anterior pelvic tilt (PT), lumbar motion (LM), and trunk flexion (TF) during forward bending. Overview of Literature Increased hamstring stiffness could be a possible contributing factor to low back injuries. Clinical observations have suggested that hamstring tightness influences lumbar pelvic rhythm. Movement restrictions or postural asymmetry likely lead to compensatory movement patterns of the lumbar spine, and subsequently to increased stress on the spinal soft tissues and an increased risk of low back pain (LBP). Methods Hamstring muscle tightness was measured using the self-monitored active knee extension (AKE) test. A bubble inclinometer was used to determine the range of motion of PT, LM, and TF during forward bending. Statistical analysis included descriptive statistics, comparisons between groups and a correlation between hamstring tightness (AKE) and anterior PT, TF, and regional LM with p≤0.05. Results The LBP group was composed of 36 participants, and the asymptomatic group consisted of 32 participants. The mean for PT in the control group was 66.7°, 64.5° for LM and 104.6° for TF. Respective values in the symptomatic group were 57.0°, 79.8°, and 82.2°. Conclusions Participants with LBP showed restriction in the pelvis and TF range of motion, but had higher amplitudes in the lumbar spine during forward bending. PMID:26240711

Influence of Hamstring Tightness in Pelvic, Lumbar and Trunk Range of Motion in Low Back Pain and Asymptomatic Volunteers during Forward Bending.

PubMed

Jandre Reis, Felipe Jose; Macedo, Adriana Ribeiro

2015-08-01

Cross-sectional study. To verify the association of hamstring tightness and range of motion in anterior pelvic tilt (PT), lumbar motion (LM), and trunk flexion (TF) during forward bending. Increased hamstring stiffness could be a possible contributing factor to low back injuries. Clinical observations have suggested that hamstring tightness influences lumbar pelvic rhythm. Movement restrictions or postural asymmetry likely lead to compensatory movement patterns of the lumbar spine, and subsequently to increased stress on the spinal soft tissues and an increased risk of low back pain (LBP). Hamstring muscle tightness was measured using the self-monitored active knee extension (AKE) test. A bubble inclinometer was used to determine the range of motion of PT, LM, and TF during forward bending. Statistical analysis included descriptive statistics, comparisons between groups and a correlation between hamstring tightness (AKE) and anterior PT, TF, and regional LM with p≤0.05. The LBP group was composed of 36 participants, and the asymptomatic group consisted of 32 participants. The mean for PT in the control group was 66.7°, 64.5° for LM and 104.6° for TF. Respective values in the symptomatic group were 57.0°, 79.8°, and 82.2°. Participants with LBP showed restriction in the pelvis and TF range of motion, but had higher amplitudes in the lumbar spine during forward bending.

Simulation of a multistage fractured horizontal well in a water-bearing tight fractured gas reservoir under non-Darcy flow

NASA Astrophysics Data System (ADS)

Zhang, Rui-Han; Zhang, Lie-Hui; Wang, Rui-He; Zhao, Yu-Long; Huang, Rui

2018-06-01

Reservoir development for unconventional resources such as tight gas reservoirs is in increasing demand due to the rapid decline of production in conventional reserves. Compared with conventional reservoirs, fluid flow in water-bearing tight gas reservoirs is subject to more nonlinear multiphase flow and gas slippage in nano/micro matrix pores because of the strong collisions between rock and gas molecules. Economic gas production from tight gas reservoirs depends on extensive application of water-based hydraulic fracturing of horizontal wells, associated with non-Darcy flow at a high flow rate, geomechanical stress sensitivity of un-propped natural fractures, complex flow geometry and multiscale heterogeneity. How to efficiently and accurately predict the production performance of a multistage fractured horizontal well (MFHW) is challenging. In this paper, a novel multicontinuum, multimechanism, two-phase simulator is established based on unstructured meshes and the control volume finite element method to analyze the production performance of MFHWs. The multiple interacting continua model and discrete fracture model are coupled to integrate the unstimulated fractured reservoir, induced fracture networks (stimulated reservoir volumes, SRVs) and irregular discrete hydraulic fractures. Several simulations and sensitivity analyses are performed with the developed simulator for determining the key factors affecting the production performance of MFHWs. Two widely applied fracturing models, classic hydraulic fracturing which generates long double-wing fractures and the volumetric fracturing aimed at creating large SRVs, are compared to identify which of them can make better use of tight gas reserves.

Clinical benefits of tight glycaemic control: focus on the intensive care unit.

PubMed

Mesotten, Dieter; Van den Berghe, Greet

2009-12-01

While stress hyperglycaemia has traditionally been regarded as an adaptive, beneficial response, it is clear that hyperglycaemia and hypoglycaemia are associated with increased risk of death in critically ill intensive care unit (ICU) patients. Recent studies on blood-glucose control failed to fully clarify whether this association is causal. Early proof-of-concept single-centre randomised controlled studies found that maintaining normoglycaemia by intensive insulin therapy, as compared with tolerating hyperglycaemia as an adaptive response, improved patient outcome. However, recent large multicentre studies VISEP, GLUCONTROL and NICE-SUGAR) could not confirm this survival benefit. Methodological disparity in the execution of the complex intervention of tight glycaemic control may have contributed significantly to the contradicting results. First, different target ranges for blood glucose were used in the control group of the GLUCONTROL and 'Normoglycemia in intensive care evaluation and survival using glucose algorithm' regulation' (NICE-SUGAR) studies. Second, problems to steer blood-glucose levels within target range in the intervention group resulted in a significant overlap of the treatment groups. Third, allowing inaccurate blood-glucose measurement devices, in combination with different blood sampling sites and types of infusion pumps, may have led to unnoticed swings in blood-glucose levels. Fourth, the level of expertise of the intensive care nurses with the therapy may have been variable due to low number of study patients per centre. Finally, the studies on tight blood-glucose control were done with vastly different nutritional and end-of-life strategies. The currently available studies do not allow to confidently recommend one optimal target for glucose in heterogeneous ICU patient groups and settings. Provided that adequate devices for blood-glucose measurement and insulin administration are available, together with an extensive experience of the nursing staff, blood-glucose levels should be controlled as close to normal as possible, without evoking unacceptable fluctuations and hypoglycaemia.

Gaining control: changing relations between executive control and processing speed and their relevance for mathematics achievement over course of the preschool period

PubMed Central

Clark, Caron A. C.; Nelson, Jennifer Mize; Garza, John; Sheffield, Tiffany D.; Wiebe, Sandra A.; Espy, Kimberly Andrews

2014-01-01

Early executive control (EC) predicts a range of academic outcomes and shows particularly strong associations with children's mathematics achievement. Nonetheless, a major challenge for EC research lies in distinguishing EC from related cognitive constructs that also are linked to achievement outcomes. Developmental cascade models suggest that children's information processing speed is a driving mechanism in cognitive development that supports gains in working memory, inhibitory control and associated cognitive abilities. Accordingly, individual differences in early executive task performance and their relation to mathematics may reflect, at least in part, underlying variation in children's processing speed. The aims of this study were to: (1) examine the degree of overlap between EC and processing speed at different preschool age points; and (2) determine whether EC uniquely predicts children's mathematics achievement after accounting for individual differences in processing speed. As part of a longitudinal, cohort-sequential study, 388 children (50% boys; 44% from low income households) completed the same battery of EC tasks at ages 3, 3.75, 4.5, and 5.25 years. Several of the tasks incorporated baseline speeded naming conditions with minimal EC demands. Multidimensional latent models were used to isolate the variance in executive task performance that did not overlap with baseline processing speed, covarying for child language proficiency. Models for separate age points showed that, while EC did not form a coherent latent factor independent of processing speed at age 3 years, it did emerge as a distinct factor by age 5.25. Although EC at age 3 showed no distinct relation with mathematics achievement independent of processing speed, EC at ages 3.75, 4.5, and 5.25 showed independent, prospective links with mathematics achievement. Findings suggest that EC and processing speed are tightly intertwined in early childhood. As EC becomes progressively decoupled from processing speed with age, it begins to take on unique, discriminative importance for children's mathematics achievement. PMID:24596563

Amyloid precursor protein controls cholesterol turnover needed for neuronal activity

PubMed Central

Pierrot, Nathalie; Tyteca, Donatienne; D'auria, Ludovic; Dewachter, Ilse; Gailly, Philippe; Hendrickx, Aurélie; Tasiaux, Bernadette; Haylani, Laetitia El; Muls, Nathalie; N'Kuli, Francisca; Laquerrière, Annie; Demoulin, Jean-Baptiste; Campion, Dominique; Brion, Jean-Pierre; Courtoy, Pierre J; Kienlen-Campard, Pascal; Octave, Jean-Noël

2013-01-01

Perturbation of lipid metabolism favours progression of Alzheimer disease, in which processing of Amyloid Precursor Protein (APP) has important implications. APP cleavage is tightly regulated by cholesterol and APP fragments regulate lipid homeostasis. Here, we investigated whether up or down regulation of full-length APP expression affected neuronal lipid metabolism. Expression of APP decreased HMG-CoA reductase (HMGCR)-mediated cholesterol biosynthesis and SREBP mRNA levels, while its down regulation had opposite effects. APP and SREBP1 co-immunoprecipitated and co-localized in the Golgi. This interaction prevented Site-2 protease-mediated processing of SREBP1, leading to inhibition of transcription of its target genes. A GXXXG motif in APP sequence was critical for regulation of HMGCR expression. In astrocytes, APP and SREBP1 did not interact nor did APP affect cholesterol biosynthesis. Neuronal expression of APP decreased both HMGCR and cholesterol 24-hydroxylase mRNA levels and consequently cholesterol turnover, leading to inhibition of neuronal activity, which was rescued by geranylgeraniol, generated in the mevalonate pathway, in both APP expressing and mevastatin treated neurons. We conclude that APP controls cholesterol turnover needed for neuronal activity. PMID:23554170

Role of chemical and mechanical stimuli in mediating bone fracture healing.

PubMed

Zhang, Lihai; Richardson, Martin; Mendis, Priyan

2012-08-01

Bone is a remarkable living tissue that provides a framework for animal body support and motion. However, under excessive loads and deformations, bone is prone is to damage through fracture. Furthermore, once the bone is weakened by osteoporosis, bone fracture can occur even after only minimal trauma. Various techniques have been developed to treat bone fractures. Successful treatment outcomes depend on a fundamental understanding of the biochemical and biomechanical environments of the fracture site. Various cell types (e.g. mesenchymal stem cells, chondrocytes, osteoblasts and osteoclasts) within the fracture site tightly control the healing process by responding to the chemical and mechanical microenvironment. However, these mechanochemical regulatory mechanisms remain poorly understood at the system level owing to the large range of variables, such as age, sex and disease-associated material properties of the tissue. Computational modelling can play an important role in unravelling this complexity by combining mechanochemical interactions, revealing the dominant controlling processes and optimizing system behaviour, thereby enabling the development and evaluation of treatment strategies for individual patients. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Dual stimuli-responsive nano-vehicles for controlled drug delivery: mesoporous silica nanoparticles end-capped with natural chitosan.

PubMed

Hakeem, Abdul; Duan, Ruixue; Zahid, Fouzia; Dong, Chao; Wang, Boya; Hong, Fan; Ou, Xiaowen; Jia, Yongmei; Lou, Xiaoding; Xia, Fan

2014-11-11

Herein, we report natural chitosan end-capped MCM-41 type MSNPs as novel, dual stimuli, responsive nano-vehicles for controlled anticancer drug delivery. The chitosan nanovalves tightly close the pores of the MSNPs to control premature cargo release under physiological conditions but respond to lysozyme and acidic media to release the trapped cargo.

The emerging role of lysosomes in copper homeostasis.

PubMed

Polishchuk, Elena V; Polishchuk, Roman S

2016-09-01

The lysosomal system operates as a focal point where a number of important physiological processes such as endocytosis, autophagy and nutrient sensing converge. One of the key functions of lysosomes consists of regulating the metabolism/homeostasis of metals. Metal-containing components are carried to the lysosome through incoming membrane flows, while numerous transporters allow metal ions to move across the lysosome membrane. These properties enable lysosomes to direct metal fluxes to the sites where metal ions are either used by cellular components or sequestered. Copper belongs to a group of metals that are essential for the activity of vitally important enzymes, although it is toxic when in excess. Thus, copper uptake, supply and intracellular compartmentalization have to be tightly regulated. An increasing number of publications have indicated that these processes involve lysosomes. Here we review studies that reveal the expanding role of the lysosomal system as a hub for the control of Cu homeostasis and for the regulation of key Cu-dependent processes in health and disease.

Corrosion of Highly Specular Vapor Deposited Aluminum (VDA) on Earthshade Door Sandwich Structure

NASA Technical Reports Server (NTRS)

Plaskon, Daniel; Hsieh, Cheng

2003-01-01

High-resolution infrared (IR) imaging requires spacecraft instrument design that is tightly coupled with overall thermal control design. The JPL Tropospheric Emission Spectrometer (TES) instrument measures the 3-dimensional distribution of ozone and its precursors in the lower atmosphere on a global scale. The TES earthshade must protect the 180-K radiator and the 230-K radiator from the Earth IR and albedo. Requirements for specularity, emissivity, and solar absorptance of inner surfaces could only be met with vapor deposited aluminum (VDA). Circumstances leading to corrosion of the VDA are described. Innovative materials and processing to meet the optical and thermal cycle requirements were developed. Examples of scanning electronmicroscope (SEM), atomic force microscope (AFM), and other surface analysis techniques used in failure analysis, problem solving, and process development are given. Materials and process selection criteria and development test results are presented in a decision matrix. Examples of conditions promoting and preventing galvanic corrosion between VDA and graphite fiber-reinforced laminates are provided.

Silaffins in Silica Biomineralization and Biomimetic Silica Precipitation

PubMed Central

Lechner, Carolin C.; Becker, Christian F. W.

2015-01-01

Biomineralization processes leading to complex solid structures of inorganic material in biological systems are constantly gaining attention in biotechnology and biomedical research. An outstanding example for biomineral morphogenesis is the formation of highly elaborate, nano-patterned silica shells by diatoms. Among the organic macromolecules that have been closely linked to the tightly controlled precipitation of silica in diatoms, silaffins play an extraordinary role. These peptides typically occur as complex posttranslationally modified variants and are directly involved in the silica deposition process in diatoms. However, even in vitro silaffin-based peptides alone, with and without posttranslational modifications, can efficiently mediate biomimetic silica precipitation leading to silica material with different properties as well as with encapsulated cargo molecules of a large size range. In this review, the biomineralization process of silica in diatoms is summarized with a specific focus on silaffins and their in vitro silica precipitation properties. Applications in the area of bio- and nanotechnology as well as in diagnostics and therapy are discussed. PMID:26295401

YY1 Controls Immunoglobulin Class Switch Recombination and Nuclear Activation-Induced Deaminase Levels

PubMed Central

Zaprazna, Kristina

2012-01-01

Activation-induced deaminase (AID) is an enzyme required for class switch recombination (CSR) and somatic hypermutation (SHM), processes that ensure antibody maturation and expression of different immunoglobulin isotypes. AID function is tightly regulated by tissue- and stage-specific expression, nuclear localization, and protein stability. Transcription factor YY1 is crucial for early B cell development, but its function at late B cell stages is unknown. Here, we show that YY1 conditional knockout in activated splenic B cells interferes with CSR. Knockout of YY1 did not affect B cell proliferation, transcription of the AID and IgM genes, or levels of various switch region germ line transcripts. However, we show that YY1 physically interacts with AID and controls the accumulation of nuclear AID, at least in part, by increasing nuclear AID stability. We show for the first time that YY1 plays a novel role in CSR and controls nuclear AID protein levels. PMID:22290437

New gene functions in megakaryopoiesis and platelet formation

PubMed Central

Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O’Reilly, Paul F.; Shin, So-Youn; Esko, Tõnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C.; Cucca, Francesco; D’Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Leach, Irene Mateo; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Völker, Uwe; Wichmann, H.-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole

2012-01-01

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. PMID:22139419

Preparation and Distribution of Cannabis and Cannabis-Derived Dosage Formulations for Investigational and Therapeutic Use in the United States

PubMed Central

Thomas, Brian F.; Pollard, Gerald T.

2016-01-01

Cannabis is classified as a schedule I controlled substance by the US Drug Enforcement Agency, meaning that it has no medicinal value. Production is legally restricted to a single supplier at the University of Mississippi, and distribution to researchers is tightly controlled. However, a majority of the population is estimated to believe that cannabis has legitimate medical or recreational value, numerous states have legalized or decriminalized possession to some degree, and the federal government does not strictly enforce its law and is considering rescheduling. The explosive increase in open sale and use of herbal cannabis and its products has occurred with widely variable and in many cases grossly inadequate quality control at all levels—growing, processing, storage, distribution, and use. This paper discusses elements of the analytical and regulatory system that need to be put in place to ensure standardization for the researcher and to reduce the hazards of contamination, overdosing, and underdosing for the end-user. PMID:27630566

USP7/HAUSP: A SUMO deubiquitinase at the heart of DNA replication.

PubMed

Smits, Veronique A J; Freire, Raimundo

2016-09-01

DNA replication is both highly conserved and controlled. Problematic DNA replication can lead to genomic instability and therefore carcinogenesis. Numerous mechanisms work together to achieve this tight control and increasing evidence suggests that post-translational modifications (phosphorylation, ubiquitination, SUMOylation) of DNA replication proteins play a pivotal role in this process. Here we discuss such modifications in the light of a recent article that describes a novel role for the deubiquitinase (DUB) USP7/HAUSP in the control of DNA replication. USP7 achieves this function by an unusual and novel mechanism, namely deubiquitination of SUMOylated proteins at the replication fork, making USP7 also a SUMO DUB (SDUB). This work extends previous observations of increased levels of SUMO and low levels of ubiquitin at the on-going replication fork. Here, we discuss this novel study, its contribution to the DNA replication and genomic stability field and what questions arise from this work. © 2016 WILEY Periodicals, Inc.

TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6.

PubMed

van Goor, Mark K C; Hoenderop, Joost G J; van der Wijst, Jenny

2017-06-01

Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport. Copyright © 2016. Published by Elsevier B.V.

Co-transcriptional nuclear actin dynamics

PubMed Central

Percipalle, Piergiorgio

2013-01-01

Actin is a key player for nuclear structure and function regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many different proteins. Among these proteins several studies have identified classical nuclear factors involved in chromatin structure and function, transcription and RNA processing as well as proteins that are normally involved in controlling the actin cytoskeleton. These discoveries have raised the possibility that nuclear actin performs its multi task activities through tight interactions with different sets of proteins. This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states. Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity. By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified. PMID:23138849

A Computational Study of the Development of Epithelial Acini: II. Necessary Conditions for Structure and Lumen Stability

PubMed Central

Rejniak, Katarzyna A.; Anderson, Alexander R.A.

2013-01-01

Simple epithelial tissues are organized as single layers of tightly packed cells that surround hollow lumens and form selective barriers separating different internal compartments of the body. The maintenance of epithelial structure and its function requires tight coordination and control of all the life processes of epithelial cells via cell-to-cell communication and signaling. These well-balanced cellular systems are, however, quite often disturbed by genetic or environmental cues that may lead to the formation of epithelial tumors (carcinomas). In fact, more than a half of all diagnosed tumors are initiated from epithelial cells. It is, therefore, important to gain a greater understanding of the factors that form and maintain the epithelial structure, as well as the features of the acinar structure that are modified during cancer development as observable in experimental and clinical research. We address these questions using the bio-mechanical model of the developing hollow epithelial acini introduced in Rejniak and Anderson (Bull. Math. Biol. 70:677–712, 2008). Here, we propose several scenarios involving various bio-mechanical interactions between neighboring cells that result in abnormal acinar development. Whenever possible, we compare our computational results with known experimental cases of mutant acini. PMID:18401665

Superior characteristics of microscale light emitting diodes through tightly lateral oxide-confined scheme

NASA Astrophysics Data System (ADS)

Huang, Shen-Che; Li, Heng; Zhang, Zhe-Han; Chen, Hsiang; Wang, Shing-Chung; Lu, Tien-Chang

2017-01-01

We report on the design of the geometry and chip size-controlled structures of microscale light-emitting diodes (micro-LEDs) with a shallow-etched oxide-refilled current aperture and their performance. The proposed structure, which combines an indium-tin-oxide layer and an oxide-confined aperture, exhibited not only uniform current distribution but also remarkably tight current confinement. An extremely high injection level of more than 90 kA/cm2 was achieved in the micro-LED with a 5-μm aperture. Current spreading and the droop mechanism in the investigated devices were characterized through electroluminescence measurements, optical microscopy, and beam-view imaging. Furthermore, we utilized the β-model and S-model to elucidate current crowding and the efficiency droop phenomenon in the investigated micro-LEDs. The luminescence results evidenced the highly favorable performance of the fabricated micro-LEDs, which is a result of their more uniform current spreading and lower junction temperature relative to conventional LEDs. Moreover, the maximum endured current density could be further increased by reducing the aperture size of the micro-LEDs. The proposed design, which is expected to be beneficial for the development of high-performance array-based micro-LEDs, is practicable through current state-of-the-art processing techniques.

Experience with long-term glucocorticoid treatment in congenital adrenal hyperplasia: growth pattern compared with genetic height potential.

PubMed

Aycan, Zehra; Ocal, Gonul; Berberoglu, Merih; Cetinkaya, Ergun; Adiyaman, Pelin; Evliyaoglu, Olcay

2006-03-01

Long-term replacement treatment with high doses of steroids in congenital adrenal hyperplasia (CAH) is known to have a negative influence on growth. We evaluated the effects of long-term steroid treatment in patients with classical CAH on height development in relation to genetic height potential. Twenty-three patients with CAH (16 females, 7 males, mean age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of steroid treatment on growth was determined by monitoring patients for 8.61 +/- 3.46 years (2-17 years) while they were treated with hydrocortisone at a mean dosage of 17.64 +/- 3.60 mg/m2/day. The height standard deviation scores (Ht-SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for all patients. Predicted adult height according to bone age was calculated and it was determined whether height was developing according to the genetic height potential. In addition, patients were grouped as 'tight control' or 'poor control' according to their mean serum 17OH-progesterone or ACTH levels while on treatment. We evaluated whether height development was different for the tight and poor control groups. The mean chronological age of our patients at the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH) 157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14. There was no significant difference between the actual Ht-SDS and TH-SDS of our patients (p >0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our patients had normal height according to their genetic potential while 71.5% were shorter than their genetic height potential. While the Ht-SDS and corrected Ht-SDS were similar in the tight and poor metabolic control groups, the predicted height was significantly greater in the tight control group. We demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m2/day in classical CAH had a negative influence on height development for genetic height potential in 8.5 years of follow-up and that it is necessary to use the lowest possible steroid dosage by individualizing the dose.

Tight glycemic control with insulin does not affect skeletal muscle degradation during the early post-operative period following pediatric cardiac surgery

PubMed Central

Fisher, Jeremy G.; Sparks, Eric A.; Khan, Faraz A.; Alexander, Jamin L.; Asaro, Lisa A.; Wypij, David; Gaies, Michael; Modi, Biren P.; Duggan, Christopher; Agus, Michael S.D.; Yu, Yong-Ming; Jaksic, Tom

2015-01-01

Objective Critical illness is associated with significant catabolism and persistent protein loss correlates with increased morbidity and mortality. Insulin is a potent anti-catabolic hormone; high-dose insulin decreases skeletal muscle protein breakdown in critically ill pediatric surgical patients. However, insulin's effect on protein catabolism when given at clinically utilized doses has not been studied. The objective was to evaluate the effect of post-operative tight glycemic control and clinically-dosed insulin on skeletal muscle degradation in children after cardiac surgery with cardiopulmonary bypass. Design Secondary analysis of a two-center, prospective randomized trial comparing tight glycemic control with standard care. Randomization was stratified by study center. Patients Children 0-36 months who were admitted to the ICU after cardiac surgery requiring cardiopulmonary bypass. Interventions In the tight glycemic control (TGC) arm, insulin was titrated to maintain blood glucose between 80-110 mg/dL. Patients in the control arm received standard care. Skeletal muscle breakdown was quantified by a ratio of urinary 3-methylhistidine to urinary creatinine (3MH:Cr). Main Results A total of 561 patients were included: 281 in the TGC arm and 280 receiving standard care. There was no difference in 3MH:Cr between groups (TGC 249 ± 127 vs. standard care 253 ± 112, mean ± standard deviation in μmol/g, P=0.72). In analyses restricted to the TGC patients, higher 3MH:Cr correlated with younger age as well as lower weight, weight-for-age z-score, length, and body surface area (P<0.005 for each), and lower post-operative day 3 serum creatinine (r=-0.17, P=0.02). Sex, prealbumin, and albumin were not associated with 3MH:Cr. During urine collection, 245 patients (87%) received insulin. However, any insulin exposure did not impact 3MH:Cr (t-test, P=0.45), and there was no dose-dependent effect of insulin on 3MH:Cr (r=-0.03, P=0.60). Conclusion Though high-dose insulin has an anabolic effect in experimental conditions, at doses necessary to achieve normoglycemia, insulin appears to have no discernible impact on skeletal muscle degradation in critically ill pediatric cardiac surgical patients. PMID:25850865

Metabolism A higher power for insulin

NASA Astrophysics Data System (ADS)

Gribble, Fiona M.

2005-04-01

Glucose output from the liver is tightly regulated by insulin. But insulin holds sway over more than the liver - an unappreciated circuit in glucose control involves the opening of ion channels in the brain.

33 CFR 401.94 - Keeping copies of regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... duplicated set of the Ship's Fire Control Plans shall be permanently stored in a prominently marked weather-tight enclosure outside the deckhouse for the assistance of shore-side fire-fighting personnel. [70 FR...

33 CFR 401.94 - Keeping copies of regulations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... duplicated set of the Ship's Fire Control Plans shall be permanently stored in a prominently marked weather-tight enclosure outside the deckhouse for the assistance of shore-side fire-fighting personnel. [70 FR...

Cognition in action: imaging brain/body dynamics in mobile humans.

PubMed

Gramann, Klaus; Gwin, Joseph T; Ferris, Daniel P; Oie, Kelvin; Jung, Tzyy-Ping; Lin, Chin-Teng; Liao, Lun-De; Makeig, Scott

2011-01-01

We have recently developed a mobile brain imaging method (MoBI), that allows for simultaneous recording of brain and body dynamics of humans actively behaving in and interacting with their environment. A mobile imaging approach was needed to study cognitive processes that are inherently based on the use of human physical structure to obtain behavioral goals. This review gives examples of the tight coupling between human physical structure with cognitive processing and the role of supraspinal activity during control of human stance and locomotion. Existing brain imaging methods for actively behaving participants are described and new sensor technology allowing for mobile recordings of different behavioral states in humans is introduced. Finally, we review recent work demonstrating the feasibility of a MoBI system that was developed at the Swartz Center for Computational Neuroscience at the University of California, San Diego, demonstrating the range of behavior that can be investigated with this method.

Surface-enhanced Raman scattering from graphene covered gold nanocap arrays

NASA Astrophysics Data System (ADS)

Long, Kailin; Luo, Xiaoguang; Nan, Haiyan; Du, Deyang; Zhao, Weiwei; Ni, Zhenhua; Qiu, Teng

2013-11-01

This work reports an efficient method to fabricate large-area flexible substrates for surface enhanced Raman scattering (SERS) application. Our technique is based on a single-step direct imprint process via porous anodic alumina stamps. Periodic hexagonal arrangements of porous anodic alumina stamps are transferred to the polyethylene terephthalate substrates by mechanically printing process. Printed nanocaps will turn into "hot spots" for electromagnetic enhancement with a deposited gold film by high vacuum evaporation. The gaps between the nanocaps are controllable with a tight correspondence to the thickness of the deposited gold, which dramatically influence the enhancement factor. After covered with a single-layer graphene sheet, the gold nanocap substrate can be further optimized with an extra enhancement of Raman signals, and it is available for the trace detection of probe molecules. This convenient, simple, and low-cost method of making flexible SERS-active substrates potentially opens a way towards biochemical analysis and disease detection.

Retrovirus maturation-an extraordinary structural transformation.

PubMed

Mattei, Simone; Schur, Florian Km; Briggs, John Ag

2016-06-01

Retroviruses such as HIV-1 assemble and bud from infected cells in an immature, non-infectious form. Subsequently, a series of proteolytic cleavages catalysed by the viral protease leads to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell. Maturation involves changes in the structures of protein domains, in the interactions between protein domains, and in the architecture of the viral components that are assembled by the proteins. Tight control of proteolytic cleavages at different sites is required for successful maturation, and the process is a major target of antiretroviral drugs. Here we will describe what is known about the structures of immature and mature retrovirus particles, and about the maturation process by which one transitions into the other. Despite a wealth of available data, fundamental questions about retroviral maturation remain unanswered. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells.

PubMed

Ramakrishnan, P; Kahn, D A; Baltimore, D

2011-04-01

Thymocyte development is a tightly controlled multi-step process involving selective elimination of self-reactive and non-functional T cells by apoptosis. This developmental process depends on signaling by Notch, IL-7 and active glucose metabolism. In this study, we explored the requirement of glucose for thymocyte survival and found that in addition to metabolic regulation, glucose leads to the expression of anti-apoptotic genes. Under hyperglycemic conditions, both mouse and human thymocytes demonstrate enhanced survival. We show that glucose-induced anti-apoptotic genes are dependent on NF-κB p65 because high glucose is unable to attenuate normal ongoing apoptosis of thymocytes isolated from p65 knockout mice. Furthermore, we demonstrate that in vivo hyperglycemia decreases apoptosis of thymocytes allowing for survival of potentially self-reactive thymocytes. These results imply that hyperglycemic conditions could contribute to the development of autoimmunity through dysregulated thymic selection. © 2011 Macmillan Publishers Limited

IR-laser assisted additive freeform optics manufacturing.

PubMed

Hong, Zhihan; Liang, Rongguang

2017-08-02

Computer-controlled additive manufacturing (AM) processes, also known as three-dimensional (3D) printing, create 3D objects by the successive adding of a material or materials. While there have been tremendous developments in AM, the 3D printing of optics is lagging due to the limits in materials and tight requirements for optical applicaitons. We propose a new precision additive freeform optics manufacturing (AFOM) method using an pulsed infrared (IR) laser. Compared to ultraviolet (UV) curable materials, thermally curable optical silicones have a number of advantages, such as strong UV stability, non-yellowing, and high transmission, making it particularly suitable for optical applications. Pulsed IR laser radiation offers a distinct advantage in processing optical silicones, as the high peak intensity achieved in the focal region allows for curing the material quickly, while the brief duration of the laser-material interaction creates a negligible heat-affected zone.

The Center for Multiscale Plasma Dynamics, Final Report

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

Gombosi, Tamas I.

The University of Michigan participated in the joint UCLA/Maryland fusion science center focused on plasma physics problems for which the traditional separation of the dynamics into microscale and macroscale processes breaks down. These processes involve large scale flows and magnetic fields tightly coupled to the small scale, kinetic dynamics of turbulence, particle acceleration and energy cascade. The interaction between these vastly disparate scales controls the evolution of the system. The enormous range of temporal and spatial scales associated with these problems renders direct simulation intractable even in computations that use the largest existing parallel computers. Our efforts focused on twomore » main problems: the development of Hall MHD solvers on solution adaptive grids and the development of solution adaptive grids using generalized coordinates so that the proper geometry of inertial confinement can be taken into account and efficient refinement strategies can be obtained.« less

Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development.

PubMed

Rodenfels, Jonathan; Lavrynenko, Oksana; Ayciriex, Sophie; Sampaio, Julio L; Carvalho, Maria; Shevchenko, Andrej; Eaton, Suzanne

2014-12-01

In Drosophila larvae, growth and developmental timing are regulated by nutrition in a tightly coordinated fashion. The networks that couple these processes are far from understood. Here, we show that the intestine responds to nutrient availability by regulating production of a circulating lipoprotein-associated form of the signaling protein Hedgehog (Hh). Levels of circulating Hh tune the rates of growth and developmental timing in a coordinated fashion. Circulating Hh signals to the fat body to control larval growth. It regulates developmental timing by controlling ecdysteroid production in the prothoracic gland. Circulating Hh is especially important during starvation, when it is also required for mobilization of fat body triacylglycerol (TAG) stores. Thus, we demonstrate that Hh, previously known only for its local morphogenetic functions, also acts as a lipoprotein-associated endocrine hormone, coordinating the response of multiple tissues to nutrient availability. © 2014 Rodenfels et al.; Published by Cold Spring Harbor Laboratory Press.

Thyroid hormone and cerebellar development.

PubMed

Anderson, Grant W

2008-01-01

Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

Selective tuning of the right inferior frontal gyrus during target detection

PubMed Central

Hampshire, Adam; Thompson, Russell; Duncan, John; Owen, Adrian M.

2010-01-01

In the human brain, a network of frontal and parietal regions is commonly recruited during tasks that demand the deliberate, focused control of thought and action. Previously, using a simple target detection task, we reported striking differences in the selectivity of the BOLD response in anatomically distinct subregions of this network. In particular, it was observed that the right inferior frontal gyrus (IFG) followed a tightly tuned function, selectively responding only to the current target object. Here, we examine this functional specialization further, using adapted versions of our original task. Our results demonstrate that the response of the right IFG to targets is a strong and replicable phenomenon. It occurs under increased attentional load, when targets and distractors are equally frequent, and when controlling for inhibitory processes. These findings support the hypothesis that the right IFG responds selectively to those items that are of the most relevance to the currently intended task schema. PMID:19246331

Deposition of hermetic silver shells onto copper flakes.

PubMed

Njagi, John I; Netzband, Christopher M; Goia, Dan V

2017-02-15

Continuous silver shells were deposited on copper flakes using a two-stage precipitation process. A tightly packed layer of silver nanoparticles was first formed on the surface of the base metal by galvanic displacement. The size of the noble metal particles and their distribution on the substrate were controlled using complexing agents and dispersants. A continuous Ag deposit was subsequently grown by reducing slowly [Ag(NH 3 ) 2 ] + ions with glucose. The final shell thickness was controlled by varying the amount of metal deposited in the second step. The electrical properties of resulting silver coated copper flakes are comparable to those measured for silver flakes of similar size and aspect ratio. By preventing the oxidation of copper cores up to 400°C, the hermetic noble metal shell dramatically extends the temperature range in which Ag/Cu flakes can successfully replace pure silver. Copyright © 2016 Elsevier Inc. All rights reserved.

Hydrogel microfluidics for the patterning of pluripotent stem cells

NASA Astrophysics Data System (ADS)

Cosson, S.; Lutolf, M. P.

2014-03-01

Biomolecular signaling is of utmost importance in governing many biological processes such as the patterning of the developing embryo where biomolecules regulate key cell-fate decisions. In vivo, these factors are presented in a spatiotemporally tightly controlled fashion. Although state-of-the-art microfluidic technologies allow precise biomolecule delivery in time and space, long-term (stem) cell culture at the micro-scale is often far from ideal due to medium evaporation, limited space for cell growth or shear stress. To overcome these challenges, we here introduce a concept based on hydrogel microfluidics for decoupling conventional, macro-scale cell culture from precise biomolecule delivery through a gel layer. We demonstrate the spatiotemporally controlled neuronal commitment of mouse embryonic stem cells via delivery of retinoic acid gradients. This technique should be useful for testing the effect of dose and timing of biomolecules, singly or in combination, on stem cell fate.

What Are the Targets of Inflammatory Bowel Disease Management.

PubMed

Lega, Sara; Dubinsky, Marla C

2018-04-25

With recent evidence suggesting that keeping the inflammatory process under tight control prevents long-term disability, the aim of treatments in inflammatory bowel disease (IBD) has shifted from symptom control toward the resolution of bowel inflammation. Mucosal healing is currently recognized as the principal treatment target to be used in a "treat to target" paradigm, whereas histologic healing and normalization of biomarkers are being evaluated as potential future targets. Although symptom relief is no longer a sufficient target, patient experience with the disease is of unquestionable importance and should be assessed in the form of patient-reported outcomes, to be used as a co-primary target with an objective measure of disease activity. IBD in is a heterogeneous disease; thus besides defining common treatment targets, every effort should be made to deliver a personalized treatment plan based on the risk factors for disease progression and individual drug metabolism to improve treatment success.

Model-Driven Configuration of SELinux Policies

NASA Astrophysics Data System (ADS)

Agreiter, Berthold; Breu, Ruth

The need for access control in computer systems is inherent. However, the complexity to configure such systems is constantly increasing which affects the overall security of a system negatively. We think that it is important to define security requirements on a non-technical level while taking the application domain into respect in order to have a clear and separated view on security configuration (i.e. unblurred by technical details). On the other hand, security functionality has to be tightly integrated with the system and its development process in order to provide comprehensive means of enforcement. In this paper, we propose a systematic approach based on model-driven security configuration to leverage existing operating system security mechanisms (SELinux) for realising access control. We use UML models and develop a UML profile to satisfy these needs. Our goal is to exploit a comprehensive protection mechanism while rendering its security policy manageable by a domain specialist.

USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin homeostasis through Ubiquilin.

PubMed

Wang, Chien-Hsiang; Huang, Yi-Chun; Chen, Pei-Yi; Cheng, Ying-Ju; Kao, Hsiu-Hua; Pi, Haiwei; Chien, Cheng-Ting

2017-05-10

Synapse formation and growth are tightly controlled processes. How synaptic growth is terminated after reaching proper size remains unclear. Here, we show that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In leon mutants, postsynaptic specializations of neuromuscular junctions are dramatically expanded, including the subsynaptic reticulum, the postsynaptic density, and the glutamate receptor cluster. Expansion of these postsynaptic features is caused by a disruption of ubiquitin homeostasis with accumulation of free ubiquitin chains and ubiquitinated substrates in the leon mutant. Accumulation of Ubiquilin (Ubqn), the ubiquitin receptor whose human homolog ubiquilin 2 is associated with familial amyotrophic lateral sclerosis, also contributes to defects in postsynaptic growth and ubiquitin homeostasis. Importantly, accumulations of postsynaptic proteins cause different aspects of postsynaptic overgrowth in leon mutants. Thus, the deubiquitinase Leon maintains ubiquitin homeostasis and proper Ubqn levels, preventing postsynaptic proteins from accumulation to confine postsynaptic growth.

Dynamics and molecular determinants of cytoplasmic lipid droplet clustering and dispersion.

PubMed

Orlicky, David J; Monks, Jenifer; Stefanski, Adrianne L; McManaman, James L

2013-01-01

Perilipin-1 (Plin1), a prominent cytoplasmic lipid droplet (CLD) binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT) induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps.

Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease

PubMed Central

Gweon, Tae-Geun; Park, Jong-Hyung; Kim, Byung-Wook; Choi, Yang Kyu; Kim, Joon Sung; Park, Sung Min; Kim, Chang Whan; Kim, Hyung-Gil; Chung, Jun-Won; Incheon

2018-01-01

Background/Aims The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). Methods GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. Results The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Conclusions Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms. PMID:29069891

Nanofiltration and Tight Ultrafiltration Membranes for the Recovery of Polyphenols from Agro-Food By-Products.

PubMed

Cassano, Alfredo; Conidi, Carmela; Ruby-Figueroa, René; Castro-Muñoz, Roberto

2018-01-24

Pressure-driven membrane-based technologies represent a valid approach to reduce the environmental pollution of several agro-food by-products. Recently, in relation to the major interest for natural compounds with biological activities, their use has been also addressed to the recovery, separation and fractionation of phenolic compounds from such by-products. In particular, tight ultrafiltration (UF) and nanolfiltration (NF) membranes have been recognized for their capability to recover phenolic compounds from several types of agro-food by-products. The separation capability of these membranes, as well as their productivity, depends on multiple factors such as membrane material, molecular weight cut-off (MWCO) and operating conditions (e.g., pressure, temperature, feed flow rate, volume reduction factor, etc.). This paper aims at providing a critical overview of the influence of these parameters on the recovery of phenolic compounds from agro-food by-products by using tight UF and NF membranes. The literature data are analyzed and discussed in relation to separation processes, molecule properties, membrane characteristics and other phenomena occurring in the process. Current extraction methodologies of phenolic compounds from raw materials are also introduced in order to drive the implementation of integrated systems for the production of actractive phenolic formulations of potential interest as food antioxidants.

Nanofiltration and Tight Ultrafiltration Membranes for the Recovery of Polyphenols from Agro-Food By-Products

PubMed Central

Conidi, Carmela; Ruby-Figueroa, René; Castro-Muñoz, Roberto

2018-01-01

Pressure-driven membrane-based technologies represent a valid approach to reduce the environmental pollution of several agro-food by-products. Recently, in relation to the major interest for natural compounds with biological activities, their use has been also addressed to the recovery, separation and fractionation of phenolic compounds from such by-products. In particular, tight ultrafiltration (UF) and nanolfiltration (NF) membranes have been recognized for their capability to recover phenolic compounds from several types of agro-food by-products. The separation capability of these membranes, as well as their productivity, depends on multiple factors such as membrane material, molecular weight cut-off (MWCO) and operating conditions (e.g., pressure, temperature, feed flow rate, volume reduction factor, etc.). This paper aims at providing a critical overview of the influence of these parameters on the recovery of phenolic compounds from agro-food by-products by using tight UF and NF membranes. The literature data are analyzed and discussed in relation to separation processes, molecule properties, membrane characteristics and other phenomena occurring in the process. Current extraction methodologies of phenolic compounds from raw materials are also introduced in order to drive the implementation of integrated systems for the production of actractive phenolic formulations of potential interest as food antioxidants. PMID:29364859

Decreased expression of zonula occludens-1 and occludin in the bladder urothelium of patients with interstitial cystitis/painful bladder syndrome.

PubMed

Lee, Jane-Dar; Lee, Ming-Huei

2014-01-01

Unique barrier properties of the urothelial surface membrane permit urine storage without contents leak into the bloodstream. Previous reports suggested that the bladder urothelial barrier might be compromised in interstitial cystitis/painful bladder syndrome (IC/PBS). We examined the changes of tight junction proteins (zonula occludens-1 (ZO-1) and occludin) in IC/PBS patients. Bladder samples were derived from of 32 patients with IC/PBS and eight controls. We detected the tight junction proteins of ZO-1 and occludin expression by immunoblotting, immunohistochemical (IHC) staining and double immunofluorescent (IF) staining with confocal microscopy. Data were analyzed using the Mann-Whitney U-test. Expression of ZO-1 and occludin in the IC/PBS group was reduced compared to the control group by immunoblotting and IHC staining. Also, the thinning and denudation of urothelium were demonstrated in the IC/PBS group by histological study. IF staining showed the interruption of bladder urothelium in IC/PBS patients under confocal microscopy. Our data showed that decreased expression of tight junction proteins (ZO-1 and occludin) and interruption of bladder urothelium in IC/PBS patients. Treatment to repair the discontinuous urothelium may be useful to relieve some clinical symptoms of patients with IC/PBS. Copyright © 2012. Published by Elsevier B.V.

Insulin Pumps: What Every School Nurse Needs to Know

ERIC Educational Resources Information Center

Bierschbach, Judy Laver; Cooper, Leslie; Liedl, Jennifer A.

2004-01-01

The results of the Diabetes Control and Complications Trial revolutionized the care of people with Type 1 diabetes mellitus (DM). The era of "tight control" of blood sugars to decrease microvascular complications dawned. The subsequent technological development of insulin pumps has made it possible for individuals with Type 1 DM, as well as those…

The knottin-like Blufensin family regulates genes involved in nuclear import and the secretory pathway in barley-powdery mildew interactions

USDA-ARS?s Scientific Manuscript database

Plants have evolved complex regulatory mechanisms to control a multi-layered defense response to microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSINs, small knottin-like...

Improving Forecast Skill by Assimilation of AIRS Temperature Soundings

NASA Technical Reports Server (NTRS)

Susskind, Joel; Reale, Oreste

2010-01-01

AIRS was launched on EOS Aqua on May 4, 2002, together with AMSU-A and HSB, to form a next generation polar orbiting infrared and microwave atmospheric sounding system. The primary products of AIRS/AMSU-A are twice daily global fields of atmospheric temperature-humidity profiles, ozone profiles, sea/land surface skin temperature, and cloud related parameters including OLR. The AIRS Version 5 retrieval algorithm, is now being used operationally at the Goddard DISC in the routine generation of geophysical parameters derived from AIRS/AMSU data. A major innovation in Version 5 is the ability to generate case-by-case level-by-level error estimates delta T(p) for retrieved quantities and the use of these error estimates for Quality Control. We conducted a number of data assimilation experiments using the NASA GEOS-5 Data Assimilation System as a step toward finding an optimum balance of spatial coverage and sounding accuracy with regard to improving forecast skill. The model was run at a horizontal resolution of 0.5 deg. latitude X 0.67 deg longitude with 72 vertical levels. These experiments were run during four different seasons, each using a different year. The AIRS temperature profiles were presented to the GEOS-5 analysis as rawinsonde profiles, and the profile error estimates delta (p) were used as the uncertainty for each measurement in the data assimilation process. We compared forecasts analyses generated from the analyses done by assimilation of AIRS temperature profiles with three different sets of thresholds; Standard, Medium, and Tight. Assimilation of Quality Controlled AIRS temperature profiles significantly improve 5-7 day forecast skill compared to that obtained without the benefit of AIRS data in all of the cases studied. In addition, assimilation of Quality Controlled AIRS temperature soundings performs better than assimilation of AIRS observed radiances. Based on the experiments shown, Tight Quality Control of AIRS temperature profile performs best on the average from the perspective of improving Global 7 day forecast skill.

Can adverse maternal and perinatal outcomes be predicted when blood pressure becomes elevated? Secondary analyses from the CHIPS (Control of Hypertension In Pregnancy Study) randomized controlled trial.

PubMed

Magee, Laura A; von Dadelszen, Peter; Singer, Joel; Lee, Terry; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E; Menzies, Jennifer; Sanchez, Johanna; Gafni, Amiram; Gruslin, Andrée; Helewa, Michael; Hutton, Eileen; Lee, Shoo K; Logan, Alexander G; Ganzevoort, Wessel; Welch, Ross; Thornton, Jim G; Moutquin, Jean Marie

2016-07-01

For women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes. This was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight <10th percentile) or maternal outcomes (severe hypertension, preeclampsia, or delivery at <34 or <37 weeks). A model containing all candidate predictors was used to start the stepwise regression process based on goodness of fit as measured by the Akaike information criterion. For face validity, these variables were forced into the model: treatment group ("less tight" or "tight" control), antihypertensive type at randomization, and blood pressure within 1 week before randomization. Continuous variables were represented continuously or dichotomized based on the smaller p-value in univariate analyses. An area-under-the-receiver-operating-curve (AUC ROC) of ≥0.70 was taken to reflect a potentially useful model. Point estimates for AUC ROC were <0.70 for all but severe hypertension (0.70, 95% CI 0.67-0.74) and delivery at <34 weeks (0.71, 95% CI 0.66-0.75). Therefore, no model warranted further assessment of performance. CHIPS data suggest that when women with chronic hypertension develop an elevated blood pressure in pregnancy, or formerly normotensive women develop new gestational hypertension, maternal and current pregnancy clinical characteristics cannot predict adverse outcomes in the index pregnancy. © 2016 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

A nonlinear OPC technique for laser beam control in turbulent atmosphere

NASA Astrophysics Data System (ADS)

Markov, V.; Khizhnyak, A.; Sprangle, P.; Ting, A.; DeSandre, L.; Hafizi, B.

2013-05-01

A viable beam control technique is critical for effective laser beam transmission through turbulent atmosphere. Most of the established approaches require information on the impact of perturbations on wavefront propagated waves. Such information can be acquired by measuring the characteristics of the target-scattered light arriving from a small, preferably diffraction-limited, beacon. This paper discusses an innovative beam control approach that can support formation of a tight laser beacon in deep turbulence conditions. The technique employs Brillouin enhanced fourwave mixing (BEFWM) to generate a localized beacon spot on a remote image-resolved target. Formation of the tight beacon doesn't require a wavefront sensor, AO system, or predictive feedback algorithm. Unlike conventional adaptive optics methods which allow wavefront conjugation, the proposed total field conjugation technique is critical for beam control in the presence of strong turbulence and can be achieved by using this non-linear BEFWM technique. The phase information retrieved from the established beacon beam can then be used in conjunction with an AO system to propagate laser beams in deep turbulence.

Physiology of ejaculation: emphasis on serotonergic control.

PubMed

Giuliano, François; Clément, Pierre

2005-09-01

Ejaculation is constituted by two distinct phases, emission and expulsion. Orgasm, a feature perhaps unique in humans, is a cerebral process that occurs, in normal conditions, concomitantly to expulsion of semen. Normal antegrade ejaculation is a highly coordinated physiological process with emission and expulsion phases being under the control of autonomic and somatic nervous systems respectively. The central command of ejaculation is located at the thoracolumbar and lumbosacral levels of the spinal cord and is activated by stimuli from genital, mainly penile, origin although cerebral descending pathways exert both inhibitory and excitatory regulatory roles. Cerebral structures specifically activated during ejaculation form a tightly interconnected network comprising hypothalamic, diencephalic and pontine areas. A rational neurobiological approach has led to identify several neurotransmitters contributing to the ejaculatory process. Amongst them, serotonin (5-HT) has received strong experimental evidences indicating its inhibitory role in the central control of ejaculation. In particular, 5-HT1A cerebral autoreceptors but also spinal 5-HT1B and, in a lesser extent, 5-HT2C receptors have been shown to mediate the effects of 5-HT on ejaculation. Pharmacological strategies, especially those targeting serotonergic system, for the treatment of ejaculatory disorders in human will undoubtedly benefit from the application of basic and clinical research findings. In this perspective, the use of selective serotonin reuptake inhibitors (SSRIs) which basically increase the amount of central 5-HT and delay ejaculation in humans seems promising.

Detrimental effects of proteasome inhibition activity in Drosophila melanogaster: implication of ER stress, autophagy, and apoptosis.

PubMed

Velentzas, Panagiotis D; Velentzas, Athanassios D; Mpakou, Vassiliki E; Antonelou, Marianna H; Margaritis, Lukas H; Papassideri, Issidora S; Stravopodis, Dimitrios J

2013-02-01

In eukaryotes, the ubiquitin-proteasome machinery regulates a number of fundamental cellular processes through accurate and tightly controlled protein degradation pathways. We have, herein, examined the effects of proteasome functional disruption in Dmp53 (+/+) (wild-type) and Dmp53 (-/-) Drosophila melanogaster fly strains through utilization of Bortezomib, a proteasome-specific inhibitor. We report that proteasome inhibition drastically shortens fly life-span and impairs climbing performance, while it also causes larval lethality and activates developmentally irregular cell death programs during oogenesis. Interestingly, Dmp53 gene seems to play a role in fly longevity and climbing ability. Moreover, Bortezomib proved to induce endoplasmic reticulum (ER) stress that was able to result in the engagement of unfolded protein response (UPR) signaling pathway, as respectively indicated by fly Xbp1 activation and Ref(2)P-containing protein aggregate formation. Larva salivary gland and adult brain both underwent strong ER stress in response to Bortezomib, thus underscoring the detrimental role of proteasome inhibition in larval development and brain function. We also propose that the observed upregulation of autophagy operates as a protective mechanism to "counterbalance" Bortezomib-induced systemic toxicity, which is tightly associated, besides ER stress, with activation of apoptosis, mainly mediated by functional Drice caspase and deregulated dAkt kinase. The reduced life-span of exposed to Bortezomib flies overexpressing Atg1_RNAi or Atg18_RNAi supports the protective nature of autophagy against proteasome inhibition-induced stress. Our data reveal the in vivo significance of proteasome functional integrity as a major defensive system against cellular toxicity likely occurring during critical biological processes and morphogenetic courses.

A new method of evaluating tight gas sands pore structure from nuclear magnetic resonance (NMR) logs

NASA Astrophysics Data System (ADS)

Xiao, Liang; Mao, Zhi-qiang; Xie, Xiu-hong

2016-04-01

Tight gas sands always display such characteristics of ultra-low porosity, permeability, high irreducible water, low resistivity contrast, complicated pore structure and strong heterogeneity, these make that the conventional methods are invalid. Many effective gas bearing formations are considered as dry zones or water saturated layers, and cannot be identified and exploited. To improve tight gas sands evaluation, the best method is quantitative characterizing rock pore structure. The mercury injection capillary pressure (MICP) curves are advantageous in predicting formation pore structure. However, the MICP experimental measurements are limited due to the environment and economy factors, this leads formation pore structure cannot be consecutively evaluated. Nuclear magnetic resonance (NMR) logs are considered to be promising in evaluating rock pore structure. Generally, to consecutively quantitatively evaluate tight gas sands pore structure, the best method is constructing pseudo Pc curves from NMR logs. In this paper, based on the analysis of lab experimental results for 20 core samples, which were drilled from tight gas sandstone reservoirs of Sichuan basin, and simultaneously applied for lab MICP and NMR measurements, the relationships of piecewise power function between nuclear magnetic resonance (NMR) transverse relaxation T2 time and pore-throat radius Rc are established. A novel method, which is used to transform NMR reverse cumulative curve as pseudo capillary pressure (Pc) curve is proposed, and the corresponding model is established based on formation classification. By using this model, formation pseudo Pc curves can be consecutively synthesized. The pore throat radius distribution, and pore structure evaluation parameters, such as the average pore throat radius (Rm), the threshold pressure (Pd), the maximum pore throat radius (Rmax) and so on, can also be precisely extracted. After this method is extended into field applications, several tight gas sandstone reservoirs are processed, and the predicted results are compared with core derived results. Good consistency between evaluated results with core derived results illustrates the dependability of the proposed method. Comparing with the previous methods, this presented model is much more theoretical, and the applicability is much improved. Combining with the evaluated results, our target tight gas sands are well evaluated, and many potential gas-bearing layers are effectively identified.

The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): Is Severe Hypertension Just an Elevated Blood Pressure?

PubMed

Magee, Laura A; von Dadelszen, Peter; Singer, Joel; Lee, Terry; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E; Menzies, Jennifer; Sanchez, Johanna; Gafni, Amiram; Helewa, Michael; Hutton, Eileen; Koren, Gideon; Lee, Shoo K; Logan, Alexander G; Ganzevoort, Wessel; Welch, Ross; Thornton, Jim G; Moutquin, Jean-Marie

2016-11-01

To determine whether clinical outcomes differed by occurrence of severe hypertension in the international CHIPS trial (Control of Hypertension in Pregnancy Study), adjusting for the interventions of "less tight" (target diastolic blood pressure [dBP] 100 mm Hg) versus "tight" control (target dBP 85 mm Hg). In this post-hoc analysis of CHIPS data from 987 women with nonsevere nonproteinuric preexisting or gestational hypertension, mixed effects logistic regression was used to compare the following outcomes according to occurrence of severe hypertension, adjusting for allocated group and the influence of baseline factors: CHIPS primary (perinatal loss or high-level neonatal care for >48 hours) and secondary outcomes (serious maternal complications), birth weight <10th percentile, preeclampsia, delivery at <34 or <37 weeks, platelets <100×10 9 /L, elevated liver enzymes with symptoms, maternal length of stay ≥10 days, and maternal readmission before 6 weeks postpartum. Three hundred and thirty-four (34.1%) women in CHIPS developed severe hypertension that was associated with all outcomes examined except for maternal readmission (P=0.20): CHIPS primary outcome, birth weight <10th percentile, preeclampsia, preterm delivery, elevated liver enzymes (all P<0.001), platelets <100×10 9 /L (P=0.006), and prolonged hospital stay (P=0.03). The association between severe hypertension and serious maternal complications was seen only in less tight control (P=0.02). Adjustment for preeclampsia (464, 47.3%) did not negate the relationship between severe hypertension and the CHIPS primary outcome (P<0.001), birth weight <10th percentile (P=0.005), delivery at <37 (P<0.001) or <34 weeks (P<0.001), or elevated liver enzymes with symptoms (P=0.02). Severe hypertension is a risk marker for adverse maternal and perinatal outcomes, independent of BP control or preeclampsia co-occurrence. URL: http://pre-empt.cfri.ca/. Unique identifier: ISRCTN 71416914. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01192412. © 2016 The Authors.

Process for strengthening silicon based ceramics

DOEpatents

Kim, Hyoun-Ee; Moorhead, A. J.

1993-01-01

A process for strengthening silicon based ceramic monolithic materials and omposite materials that contain silicon based ceramic reinforcing phases that requires that the ceramic be exposed to a wet hydrogen atmosphere at about 1400.degree. C. The process results in a dense, tightly adherent silicon containing oxide layer that heals, blunts , or otherwise negates the detrimental effect of strength limiting flaws on the surface of the ceramic body.

Process for strengthening silicon based ceramics

DOEpatents

Kim, Hyoun-Ee; Moorhead, A. J.

1993-04-06

A process for strengthening silicon based ceramic monolithic materials and omposite materials that contain silicon based ceramic reinforcing phases that requires that the ceramic be exposed to a wet hydrogen atmosphere at about 1400.degree. C. The process results in a dense, tightly adherent silicon containing oxide layer that heals, blunts , or otherwise negates the detrimental effect of strength limiting flaws on the surface of the ceramic body.

Biogeochemical Processes in Microbial Ecosystems

NASA Technical Reports Server (NTRS)

DesMarais, David J.; DeVincenzi, Donald L. (Technical Monitor)

2001-01-01

The hierarchical organization of microbial ecosystems determines process rates that shape Earth's environment, create the biomarker sedimentary and atmospheric signatures of life and define the stage upon which major evolutionary events occurred. In order to understand how microorganisms have shaped the global environment of Earth and potentially, other worlds, we must develop an experimental paradigm that links biogeochemical processes with ever-changing temporal and spatial distributions of microbial population, and their metabolic properties. Photosynthetic microbial mats offer an opportunity to define holistic functionality at the millimeter scale. At the same time, their Biogeochemistry contributes to environmental processes on a planetary scale. These mats are possibly direct descendents of the most ancient biological communities; communities in which oxygenic photosynthesis might have been invented. Mats provide one of the best natural systems to study how microbial populations associate to control dynamic biogeochemical gradients. These are self-sustaining, complete ecosystems in which light energy absorbed over a diel (24 hour) cycle drives the synthesis of spatially-organized, diverse biomass. Tightly-coupled microorganisms in the mat have specialized metabolisms that catalyze transformations of carbon, nitrogen. sulfur, and a host of other elements.

Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus.

PubMed

Zhou, Li; Liu, Ming-Zhe; Li, Qing; Deng, Juan; Mu, Di; Sun, Yan-Gang

2017-03-21

Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Occludin Independently Regulates Permeability under Hydrostatic Pressure and Cell Division in Retinal Pigment Epithelial Cells

PubMed Central

Phillips, Brett E.; Cancel, Limary; Tarbell, John M.; Antonetti, David A.

2008-01-01

Purpose The aim of this study was to determine the function of the tight junction protein occludin in the control of permeability, under diffusive and hydrostatic pressures, and its contribution to the control of cell division in retinal pigment epithelium. Methods Occludin expression was inhibited in the human retinal pigment epithelial cell line ARPE-19 by siRNA. Depletion of occludin was confirmed by Western blot, confocal microscopy, and RT-PCR. Paracellular permeability of cell monolayers to fluorescently labeled 70 kDa dextran, 10 kDa dextran, and 467 Da tetramethylrhodamine (TAMRA) was examined under diffusive conditions or after the application of 10 cm H2O transmural pressure. Cell division rates were determined by tritiated thymidine incorporation and Ki67 immunoreactivity. Cell cycle inhibitors were used to determine whether changes in cell division affected permeability. Results Occludin depletion increased diffusive paracellular permeability to 467 Da TAMRA by 15%, and permeability under hydrostatic pressure was increased 50% compared with control. Conversely, depletion of occludin protein with siRNA did not alter diffusive permeability to 70 kDa and 10 kDa RITC-dextran, and permeability to 70 kDa dextran was twofold lower in occludin-depleted cells under hydrostatic pressure conditions. Occludin depletion also increased thymidine incorporation by 90% and Ki67-positive cells by 50%. Finally, cell cycle inhibitors did not alter the effect of occludin siRNA on paracellular permeability. Conclusions The data suggest that occludin regulates tight junction permeability in response to changes in hydrostatic pressure. Furthermore, these data suggest that occludin also contributes to the control of cell division, demonstrating a novel function for this tight junction protein. PMID:18263810

Regulation of tight junction assembly and epithelial morphogenesis by the heat shock protein Apg-2

PubMed Central

Aijaz, Saima; Sanchez-Heras, Elena; Balda, Maria S; Matter, Karl

2007-01-01

Background Tight junctions are required for epithelial barrier formation and participate in the regulation of signalling mechanisms that control proliferation and differentiation. ZO-1 is a tight junction-associated adaptor protein that regulates gene expression, junction assembly and epithelial morphogenesis. We have previously demonstrated that the heat shock protein Apg-2 binds ZO-1 and thereby regulates its role in cell proliferation. Here, we addressed the question whether Apg-2 is also important for junction formation and epithelial morphogenesis. Results We demonstrate that depletion of Apg-2 by RNAi in MDCK cells did not prevent formation of functional tight junctions. Similar to ZO-1, however, reduced expression of Apg-2 retarded de novo junction assembly if analysed in a Ca-switch model. Formation of functional junctions, as monitored by measuring transepithelial electrical resistance, and recruitment of tight and adherens junction markers were retarded. If cultured in three dimensional extracellular matrix gels, Apg-2 depleted cells, as previously shown for ZO-1 depleted cells, did not form hollow polarised cysts but poorly organised, irregular structures. Conclusion Our data indicate that Apg-2 regulates junction assembly and is required for normal epithelial morphogenesis in a three-dimensional culture system, suggesting that Apg-2 is an important regulator of epithelial differentiation. As the observed phenotypes are similar to those previously described for ZO-1 depleted cells and depletion of Apg-2 retards junctional recruitment of ZO-1, regulation of ZO-1 is likely to be an important functional role for Apg-2 during epithelial differentiation. PMID:18028534

Regulation of tight junction assembly and epithelial morphogenesis by the heat shock protein Apg-2.

PubMed

Aijaz, Saima; Sanchez-Heras, Elena; Balda, Maria S; Matter, Karl

2007-11-20

Tight junctions are required for epithelial barrier formation and participate in the regulation of signalling mechanisms that control proliferation and differentiation. ZO-1 is a tight junction-associated adaptor protein that regulates gene expression, junction assembly and epithelial morphogenesis. We have previously demonstrated that the heat shock protein Apg-2 binds ZO-1 and thereby regulates its role in cell proliferation. Here, we addressed the question whether Apg-2 is also important for junction formation and epithelial morphogenesis. We demonstrate that depletion of Apg-2 by RNAi in MDCK cells did not prevent formation of functional tight junctions. Similar to ZO-1, however, reduced expression of Apg-2 retarded de novo junction assembly if analysed in a Ca-switch model. Formation of functional junctions, as monitored by measuring transepithelial electrical resistance, and recruitment of tight and adherens junction markers were retarded. If cultured in three dimensional extracellular matrix gels, Apg-2 depleted cells, as previously shown for ZO-1 depleted cells, did not form hollow polarised cysts but poorly organised, irregular structures. Our data indicate that Apg-2 regulates junction assembly and is required for normal epithelial morphogenesis in a three-dimensional culture system, suggesting that Apg-2 is an important regulator of epithelial differentiation. As the observed phenotypes are similar to those previously described for ZO-1 depleted cells and depletion of Apg-2 retards junctional recruitment of ZO-1, regulation of ZO-1 is likely to be an important functional role for Apg-2 during epithelial differentiation.

Catalystlike effect of orbital angular momentum on the conversion of transverse to three-dimensional spin states within tightly focused radially polarized beams

NASA Astrophysics Data System (ADS)

Han, Lei; Liu, Sheng; Li, Peng; Zhang, Yi; Cheng, Huachao; Zhao, Jianlin

2018-05-01

We report on the catalystlike effect of orbital angular momentum (OAM) on local spin-state conversion within the tightly focused radially polarized beams associated with optical spin-orbit interaction. It is theoretically demonstrated that the incident OAM can lead to a conversion of purely transverse spin state to a three-dimensional spin state on the focal plane. This conversion can be conveniently manipulated by altering the sign and value of the OAM. By comparing the total OAM and spin angular momentum (SAM) on the incident plane to those on the focal plane, it is indicated that the incident OAM have no participation in the angular momentum intertransfer, and just play a role as a catalyst of local SAM conversion. Such an effect of OAM sheds new light on the optical spin-orbit interaction in tight-focusing processes. The resultant three-dimensional spin states may provide more degrees of freedom in optical manipulation and spin-dependent directive coupling.

Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

PubMed

Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

2017-01-01

Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

Architecture and inherent robustness of a bacterial cell-cycle control system.

PubMed

Shen, Xiling; Collier, Justine; Dill, David; Shapiro, Lucy; Horowitz, Mark; McAdams, Harley H

2008-08-12

A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.

Overview of exocrine pancreatic pathobiology.

PubMed

Pandiri, Arun R

2014-01-01

Exocrine pancreas is a source of several enzymes that are essential for the digestive process. The exocrine pancreatic secretion is tightly regulated by the neuroendocrine system. The endocrine pancreas is tightly integrated anatomically and physiologically with the exocrine pancreas and modulates its function. Compound-induced pancreatitis is not a common event in toxicology or drug development, but it becomes a significant liability when encountered. Understanding the species-specific differences in physiology is essential to understand the underlying pathobiology of pancreatic disease in animal models and its relevance to human disease. This review will mainly focus on understanding the morphology and physiology of the pancreas, unique islet-exocrine interactions, and pancreatitis.

Loss of tight junction barrier function and its role in cancer metastasis.

PubMed

Martin, Tracey A; Jiang, Wen G

2009-04-01

As the most apical structure between epithelial and endothelial cells, tight junctions (TJ) are well known as functioning as a control for the paracellular diffusion of ions and certain molecules. It has however, become increasingly apparent that the TJ has a vital role in maintaining cell to cell integrity and that the loss of cohesion of the structure can lead to invasion and thus metastasis of cancer cells. This article will present data showing how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the successful metastasis of a number of different cancer types.

Reticle variation influence on manufacturing line and wafer device performance

NASA Astrophysics Data System (ADS)

Nistler, John L.; Spurlock, Kyle

1994-01-01

Cost effective manufacturing of devices at 0.5, 0.35 and 0.25μm geometries will be highly dependent on a companys' ability to obtain an economic return on investment. The high capital investment in equipment and facilities, not to mention the related chemical and wafer costs, for producing 200mm silicon wafers requires aspects of wafer processing to be tightly controlled. Reduction in errors and enhanced yield management requires early correction or avoidance of reticle problems. It is becoming increasingly important to recognize and track all pertinent factors impacting both the technical and financial viability of a wafer manufacturing fabrication area. Reticle related effects on wafer manufacturing can be costly and affect the total quality perceived by the device customer.

Identification of SLEEPLESS, a sleep-promoting factor.

PubMed

Koh, Kyunghee; Joiner, William J; Wu, Mark N; Yue, Zhifeng; Smith, Corinne J; Sehgal, Amita

2008-07-18

Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.

Comparative Anatomy of Phagocytic and Immunological Synapses

PubMed Central

Niedergang, Florence; Di Bartolo, Vincenzo; Alcover, Andrés

2016-01-01

The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of “phagocytic synapse.” Here, we discuss both types of structures, their organization, and the mechanisms by which they are generated and regulated. PMID:26858721

Membrane-entrapped microperoxidase as a 'solid-state' promoter in the electrochemistry of soluble metalloproteins.

PubMed Central

Brunori, M; Santucci, R; Campanella, L; Tranchida, G

1989-01-01

Immobilization of biological systems in solid matrices is presently of great interest, in view of the many potential advantages associated with both the higher stability of the immobilized macromolecules and the potential utilization for biotechnology. In the present paper the electrochemical behaviour of the undecapeptide from cytochrome c (called microperoxidase) tightly entrapped in cellulose triacetate membrane is reported; its utilization as 'solid-state' promoter in the electrochemistry of soluble metalloproteins is presented. The results obtained indicate that: (i) membrane-entrapped microperoxidase undergoes rapid reversible electron transfer at a glassy carbon electrode; (ii) the electrochemical process is diffusion-controlled; (iii) entrapped microperoxidase acts as 'solid-state' promoter in the electrochemistry of soluble cytochrome c and of azurin. PMID:2557833

Historical perspective on the moon base: the British experience

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

Jones, E.M.; Finney, B.R.

Among the many historical episodes that have relevance to the establishment of a human base, the voyages of Captain Cook, and the founding of Britain's Botany Bay colony in Australia seems particularly appropriate. The process resulting in the selection of Cook rewards study, as do his relations with the Admiralty, with the scientific establishment and with the scientists who accompanies him. Britain's tight control of the Botany Bay settlement and its unwillingness to promote early self-sufficiency may have delayed the time when Australia became self-supporting. Structuring the lunar base to offer opportunities for private initiatives may hasten the day whenmore » it becomes a self-supporting settlement rather than an externally supported scientific base on an Antarctic model.« less

Decrease of tight junction integrity in the ipsilateral thalamus during the acute stage after focal infarction and ablation of the cerebral cortex in rats.

PubMed

Li, Jing-Jing; Xing, Shi-Hui; Zhang, Jian; Hong, Hua; Li, Yi-Liang; Dang, Chao; Zhang, Yu-Sheng; Li, Chuo; Fan, Yu-Hua; Yu, Jian; Pei, Zhong; Zeng, Jin-Sheng

2011-11-01

1. Whether damage to the blood-brain barrier (BBB) occurs in remote areas after a focal cortical lesion remains unknown. The present study investigated tight junction-related proteins and tight junction microstructure in the ipsilateral thalamus during the acute stage after middle cerebral artery occlusion (MCAO) and cortical aspiration lesion (CAL) in rats. 2. Thirty-six hypertensive and normotensive rats were subjected to MCAO or CAL; another 18 rats in each group were submitted to sham operation. Zonula Occluden (ZO)-1, occludin and albumin were detected by western blotting 12 and 24 h after surgery. Tight junction microstructure was evaluated using electron microscopy, whereas albumin location in the ipsilateral thalamus was determined using double immunostaining for albumin and occludin or albumin and neuronal nuclei (NeuN) 24 h after surgery. 3. Twenty-four hours after MCAO or CAL, occludin expression was reduced to 78.4% and 81.3%, respectively, compared with control. A reduction in ZO-1 expression in the ipsilateral thalamus (to 79%) was seen only after CAL (P < 0.05). Membrane contact at the tight junction was discontinuous in the ipsilateral thalamus in both MCAO and CAL rats. Albumin levels were 23.2% and 82.5% higher in the ipsilateral thalamus after MCAO and CAL, respectively (P < 0.05). The percentage of the albumin-positive area that coincided with the occludin-positive area in the MCAO and CAL groups was 76.8% and 64.6%, respectively, indicating that albumin was mainly localized around the microvessels. 4. The results of the present study suggest that tight junction integrity decreases during the acute stage in the ipsilateral thalamus after MCAO and CAL in rats. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

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

Cuevas, F.A.; Curilef, S., E-mail: scurilef@ucn.cl; Plastino, A.R., E-mail: arplastino@ugr.es

The spread of a wave-packet (or its deformation) is a very important topic in quantum mechanics. Understanding this phenomenon is relevant in connection with the study of diverse physical systems. In this paper we apply various 'spreading measures' to characterize the evolution of an initially localized wave-packet in a tight-binding lattice, with special emphasis on information-theoretical measures. We investigate the behavior of both the probability distribution associated with the wave packet and the concomitant probability current. Complexity measures based upon Renyi entropies appear to be particularly good descriptors of the details of the delocalization process. - Highlights: > Spread ofmore » highly localized wave-packet in the tight-binding lattice. > Entropic and information-theoretical characterization is used to understand the delocalization. > The behavior of both the probability distribution and the concomitant probability current is investigated. > Renyi entropies appear to be good descriptors of the details of the delocalization process.« less

Tight Junction Protein 1a regulates pigment cell organisation during zebrafish colour patterning.

PubMed

Fadeev, Andrey; Krauss, Jana; Frohnhöfer, Hans Georg; Irion, Uwe; Nüsslein-Volhard, Christiane

2015-04-27

Zebrafish display a prominent pattern of alternating dark and light stripes generated by the precise positioning of pigment cells in the skin. This arrangement is the result of coordinated cell movements, cell shape changes, and the organisation of pigment cells during metamorphosis. Iridophores play a crucial part in this process by switching between the dense form of the light stripes and the loose form of the dark stripes. Adult schachbrett (sbr) mutants exhibit delayed changes in iridophore shape and organisation caused by truncations in Tight Junction Protein 1a (ZO-1a). In sbr mutants, the dark stripes are interrupted by dense iridophores invading as coherent sheets. Immuno-labelling and chimeric analyses indicate that Tjp1a is expressed in dense iridophores but down-regulated in the loose form. Tjp1a is a novel regulator of cell shape changes during colour pattern formation and the first cytoplasmic protein implicated in this process.

Genome Engineering of the 2,3-Butanediol Biosynthetic Pathway for Tight Regulation in Cyanobacteria.

PubMed

Nozzi, Nicole E; Atsumi, Shota

2015-11-20

Cyanobacteria have gained popularity among the metabolic engineering community as a tractable photosynthetic host for renewable chemical production. However, though a number of successfully engineered production systems have been reported, long-term genetic stability remains an issue for cyanobacterial systems. The genetic engineering toolbox for cyanobacteria is largely lacking inducible systems for expression control. The characterization of tight regulation systems for use in cyanobacteria may help to alleviate this problem. In this work we explore the function of the IPTG inducible promoter P(L)lacO1 in the model cyanobacterium Synechococcus elongatus PCC 7942 as well as the effect of gene order within an operon on pathway expression. According to our experiments, P(L)lacO1 functions well as an inducible promoter in S. elongatus. Additionally, we found that gene order within an operon can strongly influence control of expression of each gene.

Optical vortex knots in tightly-focused light beams

NASA Astrophysics Data System (ADS)

Dennis, Mark; Sugic, Danica

Optical vortices, that is, zero lines of complex amplitude in a propagating light field, can be knotted or linked in a controlled way. This was demonstrated previously in experiments where a computer-controlled hologram determined the amplitude of paraxial laser light, meaning the longitudinal extent of the knot was several orders of magnitude larger than its width. We describe what happens to these optical knots when the transverse width of the beam, and hence the knot, is reduced. Outside the paraxial regime, the field's polarization becomes highly inhomogeneous, and knotted structures occur in a variety of polarization singularities. We propose experiments realising these knotted polarization structures in tightly-focused beams, which should yield optical knots of unit aspect ratio, of several optical wavelengths in size, which could be suitable for embedding knotted defect structures in liquid crystals, Bose-Einstein condensates and photopolymers. This work was supported by the Leverhulme Trust Programme Grant ''Scientific Properties of Complex Knots''.

Managing the complexity of communication: regulation of gap junctions by post-translational modification

PubMed Central

Axelsen, Lene N.; Calloe, Kirstine; Holstein-Rathlou, Niels-Henrik; Nielsen, Morten S.

2013-01-01

Gap junctions are comprised of connexins that form cell-to-cell channels which couple neighboring cells to accommodate the exchange of information. The need for communication does, however, change over time and therefore must be tightly controlled. Although the regulation of connexin protein expression by transcription and translation is of great importance, the trafficking, channel activity and degradation are also under tight control. The function of connexins can be regulated by several post translational modifications, which affect numerous parameters; including number of channels, open probability, single channel conductance or selectivity. The most extensively investigated post translational modifications are phosphorylations, which have been documented in all mammalian connexins. Besides phosphorylations, some connexins are known to be ubiquitinated, SUMOylated, nitrosylated, hydroxylated, acetylated, methylated, and γ-carboxyglutamated. The aim of the present review is to summarize our current knowledge of post translational regulation of the connexin family of proteins. PMID:24155720

Adaptive, fast walking in a biped robot under neuronal control and learning.

PubMed

Manoonpong, Poramate; Geng, Tao; Kulvicius, Tomas; Porr, Bernd; Wörgötter, Florentin

2007-07-01

Human walking is a dynamic, partly self-stabilizing process relying on the interaction of the biomechanical design with its neuronal control. The coordination of this process is a very difficult problem, and it has been suggested that it involves a hierarchy of levels, where the lower ones, e.g., interactions between muscles and the spinal cord, are largely autonomous, and where higher level control (e.g., cortical) arises only pointwise, as needed. This requires an architecture of several nested, sensori-motor loops where the walking process provides feedback signals to the walker's sensory systems, which can be used to coordinate its movements. To complicate the situation, at a maximal walking speed of more than four leg-lengths per second, the cycle period available to coordinate all these loops is rather short. In this study we present a planar biped robot, which uses the design principle of nested loops to combine the self-stabilizing properties of its biomechanical design with several levels of neuronal control. Specifically, we show how to adapt control by including online learning mechanisms based on simulated synaptic plasticity. This robot can walk with a high speed (>3.0 leg length/s), self-adapting to minor disturbances, and reacting in a robust way to abruptly induced gait changes. At the same time, it can learn walking on different terrains, requiring only few learning experiences. This study shows that the tight coupling of physical with neuronal control, guided by sensory feedback from the walking pattern itself, combined with synaptic learning may be a way forward to better understand and solve coordination problems in other complex motor tasks.

The Application of Coherent Local Time for Optical Time Transfer and the Quantification of Systematic Errors in Satellite Laser Ranging

NASA Astrophysics Data System (ADS)

Schreiber, K. Ulrich; Kodet, Jan

2018-02-01

Highly precise time and stable reference frequencies are fundamental requirements for space geodesy. Satellite laser ranging (SLR) is one of these techniques, which differs from all other applications like Very Long Baseline Interferometry (VLBI), Global Navigation Satellite Systems (GNSS) and finally Doppler Orbitography and Radiopositioning Integrated by Satellite (DORIS) by the fact that it is an optical two-way measurement technique. That means that there is no need for a clock synchronization process between both ends of the distance covered by the measurement technique. Under the assumption of isotropy for the speed of light, SLR establishes the only practical realization of the Einstein Synchronization process so far. Therefore it is a powerful time transfer technique. However, in order to transfer time between two remote clocks, it is also necessary to tightly control all possible signal delays in the ranging process. This paper discusses the role of time and frequency in SLR as well as the error sources before it address the transfer of time between ground and space. The need of an improved signal delay control led to a major redesign of the local time and frequency distribution at the Geodetic Observatory Wettzell. Closure measurements can now be used to identify and remove systematic errors in SLR measurements.

Optimum ArFi laser bandwidth for 10nm node logic imaging performance

NASA Astrophysics Data System (ADS)

Alagna, Paolo; Zurita, Omar; Timoshkov, Vadim; Wong, Patrick; Rechtsteiner, Gregory; Baselmans, Jan; Mailfert, Julien

2015-03-01

Lithography process window (PW) and CD uniformity (CDU) requirements are being challenged with scaling across all device types. Aggressive PW and yield specifications put tight requirements on scanner performance, especially on focus budgets resulting in complicated systems for focus control. In this study, an imec N10 Logic-type test vehicle was used to investigate the E95 bandwidth impact on six different Metal 1 Logic features. The imaging metrics that track the impact of light source E95 bandwidth on performance of hot spots are: process window (PW), line width roughness (LWR), and local critical dimension uniformity (LCDU). In the first section of this study, the impact of increasing E95 bandwidth was investigated to observe the lithographic process control response of the specified logic features. In the second section, a preliminary assessment of the impact of lower E95 bandwidth was performed. The impact of lower E95 bandwidth on local intensity variability was monitored through the CDU of line end features and the LWR power spectral density (PSD) of line/space patterns. The investigation found that the imec N10 test vehicle (with OPC optimized for standard E95 bandwidth of300fm) features exposed at 200fm showed pattern specific responses, suggesting areas of potential interest for further investigation.

Controllable generation of reactive oxygen species by femtosecond-laser irradiation

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

Yan, Wei; He, Hao, E-mail: haohe@tju.edu.cn; Wang, Yintao

Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the verymore » beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca{sup 2+} release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.« less

Dynamics and Molecular Determinants of Cytoplasmic Lipid Droplet Clustering and Dispersion

PubMed Central

Stefanski, Adrianne L.; McManaman, James L.

2013-01-01

Perilipin-1 (Plin1), a prominent cytoplasmic lipid droplet (CLD) binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT) induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps. PMID:23825572

Quality Function Deployment for Large Systems

NASA Technical Reports Server (NTRS)

Dean, Edwin B.

1992-01-01

Quality Function Deployment (QFD) is typically applied to small subsystems. This paper describes efforts to extend QFD to large scale systems. It links QFD to the system engineering process, the concurrent engineering process, the robust design process, and the costing process. The effect is to generate a tightly linked project management process of high dimensionality which flushes out issues early to provide a high quality, low cost, and, hence, competitive product. A pre-QFD matrix linking customers to customer desires is described.

Age Effects in Postural Control Analyzed via a Principal Component Analysis of Kinematic Data and Interpreted in Relation to Predictions of the Optimal Feedback Control Theory

PubMed Central

Haid, Thomas H.; Doix, Aude-Clémence M.; Nigg, Benno M.; Federolf, Peter A.

2018-01-01

Optimal feedback control theory suggests that control of movement is focused on movement dimensions that are important for the task's success. The current study tested the hypotheses that age effects would emerge in the control of only specific movement components and that these components would be linked to the task relevance. Fifty healthy volunteers, 25 young and 25 older adults, performed a 80s-tandem stance while their postural movements were recorded using a standard motion capture system. The postural movements were decomposed by a principal component analysis into one-dimensional movement components, PMk, whose control was assessed through two variables, Nk and σk, which characterized the tightness and the regularity of the neuro-muscular control, respectively. The older volunteers showed less tight and more irregular control in PM2 (N2: −9.2%, p = 0.007; σ2: +14.3.0%, p = 0.017) but tighter control in PM8 and PM9 (N8: +4.7%, p = 0.020; N9: +2.5%, p = 0.043; σ9: −8.8%, p = 0.025). These results suggest that aging effects alter the postural control system not as a whole, but emerge in specific, task relevant components. The findings of the current study thus support the hypothesis that the minimal intervention principle, as described in the context of optimal feedback control (OFC), may be relevant when assessing aging effects on postural control. PMID:29459826

Design optimization of highly asymmetrical layouts by 2D contour metrology

NASA Astrophysics Data System (ADS)

Hu, C. M.; Lo, Fred; Yang, Elvis; Yang, T. H.; Chen, K. C.

2018-03-01

As design pitch shrinks to the resolution limit of up-to-date optical lithography technology, the Critical Dimension (CD) variation tolerance has been dramatically decreased for ensuring the functionality of device. One of critical challenges associates with the narrower CD tolerance for whole chip area is the proximity effect control on asymmetrical layout environments. To fulfill the tight CD control of complex features, the Critical Dimension Scanning Electron Microscope (CD-SEM) based measurement results for qualifying process window and establishing the Optical Proximity Correction (OPC) model become insufficient, thus 2D contour extraction technique [1-5] has been an increasingly important approach for complementing the insufficiencies of traditional CD measurement algorithm. To alleviate the long cycle time and high cost penalties for product verification, manufacturing requirements are better to be well handled at design stage to improve the quality and yield of ICs. In this work, in-house 2D contour extraction platform was established for layout design optimization of 39nm half-pitch Self-Aligned Double Patterning (SADP) process layer. Combining with the adoption of Process Variation Band Index (PVBI), the contour extraction platform enables layout optimization speedup as comparing to traditional methods. The capabilities of identifying and handling lithography hotspots in complex layout environments of 2D contour extraction platform allow process window aware layout optimization to meet the manufacturing requirements.

Evaluation of Heat Flux Measurement as a New Process Analytical Technology Monitoring Tool in Freeze Drying.

PubMed

Vollrath, Ilona; Pauli, Victoria; Friess, Wolfgang; Freitag, Angelika; Hawe, Andrea; Winter, Gerhard

2017-05-01

This study investigates the suitability of heat flux measurement as a new technique for monitoring product temperature and critical end points during freeze drying. The heat flux sensor is tightly mounted on the shelf and measures non-invasively (no contact with the product) the heat transferred from shelf to vial. Heat flux data were compared to comparative pressure measurement, thermocouple readings, and Karl Fischer titration as current state of the art monitoring techniques. The whole freeze drying process including freezing (both by ramp freezing and controlled nucleation) and primary and secondary drying was considered. We found that direct measurement of the transferred heat enables more insights into thermodynamics of the freezing process. Furthermore, a vial heat transfer coefficient can be calculated from heat flux data, which ultimately provides a non-invasive method to monitor product temperature throughout primary drying. The end point of primary drying determined by heat flux measurements was in accordance with the one defined by thermocouples. During secondary drying, heat flux measurements could not indicate the progress of drying as monitoring the residual moisture content. In conclusion, heat flux measurements are a promising new non-invasive tool for lyophilization process monitoring and development using energy transfer as a control parameter. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A Chimeric Kinesin-1 Head/Kinesin-5 Tail Motor Switches between Diffusive and Processive Motility

PubMed Central

Thiede, Christina; Lakämper, Stefan; Wessel, Alok D.; Kramer, Stefanie; Schmidt, Christoph F.

2013-01-01

Homotetrameric kinesin-5 motors are essential for chromosome separation and assembly of the mitotic spindle. These kinesins bind between two microtubules (MTs) and slide them apart, toward the spindle poles. This process must be tightly regulated in mitosis. In in vitro assays, Eg5 moves diffusively on single MTs and switches to a directed mode between MTs. How allosteric communication between opposing motor domains works remains unclear, but kinesin-5 tail domains may be involved. Here we present a single-molecule fluorescence study of a tetrameric kinesin-1 head/kinesin-5 tail chimera, DK4mer. This motor exhibited fast processive motility on single MTs interrupted by pauses. Like Eg5, DK4mer diffused along MTs with ADP, and slid antiparallel MTs apart with ATP. In contrast to Eg5, diffusive and processive periods were clearly distinguishable. This allowed us to measure transition rates among states and for unbinding as a function of buffer ionic strength. These data, together with results from controls using tail-less dimers, indicate that there are two modes of interaction with MTs, separated by an energy barrier. This result suggests a scheme of motor regulation that involves switching between two bound states, possibly allosterically controlled by the opposing tetramer end. Such a scheme is likely to be relevant for the regulation of native kinesin-5 motors. PMID:23442865

Nuclear-Renewable Hybrid Energy System Market Analysis Plans

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

Ruth, Mark

2016-06-09

This presentation describes nuclear-renewable hybrid energy systems (N-R HESs), states their potential benefits, provides figures for the four tightly coupled N-R HESs that NREL is currently analyzing, and outlines the analysis process that is underway.

Rotating mandrel speeds assembly of plastic inflatables

NASA Technical Reports Server (NTRS)

Mac Fadden, J. A.; Stenlund, S. J.; Wendt, A. J.

1966-01-01

Rotating mandrel permits the accurate cutting, forming, and sealing of plastic gores for assembly of an inflatable surface of revolution. The gores remain on the mandrel until the final seam is reached. Tolerances are tightly controlled by the mandrel configuration.

HbA1c below 7% as the goal of glucose control fails to maximize the cardiovascular benefits: a meta-analysis.

PubMed

Wang, Pin; Huang, Rong; Lu, Sen; Xia, Wenqing; Sun, Haixia; Sun, Jie; Cai, Rongrong; Wang, Shaohua

2015-09-22

Whether lowering glycosylated haemoglobin (HbA1c) level below 7.0% improves macro-vascular outcomes in diabetes remains unclear. Here, we aimed to assess the effect of relatively tight glucose control resulting in a follow-up HbA1c level of less or more than 7.0% on cardiovascular outcomes in diabetic patients. We systematically searched Medline, Web of science and Cochrane Library for prospective randomized controlled trials published between Jan 1, 1996 and July 1, 2015 that recorded cardiovascular outcome trials of glucose-lowering drugs or strategies in patients with type 2 diabetes mellitus. Data from 15 studies involving 88,266 diabetic patients with 4142 events of non-fatal myocardial infarction, 6997 of major cardiovascular events, 3517 of heart failure, 6849 of all-cause mortality, 2084 of non-fatal stroke, 3816 of cardiovascular death were included. A 7% reduction of major cardiovascular events was observed only when relatively tight glucose control resulted in a follow-up HbA1c level above 7.0% (OR 0.93, 95% CI 0.88-0.98; I(2) = 33%), however, the patients can benefit from reduction incidence of non-fatal myocardial infarction only when the follow-up HbA1c value below 7.0% (OR 0.85, 95% CI 0.74-0.96). Apart from the HbA1c value above 7.0% (OR 1.22, 95% CI 1.06-1.40), the application of thiazolidinediones (OR 1.39, 95% CI 1.14-1.69) also increased the risk of heart failure, while the gliptins shows neutral effects to heart failure (OR 1.14, 95% CI 0.97-1.34). Relatively tight glucose control has some cardiovascular benefits. HbA1c below 7.0% as the goal to maximize the cardiovascular benefits remains suspended.

Transcriptional Control of Antioxidant Defense by the Circadian Clock

PubMed Central

Patel, Sonal A.; Velingkaar, Nikkhil S.

2014-01-01

Abstract Significance: The circadian clock, an internal timekeeping system, is implicated in the regulation of metabolism and physiology, and circadian dysfunctions are associated with pathological changes in model organisms and increased risk of some diseases in humans. Recent Advances: Data obtained in different organisms, including humans, have established a tight connection between the clock and cellular redox signaling making it among the major candidates for a link between the circadian system and physiological processes. Critical Issues: In spite of the recent progress in understanding the importance of the circadian clock in the regulation of reactive oxygen species homeostasis, molecular mechanisms and key regulators are mostly unknown. Future Directions: Here we review, with an emphasis on transcriptional control, the circadian-clock-dependent control of oxidative stress response system as a potential mechanism in age-associated diseases. We will discuss the roles of the core clock components such as brain and muscle ARNT-like 1, Circadian Locomotor Output Cycles Kaput, the circadian-clock-controlled transcriptional factors such as nuclear factor erythroid-2-related factor, and peroxisome proliferator-activated receptor and circadian clock control chromatin modifying enzymes from sirtuin family in the regulation of cellular and organism antioxidant defense. Antioxid. Redox Signal. 20, 2997–3006. PMID:24111970

Microfluidic Experiments Studying Pore Scale Interactions of Microbes and Geochemistry

NASA Astrophysics Data System (ADS)

Chen, M.; Kocar, B. D.

2016-12-01

Understanding how physical phenomena, chemical reactions, and microbial behavior interact at the pore-scale is crucial to understanding larger scale trends in groundwater chemistry. Recent studies illustrate the utility of microfluidic devices for illuminating pore-scale physical-biogeochemical processes and their control(s) on the cycling of iron, uranium, and other important elements 1-3. These experimental systems are ideal for examining geochemical reactions mediated by microbes, which include processes governed by complex biological phenomenon (e.g. biofilm formation, etc.)4. We present results of microfluidic experiments using a model metal reducing bacteria and varying pore geometries, exploring the limitations of the microorganisms' ability to access tight pore spaces, and examining coupled biogeochemical-physical controls on the cycling of redox sensitive metals. Experimental results will provide an enhanced understanding of coupled physical-biogeochemical processes transpiring at the pore-scale, and will constrain and compliment continuum models used to predict and describe the subsurface cycling of redox-sensitive elements5. 1. Vrionis, H. A. et al. Microbiological and geochemical heterogeneity in an in situ uranium bioremediation field site. Appl. Environ. Microbiol. 71, 6308-6318 (2005). 2. Pearce, C. I. et al. Pore-scale characterization of biogeochemical controls on iron and uranium speciation under flow conditions. Environ. Sci. Technol. 46, 7992-8000 (2012). 3. Zhang, C., Liu, C. & Shi, Z. Micromodel investigation of transport effect on the kinetics of reductive dissolution of hematite. Environ. Sci. Technol. 47, 4131-4139 (2013). 4. Ginn, T. R. et al. Processes in microbial transport in the natural subsurface. Adv. Water Resour. 25, 1017-1042 (2002). 5. Scheibe, T. D. et al. Coupling a genome-scale metabolic model with a reactive transport model to describe in situ uranium bioremediation. Microb. Biotechnol. 2, 274-286 (2009).

Residents’ Self-Reported Health Effects and Annoyance in Relation to Air Pollution Exposure in an Industrial Area in Eastern-Estonia

PubMed Central

Idavain, Jane; Pindus, Mihkel; Orru, Kati; Kesanurm, Kaisa; Lang, Aavo; Tomasova, Jelena

2018-01-01

Eastern Estonia has large oil shale mines and industrial facilities mainly focused on electricity generation from oil shale and shale oil extraction, which produce high air pollution emissions. The “Study of the health impact of the oil shale sector—SOHOS” was aimed at identifying the impacts on residents’ health and annoyance due to the industrial processing. First, a population-wide survey about health effects and annoyance was carried out. Second, the total and oil shale sectors’ emitted concentrations of benzene, phenol, and PM2.5 were modelled. Third, the differences between groups were tested and relationships between health effects and environmental pollution studied using multiple regression analysis. Compared to the control groups from non-industrial areas in Tartu or Lääne-Viru, residents of Ida-Viru more frequently (p < 0.05) reported wheezing, chest tightness, shortness of breath, asthma attacks, a long-term cough, hypertension, heart diseases, myocardial infarction, stroke, and diabetes. All health effects except asthma were reported more frequently among non-Estonians. People living in regions with higher levels of PM2.5, had significantly higher odds (p < 0.05) of experiencing chest tightness (OR = 1.13, 95% CI 1.02–1.26), shortness of breath (1.16, 1.03–1.31) or an asthma attack (1.22, 1.04–1.42) during the previous year. People living in regions with higher levels of benzene had higher odds of experiencing myocardial infarction (1.98, 1.11–3.53) and with higher levels of phenol chest tightness (1.44, 1.03–2.00), long-term cough (1.48, 1.06–2.07) and myocardial infarction (2.17, 1.23–3.83). The prevalence of adverse health effects was also higher among those who had been working in the oil shale sector. Next to direct health effects, up to a quarter of the residents of Ida-Viru County were highly annoyed about air pollution. Perceived health risk from air pollution increased the odds of being annoyed. Annoyed people in Ida-Viru had significantly higher odds of experiencing respiratory symptoms during the last 12 months, e.g., wheezing (2.30, 1.31–4.04), chest tightness (2.88, 1.91–4.33 or attack of coughing (1.99, 1.34–2.95). PMID:29393920

Residents' Self-Reported Health Effects and Annoyance in Relation to Air Pollution Exposure in an Industrial Area in Eastern-Estonia.

PubMed

Orru, Hans; Idavain, Jane; Pindus, Mihkel; Orru, Kati; Kesanurm, Kaisa; Lang, Aavo; Tomasova, Jelena

2018-02-02

Eastern Estonia has large oil shale mines and industrial facilities mainly focused on electricity generation from oil shale and shale oil extraction, which produce high air pollution emissions. The "Study of the health impact of the oil shale sector-SOHOS" was aimed at identifying the impacts on residents' health and annoyance due to the industrial processing. First, a population-wide survey about health effects and annoyance was carried out. Second, the total and oil shale sectors' emitted concentrations of benzene, phenol, and PM 2.5 were modelled. Third, the differences between groups were tested and relationships between health effects and environmental pollution studied using multiple regression analysis. Compared to the control groups from non-industrial areas in Tartu or Lääne-Viru, residents of Ida-Viru more frequently ( p < 0.05) reported wheezing, chest tightness, shortness of breath, asthma attacks, a long-term cough, hypertension, heart diseases, myocardial infarction, stroke, and diabetes. All health effects except asthma were reported more frequently among non-Estonians. People living in regions with higher levels of PM 2.5 , had significantly higher odds ( p < 0.05) of experiencing chest tightness (OR = 1.13, 95% CI 1.02-1.26), shortness of breath (1.16, 1.03-1.31) or an asthma attack (1.22, 1.04-1.42) during the previous year. People living in regions with higher levels of benzene had higher odds of experiencing myocardial infarction (1.98, 1.11-3.53) and with higher levels of phenol chest tightness (1.44, 1.03-2.00), long-term cough (1.48, 1.06-2.07) and myocardial infarction (2.17, 1.23-3.83). The prevalence of adverse health effects was also higher among those who had been working in the oil shale sector. Next to direct health effects, up to a quarter of the residents of Ida-Viru County were highly annoyed about air pollution. Perceived health risk from air pollution increased the odds of being annoyed. Annoyed people in Ida-Viru had significantly higher odds of experiencing respiratory symptoms during the last 12 months, e.g., wheezing (2.30, 1.31-4.04), chest tightness (2.88, 1.91-4.33 or attack of coughing (1.99, 1.34-2.95).

Effects of Universal Mobile Telecommunications System (UMTS) electromagnetic fields on the blood-brain barrier in vitro.

PubMed

Franke, Helmut; Streckert, Joachim; Bitz, Andreas; Goeke, Johannes; Hansen, Volkert; Ringelstein, E Bernd; Nattkämper, Heiner; Galla, Hans-Joachim; Stögbauer, Florian

2005-09-01

The extensive use of mobile phone communication has raised public concerns about adverse health effects of radiofrequency (RF) electromagnetic fields (EMFs) in recent years. A central issue in this discussion is the question whether EMFs enhance the permeability of the blood-brain barrier (BBB). Here we report an investigation on the influence of a generic UMTS (Universal Mobile Telecommunications System) signal on barrier tightness, transport processes and the morphology of porcine brain microvascular endothelial cell cultures (PBEC) serving as an in vitro model of the BBB. An exposure device with integrated online monitoring system was developed for simultaneous exposure and measuring of transendothelial electrical resistance (TEER) to determine the tightness of the BBB. PBEC were exposed continuously for up to 84 h at an average electric-field strength of 3.4-34 V/m (maximum 1.8 W/kg) ensuring athermal conditions. We did not find any evidence of RF-field-induced disturbance of the function of the BBB. After and during exposure, the tightness of the BBB quantified by 14C-sucrose and serum albumin permeation as well as by TEER remained unchanged compared to sham-exposed cultures. Permeation of transporter substrates at the BBB as well as the localization and integrity of the tight-junction proteins occludin and ZO1 were not affected either.

Tightly Coupled Inertial Navigation System/Global Positioning System (TCMIG)

NASA Technical Reports Server (NTRS)

Watson, Michael D.; Jackson, Kurt (Technical Monitor)

2002-01-01

Many NASA applications planned for execution later this decade are seeking high performance, miniaturized, low power Inertial Management Units (IMU). Much research has gone into Micro-Electro-Mechanical System (MEMS) over the past decade as a solution to these needs. While MEMS devices have proven to provide high accuracy acceleration measurements, they have not yet proven to have the accuracy required by many NASA missions in rotational measurements. Therefore, a new solution has been formulated integrating the best of all IMU technologies to address these mid-term needs in the form of a Tightly Coupled Micro Inertial Navigation System (INS)/Global Positioning System (GPS) (TCMIG). The TCMIG consists of an INS and a GPS tightly coupled by a Kalman filter executing on an embedded Field Programmable Gate Array (FPGA) processor. The INS consists of a highly integrated Interferometric Fiber Optic Gyroscope (IFOG) and a MEMS accelerometer. The IFOG utilizes a tightly wound fiber coil to reduce volume and the high level of integration and advanced optical components to reduce power. The MEMS accelerometer utilizes a newly developed deep etch process to increase the proof mass and yield a highly accurate accelerometer. The GPS receiver consists of a low power miniaturized version of the Blackjack receiver. Such an IMU configuration is ideal to meet the mid-term needs of the NASA Science Enterprises and the new launch vehicles being developed for the Space Launch Initiative (SLI).

A randomized controlled comparison of stretching procedures for posterior shoulder tightness.

PubMed

McClure, Philip; Balaicuis, Jenna; Heiland, David; Broersma, Mary Ellen; Thorndike, Cheryl K; Wood, April

2007-03-01

Randomized controlled trial, To compare changes in shoulder internal rotation range of motion (ROM), for 2 stretching exercises, the "cross-body stretch" and the "sleeper stretch," in individuals with posterior shoulder tightness. Recently, some authors have expressed the belief that the sleeper stretch is better than the cross-body stretch to address glenohumeral posterior tightness because the scapula is stabilized. Fifty-four asymptomatic subjects (20 males, 34 females) participated in the study. The control group (n=24) consisted of subjects with a between-shoulder difference in internal rotation ROM of less than 10 degrees, whereas those subjects with more than a 10 degrees difference were randomly assigned to 1 of 2 intervention groups, the sleeper stretch group (n=15) or the cross-body stretch group (n=15). Shoulder internal rotation ROM, with the arm abducted to 90 degrees and scapula motion prevented, was measured before and after a 4-week intervention period. Subjects in the control group were asked not to engage in any new stretching activities, while subjects in the 2 stretching groups were asked to perform stretching exercises on the more limited side only, once daily for 5 repetitions, holding each stretch for 30 seconds. The improvements in internal rotation ROM for the subjects in the cross-body stretch group (mean +/- SD, 20.0 degrees +/- 12.9 degrees) were significantly greater than for the subjects in the control group (5.9 degrees +/- 9.4 degrees, P = .009). The gains in the sleeper stretch group (12.4 degrees +/- 10.4 degrees) were not significant compared to those of the control group (P = .586) and those of the cross-body stretch group (P = .148). The cross-body stretch in individuals with limited shoulder internal rotation ROM appears to be more effective than no stretching in controls without internal rotation asymmetry to improve shoulder internal rotation ROM. While the improvement in internal rotation from the cross-body stretch was greater than for the sleeper stretch and of a magnitude that could be clinically significant, the small sample size likely precluded statistical significance between groups.

Diagenesis and porosity evolution of tight sand reservoirs in Carboniferous Benxi Formation, Southeast Ordos Basin

NASA Astrophysics Data System (ADS)

Hu, Peng; Yu, Xinghe; Shan, Xin; Su, Dongxu; Wang, Jiao; Li, Yalong; Shi, Xin; Xu, Liqiang

2016-04-01

The Ordos Basin, situated in west-central China, is one of the oldest and most important fossil-fuel energy base, which contains large reserves of coal, oil and natural gas. The Upper Palaeozoic strata are widely distributed with rich gas-bearing and large natural gas resources, whose potential is tremendous. Recent years have witnessed a great tight gas exploration improvement of the Upper Paleozoic in Southeastern Ordos basin. The Carboniferous Benxi Formation, mainly buried more than 2,500m, is the key target strata for hydrocarbon exploration, which was deposited in a barrier island and tidal flat environment. The sandy bars and flats are the favorable sedimentary microfacies. With an integrated approach of thin-section petrophysics, constant velocity mercury injection test, scanning electron microscopy and X-ray diffractometry, diagenesis and porosity evolution of tight sand reservoirs of Benxi Formation were analyzed in detail. The result shows that the main lithology of sandstone in this area is dominated by moderately to well sorted quartz sandstone. The average porosity and permeability is 4.72% and 1.22mD. The reservoirs of Benxi Formation holds a variety of pore types and the pore throats, with obvious heterogeneity and poor connection. Based on the capillary pressure curve morphological characteristics and parameters, combined with thin section and phycical property data, the reservoir pore structure of Benxi Formation can be divided into 4 types, including mid pore mid throat type(I), mid pore fine throat type(II), small pore fine throat type(III) and micro pro micro throat type(Ⅳ). The reservoirs primarily fall in B-subsate of middle diagenesis and late diagenesis, which mainly undergo compaction, cmentation, dissolution and fracturing process. Employing the empirical formula of different sorting for unconsolideated sandstone porosity, the initial sandstone porosity is 38.32% on average. Quantitative evaluation of the increase and decrease of porosity caused by different diagenesis reveals that mechanical compaction and chemical cementation are the main mechanisms for destroying primary pores, which contribute 19.61% and 8.75% to the loss of primary posoity, respectively. Dissolution of volcanic fragments and feldspar increased reservoir porosity by 4.14%. The pores were occluded by late minerals and carbonate cements, resulting in a reduction of 9.38%. Overall, the dual influence of compaction and cementation is the key of the key, controlling formation of tight gas sandstone reservoirs. Keywords: diagenesis, porosity evolution, tight sandstone, Benxi Formation, Southeast Ordos Basin Acknowledgements: We greatfully acknowledge Yanchang Petroleum for providing the samples and data access and for permission to publish this work. The first author, Peng Hu, would like to thank the support from Prof. Xinghe Yu.

A process for the production of a scale-proof and corrosion-resistant coating on graphite and carbon bodies

NASA Technical Reports Server (NTRS)

Fitzer, E.

1981-01-01

A process for the production of a corrosion resistant coating on graphite and carbon bodies is described. The carbon or graphite body is coated or impregnated with titanium silicide under the addition of a metal containing wetting agent in a nitrogen free atmosphere, so that a tight coating is formed.

‘Patient-Centered Care’ for Complex Patients with Type 2 Diabetes Mellitus—Analysis of Two Cases

PubMed Central

Hackel, Jennifer M.

2013-01-01

Purpose This paper serves to apply and compare aspects of person centered care and recent consensus guidelines to two cases of older adults with poorly controlled diabetes in the context of relatively similar multimorbidity. Methods After review of the literature regarding the shift from guidelines promoting tight control in diabetes management to individualized person centered care, as well as newer treatment approaches emerging in diabetes care, the newer guidelines and potential treatment approaches are applied to the cases. Results By delving into the clinical, behavioral, social, cultural and economic aspects of the two cases in applying the new guidelines, divergent care goals are reached for the cases. Conclusions Primary care practitioners must be vigilant in providing individualized diabetes treatment where multiple chronic illnesses increase the complexity of care. While two older adults with multimorbidity may appear at first to have similar care goals, their unique preferences and support systems, as well as their risks and benefits from tight control, must be carefully weighed in formulating the best approach. Newer pharmaceutical agents hold promise for improving the possibilities for better glycemic control with less self-care burden and risk of hypoglycemia. PMID:24250240

Enforcing dust mass conservation in 3D simulations of tightly coupled grains with the PHANTOM SPH code

NASA Astrophysics Data System (ADS)

Ballabio, G.; Dipierro, G.; Veronesi, B.; Lodato, G.; Hutchison, M.; Laibe, G.; Price, D. J.

2018-06-01

We describe a new implementation of the one-fluid method in the SPH code PHANTOM to simulate the dynamics of dust grains in gas protoplanetary discs. We revise and extend previously developed algorithms by computing the evolution of a new fluid quantity that produces a more accurate and numerically controlled evolution of the dust dynamics. Moreover, by limiting the stopping time of uncoupled grains that violate the assumptions of the terminal velocity approximation, we avoid fatal numerical errors in mass conservation. We test and validate our new algorithm by running 3D SPH simulations of a large range of disc models with tightly and marginally coupled grains.

High-Rising Rec Centers.

ERIC Educational Resources Information Center

Whitney, Tim

2000-01-01

Examines how tight urban sites can yield sports spaces that favorably compare to their more rural campus counterparts. Potential areas of concern when recreation centers are reconfigured into high-rise structures are highlighted, including building codes, building access, noise control, building costs, and lighting. (GR)

High-performance image processing architecture

NASA Astrophysics Data System (ADS)

Coffield, Patrick C.

1992-04-01

The proposed architecture is a logical design specifically for image processing and other related computations. The design is a hybrid electro-optical concept consisting of three tightly coupled components: a spatial configuration processor (the optical analog portion), a weighting processor (digital), and an accumulation processor (digital). The systolic flow of data and image processing operations are directed by a control buffer and pipelined to each of the three processing components. The image processing operations are defined by an image algebra developed by the University of Florida. The algebra is capable of describing all common image-to-image transformations. The merit of this architectural design is how elegantly it handles the natural decomposition of algebraic functions into spatially distributed, point-wise operations. The effect of this particular decomposition allows convolution type operations to be computed strictly as a function of the number of elements in the template (mask, filter, etc.) instead of the number of picture elements in the image. Thus, a substantial increase in throughput is realized. The logical architecture may take any number of physical forms. While a hybrid electro-optical implementation is of primary interest, the benefits and design issues of an all digital implementation are also discussed. The potential utility of this architectural design lies in its ability to control all the arithmetic and logic operations of the image algebra's generalized matrix product. This is the most powerful fundamental formulation in the algebra, thus allowing a wide range of applications.

Tight-binding analysis of Si and GaAs ultrathin bodies with subatomic wave-function resolution

NASA Astrophysics Data System (ADS)

Tan, Yaohua P.; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy B.; Klimeck, Gerhard

2015-08-01

Empirical tight-binding (ETB) methods are widely used in atomistic device simulations. Traditional ways of generating the ETB parameters rely on direct fitting to bulk experiments or theoretical electronic bands. However, ETB calculations based on existing parameters lead to unphysical results in ultrasmall structures like the As-terminated GaAs ultrathin bodies (UTBs). In this work, it is shown that more transferable ETB parameters with a short interaction range can be obtained by a process of mapping ab initio bands and wave functions to ETB models. This process enables the calibration of not only the ETB energy bands but also the ETB wave functions with corresponding ab initio calculations. Based on the mapping process, ETB models of Si and GaAs are parameterized with respect to hybrid functional calculations. Highly localized ETB basis functions are obtained. Both the ETB energy bands and wave functions with subatomic resolution of UTBs show good agreement with the corresponding hybrid functional calculations. The ETB methods can then be used to explain realistically extended devices in nonequilibrium that cannot be tackled with ab initio methods.

GABAB receptor cell surface export is controlled by an endoplasmic reticulum gatekeeper

PubMed Central

Doly, Stéphane; Shirvani, Hamasseh; Gäta, Gabriel; Meye, Frank; Emerit, Michel-Boris; Enslen, Hervé; Achour, Lamia; Pardo-Lopez, Liliana; Kwon, Yang Seung; Armand, Vincent; Gardette, Robert; Giros, Bruno; Gassmann, Martin; Bettler, Bernhard; Mameli, Manuel; Darmon, Michèle; Marullo, Stefano

2016-01-01

Summary Endoplasmic reticulum (ER) release and cell surface export of many G protein-coupled receptors (GPCRs), are tightly regulated. For GABAB receptors of GABA, the major mammalian inhibitory neurotransmitter, the ligand-binding GB1 subunit is maintained in the ER by unknown mechanisms in the absence of hetero-dimerization with the GB2 subunit. We report that GB1 retention is regulated by a specific gatekeeper, PRAF2. This ER resident transmembrane protein binds to GB1, preventing its progression in the biosynthetic pathway. GB1 release occurs upon competitive displacement from PRAF2 by GB2. PRAF2 concentration, relative to that of GB1 and GB2, tightly controls cell surface receptor density and controls GABAB function in neurons. Experimental perturbation of PRAF2 levels in vivo caused marked hyperactivity disorders in mice. These data reveal an unanticipated major impact of specific ER gate-keepers on GPCR function and identify PRAF2 as a new molecular target with therapeutic potential for psychiatric and neurological diseases involving GABAB function. PMID:26033241

Ion/proton-conducting apparatus and method

DOEpatents

Yates, Matthew; Xue, Wei

2014-12-23

A c-axis-oriented HAP thin film synthesized by seeded growth on a palladium hydrogen membrane substrate. An exemplary synthetic process includes electrochemical seeding on the substrate, and secondary and tertiary hydrothermal treatments under conditions that favor growth along c-axes and a-axes in sequence. By adjusting corresponding synthetic conditions, an HAP this film can be grown to a controllable thickness with a dense coverage on the underlying substrate. The thin films have relatively high proton conductivity under hydrogen atmosphere and high temperature conditions. The c-axis oriented films may be integrated into fuel cells for application in the intermediate temperature range of 200-600.degree. C. The electrochemical-hydrothermal deposition technique may be applied to create other oriented crystal materials having optimized properties, useful for separations and catalysis as well as electronic and electrochemical applications, electrochemical membrane reactors, and in chemical sensors. Additional high-density and gas-tight HAP film compositions may be deposited using a two-step deposition method that includes an electrochemical deposition method followed by a hydrothermal deposition method. The two-step method uses a single hydrothermal deposition solution composition. The method may be used to deposit HAP films including but not limited to at least doped HAP films, and more particularly including carbonated HAP films. In addition, the high-density and gas-tight HAP films may be used in proton exchange membrane fuel cells.

Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

PubMed

Caudill, Marie A; Strupp, Barbara J; Muscalu, Laura; Nevins, Julie E H; Canfield, Richard L

2018-04-01

Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring. In contrast, the two experimental studies examining cognitive effects of maternal choline supplementation in humans produced inconsistent results, perhaps because of poor participant adherence and/or uncontrolled variation in intake of choline or other nutrients. We examined the effects of maternal choline supplementation during pregnancy on infant cognition, with intake of choline and other nutrients tightly controlled. Women entering their third trimester were randomized to consume, until delivery, either 480 mg choline/d ( n = 13) or 930 mg choline/d ( n = 13). Infant information processing speed and visuospatial memory were tested at 4, 7, 10, and 13 mo of age ( n = 24). Mean reaction time averaged across the four ages was significantly faster for infants born to mothers in the 930 ( vs. 480) mg choline/d group. This result indicates that maternal consumption of approximately twice the recommended amount of choline during the last trimester improves infant information processing speed. Furthermore, for the 480-mg choline/d group, there was a significant linear effect of exposure duration (infants exposed longer showed faster reaction times), suggesting that even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring.-Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., Canfield, R. L. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

Stable and high expression of Galectin-8 tightly controls metastatic progression of prostate cancer

PubMed Central

Gentilini, Lucas Daniel; Pérez, Ignacio González; Kotler, Monica Lidia; Chauchereau, Anne; Laderach, Diego Jose; Compagno, Daniel

2017-01-01

Two decades ago, Galectin-8 was described as a prostate carcinoma biomarker since it is only expressed in the neoplastic prostate, but not in the healthy tissue. To date, no biological function has been attributed to Galectin-8 that could explain this differential expression. In this study we silenced Galectin-8 in two human prostate cancer cell lines, PC3 and IGR-CaP1, and designed a pre-clinical experimental model that allows monitoring the pathology from its early steps to the long-term metastatic stages. We show for the first time that the natural and conserved expression of Gal-8 in tumour cells is responsible for the metastatic evolution of prostate cancer. In fact, Gal-8 controls the rearrangement of the cytoskeleton and E-Cadherin expression, with a major impact on anoikis and homotypic aggregation of tumour cells, both being essential processes for the survival of circulating tumour cells during metastasis. While localized prostate cancer can be cured, metastatic and advanced disease remains a significant therapeutic challenge, urging for the identification of prognostic markers of the metastatic process. Collectively, our results highlight Galectin-8 as a potential target for anti-metastatic therapy against prostate cancer. PMID:28591719

A new fabrication technique for complex refractive micro-optical systems

NASA Astrophysics Data System (ADS)

Tormen, Massimo; Carpentiero, Alessandro; Ferrari, Enrico; Cabrini, Stefano; Cojoc, Dan; Di Fabrizio, Enzo

2006-01-01

We present a new method that allows to fabricate structures with tightly controlled three-dimensional profiles in the 10 nm to 100 μm scale range. This consists of a sequence of lithographic steps such as Electron Beam (EB) or Focused Ion Beam (FIB) lithography, alternated with isotropic wet etching processes performed on a quartz substrate. Morphological characterization by SEM and AFM shows that 3D structures with very accurate shape control and nanometer scale surface roughness can be realized. Quartz templates have been employed as complex system of micromirrors after metal coating of the patterned surface or used as stamps in nanoimprint, hot embossing or casting processes to shape complex plastic elements. Compared to other 3D micro and nanostructuring methods, in which a hard material is directly "sculptured" by energetic beams, our technique requires a much less intensive use of expensive lithographic equipments, for comparable volumes of structured material, resulting in dramatic increase of throughput. Refractive micro-optical elements have been fabricated and characterized in transmission and reflection modes with white and monochromatic light. The elements produce a distribution of sharp focal spots and lines in the three dimensional space, opening the route for applications of image reconstruction based on refractive optics.

Cell Wall Composition, Biosynthesis and Remodeling during Pollen Tube Growth

PubMed Central

Mollet, Jean-Claude; Leroux, Christelle; Dardelle, Flavien; Lehner, Arnaud

2013-01-01

The pollen tube is a fast tip-growing cell carrying the two sperm cells to the ovule allowing the double fertilization process and seed setting. To succeed in this process, the spatial and temporal controls of pollen tube growth within the female organ are critical. It requires a massive cell wall deposition to promote fast pollen tube elongation and a tight control of the cell wall remodeling to modify the mechanical properties. In addition, during its journey, the pollen tube interacts with the pistil, which plays key roles in pollen tube nutrition, guidance and in the rejection of the self-incompatible pollen. This review focuses on our current knowledge in the biochemistry and localization of the main cell wall polymers including pectin, hemicellulose, cellulose and callose from several pollen tube species. Moreover, based on transcriptomic data and functional genomic studies, the possible enzymes involved in the cell wall remodeling during pollen tube growth and their impact on the cell wall mechanics are also described. Finally, mutant analyses have permitted to gain insight in the function of several genes involved in the pollen tube cell wall biosynthesis and their roles in pollen tube growth are further discussed. PMID:27137369

Visual Servoing for an Autonomous Hexarotor Using a Neural Network Based PID Controller.

PubMed

Lopez-Franco, Carlos; Gomez-Avila, Javier; Alanis, Alma Y; Arana-Daniel, Nancy; Villaseñor, Carlos

2017-08-12

In recent years, unmanned aerial vehicles (UAVs) have gained significant attention. However, we face two major drawbacks when working with UAVs: high nonlinearities and unknown position in 3D space since it is not provided with on-board sensors that can measure its position with respect to a global coordinate system. In this paper, we present a real-time implementation of a servo control, integrating vision sensors, with a neural proportional integral derivative (PID), in order to develop an hexarotor image based visual servo control (IBVS) that knows the position of the robot by using a velocity vector as a reference to control the hexarotor position. This integration requires a tight coordination between control algorithms, models of the system to be controlled, sensors, hardware and software platforms and well-defined interfaces, to allow the real-time implementation, as well as the design of different processing stages with their respective communication architecture. All of these issues and others provoke the idea that real-time implementations can be considered as a difficult task. For the purpose of showing the effectiveness of the sensor integration and control algorithm to address these issues on a high nonlinear system with noisy sensors as cameras, experiments were performed on the Asctec Firefly on-board computer, including both simulation and experimenta results.

Visual Servoing for an Autonomous Hexarotor Using a Neural Network Based PID Controller

PubMed Central

Lopez-Franco, Carlos; Alanis, Alma Y.; Arana-Daniel, Nancy; Villaseñor, Carlos

2017-01-01

In recent years, unmanned aerial vehicles (UAVs) have gained significant attention. However, we face two major drawbacks when working with UAVs: high nonlinearities and unknown position in 3D space since it is not provided with on-board sensors that can measure its position with respect to a global coordinate system. In this paper, we present a real-time implementation of a servo control, integrating vision sensors, with a neural proportional integral derivative (PID), in order to develop an hexarotor image based visual servo control (IBVS) that knows the position of the robot by using a velocity vector as a reference to control the hexarotor position. This integration requires a tight coordination between control algorithms, models of the system to be controlled, sensors, hardware and software platforms and well-defined interfaces, to allow the real-time implementation, as well as the design of different processing stages with their respective communication architecture. All of these issues and others provoke the idea that real-time implementations can be considered as a difficult task. For the purpose of showing the effectiveness of the sensor integration and control algorithm to address these issues on a high nonlinear system with noisy sensors as cameras, experiments were performed on the Asctec Firefly on-board computer, including both simulation and experimenta results. PMID:28805689

Intraperitoneal infection with Salmonella abortusovis is partially controlled by a gene closely linked with the Ity gene.

PubMed Central

Oswald, I P; Lantier, F; Moutier, R; Bertrand, M F; Skamene, E

1992-01-01

The aim of the present study was to determine whether the Ity gene, which controls the resistance to S. typhimurium infection in mice, also governs the resistance to S. abortusovis, a serotype specific for goat and sheep. During either i.v. or i.p. infection, BALB/c mice (Itys) were not able to control the growth of S. abortusovis and eventually died from infection. In contrast CBA (Ityr) or (C.CB)F1 (Ityr/s) mice were able to control the growth of these bacteria. Using congenic C.D2 Ityr mice, we found that the gene controlling resistance to S. abortusovis was tightly linked to the Ity gene on chromosome 1. Furthermore, in the spleen and the liver of backcross BALB/c x (CBA x BALB/c) mice, the S. abortusovis resistance phenotype cosegregated with the two alleles of the Len-1 gene, a gene tightly linked to the Ity gene. By contrast, in these backcross mice, the level of infection of the peritoneal cavity, the site of inoculation, did not correlated with the Len-1 phenotype of the animal. These results provide evidence that after i.p. inoculation the control of S. abortusovis growth in the spleen and the liver is controlled by the Ity gene, but also suggest that additional gene(s) regulate the number of bacteria at the site of inoculation. PMID:1544222

Npn-1 Contributes to Axon-Axon Interactions That Differentially Control Sensory and Motor Innervation of the Limb

PubMed Central

Bianchi, Elisa; Novitch, Bennett G.; Huber, Andrea B.

2011-01-01

The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1) in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG), we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs. PMID:21364975

Noseband Use in Equestrian Sports – An International Study

PubMed Central

Doherty, Orla

2017-01-01

Nosebands are used by riders to prevent the horse from opening its mouth, to increase control and, in some cases, to comply with the competition rules. While equestrian texts traditionally recommend that two adult human fingers should be able to fit under a fastened noseband, noseband tightness levels are not, in general, regulated in competition. Possible detrimental consequences for the horse, of excessively tight nosebands, include discomfort, pain or tissue damage. The current study investigated noseband usage in equestrian competition. Data regarding noseband type, position, width and tightness were collected from 750 horses in eventing (n = 354), dressage (n = 334) and performance hunter (n = 62) competitions in Ireland, England and Belgium. Data were collected immediately before or after the performance. Using the ISES taper gauge as a guide, results were classified according to the number of ‘fingers’ that could fit under the noseband at the nasal planum, and assigned to six groups: greater than 2 fingers; 2 fingers; 1.5 fingers; 1 finger; 0.5 fingers; zero fingers. A calliper was used to measure noseband width and position relative to the facial crest. The data were not normally distributed so Kruskall-Wallis and Mann-Whitney tests were used. In all, 44% of horses fell into the zero fingers classification while only 7% were in the two fingers classification. Significant differences emerged between disciplines (p<0.001), with the highest levels of noseband tightness measured among eventers followed by dressage horses with lowest levels among performance hunters. Noseband tightness did not differ significantly with horse age (p>0.05), which ranged from 4 to 19 years. The flash noseband was the most commonly used noseband (n = 326) and was significantly tighter than the cavesson (p < 0.001), drop noseband (p < 0.001) and the Micklem (p < 0.005). Noseband width ranged from 10 to 50 mm. Noseband position varied widely with the distance between the facial crest and upper noseband margin ranging from 0 to 70 mm. The high proportion of very tight nosebands found in this study raises concerns regarding the short and long term behavioural and physiological consequences of such tight nosebands are for the horse. Although these data are currently lacking, the findings are of concern. PMID:28045961

Generalized Hofmann quantum process fidelity bounds for quantum filters

NASA Astrophysics Data System (ADS)

Sedlák, Michal; Fiurášek, Jaromír

2016-04-01

We propose and investigate bounds on the quantum process fidelity of quantum filters, i.e., probabilistic quantum operations represented by a single Kraus operator K . These bounds generalize the Hofmann bounds on the quantum process fidelity of unitary operations [H. F. Hofmann, Phys. Rev. Lett. 94, 160504 (2005), 10.1103/PhysRevLett.94.160504] and are based on probing the quantum filter with pure states forming two mutually unbiased bases. Determination of these bounds therefore requires far fewer measurements than full quantum process tomography. We find that it is particularly suitable to construct one of the probe bases from the right eigenstates of K , because in this case the bounds are tight in the sense that if the actual filter coincides with the ideal one, then both the lower and the upper bounds are equal to 1. We theoretically investigate the application of these bounds to a two-qubit optical quantum filter formed by the interference of two photons on a partially polarizing beam splitter. For an experimentally convenient choice of factorized input states and measurements we study the tightness of the bounds. We show that more stringent bounds can be obtained by more sophisticated processing of the data using convex optimization and we compare our methods for different choices of the input probe states.

Calcium Channels and Oxidative Stress Mediate a Synergistic Disruption of Tight Junctions by Ethanol and Acetaldehyde in Caco-2 Cell Monolayers.

PubMed

Samak, Geetha; Gangwar, Ruchika; Meena, Avtar S; Rao, Roshan G; Shukla, Pradeep K; Manda, Bhargavi; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

2016-12-13

Ethanol is metabolized into acetaldehyde in most tissues. In this study, we investigated the synergistic effect of ethanol and acetaldehyde on the tight junction integrity in Caco-2 cell monolayers. Expression of alcohol dehydrogenase sensitized Caco-2 cells to ethanol-induced tight junction disruption and barrier dysfunction, whereas aldehyde dehydrogenase attenuated acetaldehyde-induced tight junction disruption. Ethanol up to 150 mM did not affect tight junction integrity or barrier function, but it dose-dependently increased acetaldehyde-mediated tight junction disruption and barrier dysfunction. Src kinase and MLCK inhibitors blocked this synergistic effect of ethanol and acetaldehyde on tight junction. Ethanol and acetaldehyde caused a rapid and synergistic elevation of intracellular calcium. Calcium depletion by BAPTA or Ca 2+ -free medium blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. Diltiazem and selective knockdown of TRPV6 or Ca V 1.3 channels, by shRNA blocked ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. Ethanol and acetaldehyde induced a rapid and synergistic increase in reactive oxygen species by a calcium-dependent mechanism. N-acetyl-L-cysteine and cyclosporine A, blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. These results demonstrate that ethanol and acetaldehyde synergistically disrupt tight junctions by a mechanism involving calcium, oxidative stress, Src kinase and MLCK.

Spatially explicit simulation of hydrologically controlled carbon and nitrogen cycles and associated feedback mechanisms in a boreal ecosystem

NASA Astrophysics Data System (ADS)

Govind, Ajit; Chen, Jing Ming; Ju, Weimin

2009-06-01

Ecosystem models that simulate biogeochemical processes usually ignore hydrological controls that govern them. It is quite possible that topographically driven water fluxes significantly influence the spatial distribution of C sources and sinks because of their large contribution to the local water balance. To investigate this, we simulated biogeochemical processes along with the associated feedback mechanisms in a boreal ecosystem using a spatially explicit hydroecological model, boreal ecosystem productivity simulator (BEPS)-TerrainLab V2.0, that has a tight coupling of ecophysiological, hydrological, and biogeochemical processes. First, the simulated dynamics of snowpack, soil temperature, net ecosystem productivity (NEP), and total ecosystem respiration (TER) were validated with high-frequency measurements for 2 years. The model was able to explain 80% of the variability in NEP and 84% of the variability in TER. Further, we investigated the influence of topographically driven subsurface base flow on soil C and N cycling and on the spatiotemporal patterns of C sources and sinks using three hydrological modeling scenarios that differed in hydrological conceptualizations. In general, the scenarios that had nonexplicit hydrological representation overestimated NEP, as opposed to the scenario that had an explicit (realistic) representation. The key processes controlling the NEP differences were attributed to the combined effects of variations in photosynthesis (due to changes in stomatal conductance and nitrogen (N) availability), heterotrophic respiration, and autotrophic respiration, all of which occur simultaneously affecting NEP. Feedback relationships were also found to exacerbate the differences. We identified six types of NEP differences (biases), of which the most commonly found was due to an underestimation of the existing C sources, highlighting the vulnerability of regional-scale ecosystem models that ignore hydrological processes.

Novel architecture for data management and control for small satellite

NASA Astrophysics Data System (ADS)

Adami, G.; Fossati, D.; Turri, M.

1995-12-01

The paper introduces an innovative architecture for the on-board units that are responsible to provide the data interface, control and processing capability normally allocated in separated electronics boxes in the data handling subsystem of the space system. A new solution for the attitude control of the space vehicle has been studied and developed and the utilization of this technological growth, in particular that concerns the GPS receiver, is matter for novel architecture. This new approach also involves in general the small satellite ground segment product as matter of a dedicated development approach. Small and medium satellites are considered an attractive solution for the low cost scientific experimentation, communication or remote sensing satellites. The functional and performance capability of the studied on-board units and ground segment are assessed in tight conjunction with the evolution of the European and the USA market. The design of these units has to be based on few and simple driving requirements, directly derived from the new modified scenario: (1) The limited budgets available for space system. (2) The quick mission data return, i.e., low development time by specific and tailored system development tools. The quick availability of data to scientists/user is requested without jeopardizing the maximum and guaranteed scientific or commercial return. The proposed system is then given thinking to an architecture based on a high degree of modularity (and reuse of existing library of modules) thus allowing to keep down costs and to speed up the time to market. The design ground rules are so established in order to cope with the following performance: (1) capability to adapt with few impacts the system interfaces, in particular for attitude sensors and actuators that are tightly mission dependent; (2) easy adaptation of on board computational performances and memory capacity (including mass memory storage capability); (3) definition of a hierarchical and modular software design for the same rationale explained for the hardware.

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice.

PubMed

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-03-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex.

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice

PubMed Central

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-01-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex. PMID:29257130

Arabidopsis HECATE genes function in phytohormone control during gynoecium development.

PubMed

Schuster, Christoph; Gaillochet, Christophe; Lohmann, Jan U

2015-10-01

The fruit, which develops from the fertilised gynoecium formed in the innermost whorl of the flower, is the reproductive organ and one of the most complex structures of an angiosperm plant. Phytohormones play important roles during flower and fruit patterning, morphogenesis and growth, and there is emerging evidence for a cross-talk between different classes of plant hormones throughout these processes. Here, we show that the bHLH transcription factors HECATE 1 (HEC1), HEC2 and HEC3, which have previously been identified as essential components of transmitting tract formation, affect both auxin and cytokinin responses during reproductive tissue development. We find that HEC1 interacts with SPATULA (SPT) to control carpel fusion and that both transcription factors restrict sensitivity to cytokinin in the gynoecium. In addition, HEC1 is tightly integrated into the auxin-signalling network at the levels of biosynthesis, transport and transcriptional response. Based on this data, we propose that HEC1 acts as a local modulator of auxin and cytokinin responses to control gynoecium development in Arabidopsis. © 2015. Published by The Company of Biologists Ltd.

A Genetic Cascade of let-7-ncl-1-fib-1 Modulates Nucleolar Size and rRNA Pool in Caenorhabditis elegans

PubMed Central

Chiou, Pey-Tsyr; Chen, Po-Hsiang; Lee, Ching-Ming; Chu, Yu-De; Yu, Hsiang; Hsiung, Kuei-Ching; Tsai, Yi-Tzang; Lee, Chi-Chang; Chang, Yu-Sun; Chan, Shih-Peng; Tan, Bertrand Chin-Ming; Lo, Szecheng J.

2015-01-01

Ribosome biogenesis takes place in the nucleolus, the size of which is often coordinated with cell growth and development. However, how metazoans control nucleolar size remains largely unknown. Caenorhabditis elegans provides a good model to address this question owing to distinct tissue distribution of nucleolar sizes and a mutant, ncl-1, which exhibits larger nucleoli than wild-type worms. Here, through a series of loss-of-function analyses, we report that the nucleolar size is regulated by a circuitry composed of microRNA let-7, translation repressor NCL-1, and a major nucleolar pre-rRNA processing protein FIB-1/fibrillarin. In cooperation with RNA binding proteins PUF and NOS, NCL-1 suppressed the translation of FIB-1/fibrillarin, while let-7 targeted the 3’UTR of ncl-1 and inhibited its expression. Consequently, the abundance of FIB-1 is tightly controlled and correlated with the nucleolar size. Together, our findings highlight a novel genetic cascade by which post-transcriptional regulators interplay in developmental control of nucleolar size and function. PMID:26492166

Cytosolic Na+ Controls an Epithelial Na+ Channel Via the Go Guanine Nucleotide-Binding Regulatory Protein

NASA Astrophysics Data System (ADS)

Komwatana, P.; Dinudom, A.; Young, J. A.; Cook, D. I.

1996-07-01

In tight Na+-absorbing epithelial cells, the rate of Na+ entry through amiloride-sensitive apical membrane Na+ channels is matched to basolateral Na+ extrusion so that cell Na+ concentration and volume remain steady. Control of this process by regulation of apical Na+ channels has been attributed to changes in cytosolic Ca2+ concentration or pH, secondary to changes in cytosolic Na+ concentration, although cytosolic Cl- seems also to be involved. Using mouse mandibular gland duct cells, we now demonstrate that increasing cytosolic Na+ concentration inhibits apical Na+ channels independent of changes in cytosolic Ca2+, pH, or Cl-, and the effect is blocked by GDP-β -S, pertussis toxin, and antibodies against the α -subunits of guanine nucleotide-binding regulatory proteins (Go). In contrast, the inhibitory effect of cytosolic anions is blocked by antibodies to inhibitory guanine nucleotide-binding regulatory proteins (Gi1/Gi2. It thus appears that apical Na+ channels are regulated by Go and Gi proteins, the activities of which are controlled, respectively, by cytosolic Na+ and Cl-.

Axon growth regulation by a bistable molecular switch.

PubMed

Padmanabhan, Pranesh; Goodhill, Geoffrey J

2018-04-25

For the brain to function properly, its neurons must make the right connections during neural development. A key aspect of this process is the tight regulation of axon growth as axons navigate towards their targets. Neuronal growth cones at the tips of developing axons switch between growth and paused states during axonal pathfinding, and this switching behaviour determines the heterogeneous axon growth rates observed during brain development. The mechanisms controlling this switching behaviour, however, remain largely unknown. Here, using mathematical modelling, we predict that the molecular interaction network involved in axon growth can exhibit bistability, with one state representing a fast-growing growth cone state and the other a paused growth cone state. Owing to stochastic effects, even in an unchanging environment, model growth cones reversibly switch between growth and paused states. Our model further predicts that environmental signals could regulate axon growth rate by controlling the rates of switching between the two states. Our study presents a new conceptual understanding of growth cone switching behaviour, and suggests that axon guidance may be controlled by both cell-extrinsic factors and cell-intrinsic growth regulatory mechanisms. © 2018 The Author(s).

Degradation of human Lipin-1 by BTRC E3 ubiquitin ligase.

PubMed

Ishimoto, Kenji; Hayase, Ayaka; Kumagai, Fumiko; Kawai, Megumi; Okuno, Hiroko; Hino, Nobumasa; Okada, Yoshiaki; Kawamura, Takeshi; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Tachibana, Keisuke; Doi, Takefumi

2017-06-17

Lipin-1 has dual functions in the regulation of lipid and energy metabolism according to its subcellular localization, which is tightly controlled. However, it is unclear how Lipin-1 degradation is regulated. Here, we demonstrate that Lipin-1 is degraded through its DSGXXS motif. We show that Lipin-1 interacts with either of two E3 ubiquitin ligases, BTRC or FBXW11, and that this interaction is DSGXXS-dependent and mediates the attachment of polyubiquitin chains. Further, we demonstrate that degradation of Lipin-1 is regulated by BTRC in the cytoplasm and on membranes. These novel insights into the regulation of human Lipin-1 stability will be useful in planning further studies to elucidate its metabolic processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Temporal variations in early developmental decisions: an engine of forebrain evolution.

PubMed

Bielen, H; Pal, S; Tole, S; Houart, C

2017-02-01

Tight control of developmental timing is pivotal to many major processes in developmental biology, such as patterning, fate specification, cell cycle dynamics, cell migration and connectivity. Temporal change in these ontogenetic sequences is known as heterochrony, a major force in the evolution of body plans and organogenesis. In the last 5 years, studies in fish and rodents indicate that heterochrony in signaling during early development generates diversity in forebrain size and complexity. Here, we summarize these findings and propose that, additionally to spatio-temporal tuning of neurogenesis, temporal and quantitative modulation of signaling events drive pivotal changes in shape, size and complexity of the forebrain across evolution, participating to the generation of diversity in animal behavior and emergence of cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dendritic protein synthesis in the normal and diseased brain

PubMed Central

Swanger, Sharon A.; Bassell, Gary J.

2015-01-01

Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases. PMID:23262237

Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases.

PubMed

Bhattacharjee, Ashima; Chakraborty, Kaustav; Shukla, Aditya

2017-10-18

Copper is a trace element essential for almost all living organisms. But the level of intracellular copper needs to be tightly regulated. Dysregulation of cellular copper homeostasis leading to various diseases demonstrates the importance of this tight regulation. Copper homeostasis is regulated not only within the cell but also within individual intracellular compartments. Inactivation of export machinery results in excess copper being redistributed into various intracellular organelles. Recent evidence suggests the involvement of glutathione in playing an important role in regulating copper entry and intracellular copper homeostasis. Therefore interplay of both homeostases might play an important role within the cell. Similar to copper, glutathione balance is tightly regulated within individual cellular compartments. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis. On the one hand, interplay of glutathione and copper homeostasis performs an important role in normal physiological processes, for example neuronal differentiation. On the other hand, perturbation of the interplay might play a key role in the pathogenesis of copper homeostasis disorders.

A Tightly-Coupled GPS/INS/UWB Cooperative Positioning Sensors System Supported by V2I Communication

PubMed Central

Wang, Jian; Gao, Yang; Li, Zengke; Meng, Xiaolin; Hancock, Craig M.

2016-01-01

This paper investigates a tightly-coupled Global Position System (GPS)/Ultra-Wideband (UWB)/Inertial Navigation System (INS) cooperative positioning scheme using a Robust Kalman Filter (RKF) supported by V2I communication. The scheme proposes a method that uses range measurements of UWB units transmitted among the terminals as augmentation inputs of the observations. The UWB range inputs are used to reform the GPS observation equations that consist of pseudo-range and Doppler measurements and the updated observation equation is processed in a tightly-coupled GPS/UWB/INS integrated positioning equation using an adaptive Robust Kalman Filter. The result of the trial conducted on the roof of the Nottingham Geospatial Institute (NGI) at the University of Nottingham shows that the integrated solution provides better accuracy and improves the availability of the system in GPS denied environments. RKF can eliminate the effects of gross errors. Additionally, the internal and external reliabilities of the system are enhanced when the UWB observables received from the moving terminals are involved in the positioning algorithm. PMID:27355947

OS082. CHIPS-Child: Testing the developmental origins hypothesis.

PubMed

Magee, L A; Synnes, A

2012-07-01

CHIPS-Child is a natural test of the Developmental Origins of Health and Disease hypothesis (DOHaD) [1,2]. Reduced fetal growth rate is associated with adult cardiovascular risk markers (e.g., obesity) and disease [3,4]. Evidence worldwide indicates that this relationship is independent of birth weight. The leading theory describes 'developmental programming'in utero leading to permanent alteration of the fetal genome. While those changes are adaptive in utero, they may be maladaptive postnatally. To directly test, for the first time in humans, whether differential blood pressure (BP) control in pregnancy has developmental programming effects, independent of birth weight. We predict that, like famine or protein malnutrition, 'tight' (vs. 'less tight') control of maternal BP will be associated with fetal under-nutrition and effects will be consistent with developmental programming. CHIPS-Child is a parallel, ancillary study to the CHIPS randomized controlled trial (RCT). CHIPS is designed to determine whether 'less tight' control [target diastolic BP (dBP) 100mmHg] or 'tight' control [target dBP 85mmHg] of non-proteinuric hypertension in pregnancy is better for the baby without increasing maternal risk. CHIPS-Child will examine offspring of CHIPS participants non-invasively at 12m corrected post-gestational age (±2m) for anthropometry, hair cortisol, buccal swabs for epigenetic testing and a maternal questionnaire about infant feeding practices and background. Annual contact will be maintained in years 2-5 and will include annual parental measurement of the child's height, weight and waist circumference. CHIPS will recruit 1028 women. We estimate that 80% of CHIPS centres will participate in CHIPS-Child, approximately 97% of babies will survive, and 90% of children will be followed to 12m resulting in a sample size of 626. Power will be >80% to detect a between-group difference of ⩾0.25 in 'change in z-score for weight' between birth and 12m (2-sided alpha=0.05, SD 1). Recruitment has begun. The primary outcome will be the between-group difference in early postnatal weight gain ('change in z score for weight') between birth and 12m (p<0.05). Secondary:outcomes are (i) hypothalamic pituitary adrenal axis function (hair cortisol for overall cortisol production); and (ii) between-groups differences in DNA methylation, using targeted (genes associated with growth, obesity, cardiovascular disease, and/or a developmental programming effect) and global (genome-wide microarray) methods. CHIPS-Child offers a unique opportunity to both clarify whether differential dBP control in pregnancy has developmental programming effects and contribute to our understanding of human biology and diversity in a way that a cross-sectional or other observational studies cannot. Copyright © 2012. Published by Elsevier B.V.

Managing Uncertainty: Thinking and Planning Strategically.

ERIC Educational Resources Information Center

Lorenzo, Albert L.

1993-01-01

Argues that rapid change and tight resources demand reality-based planning, rather than planning models that ignore internal and external customers or emphasize process over product. Describes the Strategic Guidance Model (SGM) which provides colleges with strategic visioning, organizational assessment, environmental scanning, quality improvement,…

Adverse Outcome Pathway (AOP) framework for embryonic vascular disruption and developmental defects (SOT)

EPA Science Inventory

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signal...

A hybrid data fusion method for GNSS/INS integration navigation system

NASA Astrophysics Data System (ADS)

Yang, Ling; Li, Bofeng; Shen, Yunzhong; Li, Haojun

2017-04-01

Although DGNSS is widely used and PPP-GNSS is nowadays a viable precise positioning technology option, the major disadvantage of GNSS still remains: signal blockage due to obstructions in urban and built up environments, and extreme power attenuation of the signals when operated indoors. The combination of GNSS with other sensors, such as a self-contained inertial navigation system (INS), provides an ideal position and attitude determination solution which can not only mitigate the weakness of GNSS, but also bound the INS error that otherwise would grow with time when the INS operates alone. However, the navigation accuracy provided by GNSS/INS strongly depends on the quality and geometry of the GNSS observations, the quality of the INS technology used, and the integration model applied. There are two main types of coupled schemes for integration systems: loosely coupled integration and tightly coupled integration. In loosely coupled integration, position measurements are taken from both systems and combined optimally, usually in a Kalman filter. Tightly coupled integration directly combines the raw pseudorange or carrier phase measurements of GNSS with inertial measurements in an extended Kalman filter. The latter technique improves the ability to resolve ambiguities, i.e. allows a quicker recovery from outage events such as a loss of signal under vegetation. In recent years, tightly coupled differential carrier phase GNSS/INS integration has become popular, because it has the advantage of providing accurate position information even when GPS measurements are rank-deficient in stand-alone processing and is theoretically optimal in a filtering sense, especially in urban navigation applications. However, the heavier computational burden and sensor communication usually complicate the tightly coupled integration and reduce the system efficiency, compared with the loosely coupled integration. In this paper, it has been proved that the loosely coupled and tightly coupled algorithms are equivalent when following conditions are satisfied: 1) there is enough redundancy on the GNSS raw measurements; 2) only pseudorange measurements are used; 3) If differential carrier phase measurements are used, only the float solutions of the ambiguities are considered; 4) the covariance of the loosely coupled measurement model should come from the GNSS standalone solution instead of conventional pre-determined values. Based on the equivalence proof, a dual-step loosely coupled procedure is proposed to regenerate the equal ambiguity fixing solutions in tightly coupled procedure. Accordingly, the tightly coupled differential carrier phase or pseudorange GNSS/INS integration can be simplified, which will degrade to an equivalent loosely coupled integration when there are enough measurement redundancy and recover to a tightly coupled integration when GNSS measurements are rank-deficient. By this hybrid data fusion method, both the optimality of the tightly coupled algorithm and the efficiency of the loosely coupled algorithm can be conserved. Field test results confirm the effectiveness of the proposed method.

The laser micro-machining system for diamond anvil cell experiments and general precision machining applications at the High Pressure Collaborative Access Team

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

Hrubiak, Rostislav; Sinogeikin, Stanislav; Rod, Eric

We have designed and constructed a new system for micro-machining parts and sample assemblies used for diamond anvil cells and general user operations at the High Pressure Collaborative Access Team, sector 16 of the Advanced Photon Source. The new micro-machining system uses a pulsed laser of 400 ps pulse duration, ablating various materials without thermal melting, thus leaving a clean edge. With optics designed for a tight focus, the system can machine holes any size larger than 3 μm in diameter. Unlike a standard electrical discharge machining drill, the new laser system allows micro-machining of non-conductive materials such as: amorphousmore » boron and silicon carbide gaskets, diamond, oxides, and other materials including organic materials such as polyimide films (i.e., Kapton). An important feature of the new system is the use of gas-tight or gas-flow environmental chambers which allow the laser micro-machining to be done in a controlled (e.g., inert gas) atmosphere to prevent oxidation and other chemical reactions in air sensitive materials. The gas-tight workpiece enclosure is also useful for machining materials with known health risks (e.g., beryllium). Specialized control software with a graphical interface enables micro-machining of custom 2D and 3D shapes. The laser-machining system was designed in a Class 1 laser enclosure, i.e., it includes laser safety interlocks and computer controls and allows for routine operation. Though initially designed mainly for machining of the diamond anvil cell gaskets, the laser-machining system has since found many other micro-machining applications, several of which are presented here.« less

The new car following model considering vehicle dynamics influence and numerical simulation

NASA Astrophysics Data System (ADS)

Sun, Dihua; Liu, Hui; Zhang, Geng; Zhao, Min

2015-12-01

In this paper, the car following model is investigated by considering the vehicle dynamics in a cyber physical view. In fact, that driving is a typical cyber physical process which couples the cyber aspect of the vehicles' information and driving decision tightly with the dynamics and physics of the vehicles and traffic environment. However, the influence from the physical (vehicle) view was been ignored in the previous car following models. In order to describe the car following behavior more reasonably in real traffic, a new car following model by considering vehicle dynamics (for short, D-CFM) is proposed. In this paper, we take the full velocity difference (FVD) car following model as a case. The stability condition is given on the base of the control theory. The analytical method and numerical simulation results show that the new models can describe the evolution of traffic congestion. The simulations also show vehicles with a more actual acceleration of starting process than early models.

Alternative splicing regulation in tumor necrosis factor-mediated inflammation.

PubMed

López-Urrutia, Eduardo; Campos-Parra, Alma; Herrera, Luis Alonso; Pérez-Plasencia, Carlos

2017-11-01

It is generally accepted that alternative splicing has an effect on disease when it leads to conspicuous changes in relevant proteins, but that the combinatorial effect of several small modifications can have marked outcomes as well. Inflammation is a complex process involving numerous signaling pathways, among which the tumor necrosis factor (TNF) pathway is one of the most studied. Signaling pathways are commonly represented as intricate cascades of molecular interactions that eventually lead to the activation of one or several genes. Alternative splicing is a common means of controlling protein expression in time and space; therefore, it can modulate the outcome of signaling pathways through small changes in their elements. Notably, the overall process is tightly regulated, which is easily overlooked when analyzing the pathway as a whole. The present review summarizes recent studies of the alternative splicing of key players of the TNF pathway leading to inflammation, and hypothesizes on the cumulative results of those modifications and the impact on cancer development.

Alternative splicing regulation in tumor necrosis factor-mediated inflammation

PubMed Central

López-Urrutia, Eduardo; Campos-Parra, Alma; Herrera, Luis Alonso; Pérez-Plasencia, Carlos

2017-01-01

It is generally accepted that alternative splicing has an effect on disease when it leads to conspicuous changes in relevant proteins, but that the combinatorial effect of several small modifications can have marked outcomes as well. Inflammation is a complex process involving numerous signaling pathways, among which the tumor necrosis factor (TNF) pathway is one of the most studied. Signaling pathways are commonly represented as intricate cascades of molecular interactions that eventually lead to the activation of one or several genes. Alternative splicing is a common means of controlling protein expression in time and space; therefore, it can modulate the outcome of signaling pathways through small changes in their elements. Notably, the overall process is tightly regulated, which is easily overlooked when analyzing the pathway as a whole. The present review summarizes recent studies of the alternative splicing of key players of the TNF pathway leading to inflammation, and hypothesizes on the cumulative results of those modifications and the impact on cancer development. PMID:29113151

Design of a liquid membrane target for high repetition rate neutron generation

NASA Astrophysics Data System (ADS)

Poole, Patrick; Andereck, C. David; Storm, Mike; Schumacher, Douglass

2013-10-01

Ultra-bright, pulsed, spatially-small sources of energetic neutrons have applications in radiography and non-destructive remote sensing. Neutrons can be generated by a process wherein ions accelerated from a laser-irradiated primary target subsequently bombard a converter material, causing neutron-producing nuclear reactions, such as 7Li(d,n)8Be. Deuterons from this process are suppressed by contamination that builds up on the rear of the solid primary target. To eliminate this issue we propose a self-replenishing liquid membrane target consisting of heavy water and deuterated surfactant, formed in-vacuum within a moveable wire frame. In addition to removing issues associated with solid target positioning and collateral damage, this apparatus provides flow rate and target thickness control, and allows for the high repetition rates required to generate desired neutron fluxes with a portable laser-based system. The apparatus design will be presented, as well as a novel interferometric method that measures the membrane thickness using tightly-focused light. This work was performed with support from DARPA.

Sarcomeric Pattern Formation by Actin Cluster Coalescence

PubMed Central

Friedrich, Benjamin M.; Fischer-Friedrich, Elisabeth; Gov, Nir S.; Safran, Samuel A.

2012-01-01

Contractile function of striated muscle cells depends crucially on the almost crystalline order of actin and myosin filaments in myofibrils, but the physical mechanisms that lead to myofibril assembly remains ill-defined. Passive diffusive sorting of actin filaments into sarcomeric order is kinetically impossible, suggesting a pivotal role of active processes in sarcomeric pattern formation. Using a one-dimensional computational model of an initially unstriated actin bundle, we show that actin filament treadmilling in the presence of processive plus-end crosslinking provides a simple and robust mechanism for the polarity sorting of actin filaments as well as for the correct localization of myosin filaments. We propose that the coalescence of crosslinked actin clusters could be key for sarcomeric pattern formation. In our simulations, sarcomere spacing is set by filament length prompting tight length control already at early stages of pattern formation. The proposed mechanism could be generic and apply both to premyofibrils and nascent myofibrils in developing muscle cells as well as possibly to striated stress-fibers in non-muscle cells. PMID:22685394

Mixing Metaphors in the Cerebral Hemispheres: What Happens When Careers Collide?

PubMed Central

Chettih, Selmaan; Durgin, Frank H.; Grodner, Daniel J.

2014-01-01

Are processes of figurative comparison and figurative categorization different? An experiment combining alternative-sense and matched-sense metaphor priming with a divided visual field assessment technique sought to isolate processes of comparison and categorization in the two cerebral hemispheres. For target metaphors presented in the RVF/LH, only matched-sense primes were facilitative. Literal primes and alternative-sense primes had no effect on comprehension time compared to the unprimed baseline. The effects of matched-sense primes were additive with the rated conventionality of the targets. For target metaphors presented to the LVF/RH, matched-sense primes were again additively facilitative. However, alternative-sense primes, though facilitative overall, seemed to eliminate the pre-existing advantages of conventional target metaphor senses in the LVF/RH in favor of metaphoric senses similar to those of the primes. These findings are consistent with tightly controlled categorical coding in the LH and coarse, and flexible, context dependent coding in the RH. PMID:22103787

Long non-coding RNA produced by RNA polymerase V determines boundaries of heterochromatin

PubMed Central

Böhmdorfer, Gudrun; Sethuraman, Shriya; Rowley, M Jordan; Krzyszton, Michal; Rothi, M Hafiz; Bouzit, Lilia; Wierzbicki, Andrzej T

2016-01-01

RNA-mediated transcriptional gene silencing is a conserved process where small RNAs target transposons and other sequences for repression by establishing chromatin modifications. A central element of this process are long non-coding RNAs (lncRNA), which in Arabidopsis thaliana are produced by a specialized RNA polymerase known as Pol V. Here we show that non-coding transcription by Pol V is controlled by preexisting chromatin modifications located within the transcribed regions. Most Pol V transcripts are associated with AGO4 but are not sliced by AGO4. Pol V-dependent DNA methylation is established on both strands of DNA and is tightly restricted to Pol V-transcribed regions. This indicates that chromatin modifications are established in close proximity to Pol V. Finally, Pol V transcription is preferentially enriched on edges of silenced transposable elements, where Pol V transcribes into TEs. We propose that Pol V may play an important role in the determination of heterochromatin boundaries. DOI: http://dx.doi.org/10.7554/eLife.19092.001 PMID:27779094

Shallow melt apparatus for semicontinuous czochralski crystal growth

DOEpatents

Wang, Tihu; Ciszek, Theodore F.

2006-01-10

In a single crystal pulling apparatus for providing a Czochralski crystal growth process, the improvement of a shallow melt In a single crystal pulling apparatus for providing a Czochralski crystal growth process, the improvement of a shallow melt crucible (20) to eliminate the necessity supplying a large quantity of feed stock materials that had to be preloaded in a deep crucible to grow a large ingot, comprising a gas tight container a crucible with a deepened periphery (25) to prevent snapping of a shallow melt and reduce turbulent melt convection; source supply means for adding source material to the semiconductor melt; a double barrier (23) to minimize heat transfer between the deepened periphery (25) and the shallow melt in the growth compartment; offset holes (24) in the double barrier (23) to increase melt travel length between the deepened periphery (25) and the shallow growth compartment; and the interface heater/heat sink (22) to control the interface shape and crystal growth rate.

Bio-Optics and Bio-Inspired Optical Materials.

PubMed

Tadepalli, Sirimuvva; Slocik, Joseph M; Gupta, Maneesh K; Naik, Rajesh R; Singamaneni, Srikanth

2017-10-25

Through the use of the limited materials palette, optimally designed micro- and nanostructures, and tightly regulated processes, nature demonstrates exquisite control of light-matter interactions at various length scales. In fact, control of light-matter interactions is an important element in the evolutionary arms race and has led to highly engineered optical materials and systems. In this review, we present a detailed summary of various optical effects found in nature with a particular emphasis on the materials and optical design aspects responsible for their optical functionality. Using several representative examples, we discuss various optical phenomena, including absorption and transparency, diffraction, interference, reflection and antireflection, scattering, light harvesting, wave guiding and lensing, camouflage, and bioluminescence, that are responsible for the unique optical properties of materials and structures found in nature and biology. Great strides in understanding the design principles adapted by nature have led to a tremendous progress in realizing biomimetic and bioinspired optical materials and photonic devices. We discuss the various micro- and nanofabrication techniques that have been employed for realizing advanced biomimetic optical structures.

Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration

PubMed Central

Sailland, Juliette; Tribollet, Violaine; Forcet, Christelle; Billon, Cyrielle; Barenton, Bruno; Carnesecchi, Julie; Bachmann, Alice; Gauthier, Karine Cécile; Yu, Shan; Giguère, Vincent; Chan, Franky L.; Vanacker, Jean-Marc

2014-01-01

Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration. PMID:25288732

Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration.

PubMed

Sailland, Juliette; Tribollet, Violaine; Forcet, Christelle; Billon, Cyrielle; Barenton, Bruno; Carnesecchi, Julie; Bachmann, Alice; Gauthier, Karine Cécile; Yu, Shan; Giguère, Vincent; Chan, Franky L; Vanacker, Jean-Marc

2014-10-21

Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration.

Identification of a DNA Segment Exhibiting Rearrangement Modifying Effects upon Transgenic δ-deleting Elements

PubMed Central

Janowski, Karen M.; Ledbetter, Stephanie; Mayo, Matthew S.; Hockett, Richard D.

1997-01-01

Control of the rearrangement and expression of the T cell receptor α and δ chains is critical for determining T cell type. The process of δ deletion is a candidate mechanism for maintaining separation of the α and δ loci. Mice harboring a transgenic reporter δ deletion construct show α/β T cell lineage–specific use of the transgenic elements. A 48-basepair segment of DNA, termed HPS1A, when deleted from this reporter construct, loses tight lineage-specific rearrangement control of transgenic elements, with abundant rearrangements of transgenic δ-deleting elements now in γ/δ T cells. Furthermore, HPS1A augments recombination frequency of extrachromosomal substrates in an in vitro recombination assay. DNA binding proteins recognizing HPS1A have been identified and are restricted to early B and T cells, during the time of active rearrangement of endogenous TCR and immunoglobulin loci. These data are consistent with δ deletion playing an important role in maintaining separate TCR α and δ loci. PMID:9207011

Fine-tuning of ULK1 mRNA and protein levels is required for autophagy oscillation

PubMed Central

Ciccosanti, Fabiola

2016-01-01

Autophagy is an intracellular degradation pathway whose levels are tightly controlled to secure cell homeostasis. Unc-51–like kinase 1 (ULK1) is a conserved serine–threonine kinase that plays a central role in the initiation of autophagy. Here, we report that upon autophagy progression, ULK1 protein levels are specifically down-regulated by the E3 ligase NEDD4L, which ubiquitylates ULK1 for degradation by the proteasome. However, whereas ULK1 protein is degraded, ULK1 mRNA is actively transcribed. Upon reactivation of mTOR-dependent protein synthesis, basal levels of ULK1 are promptly restored, but the activity of newly synthesized ULK1 is inhibited by mTOR. This prepares the cell for a new possible round of autophagy stimulation. Our results thus place NEDD4L and ULK1 in a key position to control oscillatory activation of autophagy during prolonged stress to keep the levels of this process under a safe and physiological threshold. PMID:27932573

Characterizing the role of the microtubule binding protein Bim1 in Cryptococcus neoformans

PubMed Central

Staudt, Mark W.; Kruzel, Emilia K.; Shimizu, Kiminori; Hull, Christina M.

2010-01-01

During sexual development the human fungal pathogen Cryptococcus neoformans undergoes a developmental transition from yeast-form growth to filamentous growth. This transition requires cellular restructuring to form a filamentous dikaryon. Dikaryotic growth also requires tightly controlled nuclear migration to ensure faithful replication and dissemination of genetic material to spore progeny. Although the gross morphological changes that take place during dikaryotic growth are largely known, the molecular underpinnings that control this process are uncharacterized. Here we identify and characterize a C. neoformans homolog of the Saccharomyces cerevisiae BIM1 gene, and establish the importance of BIM1 for proper filamentous growth of C. neoformans. Deletion of BIM1 leads to truncated sexual development filaments, a severe defect in diploid formation, and a block in monokaryotic fruiting. Our findings lead to a model consistent with a critical role for BIM1 in both filament integrity and nuclear congression that is mediated through the microtubule cytoskeleton. PMID:20044015

The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability.

PubMed

Wilms, Tobias; Swinnen, Erwin; Eskes, Elja; Dolz-Edo, Laura; Uwineza, Alice; Van Essche, Ruben; Rosseels, Joëlle; Zabrocki, Piotr; Cameroni, Elisabetta; Franssens, Vanessa; De Virgilio, Claudio; Smits, Gertien J; Winderickx, Joris

2017-06-01

The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase) to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises when deletion of SCH9 is combined with a dysfunctional V-ATPase, and the lack of Sch9 has a significant impact on cytosolic pH (pHc) homeostasis. Sch9 physically interacts with, and influences glucose-dependent assembly/disassembly of the V-ATPase, thereby integrating input from TORC1. Moreover, we show that the role of Sch9 in regulating ageing is tightly connected with V-ATPase activity and vacuolar acidity. As both Sch9 and the V-ATPase are highly conserved in higher eukaryotes, it will be interesting to further clarify their cooperative action on the cellular processes that influence growth and ageing.

The future of EUV lithography: enabling Moore's Law in the next decade

NASA Astrophysics Data System (ADS)

Pirati, Alberto; van Schoot, Jan; Troost, Kars; van Ballegoij, Rob; Krabbendam, Peter; Stoeldraijer, Judon; Loopstra, Erik; Benschop, Jos; Finders, Jo; Meiling, Hans; van Setten, Eelco; Mika, Niclas; Dredonx, Jeannot; Stamm, Uwe; Kneer, Bernhard; Thuering, Bernd; Kaiser, Winfried; Heil, Tilmann; Migura, Sascha

2017-03-01

While EUV systems equipped with a 0.33 Numerical Aperture lenses are readying to start volume manufacturing, ASML and Zeiss are ramping up their development activities on a EUV exposure tool with Numerical Aperture greater than 0.5. The purpose of this scanner, targeting a resolution of 8nm, is to extend Moore's law throughout the next decade. A novel, anamorphic lens design, has been developed to provide the required Numerical Aperture; this lens will be paired with new, faster stages and more accurate sensors enabling Moore's law economical requirements, as well as the tight focus and overlay control needed for future process nodes. The tighter focus and overlay control budgets, as well as the anamorphic optics, will drive innovations in the imaging and OPC modelling, and possibly in the metrology concepts. Furthermore, advances in resist and mask technology will be required to image lithography features with less than 10nm resolution. This paper presents an overview of the key technology innovations and infrastructure requirements for the next generation EUV systems.

Membrane-targeted WAVE mediates photoreceptor axon targeting in the absence of the WAVE complex in Drosophila

PubMed Central

Stephan, Raiko; Gohl, Christina; Fleige, Astrid; Klämbt, Christian; Bogdan, Sven

2011-01-01

A tight spatial-temporal coordination of F-actin dynamics is crucial for a large variety of cellular processes that shape cells. The Abelson interactor (Abi) has a conserved role in Arp2/3-dependent actin polymerization, regulating Wiskott-Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE). In this paper, we report that Abi exerts nonautonomous control of photoreceptor axon targeting in the Drosophila visual system through WAVE. In abi mutants, WAVE is unstable but restored by reexpression of Abi, confirming that Abi controls the integrity of the WAVE complex in vivo. Remarkably, expression of a membrane-tethered WAVE protein rescues the axonal projection defects of abi mutants in the absence of the other subunits of the WAVE complex, whereas cytoplasmic WAVE only slightly affects the abi mutant phenotype. Thus complex formation not only stabilizes WAVE, but also provides further membrane-recruiting signals, resulting in an activation of WAVE. PMID:21900504

Slush Hydrogen Technology Program

NASA Technical Reports Server (NTRS)

Cady, Edwin C.

1994-01-01

A slush hydrogen (SH2) technology facility (STF) was designed, fabricated, and assembled by a contractor team of McDonnell Douglas Aerospace (MDA), Martin Marietta Aerospace Group (MMAG), and Air Products and Chemicals, Inc. (APCI). The STF consists of a slush generator which uses the freeze-thaw production process, a vacuum subsystem, a test tank which simulates the NASP vehicle, a triple point hydrogen receiver tank, a transfer subsystem, a sample bottle, a pressurization system, and a complete instrumentation and control subsystem. The STF was fabricated, checked-out, and made ready for testing under this contract. The actual SH2 testing was performed under the NASP consortium following NASP teaming. Pre-STF testing verified SH2 production methods, validated special SH2 instrumentation, and performed limited SH2 pressurization and expulsion tests which demonstrated the need for gaseous helium pre-pressurized of SH2 to control pressure collapse. The STF represents cutting-edge technology development by an effective Government-Industry team under very tight cost and schedule constraints.

Process variation challenges and resolution in the negative-tone develop double patterning for 20nm and below technology node

NASA Astrophysics Data System (ADS)

Mehta, Sohan S.; Ganta, Lakshmi K.; Chauhan, Vikrant; Wu, Yixu; Singh, Sunil; Ann, Chia; Subramany, Lokesh; Higgins, Craig; Erenturk, Burcin; Srivastava, Ravi; Singh, Paramjit; Koh, Hui Peng; Cho, David

2015-03-01

Immersion based 20nm technology node and below becoming very challenging to chip designers, process and integration due to multiple patterning to integrate one design layer . Negative tone development (NTD) processes have been well accepted by industry experts for enabling technologies 20 nm and below. 193i double patterning is the technology solution for pitch down to 80 nm. This imposes tight control in critical dimension(CD) variation in double patterning where design patterns are decomposed in two different masks such as in litho-etch-litho etch (LELE). CD bimodality has been widely studied in LELE double patterning. A portion of CD tolerance budget is significantly consumed by variations in CD in double patterning. The objective of this work is to study the process variation challenges and resolution in the Negative Tone Develop Process for 20 nm and Below Technology Node. This paper describes the effect of dose slope on CD variation in negative tone develop LELE process. This effect becomes even more challenging with standalone NTD developer process due to q-time driven CD variation. We studied impact of different stacks with combination of binary and attenuated phase shift mask and estimated dose slope contribution individually from stack and mask type. Mask 3D simulation was carried out to understand theoretical aspect. In order to meet the minimum insulator requirement for the worst case on wafer the overlay and critical dimension uniformity (CDU) budget margins have slimmed. Besides the litho process and tool control using enhanced metrology feedback, the variation control has other dependencies too. Color balancing between the two masks in LELE is helpful in countering effects such as iso-dense bias, and pattern shifting. Dummy insertion and the improved decomposition techniques [2] using multiple lower priority constraints can help to a great extent. Innovative color aware routing techniques [3] can also help with achieving more uniform density and color balanced layouts.

Comparison of preribosomal RNA processing pathways in yeast, plant and human cells - focus on coordinated action of endo- and exoribonucleases.

PubMed

Tomecki, Rafal; Sikorski, Pawel J; Zakrzewska-Placzek, Monika

2017-07-01

Proper regulation of ribosome biosynthesis is mandatory for cellular adaptation, growth and proliferation. Ribosome biogenesis is the most energetically demanding cellular process, which requires tight control. Abnormalities in ribosome production have severe consequences, including developmental defects in plants and genetic diseases (ribosomopathies) in humans. One of the processes occurring during eukaryotic ribosome biogenesis is processing of the ribosomal RNA precursor molecule (pre-rRNA), synthesized by RNA polymerase I, into mature rRNAs. It must not only be accurate but must also be precisely coordinated with other phenomena leading to the synthesis of functional ribosomes: RNA modification, RNA folding, assembly with ribosomal proteins and nucleocytoplasmic RNP export. A multitude of ribosome biogenesis factors ensure that these events take place in a correct temporal order. Among them are endo- and exoribonucleases involved in pre-rRNA processing. Here, we thoroughly present a wide spectrum of ribonucleases participating in rRNA maturation, focusing on their biochemical properties, regulatory mechanisms and substrate specificity. We also discuss cooperation between various ribonucleolytic activities in particular stages of pre-rRNA processing, delineating major similarities and differences between three representative groups of eukaryotes: yeast, plants and humans. © 2017 Federation of European Biochemical Societies.

In Situ Fringe Projection Profilometry for Laser Power Bed Fusion Process

NASA Astrophysics Data System (ADS)

Zhang, Bin

Additive manufacturing (AM) offers an industrial solution to produce parts with complex geometries and internal structures that conventional manufacturing techniques cannot produce. However, current metal additive process, particularly the laser powder bed fusion (LPBF) process, suffers from poor surface finish and various material defects which hinder its wide applications. One way to solve this problem is by adding in situ metrology sensor onto the machine chamber. Matured manufacturing processes are tightly monitored and controlled, and instrumentation advances are needed to realize this same advantage for metal additive process. This encourages us to develop an in situ fringe projection system for the LPBF process. The development of such a system and the measurement capability are demonstrated in this dissertation. We show that this system can measure various powder bed signatures including powder layer variations, the average height drop between fused metal and unfused powder, and the height variations on the fused surfaces. The ability to measure textured surface is also evaluated through the instrument transfer function (ITF). We analyze the mathematical model of the proposed fringe projection system, and prove the linearity of the system through simulations. A practical ITF measurement technique using a stepped surface is also demonstrated. The measurement results are compared with theoretical predictions generated through the ITF simulations.

Cost and performance prospects for composite bipolar plates in fuel cells and redox flow batteries

NASA Astrophysics Data System (ADS)

Minke, Christine; Hickmann, Thorsten; dos Santos, Antonio R.; Kunz, Ulrich; Turek, Thomas

2016-02-01

Carbon-polymer-composite bipolar plates (BPP) are suitable for fuel cell and flow battery applications. The advantages of both components are combined in a product with high electrical conductivity and good processability in convenient polymer forming processes. In a comprehensive techno-economic analysis of materials and production processes cost factors are quantified. For the first time a technical cost model for BPP is set up with tight integration of material characterization measurements.

Using XML and Java for Astronomical Instrumentation Control

NASA Technical Reports Server (NTRS)

Ames, Troy; Koons, Lisa; Sall, Ken; Warsaw, Craig

2000-01-01

Traditionally, instrument command and control systems have been highly specialized, consisting mostly of custom code that is difficult to develop, maintain, and extend. Such solutions are initially very costly and are inflexible to subsequent engineering change requests, increasing software maintenance costs. Instrument description is too tightly coupled with details of implementation. NASA Goddard Space Flight Center is developing a general and highly extensible framework that applies to any kind of instrument that can be controlled by a computer. The software architecture combines the platform independent processing capabilities of Java with the power of the Extensible Markup Language (XML), a human readable and machine understandable way to describe structured data. A key aspect of the object-oriented architecture is software that is driven by an instrument description, written using the Instrument Markup Language (IML). ]ML is used to describe graphical user interfaces to control and monitor the instrument, command sets and command formats, data streams, and communication mechanisms. Although the current effort is targeted for the High-resolution Airborne Wideband Camera, a first-light instrument of the Stratospheric Observatory for Infrared Astronomy, the framework is designed to be generic and extensible so that it can be applied to any instrument.

Cadmium disorganises the scaffolding of gap and tight junction proteins in the hepatic cell line WIF B9.

PubMed

Boucherie, Sylviane; Decaens, Catherine; Verbavatz, Jean-Marc; Grosse, Brigitte; Erard, Marie; Merola, Fabienne; Cassio, Doris; Combettes, Laurent

2013-12-01

Hepatocytes, which perform the main functions of the liver, are particularly vulnerable to toxic agents such as cadmium, an environmental pollutant. To identify the molecular targets for cadmium in hepatocytes, we have studied the effects of CdCl2 on the hybrid cell line WIF-B9 that exhibits stable structural and functional hepatocytic polarity. We showed that the toxicity of CdCl2 (1 µM, 24 h) resulted in a reduction in direct intercellular communication (via gap junctions) and in an increase in paracellular permeability (decrease in the sealing of tight junctions). These effects were not related to changes in the expression of the key proteins involved, Cx32 and claudin 2, the first being constitutive of gap junctions and the second of tight junctions in this cell line. Using immunofluorescence experiments, we observed a change in the location of Cx32 and claudin 2: these two proteins were less often found in the tight junction network that closes the bile canaliculi (BC). In control cells, 'Proximity Ligation Assay' (PLA Duolink®) has confirmed in situ that molecules of claudin 2 and Cx32 are very close to each other at the BC (probably less than 16 nm). This was no longer the case after treatment with CdCl2 . Localisation of occludin and Cx32 relative to each other was not modified by CdCl2 , but CdCl2 increased the PLA signal between molecules of JAM-A and Cx32. Finally, examination of freeze-fracture replicas obtained from cultures treated with CdCl2 showed the disruption of the network of tight junctions and the depletion or the disintegration of the junctional plaques associated with tight junctions. This study demonstrates in situ the changes induced by cadmium on the organisation of cell-cell junctions and points out the importance of the association Cx32/claudin 2 for the maintenance of normal hepatocyte functions. © 2013 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

NASA Astrophysics Data System (ADS)

Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

2015-05-01

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network. Electronic supplementary information (ESI) available: Comparison of non-filtered and Savitzky-Golay filtered action potential recordings, electrical signals and corresponding optical signals. See DOI: 10.1039/c5nr01690h

Leaching behavior of coal combustion products and the environmental implication in road construction.

DOT National Transportation Integrated Search

2011-04-01

Leaching of trace elements may raise environmental concerns when using coal fly ash in road construction. US EPA is in the process : of creating the first national rule on coal ash management, including beneficial use. Meanwhile, driven by the tighte...

Improved fabrication of electrolytic capacitors

NASA Technical Reports Server (NTRS)

Gamari, F. J.; Moresi, J. L.

1975-01-01

After processing parts for assembly, insulative cup is fitted to bottom of can, then electrolytic solution consisting of white sulfuric acid gel is inserted into can. Pellet is put in can and is fitted tightly into cup. Finally, bead weld is formed between can and header plug.

Fracturing And Liquid CONvection

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

2012-02-29

FALCON has been developed to enable simulation of the tightly coupled fluid-rock behavior in hydrothermal and engineered geothermal system (EGS) reservoirs, targeting the dynamics of fracture stimulation, fluid flow, rock deformation, and heat transport in a single integrated code, with the ultimate goal of providing a tool that can be used to test the viability of EGS in the United States and worldwide. Reliable reservoir performance predictions of EGS systems require accurate and robust modeling for the coupled thermal-hydrological-mechanical processes. Conventionally, these types of problems are solved using operator-splitting methods, usually by coupling a subsurface flow and heat transport simulatormore » with a solid mechanics simulator via input files. FALCON eliminates the need for using operator-splitting methods to simulate these systems, and the scalability of the underlying MOOSE architecture allows for simulating these tightly coupled processes at the reservoir scale, allowing for examination of the system as a whole (something the operator-splitting methodologies generally cannot do).« less

The apical scaffold big bang binds to spectrins and regulates the growth of Drosophila melanogaster wing discs.

PubMed

Forest, Elodie; Logeay, Rémi; Géminard, Charles; Kantar, Diala; Frayssinoux, Florence; Heron-Milhavet, Lisa; Djiane, Alexandre

2018-03-05

During development, cell numbers are tightly regulated, ensuring that tissues and organs reach their correct size and shape. Recent evidence has highlighted the intricate connections between the cytoskeleton and the regulation of the key growth control Hippo pathway. Looking for apical scaffolds regulating tissue growth, we describe that Drosophila melanogaster big bang (Bbg), a poorly characterized multi-PDZ scaffold, controls epithelial tissue growth without affecting epithelial polarity and architecture. bbg -mutant tissues are smaller, with fewer cells that are less apically constricted than normal. We show that Bbg binds to and colocalizes tightly with the β-heavy-Spectrin/Kst subunit at the apical cortex and promotes Yki activity, F-actin enrichment, and the phosphorylation of the myosin II regulatory light chain Spaghetti squash. We propose a model in which the spectrin cytoskeleton recruits Bbg to the cortex, where Bbg promotes actomyosin contractility to regulate epithelial tissue growth. © 2018 Forest et al.

Immediate tight sealing of skin incisions using an innovative temperature-controlled laser soldering device: in vivo study in porcine skin.

PubMed

Simhon, David; Halpern, Marisa; Brosh, Tamar; Vasilyev, Tamar; Ravid, Avi; Tennenbaum, Tamar; Nevo, Zvi; Katzir, Abraham

2007-02-01

A feedback temperature-controlled laser soldering system (TCLS) was used for bonding skin incisions on the backs of pigs. The study was aimed: 1) to characterize the optimal soldering parameters, and 2) to compare the immediate and long-term wound healing outcomes with other wound closure modalities. A TCLS was used to bond the approximated wound margins of skin incisions on porcine backs. The reparative outcomes were evaluated macroscopically, microscopically, and immunohistochemically. The optimal soldering temperature was found to be 65 degrees C and the operating time was significantly shorter than with suturing. The immediate tight sealing of the wound by the TCLS contributed to rapid, high quality wound healing in comparison to Dermabond or Histoacryl cyanoacrylate glues or standard suturing. TCLS of incisions in porcine skin has numerous advantages, including rapid procedure and high quality reparative outcomes, over the common standard wound closure procedures. Further studies with a variety of skin lesions are needed before advocating this technique for clinical use.

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

PubMed

Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

2017-11-22

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

GEOLOGIC ASPECTS OF TIGHT GAS RESERVOIRS IN THE ROCKY MOUNTAIN REGION.

USGS Publications Warehouse

Spencer, Charles W.

1985-01-01

The authors describe some geologic characteristics of tight gas reservoirs in the Rocky Mountain region. These reservoirs usually have an in-situ permeability to gas of 0. 1 md or less and can be classified into four general geologic and engineering categories: (1) marginal marine blanket, (2) lenticular, (3) chalk, and (4) marine blanket shallow. Microscopic study of pore/permeability relationships indicates the existence of two varieties of tight reservoirs. One variety is tight because of the fine grain size of the rock. The second variety is tight because the rock is relatively tightly cemented and the pores are poorly connected by small pore throats and capillaries.

Universal Sign Control of Coupling in Tight-Binding Lattices

NASA Astrophysics Data System (ADS)

Keil, Robert; Poli, Charles; Heinrich, Matthias; Arkinstall, Jake; Weihs, Gregor; Schomerus, Henning; Szameit, Alexander

2016-05-01

We present a method of locally inverting the sign of the coupling term in tight-binding systems, by means of inserting a judiciously designed ancillary site and eigenmode matching of the resulting vertex triplet. Our technique can be universally applied to all lattice configurations, as long as the individual sites can be detuned. We experimentally verify this method in laser-written photonic lattices and confirm both the magnitude and the sign of the coupling by interferometric measurements. Based on these findings, we demonstrate how such universal sign-flipped coupling links can be embedded into extended lattice structures to impose a Z2-gauge transformation. This opens a new avenue for investigations on topological effects arising from magnetic fields with aperiodic flux patterns or in disordered systems.

Demonstration of a memory for tightly guided light in an optical nanofiber.

PubMed

Gouraud, B; Maxein, D; Nicolas, A; Morin, O; Laurat, J

2015-05-08

We report the experimental observation of slow-light and coherent storage in a setting where light is tightly confined in the transverse directions. By interfacing a tapered optical nanofiber with a cold atomic ensemble, electromagnetically induced transparency is observed and light pulses at the single-photon level are stored in and retrieved from the atomic medium. The decay of efficiency with storage time is also measured and related to concurrent decoherence mechanisms. Collapses and revivals can be additionally controlled by an applied magnetic field. Our results based on subdiffraction-limited optical mode interacting with atoms via the strong evanescent field demonstrate an alternative to free-space focusing and a novel capability for information storage in an all-fibered quantum network.

Tight Placement of Erich Arch Bar While Avoiding Wire Fatigue Failure.

PubMed

Kirk, Daniel; Whitney, Joseph; Shafer, David; Song, Liansheng

2016-03-01

To determine the number of wire twists needed to acquire ideal Erich arch bar tightness before wire fatigue failure (fracture) in relation to different distances and angles at which different gauge wires are grasped to provide information to improve the efficiency of arch bar application. This study mimicked surgical placement of arch bars with 24- and 26-gauge wires. The number of twists to tightness and failure was evaluated when the wire distance between the arch bar and wire holder tip changed (5 vs 10 mm) and when the degree at which the wire was held relative to the tooth axis was changed (45° vs 90°). A wire shearing test also was used to investigate the fatigability of wires tightened under these same conditions. Wires twisted to tightness, past tightness, and after shearing test movements were visualized with electron microscopy. For 24-gauge wire held at 5 mm, 2.6 to 2.8 twists were needed for wire tightness, with failure after 1.7 to 1.9 twists past tightness; for 24-gauge wire held at 10 mm, 4.4 to 4.9 twists produced tightness, with failure after 2.3 to 2.9 twists past tightness. For 26-gauge wire held at 5 mm, 3.3 to 3.5 twists provided tightness, with 1.6 to 1.8 twists past tightness causing failure; for 26-gauge wire held at 10 mm, 5.1 to 5.5 twists produced tightness, with 3.1 to 3.7 twists past tightness causing failure. At a 45° angle, the wire tightened with fewer twists and showed more resistance to failure with twists past tightness compared with 90° using 24- and 26-gauge wires. In contrast, 24-gauge wire held at a 5-mm distance showed the opposite result, with decreased resistance to failure at the 45° angle. However, the differences were not statistically meaningful. Scanning election microscopy showed no wire fatigue for either angle for 26-gauge wire held at a 5-mm distance and twisted to tightness. After overtightening and oscillation, the 90° angle trials showed fatigue, whereas the 45° angle trials did not. Holding a 24-gauge wire at 45° to the tooth axis is recommended owing to fewer twists to tightness and more resistance to failure. A 5-mm grasping distance is recommended for experienced surgeons owing to fewer twists to tightness, whereas a 10-mm grasping distance is recommended for novice surgeons owing to a greater tolerance for over-twisting before failure. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability.

PubMed

Qian, Yi-Wen; Li, Chuan; Jiang, Ai-Ping; Ge, Shengfang; Gu, Ping; Fan, Xianqun; Li, Tai-Sheng; Jin, Xia; Wang, Jian-Hua; Wang, Zhi-Liang

2016-10-28

Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstances, vascular endothelium and retinal pigment epithelium (RPE), which possess a well developed tight junction complex, form the blood-retinal barrier (BRB) to prevent pathogen invasion. We hypothesize that disruption of the BRB allows pathogen entry into ocular sites. The hypothesis was tested using in vitro models. We discovered that human RPE cells could bind to either HIV-1 gp120 glycoproteins or HIV-1 viral particles. Furthermore, the binding was mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expressed on RPE cells. Upon gp120 binding to DC-SIGN, cellular NF-κB signaling was triggered, leading to the induction of matrix metalloproteinases, which subsequently degraded tight junction proteins and disrupted the BRB integrity. DC-SIGN knockdown or prior blocking with a specific antibody abolished gp120-induced matrix metalloproteinase expression and reduced the degradation of tight junction proteins. This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Evaluation on real-time dynamic performance of BDS in PPP, RTK, and INS tightly aided modes

NASA Astrophysics Data System (ADS)

Gao, Zhouzheng; Li, Tuan; Zhang, Hongping; Ge, Maorong; Schuh, Harald

2018-05-01

Since China's BeiDou satellite navigation system (BDS) began to provide regional navigation service for Asia-Pacific region after 2012, more new generation BDS satellites have been launched to further expand BDS's coverage to be global. In this contribution, precise positioning models based on BDS and the corresponding mathematical algorithms are presented in detail. Then, an evaluation on BDS's real-time dynamic positioning and navigation performance is presented in Precise Point Positioning (PPP), Real-time Kinematic (RTK), Inertial Navigation System (INS) tightly aided PPP and RTK modes by processing a set of land-borne vehicle experiment data. Results indicate that BDS positioning Root Mean Square (RMS) in north, east, and vertical components are 2.0, 2.7, and 7.6 cm in RTK mode and 7.8, 14.7, and 24.8 cm in PPP mode, which are close to GPS positioning accuracy. Meanwhile, with the help of INS, about 38.8%, 67.5%, and 66.5% improvements can be obtained by using PPP/INS tight-integration mode. Such enhancements in RTK/INS tight-integration mode are 14.1%, 34.0%, and 41.9%. Moreover, the accuracy of velocimetry and attitude determination can be improved to be better than 1 cm/s and 0.1°, respectively. Besides, the continuity and reliability of BDS in both PPP and RTK modes can also be ameliorated significantly by INS during satellite signal missing periods.

A nuclear factor-κB signaling pathway via protein kinase C δ regulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells

PubMed Central

Masaki, Tomoyuki; Kojima, Takashi; Okabayashi, Tamaki; Ogasawara, Noriko; Ohkuni, Tsuyoshi; Obata, Kazufumi; Takasawa, Akira; Murata, Masaki; Tanaka, Satoshi; Hirakawa, Satoshi; Fuchimoto, Jun; Ninomiya, Takafumi; Fujii, Nobuhiro; Tsutsumi, Hiroyuki; Himi, Tetsuo; Sawada, Norimasa

2011-01-01

Respiratory syncytial virus (RSV) is the major cause of bronchitis, asthma, and severe lower respiratory tract disease in infants and young children. The airway epithelium, which has a well-developed barrier regulated by tight junctions, is the first line of defense during respiratory virus infection. In upper airway human nasal epithelial cells (HNECs), however, the primary site of RSV infection, the mechanisms of replication and budding of RSV, and the epithelial cell responses, including the tight junctional barrier, remain unknown. To investigate the detailed mechanisms of replication and budding of RSV in HNECs and the epithelial cell responses, we established an RSV-infected model using human telomerase reverse transcriptase–-transfected HNECs. We first found that the expression and barrier function of tight junction molecules claudin-4 and occludin were markedly induced together with production of proinflammatory cytokines interleukin 8 and tumor necrosis factor-α in HNECs after RSV infection, and the induction of tight junction molecules possibly contributed to budding of RSV. Furthermore, the replication and budding of RSV and the epithelial cell responses in HNECs were regulated via a protein kinase C δ/hypoxia-inducible factor-1α/nuclear factor-κB pathway. The control of this pathway in HNECs may be useful not only for prevention of replication and budding of RSV, but also in therapy for RSV-induced respiratory pathogenesis. PMID:21562222

Structural diversity in social contagion

PubMed Central

Ugander, Johan; Backstrom, Lars; Marlow, Cameron; Kleinberg, Jon

2012-01-01

The concept of contagion has steadily expanded from its original grounding in epidemic disease to describe a vast array of processes that spread across networks, notably social phenomena such as fads, political opinions, the adoption of new technologies, and financial decisions. Traditional models of social contagion have been based on physical analogies with biological contagion, in which the probability that an individual is affected by the contagion grows monotonically with the size of his or her “contact neighborhood”—the number of affected individuals with whom he or she is in contact. Whereas this contact neighborhood hypothesis has formed the underpinning of essentially all current models, it has been challenging to evaluate it due to the difficulty in obtaining detailed data on individual network neighborhoods during the course of a large-scale contagion process. Here we study this question by analyzing the growth of Facebook, a rare example of a social process with genuinely global adoption. We find that the probability of contagion is tightly controlled by the number of connected components in an individual's contact neighborhood, rather than by the actual size of the neighborhood. Surprisingly, once this “structural diversity” is controlled for, the size of the contact neighborhood is in fact generally a negative predictor of contagion. More broadly, our analysis shows how data at the size and resolution of the Facebook network make possible the identification of subtle structural signals that go undetected at smaller scales yet hold pivotal predictive roles for the outcomes of social processes. PMID:22474360

Heat Transfer in Health and Healing.

PubMed

Diller, Kenneth R

2015-10-01

Our bodies depend on an exquisitely sensitive and refined temperature control system to maintain a state of health and homeostasis. The exceptionally broad range of physical activities that humans engage in and the diverse array of environmental conditions we face require remarkable strategies and mechanisms for regulating internal and external heat transfer processes. On the occasions for which the body suffers trauma, therapeutic temperature modulation is often the approach of choice for reversing injury and inflammation and launching a cascade of healing. The focus of human thermoregulation is maintenance of the body core temperature within a tight range of values, even as internal rates of energy generation may vary over an order of magnitude, environmental convection, and radiation heat loads may undergo large changes in the absence of any significant personal control, surface insulation may be added or removed, all occurring while the body's internal thermostat follows a diurnal circadian cycle that may be altered by illness and anesthetic agents. An advanced level of understanding of the complex physiological function and control of the human body may be combined with skill in heat transfer analysis and design to develop life-saving and injury-healing medical devices. This paper will describe some of the challenges and conquests the author has experienced related to the practice of heat transfer for maintenance of health and enhancement of healing processes.

Food safety and nutritional quality for the prevention of non communicable diseases: the Nutrient, hazard Analysis and Critical Control Point process (NACCP).

PubMed

Di Renzo, Laura; Colica, Carmen; Carraro, Alberto; Cenci Goga, Beniamino; Marsella, Luigi Tonino; Botta, Roberto; Colombo, Maria Laura; Gratteri, Santo; Chang, Ting Fa Margherita; Droli, Maurizio; Sarlo, Francesca; De Lorenzo, Antonino

2015-04-23

The important role of food and nutrition in public health is being increasingly recognized as crucial for its potential impact on health-related quality of life and the economy, both at the societal and individual levels. The prevalence of non-communicable diseases calls for a reformulation of our view of food. The Hazard Analysis and Critical Control Point (HACCP) system, first implemented in the EU with the Directive 43/93/CEE, later replaced by Regulation CE 178/2002 and Regulation CE 852/2004, is the internationally agreed approach for food safety control. Our aim is to develop a new procedure for the assessment of the Nutrient, hazard Analysis and Critical Control Point (NACCP) process, for total quality management (TMQ), and optimize nutritional levels. NACCP was based on four general principles: i) guarantee of health maintenance; ii) evaluate and assure the nutritional quality of food and TMQ; iii) give correct information to the consumers; iv) ensure an ethical profit. There are three stages for the application of the NACCP process: 1) application of NACCP for quality principles; 2) application of NACCP for health principals; 3) implementation of the NACCP process. The actions are: 1) identification of nutritional markers, which must remain intact throughout the food supply chain; 2) identification of critical control points which must monitored in order to minimize the likelihood of a reduction in quality; 3) establishment of critical limits to maintain adequate levels of nutrient; 4) establishment, and implementation of effective monitoring procedures of critical control points; 5) establishment of corrective actions; 6) identification of metabolic biomarkers; 7) evaluation of the effects of food intake, through the application of specific clinical trials; 8) establishment of procedures for consumer information; 9) implementation of the Health claim Regulation EU 1924/2006; 10) starting a training program. We calculate the risk assessment as follows: Risk (R) = probability (P) × damage (D). The NACCP process considers the entire food supply chain "from farm to consumer"; in each point of the chain it is necessary implement a tight monitoring in order to guarantee optimal nutritional quality.

An Overview of Current and Projected Shale and Tight Gas Water Use in Texas: Implications for Local Water Resources, March 29-30, 2011

EPA Pesticide Factsheets

The objective of the study was to determine the amount of water used for different purposes (well drilling, completion, and secondary and tertiary recovery processes of conventional resources) across the state.

ULTRAPETALA trxG genes interact with KANADI transcription factor genes to regulate Aradopsis Gynoecium patterning

USDA-ARS?s Scientific Manuscript database

Organ formation relies upon precise patterns of gene expression that are under tight spatial and temporal regulation. Transcription patterns are specified by several cellular processes during development, including chromatin remodeling, but little is known about how chromatin remodeling factors cont...

METHYLMERCURY BUT NOT MERCURIC CHLORIDE INDUCES APOPTOTIC CELL DEATH IN PC12 CELLS.

EPA Science Inventory

Normal development of the nervous system requires the process of apoptosis, a form of programmed cell death, to remove superfluous neurons. Abnormal patterns of apoptosis may be a consequence of exposure to environmental neurotoxicants leading to a disruption in the tightly regul...

Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

EPA Science Inventory

Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

40 CFR 61.141 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Information on glove-bag installation, equipment and supplies, and work practices is contained in the... (or owner or operator under common control). Leak-tight means that solids or liquids cannot escape or... such as cliffs, lakes or other large bodies of water, deep and wide ravines, and mountains. Remoteness...

30 CFR 57.4431 - Surface storage restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: (1) Flammable liquids in safety cans or in other containers placed in tightly closed cabinets. The... Prevention and Control Flammable and Combustible Liquids and Gases § 57.4431 Surface storage restrictions. (a) On the surface, no unburied flammable or combustible liquids or flammable gases shall be stored...

30 CFR 57.4431 - Surface storage restrictions.

Code of Federal Regulations, 2011 CFR

2011-07-01

...: (1) Flammable liquids in safety cans or in other containers placed in tightly closed cabinets. The... Prevention and Control Flammable and Combustible Liquids and Gases § 57.4431 Surface storage restrictions. (a) On the surface, no unburied flammable or combustible liquids or flammable gases shall be stored...

A quantitative adverse outcome pathway model for thyroid axis disruption in Xenopus laevis tadpoles

EPA Science Inventory

The development of Xenopus laevis tadpoles is tightly controlled by the thyroid hormones tetraiodothyronine (T4) and triiodothyronine (T3). Toxicity testing efforts have shown that several compounds interfere with development in X. laevis tadpoles by disrupting the thyroid axis a...

189. Photographic copy of original construction drawing dated December 10, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

189. Photographic copy of original construction drawing dated December 10, 1932 (from Record Group 115, Denver Branch of the National Archives, Denver). TUNNEL NO.1 CONTROLLING WORKS; WATER TIGHT DOOR; CHANNEL VENT INLETS-PIER NOSE ANGLES. - Owyhee Dam, Across Owyhee River, Nyssa, Malheur County, OR

Differential Adipose Tissue Gene Expression Profiles in Abacavir Treated Patients That May Contribute to the Understanding of Cardiovascular Risk: A Microarray Study

PubMed Central

Shahmanesh, Mohsen; Phillips, Kenneth; Boothby, Meg; Tomlinson, Jeremy W.

2015-01-01

Objective To compare changes in gene expression by microarray from subcutaneous adipose tissue from HIV treatment naïve patients treated with efavirenz based regimens containing abacavir (ABC), tenofovir (TDF) or zidovidine (AZT). Design Subcutaneous fat biopsies were obtained before, at 6- and 18–24-months after treatment, and from HIV negative controls. Groups were age, ethnicity, weight, biochemical profile, and pre-treatment CD4 count matched. Microarray data was generated using the Agilent Whole Human Genome Microarray. Identification of differentially expressed genes and genomic response pathways was performed using limma and gene set enrichment analysis. Results There were significant divergences between ABC and the other two groups 6 months after treatment in genes controlling cell adhesion and environmental information processing, with some convergence at 18–24 months. Compared to controls the ABC group, but not AZT or TDF showed enrichment of genes controlling adherence junction, at 6 months and 18–24 months (adjusted p<0.05) and focal adhesions and tight junction at 6 months (p<0.5). Genes controlling leukocyte transendothelial migration (p<0.05) and ECM-receptor interactions (p = 0.04) were over-expressed in ABC compared to TDF and AZT at 6 months but not at 18–24 months. Enrichment of pathways and individual genes controlling cell adhesion and environmental information processing were specifically dysregulated in the ABC group in comparison with other treatments. There was little difference between AZT and TDF. Conclusion After initiating treatment, there is divergence in the expression of genes controlling cell adhesion and environmental information processing between ABC and both TDF and AZT in subcutaneous adipose tissue. If similar changes are also taking place in other tissues including the coronary vasculature they may contribute to the increased risk of cardiovascular events reported in patients recently started on abacavir-containing regimens. PMID:25617630

The Pharmaceutical Capping Process-Correlation between Residual Seal Force, Torque Moment, and Flip-off Removal Force.

PubMed

Mathaes, Roman; Mahler, Hanns-Christian; Vorgrimler, Lothar; Steinberg, Henrik; Dreher, Sascha; Roggo, Yves; Nieto, Alejandra; Brown, Helen; Roehl, Holger; Adler, Michael; Luemkemann, Joerg; Huwyler, Joerg; Lam, Philippe; Stauch, Oliver; Mohl, Silke; Streubel, Alexander

2016-01-01

The majority of parenteral drug products are manufactured in glass vials with an elastomeric rubber stopper and a crimp cap. The vial sealing process is a critical process step during fill-and-finish operations, as it defines the seal quality of the final product. Different critical capping process parameters can affect rubber stopper defects, rubber stopper compression, container closure integrity, and also crimp cap quality. A sufficiently high force to remove the flip-off button prior to usage is required to ensure quality of the drug product unit by the flip-off button during storage, transportation, and until opening and use. Therefore, the final product is 100% visually inspected for lose or defective crimp caps, which is subjective as well as time- and labor-intensive. In this study, we sealed several container closure system configurations with different capping equipment settings (with corresponding residual seal force values) to investigate the torque moment required to turn the crimp cap. A correlation between torque moment and residual seal force has been established. The torque moment was found to be influenced by several parameters, including diameter of the vial head, type of rubber stopper (serum or lyophilized) and type of crimp cap (West(®) or Datwyler(®)). In addition, we measured the force required to remove the flip-off button of a sealed container closure system. The capping process had no influence on measured forces; however, it was possible to detect partially crimped vials. In conclusion, a controlled capping process with a defined target residual seal force range leads to a tight crimp cap on a sealed container closure system and can ensure product quality. The majority of parenteral drug products are manufactured in a glass vials with an elastomeric rubber stopper and a crimp cap. The vial sealing process is a critical process step during fill-and-finish operations, as it defines the seal quality of the final product. An adequate force to remove the flip-off button prior to usage is required to ensure product quality during storage and transportation until use. In addition, the complete crimp cap needs to be fixed in a tight position on the vial. In this study, we investigated the torque moment required to turn the crimp cap and the force required to remove the flip-off button of container closure system sealed with different capping equipment process parameters (having different residual seal force values). © PDA, Inc. 2016.

Glucocorticoids, epigenetic control and stress resilience

PubMed Central

Reul, Johannes M.H.M.; Collins, Andrew; Saliba, Richard S.; Mifsud, Karen R.; Carter, Sylvia D.; Gutierrez-Mecinas, Maria; Qian, Xiaoxiao; Linthorst, Astrid C.E.

2014-01-01

Glucocorticoid hormones play a pivotal role in the response to stressful challenges. The surge in glucocorticoid hormone secretion after stress needs to be tightly controlled with characteristics like peak height, curvature and duration depending on the nature and severity of the challenge. This is important as chronic hyper- or hypo-responses are detrimental to health due to increasing the risk for developing a stress-related mental disorder. Proper glucocorticoid responses to stress are critical for adaptation. Therefore, the tight control of baseline and stress-evoked glucocorticoid secretion are important constituents of an organism's resilience. Here, we address a number of mechanisms that illustrate the multitude and complexity of measures safeguarding the control of glucocorticoid function. These mechanisms include the control of mineralocorticoid (MR) and glucocorticoid receptor (GR) occupancy and concentration, the dynamic control of free glucocorticoid hormone availability by corticosteroid-binding globulin (CBG), and the control exerted by glucocorticoids at the signaling, epigenetic and genomic level on gene transcriptional responses to stress. We review the beneficial effects of regular exercise on HPA axis and sleep physiology, and cognitive and anxiety-related behavior. Furthermore, we describe that, possibly through changes in the GABAergic system, exercise reduces the impact of stress on a signaling pathway specifically in the dentate gyrus that is strongly implicated in the behavioral response to that stressor. These observations underline the impact of life style on stress resilience. Finally, we address how single nucleotide polymorphisms (SNPs) affecting glucocorticoid action can compromise stress resilience, which becomes most apparent under conditions of childhood abuse. PMID:27589660

Execution environment for intelligent real-time control systems

NASA Technical Reports Server (NTRS)

Sztipanovits, Janos

1987-01-01

Modern telerobot control technology requires the integration of symbolic and non-symbolic programming techniques, different models of parallel computations, and various programming paradigms. The Multigraph Architecture, which has been developed for the implementation of intelligent real-time control systems is described. The layered architecture includes specific computational models, integrated execution environment and various high-level tools. A special feature of the architecture is the tight coupling between the symbolic and non-symbolic computations. It supports not only a data interface, but also the integration of the control structures in a parallel computing environment.

A Electro-Optical Image Algebra Processing System for Automatic Target Recognition

NASA Astrophysics Data System (ADS)

Coffield, Patrick Cyrus

The proposed electro-optical image algebra processing system is designed specifically for image processing and other related computations. The design is a hybridization of an optical correlator and a massively paralleled, single instruction multiple data processor. The architecture of the design consists of three tightly coupled components: a spatial configuration processor (the optical analog portion), a weighting processor (digital), and an accumulation processor (digital). The systolic flow of data and image processing operations are directed by a control buffer and pipelined to each of the three processing components. The image processing operations are defined in terms of basic operations of an image algebra developed by the University of Florida. The algebra is capable of describing all common image-to-image transformations. The merit of this architectural design is how it implements the natural decomposition of algebraic functions into spatially distributed, point use operations. The effect of this particular decomposition allows convolution type operations to be computed strictly as a function of the number of elements in the template (mask, filter, etc.) instead of the number of picture elements in the image. Thus, a substantial increase in throughput is realized. The implementation of the proposed design may be accomplished in many ways. While a hybrid electro-optical implementation is of primary interest, the benefits and design issues of an all digital implementation are also discussed. The potential utility of this architectural design lies in its ability to control a large variety of the arithmetic and logic operations of the image algebra's generalized matrix product. The generalized matrix product is the most powerful fundamental operation in the algebra, thus allowing a wide range of applications. No other known device or design has made this claim of processing speed and general implementation of a heterogeneous image algebra.

Tight junctions and human diseases.

PubMed

Sawada, Norimasa; Murata, Masaki; Kikuchi, Keisuke; Osanai, Makoto; Tobioka, Hirotoshi; Kojima, Takashi; Chiba, Hideki

2003-09-01

Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

Recent developments in plasma spray processes for applications in energy technology

NASA Astrophysics Data System (ADS)

Mauer, G.; Jarligo, M. O.; Marcano, D.; Rezanka, S.; Zhou, D.; Vaßen, R.

2017-03-01

This work focuses on recent developments of plasma spray processes with respect to specific demands in energy technology. High Velocity Atmospheric Plasma Spraying (HV-APS) is a novel variant of plasma spraying devoted to materials which are prone to oxidation or decomposition. It is shown how this process can be used for metallic bondcoats in thermal barrier coating systems. Furthermore, Suspension Plasma Spraying (SPS) is a new method to process submicron-sized feedstock powders which are not sufficiently flowable to feed them in dry state. SPS is presently promoted by the development of novel torch concepts with axial feedstock injection. An example for a columnar structured double layer thermal barrier coating is given. Finally, Plasma Spray-Physical Vapor Deposition (PS-PVD) is a novel technology operating in controlled atmosphere at low pressure and high plasma power. At such condition, vaporization even of high-melting oxide ceramics is possible enabling the formation of columnar structured, strain tolerant coatings with low thermal conductivity. Applying different conditions, the deposition is still dominated by liquid splats. Such process is termed Low Pressure Plasma Spraying-Thin Film (LPPS-TF). Two examples of applications are gas-tight and highly ionic and electronic conductive electrolyte and membrane layers which were deposited on porous metallic substrates.

A Question of Control? Examining the Role of Control Conditions in Experimental Psychopathology using the Example of Cognitive Bias Modification Research.

PubMed

Blackwell, Simon E; Woud, Marcella L; MacLeod, Colin

2017-10-26

While control conditions are vitally important in research, selecting the optimal control condition can be challenging. Problems are likely to arise when the choice of control condition is not tightly guided by the specific question that a given study aims to address. Such problems have become increasingly apparent in experimental psychopathology research investigating the experimental modification of cognitive biases, particularly as the focus of this research has shifted from theoretical questions concerning mechanistic aspects of the association between cognitive bias and emotional vulnerability, to questions that instead concern the clinical efficacy of 'cognitive bias modification' (CBM) procedures. We discuss the kinds of control conditions that have typically been employed in CBM research, illustrating how difficulties can arise when changes in the types of research questions asked are not accompanied by changes in the control conditions employed. Crucially, claims made on the basis of comparing active and control conditions within CBM studies should be restricted to those conclusions allowed by the specific control condition employed. CBM studies aiming to establish clinical utility are likely to require quite different control conditions from CBM studies aiming to illuminate mechanisms. Further, conclusions concerning the clinical utility of CBM interventions cannot necessarily be drawn from studies in which the control condition has been chosen to answer questions concerning mechanisms. Appreciating the need to appropriately alter control conditions in the transition from basic mechanisms-focussed investigations to applied clinical research could greatly facilitate the translational process.

Insulin analogues in type 1 diabetes mellitus: getting better all the time.

PubMed

Mathieu, Chantal; Gillard, Pieter; Benhalima, Katrien

2017-07-01

The treatment of type 1 diabetes mellitus consists of external replacement of the functions of β cells in an attempt to achieve blood levels of glucose as close to the normal range as possible. This approach means that glucose sensing needs to be replaced and levels of insulin need to mimic physiological insulin-action profiles, including basal coverage and changes around meals. Training and educating patients are crucial for the achievement of good glycaemic control, but having insulin preparations with action profiles that provide stable basal insulin coverage and appropriate mealtime insulin peaks helps people with type 1 diabetes mellitus to live active lives without sacrificing tight glycaemic control. Insulin analogues enable patients to achieve this goal, as some have fast action profiles, and some have very slow action profiles, which gives people with type 1 diabetes mellitus the tools to achieve dynamic insulin-action profiles that enable tight glycaemic control with a risk of hypoglycaemia that is lower than that with human short-acting and long-acting insulins. This Review discusses the established and novel insulin analogues that are used to treat patients with type 1 diabetes mellitus and provides insights into the future development of insulin analogues.

The Tumor Suppressor Cdkn3 Is Required for Maintaining the Proper Number of Centrosomes by Regulating the Centrosomal Stability of Mps1.

PubMed

Srinivas, Vinayaka; Kitagawa, Mayumi; Wong, Jasmine; Liao, Pei-Ju; Lee, Sang Hyun

2015-11-24

Supernumerary centrosomes promote the assembly of abnormal spindles in many human cancers. The observation that modest changes in the centrosomal levels of Mps1 kinase can cause centrosome overduplication in human cells suggests the existence of a regulatory system that may tightly control its centrosomal stability. Here, we show that Cdkn3, a Cdk-associated phosphatase, prevents Mps1-mediated centrosome overduplication. We identify Cdkn3 as a direct binding partner of Mps1. The interaction between Mps1 and Cdkn3 is required for Mps1 to recruit Cdkn3 to centrosomes. Subsequently, Mps1-bound Cdkn3 forms a regulatory system that controls the centrosomal levels of Mps1 through proteasome-mediated degradation and thereby prevents Mps1-mediated centrosome overduplication. Conversely, knockdown of Cdkn3 stabilizes Mps1 at centrosomes, which promotes centrosome overduplication. We suggest that Mps1 and Cdkn3 form a self-regulated feedback loop at centrosomes to tightly control the centrosomal levels of Mps1, which prevents centrosome overduplication in human cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Software requirements flow-down and preliminary software design for the G-CLEF spectrograph

NASA Astrophysics Data System (ADS)

Evans, Ian N.; Budynkiewicz, Jamie A.; DePonte Evans, Janet; Miller, Joseph B.; Onyuksel, Cem; Paxson, Charles; Plummer, David A.

2016-08-01

The Giant Magellan Telescope (GMT)-Consortium Large Earth Finder (G-CLEF) is a fiber-fed, precision radial velocity (PRV) optical echelle spectrograph that will be the first light instrument on the GMT. The G-CLEF instrument device control subsystem (IDCS) provides software control of the instrument hardware, including the active feedback loops that are required to meet the G-CLEF PRV stability requirements. The IDCS is also tasked with providing operational support packages that include data reduction pipelines and proposal preparation tools. A formal, but ultimately pragmatic approach is being used to establish a complete and correct set of requirements for both the G-CLEF device control and operational support packages. The device control packages must integrate tightly with the state-machine driven software and controls reference architecture designed by the GMT Organization. A model-based systems engineering methodology is being used to develop a preliminary design that meets these requirements. Through this process we have identified some lessons that have general applicability to the development of software for ground-based instrumentation. For example, tasking an individual with overall responsibility for science/software/hardware integration is a key step to ensuring effective integration between these elements. An operational concept document that includes detailed routine and non- routine operational sequences should be prepared in parallel with the hardware design process to tie together these elements and identify any gaps. Appropriate time-phasing of the hardware and software design phases is important, but revisions to driving requirements that impact software requirements and preliminary design are inevitable. Such revisions must be carefully managed to ensure efficient use of resources.

Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair - Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial.

PubMed

Moppett, Iain Keith; White, Stuart; Griffiths, Richard; Buggy, Donal

2017-07-25

Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-morbidities. This is consistent with data derived from the wider surgical population, where magnitude and duration of hypotension are associated with mortality and peri-operative complications. However, there are no trial to data to support more aggressive blood pressure control. We are conducting a three-centre, randomised, double-blinded pilot study in three hospitals in the United Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation will be done using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be aged >70 years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to give informed consent and admitted directly through the emergency department with a fractured neck of the femur requiring operative repair. Patients randomised to tight blood pressure control or avoidance of intra-operative hypotension will receive active treatment as required to maintain both of the following: systolic arterial blood pressure >80% of baseline pre-operative value and mean arterial pressure >75 mmHg throughout. All participants will receive standard hospital care, including spinal or general anaesthesia, at the discretion of the clinical team. The primary outcome is a composite of the presence or absence of defined cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial injury, stroke, acute kidney injury, delirium). Secondary endpoints will include the defined individual morbidities, mortality, early mobility and discharge to usual residence. This is a small-scale pilot study investigating the feasibility of a trial of tight intra-operative blood pressure control in a frail elderly patient group with known high morbidity and mortality. Positive findings will provide the basis for a larger-scale study. ISRCTN Registry identifier: ISRCTN89812075 . Registered on 30 August 2016.

Exploring Higher Education Trustee Perception of Institutional Culture

ERIC Educational Resources Information Center

Murnane, Ryan P.

2017-01-01

Today's higher education landscape is in a state of flux as institutions adjust their processes and internal culture to effectively adapt to influential, shifting forces. The complex nature of higher education institutions consists of loosely and tightly coupled components designed to educate students and produce scholarly research while governed…

Toward a Science of Learning Games

ERIC Educational Resources Information Center

Howard-Jones, Paul; Demetriou, Skevi; Bogacz, Rafal; Yoo, Jee H.; Leonards, Ute

2011-01-01

Reinforcement learning involves a tight coupling of reward-associated behavior and a type of learning that is very different from that promoted by education. However, the emerging understanding of its underlying processes may help derive principles for effective learning games that have, until now, been elusive. This article first reviews findings…

An Examination of the Navy’s Future Naval Capability Technology Transition Process

DTIC Science & Technology

2004-12-01

managing innovation , innovation is a lot of art and a little science. b. Innovation Skills The President of the small manufacturing company...34 managing innovation ", the breakthroughs do not come from managed, tightly structured programs. The development of those breakthroughs into truly useful

Enhanced resistance to soybean cyst nematode Heterodera glycines in transgenic soybean by silencing putative CLE receptors

USDA-ARS?s Scientific Manuscript database

CLE peptides are small extracellular proteins important in regulating plant meristematic activity through the CLE-receptor kinase-WOX signaling module. Stem cell pools in the SAM (shoot apical meristem), RAM (root apical meristem), and vascular cambium are tightly controlled by CLE signaling pathway...

10 CFR 36.61 - Inspection and maintenance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... for radioactive contamination in pool water required by § 36.59(b) using a radiation check source, if... emergency source return control required by § 36.31(c). (7) Leak-tightness of systems through which pool water circulates (visual inspection). (8) Operability of the heat and smoke detectors and extinguisher...

Distance Education and Corporate Training in Brazil: Regulations and Interrelationships

ERIC Educational Resources Information Center

Porto, Stella C. S.; Berge, Zane L.

2008-01-01

Distance education in Brazil has evolved more slowly than distance education offerings in other developing countries. This is because all aspects of Brazil's publicly-funded educational system are excessively regulated, highly bureaucratic, and tightly centralized. Such highly centralized bureaucracy and strict control has resulted in tremendous…

Forty-five years after Broadbent (1958): still no identification without attention

NASA Technical Reports Server (NTRS)

Lachter, Joel; Forster, Kenneth I.; Ruthruff, Eric

2004-01-01

According to D. E. Broadbent's (1958) selective filter theory, people do not process unattended stimuli beyond the analysis of basic physical properties. This theory was later rejected on the basis of numerous findings that people identify irrelevant (and supposedly unattended) stimuli. A careful review of this evidence, however, reveals strong reasons to doubt that these irrelevant stimuli were in fact unattended. This review exposed a clear need for new experiments with tight control over the locus of attention. The authors present 5 such experiments using a priming paradigm. When steps were taken to ensure that irrelevant stimuli were not attended, these stimuli produced no priming effects. Hence, the authors found no evidence that unattended stimuli can be identified. The results support a modern version of Broadbent's selective theory, updated to reflect recent research advances. 2004 APA.

Optical studies of oxidative stress in pulmonary artery endothelial cells

NASA Astrophysics Data System (ADS)

Ghanian, Zahra; Sepehr, Reyhaneh; Eis, Annie; Kondouri, Ganesh; Ranji, Mahsa

2015-03-01

Reactive oxygen species (ROS) play an essential role in facilitating signal transduction processes within the cell and modulating the injuries. However, the generation of ROS is tightly controlled both spatially and temporally within the cell, making the study of ROS dynamics particularly difficult. This study present a novel protocol to quantify the dynamic of the mitochondrial superoxide as a precursor of reactive oxygen species. To regulate the mitochondrial superoxide level, metabolic perturbation was induced by administration of potassium cyanide (KCN). The presented method was able to monitor and measure the superoxide production rate over time. Our results demonstrated that the metabolic inhibitor, potassium cyanide (KCN) induced a significant increase in the rate of superoxide production in mitochondria of fetal pulmonary artery endothelial cells (FPAEC). Presented method sets the stage to study different ROS mediated injuries in vitro.

Barriers and Facilitators to Implementing Functional Family Therapy in a Community Setting: Client and Practitioner Perspectives.

PubMed

McPherson, Kerri E; Kerr, Susan; Casey, Beth; Marshall, John

2017-10-01

While Functional Family Therapy (FFT) is known to be effective in addressing adolescent behavioral problems, there has been little exploration of issues relevant to its transport from the tightly controlled setting of clinical trials into routine service delivery. This study sought the views of key stakeholders, clients, and practitioners, on barriers and facilitators to the successful implementation of FFT. Undertaken in a community setting in Scotland, interviews were carried out with 12 adolescents, 14 parents/caregivers, and 6 practitioners. Results focus on: Referral process and pre-intervention contact; Engagement of families; Structure and delivery; Organizational factors. Although barriers to engagement were identified, FFT was viewed as an acceptable, appropriate and feasible intervention with the potential to improve adolescent wellbeing in 'real-world' settings. © 2017 American Association for Marriage and Family Therapy.

Mitochondrial metals as a potential therapeutic target in neurodegeneration

PubMed Central

Grubman, A; White, A R; Liddell, J R

2014-01-01

Transition metals are critical for enzyme function and protein folding, but in excess can mediate neurotoxic oxidative processes. As mitochondria are particularly vulnerable to oxidative damage due to radicals generated during ATP production, mitochondrial biometal homeostasis must therefore be tightly controlled to safely harness the redox potential of metal enzyme cofactors. Dysregulation of metal functions is evident in numerous neurological disorders including Alzheimer's disease, stroke, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and Friedrich's ataxia. This review describes the mitochondrial metal defects in these disorders and highlights novel metal-based therapeutic approaches that target mitochondrial metal homeostasis in neurological disorders. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24206195

Epigenetic dysregulation in cognitive disorders.

PubMed

Gräff, Johannes; Mansuy, Isabelle M

2009-07-01

Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of 'epigenetic medicine' as a promising cure.

Fundamental mechanisms of telomerase action in yeasts and mammals: understanding telomeres and telomerase in cancer cells.

PubMed

Armstrong, Christine A; Tomita, Kazunori

2017-03-01

Aberrant activation of telomerase occurs in 85-90% of all cancers and underpins the ability of cancer cells to bypass their proliferative limit, rendering them immortal. The activity of telomerase is tightly controlled at multiple levels, from transcriptional regulation of the telomerase components to holoenzyme biogenesis and recruitment to the telomere, and finally activation and processivity. However, studies using cancer cell lines and other model systems have begun to reveal features of telomeres and telomerase that are unique to cancer. This review summarizes our current knowledge on the mechanisms of telomerase recruitment and activation using insights from studies in mammals and budding and fission yeasts. Finally, we discuss the differences in telomere homeostasis between normal cells and cancer cells, which may provide a foundation for telomere/telomerase targeted cancer treatments. © 2017 The Authors.

Conformation-controlled binding kinetics of antibodies

NASA Astrophysics Data System (ADS)

Galanti, Marta; Fanelli, Duccio; Piazza, Francesco

2016-01-01

Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.

Genome-wide overlap in the binding location and function of chromatin-remodeling proteins | Center for Cancer Research

Cancer.gov

A single strand of DNA can stretch several meters. Yet dozens of these strands, which can be one-tenth as thin as a human hair, need to fit into the cell’s nucleus. To pack those strands into such a small space, DNA tightly winds itself around histone proteins, forming nucleosomes that are strung together into complexes called chromatin. Beyond efficiently packaging DNA, chromatin also regulates how and when DNA is used. The condensed coiling of the genome makes it inaccessible to proteins such as RNA polymerases and transcription factors that control the expression of specific genes. For DNA to become accessible local chromatin regions need to be “opened” up. This process is called chromatin remodeling, and involves the ATP-dependent removal, ejection, or restructuring of nucleosomes by large, multiprotein enzymes.

Regulation of Hedgehog Signalling Inside and Outside the Cell

PubMed Central

Ramsbottom, Simon A.; Pownall, Mary E.

2016-01-01

The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis. Many levels of regulation exist that control the release, reception, and interpretation of the hedgehog signal. The fatty nature of the Shh ligand means that it tends to associate tightly with the cell membrane, and yet it is known to act as a morphogen that diffuses to elicit pattern formation. Heparan sulfate proteoglycans (HSPGs) play a major role in the regulation of Hh distribution outside the cell. Inside the cell, the primary cilium provides an important hub for processing the Hh signal in vertebrates. This review will summarise the current understanding of how the Hh pathway is regulated from ligand production, release, and diffusion, through to signal reception and intracellular transduction. PMID:27547735

Shallow Melt Apparatus for Semicontinuous Czochralski Crystal Growth

DOEpatents

Wang, T.; Ciszek, T. F.

2006-01-10

In a single crystal pulling apparatus for providing a Czochralski crystal growth process, the improvement of a shallow melt crucible (20) to eliminate the necessity supplying a large quantity of feed stock materials that had to be preloaded in a deep crucible to grow a large ingot, comprising a gas tight container a crucible with a deepened periphery (25) to prevent snapping of a shallow melt and reduce turbulent melt convection; source supply means for adding source material to the semiconductor melt; a double barrier (23) to minimize heat transfer between the deepened periphery (25) and the shallow melt in the growth compartment; offset holes (24) in the double barrier (23) to increase melt travel length between the deepened periphery (25) and the shallow growth compartment; and the interface heater/heat sink (22) to control the interface shape and crystal growth rate.

Advanced teleprocessing systems

NASA Astrophysics Data System (ADS)

Kleinrock, L.; Gerla, M.

1982-09-01

This Annual Technical Report covers research covering the period from October 1, 1981 to September 30, 1982. This contract has three primary designated research areas: packet radio systems, resource sharing and allocation, and distributed processing and control. This report contains abstracts of publications which summarize research results in these areas followed by the main body of the report which is devoted to a study of channel access protocols that are executed by the nodes of a network to schedule their transmissions on multi-access broadcast channel. In particular the main body consists of a Ph.D. dissertation, Channel Access Protocols for Multi-Hop Broadcast Packet Radio Networks. This work discusses some new channel access protocols useful for mobile radio networks. Included is an analysis of slotted ALOHA and some tight bounds on the performance of all possible protocols in a mobile environment.

More than a Tad: spatiotemporal control of Caulobacter pili.

PubMed

Mignolet, Johann; Panis, Gaël; Viollier, Patrick H

2018-04-01

The Type IV pilus (T4P) is a powerful and sophisticated bacterial nanomachine involved in numerous cellular processes, including adhesion, DNA uptake and motility. Aside from the well-described subtype T4aP of the Gram-negative genera, including Myxococcus, Pseudomonas and Neisseria, the Tad (tight adherence) pilus secretion system re-shuffles homologous parts from other secretion systems along with uncharacterized components into a new type of protein translocation apparatus. A representative of the Tad apparatus, the Caulobacter crescentus pilus assembly (Cpa) machine is built exclusively at the newborn cell pole once per cell cycle. Recent comprehensive genetic analyses unearthed a myriad of spatiotemporal determinants acting on the Tad/Cpa system, many of which are conserved in other α-proteobacteria, including obligate intracellular pathogens and symbionts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transferable tight-binding model for strained group IV and III-V materials and heterostructures

NASA Astrophysics Data System (ADS)

Tan, Yaohua; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy B.; Klimeck, Gerhard

2016-07-01

It is critical to capture the effect due to strain and material interface for device level transistor modeling. We introduce a transferable s p3d5s* tight-binding model with nearest-neighbor interactions for arbitrarily strained group IV and III-V materials. The tight-binding model is parametrized with respect to hybrid functional (HSE06) calculations for varieties of strained systems. The tight-binding calculations of ultrasmall superlattices formed by group IV and group III-V materials show good agreement with the corresponding HSE06 calculations. The application of the tight-binding model to superlattices demonstrates that the transferable tight-binding model with nearest-neighbor interactions can be obtained for group IV and III-V materials.

Joint digital signal processing for superchannel coherent optical communication systems.

PubMed

Liu, Cheng; Pan, Jie; Detwiler, Thomas; Stark, Andrew; Hsueh, Yu-Ting; Chang, Gee-Kung; Ralph, Stephen E

2013-04-08

Ultra-high-speed optical communication systems which can support ≥ 1Tb/s per channel transmission will soon be required to meet the increasing capacity demand. However, 1Tb/s over a single carrier requires either or both a high-level modulation format (i.e. 1024QAM) and a high baud rate. Alternatively, grouping a number of tightly spaced "sub-carriers" to form a terabit superchannel increases channel capacity while minimizing the need for high-level modulation formats and high baud rate, which may allow existing formats, baud rate and components to be exploited. In ideal Nyquist-WDM superchannel systems, optical subcarriers with rectangular spectra are tightly packed at a channel spacing equal to the baud rate, thus achieving the Nyquist bandwidth limit. However, in practical Nyquist-WDM systems, precise electrical or optical control of channel spectra is required to avoid strong inter-channel interference (ICI). Here, we propose and demonstrate a new "super receiver" architecture for practical Nyquist-WDM systems, which jointly detects and demodulates multiple channels simultaneously and mitigates the penalties associated with the limitations of generating ideal Nyquist-WDM spectra. Our receiver-side solution relaxes the filter requirements imposed on the transmitter. Two joint DSP algorithms are developed for linear ICI cancellation and joint carrier-phase recovery. Improved system performance is observed with both experimental and simulation data. Performance analysis under different system configurations is conducted to demonstrate the feasibility and robustness of the proposed joint DSP algorithms.

The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial

PubMed Central

Mujagic, Zlatan; de Vos, Paul; Boekschoten, Mark V.; Govers, Coen; Pieters, Harm-Jan H. M.; de Wit, Nicole J. W.; Bron, Peter A.; Masclee, Ad A. M.; Troost, Freddy J.

2017-01-01

The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gut mucosal gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP104448, TIFN101 or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06 ± 0.04 to 0.10 ± 0.06, p = 0.001), but was not significantly affected by the bacterial interventions. However, analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated gene transcription pathways related to cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific gene transcriptional effects on repair processes in the compromised intestine of healthy subjects. PMID:28045137

Single-phase and two-phase flow properties of mesaverde tight sandstone formation; random-network modeling approach

NASA Astrophysics Data System (ADS)

Bashtani, Farzad; Maini, Brij; Kantzas, Apostolos

2016-08-01

3D random networks are constructed in order to represent the tight Mesaverde formation which is located in north Wyoming, USA. The porous-space is represented by pore bodies of different shapes and sizes which are connected to each other by pore throats of varying length and diameter. Pore bodies are randomly distributed in space and their connectivity varies based on the connectivity number distribution which is used in order to generate the network. Network representations are then validated using publicly available mercury porosimetry experiments. The network modeling software solves the fundamental equations of two-phase immiscible flow incorporating wettability and contact angle variability. Quasi-static displacement is assumed. Single phase macroscopic properties (porosity, permeability) are calculated and whenever possible are compared to experimental data. Using this information drainage and imbibition capillary pressure, and relative permeability curves are predicted and (whenever possible) compared to experimental data. The calculated information is grouped and compared to available literature information on typical behavior of tight formations. Capillary pressure curve for primary drainage process is predicted and compared to experimental mercury porosimetry in order to validate the virtual porous media by history matching. Relative permeability curves are also calculated and presented.

Technical tip: tightrope fixation of neer type II distal clavicle fracture supported by a case series.

PubMed

Haque, Syed; Khan, Anwar; Sharma, A; Sundararajan, Sabapathy

2014-03-27

We present a case series of 3 patients who underwent a novel technique of tight rope fixation for Neer type II distal clavicle fracture. 2-3 cm incision was made lateral to the fracture site moving inferomedially. Part of the distal end of clavicle was exposed close to fracture site and further dissection was carried out to reveal the coracoid process. Tight rope fixation of the distal ends of clavicle and coracoid was performed to achieve satisfactory fracture reduction on x-ray. 4 weeks of sling with gentle pendulum movement were followed by active shoulder movement exercises. Radiographic union was reached at 6 weeks' time, while the patients achieved proper shoulder functionality 3 months following the operation. Neer type II distal clavicle fractures are characterized by disruption of the coracoclavicular ligament with wide proximal fragment displacement. Overall, type II distal clavicle fractures have a 20-30% nonunion rate if treated non-surgically. Various techniques have been described for the treatment of these fractures, including hook plate and nailing. Tight rope fixation provides proper apposition of the fracture fragments for union by maintaining a reduced coracoclavicular interval.

Multi-layer thin-film electrolytes for metal supported solid oxide fuel cells

NASA Astrophysics Data System (ADS)

Haydn, Markus; Ortner, Kai; Franco, Thomas; Uhlenbruck, Sven; Menzler, Norbert H.; Stöver, Detlev; Bräuer, Günter; Venskutonis, Andreas; Sigl, Lorenz S.; Buchkremer, Hans-Peter; Vaßen, Robert

2014-06-01

A key to the development of metal-supported solid oxide fuel cells (MSCs) is the manufacturing of gas-tight thin-film electrolytes, which separate the cathode from the anode. This paper focuses the electrolyte manufacturing on the basis of 8YSZ (8 mol.-% Y2O3 stabilized ZrO2). The electrolyte layers are applied by a physical vapor deposition (PVD) gas flow sputtering (GFS) process. The gas-tightness of the electrolyte is significantly improved when sequential oxidic and metallic thin-film multi-layers are deposited, which interrupt the columnar grain structure of single-layer electrolytes. Such electrolytes with two or eight oxide/metal layers and a total thickness of about 4 μm obtain leakage rates of less than 3 × 10-4 hPa dm3 s-1 cm-2 (Δp: 100 hPa) at room temperature and therefore fulfill the gas tightness requirements. They are also highly tolerant with respect to surface flaws and particulate impurities which can be present on the graded anode underground. MSC cell tests with double-layer and multilayer electrolytes feature high power densities more than 1.4 W cm-2 at 850 °C and underline the high potential of MSC cells.

A clinically guided approach for improving performance measurement for hypertension.

PubMed

Steinman, Michael A; Lee, Sei J; Peterson, Carolyn A; Fung, Kathy Z; Goldstein, Mary K

2012-05-01

Performance measures often fail to account for legitimate reasons why patients do not achieve recommended treatment targets. We tested a novel performance measurement system for blood pressure (BP) control that was designed to mimic clinical reasoning. This clinically guided approach focuses on (1) exempting patients for whom tight BP control may not be appropriate or feasible and (2) assessing BP over time. Trained abstractors conducted structured chart reviews of 201 adults with hypertension in 2 VA health care systems. Results were compared with traditional methods of performance measurement. Among 201 veterans, 183 (91%) were male, and the mean age was 71±11 years. Using the clinically guided approach, 61 patients (30%) were exempted from performance measurement. The most common reasons for exemption were inadequate opportunity to manage BP (35 patients, 17%) and the use of 4 or more antihypertensive medications (19 patients, 9%). Among patients eligible for performance measurement, there was little agreement on the presence of controlled versus uncontrolled BP when comparing the most recent BP (the traditional approach) with an integrated assessment of BP control (κ 0.14). After accounting for clinically guided exemptions and methods of BP assessment, only 15 of 72 patients (21%) whose last BP was ≥140/90 mm Hg were classified as problematic by the clinically guided approach. Many patients have legitimate reasons for not achieving tight BP control, and the methods used for BP assessment have marked effects on whether a patient is classified as having adequate or inadequate BP control.

Monogamy relations of nonclassical correlations for multi-qubit states

NASA Astrophysics Data System (ADS)

Cheng, Shuming; Liu, Lijun

2018-07-01

Nonclassical correlations have been found useful in many quantum information processing tasks, and various measures have been proposed to quantify these correlations. In this work, we mainly study one of nonclassical correlations, called measurement-induced nonlocality (MIN). First, we establish a close connection between this nonlocal effect and the Bell nonlocality for two-qubit states. Then, we derive a tight monogamy relation of MIN for any pure three-qubit state and provide an alternative way to obtain similar monogamy relations for other nonclassical correlation measures, including squared negativity, quantum discord, and geometric quantum discord. Finally, we find that the tight monogamy relation of MIN is violated by some mixed three-qubit states, however, a weaker monogamy relation of MIN for mixed states and even multi-qubit states is still obtained.

Identification of iron-regulated genes of Bifidobacterium breve UCC2003 as a basis for controlled gene expression

PubMed Central

Cronin, Michelle; Zomer, Aldert; Fitzgerald, Gerald; van Sinderen, Douwe

2012-01-01

Iron is an essential growth factor for virtually all organisms. However, iron is not readily available in most environments and microorganisms have evolved specialized mechanisms, such as the use of siderophores and high-affinity transport systems, to acquire iron when confronted with iron-limiting conditions. In general these systems are tightly regulated to prevent iron-induced toxicity and because they are quite costly to the microbe. Because of this tight regulation we chose to explore the response of Bifidobacterium breve UCC2003 to iron limitation. Through microarray and complementation analyses we identified and characterized a presumed ferrous iron uptake system, encoded by bfeUOB, from B. breve UCC2003 and exploited its regulated transcription to develop an inducible expression system for use in bifidobacteria. PMID:22179149

Alternative Oxidase: A Mitochondrial Respiratory Pathway to Maintain Metabolic and Signaling Homeostasis during Abiotic and Biotic Stress in Plants

PubMed Central

Vanlerberghe, Greg C.

2013-01-01

Alternative oxidase (AOX) is a non-energy conserving terminal oxidase in the plant mitochondrial electron transport chain. While respiratory carbon oxidation pathways, electron transport, and ATP turnover are tightly coupled processes, AOX provides a means to relax this coupling, thus providing a degree of metabolic homeostasis to carbon and energy metabolism. Beside their role in primary metabolism, plant mitochondria also act as “signaling organelles”, able to influence processes such as nuclear gene expression. AOX activity can control the level of potential mitochondrial signaling molecules such as superoxide, nitric oxide and important redox couples. In this way, AOX also provides a degree of signaling homeostasis to the organelle. Evidence suggests that AOX function in metabolic and signaling homeostasis is particularly important during stress. These include abiotic stresses such as low temperature, drought, and nutrient deficiency, as well as biotic stresses such as bacterial infection. This review provides an introduction to the genetic and biochemical control of AOX respiration, as well as providing generalized examples of how AOX activity can provide metabolic and signaling homeostasis. This review also examines abiotic and biotic stresses in which AOX respiration has been critically evaluated, and considers the overall role of AOX in growth and stress tolerance. PMID:23531539

Autophagy in Drosophila ovaries is induced by starvation and is required for oogenesis.

PubMed

Barth, J M I; Szabad, J; Hafen, E; Köhler, K

2011-06-01

Autophagy, an evolutionarily conserved lysosome-mediated degradation, promotes cell survival under starvation and is controlled by insulin/target of rapamycin (TOR) signaling. In Drosophila, nutrient depletion induces autophagy in the fat body. Interestingly, nutrient availability and insulin/TOR signaling also influence the size and structure of Drosophila ovaries, however, the role of nutrient signaling and autophagy during this process remains to be elucidated. Here, we show that starvation induces autophagy in germline cells (GCs) and in follicle cells (FCs) in Drosophila ovaries. This process is mediated by the ATG machinery and involves the upregulation of Atg genes. We further demonstrate that insulin/TOR signaling controls autophagy in FCs and GCs. The analysis of chimeric females reveals that autophagy in FCs, but not in GCs, is required for egg development. Strikingly, when animals lack Atg gene function in both cell types, ovaries develop normally, suggesting that the incompatibility between autophagy-competent GCs and autophagy-deficient FCs leads to defective egg development. As egg morphogenesis depends on a tightly linked signaling between FCs and GCs, we propose a model in which autophagy is required for the communication between these two cell types. Our data establish an important function for autophagy during oogenesis and contributes to the understanding of the role of autophagy in animal development.

Quality standards for real-world research. Focus on observational database studies of comparative effectiveness.

PubMed

Roche, Nicolas; Reddel, Helen; Martin, Richard; Brusselle, Guy; Papi, Alberto; Thomas, Mike; Postma, Dirjke; Thomas, Vicky; Rand, Cynthia; Chisholm, Alison; Price, David

2014-02-01

Real-world research can use observational or clinical trial designs, in both cases putting emphasis on high external validity, to complement the classical efficacy randomized controlled trials (RCTs) with high internal validity. Real-world research is made necessary by the variety of factors that can play an important a role in modulating effectiveness in real life but are often tightly controlled in RCTs, such as comorbidities and concomitant treatments, adherence, inhalation technique, access to care, strength of doctor-caregiver communication, and socio-economic and other organizational factors. Real-world studies belong to two main categories: pragmatic trials and observational studies, which can be prospective or retrospective. Focusing on comparative database observational studies, the process aimed at ensuring high-quality research can be divided into three parts: preparation of research, analyses and reporting, and discussion of results. Key points include a priori planning of data collection and analyses, identification of appropriate database(s), proper outcomes definition, study registration with commitment to publish, bias minimization through matching and adjustment processes accounting for potential confounders, and sensitivity analyses testing the robustness of results. When these conditions are met, observational database studies can reach a sufficient level of evidence to help create guidelines (i.e., clinical and regulatory decision-making).

The contribution of oxidative stress to drug-induced organ toxicity and its detection in vitro and in vivo.

PubMed

Pereira, Claudia V; Nadanaciva, Sashi; Oliveira, Paulo J; Will, Yvonne

2012-02-01

Nowadays the 'redox hypothesis' is based on the fact that thiol/disulfide couples such as glutathione (GSH/GSSG), cysteine (Cys/CySS) and thioredoxin ((Trx-(SH)2/Trx-SS)) are functionally organized in redox circuits controlled by glutathione pools, thioredoxins and other control nodes, and they are not in equilibrium relative to each other. Although ROS can be important intermediates of cellular signaling pathways, disturbances in the normal cellular redox can result in widespread damage to several cell components. Moreover, oxidative stress has been linked to a variety of age-related diseases. In recent years, oxidative stress has also been identified to contribute to drug-induced liver, heart, renal and brain toxicity. This review provides an overview of current in vitro and in vivo methods that can be deployed throughout the drug discovery process. In addition, animal models and noninvasive biomarkers are described. Reducing post-market drug withdrawals is essential for all pharmaceutical companies in a time of increased patient welfare and tight budgets. Predictive screens positioned early in the drug discovery process will help to reduce such liabilities. Although new and more efficient assays and models are being developed, the hunt for biomarkers and noninvasive techniques is still in progress.

A new approach to process control using Instability Index

NASA Astrophysics Data System (ADS)

Weintraub, Jeffrey; Warrick, Scott

2016-03-01

The merits of a robust Statistical Process Control (SPC) methodology have long been established. In response to the numerous SPC rule combinations, processes, and the high cost of containment, the Instability Index (ISTAB) is presented as a tool for managing these complexities. ISTAB focuses limited resources on key issues and provides a window into the stability of manufacturing operations. ISTAB takes advantage of the statistical nature of processes by comparing the observed average run length (OARL) to the expected run length (ARL), resulting in a gap value called the ISTAB index. The ISTAB index has three characteristic behaviors that are indicative of defects in an SPC instance. Case 1: The observed average run length is excessively long relative to expectation. ISTAB > 0 is indicating the possibility that the limits are too wide. Case 2: The observed average run length is consistent with expectation. ISTAB near zero is indicating that the process is stable. Case 3: The observed average run length is inordinately short relative to expectation. ISTAB < 0 is indicating that the limits are too tight, the process is unstable or both. The probability distribution of run length is the basis for establishing an ARL. We demonstrate that the geometric distribution is a good approximation to run length across a wide variety of rule sets. Excessively long run lengths are associated with one kind of defect in an SPC instance; inordinately short run lengths are associated with another. A sampling distribution is introduced as a way to quantify excessively long and inordinately short observed run lengths. This paper provides detailed guidance for action limits on these run lengths. ISTAB as a statistical method of review facilitates automated instability detection. This paper proposes a management system based on ISTAB as an enhancement to more traditional SPC approaches.

Co-optimization of lithographic and patterning processes for improved EPE performance

NASA Astrophysics Data System (ADS)

Maslow, Mark J.; Timoshkov, Vadim; Kiers, Ton; Jee, Tae Kwon; de Loijer, Peter; Morikita, Shinya; Demand, Marc; Metz, Andrew W.; Okada, Soichiro; Kumar, Kaushik A.; Biesemans, Serge; Yaegashi, Hidetami; Di Lorenzo, Paolo; Bekaert, Joost P.; Mao, Ming; Beral, Christophe; Larivière, Stephane

2017-03-01

Complimentary lithography is already being used for advanced logic patterns. The tight pitches for 1D Metal layers are expected to be created using spacer based multiple patterning ArF-i exposures and the more complex cut/block patterns are made using EUV exposures. At the same time, control requirements of CDU, pattern shift and pitch-walk are approaching sub-nanometer levels to meet edge placement error (EPE) requirements. Local variability, such as Line Edge Roughness (LER), Local CDU, and Local Placement Error (LPE), are dominant factors in the total Edge Placement error budget. In the lithography process, improving the imaging contrast when printing the core pattern has been shown to improve the local variability. In the etch process, it has been shown that the fusion of atomic level etching and deposition can also improve these local variations. Co-optimization of lithography and etch processing is expected to further improve the performance over individual optimizations alone. To meet the scaling requirements and keep process complexity to a minimum, EUV is increasingly seen as the platform for delivering the exposures for both the grating and the cut/block patterns beyond N7. In this work, we evaluated the overlay and pattern fidelity of an EUV block printed in a negative tone resist on an ArF-i SAQP grating. High-order Overlay modeling and corrections during the exposure can reduce overlay error after development, a significant component of the total EPE. During etch, additional degrees of freedom are available to improve the pattern placement error in single layer processes. Process control of advanced pitch nanoscale-multi-patterning techniques as described above is exceedingly complicated in a high volume manufacturing environment. Incorporating potential patterning optimizations into both design and HVM controls for the lithography process is expected to bring a combined benefit over individual optimizations. In this work we will show the EPE performance improvement for a 32nm pitch SAQP + block patterned Metal 2 layer by cooptimizing the lithography and etch processes. Recommendations for further improvements and alternative processes will be given.

Beyond Ussing's chambers: contemporary thoughts on integration of transepithelial transport

PubMed Central

Herrmann, Jeremy R.

2016-01-01

In the mid-20th century, Hans Ussing developed a chamber that allowed for the simultaneous measurement of current and labeled probe flux across epithelia. Using frog skin as a model, Ussing used his results to propose mechanisms of transcellular Na+ and K+ transport across apical (exterior/luminal) and basolateral (interior) membranes that is essentially unchanged today. Others took advantage of Ussing's chambers to study mucosal tissues, including bladder and intestines. It quickly became clear that, in some tissues, passive paracellular flux, i.e., across the tight junction, was an important component of overall transepithelial transport. Subsequent work demonstrated that activation of the apical Na+-glucose cotransporter SGLT1 regulated paracellular permeability such that intestinal paracellular transport could coordinate with and amplify transcellular transport. Intermediates in this process include activation of p38 MAPK, the apical Na+/H+ exchanger NHE3, and myosin light chain kinase (MLCK). Investigators then focused on these processes in disease. They found that TNF induces barrier dysfunction via MLCK activation and downstream caveolin-1-dependent endocytosis of the tight junction protein occludin. TNF also inhibited NHE3, and both barrier loss and PKCα-dependent NHE3 inhibition were required for TNF-induced acute diarrhea, emphasizing the interplay between transcellular and paracellular transport. Finally, studies using immune-mediated inflammatory bowel disease models showed that mice lacking epithelial MLCK were initially protected, but became ill as epithelial damage progressed and provided a tight junction-independent means of barrier loss. None of these advances would have been possible without the insights provided by Ussing and others using Ussing's ingenious, and still useful, chambers. PMID:26702131

Fractal Nature of Porosity in Volcanic Tight Reservoirs of the Santanghu Basin and its Relationship to Pore Formation Processes

NASA Astrophysics Data System (ADS)

Wang, Weiming; Wang, Zhixuan; Chen, Xuan; Long, Fei; Lu, Shuangfang; Liu, Guohong; Tian, Weichao; Su, Yue

In this paper, in a case study of Santanghu Basin in China, the morphological characteristics and size distribution of nanoscale pores in the volcanic rocks of the Haerjiawu Formation were investigated using the results of low temperature nitrogen adsorption experiments. This research showed that within the target layer, a large number of nanoscale, eroded pores showed an “ink bottle” morphology with narrow pore mouths and wide bodies. The fractal dimension of pores increases gradually with increasing depth. Moreover, as fractal dimension increases, BET-specific surface area gradually increases, average pore diameter decreases and total pore volume gradually increases. The deeper burial of the Haerjiawu volcanic rocks in the Santanghu Basin leads to more intense erosion by organic acids derived from the basin’s source rocks. Furthermore, the internal surface roughness of these corrosion pores results in poor connectivity. As stated above, the corrosion process is directly related to the organic acids generated by the source rock of the interbedded volcanic rocks. The deeper the reservoir, the more the organic acids being released from the source rock. However, due to the fact that the Haerjiawu volcanic rocks are tight reservoirs and have complicated pore-throat systems, while organic acids dissolve unstable minerals such as feldspars which improve the effective reservoir space; the dissolution of feldspars results in the formation of new minerals, which cannot be expelled from the tight reservoirs. They are instead precipitated in the fine pore throats, thereby reducing pore connectivity, while enhancing reservoir micro-preservation conditions.

In Vitro Evaluation of the Impact of the Probiotic E. coli Nissle 1917 on Campylobacter jejuni's Invasion and Intracellular Survival in Human Colonic Cells.

PubMed

Helmy, Yosra A; Kassem, Issmat I; Kumar, Anand; Rajashekara, Gireesh

2017-01-01

Campylobacter jejuni is a leading cause of bacterial food poisoning in humans. Due to the rise in antibiotic-resistant Campylobacter , there exists a need to develop antibiotic-independent interventions to control infections in humans. Here, we evaluated the impact of Escherichia coli Nissle 1917 (EcN), a probiotic strain, on C. jejuni's invasion and intracellular survival in polarized human colonic cells (HT-29). To further understand how EcN mediates its impact, the expression of 84 genes associated with tight junctions and cell adhesion was profiled in HT-29 cells after treatment with EcN and challenge with C. jejuni . The pre-treatment of polarized HT-29 cells with EcN for 4 h showed a significant effect on C. jejuni 's invasion (∼2 log reduction) of the colonic cells. Furthermore, no intracellular C. jejuni were recovered from EcN pre-treated HT-29 cells at 24 h post-infection. Other probiotic strains tested had no significant impact on C. jejuni invasion and intracellular survival. C. jejuni decreased the expression of genes associated with epithelial cells permeability and barrier function in untreated HT-29 cells. However, EcN positively affected the expression of genes that are involved in enhanced intestinal barrier function, decreased cell permeability, and increased tight junction integrity. The results suggest that EcN impedes C. jejuni invasion and subsequent intracellular survival by affecting HT-29 cells barrier function and tight junction integrity. We conclude that EcN might be a viable alternative for controlling C. jejuni infections.

Possible Involvement of Tight Junctions, Extracellular Matrix and Nuclear Receptors in Epithelial Differentiation

PubMed Central

Ichikawa-Tomikawa, Naoki; Sugimoto, Kotaro; Satohisa, Seiro; Nishiura, Keisuke; Chiba, Hideki

2011-01-01

Tight junctions are intercellular junctions localized at the most apical end of the lateral plasma membrane. They consist of four kinds of transmembrane proteins (occludin, claudins, junctional adhesion molecules, and tricellulin) and huge numbers of scaffolding proteins and contribute to the paracellular barrier and fence function. The mutation and deletion of these proteins impair the functions of tight junctions and cause various human diseases. In this paper, we provide an overview of recent studies on transmembrane proteins of tight junctions and highlight the functional significance of tight junctions, extracellular matrix, and nuclear receptors in epithelial differentiation. PMID:22162632

Particle dynamics and pair production in tightly focused standing wave

NASA Astrophysics Data System (ADS)

Jirka, M.; Klimo, O.; Vranić, M.; Weber, S.; Korn, G.

2017-05-01

With the advent of 10 PW laser facilities, new regimes of laser-matter interaction are opening since effects of quantum electrodynamics, such as electron-positron pair production and cascade development, start to be important. The dynamics of light charged particles, such as electrons and positrons, is affected by the radiation reaction force. This effect can strongly influence the interaction of intense laser pulses with matter since it lowers the energy of emitting particles and transforms their energy to the gamma radiation. Consequently, electron-positron pairs can be generated via Breit-Wheeler process. To study this new regime of interaction, numerical simulations are required. With their help it is possible to predict and study quantum effects which may occur in future experiments at modern laser facilities. In this work we present results of electron interaction with an intense standing wave formed by two colliding laser pulses. Due to the necessity to achieve ultra intense laser field, the laser beam has to be focused to a μm-diameter spot. Since the paraxial approximation is not valid for tight focusing, the appropriate model describing the tightly focused laser beam has to be employed. In tightly focused laser beam the longitudinal component of the electromagnetic field becomes significant and together with the ponderomotive force they affect the dynamics of interacting electrons and also newly generated Breit-Wheeler electron-positron pairs. Using the Particle-In-Cell code we study electron dynamics, gamma radiation and pair production in such a configuration for linear polarization and different types of targets.

Coronal plane radiographic evaluation of the single TightRope technique in the treatment of acute acromioclavicular joint injury.

PubMed

Yi, Young; Kim, Jeong Woo

2015-10-01

This study aimed to demonstrate the technical aspects of the single TightRope (Arthrex, Naples, FL, USA) procedure for acute acromioclavicular-coracoclavicular joint dislocation, identify the predictive factors influencing its outcome, and assess and validate the significance of specific radiologic parameters. We reviewed true anteroposterior shoulder radiographs of 62 consecutive patients who had undergone surgical reconstruction using TightRope for an acute acromioclavicular-coracoclavicular injury. All patients were followed up for at least 12 months between October 2009 and March 2012 and were divided into dissociated or nondissociated groups according to their surgical outcome. We measured the clavicle tunnel anteroposterior angle, distal clavicular tunnel placement, and tunnel-to-medial coracoid ratio, and compared the parameters in each group after a satisfactory intraclass correlation coefficient reliability test result. The angles of patients in the dissociated group were more acute compared with the angles of those in the nondissociated group, which were perpendicular, as verified statistically using the paired t test. The difference in the distal clavicular tunnel placement and tunnel-to-medial coracoid ratio between the groups was not significant. Therefore, tunnel placement is not influenced by coracoclavicular dissociation. The clavicle tunnel anteroposterior angle can be used as a predictor of surgical outcome in coracoclavicular augmentation surgery. The surgeon should strive to place a perpendicular hole from the clavicle to the coracoid process for the TightRope fixation to enable a successful reconstruction of the acute acromioclavicular-coracoclavicular injury. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Multi-Faceted Functions of Secretory IgA at Mucosal Surfaces

PubMed Central

Corthésy, Blaise

2013-01-01

Secretory IgA (SIgA) plays an important role in the protection and homeostatic regulation of intestinal, respiratory, and urogenital mucosal epithelia separating the outside environment from the inside of the body. This primary function of SIgA is referred to as immune exclusion, a process that limits the access of numerous microorganisms and mucosal antigens to these thin and vulnerable mucosal barriers. SIgA has been shown to be involved in avoiding opportunistic pathogens to enter and disseminate in the systemic compartment, as well as tightly controlling the necessary symbiotic relationship existing between commensals and the host. Clearance by peristalsis appears thus as one of the numerous mechanisms whereby SIgA fulfills its function at mucosal surfaces. Sampling of antigen-SIgA complexes by microfold (M) cells, intimate contact occurring with Peyer’s patch dendritic cells (DC), down-regulation of inflammatory processes, modulation of epithelial, and DC responsiveness are some of the recently identified processes to which the contribution of SIgA has been underscored. This review aims at presenting, with emphasis at the biochemical level, how the molecular complexity of SIgA can serve these multiple and non-redundant modes of action. PMID:23874333

A viral deubiquitylating enzyme targets viral RNA-dependent RNA polymerase and affects viral infectivity

PubMed Central

Chenon, Mélanie; Camborde, Laurent; Cheminant, Soizic; Jupin, Isabelle

2012-01-01

Selective protein degradation via the ubiquitin-proteasome system (UPS) plays an essential role in many major cellular processes, including host–pathogen interactions. We previously reported that the tightly regulated viral RNA-dependent RNA polymerase (RdRp) of the positive-strand RNA virus Turnip yellow mosaic virus (TYMV) is degraded by the UPS in infected cells, a process that affects viral infectivity. Here, we show that the TYMV 98K replication protein can counteract this degradation process thanks to its proteinase domain. In-vitro assays revealed that the recombinant proteinase domain is a functional ovarian tumour (OTU)-like deubiquitylating enzyme (DUB), as is the 98K produced during viral infection. We also demonstrate that 98K mediates in-vivo deubiquitylation of TYMV RdRp protein—its binding partner within replication complexes—leading to its stabilization. Finally, we show that this DUB activity contributes to viral infectivity in plant cells. The identification of viral RdRp as a specific substrate of the viral DUB enzyme thus reveals the intricate interplay between ubiquitylation, deubiquitylation and the interaction between viral proteins in controlling levels of RdRp and viral infectivity. PMID:22117220

Sordaria macrospora, a model organism to study fungal cellular development.

PubMed

Engh, Ines; Nowrousian, Minou; Kück, Ulrich

2010-12-01

During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three-dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. Copyright © 2010 Elsevier GmbH. All rights reserved.

Improving the Quality of Hot Stamping Parts with Innovative Press Technology and Inline Process Control

NASA Astrophysics Data System (ADS)

Vollmer, R.; Palm, C.

2017-09-01

The increasing number of hot stamped parts in the automotive industry is challenging different process areas. This paper presents a method how to improve the production rates over the whole life cycle of a hot forming part. In the core element of a hot forming line, the hydraulic press, mainly two processing steps are performed. Forming and quenching of the sheet metal part. In addition to the forming operation, it is inevitable to optimize the quenching condition in the bottom dead centre in order to reach a fully martensitic structure and tight geometrical tolerances of the part. Deviations in the blank thickness, tool wear, polishing of classical tools impair the quenching condition and therefore the part quality over the time. A new press and tool design has been developed to counter this effect by providing homogenous contact pressure over the whole die. Especially with a multi cavity tool, the new method is advantageous. Test series have shown that the new tool and press concept can produce parts with a blank thickness of 1.0 mm within 8.0 s cycle time. The so called PCH flex principle makes it possible to produce such high output rates under reliable conditions.

Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis

PubMed Central

Vanhollebeke, Benoit; Stone, Oliver A; Bostaille, Naguissa; Cho, Chris; Zhou, Yulian; Maquet, Emilie; Gauquier, Anne; Cabochette, Pauline; Fukuhara, Shigetomo; Mochizuki, Naoki; Nathans, Jeremy; Stainier, Didier YR

2015-01-01

Despite the critical role of endothelial Wnt/β-catenin signaling during central nervous system (CNS) vascularization, how endothelial cells sense and respond to specific Wnt ligands and what aspects of the multistep process of intra-cerebral blood vessel morphogenesis are controlled by these angiogenic signals remain poorly understood. We addressed these questions at single-cell resolution in zebrafish embryos. We identify the GPI-anchored MMP inhibitor Reck and the adhesion GPCR Gpr124 as integral components of a Wnt7a/Wnt7b-specific signaling complex required for brain angiogenesis and dorsal root ganglia neurogenesis. We further show that this atypical Wnt/β-catenin signaling pathway selectively controls endothelial tip cell function and hence, that mosaic restoration of single wild-type tip cells in Wnt/β-catenin-deficient perineural vessels is sufficient to initiate the formation of CNS vessels. Our results identify molecular determinants of ligand specificity of Wnt/β-catenin signaling and provide evidence for organ-specific control of vascular invasion through tight modulation of tip cell function. DOI: http://dx.doi.org/10.7554/eLife.06489.001 PMID:26051822