Mitochondrial redox signaling by p66Shc is involved in regulating androgenic growth stimulation of human prostate cancer cells

PubMed Central

Veeramani, S; Yuan, T-C; Lin, F-F; Lin, M-F

2009-01-01

p66Shc is shown to negatively regulate the life span in mice through reactive oxygen species (ROS) production. Recent reports, however, revealed that p66Shc protein level is significantly elevated in several human cancer tissues and growth-stimulated carcinoma cells, suggesting a mitogenic and carcinogenic role for p66Shc. In this communication, we demonstrate for the first time that p66Shc mediates androgenic growth signals in androgen-sensitive human prostate cancer cells through mitochondrial ROS production. Growth stimulation of prostate cancer cells with 5α-dihydrotestosterone (DHT) is accompanied by increased p66Shc level and ROS production, which is abolished by antioxidant treatments. However, antioxidant treatments do not affect the transcriptional activity of androgen receptor (AR) as observed by its inability to block DHT-induced prostate-specific antigen expression, an AR-dependent correlate of prostate cancer progression. Elevated expression of p66Shc by cDNA transfection increases the basal cell proliferation and, thus, reduces additional DHT-induced cell proliferation. Furthermore, DHT increases the translocation of p66Shc into mitochondria and its interaction with cytochrome c. Conversely, both redox-negative p66Shc mutant (W134F), which is deficient in cytochrome c interaction, and p66Shc small interfering RNA decrease DHT-induced cell proliferation. These results collectively reveal a novel role for p66Shc–ROS pathway in androgen-induced prostate cancer cell proliferation and, thus, may play a role in early prostate carcinogenesis. PMID:18504439

Dual Role of Endothelial Nitric Oxide Synthase in Oxidized LDL-Induced, p66Shc-Mediated Oxidative Stress in Cultured Human Endothelial Cells

PubMed Central

Shi, Yi; Lüscher, Thomas F.; Camici, Giovanni G.

2014-01-01

Background The aging gene p66Shc, is an important mediator of oxidative stress-induced vascular dysfunction and disease. In cultured human aortic endothelial cells (HAEC), p66Shc deletion increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability via protein kinase B. However, the putative role of the NO pathway on p66Shc activation remains unclear. This study was designed to elucidate the regulatory role of the eNOS/NO pathway on p66Shc activation. Methods and Results Incubation of HAEC with oxidized low density lipoprotein (oxLDL) led to phosphorylation of p66Shc at Ser-36, resulting in an enhanced production of superoxide anion (O2 -). In the absence of oxLDL, inhibition of eNOS by small interfering RNA or L-NAME, induced p66Shc phosphorylation, suggesting that basal NO production inhibits O2 - production. oxLDL-induced, p66Shc-mediated O2- was prevented by eNOS inhibition, suggesting that when cells are stimulated with oxLDL eNOS is a source of reactive oxygen species. Endogenous or exogenous NO donors, prevented p66Shc activation and reduced O2- production. Treatment with tetrahydrobiopterin, an eNOS cofactor, restored eNOS uncoupling, prevented p66Shc activation, and reduced O2- generation. However, late treatment with tetrahydropterin did not yield the same result suggesting that eNOS uncoupling is the primary source of reactive oxygen species. Conclusions The present study reports that in primary cultured HAEC treated with oxLDL, p66Shc-mediated oxidative stress is derived from eNOS uncoupling. This finding contributes novel information on the mechanisms of p66Shc activation and its dual interaction with eNOS underscoring the importance eNOS uncoupling as a putative antioxidant therapeutical target in endothelial dysfunction as observed in cardiovascular disease. PMID:25247687

Dual role of endothelial nitric oxide synthase in oxidized LDL-induced, p66Shc-mediated oxidative stress in cultured human endothelial cells.

PubMed

Shi, Yi; Lüscher, Thomas F; Camici, Giovanni G

2014-01-01

The aging gene p66Shc, is an important mediator of oxidative stress-induced vascular dysfunction and disease. In cultured human aortic endothelial cells (HAEC), p66Shc deletion increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability via protein kinase B. However, the putative role of the NO pathway on p66Shc activation remains unclear. This study was designed to elucidate the regulatory role of the eNOS/NO pathway on p66Shc activation. Incubation of HAEC with oxidized low density lipoprotein (oxLDL) led to phosphorylation of p66Shc at Ser-36, resulting in an enhanced production of superoxide anion (O2-). In the absence of oxLDL, inhibition of eNOS by small interfering RNA or L-NAME, induced p66Shc phosphorylation, suggesting that basal NO production inhibits O2- production. oxLDL-induced, p66Shc-mediated O2- was prevented by eNOS inhibition, suggesting that when cells are stimulated with oxLDL eNOS is a source of reactive oxygen species. Endogenous or exogenous NO donors, prevented p66Shc activation and reduced O2- production. Treatment with tetrahydrobiopterin, an eNOS cofactor, restored eNOS uncoupling, prevented p66Shc activation, and reduced O2- generation. However, late treatment with tetrahydropterin did not yield the same result suggesting that eNOS uncoupling is the primary source of reactive oxygen species. The present study reports that in primary cultured HAEC treated with oxLDL, p66Shc-mediated oxidative stress is derived from eNOS uncoupling. This finding contributes novel information on the mechanisms of p66Shc activation and its dual interaction with eNOS underscoring the importance eNOS uncoupling as a putative antioxidant therapeutical target in endothelial dysfunction as observed in cardiovascular disease.

Screening and Brief Intervention for Alcohol Problems in a University Student Health Clinic

ERIC Educational Resources Information Center

Ehrlich, Peter F.; Haque, Arshaud; Swisher-McClure, Sam; Helmkamp, James

2006-01-01

The purposes of this study were (1) to determine whether a university student health center (SHC) is a feasible location to introduce a campus-based screening and brief intervention (SBI) program for alcohol and (2) to determine whether the patients seen in the SHC differ in terms of the prevalence and severity of alcohol-related problems compared…

Protecting location privacy for outsourced spatial data in cloud storage.

PubMed

Tian, Feng; Gui, Xiaolin; An, Jian; Yang, Pan; Zhao, Jianqiang; Zhang, Xuejun

2014-01-01

As cloud computing services and location-aware devices are fully developed, a large amount of spatial data needs to be outsourced to the cloud storage provider, so the research on privacy protection for outsourced spatial data gets increasing attention from academia and industry. As a kind of spatial transformation method, Hilbert curve is widely used to protect the location privacy for spatial data. But sufficient security analysis for standard Hilbert curve (SHC) is seldom proceeded. In this paper, we propose an index modification method for SHC (SHC(∗)) and a density-based space filling curve (DSC) to improve the security of SHC; they can partially violate the distance-preserving property of SHC, so as to achieve better security. We formally define the indistinguishability and attack model for measuring the privacy disclosure risk of spatial transformation methods. The evaluation results indicate that SHC(∗) and DSC are more secure than SHC, and DSC achieves the best index generation performance.

Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway.

PubMed

Tauchi, T; Boswell, H S; Leibowitz, D; Broxmeyer, H E

1994-01-01

Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF-responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

Improved repeatability of nasal potential difference with a larger surface catheter.

PubMed

Vermeulen, François; Proesmans, Marijke; Boon, Mieke; De Boeck, Kris

2015-05-01

To increase the power of nasal potential difference (NPD) as a biomarker of CFTR function, improvement of its repeatability is needed. We evaluated the improvement in repeatability resulting from measuring NPD (1) over a larger surface area and (2) at a fixed location. To assess repeatability, NPD was measured on two occasions with a new method using a larger surface catheter at fixed locations on the nasal floor (LSC-floor(5cm) and LSC-floor(3cm)) or at the most negative basal potential (LSC-floor(max)); with a sidehole catheter on the nasal floor at 5 cm) from the nasal margin (SHC-floor(5cm)) or at the most negative potential (SHC-floor(max)); and with an endhole catheter below the inferior surface of the lower turbinate at the most negative potential (EHC-turb(max)). The within-subject standard deviation (S(w)) for repeated measurements of the total chloride response in the controls was smallest with the LSC-floor at a fixed location (LSC-floor(5cm) 3.1 mV; 95% CI 2.3-4.6 mV) and highest with the SHC-floor (SHC-floor(max) 14.6 mV; 95% CI 10.9-22.2 mV) or the EHC-turbinate (EHC-turb(max) 12.5 mV; 95% CI 10.7-23.0 mV) at the most negative basal potential. Measuring with the LSC-floor at the maximal potential increased the Sw (LSC-floor(max) 8.8 mV, 95% CI 6.0-16.1 mV, p=0.009 vs LSC-floor(5cm)), while measuring with the SHC-floor at a fixed location slightly decreased the Sw (SHC-floor(5cm) 9.8 mV, 95% CI 8.9-20.6 mV, p=0.06 vs SHC-floor(max)). In patients with cystic fibrosis, the S(w) was comparable, between 2.2 mV and 4.3 mV. Sample size calculations for trials using NPD to assess changes in ion transport showed that the number of subjects to be included could be approximately halved measuring with the larger surface catheter at a fixed location vs SHC or EHC at fixed locations. Measuring the NPD at a fixed location and over a larger surface resulted in increased repeatability and thereby also power as a biomarker of CFTR modulation. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Measuring school health center impact on access to and quality of primary care.

PubMed

Gibson, Erica J; Santelli, John S; Minguez, Mara; Lord, Alyssa; Schuyler, Ashley C

2013-12-01

School health centers (SHC) that provide comprehensive health care may improve access and quality of care for students; however, published impact data are limited. We evaluated access and quality of health services at an urban high school with a SHC compared with a school without a SHC, using a quasiexperimental research design. Data were collected at the beginning of the school year, using a paper and pencil classroom questionnaire (n = 2,076 students). We measured SHC impact in several ways including grade by school interaction terms. Students at the SHC school were more likely to report having a regular healthcare provider, awareness of confidential services, support for health services in their school, and willingness to utilize those services. Students in the SHC school reported higher quality of care as measured by: respect for their health concerns, adequate time with the healthcare provider, understandable provider communications, and greater provider discussion at their last visit on topics such as sexual activity, birth control, emotions, future plans, diet, and exercise. Users of the SHC were also more likely to report higher quality of care, compared with either nonusers or students in the comparison school. Access to comprehensive health services via a SHC led to improved access to health care and improved quality of care. Impact was measureable on a school-wide basis but was greater among SHC users. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

The silence of p66(Shc) in HCT8 cells inhibits the viability via PI3K/AKT/Mdm-2/p53 signaling pathway.

PubMed

Zhang, Ling; Zhu, Shengtao; Shi, Xuesen; Sha, Weihong

2015-01-01

Colon cancer is the second most common cause of cancer-related death, indicating that some of its cancer cells are not eradicated by current therapies. The previous studies demonstrated that p66(Shc) protein, a member of Shc family, is highly expressed in colon cancer cells, but the role of p66(Shc) in the progress of colon cancer still unknown. In this study, we found that p66(Shc) highly expressed in colon cancer tissue and colon cancer cell line SW620 cells, HCT8 cells, HCT116 cells and CaCO2 cells. The silence of p66(Shc) in HCT8 cells reduced the proliferation and accelerated the apoptosis, in addition, the expression of pro-apoptotic proteins caspase-3, caspase-9, Bax was enhanced and the expression of anti-apoptotic protein Bcl-2 was declined. Moreover, the cell cycle arrest in G0/G1 phase after HCT8 cells treated with p66(Shc) siRNA. Furthermore, after HCT8 cells treated with p66(Shc) siRNA, the phosphorylation of PI3K and AKT was significantly suppressed, and the expression of Mdm-2, a downstream of AKT, was obviously prohibited, while the expression of p53 was enhanced. These results indicate that the silence of p66(Shc) in HCT8 cells inhibits the viability via PI3K/AKT/Mdm-2/p53 signaling pathway, it may provide a promising approach to prevent the progress of colon cancer cell.

The silence of p66Shc in HCT8 cells inhibits the viability via PI3K/AKT/Mdm-2/p53 signaling pathway

PubMed Central

Zhang, Ling; Zhu, Shengtao; Shi, Xuesen; Sha, Weihong

2015-01-01

Colon cancer is the second most common cause of cancer-related death, indicating that some of its cancer cells are not eradicated by current therapies. The previous studies demonstrated that p66Shc protein, a member of Shc family, is highly expressed in colon cancer cells, but the role of p66Shc in the progress of colon cancer still unknown. In this study, we found that p66Shc highly expressed in colon cancer tissue and colon cancer cell line SW620 cells, HCT8 cells, HCT116 cells and CaCO2 cells. The silence of p66Shc in HCT8 cells reduced the proliferation and accelerated the apoptosis, in addition, the expression of pro-apoptotic proteins caspase-3, caspase-9, Bax was enhanced and the expression of anti-apoptotic protein Bcl-2 was declined. Moreover, the cell cycle arrest in G0/G1 phase after HCT8 cells treated with p66Shc siRNA. Furthermore, after HCT8 cells treated with p66Shc siRNA, the phosphorylation of PI3K and AKT was significantly suppressed, and the expression of Mdm-2, a downstream of AKT, was obviously prohibited, while the expression of p53 was enhanced. These results indicate that the silence of p66Shc in HCT8 cells inhibits the viability via PI3K/AKT/Mdm-2/p53 signaling pathway, it may provide a promising approach to prevent the progress of colon cancer cell. PMID:26464652

Insulin receptor substrates 1 and 2 but not Shc can activate the insulin receptor independent of insulin and induce proliferation in CHO-IR cells

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

Niessen, Markus; Jaschinski, Frank; Item, Flurin

2007-02-15

Ligand-activated insulin receptor (IR) attracts and phosphorylates various substrates such as insulin receptor substrates 1-4 (IRS) and Shc. To investigate how binding affinity for substrate affects signalling we generated chimeric receptors with the {beta}-chain of the insulin receptor containing NPXY motives with different affinities for receptor substrates. We found that the extent of receptor tyrosine phosphorylation positively correlates with binding affinity towards IRS1/2 but not towards Shc. Moreover, overexpression of IRS1 or IRS2 but not of Shc increased IR tyrosine phosphorylation in a dose-dependent manner, also independent of insulin. Molecular truncations of IRS1 revealed that neither the isolated PH andmore » PTB domains nor the C-terminus with the tyrosine phosphorylation sites alone are sufficient for substrate-dependent receptor activation. Overexpression of IRS1 and IRS2 impaired insulin-induced internalization of the IR in a dose-dependent manner suggesting that IRS proteins prevent endosome-associated receptor dephosphorylation/inactivation. IRS1 and IRS2 could therefore target the activated IR to different cellular compartments. Overexpression of IRS1 and IRS2 inhibited insulin-stimulated activation of the MAP kinases Erk1/2 while it increased/induced activation of Akt/PKB. Finally, overexpression of IRS1 and IRS2 but not of Shc induced DNA synthesis in starved CHO-IR cells independent of exogenous growth factors. Our results demonstrate that variations in cellular IRS1 and IRS2 concentration affect insulin signalling both upstream and downstream and that IRS proteins could play instructive rather than just permissive roles in signal transmission.« less

Real-world dose-relativity, tablet burden, and cost comparison of conversion between sevelamer hydrochloride/carbonate and lanthanum carbonate monotherapies.

PubMed

Keith, Michael S; Sibbel, Scott; Copley, J Brian; Wilson, Rosamund J; Brunelli, Steven M

2014-10-01

Sevelamer hydrochloride/carbonate (SH/C) and lanthanum carbonate (LC) are noncalcium-based phosphate binders used for the management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objectives of this study were to examine the dose-relativity, tablet burden, and cost difference of bidirectional conversion between SH/C and LC monotherapy in a large cohort of real-world patients with ESRD. This retrospective cohort study included three 30-day preconversion periods (days -90 to -61, -60 to -31, and -30 to -1) followed by three 30-day postconversion periods (days 1 to 30, 31 to 60, and 61 to 90); day 0 was the index date of conversion. The full analysis population (FAP) comprised two cohorts: SH/C to LC (S-L) converters and LC to SH/C (L-S) converters. The SH/C:LC dose-relativity ratio was assessed in the dose-relativity subset, defined as patients whose serum phosphate levels fell within a caliper range of ± 0.5 mg/dL in the final preconversion (days -30 to -1) and postconversion (days 61 to 90) periods. Tablet burden and phosphate binder costs were assessed in the FAP. Phosphate binder costs were based on average wholesale prices. The FAP contained a total of 303 patients, comprising the S-L (128 patients) and L-S (175 patients) converter cohorts. The dose-relativity subset contained 159 patients, 72 from the S-L cohort and 87 from the L-S cohort. The overall mean SH/C:LC dose-relativity ratio was 2.27 (95% CI, 2.04 to 2.52). In SH/C dose strata >800 to 2400, >2400 to 4800, >4800 to 7200, and >7200 mg/d, overall mean dose-relativity ratios were 0.79 (95% CI, 0.57 to 1.10), 1.45 (95% CI, 1.20 to 1.75), 2.05 (95% CI, 1.75 to 2.39), and 3.24 (95% CI, 2.89 to 3.66), respectively. The overall mean tablet burden was 6.6 tablets per day lower with LC monotherapy than with SH/C monotherapy (95% CI, -7.1 to -6.0; P < 0.0001). The overall mean binder cost/patient per month was $1080.40 for SH/C compared with $1006.20 for LC, corresponding to a mean binder cost saving for LC of $74.20/patient per month (95% CI, -141.80 to -6.63; P = 0.032). SH/C >7800 mg/d was the inflection point at which conversion to LC resulted in mean cost savings. Patients requiring SH/C >7800 mg/d comprised 50% of the FAP. Converting patients with ESRD and hyperphosphatemia from SH/C to LC monotherapy offers potential drug cost savings and a significant reduction in the daily tablet burden, without compromising the effective management of serum phosphate levels. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Sample dimensions effect on prediction of soil water retention curve and saturated hydraulic conductivity

USDA-ARS?s Scientific Manuscript database

Soil water retention curve (SWRC) and saturated hydraulic conductivity (SHC) are key hydraulic properties for unsaturated zone hydrology and groundwater. Not only are the SWRC and SHC measurements time-consuming, their results are scale dependent. Although prediction of the SWRC and SHC from availab...

Self-rated health status and subjective health complaints associated with health-promoting lifestyles among urban Chinese women: a cross-sectional study.

PubMed

Cheng, Jingru; Wang, Tian; Li, Fei; Xiao, Ya; Bi, Jianlu; Chen, Jieyu; Sun, Xiaomin; Wu, Liuguo; Wu, Shengwei; Liu, Yanyan; Luo, Ren; Zhao, Xiaoshan

2015-01-01

This study aimed to investigate whether self-rated health status (SRH) and subjective health complaints (SHC) of urban Chinese women are associated with their health-promoting lifestyles (HPL). We conducted a cross-sectional study on 8142 eligible Chinese participants between 2012 and 2013. Demographic and SHC data were collected. Each subject completed the SRH questionnaire and the Chinese version of the Health-Promoting Lifestyle Profile-II (HPLP-II). Correlation and binary regression analyses were performed to examine the associations of SRH and SHC with HPL. Both SRH and HPL of urban Chinese women were moderate. The most common complaints were fatigue (1972, 24.2%), eye discomfort (1571, 19.3%), and insomnia (1542, 18.9%). Teachers, highly educated subjects and elderly women had lower SRH scores, while college students and married women had better HPL. All items of HPLP-II were positively correlated with SRH (r = 0.127-0.533, P = 0.000) and negatively correlated with SHC to a significant extent (odds ratio [OR] = 1.40-11.37). Aspects of HPL, particularly stress management and spiritual growth, are associated with higher SRH and lower SHC ratings among urban Chinese women. Physical activity and health responsibility are additionally related to reduced fatigue and nervousness. We believe that these findings will be instrumental in encouraging researchers and urban women to adopt better health-promoting lifestyles with different priorities in their daily lives.

Selected family characteristics are associated with adolescents' subjective health complaints.

PubMed

Petanidou, Dimitra; Mihas, Constantinos; Dimitrakaki, Christine; Kolaitis, Gerasimos; Tountas, Yannis

2014-02-01

This national study of schoolchildren in Greece investigated the association between adolescents' subjective health complaints (SHC) and a number of family characteristics. Questionnaires were completed by a random, school-based sample of children from 12 to 18 years of age, and one of their parents (76.6% mothers), in 2003. Data from 1041 adolescent-parent pairs were analysed. Multiple linear regression analysis was used to assess the associations between the adolescent's SHC and the following characteristics: parent's marital status, parent's physical and mental health status, parent's worries about their child's SHC, the parent-child relationship, family cohesion, family socio-economic status and the adolescent's sex and age. The analysis showed that the adolescents' SHC were independently and significantly correlated with poor parental subjective mental health status, poor quality parent-child relationships and parental worry. There were also associations between levels of SHC and female and older adolescents. Certain family features can be seen as potential contributing factors to SHC in adolescence and should therefore constitute complementary targets for prevention and treatment planning. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66shc-dependent antioxidant responses.

PubMed

Arany, Istvan; Carter, Anthony; Hall, Samuel; Fulop, Tibor; Dixit, Mehul

2017-02-01

Chronic nicotine exposure (via smoking, E-cigarettes) increases oxidative stress in the kidney that sensitizes it to additional injury in experimental models and in the renal patient. The pro-apoptotic p66 shc protein-via serine36 phosphorylation that facilitates its mitochondrial translocation and therein cytochrome c binding-generates oxidative stress that leads to injury of renal proximal tubule cells during chronic nicotine exposure. Coenzyme Q10-a clinically safe antioxidant-has been used against nicotine/smoke extract-associated oxidative stress in various non-renal cells. This study explored the anti-oxidant/anti-apoptotic effect of Coenzyme Q10 on nicotine-induced oxidative stress and its impact on p66shc in cultured rat renal proximal tubule cells (NRK52E). We studied the anti-oxidant effect of 10 µM Coenzyme Q10 using various mutants of the p66shc gene and also determined the induction of selected anti-oxidant entities (antioxidant response element, promoter of the manganese superoxide dismutase gene) in reporter luciferase assay during oxidative stress induced by 200 µM nicotine. Our studies revealed that Coenzyme Q10 strongly inhibits nicotine-mediated production of reactive oxygen species and consequent apoptosis that requires serine36 phosphorylation but not mitochondrial translocation/cytochrome c binding of p66 shc . While both nicotine and Coenzyme Q10 stimulates the p66shc promoter, only nicotine exposure results in mitochondrial translocation of p66 shc . In contrast, the Coenzyme Q10-stimulated and non-mitochondrial p66 shc activates the anti-oxidant manganese superoxide dismutase promoter via the antioxidant response elements and hence, rescues cells from nicotine-induced oxidative stress and consequent apoptosis.

[Virological and clinical features of patients with sporadic hepatitis C].

PubMed

Tang, Z; Wang, Y; Yu, Z; Yang, D; Hao, L

1997-06-01

In this study, the transmission route in 16 sporadic hepatitis C (SHC) patients was investigated. Three of them were surgeons who had often had occupational needlestick accidents, another 3 had close household contact with their spouses who had been diagnosed as chronic posttransfusion viral hepatitis C (PTHC), and the remaining 5 had potential parenteral exposure such as tooth extraction, injection or inoculation and so on. Five patients with SHC didn't have such history, their transmission route was not determined. Our result showed a lower viremia level in patients with SHC when compared to PTHC patients (the serum dilutions for HCV RNA detection was 10-100 times in the former and 100-10000 times in the latter. P<0.01). Only 1 patient with SHC was anti-HCV positive. Comparing to PTHC, the patients with SHC in our study had milder liver demage and lower ALT levels, and most of them (10/16) were symptomless.

24(S)-Hydroxycholesterol as a modulator of neuronal signaling and survival

PubMed Central

Sun, Min Yu; Linsenbardt, Andrew; Emnett, Christine; Eisenman, Lawrence N.; Izumi, Yukitoshi; Zorumski, Charles; Mennerick, Steve

2016-01-01

The major cholesterol metabolite in brain, 24S-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on NMDA receptor (NMDAR) function. This could have implications for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and downregulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders. PMID:25628343

Using the eSexual Health Clinic to access chlamydia treatment and care via the internet: a qualitative interview study.

PubMed

Aicken, Catherine R H; Sutcliffe, Lorna J; Gibbs, Jo; Tickle, Laura J; Hone, Kate; Harding-Esch, Emma M; Mercer, Catherine H; Sonnenberg, Pam; Sadiq, S Tariq; Estcourt, Claudia S; Shahmanesh, Maryam

2018-06-01

We developed the eSexual Health Clinic (eSHC), an innovative, complex clinical and public health intervention, embedded within a specialist sexual health service. Patients with genital chlamydia access their results online and are offered medical management via an automated online clinical consultation, leading to antibiotic collection from community pharmacy. A telephone helpline, staffed by Sexual Health Advisers, is available to support patients and direct them to conventional services if appropriate. We sought to understand how patients used this ehealth intervention. Within exploratory studies of the eSHC (2014-2015), we conducted in-depth interviews with a purposive sample of 36 patients diagnosed with chlamydia, who had chosen to use the eSHC (age 18-35, 20 female, 16 male). Thematic analysis was conducted. Participants described choosing to use this ehealth intervention to obtain treatment rapidly, conveniently and privately, within busy lifestyles that hindered clinic access. They described completing the online consultation promptly, discreetly and with ease. The information provided online was considered comprehensive, reassuring and helpful, but some overlooked it in their haste to obtain treatment. Participants generally described being able to collect treatment from pharmacies discreetly and promptly, but for some, poor awareness of the eSHC by pharmacy staff undermined their ability to do this. Those unsuitable for remote management, who were directed to clinic, described frustration and concern about health implications and clinic attendance. However, the helpline was a highly valued source of information, assistance and support. The eSHC is a promising adjunct to traditional care. Its users have high expectations for convenience, speed and privacy, which may be compromised when transitioning from online to face-to-face elements of the eSHC. Managing expectations and improving implementation of the pharmacy process, could improve their experiences. Positive views on the helpline provide further support for embedding this ehealth intervention within a specialist clinical service. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protecting Location Privacy for Outsourced Spatial Data in Cloud Storage

PubMed Central

Gui, Xiaolin; An, Jian; Zhao, Jianqiang; Zhang, Xuejun

2014-01-01

As cloud computing services and location-aware devices are fully developed, a large amount of spatial data needs to be outsourced to the cloud storage provider, so the research on privacy protection for outsourced spatial data gets increasing attention from academia and industry. As a kind of spatial transformation method, Hilbert curve is widely used to protect the location privacy for spatial data. But sufficient security analysis for standard Hilbert curve (SHC) is seldom proceeded. In this paper, we propose an index modification method for SHC (SHC∗) and a density-based space filling curve (DSC) to improve the security of SHC; they can partially violate the distance-preserving property of SHC, so as to achieve better security. We formally define the indistinguishability and attack model for measuring the privacy disclosure risk of spatial transformation methods. The evaluation results indicate that SHC∗ and DSC are more secure than SHC, and DSC achieves the best index generation performance. PMID:25097865

Sch proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation.

PubMed Central

Lotti, L V; Lanfrancone, L; Migliaccio, E; Zompetta, C; Pelicci, G; Salcini, A E; Falini, B; Pelicci, P G; Torrisi, M R

1996-01-01

The intracellular localization of Shc proteins was analyzed by immunofluorescence and immunoelectron microscopy in normal cells and cells expressing the epidermal growth factor receptor or the EGFR/erbB2 chimera. In unstimulated cells, the immunolabeling was localized in the central perinuclear area of the cell and mostly associated with the cytosolic side of rough endoplasmic reticulum membranes. Upon epidermal growth factor treatment and receptor tyrosine kinase activation, the immunolabeling became peripheral and was found to be associated with the cytosolic surface of the plasma membrane and endocytic structures, such as coated pits and endosomes, and with the peripheral cytosol. Receptor activation in cells expressing phosphorylation-defective mutants of Shc and erbB-2 kinase showed that receptor autophosphorylation, but not Shc phosphorylation, is required for redistribution of Shc proteins. The rough endoplasmic reticulum localization of Shc proteins in unstimulated cells and their massive recruitment to the plasma membrane, endocytic structures, and peripheral cytosol following receptor tyrosine kinase activation could account for multiple putative functions of the adaptor protein. PMID:8628261

Amyloid precursor protein modulates ERK-1 and -2 signaling.

PubMed

Venezia, Valentina; Nizzari, Mario; Repetto, Emanuela; Violani, Elisabetta; Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Carlo, Pia; Schettini, Gennaro; Florio, Tullio; Russo, Claudio

2006-12-01

The amyloid precursor protein (APP) is a transmembrane protein with a short cytoplasmic tail whose physiological function is unclear, although it is well documented that the proteolytic processing of APP could influence the development of Alzheimer's disease (AD) through the formation of membrane-bound C-terminal fragments (CTFs) and of beta-amyloid peptides (Abeta). We have recently shown that tyrosine-phosphorylated APP and CTFs may interact with Grb2 and ShcA adaptor proteins and that this coupling occurs at a higher extent in AD subjects only. To study the interaction between APP or CTFs and ShcA/Grb2 and to investigate their molecular target we have used as experimental model two different cell lines: H4 human neuroglioma cells and APP/APLP null mouse embryonic fibroblast cells (MEFs). Here we show that in H4 cells APP interacts with Grb2; conversely in APP/APLP-null MEF cells this interaction is possible only after the reintroduction of human APP by transfection. We have also shown that in MEF cells the transfection of a plasmid encoding for human APP wild-type enhances the phosphorylation of ERK-1 and -2 as revealed by Western blotting and immunofluorescence experiments. Finally, also in H4 cells the overexpression of APP upregulates the levels of phospho-ERK-1 and -2. In summary our data suggest that APP may influence phospho-ERK-1 and -2 signaling through its binding with Grb2 and ShcA adaptors. The meaning of this event is not clear, but APP interaction with these adaptors could be relevant to regulate mitogenic pathway.

SentiHealth-Cancer: A sentiment analysis tool to help detecting mood of patients in online social networks.

PubMed

Rodrigues, Ramon Gouveia; das Dores, Rafael Marques; Camilo-Junior, Celso G; Rosa, Thierson Couto

2016-01-01

Cancer is a critical disease that affects millions of people and families around the world. In 2012 about 14.1 million new cases of cancer occurred globally. Because of many reasons like the severity of some cases, the side effects of some treatments and death of other patients, cancer patients tend to be affected by serious emotional disorders, like depression, for instance. Thus, monitoring the mood of the patients is an important part of their treatment. Many cancer patients are users of online social networks and many of them take part in cancer virtual communities where they exchange messages commenting about their treatment or giving support to other patients in the community. Most of these communities are of public access and thus are useful sources of information about the mood of patients. Based on that, Sentiment Analysis methods can be useful to automatically detect positive or negative mood of cancer patients by analyzing their messages in these online communities. The objective of this work is to present a Sentiment Analysis tool, named SentiHealth-Cancer (SHC-pt), that improves the detection of emotional state of patients in Brazilian online cancer communities, by inspecting their posts written in Portuguese language. The SHC-pt is a sentiment analysis tool which is tailored specifically to detect positive, negative or neutral messages of patients in online communities of cancer patients. We conducted a comparative study of the proposed method with a set of general-purpose sentiment analysis tools adapted to this context. Different collections of posts were obtained from two cancer communities in Facebook. Additionally, the posts were analyzed by sentiment analysis tools that support the Portuguese language (Semantria and SentiStrength) and by the tool SHC-pt, developed based on the method proposed in this paper called SentiHealth. Moreover, as a second alternative to analyze the texts in Portuguese, the collected texts were automatically translated into English, and submitted to sentiment analysis tools that do not support the Portuguese language (AlchemyAPI and Textalytics) and also to Semantria and SentiStrength, using the English option of these tools. Six experiments were conducted with some variations and different origins of the collected posts. The results were measured using the following metrics: precision, recall, F1-measure and accuracy The proposed tool SHC-pt reached the best averages for accuracy and F1-measure (harmonic mean between recall and precision) in the three sentiment classes addressed (positive, negative and neutral) in all experimental settings. Moreover, the worst accuracy value (58%) achieved by SHC-pt in any experiment is 11.53% better than the greatest accuracy (52%) presented by other addressed tools. Finally, the worst average F1 (48.46%) reached by SHC-pt in any experiment is 4.14% better than the greatest average F1 (46.53%) achieved by other addressed tools. Thus, even when we compare the SHC-pt results in complex scenario versus others in easier scenario the SHC-pt is better. This paper presents two contributions. First, it proposes the method SentiHealth to detect the mood of cancer patients that are also users of communities of patients in online social networks. Second, it presents an instantiated tool from the method, called SentiHealth-Cancer (SHC-pt), dedicated to automatically analyze posts in communities of cancer patients, based on SentiHealth. This context-tailored tool outperformed other general-purpose sentiment analysis tools at least in the cancer context. This suggests that the SentiHealth method could be instantiated as other disease-based tools during future works, for instance SentiHealth-HIV, SentiHealth-Stroke and SentiHealth-Sclerosis. Copyright © 2015. Published by Elsevier Ireland Ltd.

ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis.

PubMed

Kim, Young-Mee; Kim, Seok-Jo; Tatsunami, Ryosuke; Yamamura, Hisao; Fukai, Tohru; Ushio-Fukai, Masuko

2017-06-01

Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch from a quiescent to an angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible ROS produced from different sources can coordinate to stimulate VEGF signaling and drive the angiogenic process remains unknown. Using the cytosol- and mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min, which continues at least for 60 min. Silencing of Nox4 or Nox2 or overexpression of mitochondria-targeted catalase significantly inhibits VEGF-induced tyrosine phosphorylation of VEGF receptor type 2 (VEGFR2-pY), EC migration and proliferation at the similar extent. Exogenous hydrogen peroxide (H 2 O 2 ) or overexpression of Nox4, which produces H 2 O 2 , increases mitochondrial ROS (mtROS), which is prevented by Nox2 siRNA, suggesting that Nox2 senses Nox4-derived H 2 O 2 to promote mtROS production. Mechanistically, H 2 O 2 increases S36 phosphorylation of p66Shc, a key mtROS regulator, which is inhibited by siNox2, but not by siNox4. Moreover, Nox2 or Nox4 knockdown or overexpression of S36 phosphorylation-defective mutant p66Shc(S36A) inhibits VEGF-induced mtROS, VEGFR2-pY, EC migration, and proliferation. In summary, Nox4-derived H 2 O 2 in part activates Nox2 to increase mtROS via pSer36-p66Shc, thereby enhancing VEGFR2 signaling and angiogenesis in ECs. This may represent a novel feed-forward mechanism of ROS-induced ROS release orchestrated by the Nox4/Nox2/pSer36-p66Shc/mtROS axis, which drives sustained activation of angiogenesis signaling program. Copyright © 2017 the American Physiological Society.

Sustainable and Healthy Communities (SHC) Topic 3 Fact Sheets

EPA Pesticide Factsheets

These documents provide a condensed overview of the Sustainable and Healthy Communities (SHC) Research Program's Projects 3.61 Contaminated Sites, 3.62 Environmental Releases of Oils and Fuels, and 3.63 Sustainable Materials Management.

Specific heat capacity of molten salt-based alumina nanofluid.

PubMed

Lu, Ming-Chang; Huang, Chien-Hsun

2013-06-21

There is no consensus on the effect of nanoparticle (NP) addition on the specific heat capacity (SHC) of fluids. In addition, the predictions from the existing model have a large discrepancy from the measured SHCs in nanofluids. We show that the SHC of the molten salt-based alumina nanofluid decreases with reducing particle size and increasing particle concentration. The NP size-dependent SHC is resulted from an augmentation of the nanolayer effect as particle size reduces. A model considering the nanolayer effect which supports the experimental results was proposed.

Specific heat capacity of molten salt-based alumina nanofluid

PubMed Central

2013-01-01

There is no consensus on the effect of nanoparticle (NP) addition on the specific heat capacity (SHC) of fluids. In addition, the predictions from the existing model have a large discrepancy from the measured SHCs in nanofluids. We show that the SHC of the molten salt-based alumina nanofluid decreases with reducing particle size and increasing particle concentration. The NP size-dependent SHC is resulted from an augmentation of the nanolayer effect as particle size reduces. A model considering the nanolayer effect which supports the experimental results was proposed. PMID:23800321

Novel adapter proteins that link the human GM-CSF receptor to the phosphatidylino-sitol 3-kinase and Shc/Grb2/ras signaling pathways.

PubMed

Jücker, M; Feldman, R A

1996-01-01

We have used a human GM-CSF-dependent hematopoietic cell line that responds to physiological concentrations of hGM-CSF to analyze a set of signaling events that occur in normal myelopoiesis and whose deregulation may lead to leukemogenesis. Stimulation of these cells with hGM-CSF induced the assembly of multimeric complexes that contained known and novel phosphotyrosyl proteins. One of the new proteins was a major phosphotyrosyl substrate of 76-85 kDa (p80) that was directly associated with the p85 subunit of phosphatidylinositol (PI) 3-kinase through the SH2 domains of p85. p80 also associated with the beta subunit of the activated hGM-CSF receptor, and assembly of this complex correlated with activation of PI 3-kinase. A second phosphotyrosyl protein we identified, p140, associated with the Shc and Grb2 adapter proteins by direct binding to a novel phosphotyrosine-interacting domain located at the N-terminus of Shc. and to the SH3 domains of Grb2, respectively. The Shc/p140/Grb2 complex was found to be constitutively activated in acute myeloid leukemia cells, indicating that activation of this pathway may be a necessary step in the development of some leukemias. The p80/p85/PI 3-kinase and the Shc/Grb2/p140 complexes were tightly associated with Src family kinases, which were prime candidates for phosphorylation of Shc, p80, p140 and other phosphotyrosyl substrates present in these complexes. Our studies suggest that p80 and p140 may link the hGM-CSF receptor to the PI 3-kinase and Shc/Grb2/ras signaling pathways, respectively, and that abnormal activation of hGM-CSF-dependent targets may play a role in leukemogenesis.

The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors.

PubMed

Paul, Steven M; Doherty, James J; Robichaud, Albert J; Belfort, Gabriel M; Chow, Brian Y; Hammond, Rebecca S; Crawford, Devon C; Linsenbardt, Andrew J; Shu, Hong-Jin; Izumi, Yukitoshi; Mennerick, Steven J; Zorumski, Charles F

2013-10-30

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABAA receptors (GABA(A)Rs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations ≤10 μM. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development.

Signal transduction by beta1 integrin receptors in human chondrocytes in vitro: collaboration with the insulin-like growth factor-I receptor.

PubMed

Shakibaei, M; John, T; De Souza, P; Rahmanzadeh, R; Merker, H J

1999-09-15

We have examined the mechanism by which collagen-binding integrins co-operate with insulin-like growth factor-I (IGF-I) receptors (IGF-IR) to regulate chondrocyte phenotype and differentiation. Adhesion of chondrocytes to anti-beta1 integrin antibodies or collagen type II leads to phosphorylation of cytoskeletal and signalling proteins localized at focal adhesions, including alpha-actinin, vinculin, paxillin and focal adhesion kinase (FAK). These stimulate docking proteins such as Shc (Src-homology collagen). Moreover, exposure of collagen type II-cultured chondrocytes to IGF-I leads to co-immunoprecipitation of Shc protein with the IGF-IR and with beta1, alpha1 and alpha5 integrins, but not with alpha3 integrin. Shc then associates with growth factor receptor-bound protein 2 (Grb2), an adaptor protein and extracellular signal-regulated kinase. The expression of the docking protein Shc occurs only when chondrocytes are bound to collagen type II or integrin antibodies and increases when IGF-I is added, suggesting a collaboration between integrins and growth factors in a common/shared biochemical signalling pathway. Furthermore, these results indicate that focal adhesion assembly may facilitate signalling via Shc, a potential common target for signal integration between integrin and growth-factor signalling regulatory pathways. Thus, the collagen-binding integrins and IGF-IR co-operate to regulate focal adhesion components and these signalling pathways have common targets (Shc-Grb2 complex) in subcellular compartments, thereby linking to the Ras-mitogen-activated protein kinase signalling pathway. These events may play a role during chondrocyte differentiation.

Process Evaluation of an Intervention to Increase Provision of Adolescent Vaccines at School Health Centers

ERIC Educational Resources Information Center

Golden, Shelley D.; Moracco, Kathryn E.; Feld, Ashley L.; Turner, Kea L.; DeFrank, Jessica T.; Brewer, Noel T.

2014-01-01

Background: Vaccination programs in school health centers (SHCs) may improve adolescent vaccine coverage. We conducted a process evaluation of an intervention to increase SHC-located vaccination to better understand the feasibility and challenges of such interventions. Method: Four SHCs participated in an intervention to increase provision of…

Modification of Pectin and Hemicellulose Polysaccharides in Relation to Aril Breakdown of Harvested Longan Fruit

PubMed Central

Wang, Duoduo; Zhang, Haiyan; Wu, Fuwang; Li, Taotao; Liang, Yuxiang; Duan, Xuewu

2013-01-01

To investigate the modification of cell wall polysaccharides in relation to aril breakdown in harvested longan fruit, three pectin fractions (WSP, water soluble pectin; CSP, CDTA-soluble pectin; ASP, alkali soluble pectin) and one hemicellulose fraction (4 M KOH-SHC, 4 M KOH-soluble hemicellulose) were extracted, and their contents, monosaccharide compositions and molecular weights were evaluated. As aril breakdown intensified, CSP content increased while ASP and 4 M KOH-SHC contents decreased, suggesting the solubilization and conversion of cell wall components. Furthermore, the molar percentage of arabinose (Ara), as the main component of the side-chains, decreased largely in CSP and ASP while that of rhamnose (Rha), as branch point for the attachment of neutral sugar side chains, increased during aril breakdown. Analysis of (Ara + Gal)/Rha ratio showed that the depolymerization of CSP and ASP happened predominantly in side-chains formed of Ara residues. For 4 M KOH-SHC, more backbones were depolymerized during aril breakdown. Moreover, it was found that the molecular weights of CSP, ASP and 4 M KOH-SHC polysaccharides tended to decrease as aril breakdown intensified. These results suggest that both enhanced depolymerization and structural modifications of polysaccharides in the CSP, ASP and 4 M KOH-SHC fractions might be responsible for aril breakdown of harvested longan fruit. PMID:24287911

Physicians' assessments of work capacity in patients with severe subjective health complaints: a cross-sectional study on differences between five European countries

PubMed Central

Werner, Erik L; Merkus, Suzanne L; Mæland, Silje; Jourdain, Maud; Schaafsma, Frederieke; Canevet, Jean Paul; Weerdesteijn, Kristel H N; Rat, Cédric; Anema, Johannes R

2016-01-01

Objectives A comparison of appraisals made by general practitioners (GPs) in France and occupational physicians (OPs) and insurance physicians (IPs) in the Netherlands with those made by Scandinavian GPs on work capacity in patients with severe subjective health complaints (SHCs). Setting GPs in France and OPs/IPs in the Netherlands gathered to watch nine authentic video recordings from a Norwegian general practice. Participants 46 GPs in France and 93 OPs/IPs in the Netherlands were invited to a 1-day course on SHC. Outcomes Recommendation of sick leave (full or partial) or no sick leave for each of the patients. Results Compared with Norwegian GPs, sick leave was less likely to be granted by Swedish GPs (OR 0.51, 95% CI 0.30 to 0.86) and by Dutch OPs/IPs (OR 0.53, 95% CI 0.37 to 0.78). The differences between Swedish and Norwegian GPs were maintained in the adjusted analyses (OR 0.43, 95% CI 0.23 to 0.79). This was also true for the differences between Dutch and Norwegian physicians (OR 0.55, 95% CI 0.36 to 0.86). Overall, compared with the GPs, the Dutch OPs/IPs were less likely to grant sick leave (OR 0.60, 95% CI 0.45 to 0.87). Conclusions Swedish GPs and Dutch OPs/IPs were less likely to grant sick leave to patients with severe SHC compared with GPs from Norway, while GPs from Denmark and France were just as likely to grant sick leave as the Norwegian GPs. We suggest that these findings may be due to the guidelines on sick-listing and on patients with severe SHC which exist in Sweden and the Netherlands, respectively. Differences in the working conditions, relationships with patients and training of specialists in occupational medicine may also have affected the results. However, a pattern was observed in which of the patients the physicians in all countries thought should be sick-listed, suggesting that the physicians share tacit knowledge regarding sick leave decision-making in patients with severe SHC. PMID:27417198

Effects of screenhouse cultivation and organic materials incorporation on global warming potential in rice fields.

PubMed

Xu, Guochun; Liu, Xin; Wang, Qiangsheng; Xiong, Ruiheng; Hang, Yuhao

2017-03-01

Global rice production will be increasingly challenged by providing healthy food for a growing population at minimal environmental cost. In this study, a 2-year field experiment was conducted to investigate the effects of a novel rice cultivation mode (screenhouse cultivation, SHC) and organic material (OM) incorporation (wheat straw and wheat straw-based biogas residue) on methane (CH 4 ) and nitrous oxide (N 2 O) emissions and rice yields. In addition, the environmental factors and soil properties were also determined. Relative to the traditional open-field cultivation (OFC), SHC decreased the CH 4 and N 2 O emissions by 6.58-18.73 and 2.51-21.35%, respectively, and the global warming potential (GWP) was reduced by 6.49-18.65%. This trend was mainly because of lower soil temperature and higher soil redox potential in SHC. Although the rice grain yield for SHC were reduced by 2.51-4.98% compared to the OFC, the CH 4 emissions and GWP per unit of grain yield (yield-scaled CH 4 emissions and GWP) under SHC were declined. Compared to use of inorganic fertilizer only (IN), combining inorganic fertilizer with wheat straw (WS) or wheat straw-based biogas residue (BR) improved rice grain yield by 2.12-4.10 and 4.68-5.89%, respectively. However, OM incorporation enhanced CH 4 emissions and GWP, leading to higher yield-scaled CH 4 emissions and GWP in WS treatment. Due to rice yield that is relatively high, there was no obvious effect of BR treatment on them. These findings suggest that apparent environmental benefit can be realized by applying SHC and fermenting straw aerobically before its incorporation.

Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30.

PubMed

Quinn, Jeffrey A; Graeber, C Thomas; Frackelton, A Raymond; Kim, Minsoo; Schwarzbauer, Jean E; Filardo, Edward J

2009-07-01

Estrogen promotes changes in cytoskeletal architecture not easily attributed to the biological action of estrogen receptors, ERalpha and ERbeta. The Gs protein-coupled transmembrane receptor, GPR30, is linked to specific estrogen binding and rapid estrogen-mediated release of heparin-bound epidermal growth factor. Using marker rescue and dominant interfering mutant strategies, we show that estrogen action via GPR30 promotes fibronectin (FN) matrix assembly by human breast cancer cells. Stimulation with 17beta-estradiol or the ER antagonist, ICI 182, 780, results in the recruitment of FN-engaged integrin alpha5beta1 conformers to fibrillar adhesions and the synthesis of FN fibrils. Concurrent with this cellular response, GPR30 promotes the formation of Src-dependent, Shc-integrin alpha5beta1 complexes. Function-blocking antibodies directed against integrin alpha5beta1 or soluble Arg-Gly-Asp peptide fragments derived from FN specifically inhibited GPR30-mediated epidermal growth factor receptor transactivation. Estrogen-mediated FN matrix assembly and epidermal growth factor receptor transactivation were similarly disrupted in integrin beta1-deficient GE11 cells, whereas reintroduction of integrin beta1 into GE11 cells restored these responses. Mutant Shc (317Y/F) blocked GPR30-induced FN matrix assembly and tyrosyl phosphorylation of erbB1. Interestingly, relative to recombinant wild-type Shc, 317Y/F Shc was more readily retained in GPR30-induced integrin alpha5beta1 complexes, yet this mutant did not prevent endogenous Shc-integrin alpha5beta1 complex formation. Our results suggest that GPR30 coordinates estrogen-mediated FN matrix assembly and growth factor release in human breast cancer cells via a Shc-dependent signaling mechanism that activates integrin alpha5beta1.

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

Scardino, A.J.; Zhang, H.; Cookson, D.J.

Nano-engineered superhydrophobic surfaces have been investigated for potential fouling resistance properties. Integrating hydrophobic materials with nanoscale roughness generates surfaces with superhydrophobicity that have water contact angles ({theta}) >150{sup o} and concomitant low hysteresis (<10{sup o}). Three superhydrophobic coatings (SHCs) differing in their chemical composition and architecture were tested against major fouling species (Amphora sp., Ulva rigida, Polysiphonia sphaerocarpa, Bugula neritina, Amphibalanus amphitrite) in settlement assays. The SHC which had nanoscale roughness alone (SHC 3) deterred the settlement of all the tested fouling organisms, compared to selective settlement on the SHCs with nano- and micro-scale architectures. The presence of air incursionsmore » or nanobubbles at the interface of the SHCs when immersed was characterized using small angle X-ray scattering, a technique sensitive to local changes in electron density contrast resulting from partial or complete wetting of a rough interface. The coating with broad spectrum antifouling properties (SHC 3) had a noticeably larger amount of unwetted interface when immersed, likely due to the comparatively high work of adhesion (60.77 mJ m{sup -2} for SHC 3 compared to 5.78 mJ m-2 for the other two SHCs) required for creating solid/liquid interface from the solid/vapour interface. This is the first example of a non-toxic, fouling resistant surface against a broad spectrum of fouling organisms ranging from plant cells and non-motile spores, to complex invertebrate larvae with highly selective sensory mechanisms. The only physical property differentiating the immersed surfaces is the nano-architectured roughness which supports longer standing air incursions providing a novel non-toxic broad spectrum mechanism for the prevention of biofouling.« less

SHC Meeting Documents for November 2-4, 2016: Charge Questions

EPA Pesticide Factsheets

This document contains three (3) questions that the Sustainable and Healthy Communities Research Program is asking the BOSC Subcommitte to answer at the Nov 2-4 BOSC meeting. The answers to these questions will help SHC evaluate if their ongoing and future

Clustering PPI data by combining FA and SHC method.

PubMed

Lei, Xiujuan; Ying, Chao; Wu, Fang-Xiang; Xu, Jin

2015-01-01

Clustering is one of main methods to identify functional modules from protein-protein interaction (PPI) data. Nevertheless traditional clustering methods may not be effective for clustering PPI data. In this paper, we proposed a novel method for clustering PPI data by combining firefly algorithm (FA) and synchronization-based hierarchical clustering (SHC) algorithm. Firstly, the PPI data are preprocessed via spectral clustering (SC) which transforms the high-dimensional similarity matrix into a low dimension matrix. Then the SHC algorithm is used to perform clustering. In SHC algorithm, hierarchical clustering is achieved by enlarging the neighborhood radius of synchronized objects continuously, while the hierarchical search is very difficult to find the optimal neighborhood radius of synchronization and the efficiency is not high. So we adopt the firefly algorithm to determine the optimal threshold of the neighborhood radius of synchronization automatically. The proposed algorithm is tested on the MIPS PPI dataset. The results show that our proposed algorithm is better than the traditional algorithms in precision, recall and f-measure value.

Clustering PPI data by combining FA and SHC method

PubMed Central

2015-01-01

Clustering is one of main methods to identify functional modules from protein-protein interaction (PPI) data. Nevertheless traditional clustering methods may not be effective for clustering PPI data. In this paper, we proposed a novel method for clustering PPI data by combining firefly algorithm (FA) and synchronization-based hierarchical clustering (SHC) algorithm. Firstly, the PPI data are preprocessed via spectral clustering (SC) which transforms the high-dimensional similarity matrix into a low dimension matrix. Then the SHC algorithm is used to perform clustering. In SHC algorithm, hierarchical clustering is achieved by enlarging the neighborhood radius of synchronized objects continuously, while the hierarchical search is very difficult to find the optimal neighborhood radius of synchronization and the efficiency is not high. So we adopt the firefly algorithm to determine the optimal threshold of the neighborhood radius of synchronization automatically. The proposed algorithm is tested on the MIPS PPI dataset. The results show that our proposed algorithm is better than the traditional algorithms in precision, recall and f-measure value. PMID:25707632

SHC Project 3.63, Task 2, Beneficial Use of Waste Materials

EPA Science Inventory

SHC Project 3.63, Task 2, “Beneficial Use of Waste Materials”, is designed to conduct research and analyses to characterize and quantify the risks and benefits of using or reusing waste materials. There are 6 primary research areas in Task 2 that cover a broad spectr...

Performance of syndromic management for the detection and treatment of genital Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among women attending antenatal, well woman and sexual health clinics in Papua New Guinea: a cross-sectional study

PubMed Central

Vallely, Lisa M; Toliman, Pamela; Ryan, Claire; Rai, Glennis; Wapling, Johanna; Gabuzzi, Josephine; Allen, Joyce; Opa, Christine; Munnull, Gloria; Kaima, Petronia; Kombuk, Benny; Kumbia, Antonia; Kombati, Zure; Law, Greg; Kelly-Hanku, Angela; Wand, Handan; Siba, Peter M; Mola, Glen D L; Kaldor, John M

2017-01-01

Objective Papua New Guinea (PNG) has among the highest estimated prevalences of genital Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) of any country in the Asia-Pacific region. Diagnosis and treatment of these infections have relied on the WHO-endorsed syndromic management strategy that uses clinical presentation without laboratory confirmation to make treatment decisions. We evaluated the performance of this strategy in clinical settings in PNG. Design Women attending antenatal (ANC), well woman (WWC) and sexual health (SHC) clinics in four provinces were invited to participate, completed a face-to-face interview and clinical examination, and provided genital specimens for laboratory testing. We estimated the performance characteristics of syndromic diagnoses against combined laboratory diagnoses. Results 1764 women were enrolled (ANC=765; WWC=614; SHC=385). The prevalences of CT, NG and TV were highest among women attending ANC and SHC. Among antenatal women, syndromic diagnosis of sexually transmitted infection had low sensitivity (9%–21%) and positive predictive value (PPV) (7%–37%), but high specificity (76%–89%) and moderate negative predictive value (NPV) (55%–86%) for the combined endpoint of laboratory-confirmed CT, NG or TV. Among women attending WWC and SHC, ‘vaginal discharge syndrome’ had moderate to high sensitivity (72%–78%) and NPV (62%–94%), but low specificity (26%–33%) and PPV (8%–38%). ‘Lower abdominal pain syndrome’ had low sensitivity (26%–41%) and PPV (8%–23%) but moderate specificity (66%–68%) and high NPV (74%–93%) among women attending WWC, and moderate-high sensitivity (67%–79%) and NPV (62%–86%) but low specificity (26%–28%) and PPV (14%–33%) among SHC attendees. Conclusion The performance of syndromic management for the detection and treatment of genital chlamydia, gonorrhoea and trichomonas was poor among women in different clinical settings in PNG. New diagnostic strategies are needed to control these infections and to prevent their adverse health outcomes in PNG and other high-burden countries. PMID:29288183

Upregulation of cholesterol 24-hydroxylase following hypoxia-ischemia in neonatal mouse brain.

PubMed

Lu, Fuxin; Zhu, Jun; Guo, Selena; Wong, Brandon J; Chehab, Farid F; Ferriero, Donna M; Jiang, Xiangning

2018-06-01

BackgroundMaintenance of cholesterol homeostasis is crucial for brain development. Brain cholesterol relies on de novo synthesis and is cleared primarily by conversion to 24S-hydroxycholesterol (24S-HC) with brain-specific cholesterol 24-hydroxylase (CYP46A1). We aimed to investigate the impact of hypoxia-ischemia (HI) on brain cholesterol metabolism in the neonatal mice.MethodsPostnatal day 9 C57BL/6 pups were subjected to HI using the Vannucci model. CYP46A1 expression was assessed with western blotting and its cellular localization was determined using immunofluorescence staining. The amount of brain cholesterol, 24S-HC in the cortex and in the serum, was measured with enzyme-linked immunosorbent assay (ELISA).ResultsThere was a transient cholesterol loss at 6 h after HI. CYP46A1 was significantly upregulated at 6 and 24 h following HI with a concomitant increase of 24S-HC in the ipsilateral cortex and in the serum. The serum levels of 24S-HC correlated with those in the brain, as well as with necrotic and apoptotic cell death evaluated by the expression of spectrin breakdown products and cleaved caspase-3 at 6 and 24 h after HI.ConclusionEnhanced cholesterol turnover by activation of CYP46A1 represents disrupted brain cholesterol homeostasis early after neonatal HI. 24S-HC might be a novel blood biomarker for severity of hypoxic-ischemic encephalopathy with potential clinical application.

Health-Related Quality of Life, Subjective Health Complaints, Psychological Distress and Coping in Pakistani Immigrant Women With and Without the Metabolic Syndrome : The InnvaDiab-DEPLAN Study on Pakistani Immigrant Women Living in Oslo, Norway.

PubMed

Hjellset, Victoria Telle; Ihlebæk, Camilla M; Bjørge, Benedikte; Eriksen, Hege R; Høstmark, Arne T

2011-08-01

The increasingly high number of immigrants from South-East Asia with The Metabolic Syndrome (MetS) is an important challenge for the public health sector. Impaired glucose is essential in MetS. The blood glucose concentration is not only governed by diet and physical activity, but also by psychological distress which could contribute to the development of MetS. The aim of this study is to describe health-related quality of life, subjective health complaints (SHC), psychological distress, and coping in Pakistani immigrant women, with and without MetS. As a part of an randomized controlled intervention study in Oslo, Norway, female Pakistani immigrants (n = 198) answered questionnaires regarding health related quality of life, SHC, psychological distress, and coping. Blood variables were determined and a standardized oral glucose tolerance test was performed. The participants had a high score on SHC and psychological distress. About 40% of the participants had MetS, and this group showed significantly lower general health, lower physical function, and more bodily pain, than those without MetS. Those with MetS also had more SHC, depressive symptoms, higher levels of somatisation, and scored significantly lower on the coping strategy of active problem solving. Pakistani immigrant women seem to have a high prevalence of SHC and psychological distress, especially those with MetS.

Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin.

PubMed

Pruett, W; Yuan, Y; Rose, E; Batzer, A G; Harada, N; Skolnik, E Y

1995-03-01

Insulin receptor substrate 1 (IRS-1) mediates the activation of a variety of signaling pathways by the insulin and insulin-like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH2 domains. We and others have shown that in response to insulin stimulation IRS-1 binds GRB2/Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor. Recently, it has been shown that the interleukin (IL)-4 receptor also phosphorylates IRS-1 and an IRS-1-related molecule, 4PS. Unlike insulin, however, IL-4 fails to activate Ras, extracellular signal-regulated kinases (ERKs), or mitogen-activated protein kinases. We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. In agreement with previous findings, IL-4 failed to activate the ERKs in this cell line or to stimulate DNA synthesis, whereas the same responses were activated by insulin. Surprisingly, IL-4's failure to activate ERKs was not due to a failure to stimulate the association of tyrosine-phosphorylated IRS-1 with GRB2/Sos; the amounts of GRB2/Sos associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. Moreover, the amounts of phosphatidylinositol 3-kinase activity associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. In contrast to insulin, however, IL-4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB2. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Previous studies have indicated that activation of ERks in this cell line is dependent upon Ras since a dominant-negative Ras (Asn-17) blocks ERK activation by insulin. Our findings, taken in the context of previous work, suggest that binding of GRB2/Sos to Shc may be the predominant mechanism whereby insulin as well as cytokine receptors activate Ras.

76 FR 35934 - In the Matter of: SHC Corp. (f/k/a Victormaxx Technologies, Inc.), Shells Seafood Restaurants...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] In the Matter of: SHC Corp. (f/k/a Victormaxx Technologies, Inc.), Shells Seafood Restaurants, Inc., SI Restructuring, Inc. (f/k/a Schlotzsky's, Inc.), SLS... a lack of current and accurate information concerning the securities of Shells Seafood Restaurants...

Socioeconomic Disparities in Adverse Birth Outcomes in Urban and Rural Contexts: a French Mother-Child Cohort.

PubMed

Bertin, Mélanie; Viel, Jean-François; Monfort, Christine; Cordier, Sylvaine; Chevrier, Cécile

2015-09-01

Although adverse birth outcomes have been associated with neighbourhood deprivation in urban areas, few studies have addressed this issue in rural zones. This study examines whether associations between neighbourhood deprivation and adverse birth outcomes differ in urban and rural contexts, while taking individual characteristics and spatial accessibility of prenatal care (SAPC) into account. Pregnant women from a French mother-child cohort were recruited from 2002 to 2006 in Brittany. Their residential addresses were geocoded into their census blocks (the finest geographical resolution available). Deprivation was assessed at the same neighbourhood level. Models to assess the associations of deprivation, stratified by urban/rural status, with preterm delivery (PTD), with small for gestational age birth weight (SGA) and with small for gestational age head circumference at birth (SHC), estimated odds ratios (ORs), adjusted for maternal socioeconomic characteristics and SAPC. This study considered 2929 liveborn singleton pregnancies from 780 census blocks. Neighbourhood deprivation was associated with increased risks of SGA and SHC (P trend < 0.01 and 0.03 respectively), only among mothers residing in rural areas. Neighbourhood deprivation had statistically significantly heterogeneous effects on SGA and SHC according to the urban/rural status of maternal residence. These findings suggest that neighbourhood deprivation affects fetal growth differentially in urban and rural areas and that SAPC does not seem to be responsible for this difference. Comparison of these findings with the literature requires caution in the conceptualisation of urban and rural settings. © 2015 John Wiley & Sons Ltd.

Comorbid subjective health complaints in patients with sciatica: a prospective study including comparison with the general population.

PubMed

Grøvle, Lars; Haugen, Anne J; Ihlebaek, Camilla M; Keller, Anne; Natvig, Bård; Brox, Jens I; Grotle, Margreth

2011-06-01

Chronic nonspecific low back pain is accompanied by high rates of comorbid mental and physical conditions. The aims of this study were to investigate if patients with specific back pain, that is, sciatica caused by lumbar herniation, report higher rates of subjective health complaints (SHCs) than the general population and if there is an association between change in sciatica symptoms and change in SHCs over a 12-month period. A multicenter cohort study of 466 sciatica patients was conducted with follow-up at 3 months and 1 year. Comorbid SHCs were measured by 27 items of the SHC inventory. Odds ratios (ORs) for each SHC were calculated with comparison to a general population sample (n=928) by logistic regression. The SHC number was calculated by summing all complaints present. At baseline, the ORs for reporting SHCs for the sciatica patients were significantly elevated in 15 of the 27 items with a mean (S.D.) SHC number of 7.5 (4.4), compared to 5.2 (4.4) in the general population (P<.01). Among those who during the 1-year follow-up period fully recovered from their sciatica, the SHC number was reduced to normal levels. Among those with persisting or worsening sciatica, the number increased to a level almost double that of the general population. Compared to the general population, the prevalence of subjective health complaints in sciatica is increased. During follow-up, the number of health complaints increased in patients with persisting or worsening sciatica. Copyright © 2010 Elsevier Inc. All rights reserved.

P66Shc signals to age

PubMed Central

Trinei, Mirella; Berniakovich, Ina; Beltrami, Elena; Migliaccio, Enrica; Fassina, Ambrogio; Pelicci, PierGiuseppe; Giorgio, Marco

2009-01-01

Oxygen metabolism is thought to impact on aging through the formation of reactive oxygen species (ROS) that are supposed to damage biological molecules. The study of p66Shc, a crucial regulator of ROS level involved in aging dysfunction, suggests that the incidence of degenerative disease and longevity are determined by a specific signaling function of ROS other than their unspecific damaging property. PMID:20157533

The devil is in the details: maximizing revenue for daily trauma care.

PubMed

Barnes, Stephen L; Robinson, Bryce R H; Richards, J Taliesin; Zimmerman, Cindy E; Pritts, Tim A; Tsuei, Betty J; Butler, Karyn L; Muskat, Peter C; Davis, Kenneth; Johannigman, Jay A

2008-10-01

Falling reimbursement rates for trauma care demand a concerted effort of charge capture for the fiscal survival of trauma surgeons. We compared current procedure terminology code distribution and billing patterns for Subsequent Hospital Care (SHC) before and after the institution of standardized documentation. Standardized SHC progress notes were created. The note was formulated with an emphasis on efficiency and accuracy. Documentation was completed by residents in conjunction with attendings following standard guidelines of linkage. Year-to-year patient volume, length of stay (LOS), injury severity, bills submitted, coding of service, work relative value units (wRVUs), revenue stream, and collection rate were compared with and without standardized documentation. A 394% average revenue increase was observed with the standardization of SHC documentation. Submitted charges more than doubled in the first year despite a 14% reduction in admissions and no change in length of stay. Significant increases in level II and level III billing and billing volume (P < .05) were sustainable year to year and resulted in an average per patient admission SHC income increase from $91.85 to $362.31. Use of a standardized daily progress note dramatically increases the accuracy of coding and associated billing of subsequent hospital care for trauma services.

2015 SHC BOSC Poster on the EPA/NIMHD Centers of ...

EPA Pesticide Factsheets

EPA supports research that will help in the understanding and prevention of health disparities from environmental conditions and pollution. Racial/ethnic and economic disparities cause many health problems and are very costly to our society. EPA seeks to ensure that no community bears a disproportionate burden, especially those which are susceptible, vulnerable, or socioeconomically disadvantaged. The 2015 SHC BOSC Poster on the EPA/NIMHD Centers of Excellence on Environmental Health Disparities Research provides a summary of the EPA/NIMHD joint Centers. It discusses the purpose and utility of the research, its connection to the SHC portfolio, research highlights, as well as potential application and translation of the results. The poster also includes a list of intended users for the research, potential lessons learned, and provides a snapshot of future health disparities research.

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

Xu, Xiaomei; Hu, Yan; Zhai, Xiaohan

Salvianolic acid A (SalA) is a phenolic carboxylic acid derivative extracted from Salvia miltiorrhiza. It has many biological and pharmaceutical activities. The purpose of this study was to investigate the effect of SalA on concanavalin A (ConA)-induced acute hepatic injury in Kunming mice and to explore the role of SIRT1 in such an effect. The results showed that in vivo pretreatment with SalA significantly reduced ConA-induced elevation in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and decreased levels of the hepatotoxic cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Moreover, the SalA pretreatment ameliorated the increasesmore » in NF-κB and in cleaved caspase-3 caused by ConA exposure. Whereas, the pretreatment completely reversed expression of the B-cell lymphoma-extra large (Bcl-xL). More importantly, the SalA pretreatment significantly increased the expression of SIRT1, a NAD{sup +}-dependent deacetylase, which was known to attenuate acute hypoxia damage and metabolic liver diseases. In our study, the increase in SIRT1 was closely associated with down-regulation of the p66 isoform (p66shc) of growth factor adapter Shc at both protein and mRNA levels. In HepG2 cell culture, SalA pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly reversed the decreased expression of p66shc, and attenuated SalA-induced p66shc down-regulation. Collectively, the present study indicated that SalA may be a potent activator of SIRT and that SalA can alleviate ConA-induced hepatitis through SIRT1-mediated repression of the p66shc pathway. - Highlights: • We report for the first time that SalA protects against ConA-induced hepatitis. • We find that SalA is a potential activator of SIRT1. • SalA's protection against hepatitis involves SIRT1-mediated repression of p66shc.« less

Shc and the mechanotransduction of cellular anchorage and metastasis.

PubMed

Terada, Lance S

2017-02-17

Tissue cells continually monitor anchorage conditions by gauging the physical properties of their underlying matrix and surrounding environment. The Rho and Ras GTPases are essential components of these mechanosensory pathways. These molecular switches control both cytoskeletal as well as cell fate responses to anchorage conditions and are thus critical to our understanding of how cells respond to their physical environment and, by extension, how malignant cells gainsay these regulatory pathways. Recent studies indicate that 2 proteins produced by the SHC1 gene, thought for the most part to functionally oppose each other, collaborate in their ability to respond to mechanical force by initiating respective Rho and Ras signals. In this review, we focus on the coupling of Shc and GTPases in the cellular response to mechanical anchorage signals, with emphasis on its relevance for cancer.

Expression of hygromycin B resistance in oyster culinary-medicinal mushroom, Pleurotus ostreatus (Jacq.:Fr.)P. Kumm. (higher Basidiomycetes) using three gene expression systems.

PubMed

Dong, Xiaoya; Zhang, Ke; Gao, Yuqian; Qi, Yuancheng; Shen, Jinwen; Qiu, Liyou

2012-01-01

Three hygromycin B phosphotransferase (hph) gene expression systems for culinary-medicinal Oyster mushroom, Pleurotus ostreatus, plasmid pSHC, pAN7-1, and pBHt1 were evaluated through PEG/CaCl(2)-mediated protoplast transformation. Plasmid pSHC is a newly constructed hph gene expression system, composed of Escherichia coli hph gene, the P. ostreatus sdi promoter, and the CaMV35S terminator. The vector pAN7-1 was commonly used for integrative transformation in filamentous fungi. Plasmid pBHtl is a T-DNA binary vector, usually introduced into fungi by Agrobacterium-mediated transformation. The results showed that plasmids pSHC, pAN7-1, and pBHt1 were all integrated into the host chromosomes and expressed hygromycin B resistance in P. ostreatus. pAN7-1 had the highest transformation efficiency and hph gene expression level, pSHC the second, and pBHt1 the lowest. Growth rates of the transformants on plates containing hygromycin B were in correspondence with their hph gene expression levels. To our knowledge, this is the first report on integrated transformation of plasmid pAN7-1 and pBHt1 in P. ostreatus.

Tunable Intrinsic Spin Hall Conductivities in Bi2(Se,Te)3 Topological Insulators

NASA Astrophysics Data System (ADS)

Şahin, Cüneyt; Flatté, Michael E.

2015-03-01

It has been recently shown by spin-transfer torque measurements that Bi2Se3 exhibits a very large spin Hall conductivity (SHC). It is expected that Bi2Te3, a topological insulator with similar crystal and band structures as well as large spin-orbit coupling, would also exhibit a giant SHC. In this study we have calculated intrinsic spin Hall conductivities of Bi2Se3andBi2Te3 topological insulators from a tight-binding Hamiltonian including two nearest-neighbor interactions. We have calculated the Berry curvature, used the Kubo formula in the static, clean limit and shown that both materials exhibit giant spin Hall conductivities, consistent with the results of Ref. 1 and larger than previously reported Bi1-xSbx alloys. The density of Berry curvature has also been computed from the full Brillouin zone in order to compute the dependence of the SHC in these materials on the Fermi energy. Finally we report the intrinsic SHC for Bi2(Se,Te)3 topological insulators, which changes dramatically with doping or gate voltage. This work was supported in part by C-SPIN, one of six centers of STARnet, a Semiconductor Research Corporation program, sponsored by MARCO and DARPA.

Heterogeneity of porcine alveolar macrophages in experimental pneumonia.

PubMed

Berndt, A; Müller, G

1997-07-01

The aim of the study was the morphological and the phenotypic characterization of the porcine non-lymphocytic bronchoalveolar lavage (BAL) cell population of unaffected- and intrabronchial with Pasteurella multocida- (P.m.) infected swine using flow cytometry. Three non-lymphocytic cell populations of the porcine bronchoalveolar lavage could be differentiated: (1) large, high autofluorescent cells, (LHC); (2) small, high autofluorescent cells, (SHC); (3) small, low autofluorescent cells, (SLC). In comparison with the control animals, the percentage of the LHC and SHC within the whole non-lymphocytic cell population was decreased, whereas the SLC was significantly enhanced after infection. In order to investigate the phenotype of these cell populations, monoclonal antibodies against porcine antigens (SWC1, SWC3a, MHC class II, 2G6 (against macrophages)) were used. The results showed that the cells of the SLC seem to belong to the granulocytes, whereas the LHC and the SHC are lung macrophages. After the infection of the animals the percentage of the SWC1 positive cells of LHC and SHC were significantly increased, indicating an entrance of more immature macrophages. The percentage of the MHC class II antibody binding cells of all three non-lymphocytic populations was-decreased after infection, indicating a restricted MHC class II dependent antigen recognition in P.m. pneumonia.

Subjective health complaints of teachers from primary and secondary schools in Hong Kong.

PubMed

Chong, Elaine Y L; Chan, Alan H S

2010-01-01

This study aimed to investigate the subjective health complaints (SHC) in the teaching profession of Hong Kong. On the basis of the SHC inventory, a questionnaire was prepared for data collection through a mail survey. A total of 1710 usable questionnaires were returned by the primary or secondary school teachers. The results showed that 99.5% (n = 1702) of respondents suffered at least one type of the 39 single health problems on the total SHC scale during the preceding 30 days. The 10 most frequently reported health complaints among the teachers were tiredness, eyestrain, anxiety, sleep problems, voice disorder, shoulder pain, neck pain, headache, cold/flu, and lower-back pain. With the exception of the category of pseudoneurological complaints, primary school teachers showed a statistically higher prevalence in reporting problems in 6 of 7 subscales. The 5 most severe complaints were tiredness, eyestrain, sleep problems, shoulder pain, and voice disorder.

Spherical Hecke algebra in the Nekrasov-Shatashvili limit

NASA Astrophysics Data System (ADS)

Bourgine, Jean-Emile

2015-01-01

The Spherical Hecke central (SHc) algebra has been shown to act on the Nekrasov instanton partition functions of gauge theories. Its presence accounts for both integrability and AGT correspondence. On the other hand, a specific limit of the Omega background, introduced by Nekrasov and Shatashvili (NS), leads to the appearance of TBA and Bethe like equations. To unify these two points of view, we study the NS limit of the SHc algebra. We provide an expression of the instanton partition function in terms of Bethe roots, and define a set of operators that generates infinitesimal variations of the roots. These operators obey the commutation relations defining the SHc algebra at first order in the equivariant parameter ɛ 2. Furthermore, their action on the bifundamental contributions reproduces the Kanno-Matsuo-Zhang transformation. We also discuss the connections with the Mayer cluster expansion approach that leads to TBA-like equations.

Mixed-methods evaluation of a novel online STI results service.

PubMed

Gibbs, Jo; Aicken, Catherine R H; Sutcliffe, Lorna J; Gkatzidou, Voula; Tickle, Laura J; Hone, Kate; Sadiq, S Tariq; Sonnenberg, Pam; Estcourt, Claudia S

2018-01-11

Evidence on optimal methods for providing STI test results is lacking. We evaluated an online results service, developed as part of an eSexual Health Clinic (eSHC). We evaluated the online results service using a mixed-methods approach within large exploratory studies of the eSHC. Participants were chlamydia- positive and negative users of online postal self-sampling services in six National Chlamydia Screening Programme (NCSP) areas and chlamydia-positive patients from two genitourinary medicine (GUM) clinics between 21 July 2014 and 13 March 2015. Participants received a discreetly worded National Health Service 'NHS no-reply' text message (SMS) informing them that their test results were ready and providing a weblink to a secure website. Participants logged in with their date of birth and mobile telephone or clinic number. Chlamydia-positive patients were offered online management. All interactions with the eSHC system were automatically logged and their timing recorded. Post-treatment, a service evaluation survey (n=152) and qualitative interviews (n=36) were conducted by telephone. Chlamydia-negative patients were offered a short online survey (n=274). Data were integrated. 92% (134/146) of NCSP chlamydia-positive patients, 82% (161/197) of GUM chlamydia-positive patients and 89% (1776/1997) of NCSP chlamydia-negative participants accessed test results within 7 days. 91% of chlamydia-positive patients were happy with the results service; 64% of those who had tested previously found the results service better or much better than previous experiences. 90% of chlamydia-negative survey participants agreed they would be happy to receive results this way in the future. Interviewees described accessing results with ease and appreciated the privacy and control the two-step process gave them. A discreet SMS to alert users/patients that results are available, followed by provision of results via a secure website, was highly acceptable, irrespective of test result and testing history. The eSHC results service afforded users privacy and control over when they viewed results without compromising access. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Aging mechanisms in bone

PubMed Central

Almeida, Maria

2012-01-01

Advancing age and loss of bone mass and strength are closely linked. Elevated osteoblast and osteocyte apoptosis and decreased osteoblast number characterize the age-related skeletal changes in humans and rodents. Similar to other tissues, oxidative stress increases in bone with age. This article reviews current knowledge on the effects of the aging process on bone and its cellular constituents, with particular emphasis on the role of reactive oxygen species (ROS). FoxOs, sirtuins and the p53/p66shc signaling cascade alter osteoblast number and bone formation via ROS-dependent and -independent mechanisms. Specifically, activation of the p53/p66shc signaling increases osteoblast/osteocyte apoptosis in the aged skeleton and decreases bone mass. FoxO activation in osteoblasts prevents oxidative stress to preserve skeletal homeostasis. However, while defending against stress FoxOs bind to β-catenin and attenuate Wnt/T-cell cell factor transcriptional activity and osteoblast generation. Thus, pathways that impact longevity and several diseases of ageing might also contribute to age-related osteoporosis. PMID:23705067

The fibroblast growth factor receptor (FGFR) agonist FGF1 and the neural cell adhesion molecule-derived peptide FGL activate FGFR substrate 2alpha differently.

PubMed

Chen, Yongshuo; Li, Shizhong; Berezin, Vladimir; Bock, Elisabeth

2010-07-01

Activation of fibroblast growth factor (FGF) receptors (FGFRs) both by FGFs and by the neural cell adhesion molecule (NCAM) is crucial in the development and function of the nervous system. We found that FGFR substrate 2alpha (FRS2alpha), Src homologous and collagen A (ShcA), and phospholipase-Cgamma (PLCgamma) were all required for neurite outgrowth from cerebellar granule neurons (CGNs) induced by FGF1 and FGL (an NCAM-derived peptide agonist of FGFR1). Like FGF1, FGL induced tyrosine phosphorylation of FGFR1, FRS2alpha, ShcA, and PLCgamma in a time- and dose-dependent manner. However, the activation of FRS2alpha by FGL was significantly lower than the activation by FGF1, indicating a differential signaling profile induced by NCAM compared with the cognate growth factor.

Vascular dysfunction and fibrosis in stroke-prone spontaneously hypertensive rats: The aldosterone-mineralocorticoid receptor-Nox1 axis.

PubMed

Harvey, Adam P; Montezano, Augusto C; Hood, Katie Y; Lopes, Rheure A; Rios, Francisco; Ceravolo, Graziela; Graham, Delyth; Touyz, Rhian M

2017-06-15

We questioned whether aldosterone and oxidative stress play a role in vascular damage in severe hypertension and investigated the role of Nox1 in this process. We studied mesenteric arteries, aortas and vascular smooth muscle cells (VSMC) from WKY and SHRSP rats. Vascular effects of eplerenone or canrenoic acid (CA) (mineralocorticoid receptor (MR) blockers), ML171 (Nox1 inhibitor) and EHT1864 (Rac1/2 inhibitor) were assessed. Nox1-knockout mice were also studied. Vessels and VSMCs were probed for Noxs, reactive oxygen species (ROS) and pro-fibrotic/inflammatory signaling. Blood pressure and plasma levels of aldosterone and galectin-3 were increased in SHRSP versus WKY. Acetylcholine-induced vasorelaxation was decreased (61% vs 115%) and phenylephrine-induced contraction increased in SHRSP versus WKY (E max 132.8% vs 96.9%, p<0.05). Eplerenone, ML171 and EHT1864 attenuated hypercontractility in SHRSP. Vascular expression of collagen, fibronectin, TGFβ, MCP-1, RANTES, MMP2, MMP9 and p66Shc was increased in SHRSP versus WKY. These changes were associated with increased ROS generation, 3-nitrotyrosine expression and Nox1 upregulation. Activation of vascular p66Shc and increased expression of Nox1 and collagen I were prevented by CA in SHRSP. Nox1 expression was increased in aldosterone-stimulated WKY VSMCs, an effect that was amplified in SHRSP VSMCs (5.2vs9.9 fold-increase). ML171 prevented aldosterone-induced VSMC Nox1-ROS production. Aldosterone increased vascular expression of fibronectin and PAI-1 in wild-type mice but not in Nox1-knockout mice. Our findings suggest that aldosterone, which is increased in SHRSP, induces vascular damage through MR-Nox1-p66Shc-mediated processes that modulate pro-fibrotic and pro-inflammatory signaling pathways. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion.

PubMed

Stanicka, Joanna; Rieger, Leonie; O'Shea, Sandra; Cox, Orla; Coleman, Michael; O'Flanagan, Ciara; Addario, Barbara; McCabe, Nuala; Kennedy, Richard; O'Connor, Rosemary

2018-06-01

IGF-1 receptor (IGF-1R) and integrin cooperative signaling promotes cancer cell survival, proliferation, and motility, but whether this influences cancer progression and therapy responses is largely unknown. Here we investigated the non-receptor tyrosine adhesion kinase FES-related (FER), following its identification as a potential mediator of sensitivity to IGF-1R kinase inhibition in a functional siRNA screen. We found that FER and the IGF-1R co-locate in cells and can be co-immunoprecipitated. Ectopic FER expression strongly enhanced IGF-1R expression and phosphorylation on tyrosines 950 and 1131. FER phosphorylated these sites in an IGF-1R kinase-independent manner and also enhanced IGF-1-mediated phosphorylation of SHC, and activation of either AKT or MAPK-signaling pathways in different cells. The IGF-1R, β1 Integrin, FER, and its substrate cortactin were all observed to co-locate in cell adhesion complexes, the disruption of which reduced IGF-1R expression and activity. High FER expression correlates with phosphorylation of SHC in breast cancer cell lines and with a poor prognosis in patient cohorts. FER and SHC phosphorylation and IGF-1R expression could be suppressed with a known anaplastic lymphoma kinase inhibitor (AP26113) that shows high specificity for FER kinase. Overall, we conclude that FER enhances IGF-1R expression, phosphorylation, and signaling to promote cooperative growth and adhesion signaling that may facilitate cancer progression.

Health-Related Quality of Life Measures for Physically Active Elderly in Community Exercise Programs in Catalonia: Comparative Analysis with Sedentary People

PubMed Central

Fortuño-Godes, Jesús; Guerra-Balic, Myriam; Cabedo-Sanromà, Josep

2013-01-01

Objective. To evaluate Health-Related Quality of Life (HRQoL), medication used, and Stock of Health Capital (SHC) in physically active elderly participants in Community Exercise Programs (CEPs) compared to a sedentary group. Methods. EuroQol standardized instrument was completed by physically active elderly (n = 2,185) who participated in CEPs. Common items were compared to HRQoL data of 1,874 sedentary elderly people, taken from the Catalan Health Survey 2006 (CHS'06). Visual Analogue Scale (VAS) outcomes and medication used were assessed through parametric statistics. Dimensions of health conditions were compared, between sedentary people and physically active elderly participants in CEPs. SHC results were obtained combining the EuroQol scores and Life Expectancy (LE) values. An economic value of €34,858.70 was assigned to these years of LE. Results. Physically active subjects had better HRQoL values (75.36 in males and 70.71 in females) than CHS'06 sedentary subjects (58.35 in males and 50.59 in females). Medication used was different between physically active subjects (1.89 in males and 2.87 in females) and CHS'06 sedentary subjects (4.34 in males and 4.21 in females). SHC data for physically active elderly (€465,988.31/QALY in males and €522,550.31/QALY in females) were higher than for CHS'06 sedentary subjects (€363,689.33/QALY in males and €346,615.91/QALY in females). PMID:24454357

Investigation of Non-linear Chirp Coding for Improved Second Harmonic Pulse Compression.

PubMed

Arif, Muhammad; Ali, Muhammad Asim; Shaikh, Muhammad Mujtaba; Freear, Steven

2017-08-01

Non-linear frequency-modulated (NLFM) chirp coding was investigated to improve the pulse compression of the second harmonic chirp signal by reducing the range side lobe level. The problem of spectral overlap between the fundamental component and second harmonic component (SHC) was also investigated. Therefore, two methods were proposed: method I for the non-overlap condition and method II with the pulse inversion technique for the overlap harmonic condition. In both methods, the performance of the NLFM chirp was compared with that of the reference LFM chirp signals. Experiments were performed using a 2.25 MHz transducer mounted coaxially at a distance of 5 cm with a 1 mm hydrophone in a water tank, and the peak negative pressure of 300 kPa was set at the receiver. Both simulations and experimental results revealed that the peak side lobe level (PSL) of the compressed SHC of the NLFM chirp was improved by at least 13 dB in method I and 5 dB in method II when compared with the PSL of LFM chirps. Similarly, the integrated side lobe level (ISL) of the compressed SHC of the NLFM chirp was improved by at least 8 dB when compared with the ISL of LFM chirps. In both methods, the axial main lobe width of the compressed NLFM chirp was comparable to that of the LFM signals. The signal-to-noise ratio of the SHC of NLFM was improved by as much as 0.8 dB, when compared with the SHC of the LFM signal having the same energy level. The results also revealed the robustness of the NLFM chirp under a frequency-dependent attenuation of 0.5 dB/cm·MHz up to a penetration depth of 5 cm and a Doppler shift up to 12 kHz. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Identification of a Potent Apoptotic Peptide Produced by Fibroblasts; Studies Towards the Design of a Novel Agent for Breast Cancer Therapy

DTIC Science & Technology

2007-09-05

Mannucci, R., Nicoletti, I., Lanfrancone, L., Giorgio, M., and Pelicci, P. G. (2004). The life span determinant p66Shc localizes to mitochondria where it... mitochondria and promoting the generation of intracellular reactive oxygen species (ROS) [13-15]. p66Shc possesses an additional N-terminal domain, and...PP2A, which in turn could dephosphorylate and ac- tivate Bax [21]. Once activated, Bax could translocate to the mitochondria and perturb the

Transient analysis and energy optimization of solar heating and cooling systems in various configurations

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

Calise, F.; Dentice d'Accadia, M.; Palombo, A.

2010-03-15

In this paper, a transient simulation model of solar-assisted heating and cooling systems (SHC) is presented. A detailed case study is also discussed, in which three different configurations are considered. In all cases, the SHC system is based on the coupling of evacuated solar collectors with a single-stage LiBr-H{sub 2}O absorption chiller, and a gas-fired boiler is also included for auxiliary heating, only during the winter season. In the first configuration, the cooling capacity of the absorption chiller and the solar collector area are designed on the basis of the maximum cooling load, and an electric chiller is used asmore » the auxiliary cooling system. The second layout is similar to the first one, but, in this case, the absorption chiller and the solar collector area are sized in order to balance only a fraction of the maximum cooling load. Finally, in the third configuration, there is no electric chiller, and the auxiliary gas-fired boiler is also used in summer to feed the absorption chiller, in case of scarce solar irradiation. The simulation model was developed using the TRNSYS software, and included the analysis of the dynamic behaviour of the building in which the SHC systems were supposed to be installed. The building was simulated using a single-lumped capacitance model. An economic model was also developed, in order to assess the operating and capital costs of the systems under analysis. Furthermore, a mixed heuristic-deterministic optimization algorithm was implemented, in order to determine the set of the synthesis/design variables that maximize the energy efficiency of each configuration under analysis. The results of the case study were analyzed on monthly and weekly basis, paying special attention to the energy and monetary flows of the standard and optimized configurations. The results are encouraging as for the potential of energy saving. On the contrary, the SHC systems appear still far from the economic profitability: however, this is notoriously true for the great majority of renewable energy systems. (author)« less

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.

PubMed

Menachery, Vineet D; Yount, Boyd L; Debbink, Kari; Agnihothram, Sudhakar; Gralinski, Lisa E; Plante, Jessica A; Graham, Rachel L; Scobey, Trevor; Ge, Xing-Yi; Donaldson, Eric F; Randell, Scott H; Lanzavecchia, Antonio; Marasco, Wayne A; Shi, Zhengli-Li; Baric, Ralph S

2015-12-01

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.

Landscape metrics as predictors of hydrologic connectivity between Coastal Plain forested wetlands and streams

PubMed Central

Epting, Steven M.; Hosen, Jacob D.; Alexander, Laurie C.; Lang, Megan W.; Armstrong, Alec W.

2018-01-01

Abstract Geographically isolated wetlands, those entirely surrounded by uplands, provide numerous landscape‐scale ecological functions, many of which are dependent on the degree to which they are hydrologically connected to nearby waters. There is a growing need for field‐validated, landscape‐scale approaches for classifying wetlands on the basis of their expected degree of hydrologic connectivity with stream networks. This study quantified seasonal variability in surface hydrologic connectivity (SHC) patterns between forested Delmarva bay wetland complexes and perennial/intermittent streams at 23 sites over a full‐water year (2014–2015). Field data were used to develop metrics to predict SHC using hypothesized landscape drivers of connectivity duration and timing. Connection duration was most strongly related to the number and area of wetlands within wetland complexes as well as the channel width of the temporary stream connecting the wetland complex to a perennial/intermittent stream. Timing of SHC onset was related to the topographic wetness index and drainage density within the catchment. Stepwise regression modelling found that landscape metrics could be used to predict SHC duration as a function of wetland complex catchment area, wetland area, wetland number, and soil available water storage (adj‐R 2 = 0.74, p < .0001). Results may be applicable to assessments of forested depressional wetlands elsewhere in the U.S. Mid‐Atlantic and Southeastern Coastal Plain, where climate, landscapes, and hydrological inputs and losses are expected to be similar to the study area. PMID:29576682

Nonlinear dynamics of emotion-cognition interaction: when emotion does not destroy cognition?

PubMed

Afraimovich, Valentin; Young, Todd; Muezzinoglu, Mehmet K; Rabinovich, Mikhail I

2011-02-01

Emotion (i.e., spontaneous motivation and subsequent implementation of a behavior) and cognition (i.e., problem solving by information processing) are essential to how we, as humans, respond to changes in our environment. Recent studies in cognitive science suggest that emotion and cognition are subserved by different, although heavily integrated, neural systems. Understanding the time-varying relationship of emotion and cognition is a challenging goal with important implications for neuroscience. We formulate here the dynamical model of emotion-cognition interaction that is based on the following principles: (1) the temporal evolution of cognitive and emotion modes are captured by the incoming stimuli and competition within and among themselves (competition principle); (2) metastable states exist in the unified emotion-cognition phase space; and (3) the brain processes information with robust and reproducible transients through the sequence of metastable states. Such a model can take advantage of the often ignored temporal structure of the emotion-cognition interaction to provide a robust and generalizable method for understanding the relationship between brain activation and complex human behavior. The mathematical image of the robust and reproducible transient dynamics is a Stable Heteroclinic Sequence (SHS), and the Stable Heteroclinic Channels (SHCs). These have been hypothesized to be possible mechanisms that lead to the sequential transient behavior observed in networks. We investigate the modularity of SHCs, i.e., given a SHS and a SHC that is supported in one part of a network, we study conditions under which the SHC pertaining to the cognition will continue to function in the presence of interfering activity with other parts of the network, i.e., emotion.

Universality in stochastic exponential growth.

PubMed

Iyer-Biswas, Srividya; Crooks, Gavin E; Scherer, Norbert F; Dinner, Aaron R

2014-07-11

Recent imaging data for single bacterial cells reveal that their mean sizes grow exponentially in time and that their size distributions collapse to a single curve when rescaled by their means. An analogous result holds for the division-time distributions. A model is needed to delineate the minimal requirements for these scaling behaviors. We formulate a microscopic theory of stochastic exponential growth as a Master Equation that accounts for these observations, in contrast to existing quantitative models of stochastic exponential growth (e.g., the Black-Scholes equation or geometric Brownian motion). Our model, the stochastic Hinshelwood cycle (SHC), is an autocatalytic reaction cycle in which each molecular species catalyzes the production of the next. By finding exact analytical solutions to the SHC and the corresponding first passage time problem, we uncover universal signatures of fluctuations in exponential growth and division. The model makes minimal assumptions, and we describe how more complex reaction networks can reduce to such a cycle. We thus expect similar scalings to be discovered in stochastic processes resulting in exponential growth that appear in diverse contexts such as cosmology, finance, technology, and population growth.

Universality in Stochastic Exponential Growth

NASA Astrophysics Data System (ADS)

Iyer-Biswas, Srividya; Crooks, Gavin E.; Scherer, Norbert F.; Dinner, Aaron R.

2014-07-01

Recent imaging data for single bacterial cells reveal that their mean sizes grow exponentially in time and that their size distributions collapse to a single curve when rescaled by their means. An analogous result holds for the division-time distributions. A model is needed to delineate the minimal requirements for these scaling behaviors. We formulate a microscopic theory of stochastic exponential growth as a Master Equation that accounts for these observations, in contrast to existing quantitative models of stochastic exponential growth (e.g., the Black-Scholes equation or geometric Brownian motion). Our model, the stochastic Hinshelwood cycle (SHC), is an autocatalytic reaction cycle in which each molecular species catalyzes the production of the next. By finding exact analytical solutions to the SHC and the corresponding first passage time problem, we uncover universal signatures of fluctuations in exponential growth and division. The model makes minimal assumptions, and we describe how more complex reaction networks can reduce to such a cycle. We thus expect similar scalings to be discovered in stochastic processes resulting in exponential growth that appear in diverse contexts such as cosmology, finance, technology, and population growth.

Tretinoin-loaded lipid-core nanocapsules decrease reactive oxygen species levels and improve bovine embryonic development during in vitro oocyte maturation.

PubMed

Lucas, Caroline Gomes; Remião, Mariana Härter; Komninou, Eliza Rossi; Domingues, William Borges; Haas, Cristina; Leon, Priscila Marques Moura de; Campos, Vinicius Farias; Ourique, Aline; Guterres, Silvia S; Pohlmann, Adriana R; Basso, Andrea Cristina; Seixas, Fabiana Kömmling; Beck, Ruy Carlos Ruver; Collares, Tiago

2015-12-01

In vitro oocyte maturation (IVM) protocols can be improved by adding chemical supplements to the culture media. Tretinoin is considered an important retinoid in embryonic development and its association with lipid-core nanocapsules (TTN-LNC) represents an innovative way of improving its solubility, and chemical stability, and reducing its toxicity. The effects of supplementing IVM medium with TTN-LNC was evaluated by analyzing production of reactive oxygen species (ROS), S36-phosphorilated-p66Shc levels and caspase activity in early embryonic development, and expression of apoptosis and pluripotency genes in blastocysts. The lowest concentration tested (0.25μM) of TTN-LNC generated higher blastocyst rate, lower ROS production and S36-p66Shc amount. Additionally, expression of BAX and SHC1 were lower in both non-encapsulated tretinoin (TTN) and TTN-LNC-treated groups. Nanoencapsulation allowed the use of smaller concentrations of tretinoin to supplement IVM medium thus reducing toxic effects related with its use, decreasing ROS levels and apoptose frequency, and improving the blastocyst rates. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation of Cr(VI) adsorption onto chemically treated Helianthus annuus: optimization using response surface methodology.

PubMed

Jain, Monika; Garg, V K; Kadirvelu, K

2011-01-01

In the present study, chemically treated Helianthus annuus flowers (SHC) were used to optimize the removal efficiency for Cr(VI) by applying Response Surface Methodological approach. The surface structure of SHC was analyzed by Scanning Electron Microscopy (SEM) coupled with Energy Dispersive X-ray Analysis (EDX). Batch mode experiments were also carried out to assess the adsorption equilibrium in aqueous solution. The adsorption capacity (qe) was found to be 7.2 mg/g. The effect of three parameters, that is pH of the solution (2.0-7.0), initial concentration (10-70 mg/L) and adsorbent dose (0.05-0.5 g/100 mL) was studied for the removal of Cr(VI) by SHC. Box-Behnken model was used as an experimental design. The optimum pH, adsorbent dose and initial Cr(VI) concentration were found to be 2.0, 5.0 g/L and 40 mg/L, respectively. Under these conditions, removal efficiency of Cr(VI) was found to be 90.8%. Copyright © 2010 Elsevier Ltd. All rights reserved.

Bioaccumulation of petroleum hydrocarbons in arctic amphipods in the oil development area of the Alaskan Beaufort Sea.

PubMed

Neff, Jerry M; Durell, Gregory S

2012-04-01

An objective of a multiyear monitoring program, sponsored by the US Department of the Interior, Bureau of Ocean Energy Management was to examine temporal and spatial changes in chemical and biological characteristics of the Arctic marine environment resulting from offshore oil exploration and development activities in the development area of the Alaskan Beaufort Sea. To determine if petroleum hydrocarbons from offshore oil operations are entering the Beaufort Sea food web, we measured concentrations of hydrocarbons in tissues of amphipods, Anonyx nugax, sediments, Northstar crude oil, and coastal peat, collected between 1999 and 2006 throughout the development area. Mean concentrations of polycyclic aromatic hydrocarbons (PAH), saturated hydrocarbons (SHC), and sterane and triterpane petroleum biomarkers (StTr) were not significantly different in amphipods near the Northstar oil production facility, before and after it came on line in 2001, and in amphipods from elsewhere in the study area. Forensic analysis of the profiles (relative composition and concentrations) of the 3 hydrocarbon classes revealed that hydrocarbon compositions were different in amphipods, surface sediments where the amphipods were collected, Northstar crude oil, and peat from the deltas of 4 North Slope rivers. Amphipods and sediments contained a mixture of petrogenic, pyrogenic, and biogenic PAH. The SHC in amphipods were dominated by pristane derived from zooplankton, indicating that the SHC were primarily from the amphipod diet of zooplankton detritus. The petroleum biomarker StTr profiles did not resemble those in Northstar crude oil. The forensic analysis revealed that hydrocarbons in amphipod tissues were not from oil production at Northstar. Hydrocarbons in amphipod tissues were primarily from their diet and from river runoff and coastal erosion of natural diagenic and fossil terrestrial materials, including seep oils, kerogens, and peat. Offshore oil and gas exploration and development do not appear to be causing an increase in petroleum hydrocarbon contamination of the Beaufort Sea food web. Copyright © 2011 SETAC.

Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

PubMed Central

Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J

2008-01-01

Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724

Sexual health clinic attendance and non-attendance in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

PubMed Central

Geary, Rebecca S; Clifton, Soazig; Field, Nigel; Heap, Katie L; Mapp, Fiona; Johnson, Anne M; Cassell, Jackie A; Sonnenberg, Pam; Mercer, Catherine H

2018-01-01

Objectives In Britain, sexual health clinics (SHCs) are the most common location for STI diagnosis but many people with STI risk behaviours do not attend. We estimate prevalence of SHC attendance and how this varies by sociodemographic and behavioural factors (including unsafe sex) and describe hypothetical service preferences for those reporting unsafe sex. Methods Complex survey analyses of data from Britain’s third National Survey of Sexual Attitudes and Lifestyles, a probability survey of 15 162 people aged 16–74 years, undertaken 2010–2012. Results Overall, recent attendance (past year) was highest among those aged 16–24 years (16.6% men, 22.4% women), decreasing with age (<1.5% among those 45–74 years). Approximately 15% of sexually-active 16–74 year olds (n=1002 men; n=1253 women) reported ‘unsafe sex’ (condomless first sex with a new partner and/or ≥2 partners and no condom use, past year); >75% of these had not attended a SHC (past year). However, of non-attenders aged 16–44 years, 18.7% of men and 39.0% of women reported chlamydia testing (past year) with testing highest in women aged <25 years. Of those aged 16–44 years reporting unsafe sex, the majority who reported previous SHC attendance would seek STI care there, whereas the majority who had not would use general practice. Conclusion While most reporting unsafe sex had not attended a SHC, many, particularly younger women, had tested for chlamydia suggesting engagement with sexual health services more broadly. Effective, diverse service provision is needed to engage those at-risk and ensure that they can attend services appropriate to their needs. PMID:28974552

Activation of miR-34a-5p/Sirt1/p66shc pathway contributes to doxorubicin-induced cardiotoxicity.

PubMed

Zhu, Jie-Ning; Fu, Yong-Heng; Hu, Zhi-Qin; Li, Wen-Yu; Tang, Chun-Mei; Fei, Hong-Wen; Yang, Hui; Lin, Qiu-Xiong; Gou, De-Ming; Wu, Shu-Lin; Shan, Zhi-Xin

2017-09-19

The molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments. Human miR-34a-5p was also observed increased in the plasma of patients with diffuse large B-cell lymphoma after 9- and 16-week epirubicin therapy. Up-regulation of miR-34a-5p was observed in Dox-induced rat cardiomyocyte H9c2 cells. MiR-34a-5p could augment Bax expression, but inhibited Bcl-2 expression, along with the increases of the activated caspase-3 and mitochondrial potentials in H9C2 cells. MiR-34a-5p was verified to modulate Sirt1 expression post-transcriptionally. In parallel to Sirt1 siRNA, miR-34a-5p could enhance p66shc expression, accompanied by increases of Bax and the activated caspase-3 and a decrease of Bcl-2 in H9c2 cells. Moreover, enforced expression of Sirt1 alleviated Dox-induced apoptosis of H9c2 cells, with suppressing levels of p66shc, Bax, the activated caspase-3 and miR-34a-5p, and enhancing Bcl-2 expression. Therefore, miR-34a-5p enhances cardiomyocyte apoptosis by targeting Sirt1, activation of miR-34a-5p/Sirt1/p66shc pathway contributes to Dox-induced cardiotoxicity, and blockage of this pathway represents a potential cardioprotective effect against anthracyclines.

Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

PubMed

Bahi, Amine

2013-07-01

Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

Sex-specific differences in fetal growth in newborns exposed prenatally to traffic-related air pollution in the PELAGIE mother-child cohort (Brittany, France).

PubMed

Bertin, Mélanie; Chevrier, Cécile; Serrano, Tania; Monfort, Christine; Cordier, Sylvaine; Viel, Jean-François

2015-10-01

Numerous studies have linked prenatal traffic-related air pollution exposure to fetal growth. Recently, several studies have suggested exploring this association independently among boys and girls because of potential sex-specific biological vulnerability to air pollution. Residence-based factors can also influence fetal growth by enhancing susceptibility to the toxic effects of air pollution and must also be considered in these relations. We examined sex-specific associations between prenatal air pollution exposure and fetal growth and explored whether they differed by the urban-rural status of maternal residence. This study relied on the PELAGIE mother-child cohort (2521 women, Brittany, France, 2002-2006). Fetal growth was assessed through birth weight, head circumference and small weight (SGA) and small head circumference (SHC) for gestational age. Nitrogen dioxide (NO2) concentrations at mothers' homes were estimated by using a land use regression model taking into account temporal variation during pregnancy. Associations between estimated NO2 concentrations and fetal growth were assessed with linear regression or logistic regression models, depending on the outcome investigated. An interquartile range (8.8 µg m(-3)) increase in NO2 exposure estimates was associated with a 27.4 g (95% CI 0.8 to 55.6) increase in birth weight and a 0.09 cm (95% CI 0.00-0.17) significant increase in head circumference, among newborn boys only. Their risks of SGA and SHC were reduced (OR 0.70, 95% CI 0.53-0.92, OR 0.76, 95% CI 0.56-1.03, respectively, for an increase of 8.8 µg m(-3)). No statistically significant trends were observed among girls. Urban-rural status modified the effect of air pollution only for SHC and again only for newborn boys. Findings from this study confirm the need to consider sex-specific associations between air pollution and fetal growth and to investigate possible mechanisms by which traffic-related air pollution may increase anthropometric parameters at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

Subjective health complaints in adolescent victims of cyber harassment: moderation through support from parents/friends - a Swedish population-based study.

PubMed

Fridh, Maria; Lindström, Martin; Rosvall, Maria

2015-09-23

Victimization in cyberspace has emerged as a new public health issue among the young. The main purpose of this study was to analyze associations between cyber victimization defined as cyber harassment (CH) (a somewhat broader concept than cyberbullying) and subjective health complaints (SHC), to study whether these associations were modified by parental/friend support (measured as communication), and to explore the influence of traditional bullying victimization (TBV) on the association between CH and SHC. The study population consisted of 8544 students in 9th grade (around 15 years old) who participated in the 2012 Scania public health survey of children and adolescents. The survey was a cross-sectional total-population study conducted in school, with a response rate of 83 %. Main and interaction (stress-buffering) effects of social support on the relationship between CH and SCH were investigated by hierarchical multiple linear regression analyses, adjusted for potential confounders, including TBV. The past-year prevalence of CH (once or several times) was 14 % among boys and 20 % among girls. Having been cyber harassed once or several times during the past year was associated with higher levels of SHC, controlling for age, parental occupation, parental origin, daily smoking, intense alcohol consumption, and disability. Among both boys and girls, the associations were stronger for CH occurring several times than for CH occurring only once. Main effects of parental/friend support were seen for both boys and girls, while stress-buffering effects were indicated for boys only. Additional analysis further adjusting for TBV did not change the associations substantially, indicating that CH has an effect of its own on SHC. Intervention programs aimed at improving the quality of peer and family relationships among children and adolescents might reduce the incidence of both cyber harassment and traditional bullying and lower the prevalence of psychosomatic complaints.

Bioethanol Potential of Energy Sorghum Grown on Marginal and Arable Lands

PubMed Central

Tang, Chaochen; Li, Songbo; Li, Meng; Xie, Guang H.

2018-01-01

Field experiments were conducted in marginal lands, i.e., sub-humid climate and saline-land (SHS) and semi-arid climate and wasteland (SAW), to evaluate ethanol potential based on the biomass yield and chemical composition of biomass type (var. GN-2, GN-4, and GN-10) and sweet type (var. GT-3 and GT-7) hybrids of energy sorghum [Sorghum bicolor (L.) Moench] in comparison with sub-humid climate and cropland (SHC) in northern China. Results showed that environment significantly (p < 0.05) influenced plant growth, biomass yield and components, and subsequently the ethanol potential of energy sorghum. Biomass and theoretical ethanol yield of the crop grown at SHS (12.2 t ha−1 and 3,425 L ha−1, respectively) and SAW (8.6 t ha−1 and 2,091 L ha−1, respectively) were both statistically (p < 0.001) lower than values at the SHC site (32.6 t ha−1 and 11,853 L ha−1, respectively). Higher desirable contents of soluble sugar, cellulose, and hemicellulose were observed at SHS and SHC sites, while sorghum grown at SAW possessed higher lignin and ash contents. Biomass type sorghum was superior to sweet type as non-food ethanol feedstock. In particular, biomass type hybrid GN-10 achieved the highest biomass (17.4 t ha−1) and theoretical ethanol yields (5,423 L ha−1) after averaging data for all environmental sites. The most productive hybrid, biomass type GN-4, exhibited biomass and theoretical ethanol yields >42.1 t ha−1 and 14,913 L ha−1, respectively, at the cropland SHC site. In conclusion, energy sorghum grown on marginal lands showed a very lower ethanol potential, indicating a considerable lower possibility for being used as commercial feedstock supply when compared with that grown on regular croplands. Moreover, screening suitable varieties may improve energy sorghum growth and chemical properties for ethanol production on marginal lands. PMID:29686688

Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl.

PubMed

Odai, H; Sasaki, K; Iwamatsu, A; Nakamoto, T; Ueno, H; Yamagata, T; Mitani, K; Yazaki, Y; Hirai, H

1997-04-15

Grb2/Ash and Shc are the adapter proteins that link tyrosine-kinase receptors to Ras and make tyrosine-kinase functionally associated with receptors and Ras in fibroblasts and hematopoietic cells. Grb2/Ash and Shc have the SH3, SH2, or phosphotyrosine binding domains. These domains bind to proteins containing proline-rich regions or tyrosine-phosphorylated proteins and contribute to the association of Grb2/Ash and Shc with other signaling molecules. However, there could remain unidentified signaling molecules that physically and functionally interact with these adapter proteins and have biologically important roles in the signaling pathways. By using the GST fusion protein including the full length of Grb2/Ash, we have found that c-Cbl and an unidentified 135-kD protein (pp135) are associated with Grb2/Ash. We have also found that they become tyrosine-phosphorylated by treatment of a human leukemia cell line, UT-7, with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have purified the pp135 by using GST-Grb2/Ash affinity column and have isolated the full-length complementary DNA (cDNA) encoding the pp135 using a cDNA probe, which was obtained by the degenerate polymerase chain reaction based on a peptide sequence of the purified pp135. The cloned cDNA has 3,958 nucleotides that contain a single long open reading frame of 3,567 nucleotides, encoding a 1,189 amino acid protein with a predicted molecular weight of approximately 133 kD. The deduced amino acid sequence reveals that pp135 is a protein that has one SH2, one SH3, and one proline-rich domain. The pp135, which contains two motifs conserved among the inositol polyphosphate-5-phosphatase proteins, was shown to have the inositol polyphosphate-5-phosphatase activity. The pp135 was revealed to associate constitutively with Grb2/Ash and inducibly with Shc using UT-7 cells stimulated with GM-CSF. In the cell lines derived from human chronic myelogenous leukemia, pp135 was constitutively tyrosine-phosphorylated and associated with Shc and Bcr-Abl. These facts suggest that pp135 is a signaling molecule that has a unique enzymatic activity and should play an important role in the signaling pathway triggered by GM-CSF and in the transformation of hematopoietic cells caused by Bcr-Abl.

The eSexual Health Clinic system for management, prevention, and control of sexually transmitted infections: exploratory studies in people testing for Chlamydia trachomatis.

PubMed

Estcourt, Claudia S; Gibbs, Jo; Sutcliffe, Lorna J; Gkatzidou, Voula; Tickle, Laura; Hone, Kate; Aicken, Catherine; Lowndes, Catherine M; Harding-Esch, Emma M; Eaton, Sue; Oakeshott, Pippa; Szczepura, Ala; Ashcroft, Richard E; Copas, Andrew; Nettleship, Anthony; Sadiq, S Tariq; Sonnenberg, Pam

2017-04-01

Self-directed and internet-based care are key elements of eHealth agendas. We developed a complex online clinical and public health intervention, the eSexual Health Clinic (eSHC), in which patients with genital chlamydia are diagnosed and medically managed via an automated online clinical consultation, leading to antibiotic collection from a pharmacy. Partner notification, health promotion, and capture of surveillance data are integral aspects of the eSHC. We aimed to assess the safety and feasibility of the eSHC as an alternative to routine care in non-randomised, exploratory proof-of-concept studies. Participants were untreated patients with chlamydia from genitourinary medicine clinics, untreated patients with chlamydia from six areas in England in the National Chlamydia Screening Programme's (NCSP) online postal testing service, or patients without chlamydia tested in the same six NCSP areas. All participants were aged 16 years or older. The primary outcome was the proportion of patients with chlamydia who consented to the online chlamydia pathway who then received appropriate clinical management either exclusively through online treatment or via a combination of online management and face-to-face care. We captured adverse treatment outcomes. Between July 21, 2014, and March 13, 2015, 2340 people used the eSHC. Of 197 eligible patients from genitourinary medicine clinics, 161 accessed results online. Of the 116 who consented to be included in the study, 112 (97%, 95% CI 91-99) received treatment, and 74 of those were treated exclusively online. Of the 146 eligible NCSP patients, 134 accessed their results online, and 105 consented to be included. 93 (89%, 95% CI 81-94) received treatment, and 60 were treated exclusively online. In both groups, median time to collection of treatment was within 1 day of receiving their diagnosis. 1776 (89%) of 1936 NCSP patients without chlamydia accessed results online. No adverse events were recorded. The eSHC is safe and feasible for management of patients with chlamydia, with preliminary evidence of similar treatment outcomes to those in traditional services. This innovative model could help to address growing clinical and public health needs. A definitive trial is needed to assess the efficacy, cost-effectiveness, and public health impact of this intervention. UK Clinical Research Collaboration. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Comparative anti-microbial efficacy of Azadirachta indica irrigant with standard endodontic irrigants: A preliminary study

PubMed Central

Dutta, Arindam; Kundabala, Mala

2014-01-01

Objective: The anti-microbial efficacy of 2.5% sodium hypochlorite (SHC) and 0.2% chlorhexidine gluconate were compared with an experimental irrigant formulated from the Neem tree, Azadirachta indica A. Juss. Materials and Methods: A sample of 36 single rooted anterior teeth with periapical radiolucency and absence of response to vitality tests that required root canal treatment were selected for this study. The test irrigants and their combinations were assigned to five different groups and saline served as the control. Access cavities were prepared using an aseptic technique and samples collected for both anaerobic culture and Gram stained smears, followed by irrigation and sample collection again. The number of organisms were expressed in colony forming units/ml after 72 h of incubation; the smears were analyzed for their microbial loads and tissue clearance and assessed as per defined criteria. Results: Our results found the maximum reduction in microbial loads, when analyzed by culture method, with a combination of SHC and the experimental neem irrigant. Maximum tissue clearance on the Gram Stained smears was also found with the same combination. Conclusion: Neem irrigant has anti-microbial efficacy and can be considered for endodontic use. PMID:24778508

Self-cementing properties of oil shale solid heat carrier retorting residue.

PubMed

Talviste, Peeter; Sedman, Annette; Mõtlep, Riho; Kirsimäe, Kalle

2013-06-01

Oil shale-type organic-rich sedimentary rocks can be pyrolysed to produce shale oil. The pyrolysis of oil shale using solid heat carrier (SHC) technology is accompanied by large amount of environmentally hazardous solid residue-black ash-which needs to be properly landfilled. Usage of oil shale is growing worldwide, and the employment of large SHC retorts increases the amount of black ash type of waste, but little is known about its physical and chemical properties. The objectives of this research were to study the composition and self-cementing properties of black ash by simulating different disposal strategies in order to find the most appropriate landfilling method. Three disposal methods were simulated in laboratory experiment: hydraulic disposal with and without grain size separation, and dry dumping of moist residue. Black ash exhibited good self-cementing properties with maximum compressive strength values of >6 MPa after 90 days. About 80% of strength was gained in 30 days. However, the coarse fraction (>125 µm) did not exhibit any cementation, thus the hydraulic disposal with grain size separation should be avoided. The study showed that self-cementing properties of black ash are governed by the hydration of secondary calcium silicates (e.g. belite), calcite and hydrocalumite.

Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1

PubMed Central

Ma, Yan; Zhang, Chen; Gao, Xiao-Bo; Luo, Hai-Yan; Chen, Yang; Li, Hui-hua; Ma, Xu; Lu, Cai-Ling

2015-01-01

As a nutritional factor, folic acid can prevent cardiac and neural defects during embryo development. Our previous study showed that arsenic impairs embryo development by down-regulating Dvr1/GDF1 expression in zebrafish. Here, we investigated whether folic acid could protect against arsenic-mediated embryo toxicity. We found that folic acid supplementation increases hatching and survival rates, decreases malformation rate and ameliorates abnormal cardiac and neural development of zebrafish embryos exposed to arsenite. Both real-time PCR analysis and whole in-mount hybridization showed that folic acid significantly rescued the decrease in Dvr1 expression caused by arsenite. Subsequently, our data demonstrated that arsenite significantly decreased cell viability and GDF1 mRNA and protein levels in HEK293ET cells, while folic acid reversed these effects. Folic acid attenuated the increase in subcellular reactive oxygen species (ROS) levels and oxidative adaptor p66Shc protein expression in parallel with the changes in GDF1 expression and cell viability. P66Shc knockdown significantly inhibited the production of ROS and the down-regulation of GDF1 induced by arsenite. Our data demonstrated that folic acid supplementation protected against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1/GDF1, and folic acid enhanced the expression of GDF1 by decreasing p66Shc expression and subcellular ROS levels. PMID:26537450

SHC Project 3.63, Task 2, Beneficial Use of Waste Materials ...

EPA Pesticide Factsheets

SHC Project 3.63, Task 2, “Beneficial Use of Waste Materials”, is designed to conduct research and analyses to characterize and quantify the risks and benefits of using or reusing waste materials. There are 6 primary research areas in Task 2 that cover a broad spectrum of topics germane to the beneficial use of waste materials and address Agency, Office, Region and other client needs. The 6 research areas include: 1) Materials Recovery Technology, 2) Beneficial Use of Materials Optimization, 3) Novel Products from Waste Materials, 4) Land Application of Biosolids, 5) Soil Remediation Amendments and 6) Improved Leaching Methods for More Accurate Prediction of Environmental Release of Metals. The objectives of each research area, their intended products and progress to date will be presented. The products of this Task will enable communities and the Agency to better protect and enhance human health, well-being and the environment for current and future generations, through the reduction in material consumption, reuse, and recycling of materials. This presentation is designed to convey the rational, purpose and planned research in EPAs Safe and Healthy Communities (SHC) National Research Program Project 3.63 (Sustainable Materials Management) Task 2, “Beneficial Use of Waste Materials”, which is designed to conduct research and analyses to characterize and quantify the risks and benefits of using or reusing waste materials. . This presentation has bee

SARS-like cluster of circulating bat coronavirus pose threat for human emergence

PubMed Central

Menachery, Vineet D.; Yount, Boyd L.; Debbink, Kari; Agnihothram, Sudhakar; Gralinski, Lisa E.; Plante, Jessica A.; Graham, Rachel L.; Scobey, Trevor; Ge, Xing-Yi; Donaldson, Eric F.; Randell, Scott H.; Lanzavecchia, Antonio; Marasco, Wayne A.; Shi, Zhengli-Li; Baric, Ralph S.

2016-01-01

The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. In this study, we examine the disease potential for SARS-like CoVs currently circulating in Chinese horseshoe bat populations. Utilizing the SARS-CoV infectious clone, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild type backbone can efficiently utilize multiple ACE2 receptor orthologs, replicate efficiently in primary human airway cells, and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from CoVs utilizing the novel spike protein. Importantly, based on these findings, we synthetically rederived an infectious full length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Together, the work highlights a continued risk of SARS-CoV reemergence from viruses currently circulating in bat populations. PMID:26552008

Temperature-insensitive refractive index sensing by use of micro Fabry-Pérot cavity based on simplified hollow-core photonic crystal fiber.

PubMed

Wang, Ying; Wang, D N; Liao, C R; Hu, Tianyi; Guo, Jiangtao; Wei, Huifeng

2013-02-01

A temperature-insensitive micro Fabry-Pérot (FP) cavity based on simplified hollow-core (SHC) photonic crystal fiber (PCF) is demonstrated. Such a device is fabricated by splicing a section of SHC PCF with single mode fibers at both cleaved ends. An extremely low temperature sensitivity of ~0.273 pm/°C is obtained between room temperature and 900°C. By drilling vertical micro-channels using a femtosecond laser, the micro FP cavity can be filled with liquids and functions as a sensitive refractometer and the refractive index sensitivity obtained is ~851.3 nm/RIU (refractive index unit), which indicates an ultra low temperature cross-sensitivity of ~3.2×10(-7) RIU/°C.

Hydrogeologic investigations of the Miocene Nogales Formation in the Nogales Area, Upper Santa Cruz Basin, Arizona

USGS Publications Warehouse

Page, William R.; Gray, Floyd; Bultman, Mark W.; Menges, Christopher M.

2016-07-28

Hydrogeologic investigations were conducted to evaluate the groundwater resource potential for the Miocene Nogales Formation in the Nogales area, southern Arizona. Results indicate that parts of the formation may provide new, deeper sources of groundwater for the area. Geologic mapping determined the hydrogeologic framework of the formation by defining lithologic, mineralogic, and stratigraphic characteristics; identifying potential aquifers and confining units; and mapping faults and fractures which likely influence groundwater flow. Geophysical modeling was used to determine the basin geometry and thickness of the Nogales Formation and younger alluvial aquifers and to identify target areas (deep subbasins) which may prove to be productive aquifers.Volcaniclastic sandstone samples from the formation were analyzed for porosity, bulk density, saturated hydraulic conductivity, and fabric. Effective porosity ranges from 16 to 42 percent, bulk density from 1.6 to 2.47 grams per cubic centimeter, and saturated hydraulic conductivity (SHC) from 4 to 57 centimeters per day (4.9×10-5 to 6.7×10-4 centimeters per second). Thin sections show that sandstone framework grains consist of quartz, feldspar, biotite, hornblende, pumice, volcanic glass, and opaque minerals. The matrix in most samples consists of pumice fragments, and some contain predominantly silt and clay. Samples with a mostly silt and clay matrix have lower porosity and SHC compared to samples with mostly pumice, which have higher and wider ranges of porosity and SHC. Pore space in the Nogales Formation sediments includes moldic, intercrystalline, and fracture porosity. Some intercrystalline pore space is partially filled with calcite cement. About one third of the samples contain fractures, which correspond to fractures noted in outcrops in all members of the formation.Scanning electron microscope (SEM) and x-ray diffraction (XRD) analyses indicate that most of the samples contained the zeolite clinoptilolite and mixed-layer clay. X-ray diffraction analyses verified clinoptilolite as the only zeolite in Nogales Formation samples; they also verified the presence of smectite and illite clay and some kaolinite. Samples which contain greater amounts of clinoptilolite and lesser amounts of smectite have high porosity and SHC in narrow ranges. However, samples with abundant smectite and lesser amounts of clinoptilolite span the entire ranges of porosity and SHC for the formation.All members of the Nogales Formation are fractured and faulted as a result of Tertiary Basin and Range extensional deformation, which was broadly contemporaneous with deposition of the formation. These structures may have significant influence on groundwater flow in the upper Santa Cruz basin because, although many of the sediments in the formation have characteristics indicating they may be productive aquifers based only on porous-media flow, fracturing in these sediments may further enhance permeability and groundwater flow in these basin-fill aquifers by orders of magnitude.

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

Watrous, Jeramie D.; Roach, Patrick J.; Alexandrov, Theodore

Integrating the governing chemistry with the genomics and phenotypes of microbial colonies has been a "holy grail" in microbiology. This work describes a highly sensitive, broadly applicable, and costeffective approach that allows metabolic profiling of live microbial colonies directly from a Petri dish without any sample preparation. Nanospray desorption electrospray ionization mass spectrometry (MS), combined with alignment of MS data and molecular networking, enabled monitoring of metabolite production from live microbial colonies from diverse bacterial genera, including Bacillus subtilis, Streptomyces coelicolor, Mycobacterium smegmatis, and Pseudomonas aeruginosa. This work demonstrates that, by using these tools to visualize small molecular changes withinmore » bacterial interactions, insights can be gained into bacterial developmental processes as a result of the improved organization of MS/MS data. To validate this experimental platform, metabolic profiling was performed on Pseudomonas sp. SH-C52, which protects sugar beet plants from infections by specific soil-borne fungi [R. Mendes et al. (2011) Science 332:1097–1100]. The antifungal effect of strain SHC52 was attributed to thanamycin, a predicted lipopeptide encoded by a nonribosomal peptide synthetase gene cluster. Our technology, in combination with our recently developed peptidogenomics strategy, enabled the detection and partial characterization of thanamycin and showed that it is amonochlorinated lipopeptide that belongs to the syringomycin family of antifungal agents. In conclusion, the platform presented here provides a significant advancement in our ability to understand the spatiotemporal dynamics of metabolite production in live microbial colonies and communities.« less

Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant.

PubMed

van Roosmalen, Wies; Le Dévédec, Sylvia E; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M; Look, Maxime P; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A C 't; Martens, John W M; Foekens, John A; Geiger, Benjamin; van de Water, Bob

2015-04-01

Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3-binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis.

Sustainable and Healthy Communities Research Overview Fact Sheet

EPA Pesticide Factsheets

SHC researchers consider the full range of interactions between people and our environment to incorporate the three pillars of sustainability—economics, society, and the environment—into a seamless research portfolio.

Rationale and design for SHAREHD: a quality improvement collaborative to scale up Shared Haemodialysis Care for patients on centre based haemodialysis.

PubMed

Fotheringham, James; Barnes, Tania; Dunn, Louese; Lee, Sonia; Ariss, Steven; Young, Tracey; Walters, Stephen J; Laboi, Paul; Henwood, Andy; Gair, Rachel; Wilkie, Martin

2017-11-24

The study objective is to assess the effectiveness and economic impact of a structured programme to support patient involvement in centre-based haemodialysis and to understand what works for whom in what circumstances and why. It implements a program of Shared Haemodialysis Care (SHC) that aims to improve experience and outcomes for those who are treated with centre-based haemodialysis, and give more patients the confidence to dialyse independently both at centres and at home. The 24 month mixed methods cohort evaluation of 600 prevalent centre based HD patients is nested within a 30 month quality improvement program that aims to scale up SHC at 12 dialysis centres across England. SHC describes an intervention where patients who receive centre-based haemodialysis are given the opportunity to learn, engage with and undertake tasks associated with their treatment. Following a 6-month set up period, a phased implementation programme is initiated across 12 dialysis units using a randomised stepped wedge design with 6 centres participating in each of 2 steps, each lasting 6 months. The intervention utilises quality improvement methodologies involving rapid tests of change to determine the most appropriate mechanisms for implementation in the context of a learning collaborative. Running parallel with the stepped wedge intervention is a mixed methods cohort evaluation that employs patient questionnaires and interviews, and will link with routinely collected data at the end of the study period. The primary outcome measure is the number of patients performing at least 5 dialysis-related tasks collected using 3 monthly questionnaires. Secondary outcomes measures include: the number of people choosing to perform home haemodialysis or dialyse independently in-centre by the end of the study period; end-user recommendation; home dialysis establishment delay; staff impact and confidence; hospitalisation; infection and health economics. The results from this study will provide evidence of impact of SHC, barriers to patient and centre level adoption and inform development of future interventions to support its implementation. ISRCTN Number: 93999549 , (retrospectively registered 1 st May 2017); NIHR Research Portfolio: 31566.

The Fermata-- Fall 2016

EPA Pesticide Factsheets

SHC scientists are embracing a truly cross-disciplinary research portfolio to deliver knowledge, data, and tools needed to meet the most pressing environmental challenges of the day. We continually engage with our partners and stakeholders.

Tribal Science 2016 Webinar Series: ecoAmbassadors Program

EPA Pesticide Factsheets

The U.S. EPA Sustainable and Healthy Communities (SHC) Seminar Series presents the Tribal Science Webinar Series, co-hosted by the National Center for Environmental Research (NCER) and the Office of Science Policy.

New trend- trigonometric model for interpolation and prediction of the geomagnetic field utilizing the new DGRF models.

USGS Publications Warehouse

Alldredge, L.R.

1988-01-01

At the IUGG Assembly at Vancouver during August 1987 new definitive geomagnetic reference field (DGRF) models to degree 10 for 1945, 1950, 1955, and 1960 were adopted by IAGA. Before these new DGRF models were accepted, the author developed a trend and trigonometric model (old trig model) based on the models IGRF 1945, IGRF 1950, IGRF 1955, IGRF 1960, DGRF 1965, DGRF 1970, DGRF 1975, DGRF 1980, and IGRF 1985, which were all approved by IAGA in Prague in August 1985. The old trig model consists of 720 trend and trigonometric coefficients for the calculation of spherical harmonic coefficients (SHC) only to degree eight because the early IGRF models were truncated there. These trend and Fourier sine coefficients can replace the equal number of SHC contained in the 9 DGRF-IGRF models. -from Authors

Structured health care for subjects with diabetic foot ulcers results in a reduction of major amputation rates.

PubMed

Weck, Matthias; Slesaczeck, Torsten; Paetzold, Hartmut; Muench, Dirk; Nanning, Thomas; von Gagern, Georg; Brechow, Andrej; Dietrich, Ulf; Holfert, Mandy; Bornstein, Stefan; Barthel, Andreas; Thomas, Antje; Koehler, Carsta; Hanefeld, Markolf

2013-03-13

We tested the effects of structured health care for the diabetic foot in one region in Germany aiming to reduce the number of major amputations. In a prospective study we investigated patients with diabetic foot in a structured system of outpatient, in-patient and rehabilitative treatment. Subjects were recruited between January 1st, 2000 and December 31, 2007. All participants underwent a two-year follow-up. The modified University of Texas Wound Classification System (UT) was the basis for documentation and data analysis. We evaluated numbers of major amputations, rates of ulcer healing and mortality. In order to compare the effect of the structured health care program with usual care in patients with diabetic foot we evaluated the same parameters at another regional hospital without interdisciplinary care of diabetic foot (controls). 684 patients with diabetic foot and 508 controls were investigated. At discharge from hospital 28.3% (structured health care program, SHC) vs. 23.0% (controls) of all ulcers had healed completely. 51.5% (SHC) vs. 49.8% (controls) were in UT grade 1.Major amputations were performed in 32 subjects of the structured health care program group (4.7%) vs. 110 (21.7%) in controls (p<0.0001). Mortality during hospitalization was 2.5% (SHC) vs. 9.4% in controls (p<0.001). With the structured health care program we achieved a significant reduction of major amputation rates by more than 75% as compared to standard care.

Federal Register for Sustainable and Healthy Communities Subcommittee Teleconference

EPA Pesticide Factsheets

The Sustainable and Healthy Communities (SHC) Subcommittee will host a public teleconference meeting on Wednesday, November 4, 2015, that will focus on a draft report summarizing the findings and recommendations from its September 2015 meeting.

76 FR 5249 - Departmental Offices; Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

..., 2010 (Form SHLA (2010)), and are available on the Treasury's TIC webpage for ``Forms SHL/SHLA & SHC/SHCA'' (Part I.A), at: http://www.treasury.gov/resource-center/data-chart-center/tic/Pages/forms-sh...

Thermal Storage Properties of Molten Nitrate Salt-Based Nanofluids with Graphene Nanoplatelets.

PubMed

Xie, Qiangzhi; Zhu, Qunzhi; Li, Yan

2016-12-01

In this study, the effect of concentration of nanoparticles on the thermal storage properties of molten nitrate salt-based nanofluids with graphene nanoplatelets (GNPs) was investigated. Solar salt consisting of sodium nitrate and potassium nitrate was utilized as the base material for the nanofluids. Homogeneous dispersion of GNPs within the solar salt was observed through scanning electron microscopy analysis. For both solar salt and resultant nanofluids, differential scanning calorimetry was employed to measure the thermal storage properties, including characteristic temperatures of phase change, startup heat, and specific heat capacity (SHC). A maximum increase of 16.7 % in SHC at the liquid phase was found at an optimal concentration of 1 wt% of GNPs. At the same concentration, the onset temperature decreased by 10.4 °C, the endset temperature decreased by 4.7 °C, and the startup heat decreased by 9 %.

Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant

PubMed Central

van Roosmalen, Wies; Le Dévédec, Sylvia E.; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M.; Look, Maxime P.; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A.C. ‘t; Martens, John W.M.; Foekens, John A.; Geiger, Benjamin; van de Water, Bob

2015-01-01

Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3–binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis. PMID:25774502

Modeling and Advanced Control for Sustainable Process ...

EPA Pesticide Factsheets

This book chapter introduces a novel process systems engineering framework that integrates process control with sustainability assessment tools for the simultaneous evaluation and optimization of process operations. The implemented control strategy consists of a biologically-inspired, multi-agent-based method. The sustainability and performance assessment of process operating points is carried out using the U.S. E.P.A.’s GREENSCOPE assessment tool that provides scores for the selected economic, material management, environmental and energy indicators. The indicator results supply information on whether the implementation of the controller is moving the process towards a more sustainable operation. The effectiveness of the proposed framework is illustrated through a case study of a continuous bioethanol fermentation process whose dynamics are characterized by steady-state multiplicity and oscillatory behavior. This book chapter contribution demonstrates the application of novel process control strategies for sustainability by increasing material management, energy efficiency, and pollution prevention, as needed for SHC Sustainable Uses of Wastes and Materials Management.

The G Protein-Coupled Estrogen Receptor-1, GPER-1, Promotes Fibrillogenesis via a Shc-Dependent Pathway Resulting in Anchorage-Independent Growth

PubMed Central

Magruder, Hilary T.; Quinn, Jeffrey A.; Schwartzbauer, Jean E.; Reichner, Jonathan; Huang, Allan

2016-01-01

The G protein-coupled estrogen receptor-1, GPER-1, coordinates fibronectin (FN) matrix assembly and release of heparan-bound epidermal growth factor (HB-EGF). This mechanism of action results in the recruitment of FN-engaged integrin α5β1 to fibrillar adhesions and the formation of integrin α5β1-Shc adaptor protein complexes. Here, we show that GPER-1 stimulation of murine 4 T1 or human SKBR3 breast cancer cells with 17β-estradiol (E2β) promotes the formation of focal adhesions and actin stress fibers and results in increased cellular adhesion and haptotaxis on FN, but not collagen. These actions are also induced by the xenoestrogen, bisphenol A, and the estrogen receptor (ER) antagonist, ICI 182, 780, but not the inactive stereoisomer, 17α-estradiol (E2α). In addition, we show that GPER-1 stimulation of breast cancer cells allows for FN-dependent, anchorage-independent growth and FN fibril formation in “hanging drop” assays, indicating that these GPER-1-mediated actions occur independently of adhesion to solid substrata. Stable expression of Shc mutant Y317F lacking its primary tyrosyl phosphorylation site disrupts E2β-induced focal adhesion and actin stress fiber formation and abolishes E2β-enhanced haptotaxis on FN and anchorage-dependent growth. Collectively, these data demonstrate that E2β action via GPER-1 enhances cellular adhesivity and FN matrix assembly and allows for anchorage-independent growth, cellular events that may allow for cellular survival, and tumor progression. PMID:25096985

The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor.

PubMed

Ingham, R J; Holgado-Madruga, M; Siu, C; Wong, A J; Gold, M R

1998-11-13

Gab1 is a member of the docking/scaffolding protein family which includes IRS-1, IRS-2, c-Cbl, p130(cas), and p62(dok). These proteins contain a variety of protein-protein interaction motifs including multiple tyrosine residues that when phosphorylated can act as binding sites for Src homology 2 (SH2) domain-containing signaling proteins. We show in the RAMOS human B cell line that Gab1 is tyrosine-phosphorylated in response to B cell antigen receptor (BCR) engagement. Moreover, tyrosine phosphorylation of Gab1 correlated with the binding of several SH2-containing signaling proteins to Gab1 including Shc, Grb2, phosphatidylinositol 3-kinase, and the SHP-2 tyrosine phosphatase. Far Western analysis showed that the SH2 domains of Shc, SHP-2, and the p85 subunit of phosphatidylinositol 3-kinase could bind directly to tyrosine-phosphorylated Gab1 isolated from activated RAMOS cells. In contrast, the Grb2 SH2 domain did not bind directly to Gab1 but instead to the Shc and SHP-2 associated with Gab1. We also show that Gab1 is present in the membrane-enriched particulate fraction of RAMOS cells and that Gab1/signaling protein complexes are found in this fraction after BCR engagement. Thus, tyrosine-phosphorylated Gab1 may recruit cytosolic signaling proteins to cellular membranes where they can act on membrane-bound targets. This may be a critical step in the activation of multiple BCR signaling pathways.

Structured health care for subjects with diabetic foot ulcers results in a reduction of major amputation rates

PubMed Central

2013-01-01

Objective We tested the effects of structured health care for the diabetic foot in one region in Germany aiming to reduce the number of major amputations. Research design and methods In a prospective study we investigated patients with diabetic foot in a structured system of outpatient, in-patient and rehabilitative treatment. Subjects were recruited between January 1st, 2000 and December 31, 2007. All participants underwent a two-year follow-up. The modified University of Texas Wound Classification System (UT) was the basis for documentation and data analysis. We evaluated numbers of major amputations, rates of ulcer healing and mortality. In order to compare the effect of the structured health care program with usual care in patients with diabetic foot we evaluated the same parameters at another regional hospital without interdisciplinary care of diabetic foot (controls). Results 684 patients with diabetic foot and 508 controls were investigated. At discharge from hospital 28.3% (structured health care program, SHC) vs. 23.0% (controls) of all ulcers had healed completely. 51.5% (SHC) vs. 49.8% (controls) were in UT grade 1. Major amputations were performed in 32 subjects of the structured health care program group (4.7%) vs. 110 (21.7%) in controls (p<0.0001). Mortality during hospitalization was 2.5% (SHC) vs. 9.4% in controls (p<0.001). Conclusions With the structured health care program we achieved a significant reduction of major amputation rates by more than 75% as compared to standard care. PMID:23497152

Morphological assessment of the stylohyoid complex variations with cone beam computed tomography in a Turkish population.

PubMed

Buyuk, C; Gunduz, K; Avsever, H

2018-01-01

The aim of this investigation was to evaluate the length, thickness, sagittal and transverse angulations and the morphological variations of the stylohyoid complex (SHC), to assess their probable associations with age and gender, and to investigate the prevalence of it in a wide range of a Turkish sub-population by using cone beam computed tomography (CBCT). The CBCT images of the 1000 patients were evaluated retrospectively. The length, thickness, sagittal and transverse angulations, morphological variations and ossification degrees of SHC were evaluated on multiplanar reconstructions (MPR) adnd three-dimensional (3D) volume rendering (3DVR) images. The data were analysed statistically by using nonparametric tests, Pearson's correlation coefficient, Student's t test, c2 test and one-way ANOVA. Statistical significance was considered at p < 0.05. It was determined that 684 (34.2%) of all 2000 SHCs were elongated (> 35 mm). The mean sagittal angle value was measured to be 72.24° and the mean transverse angle value was 70.81°. Scalariform shape, elongated type and nodular calcification pattern have the highest mean age values between the morphological groups, respectively. Calcified outline was the most prevalent calcification pattern in males. There was no correlation between length and the calcification pattern groups while scalariform shape and pseudoarticular type were the longest variations. We observed that as the anterior sagittal angle gets wider, SHC tends to get longer. The most observed morphological variations were linear shape, elongated type and calcified outline pattern. Detailed studies on the classification will contribute to the literature. (Folia Morphol 2018; 77, 1: 79-89).

The Multi-Sector Sustainability Browser (MSSB): Planning and Developing Sustainability Initiatives Affecting Land Use

EPA Science Inventory

The United States Environmental Protection Agency (EPA) Sustainable and Healthy Communities (SHC) Research Program develops methodologies, resources, and tools to assist local and regional community planners, community members, and local decision makers in implementing sustainabl...

ORD's Sustainable & Healthy Communities (SHC) Nutrient research

EPA Science Inventory

Sustainable and healthy communities project 3.3.1 "Integrated Management of Reactive Nitrogen" aims to comprehensively examine the cascade of environmental economic and human health problems stemming from excess reactive N. Our goals are to improve understanding of the impacts o...

Benthic incubation chambers for estimating nitrogen flux at the sediment water interface

EPA Science Inventory

USEPA’s Sustainable and Healthy Communities (SHC) research program seeks to better understand how ecosystem functions produce ecosystem goods and services (EGS) in order to develop quantitative tools for informing decisions that lead to more sustainable results. Our incompl...

Fatigue, anxiety and depression overrule the role of oncological treatment in predicting self-reported health complaints in women with breast cancer compared to healthy controls.

PubMed

Hagen, Kari Britt; Aas, Turid; Kvaløy, Jan Terje; Eriksen, Hege R; Søiland, Håvard; Lind, Ragna

2016-08-01

Women with breast cancer often attribute their health problems as side effects caused by oncological treatments. The aim of the study was to examine and compare self-reported health complaints (SHC) in postmenopausal patients with breast cancer to healthy controls. Women with breast cancer (N = 196) filled in 5 questionnaires 1-2 years after surgery; SHC Inventory, Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), Fatigue - Functional Assessment of Cancer Therapy-Fatigue subscale (FACIT-F), Fatigue Visual Analog Scale (Fatigue VAS), and Hospital Anxiety and Depression Scale (HADS). Controls comprised 101 blood donors who reported on the questionnaires except for HADS. Bonferroni adjustment and p < 0.0017 was considered statistically significant for SHC Inventory, p < 0.05 for the remaining questionnaires. The patients, mean age 58.0 (SD 9.5), reported significantly more self-reported health complaints, whereof 6 of 29 complaints were significantly elevated compared to the controls, mean age 57.0 (SD 5.8) (p < 0.001). HADS scores in patients fell into normal range, mean 6.3 (SD 5.7). A subgroup of 48 patients experienced more frequent and severe symptoms in all the questionnaires compared to the remaining 148 patients, and the 101 controls. Among the patients, fatigue, anxiety and depression explained 49% of the total variance in self-reported health complaints (p ≤ 0.001). Most women with breast cancer (76%) reported health complaints equal to the healthy controls. Fatigue, anxiety and depression, not oncological treatments, were significant predictors for the complaints. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pulse compression of harmonic chirp signals using the fractional fourier transform.

PubMed

Arif, M; Cowell, D M J; Freear, S

2010-06-01

In ultrasound harmonic imaging with chirp-coded excitation, a harmonic matched filter (HMF) is typically used on the received signal to perform pulse compression of the second harmonic component (SHC) to recover signal axial resolution. Designing the HMF for the compression of the SHC is a problematic issue because it requires optimal window selection. In the compressed second harmonic signal, the sidelobe level may increase and the mainlobe width (MLW) widen under a mismatched condition, resulting in loss of axial resolution. We propose the use of the fractional Fourier transform (FrFT) as an alternative tool to perform compression of the chirp-coded SHC generated as a result of the nonlinear propagation of an ultrasound signal. Two methods are used to experimentally assess the performance benefits of the FrFT technique over the HMF techniques. The first method uses chirp excitation with central frequency of 2.25 MHz and bandwidth of 1 MHz. The second method uses chirp excitation with pulse inversion to increase the bandwidth to 2 MHz. In this study, experiments were performed in a water tank with a single-element transducer mounted coaxially with a hydrophone in a pitch-catch configuration. Results are presented that indicate that the FrFT can perform pulse compression of the second harmonic chirp component, with a 14% reduction in the MLW of the compressed signal when compared with the HMF. Also, the FrFT provides at least 23% reduction in the MLW of the compressed signal when compared with the harmonic mismatched filter (HMMF). The FrFT maintains comparable peak and integrated sidelobe levels when compared with the HMF and HMMF techniques. Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Upregulation of cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on magnesium alloy surface coating with tricalcium phosphate.

PubMed

Jiang, Tianlong; Guo, Lei; Ni, Shenghui; Zhao, Yuyan

2015-04-01

Magnesium (Mg) alloys have been demonstrated to be viable orthopedic implants because of mechanical and biocompatible properties similar to natural bone. In order to improve its osteogenic properties, a porous β-tricalcium phosphate (β-TCP) was coated on the Mg-3AI-1Zn alloy by alkali-heat treatment technique. The human bone-derived cells (SaOS-2) were cultured on (β-TCP)-Mg-3AI-1Zn in vitro, and the osteoblast response, the morphology and the elements on this alloy surface were investigated. Also, the regulation of key intracellular signalling proteins was investigated in the SaOS-2 cells cultured on alloy surface. The results from scanning electron microscope and immunofluorescence staining demonstrated that (β-TCP)-Mg-3AI-1Zn induced significant osteogenesis. SaOS-2 cell proliferation was improved by β-TCP coating. Moreover, the (β-TCP)-Mg-3AI-1Zn surface induced activation of key intracellular signalling proteins in SaOS-2 cells. We observed an enhanced activation of Src homology and collagen (Shc), a common point of integration between bone morphogenetic protein 2, and the Ras/mitogen-activated protein kinase (MAPK) pathway. ERK1/2 MAP kinase activation was also upregulated, suggesting a role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the (β-TCP)-Mg-3AI-1Zn. These results suggest that β-TCP coating may contribute to successful osteoblast function on Mg alloy surface. (β-TCP)-Mg-3AI-1Zn may upregulate cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on Mg alloy surface.

Ageing, metabolism and cardiovascular disease.

PubMed

Costantino, Sarah; Paneni, Francesco; Cosentino, Francesco

2016-04-15

Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

A System Dynamics Model for Integrated Decision Making: The Durham-Orange Light Rail Project

EPA Science Inventory

EPA’s Sustainable and Healthy Communities Research Program (SHC) is conducting transdisciplinary research to inform and empower decision-makers. EPA tools and approaches are being developed to enable communities to effectively weigh and integrate human health, socioeconomic, envi...

Ecosystem Goods & Services and their Direct Linkages to Human Health & Well-Being

EPA Science Inventory

This presentation provides an overview of the SHC 2.61 Community-Based Final Ecosystem Goods and Services Project and other ecosystem services activities in the Office of Research and Development. Specifically, this presentation addressed a series of topics: Provide an overview ...

Red fluorescence of dental biofilm as an indicator for assessing the efficacy of antimicrobials

NASA Astrophysics Data System (ADS)

Lee, Eun-Song; de Josselin de Jong, Elbert; Jung, Hoi-In; Kim, Baek-Il

2018-01-01

The study aimed to determine whether the red fluorescence (RF) of a dental microcosm biofilm as measured with quantitative light-induced fluorescence (QLF) technology is useful for assessing the efficacy of antimicrobials. Dental microcosm biofilms were formed on bovine enamel discs and grown under 0.3% sucrose challenge and treated with chlorhexidine (CHX) solutions at different concentrations (0.05%, 0.1%, and 0.5%) plus a negative control [sterile distilled water (DW)] twice daily for 7 days. The biofilms were photographed using a QLF-digital system to evaluate the RF by calculating the red/green ratio, and pH values of the medium were measured daily. After 7 days, the bacterial viability of the biofilm was assessed by measuring the counts of viable total bacteria and aciduric bacteria, and the percentage surface microhardness changes (%SHC) was evaluated. The RF and cariogenic properties were compared for the different concentrations of CHX, and their correlations were examined. The RF and its increase rate were much lower for CHX-treated biofilms than for DW-treated biofilms. The RF after 7 days of maturation decreased significantly with increasing CHX concentrations (p<0.001) and was from 31% (for 0.05% CHX) to 46% (for 0.5% CHX) lower than that of the DW group. Strong correlations were reported between the RF of the 7-day-maturation biofilms and cariogenic properties, such as the number of total bacteria (r=0.93), number of aciduric bacteria (r=0.97), supernatant pH (r=0.43), and %SHC (r=0.98). In conclusion, the RF of dental biofilms as measured with QLF technology can be used to nondestructively assess and monitor the effect of antimicrobials against biofilm.

SHCBP1 is over-expressed in breast cancer and is important in the proliferation and apoptosis of the human malignant breast cancer cell line.

PubMed

Feng, Wen; Li, Hong-Chang; Xu, Ke; Chen, Ya-Feng; Pan, Li-Yun; Mei, Yi; Cai, Han; Jiang, Yi-Ming; Chen, Teng; Feng, Dian-Xu

2016-08-01

SHC SH2-binding protein 1, a member of Src homolog and collagen homolog (Shc) family, has been recently identified in different contexts in unbiased screening assays. It has been reported to be over-expressed in several malignant cancers. Immunohistochemistry of SHCBP1 on 128 breast cancer tissues and adjacent normal tissues were used to evaluate the prognostic significance of SHCBP1. Survival analyses were performed by Kaplan-Meier method. CRISPR/CAS9 method was used to knockout SHCBP1 expression. CRISPR/CAS9 technology was used to knockout SHCBP1 in 2 breast cancer cell lines. MTT assay, BrdU assay, colony formation assay, cell cycle assay and apoptosis analysis in MCF-7 and MDA-MB-231 cell lines were carried out to evaluate the effects of SHCBP1 on breast cancer in vitro. Immunohistochemical analysis revealed SHCBP1 was significantly up-regulated in breast cancer tissues compared with adjacent normal tissues (82 of 128, 64%). Over-expressed SHCBP1 was correlated with advanced clinical stage and poorer survival. Ablation of SHCBP1 inhibited the proliferation in vitro. SHCBP1 knockout increased cyclin-dependent kinase inhibitor p21, and decreased the Cyclin B1 and CDK1. Our study suggests SHCBP1 is dysregulated expressed in breast cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of breast cancer. Copyright © 2016. Published by Elsevier B.V.

School differences in adolescent health and wellbeing: findings from the Canadian Health Behaviour in School-aged Children Study.

PubMed

Saab, Hana; Klinger, Don

2010-03-01

The goal of this study was to assess the relationship between student- and school-level factors and student health and wellbeing outcomes, and to estimate the variability present at each of the student and school levels for each of three selected health-related outcomes. The data are from the 2006 Canadian Health Behaviour in School-aged children (HBSC) study in which Grades 6-10 students (N=9670) and administrators (N=187) were surveyed. The three outcome measures are Self-Rated Health (SRH), Emotional Wellbeing (EWB), and Subjective Health Complaints (SHC). Individual and school-level effects on the three outcomes were estimated using multi-level modeling. Both individual and school-level factors were associated with students' health. Gender, family wealth, family structure, academic achievement and neighbourhood were significant student-level predictors. We identified random associations between the student-level variables and reported health outcomes. These random effects indicate that the relationships between these student variables and health are not consistent across schools. Student Problem Behaviours at the school were significant predictors of SRH and SHC, while Student Aggression and the school's average socioeconomic standing were significant school-level predictors of EWB. Findings suggest that the environment and disciplinary climate in schools can predict student health and wellbeing outcomes, and may have important implications for school initiatives aimed at students who are struggling both emotionally and academically. Copyright 2009 Elsevier Ltd. All rights reserved.

Measuring Sustainability of Urban Systems: An Exploration based on Two Metrics for the Chicago Metropolitan Area

EPA Science Inventory

This presentation is comprised of two sustainability metrics that have been developed for the Chicago Metropolitan Area under SHC research program. The first sustainability metrics is Ecological Foot Print Analysis. Ecological Footprint Analysis (EFA) has been extensively deploy...

EPA Technical Support Centers (TSC): FY14 Lessons Learned

EPA Science Inventory

EPA’s Technical Support Centers (TSC) included in ORD’s Safe and Healthy Communities (SHC) Research Action Plan fill the need for supplying subject-matter experts to continually assess state-of-the-art research and practices and channel this information to users in both direct ap...

Influence of Unweighting on Insulin Signal Transduction in Muscle

NASA Technical Reports Server (NTRS)

Tischler, Marc E.

2002-01-01

Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

Chunking dynamics: heteroclinics in mind

PubMed Central

Rabinovich, Mikhail I.; Varona, Pablo; Tristan, Irma; Afraimovich, Valentin S.

2014-01-01

Recent results of imaging technologies and non-linear dynamics make possible to relate the structure and dynamics of functional brain networks to different mental tasks and to build theoretical models for the description and prediction of cognitive activity. Such models are non-linear dynamical descriptions of the interaction of the core components—brain modes—participating in a specific mental function. The dynamical images of different mental processes depend on their temporal features. The dynamics of many cognitive functions are transient. They are often observed as a chain of sequentially changing metastable states. A stable heteroclinic channel (SHC) consisting of a chain of saddles—metastable states—connected by unstable separatrices is a mathematical image for robust transients. In this paper we focus on hierarchical chunking dynamics that can represent several forms of transient cognitive activity. Chunking is a dynamical phenomenon that nature uses to perform information processing of long sequences by dividing them in shorter information items. Chunking, for example, makes more efficient the use of short-term memory by breaking up long strings of information (like in language where one can see the separation of a novel on chapters, paragraphs, sentences, and finally words). Chunking is important in many processes of perception, learning, and cognition in humans and animals. Based on anatomical information about the hierarchical organization of functional brain networks, we propose a cognitive network architecture that hierarchically chunks and super-chunks switching sequences of metastable states produced by winnerless competitive heteroclinic dynamics. PMID:24672469

Chunking dynamics: heteroclinics in mind.

PubMed

Rabinovich, Mikhail I; Varona, Pablo; Tristan, Irma; Afraimovich, Valentin S

2014-01-01

Recent results of imaging technologies and non-linear dynamics make possible to relate the structure and dynamics of functional brain networks to different mental tasks and to build theoretical models for the description and prediction of cognitive activity. Such models are non-linear dynamical descriptions of the interaction of the core components-brain modes-participating in a specific mental function. The dynamical images of different mental processes depend on their temporal features. The dynamics of many cognitive functions are transient. They are often observed as a chain of sequentially changing metastable states. A stable heteroclinic channel (SHC) consisting of a chain of saddles-metastable states-connected by unstable separatrices is a mathematical image for robust transients. In this paper we focus on hierarchical chunking dynamics that can represent several forms of transient cognitive activity. Chunking is a dynamical phenomenon that nature uses to perform information processing of long sequences by dividing them in shorter information items. Chunking, for example, makes more efficient the use of short-term memory by breaking up long strings of information (like in language where one can see the separation of a novel on chapters, paragraphs, sentences, and finally words). Chunking is important in many processes of perception, learning, and cognition in humans and animals. Based on anatomical information about the hierarchical organization of functional brain networks, we propose a cognitive network architecture that hierarchically chunks and super-chunks switching sequences of metastable states produced by winnerless competitive heteroclinic dynamics.

The Identification and Role of Non-Chemical Stressors as Modifiers of Chemical Exposures that Lead to Changes in Health and Well-Being in Children

EPA Science Inventory

Describe the Sustainable and Health Communities (SHC) Research Program at the U.S. EPA Discuss non-chemical stressors found in the social environment, What are they? Why are they important? Summarize current and planned work

77 FR 70526 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... DEPARTMENT OF STATE [Public Notice 8093] Shipping Coordinating Committee; Notice of Committee Meeting The Shipping Coordinating Committee (SHC) will conduct an open meeting at 10 a.m. on Tuesday... amendments to the requirements for foam-type fire extinguishers in SOLAS regulation II-2/10.5 --Development...

75 FR 27614 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... of vital shipping lanes. --External relations: --Report on the status of the Convention and.... Additional information regarding this and other IMO SHC public meetings may be found at: http://www.uscg.mil.... The Department of State finds that there is an exceptional circumstance in that this advisory...

The wind god promotes lung cancer.

PubMed

Frisch, Steven M; Schaller, Michael D

2014-05-12

In this issue of Cancer Cell, Li and colleagues demonstrate that the hematopoietic transcription factor Aiolos (named after the Wind God of Greek mythology) confers anoikis resistance in lung tumor cells through repression of cell adhesion-related genes including the mechanosensor p66Shc. Copyright © 2014 Elsevier Inc. All rights reserved.

Green Infrastructure and Watershed-Scale Hydrology in a Mixed Land Cover System

NASA Astrophysics Data System (ADS)

Hoghooghi, N.; Golden, H. E.; Bledsoe, B. P.

2017-12-01

Urbanization results in replacement of pervious areas (e.g., vegetation, topsoil) with impervious surfaces such as roads, roofs, and parking lots, which cause reductions in interception, evapotranspiration, and infiltration, and increases in surface runoff (overland flow) and pollutant loads and concentrations. Research on the effectiveness of different Green Infrastructure (GI), or Low Impact Development (LID), practices to reduce these negative impacts on stream flow and water quality has been mostly focused at the local scale (e.g., plots, small catchments). However, limited research has considered the broader-scale effects of LID, such as how LID practices influence water quantity, nutrient removal, and aquatic ecosystems at watershed scales, particularly in mixed land cover and land use systems. We use the Visualizing Ecosystem Land Management Assessments (VELMA) model to evaluate the effects of different LID practices on daily and long-term watershed-scale hydrology, including infiltration surface runoff. We focus on Shayler Crossing (SHC) watershed, a mixed land cover (61% urban, 24% agriculture, 15% forest) subwatershed of the East Fork Little Miami River watershed, Ohio, United States, with a drainage area of 0.94 km2. The model was calibrated to daily stream flow at the outlet of SHC watershed from 2009 to 2010 and was applied to evaluate diverse distributions (at 25% to 100% implementation levels) and types (e.g., pervious pavement and rain gardens) of LID across the watershed. Results show reduced surface water runoff and higher rates of infiltration concomitant with increasing LID implementation levels; however, this response varies between different LID practices. The highest magnitude response in streamflow at the watershed outlet is evident when a combination of LID practices is applied. The combined scenarios elucidate that the diverse watershed-scale hydrological responses of LID practices depend primarily on the type and extent of the implemented practices. Our work provides a key advancement toward improving current understanding of the effectiveness and efficiencies of LID approaches in mixed land cover watersheds.

Transforming Student Health Services through Purpose-Driven Assessment Techniques

ERIC Educational Resources Information Center

Knoll, Dorothy; Meiers, Chris; Honeck, Sara

2006-01-01

The University of Kansas Medical Center did a comprehensive review of the services provided in the Student Health Center (SHC). Using purpose-driven assessment techniques, areas needing improvement were identified. The results of the survey were presented to students and, with student support, student health fees were increased to fund desired…

77 FR 9260 - Establishment of Dakota Grassland Conservation Area, North Dakota and South Dakota

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-R6-R-2011-N212; FF06R06000...: Fish and Wildlife Service, Interior. ACTION: Notice. SUMMARY: This notice advises the public that the U... conservation. SHC entails strategic biological planning and conservation design, integrated conservation...

Sustainability at the community level: Searching for common ground as a part of a national strategy for decision support

EPA Science Inventory

The Sustainable and Healthy Communities (SHC) research program is intended to support resource sustainability and decision making at the community level. Sustainability is defined as the ability of a community to meet present needs without compromising the ability of society and ...

OpenARC: Extensible OpenACC Compiler Framework for Directive-Based Accelerator Programming Study

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

Lee, Seyong; Vetter, Jeffrey S

2014-01-01

Directive-based, accelerator programming models such as OpenACC have arisen as an alternative solution to program emerging Scalable Heterogeneous Computing (SHC) platforms. However, the increased complexity in the SHC systems incurs several challenges in terms of portability and productivity. This paper presents an open-sourced OpenACC compiler, called OpenARC, which serves as an extensible research framework to address those issues in the directive-based accelerator programming. This paper explains important design strategies and key compiler transformation techniques needed to implement the reference OpenACC compiler. Moreover, this paper demonstrates the efficacy of OpenARC as a research framework for directive-based programming study, by proposing andmore » implementing OpenACC extensions in the OpenARC framework to 1) support hybrid programming of the unified memory and separate memory and 2) exploit architecture-specific features in an abstract manner. Porting thirteen standard OpenACC programs and three extended OpenACC programs to CUDA GPUs shows that OpenARC performs similarly to a commercial OpenACC compiler, while it serves as a high-level research framework.« less

Assessment of quality of prescribing in patients of hypertension at primary and secondary health care facilities using the Prescription Quality Index (PQI) tool.

PubMed

Suthar, Jalpa Vashishth; Patel, Varsha J

2014-01-01

To determine the quality of prescribing in hypertension in primary and secondary health care settings using the Prescription Quality Index (PQI) tool and to assess the reliability of this tool. An observational cross-sectional study was carried out for 6 months in order to assess quality of prescribing of antihypertensive drugs using Prescription Quality Index (PQI) at four primary (PHC) and two secondary (SHC) health care facilities. Patients attending these facilities for at least 3 months were included. Complete medical history and prescriptions received were noted. Total and criteria wise PQI scores were derived for each prescription. Prescriptions were categorized as poor (score of ≤31), medium (score 32-33) and high quality (score 34-43) based on PQI total score. Psychometric analysis using factor analysis was carried out to assess reliability and validity. Total 73 hypertensive patients were included. Mean age was 61.2 ± 11 years with 35 (48%) patients above 65 years of age. Total PQI score was 26 ± 11. There was a significant difference in PQI score between PHC and SHC (P < 0.05) Out of 73 prescriptions, 43 (59%) were of poor quality with PQI score <31. The value of Cronbach's α for the entire 22 criteria of PQI was 0.71 suggesting good reliability of PQI tool in our setting. Based on PQI scores, quality of prescribing in hypertensive patients was poor, somewhat better in primary as compared to secondary health care facility. PQI is reliable for measuring prescribing quality in hypertension in Indian set up.

MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus.

PubMed

Wang, Jie-Mei; Tao, Jun; Chen, Dan-Dan; Cai, Jing-Jing; Irani, Kaikobad; Wang, Qinde; Yuan, Hong; Chen, Alex F

2014-01-01

Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice. BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.

A pill for the partner via the chlamydia patient? Results from a mixed method study among sexual health care providers in the Netherlands.

PubMed

Nanhoe, Anita C; Visser, Maartje; Omlo, Jurriaan J; Watzeels, Anita J C M; van den Broek, Ingrid V; Götz, Hannelore M

2018-05-29

Chlamydia prevalence in the Netherlands remains high despite targeted efforts. Effective Partner Notification (PN) and Partner Treatment (PT) can interrupt transmission and prevent re-infections. Patient Initiated Partner Treatment (PIPT) may strengthen chlamydia control. This study explores the current practice of PN and PT, and benefits of, and barriers and facilitators for PIPT among professionals in sexual health care in the Netherlands. A qualitative study was performed among GPs, GP-assistants (GPAs), physicians and nurses working at Sexual Health Clinics (SHC) and key-informants on ethnical diversity using topic lists in focus groups (N = 40) and semi-structured questionnaires in individual interviews (N = 9). Topics included current practices regarding PN and PT, attitude regarding PIPT, and perceived barriers and facilitators for PIPT. Interviews were taped, transcribed verbatim, and coded using ATLAS.ti. A quantitative online questionnaire on the same topics was sent to all physicians and nurses employed at Dutch SHC (complete response rate 26% (84/321)). The qualitative study showed that all professionals support the need for more attention to PN, and that they saw advantages in PIPT. Mentioned barriers included unwilling PN-behaviour, Dutch legislation, several medical considerations and inadequate skills of GPs. Also, concerns about limited knowledge of cultural sensitivity around PN and PT were raised. Mentioned facilitators of PIPT were reliable home based test-kits, phone-contact between professionals and notified partners, more consultation time for GPs or GPAs and additional training. The online questionnaire showed that SHC employees agreed that partners should be treated as soon as possible, but also that they were reluctant towards PIPT without counselling and testing. Professionals saw advantages in PIPT, but they also identified barriers hampering the potential introduction of PIPT. Improving PN and counselling skills with specific focus on cultural sensitivity is needed. PIPT could be considered for specific partners. PIPT in combination with home based testing and using e-healthcare should be further explored and developed.

Multi-Sector Sustainability Browser (MSSB) User Manual: A Decision Support Tool (DST) for Supporting Sustainability Efforts in Four Areas - Land Use, Transportation, Buildings and Infrastructure, and Materials Management

EPA Science Inventory

EPA’s Sustainable and Healthy Communities (SHC) Research Program is developing methodologies, resources, and tools to assist community members and local decision makers in implementing policy choices that facilitate sustainable approaches in managing their resources affecti...

78 FR 2479 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-11

... Meeting The Shipping Coordinating Committee (SHC) will conduct an open meeting at 9:30 a.m. on Thursday... Equipment to be held at the IMO Headquarters, United Kingdom, March 18-22, 2013. The agenda items to be... provisions of MSC.1/Circ.1206/Rev.1 mandatory; --Development of new framework of requirements for life-saving...

Effects of Csk Homologous Kinase Overexpression on HER2/Neu-Mediated Signal Transduction Pathways in Breast Cancer Cells

DTIC Science & Technology

2005-04-01

several SH2 domains. The 5112 domains of CHE, Csk, Src, Lck, Shc, and phospholipase Cyl (PLCy1) were aligned using the T- COFFEE program (available at...iSC-Double-labeled protein samples or 15N_ acrylamide gel and then transferred onto Immobilon-PM membranes. bacteria in Bound proteins were

Odour as a determinant of persistent symptoms after a chemical explosion, a longitudinal study

PubMed Central

TJALVIN, Gro; MAGERØY, Nils; BRÅTVEIT, Magne; LYGRE, Stein Håkon Låstad; HOLLUND, Bjørg Eli; MOEN, Bente Elisabeth

2016-01-01

Foul-smelling environmental pollution was a major concern following a chemical workplace explosion. Malodorous pollution has previously been associated with aggravated physical and psychological health, and in persons affected by a trauma, an incidence-related odour can act as a traumatic reminder. Olfaction may even be of significance in the development and persistence of post-traumatic stress symptoms (PTSS). The present longitudinal study assessed whether perceived smell related to malodorous environmental pollution in the aftermath of the explosion was a determinant of subjective health complaints (SHC) and PTSS among gainfully employed adults, when the malodorous pollution was present, and after pollution clean-up. Questionnaire data from validated instruments were analysed using mixed effects models. Individual odour scores were computed, and the participants (n=486) were divided into high and low odour score groups, respectively. Participants in the high odour score group (n=233) reported more SHC and PTSS than those in the low odour score group (n=253), before and even after the pollution was eliminated. These associations lasted for at least three years after the pollution was removed, and might indicate that prompt clean-up is important to avoid persistent health effects after malodorous chemical spills. PMID:27916759

Odour as a determinant of persistent symptoms after a chemical explosion, a longitudinal study.

PubMed

Tjalvin, Gro; Magerøy, Nils; Bråtveit, Magne; Lygre, Stein Håkon Låstad; Hollund, Bjørg Eli; Moen, Bente Elisabeth

2017-04-07

Foul-smelling environmental pollution was a major concern following a chemical workplace explosion. Malodorous pollution has previously been associated with aggravated physical and psychological health, and in persons affected by a trauma, an incidence-related odour can act as a traumatic reminder. Olfaction may even be of significance in the development and persistence of post-traumatic stress symptoms (PTSS). The present longitudinal study assessed whether perceived smell related to malodorous environmental pollution in the aftermath of the explosion was a determinant of subjective health complaints (SHC) and PTSS among gainfully employed adults, when the malodorous pollution was present, and after pollution clean-up. Questionnaire data from validated instruments were analysed using mixed effects models. Individual odour scores were computed, and the participants (n=486) were divided into high and low odour score groups, respectively. Participants in the high odour score group (n=233) reported more SHC and PTSS than those in the low odour score group (n=253), before and even after the pollution was eliminated. These associations lasted for at least three years after the pollution was removed, and might indicate that prompt clean-up is important to avoid persistent health effects after malodorous chemical spills.

Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes

PubMed Central

DeFronzo, Ralph A.; Hompesch, Marcus; Kasichayanula, Sreeneeranj; Liu, Xiaoni; Hong, Ying; Pfister, Marc; Morrow, Linda A.; Leslie, Bruce R.; Boulton, David W.; Ching, Agatha; LaCreta, Frank P.; Griffen, Steven C.

2013-01-01

OBJECTIVE To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [TmG], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique. RESEARCH DESIGN AND METHODS Subjects with type 2 diabetes (n = 12) and matched healthy subjects (n = 12) underwent pancreatic/SHC (plasma glucose range 5.5–30.5 mmol/L) at baseline and after 7 days of dapagliflozin treatment. A pharmacodynamic model was developed to describe the major components of renal glucose reabsorption for both groups and then used to estimate these parameters from individual glucose titration curves. RESULTS At baseline, type 2 diabetic subjects had elevated TmG, splay, and threshold compared with controls. Dapagliflozin treatment reduced the TmG and splay in both groups. However, the most significant effect of dapagliflozin was a reduction of the renal threshold for glucose excretion in type 2 diabetic and control subjects. CONCLUSIONS The SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the TmG and threshold at which glucose is excreted in the urine. PMID:23735727

Evaluating the capacity of California's publicly funded universities to provide medication abortion.

PubMed

Raifman, Sarah; Anderson, Patricia; Kaller, Shelly; Tober, Diane; Grossman, Daniel

2018-05-18

To explore capacity of University of California (UC) and California State University (CSU) student health centers (SHCs) to provide medication abortion (MA) and SHC staff perspectives on providing MA. SHC staff completed an online survey; we conducted site visits and conference calls with a subset of SHCs. The survey focused on barriers to abortion, resources needed for MA, and potential benefits and challenges. 11 UCs (100%) and 20 CSUs (87%) completed surveys. All facilities provided basic primary care, including sexual and reproductive health services and some contraceptive services, but not abortion. All sites had adequate staffing and physical plant, but most would require training, access to ultrasound when needed, 24-hour hotlines (CSUs), and back-up care to provide MA. It would be feasible to provide MA at SHCs, but investment is needed to support staff training, equipment, 24-hour hotlines, back-up care, and minimal security upgrades, in order to implement MA services. If SB320 is passed, provision of MA services at student health centers could improve access to early abortion for students in California. This model may be scaled up at other universities around the country. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Nagarse treatment of cardiac subsarcolemmal and interfibrillar mitochondria leads to artefacts in mitochondrial protein quantification.

PubMed

Koncsos, Gábor; Varga, Zoltán V; Baranyai, Tamás; Ferdinandy, Péter; Schulz, Rainer; Giricz, Zoltán; Boengler, Kerstin

In the heart, subsarcolemmal (SSM), interfibrillar (IFM) and perinuclear mitochondria represent three subtypes of mitochondria. The most commonly used protease during IFM isolation is the nagarse, however, its effect on the detection of mitochondrial proteins is still unclear. Therefore, we investigated whether nagarse treatment influences the quantification of mitochondrial proteins. SSM and IFM were isolated from hearts of mice and rats. During IFM isolation, nagarse activity was either stopped by centrifugation (common protocol, IFM+N) or inhibited by phenylmethylsulfonyl fluoride (PMSF, IFM+N+I). The amounts of proteins located in different mitochondrial compartments (outer membrane: mitofusin 1 (MFN1) and 2 (MFN2); intermembrane space: p66shc; inner membrane (connexin 43 (Cx43)), and of protein deglycase DJ-1 were determined by Western blot. MFN2 and Cx43 were found predominantly in SSM isolated from mouse and rat hearts. MFN1 and p66shc were present in similar amounts in SSM and IFM+N, whereas the level of DJ-1 was higher in IFM+N compared to SSM. In IFM+N+I samples from mice, the amount of MFN2, but not that of Cx43 increased. Nagarse or nagarse inhibition by PMSF had no effect on oxygen consumption of SSM or IFM. Whereas the use of the common protocol indicates the localization of MFN2 predominantly in SSM, the inhibition of nagarse by PMSF increases the signal of MFN2 in IFM to that of in SSM, indicating an underestimation of MFN2 in IFM. Therefore, protease sensitivity should be considered when assessing distribution of mitochondrial proteins using nagarse-based isolation. Copyright © 2018 Elsevier Inc. All rights reserved.

Subjective health complaints, work-related stress and self-efficacy in Norwegian aircrew.

PubMed

Omholt, M L; Tveito, T H; Ihlebæk, C

2017-03-01

The European civilian aviation industry has undergone major changes in the last decade. Despite this, there is little knowledge about work-related stress and subjective health complaints (SHCs) affecting Norwegian aircrew. To investigate the relationships between work-related stress, self-efficacy and SHCs in commercial aircrew in Norway and to explore differences between cockpit and cabin crew. Aircrew members from the three major airlines operating from Norway completed an electronically distributed questionnaire. Linear regression analyses were used to investigate the association between work-related stress, self-efficacy and SHCs. There was a 21% response rate. Among the 843 study subjects, tiredness, sleep problems, bloating, low back pain, headaches and neck pain were the most prevalent SHCs. Cabin crew reported significantly higher numbers, prevalences and mean values for all SHCs compared with cockpit crew (P < 0.05). In total, 20% reported high stress levels. High levels of work-related stress were significantly associated with all SHC factors in both groups. Self-efficacy partly moderated the relationship between stress and psychological complaints in both cockpit and cabin crew, and for musculoskeletal complaints in cockpit crew. The model explained 23 and 32% of the variance in psychological complaints for cockpit and cabin crew, respectively. Commercial aircrew in Norway reported high numbers of SHCs, and high levels of work-related stress were associated with high numbers of SHC. More knowledge is needed on the physical, organizational and psychosocial stressors affecting cockpit and cabin crew in order to create a healthier work environment for these groups. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The Shc protein RAI promotes an adaptive cell survival program in hypoxic neuroblastoma cells.

PubMed

Criscuoli, Mattia; Filippi, Irene; Osti, Daniela; Aldinucci, Carlo; Guerrini, Giuditta; Pelicci, Giuliana; Carraro, Fabio; Naldini, Antonella

2018-05-01

Neuroblastoma (NB) is a highly malignant pediatric solid tumor where a hypoxic signature correlates with unfavorable patient outcome. The hypoxia-inducible factor (HIF)-1α plays an important role in NB progression, contributing to cell proliferation and invasiveness. RAI belongs to the Shc family proteins, it is mainly neuron specific and protects against cerebral ischemia. RAI is also expressed in several NB cell lines, where it promotes cell survival. In this work, hypoxia differently affected cell survival and pro-apoptotic program in two NB cell lines, either expressing RAI (SKNBE) or not (SKNMC). RAI expression appeared to promote NB cell survival and to reduce some pro-apoptotic markers under hypoxia. Accordingly, the RAI silencing in SKNBE cells resulted in a reduction of cell survival and HIF-1α expression. Furthermore, using SKNMC cells stably expressing RAI, we defined a role of RAI in NB cell responses to hypoxia. Of interest, in hypoxic SKNMC cells expressing RAI HIF-1α protein levels were higher than in control cells. This was associated with a) an increased cell survival; b) an increased expression of anti-apoptotic markers; c) a pro-autophagic and not pro-apoptotic phenotype; and d) an increased metabolic activity. We may conclude that RAI plays an important role in hypoxic signaling in NB cells and the interplay between RAI and HIF-1α may be relevant in the protection of NB cells against hypoxia. Our results may contribute to a further understanding the physiology of NB cells and the molecular mechanisms involved in their survival, with important implications in NB progression. © 2017 Wiley Periodicals, Inc.

How Bullying Involvement Is Associated with the Distribution of Parental Background and with Subjective Health Complaints among Swedish Boys and Girls

ERIC Educational Resources Information Center

Carlerby, Heidi; Viitasara, Eija; Knutsson, Anders; Gadin, Katja Gillander

2013-01-01

This study aimed to analyze how bullying involvement is associated with the distribution of parental background and with subjective health complaints (SHC) among Swedish boys and girls. Data were collected from the World Health Organization, Health Behavior in School-aged Children (WHO/HBSC) survey, measurement years 1997/1998, 2001/2002 and…

Chordin-Like 1 Suppresses Bone Morphogenetic Protein 4-Induced Breast Cancer Cell Migration and Invasion

PubMed Central

Cyr-Depauw, Chanèle; Northey, Jason J.; Tabariès, Sébastien; Annis, Matthew G.; Dong, Zhifeng; Cory, Sean; Hallett, Michael; Rennhack, Jonathan P.; Andrechek, Eran R.

2016-01-01

ShcA is an important mediator of ErbB2- and transforming growth factor β (TGF-β)-induced breast cancer cell migration, invasion, and metastasis. We show that in the context of reduced ShcA levels, the bone morphogenetic protein (BMP) antagonist chordin-like 1 (Chrdl1) is upregulated in numerous breast cancer cells following TGF-β stimulation. BMPs have emerged as important modulators of breast cancer aggressiveness, and we have investigated the ability of Chrdl1 to block BMP-induced increases in breast cancer cell migration and invasion. Breast cancer-derived conditioned medium containing elevated concentrations of endogenous Chrdl1, as well as medium containing recombinant Chrdl1, suppresses BMP4-induced signaling in multiple breast cancer cell lines. Live-cell migration assays reveal that BMP4 induces breast cancer migration, which is effectively blocked by Chrdl1. We demonstrate that BMP4 also stimulated breast cancer cell invasion and matrix degradation, in part, through enhanced metalloproteinase 2 (MMP2) and MMP9 activity that is antagonized by Chrdl1. Finally, high Chrdl1 expression was associated with better clinical outcomes in patients with breast cancer. Together, our data reveal that Chrdl1 acts as a negative regulator of malignant breast cancer phenotypes through inhibition of BMP signaling. PMID:26976638

Chlorogenic acid inhibits hypoxia-induced pulmonary artery smooth muscle cells proliferation via c-Src and Shc/Grb2/ERK2 signaling pathway.

PubMed

Li, Qun-Yi; Zhu, Ying-Feng; Zhang, Meng; Chen, Li; Zhang, Zhen; Du, Yong-Li; Ren, Guo-Qiang; Tang, Jian-Min; Zhong, Ming-Kang; Shi, Xiao-Jin

2015-03-15

Chlorogenic acid (CGA), abundant in coffee and particular fruits, can modulate hypertension and vascular dysfunction. Hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) proliferation has been tightly linked to vascular remodeling in pulmonary arterial hypertension (PAH). Thus, the present study was designed to investigate the effect of CGA on hypoxia-induced proliferation in cultured rat PASMCs. The data showed that CGA potently inhibited PASMCs proliferation and DNA synthesis induced by hypoxia. These inhibitory effects were associated with G1 cell cycle arrest and down-regulation of cell cycle proteins. Treatment with CGA reduced hypoxia-induced hypoxia inducible factor 1α (HIF-1α) expression and trans-activation. Furthermore, hypoxia-evoked c-Src phosphorylation was inhibited by CGA. In vitro ELISA-based tyrosine kinase assay indicated that CGA was a direct inhibitor of c-Src. Moreover, CGA attenuated physical co-association of c-Src/Shc/Grb2 and ERK2 phosphorylation in PASMCs. These results suggest that CGA inhibits hypoxia-induced proliferation in PASMCs via regulating c-Src-mediated signaling pathway. In vivo investigation showed that chronic CGA treatment inhibits monocrotaline-induced PAH in rats. These findings presented here highlight the possible therapeutic use of CGA in hypoxia-related PAH. Copyright © 2015 Elsevier B.V. All rights reserved.

EPA Technical Support Centers (TSC): FY14 Lessons ...

EPA Pesticide Factsheets

EPA’s Technical Support Centers (TSC) included in ORD’s Safe and Healthy Communities (SHC) Research Action Plan fill the need for supplying subject-matter experts to continually assess state-of-the-art research and practices and channel this information to users in both direct applications (i.e., site-specific technical support) and general applications (i.e., technical transfer activities such as technical guidance documents, conferences, or workshops) . The TSCs are charged with providing solutions by: 1) linking EPA research to Agency decision-makers; 2) applying best practices to real world field applications; and 3) channeling feedback from field application to research communities. The TSP goal is to provide Regional Remedial Project Managers (RPMs), Corrective Action Staff, and On-Scene Coordinators (OSCs) with a diverse set of readily-accessible resources for technical assistance. This research summary provides six case studies – two from each of the three TSCs (Ground Water Technical Support Center, Engineering Technical Support Center, and Site Characterization Technical Support Center) – to exemplify and summarize the variety of TSC approaches that contribute to fulfilling the TSP mission. EPA’s Technical Support Centers (TSC) included in ORD’s Safe and Healthy Communities (SHC) Research Action Plan fill the need for supplying subject-matter experts to continually assess state-of-the-art research and practices and channel this informati

Novel Luciferase-Based Reporter System to Monitor Activation of ErbB2/Her2/neu Pathway Noninvasively During Radiotherapy

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

Wolf, Frank; Li Wenrong; Li Fang

2011-01-01

Purpose: To develop a split-luciferase-based reporter system that allows for noninvasive monitoring of activation of the Her2/neu pathway in vivo in a quantitative and sensitive manner. Methods and Materials: Fusion proteins of the ErbB2/Her2/neu receptor to the N-terminal fragment of luciferase and of its downstream binding partner Shc to the C-terminal fragment of luciferase have been engineered owing to the rationale that on activation and binding of the Her2 receptor molecule to Shc, luciferase function will be reconstituted. Thus, the resulting bioluminescence signals can serve as a surrogate measure of receptor activation. Results: We have shown that our reporter systemsmore » functions well in vitro in breast cancer cells and in vivo in xenograft tumors. In particular, the activities of Her2/neu in xenograft tumors could be monitored serially for an extended period after radiotherapy. Conclusions: We believe that the novel ErbB2/Her2/neu reporter we have presented is a powerful tool to study the biology of the Her2-neu pathway in vitro and in vivo. It should also facilitate the development and rapid evaluation of new Her2/neu-targeted therapeutic agents.« less

Sustainability at the community level: Searching for common ...

EPA Pesticide Factsheets

The Sustainable and Healthy Communities (SHC) research program is intended to support resource sustainability and decision making at the community level. Sustainability is defined as the ability of a community to meet present needs without compromising the ability of society and the environment to meet the economic, social, and environmental needs of future generations. The USEPA and its partners seek a national strategy that maximizes impacts by identifying common ground among communities that can inform the decision process. In this report, communities are compared based on four distinct metrics (community type; human well-being index; stakeholder priorities; and availability of ecosystem goods and services) with the purpose of seeking common ground for defining and measuring sustainability at the local scale. Overlying this comparison is the question of the usefulness of a community classification system (CCS) for generalizing the findings to new communities. Community type was found to be informative regarding the relative importance of elements of well-being. Two major delineations of community type are considered here. First is geographic, or simply asking if place defines how communities measure well-being. The second was the CCS described in report Section 2. We then examine whether values of a specific measure of well-being, the human well-being index (HWBI), differ either geographically or by community type. Stakeholder priorities are then examined in

Physiological, evolutionary, and genetic experiments with hopanoids in Methylobacterium: probing the function of geologically stable molecules

NASA Astrophysics Data System (ADS)

Bradley, A. S.; Muller, E.; Bringel, F.; Vuilleumier, S.; Pearson, A.; Marx, C. J.

2010-12-01

Hopanoids are geologically stable triterpenoids with a rock record extending to the Archean (1), but little information exists regarding their physiological role in modern organisms. Determining the physiological role of hopanoids is a key step in deciphering their geological and evolutionary history. To this end, we are investigating the function of hopanoids in the facultative methylotrophic bacterium Methylobacterium through a series of experiments in which we compare the behavior of wild type strains to mutants deficient in key genes associated with hopanoid biosynthesis. Mutant strains of bacteria deficient in the gene shc for squalene-hopene cyclase (SHC) lack hopanoids, but show only a subtle growth defect under pH and temperature stress in Rhodopseudomonas (2), and no growth defect in Streptomyces (3). In contrast, mutant strains of Methylobacterium deficient in SHC show a severe growth defect under usual growth conditions, with slower growth rates, alterations in cell morphology, increased sensitivity to toxic compounds, and severe flocculation during growth in liquid media. This severe phenotype offered an opportunity to investigate the function of hopanoids through an experimental evolution protocol. By serial passage through batch culture, sixteen replicate populations of the mutant strain were evolved in liquid media for approximately 120 generations. Populations evolved on each substrate show improved growth rates, approaching that of wild type strains. Current work is aimed at characterizing the physiology, and resequencing genomes of evolved isolates to determine the adaptations corresponding improved fitness. We predict that these adaptations will lead to hypotheses regarding hopanoid function. Mutations of other hopanoid-associated genes in Methylobacterium produce an altered suite of hopanoid compounds. Through mutation of hopanoid-associated genes, we have identified the first steps of hopanoid side chain biosynthesis (4). These mutant strains offer the opportunity for further evolutionary experiments, which may elucidate the function of specific hopanoid structures. 1. J. J. Brocks, R. E. Summons, in Biogeochemistry W. H. Schlesinger, Ed. (Elsevier, Oxford, 2004), vol. 8, pp. 63-116. 2. P. V. Welander et al., Journal of Bacteriology 191, 6145 (2009). 3. R. F. Seipke, R. Loria, Journal of Bacteriology 191, 5216 (2009). 4. A. S. Bradley, A. Pearson, J. P. Sáenz, C. J. Marx, Organic Geochemistry, in press (2010).

Influence of oxygen partial pressure on the characteristics of human hepatocarcinoma cells.

PubMed

Trepiana, Jenifer; Meijide, Susana; Navarro, Rosaura; Hernández, M Luisa; Ruiz-Sanz, José Ignacio; Ruiz-Larrea, M Begoña

2017-08-01

Most of the in vitro studies using liver cell lines have been performed under atmospheric oxygen partial pressure (21% O 2 ). However, the oxygen concentrations in the liver and cancer cells are far from this value. In the present study, we have evaluated the influence of oxygen on 1) the tumor cell lines features (growth, steady-state ROS levels, GSH content, activities of antioxidant enzymes, p66 Shc and SOD expressions, metalloproteinases secretion, migration, invasion, and adhesion) of human hepatocellular carcinoma cell lines, and b) the response of the cells to an oxidant stimulus (aqueous leaf extract of the V. baccifera plant species). For this purpose, three hepatocarcinoma cell lines with different p53 status, HepG2 (wild-type), Huh7 (mutated), and Hep3B (deleted), were cultured (6-30 days) under atmospheric (21%) and more physiological (8%) pO 2 . Results showed that after long-term culturing at 8% versus 21% O 2 , the cellular proliferation rate and the steady-state levels of mitochondrial O 2 - were unaffected. However, the intracellular basal ROS levels were higher independently of the characteristics of the cell line. Moreover, the lower pO 2 was associated with lower glutathione content, the induction of p66 Shc and Mn-SOD proteins, and increased SOD activity only in HepG2. This cell line also showed a higher migration rate, secretion of active metalloproteinases, and a faster invasion. HepG2 cells were more resistant to the oxidative stress induced by V. baccifera. Results suggest that the long-term culturing of human hepatoma cells at a low, more physiological pO 2 induces antioxidant adaptations that could be mediated by p53, and may alter the cellular response to a subsequent oxidant challenge. Data support the necessity of validating outcomes from studies performed with hepatoma cell cultures under ambient O 2 . Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Human papillomavirus vaccination and genital warts in young Indigenous Australians: national sentinel surveillance data.

PubMed

Ali, Hammad; McManus, Hamish; O'Connor, Catherine C; Callander, Denton; Kong, Marlene; Graham, Simon; Saulo, Dina; Fairley, Christopher K; Regan, David G; Grulich, Andrew; Low, Nicola; Guy, Rebecca J; Donovan, Basil

2017-03-20

To examine the impact of the national human papillomavirus (HPV) vaccination program (available to girls and women [12-26 years] since 2007 and to boys [12-15 years] since 2013) on the number of diagnoses of genital warts in Australian Aboriginal and Torres Strait Islander (Indigenous) people. Analysis of routinely collected data from patients attending 39 sexual health clinics (SHCs) in the Genital Warts Surveillance Network for the first time.Major outcome: The average annual proportion of Indigenous and non-Indigenous SHC patients diagnosed with genital warts during the pre-vaccination (2004-2007) and vaccination periods (2008-2014), stratified by age group and sex. 7.3% of the 215 599 Australian-born patients with known Indigenous status and seen for the first time at participating SHCs during 2004-2014 were Indigenous Australians. The average proportion of female Indigenous patients diagnosed with warts was lower during the vaccination period than during the pre-vaccination period (in those under 21, summary rate ratio [SRR], 0.12; 95% CI, 0.07-0.21; P < 0.001); in 21-30-year olds: SRR, 0.41; 95% CI, 0.27-0.61; P < 0.001); there was no significant difference for women over 30 (SRR, 0.84; 95% CI, 0.51-1.36; P = 0.47). The proportion of male Indigenous heterosexual SHC patients under 21 diagnosed with warts was also lower during the vaccination period (SRR, 0.25; 95% CI, 0.12-0.49; P < 0.001), with no significant changes among older Indigenous men over 30. There were marked declines in the proportions of diagnoses of genital warts in young Indigenous women and men attending SHCs after the introduction of the HPV vaccination program. If high levels of HPV vaccine coverage are sustained, HPV-related cancer rates should also decline.

A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling.

PubMed

Denis, Deborah; Rouleau, Cecile; Schaffhausen, Brian S

2017-01-15

Middle T antigen (MT), the principal oncoprotein of murine polyomavirus, transforms by association with cellular proteins. Protein phosphatase 2A (PP2A), YAP, Src family tyrosine kinases, Shc, phosphatidylinositol 3-kinase (PI3K), and phospholipase C-γ1 (PLCγ1) have all been implicated in MT transformation. Mutant dl1015, with deletion of residues 338 to 347 in the C-terminal region, has been an enigma, because the basis for its transformation defect has not been apparent. This work probes the dl1015 region of MT. Because the region is proline rich, the hypothesis that it targets Src homology domain 3 (SH3) domains was tested, but mutation of the putative SH3 binding motif did not affect transformation. During this work, two point mutants, W348R and E349K, were identified as transformation defective. Extensive analysis of the E349K mutant is described here. Similar to wild-type MT, the E349K mutant associates with PP2A, YAP, tyrosine kinases, Shc, PI3 kinase, and PLCγ1. The E349K mutant was examined to determine the mechanism for its transformation defect. Assays of cell localization and membrane targeting showed no obvious difference in localization. Src association was normal as assayed by in vitro kinase and MT phosphopeptide mapping. Shc activation was confirmed by its tyrosine phosphorylation. Association of type 1 PI3K with MT was demonstrated by coimmunoprecipitation, showing both PI3K subunits and in vitro activity. Nonetheless, expression of the mutants failed to lead to the activation of two known downstream targets of PI3K, Akt and Rac-1. Strikingly, despite normal association of the E349K mutant with PI3K, cells expressing the mutant failed to elevate phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in mutant-expressing cells. These results indicate a novel unsuspected aspect to PI3K control. The gene coding for middle T antigen (MT) is the murine polyomavirus oncogene most responsible for tumor formation. Its study has a history of uncovering novel aspects of mammalian cell regulation. The importance of PI3K activity and tyrosine phosphorylation are two examples of insights coming from MT. This study describes new mutants unable to transform like the wild type that point to novel regulation of PI3K signaling. Previous mutants were defective in PI3K because they failed to bind the enzyme and bring the activity to the membrane. These mutants recruit PI3K activity like the wild type, but fail to elevate the cellular level of PIP3, the product used to signal downstream of PI3K. As a result, they fail to activate either Akt or Rac1, explaining the transformation defect. Copyright © 2017 American Society for Microbiology.

Determination of the Impregnant Concentrations on ASC Type Charcoal. A Magnetic Susceptibility Study

DTIC Science & Technology

1987-10-01

commercial magnetic susceptometers were used on site at the Geological Division of CANMET , whose help is greatly appreciated. One of the susceptometers was a...CHARCOAL. A MAGNETIC SUSCEPTIBILITY STUDY (U) by S.H.C. Liang, B.H. Harrison and J.G. Pagotto Chemical Protection Section Protective Sciences Division ...analysis (11, 16-18), and surveys of literature reports (19-23). Some recent advances in instrumentation, such as the vibrating sample magnetometer (24

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

PubMed Central

Kim, Hyo Jung; Cha, Jiyoung Y.; Seok, Jo Woon; Choi, Yoonjeong; Yoon, Bo Kyung; Choi, Hyeonjin; Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Lee, Hyemin; Kim, Daeun; Han, Ji Yoon; Kim, Jae-woo

2016-01-01

Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223–276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis. PMID:27345868

Integrin activation and focal complex formation in cardiac hypertrophy.

PubMed

Laser, M; Willey, C D; Jiang, W; Cooper, G; Menick, D R; Zile, M R; Kuppuswamy, D

2000-11-10

Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

Integrin activation and focal complex formation in cardiac hypertrophy

NASA Technical Reports Server (NTRS)

Laser, M.; Willey, C. D.; Jiang, W.; Cooper, G. 4th; Menick, D. R.; Zile, M. R.; Kuppuswamy, D.

2000-01-01

Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

A System Dynamics Model for Integrated Decision Making ...

EPA Pesticide Factsheets

EPA’s Sustainable and Healthy Communities Research Program (SHC) is conducting transdisciplinary research to inform and empower decision-makers. EPA tools and approaches are being developed to enable communities to effectively weigh and integrate human health, socioeconomic, environmental, and ecological factors into their decisions to promote community sustainability. To help achieve this goal, EPA researchers have developed systems approaches to account for the linkages among resources, assets, and outcomes managed by a community. System dynamics (SD) is a member of the family of systems approaches and provides a framework for dynamic modeling that can assist with assessing and understanding complex issues across multiple dimensions. To test the utility of such tools when applied to a real-world situation, the EPA has developed a prototype SD model for community sustainability using the proposed Durham-Orange Light Rail Project (D-O LRP) as a case study.The EPA D-O LRP SD modeling team chose the proposed D-O LRP to demonstrate that an integrated modeling approach could represent the multitude of related cross-sectoral decisions that would be made and the cascading impacts that could result from a light rail transit system connecting Durham and Chapel Hill, NC. In keeping with the SHC vision described above, the proposal for the light rail is a starting point solution for the more intractable problems of population growth, unsustainable land use, environmenta

Involvement of phenazines and lipopeptides in interactions between Pseudomonas species and Sclerotium rolfsii, causal agent of stem rot disease on groundnut.

PubMed

Le, C N; Kruijt, M; Raaijmakers, J M

2012-02-01

To determine the role of phenazines (PHZ) and lipopeptide surfactants (LPs) produced by Pseudomonas in suppression of stem rot disease of groundnut, caused by the fungal pathogen Sclerotium rolfsii. In vitro assays showed that PHZ-producing Pseudomonas chlororaphis strain Phz24 significantly inhibited hyphal growth of S. rolfsii and suppressed stem rot disease of groundnut under field conditions. Biosynthesis and regulatory mutants of Phz24 deficient in PHZ production were less effective in pathogen suppression. Pseudomonas strains SS101, SBW25 and 267, producing viscosin or putisolvin-like LPs, only marginally inhibited hyphal growth of S. rolfsii and did not suppress stem rot disease. In contrast, Pseudomonas strain SH-C52, producing the chlorinated LP thanamycin, inhibited hyphal growth of S. rolfsii and significantly reduced stem rot disease of groundnut in nethouse and field experiments, whereas its thanamycin-deficient mutant was less effective. Phenazines and specific lipopeptides play an important role in suppression of stem rot disease of groundnut by root-colonizing Pseudomonas strains. Pseudomonas strains Phz24 and SH-C52 showed significant control of stem rot disease. Treatment of seeds or soil with these strains provides a promising supplementary strategy to control stem rot disease of groundnut. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR.

PubMed

Tzatsos, Alexandros

2009-08-21

In normal physiological states mTOR phosphorylates and activates Akt. However, under diabetic-mimicking conditions mTOR inhibits phosphatidylinositol (PI) 3-kinase/Akt signaling by phosphorylating insulin receptor substrate-1 (IRS-1) at Ser-636/639. The molecular basis for the differential effect of mTOR signaling on Akt is poorly understood. Here, it has been shown that knockdown of mTOR, Raptor, and mLST8, but not Rictor and mSin1, suppresses insulin-stimulated phosphorylation of IRS-1 at Ser-636/639 and stabilizes IRS-1 after long term insulin stimulation. This phosphorylation depends on the PI 3-kinase/PDK1 axis but is Akt-independent. At the molecular level, Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR. IRS-1 lacking the SAIN domain does not interact with Raptor, is not phosphorylated at Ser-636/639, and favorably interacts with PI 3-kinase. Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold-dependent.

Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

PubMed

Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

2008-09-14

PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

Regulating Prostate Cancer Sensitivity to Chemotherapy through Translational Control of CCAAT Enhancer Binding Proteins

DTIC Science & Technology

2015-08-01

ratio in LNCaP and PC3 cells and suppression of CEBPB sensitized these cells to bortezomib in vitro. PC3 xenografts deficient in CEBPB showed...resistant growth of PCa tumors in a mouse xenograft model. shNTV or shCEBPB LNCaP cells were subcutaneously engrafted into male NSG mice and when tumors...was monitored weekly by caliper measurement for 8-weeks (Fig. 3B). We observed significant suppression of CRPC growth in xenografts expressing shC

Membrane Estrogen Receptor Alpha Targeting and its Association with SHC in Regulating Breast Cancer Cell Proliferation

DTIC Science & Technology

2004-06-01

American Society for Cell Biology, San Francisco , California, Dec. 13-17, 2003. 3. Invited speaker in one of symposiums "Recognition of estrogen receptor in...Oncology, Bahamonde MI, Mann GE, Vergara C, Latorre R 1999 University of Virginia Health Science Center, Charlottesville, Acute activation of Maxi-K...intracellular Bahamonde, G.E. Mann, C. Vergara , R. Latorre, Acute activa- calcium, Proc. Nati. Acad. Sci. USA. 96 (1999) 4686-4691. tion of Maxi-K channels by

Using EnviroAtlas Data to Identify Cost-Effective Locations for ...

EPA Pesticide Factsheets

Manure Management Use Case A use case walks through an example application of how EnviroAtlas data, in conjunction with other available data or resources, may be used to address real-world questions. Use cases may be hypothetical or based on actual cases where EnviroAtlas has been used in decision making at the local, regional or national scale. The use case is a deliverable for the EnviroAtlas project under the SHC 1.62 and will be incorporated on the EnviroAtlas website.

Optimization Process for Configuration of Flexible Joined-Wing

DTIC Science & Technology

2004-03-01

T5NQX&bYX& hYU deZQX&N�b p hYLvVWy p SE� p SZQyvX,L � TY�qdeZM\\CTHaMShc\\�SZWN�hYdek�b p de��OZWX[TYT deZ�b p X���deZWy3klLc��kOP�NWX[b|X[ hYU deZWdeZQy...LvdeZQX&N ��deZWy�[LvZQ�&X&aWb p ST�ZWL Z oedeZWXqSh(NWX&��L hYU �SbYdeLvZ � p ShcS�[b|X[hYdeTYbYde�[Tc\\�b p X�THbYhYVW�&bYVWhcSoOL aWbYdeUd`uOS...5^5^5^5^5^5^5^;^5^5^5^5^5^ ^e­v^ r X[bYX& hYU deZQX&N © aQbYdeU�So�KfLvZQnWy VWhcSbYdeL Z¿^5^5^5^5^5^ ^e­v^`ª ] VW��OoedeZQy

Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells.

PubMed

Kurotsuchi, Ai; Murakumo, Yoshiki; Jijiwa, Mayumi; Kurokawa, Kei; Itoh, Yasutomo; Kodama, Yoshinori; Kato, Takuya; Enomoto, Atsushi; Asai, Naoya; Terasaki, Hiroko; Takahashi, Masahide

2010-05-01

Point mutations and structural alterations of the RET tyrosine kinase gene cause multiple endocrine neoplasia type 2 (MEN 2) and papillary thyroid carcinoma, respectively. RET activation by glial cell line-derived neurotrophic factor (GDNF) is essential for the development of the enteric nervous system and the kidney. The signal through RET tyrosine kinase requires several adaptor proteins including the DOK (downstream of kinase) family of proteins. Of the seven members of the DOK protein family, DOK-1, -4, -5, and -6 have been reported to play roles in the GDNF-RET signaling pathway. Although DOK-6 has been shown to bind to RET and promote GDNF-induced neurite outgrowth in mouse Neuro2A cells, DOK-6 function in human cells remains unclear. In the present study, we investigated the role of DOK-6 in GDNF-RET signaling in human cells including neuroblastoma cells. DOK-6 was constitutively localized to the plasma membrane via its pleckstrin homology (PH) domain, and was phosphorylated following RET activation via a MEN2A mutation or GDNF stimulation. However, DOK-6 could not significantly affect downstream signaling and neurite outgrowth in human neuroblastoma cells. The binding affinity of the DOK-6 phosphotyrosine-binding (PTB) domain to RET was much lower than that of the DOK-1, DOK-4, and SHC PTB domains to RET. These findings indicate that DOK-6 is involved in RET signaling with less influence when compared with DOK-1, DOK-4, and SHC.

Neuroprotective Effects of Reactive Oxygen Species Mediated by BDNF-Independent Activation of TrkB

PubMed Central

Huang, Yang Zhong; McNamara, James O.

2012-01-01

Reactive oxygen species (ROS) have diverse biological consequences in the mammalian CNS, but the molecular targets mediating these pleiotropic effects are incompletely understood. Like ROS, the neurotrophin receptor, TrkB receptor tyrosine kinase, has diverse effects in the developing and mature mammalian brain. Our discovery that zinc can transactivate TrkB, together with the finding that ROS can trigger zinc release from cytosolic zinc binding proteins, led us to hypothesize that ROS can transactivate TrkB in CNS neurons by a zinc-dependent mechanism. We found that both exogenous H2O2 and endogenous ROS activate TrkB signaling by a Src family kinase-dependent but brain-derived neurotrophic factor-independent mechanism in cultured rat cortical neurons. Exogenous H2O2 enhances cytosolic zinc content in a metallothionein-3 (MT-3)-requiring manner. Both exogenous H2O2 and endogenous ROS mediated transactivation of TrkB requires intracellular zinc and MT-3. The ROS-triggered transactivation of TrkB exerts neuroprotective effects, because inhibition of TrkB kinase activity or uncoupling Shc signaling from TrkB exacerbates neuronal cell death induced by H2O2. Thus, we propose a molecular signaling event whereby ROS induce release of zinc from cytosolic MT-3, the increased cytosolic zinc transactivates TrkB, and the enhanced Shc signaling downstream from TrkB promotes prosurvival effects. We suggest that such neuroprotective effects mediated by ROS are operative in diverse acute and chronic neurological disorders. PMID:23115189

Effects of a sexual health care nursing record on the attitudes and practice of oncology nurses.

PubMed

Jung, Dukyoo; Kim, Jung-Hee

2016-10-01

A nursing record focused on sexual health care for patients with cancer could encourage oncology nurses to provide sexual health care for oncology patients in a simple and effective manner. However, existing electronic information systems focus on professional use and not sexual health care, which could lead to inefficiencies in clinical practice. To examine the effects of a sexual health care nursing record on the attitudes and practice of oncology nurses. Twenty-four full-time registered nurses caring for oncology patients were randomly assigned to the intervention and control groups in Korea. The researchers developed a sexual health care record and applied it to the intervention group for one month. Data were analyzed by Mann-Whitney U test and chi-square test. Content analysis was used to analyze interviews. Oncology nurses using the sexual health care record had significantly higher levels of sexual health care practice at 4 weeks post-intervention as compared to those who provided usual care to patients with cancer. A sexual health care record may have the potential to facilitate oncology nurses' practice of sexual health care. This study highlighted the importance of using SHC records with oncology patients to improve nursing practice related to sexuality issues. A nursing record focused on SHC for patients with cancer could make it easier and more effective for oncology nurses to provide such care to their patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

PubMed

Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

2018-06-08

Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

Developing and promoting an intranet site for a drug information service.

PubMed

Costerison, Emily C; Graham, Angie S

2008-04-01

The development and promotion of a drug information service (DIS) intranet site are described. Stanford Hospital and Clinics (SHC) is an acute and tertiary care facility with 613 licensed inpatient beds and 48 outpatient clinics. A DIS intranet site was developed to allow better accessibility to pharmacy forms and products (e.g., drug shortage list, reference guides) and to reduce repetitive requests to the DIS. The goal was to continue to provide information to SHC health care providers but allow the drug information specialist to focus on answering clinical questions. The intranet site was completed over a four-month period. The intranet site was divided into seven webpages: DIS overview, pharmacy and therapeutics, frequently asked questions, quick drug reference guide, ask the pharmacist, drug information resources, and referral center. The preparation for and implementation of the promotional phase took approximately two months. Promotional strategies included the creation and dissemination of brochures and stickers. The intranet site went live on January 1, 2007, and the advertising campaign began one month later. The utility of the site was measured for five months by tracking the number of visits to the site, the number of visits to each webpage, and the number of downloaded files. Request volume, caller affiliation, and question types received by the DIS call center were also recorded. Establishing a DIS intranet site required a considerable time investment and a willingness to work with existing infrastructures, such as the marketing and communications department and Web marketing staff.

Time-dependent patterns in quasivertical cylindrical binary convection.

PubMed

Alonso, Arantxa; Mercader, Isabel; Batiste, Oriol

2018-02-01

This paper reports on numerical investigations of the effect of a slight inclination α on pattern formation in a shallow vertical cylindrical cell heated from below for binary mixtures with a positive value of the Soret coefficient. By using direct numerical simulation of the three-dimensional Boussinesq equations with Soret effect in cylindrical geometry, we show that a slight inclination of the cell in the range α≈0.036rad=2^{∘} strongly influences pattern selection. The large-scale shear flow (LSSF) induced by the small tilt of gravity overcomes the squarelike arrangements observed in noninclined cylinders in the Soret regime, stratifies the fluid along the direction of inclination, and produces an enhanced separation of the two components of the mixture. The competition between shear effects and horizontal and vertical buoyancy alters significantly the dynamics observed in noninclined convection. Additional unexpected time-dependent patterns coexist with the basic LSSF. We focus on an unsual periodic state recently discovered in an experiment, the so-called superhighway convection state (SHC), in which ascending and descending regions of fluid move in opposite directions. We provide numerical confirmation that Boussinesq Navier-Stokes equations with standard boundary conditions contain the essential ingredients that allow for the existence of such a state. Also, we obtain a persistent heteroclinic structure where regular oscillations between a SHC pattern and a state of nearly stationary longitudinal rolls take place. We characterize numerically these time-dependent patterns and investigate the dynamics around the threshold of convection.

Time-dependent patterns in quasivertical cylindrical binary convection

NASA Astrophysics Data System (ADS)

Alonso, Arantxa; Mercader, Isabel; Batiste, Oriol

2018-02-01

This paper reports on numerical investigations of the effect of a slight inclination α on pattern formation in a shallow vertical cylindrical cell heated from below for binary mixtures with a positive value of the Soret coefficient. By using direct numerical simulation of the three-dimensional Boussinesq equations with Soret effect in cylindrical geometry, we show that a slight inclination of the cell in the range α ≈0.036 rad =2∘ strongly influences pattern selection. The large-scale shear flow (LSSF) induced by the small tilt of gravity overcomes the squarelike arrangements observed in noninclined cylinders in the Soret regime, stratifies the fluid along the direction of inclination, and produces an enhanced separation of the two components of the mixture. The competition between shear effects and horizontal and vertical buoyancy alters significantly the dynamics observed in noninclined convection. Additional unexpected time-dependent patterns coexist with the basic LSSF. We focus on an unsual periodic state recently discovered in an experiment, the so-called superhighway convection state (SHC), in which ascending and descending regions of fluid move in opposite directions. We provide numerical confirmation that Boussinesq Navier-Stokes equations with standard boundary conditions contain the essential ingredients that allow for the existence of such a state. Also, we obtain a persistent heteroclinic structure where regular oscillations between a SHC pattern and a state of nearly stationary longitudinal rolls take place. We characterize numerically these time-dependent patterns and investigate the dynamics around the threshold of convection.

Mitochondrial ROS Metabolism: 10 Years Later

PubMed Central

Kushnareva, Y. E.; Murphy, A. N.

2015-01-01

The role of mitochondria in oxidative stress is well recognized, but many questions are still to be answered. This article is intended to update our comprehensive review in 2005 by highlighting the progress in understanding of mitochondrial reactive oxygen species (ROS) metabolism over the past 10 years. We review the recently identified or re-appraised sources of ROS generation in mitochondria, such as p66shc protein, succinate dehydrogenase, and recently discovered properties of the mitochondrial antioxidant system. We also reflect upon some controversies, disputes, and misconceptions that confound the field. PMID:26071769

Cell Signaling by a Novel SH2 Domain Protein that is Overexpressed with Her2 in Breast Cancer

DTIC Science & Technology

1998-01-01

1990) Methods Enzymol. 185, 51. Wary, K. K, Mainiero, F ., Isakoff, S. J., Marcantonio , E. E., and Giancotti 527-537 F . G. (1996) Cell 87, 733-743...family of SH2 domain proteins and acts cell nonautonomously in excretory canal development. Dev. Biol. 184:150-164. 3. Pelicci, G., L. Lanfrancone, F ...Grignani, J. McGlade, F . Cavallo, G. Forni, I. Nicoletti, T. Pawson, and P. G. Pelicci. 1992. A novel transforming protein (SHC) with an SH2

Circular current loops, magnetic dipoles and spherical harmonic analysis.

USGS Publications Warehouse

Alldredge, L.R.

1980-01-01

Spherical harmonic analysis (SHA) is the most used method of describing the Earth's magnetic field, even though spherical harmonic coefficients (SHC) almost completely defy interpretation in terms of real sources. Some moderately successful efforts have been made to represent the field in terms of dipoles placed in the core in an effort to have the model come closer to representing real sources. Dipole sources are only a first approximation to the real sources which are thought to be a very complicated network of electrical currents in the core of the Earth. -Author

Implementation of Local Wellness Policies in Schools: Role of School Systems, School Health Councils, and Health Disparities.

PubMed

Hager, Erin R; Rubio, Diana S; Eidel, G Stewart; Penniston, Erin S; Lopes, Megan; Saksvig, Brit I; Fox, Renee E; Black, Maureen M

2016-10-01

Written local wellness policies (LWPs) are mandated in school systems to enhance opportunities for healthy eating/activity. LWP effectiveness relies on school-level implementation. We examined factors associated with school-level LWP implementation. Hypothesized associations included system support for school-level implementation and having a school-level wellness team/school health council (SHC), with stronger associations among schools without disparity enrollment (majority African-American/Hispanic or low-income students). Online surveys were administered: 24 systems (support), 1349 schools (LWP implementation, perceived system support, SHC). The state provided school demographics. Analyses included multilevel multinomial logistic regression. Response rates were 100% (systems)/55.2% (schools). Among schools, 44.0% had SHCs, 22.6% majority (≥75%) African-American/Hispanic students, and 25.5% majority (≥75%) low-income (receiving free/reduced-price meals). LWP implementation (17-items) categorized as none = 36.3%, low (1-5 items) = 36.3%, high (6+ items) = 27.4%. In adjusted models, greater likelihood of LWP implementation was observed among schools with perceived system support (high versus none relative risk ratio, RRR = 1.63, CI: 1.49, 1.78; low versus none RRR = 1.26, CI: 1.18, 1.36) and SHCs (high versus none RRR = 6.8, CI: 4.07, 11.37; low versus none RRR = 2.24, CI: 1.48, 3.39). Disparity enrollment did not moderate associations (p > .05). Schools with perceived system support and SHCs had greater likelihood of LWP implementation, with no moderating effect of disparity enrollment. SHCs/support may overcome LWP implementation obstacles related to disparities. © 2016, American School Health Association.

Solid-state probe based electrochemical aptasensor for cocaine: a potentially convenient, sensitive, repeatable, and integrated sensing platform for drugs.

PubMed

Du, Yan; Chen, Chaogui; Yin, Jianyuan; Li, Bingling; Zhou, Ming; Dong, Shaojun; Wang, Erkang

2010-02-15

Aptamers, which are artificial oligonucleotides selected in vitro, have been employed to design novel biosensors (i.e., aptasensors). In this work, we first constructed a label-free electrochemical aptasensor introducing a probe immobilization technique by the use of a layer-by-layer (LBL) self-assembled multilayer with ferrocene-appended poly(ethyleneimine) (Fc-PEI) on an indium tin oxide (ITO) array electrode for detection of cocaine. The Fc-PEI and gold nanoparticles (AuNPs) were LBL assembled on the electrode surface via electrostatic interaction. Then, cocaine aptamer fragments, SH-C2, were covalently labeled onto the outermost AuNP layer. When the target cocaine and cocaine aptamer C1 were present simultaneously, the SH-C2 layer hybridized partly with C1 to bind the cocaine, which led to a decreased differential pulse voltammetry (DPV) signal of Fc-PEI. This DPV signal change could be used to sensitively detect cocaine with the lowest detectable concentration down to 0.1 microM and the detection range up to 38.8 microM, which falls in the the expected range for medical use of detecting drug abuse involving cocaine. Meanwhile, the sensor was specific to cocaine in complex biologic fluids such as human plasma, human saliva, etc. The sensing strategy had general applicability, and the detection of thrombin could also be realized, displayed a low detection limit, and exhibited worthiness to other analytes. The aptasensor based on the array electrode held promising potential for integration of the sensing ability in multianalysis for simultaneous detection.

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

PubMed

Saafan, Hisham; Foerster, Sarah; Parra-Guillen, Zinnia P; Hammer, Elke; Michaelis, Martin; Cinatl, Jindrich; Völker, Uwe; Fröhlich, Holger; Kloft, Charlotte; Ritter, Christoph A

2016-10-30

Drug treatment of epidermal growth factor receptor (EGFR) positive non-small cell lung cancer has improved substantially by targeting activating mutations within the receptor tyrosine kinase domain. However, the development of drug resistance still limits this approach. As root causes, large heterogeneity between tumour entities but also within tumour cells have been suggested. Therefore, approaches to identify these multitude and complex mechanisms are urgently required. Affinity purification coupled with high resolution mass spectrometry was applied to isolate and characterise the EGFR interactome from HCC4006 non-small cell lung cancer cells and their variant HCC4006 r ERLO 0.5 adapted to grow in the presence of therapeutically relevant concentrations of erlotinib. Bioinformatics analyses were carried out to identify proteins and their related molecular functions that interact differentially with EGFR in the untreated state or when incubated with erlotinib prior to EGFR activation. Across all experimental conditions 375 proteins were detected to participate in the EGFR interactome, 90% of which constituted a complex protein interaction network that was bioinformatically reconstructed from literature data. Treatment of HCC4006 r ERLO 0.5 cells carrying a resistance phenotype to erlotinib was associated with an increase of protein levels of members of the clathrin-associated adaptor protein family AP2 (AP2A1, AP2A2, AP2B1), structural proteins of cytoskeleton rearrangement as well as signalling molecules such as Shc. Validation experiments confirmed activation of the Ras-Raf-Mek-Erk (MAPK)-pathway, of which Shc is an initiating adaptor molecule, in HCC4006 r ERLO 0.5 cells. Taken together, differential proteins in the EGFR interactome of HCC4006 r ERLO 0.5 cells were identified that could be related to multiple resistance mechanisms including alterations in growth factor receptor expression, cellular remodelling processes suggesting epithelial-to-mesenchymal transition as well as alterations in downstream signalling. Knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigating the Mechanism of Mena(INV)-Driven Metastasis

DTIC Science & Technology

2013-12-01

GAB1 ,  ZO2,  BCAR1,  EGFR,  TYK2,  INPPL,   GRLF1,  Pragmin,  GSK3,  ARHGAP12,  EphA2...endosomes   ITSN2,   Gab1 ,  EGFR,  SHC1,  Ship2,  NWASP,  MAPK1,  MAPK3   Interaction  with  Mena   INPPL,  EGFR   Table 1: A...addition, the effect of FN on MenaINV-expressing cells was blocked by an antibody specifically blocking active α5 (P1D6) but not by cilengitide, a

Giant spin Hall angle from topological insulator BixSe(1 - x) thin films

NASA Astrophysics Data System (ADS)

Dc, Mahendra; Jamali, Mahdi; Chen, Junyang; Hickey, Danielle; Zhang, Delin; Zhao, Zhengyang; Li, Hongshi; Quarterman, Patrick; Lv, Yang; Mkhyon, Andre; Wang, Jian-Ping

Investigation on the spin-orbit torque (SOT) from large spin-orbit coupling materials has been attracting interest because of its low power switching of the magnetization and ultra-fast driving of the domain wall motion that can be used in future spin based memory and logic devices. We investigated SOT from topological insulator BixSe(1 - x) thin film in BixSe(1 - x) /CoFeB heterostructure by using the dc planar Hall method, where BixSe(1 - x) thin films were prepared by a unique industry-compatible deposition process. The angle dependent Hall resistance was measured in the presence of a rotating external in-plane magnetic field at bipolar currents. The spin Hall angle (SHA) from this BixSe(1 - x) thin film was found to be as large as 22.41, which is the largest ever reported at room temperature (RT). The giant SHA and large spin Hall conductivity (SHC) make this BixSe(1 - x) thin film a very strong candidate as an SOT generator in SOT based memory and logic devices.

Multi-Sector Sustainability Browser (MSSB) User Manual: A ...

EPA Pesticide Factsheets

EPA’s Sustainable and Healthy Communities (SHC) Research Program is developing methodologies, resources, and tools to assist community members and local decision makers in implementing policy choices that facilitate sustainable approaches in managing their resources affecting the built environment, natural environment, and human health. In order to assist communities and decision makers in implementing sustainable practices, EPA is developing computer-based systems including models, databases, web tools, and web browsers to help communities decide upon approaches that support their desired outcomes. Communities need access to resources that will allow them to achieve their sustainability objectives through intelligent decisions in four key sustainability areas: • Land Use • Buildings and Infrastructure • Transportation • Materials Management (i.e., Municipal Solid Waste [MSW] processing and disposal) The Multi-Sector Sustainability Browser (MSSB) is designed to support sustainable decision-making for communities, local and regional planners, and policy and decision makers. Document is an EPA Technical Report, which is the user manual for the Multi-Sector Sustainability Browser (MSSB) tool. The purpose of the document is to provide basic guidance on use of the tool for users

Hopanoids play a role in stress tolerance and nutrient storage in the cyanobacterium Nostoc punctiforme.

PubMed

Ricci, J N; Morton, R; Kulkarni, G; Summers, M L; Newman, D K

2017-01-01

Hopanes are abundant in ancient sedimentary rocks at discrete intervals in Earth history, yet interpreting their significance in the geologic record is complicated by our incomplete knowledge of what their progenitors, hopanoids, do in modern cells. To date, few studies have addressed the breadth of diversity of physiological functions of these lipids and whether those functions are conserved across the hopanoid-producing bacterial phyla. Here, we generated mutants in the filamentous cyanobacterium, Nostoc punctiforme, that are unable to make all hopanoids (shc) or 2-methylhopanoids (hpnP). While the absence of hopanoids impedes growth of vegetative cells at high temperature, the shc mutant grows faster at low temperature. This finding is consistent with hopanoids acting as membrane rigidifiers, a function shared by other hopanoid-producing phyla. Apart from impacting fitness under temperature stress, hopanoids are dispensable for vegetative cells under other stress conditions. However, hopanoids are required for stress tolerance in akinetes, a resting survival cell type. While 2-methylated hopanoids do not appear to contribute to any stress phenotype, total hopanoids and to a lesser extent 2-methylhopanoids were found to promote the formation of cyanophycin granules in akinetes. Finally, although hopanoids support symbiotic interactions between Alphaproteobacteria and plants, they do not appear to facilitate symbiosis between N. punctiforme and the hornwort Anthoceros punctatus. Collectively, these findings support interpreting hopanes as general environmental stress biomarkers. If hopanoid-mediated enhancement of nitrogen-rich storage products turns out to be a conserved phenomenon in other organisms, a better understanding of this relationship may help us parse the enrichment of 2-methylhopanes in the rock record during episodes of disrupted nutrient cycling. © 2016 John Wiley & Sons Ltd.

Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes.

PubMed

Price, D J; Rivnay, B; Fu, Y; Jiang, S; Avraham, S; Avraham, H

1997-02-28

The Csk homologous kinase (CHK), formerly MATK, has previously been shown to bind to activated c-KIT. In this report, we characterize the binding of SH2(CHK) to specific phosphotyrosine sites on the c-KIT protein sequence. Phosphopeptide inhibition of the in vitro interaction of SH2(CHK)-glutathione S-transferase fusion protein/c-KIT from SCF/KL-treated Mo7e megakaryocytic cells indicated that two sites on c-KIT were able to bind SH2(CHK). These sites were the Tyr568/570 diphosphorylated sequence and the monophosphorylated Tyr721 sequence. To confirm this, we precipitated native CHK from cellular extracts using phosphorylated peptides linked to Affi-Gel 15. In addition, purified SH2(CHK)-glutathione S-transferase fusion protein was precipitated with the same peptide beads. All of the peptide bead-binding studies were consistent with the direct binding of SH2(CHK) to phosphorylated Tyr568/570 and Tyr721 sites. Binding of FYN and SHC to the diphosphorylated Tyr568/570 site was observed, while binding of Csk to this site was not observed. The SH2(CHK) binding to the two sites is direct and not through phosphorylated intermediates such as FYN or SHC. Site-directed mutagenesis of the full-length c-KIT cDNA followed by transient transfection indicated that only the Tyr568/570, and not the Tyr721, is able to bind SH2(CHK). This indicates that CHK binds to the same site on c-KIT to which FYN binds, possibly bringing the two into proximity on associated c-KIT subunits and leading to the down-regulation of FYN by CHK.

Modulation of mitochondrial biomarkers by intermittent hypobaric hypoxia and aerobic exercise after eccentric exercise in trained rats.

PubMed

Rizo-Roca, David; Ríos-Kristjánsson, Juan Gabriel; Núñez-Espinosa, Cristian; Santos-Alves, Estela; Magalhães, José; Ascensão, António; Pagès, Teresa; Viscor, Ginés; Torrella, Joan Ramon

2017-07-01

Unaccustomed eccentric contractions induce muscle damage, calcium homeostasis disruption, and mitochondrial alterations. Since exercise and hypoxia are known to modulate mitochondrial function, we aimed to analyze the effects on eccentric exercise-induced muscle damage (EEIMD) in trained rats using 2 recovery protocols based on: (i) intermittent hypobaric hypoxia (IHH) and (ii) IHH followed by exercise. The expression of biomarkers related to mitochondrial biogenesis, dynamics, oxidative stress, and bioenergetics was evaluated. Soleus muscles were excised before (CTRL) and 1, 3, 7, and 14 days after an EEIMD protocol. The following treatments were applied 1 day after the EEIMD: passive normobaric recovery (PNR), 4 h daily exposure to passive IHH at 4000 m (PHR) or IHH exposure followed by aerobic exercise (AHR). Citrate synthase activity was reduced at 7 and 14 days after application of the EEIMD protocol. However, this reduction was attenuated in AHR rats at day 14. PGC-1α and Sirt3 and TOM20 levels had decreased after 1 and 3 days, but the AHR group exhibited increased expression of these proteins, as well as of Tfam, by the end of the protocol. Mfn2 greatly reduced during the first 72 h, but returned to basal levels passively. At day 14, AHR rats had higher levels of Mfn2, OPA1, and Drp1 than PNR animals. Both groups exposed to IHH showed a lower p66shc(ser 36 )/p66shc ratio than PNR animals, as well as higher complex IV subunit I and ANT levels. These results suggest that IHH positively modulates key mitochondrial aspects after EEIMD, especially when combined with aerobic exercise.

Psychometric Properties of the Chinese Shortened Version of the Zuckerman–Kuhlman Personality Questionnaire in a Sample of Adolescents and Young Adults

PubMed Central

Wang, Daoyang; Hu, Mingming; Zheng, Chanjin; Liu, Zhengguang

2017-01-01

Introduction: The original 89-item Zuckerman–Kuhlman Personality Questionnaire (form III Revised, ZKPQ-III-R) is a widely accepted and used self-report measure for personality traits. This study assessed the reliability and construct validity of the Chinese short 46-item version of the ZKPQ-III-R in a sample of adolescents and young adults. Methodology: A total of 1,019 Chinese adolescents and young adults completed the Chinese version of the original 89-item version ZKPQ-III-R and short 46-item version ZKPQ-III-R, self-report measures of depression, life satisfaction, and subjective health complaints (SHC), the Big Five personality traits, and a substance use risk profile. We explored the internal consistency of five dimensions of the short 46-item version ZKPQ-III-R and compared it with observations in previous studies of Chinese and other populations. The structure of the questionnaire was analyzed by confirmatory factor analysis and exploratory structural equation modeling. Results: The short 46-item version ZKPQ-III-R had adequate internal reliability for all five dimensions, with Cronbach’s α coefficients of 0.63 to 0.84. The concurrent validity of the short 46-item version ZKPQ-III-R was supported by significant correlations with depression, life satisfaction, and SHC. The short 46-item version ZKPQ-III-R had better fit, similar reliability coefficients, and slightly better construct and convergent validity than the 89-item version. Conclusion: The Chinese version of the 46-item ZKPQ-III-R presented reliability and validity in measuring personality in Chinese adolescents and young adults. PMID:28326057

The need for an improved risk index for phosphorus losses to water from tile-drained agricultural land

NASA Astrophysics Data System (ADS)

Ulén, Barbro; Djodjic, Faruk; Etana, Araso; Johansson, Göran; Lindström, Jan

2011-03-01

SummaryA refined version of a conditional phosphorus risk index (PRI) for P losses to waters was developed based on monitoring and analyses of PRI factors from an agricultural catchment in Sweden. The catchment has a hummocky landscape of heavy glacial till overlying moraine and an overall balanced soil P level. Single P source factors and combinations of factors were tested and discussed together with water movement and water management factors important for catchments dominated by drained clay soils. An empirical relationship was established (Pearson correlation coefficient 0.861, p < 0.001) between phosphorus sorption index (PSI-CaCl 2), measured in a weak calcium chloride solution, and iron (Fe-AL) aluminium (Al-AL) and phosphorus (P-AL) in soil extract with acid ammonium lactate. Differing relationships were found for a field that had not received any manure in the last 15 years and a field that had received chicken litter very recently. In addition, a general relationship (Pearson correlation coefficient 0.839, p < 0.001) was found between the ratio of phosphorus extracted from fresh soil in water (Pw) to PSI-CaCl 2 and the degree of phosphorus saturation in lactate extract (DPS-AL). One exception was a single field, representing 7% of agricultural land in the catchment, that had been treated with glyphosate shortly before soil sampling. Saturated hydraulic conductivity (SHC) in heavy clay in contact with the moraine base (at 1 m depth) was on average 0.06 m day -1. In clay not in contact with moraine, SHC was significantly lower (mean 0.007 m day -1). A reduction in the present tile drain spacing (from 14-16 m to 11 m) is theoretically required to maintain satisfactory water discharge and groundwater level. Up to 10% of the arable land was estimated to be a potential source area for P, based on different indices. Parts of a few fields close to farm buildings (1% of total arable land) were identified as essential P source areas, with high DPS-AL values and low PSI-CaCl 2 values throughout the soil profile. A further 2% of arable land was identified as potential important transport areas, based on visible surface water rills or frequent water-ponded conditions. Fields comprising 10% of the total arable land in the catchment should be re-drained in the near future to improve water infiltration and avoid unnecessary channelised water flow. The need for an improved PRI for erosion and water transport is discussed.

Differential signaling and regulation of apical vs. basolateral EGFR in polarized epithelial cells.

PubMed

Kuwada, S K; Lund, K A; Li, X F; Cliften, P; Amsler, K; Opresko, L K; Wiley, H S

1998-12-01

Overexpression of the epidermal growth factor receptors (EGFR) in polarized kidney epithelial cells caused them to appear in high numbers at both the basolateral and apical cell surfaces. We utilized these cells to look for differences in the regulation and signaling of apical vs. basolateral EGFR. Apical and basolateral EGFR were biologically active and mediated EGF-induced cell proliferation to similar degrees. Receptor downregulation and endocytosis were less efficient at the apical surface, resulting in prolonged EGF-induced tyrosine kinase activity at the apical cell membrane. Tyrosine phosphorylation of EGFR substrates known to mediate cell proliferation, Src-homologous and collagen protein (SHC), extracellularly regulated kinase 1 (ERK1), and ERK2 could be induced similarly by activation of apical or basolateral EGFR. Focal adhesion kinase was tyrosine phosphorylated more by basolateral than by apical EGFR; however, beta-catenin was tyrosine phosphorylated to a much greater degree following the activation of mislocalized apical EGFR. Thus EGFR regulation and EGFR-mediated phosphorylation of certain substrates differ at the apical and basolateral cell membrane domains. This suggests that EGFR mislocalization could result in abnormal signal transduction and aberrant cell behavior.

[Epidemiologic and therapeutic status study of patients with hepatitis C].

PubMed

Xu, Min; Shi, Hai-yan; Cai, Wei-ping

2011-04-01

To investigate the different infective mode, the time from be infectived to be diagnosed and the time from be diagnosed to be treated of patients with hepatitis C. The different infective mode, the time from be infectived to be diagnosed and the time from be diagnosed to be treated of 216 patients with hepatitis C from march 2004 to march 2009 were retrospectively analyzed. 72.22 percents patients suffered from post transfusion hepatitis C (PTHC) and 27.78 percents patients suffered from sporadic hepatitisC (SHC). 32.61 percents patients were diagnosed after be infectived 15-20 years later. 3.26 percents patients were diagnosed after be infectived more than 20 years later. 33.80 percents patients were treated after be diagnosed more than 5 years later. 17.13 percents patients were treated after be diagnosed 10-15 years later. Most patients were infectived with hepatitis C by transfusing blood or blood products. Most patients were diagnosed after be infectived more than 15 years later. Almost half of patients were treated after be diagnosed more than 5 years later, and a significant portion of percents patients were treated after be diagnosed more than 10 years later.

The RNA-Binding Protein Musashi1 Affects Medulloblastoma Growth via a Network of Cancer-Related Genes and Is an Indicator of Poor Prognosis

PubMed Central

Vo, Dat T.; Subramaniam, Dharmalingam; Remke, Marc; Burton, Tarea L.; Uren, Philip J.; Gelfond, Jonathan A.; de Sousa Abreu, Raquel; Burns, Suzanne C.; Qiao, Mei; Suresh, Uthra; Korshunov, Andrey; Dubuc, Adrian M.; Northcott, Paul A.; Smith, Andrew D.; Pfister, Stefan M.; Taylor, Michael D.; Janga, Sarath C.; Anant, Shrikant; Vogel, Christine; Penalva, Luiz O.F.

2013-01-01

Musashi1 (Msi1) is a highly conserved RNA-binding protein that is required during the development of the nervous system. Msi1 has been characterized as a stem cell marker, controlling the balance between self-renewal and differentiation, and has also been implicated in tumorigenesis, being highly expressed in multiple tumor types. We analyzed Msi1 expression in a large cohort of medulloblastoma samples and found that Msi1 is highly expressed in tumor tissue compared with normal cerebellum. Notably, high Msi1 expression levels proved to be a sign of poor prognosis. Msi1 expression was determined to be particularly high in molecular subgroups 3 and 4 of medulloblastoma. We determined that Msi1 is required for tumorigenesis because inhibition of Msi1 expression by small-interfering RNAs reduced the growth of Daoy medulloblastoma cells in xenografts. To characterize the participation of Msi1 in medulloblastoma, we conducted different high-throughput analyses. Ribonucleoprotein immunoprecipitation followed by microarray analysis (RIP-chip) was used to identify mRNA species preferentially associated with Msi1 protein in Daoy cells. We also used cluster analysis to identify genes with similar or opposite expression patterns to Msi1 in our medulloblastoma cohort. A network study identified RAC1, CTGF, SDCBP, SRC, PRL, and SHC1 as major nodes of an Msi1-associated network. Our results suggest that Msi1 functions as a regulator of multiple processes in medulloblastoma formation and could become an important therapeutic target. PMID:22985791

A Framework for Multi-Stakeholder Decision-Making and ...

EPA Pesticide Factsheets

This contribution describes the implementation of the conditional-value-at-risk (CVaR) metric to create a general multi-stakeholder decision-making framework. It is observed that stakeholder dissatisfactions (distance to their individual ideal solutions) can be interpreted as random variables. We thus shape the dissatisfaction distribution and find an optimal compromise solution by solving a CVaR minimization problem parameterized in the probability level. This enables us to generalize multi-stakeholder settings previously proposed in the literature that minimizes average and worst-case dissatisfactions. We use the concept of the CVaR norm to give a geometric interpretation to this problem and use the properties of this norm to prove that the CVaR minimization problem yields Pareto optimal solutions for any choice of the probability level. We discuss a broad range of potential applications of the framework. We demonstrate the framework in a bio-waste processing facility location case study, where we seek compromise solutions (facility locations) that balance stakeholder priorities on transportation, safety, water quality, and capital costs. This conference presentation abstract explains a new decision-making framework that computes compromise solution alternatives (reach consensus) by mitigating dissatisfactions among stakeholders as needed for SHC Decision Science and Support Tools project.

Human Protein Kinases and Obesity.

PubMed

Engin, Atilla

2017-01-01

The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified by the target amino acid in their substrates. Some protein kinases can phosphorylate both serine/threonine, as well as tyrosine residues. This group of kinases has been known as dual specificity kinases. Unlike the dual specificity kinases, a heterogeneous group of protein phosphatases are known as dual-specificity phosphatases. These phosphatases remove phosphate groups from tyrosine and serine/threonine residues on their substrate. Dual-specificity phosphatases are important signal transduction enzymes that regulate various cellular processes in coordination with protein kinases. The protein kinase-phosphoproteins interactions play an important role in obesity . In obesity, the pro- and anti-inflammatory effects of adipokines and cytokines through intracellular signaling pathways mainly involve the nuclear factor kappa B (NF-kappaB) and the c-Jun N-terminal kinase (JNK) systems as well as the inhibitor of kappaB-kinase beta (IKK beta). Impairment of insulin signaling in obesity is largely mediated by the activation of the IKKbeta and the JNK. Furthermore, oxidative stress and endoplasmic reticulum (ER) stress activate the JNK pathway which suppresses insulin biosynthesis. Additionally, obesity-activated calcium/calmodulin dependent-protein kinase II/p38 suppresses insulin-induced protein kinase B phosphorylation by activating the ER stress effector, activating transcription factor-4. Obese adults with vascular endothelial dysfunction have greater endothelial cells activation of unfolded protein response stress sensors, RNA-dependent protein kinase-like ER eukaryotic initiation factor-2alpha kinase (PERK) and activating transcription factor-6. The transcriptional regulation of adipogenesis in obesity is influenced by AGC (protein kinase A (PKA), PKG, PKC) family signaling kinases. Obesity may induce systemic oxidative stress and increase reactive oxygen species in adipocytes. Increase in intracellular oxidative stress can promote PKC-beta activation. Activated PKC-beta induces growth factor adapter Shc phosphorylation. Shc-generated peroxides reduce mitochondrial oxygen consumption and enhances triglyceride accumulation. Obesity is fundamentally caused by cellular energy imbalance and dysregulation. Like adenosine monophosphate (AMP)-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), N-terminal Per-ARNT-Sim (PAS) kinase are nutrient responsive protein kinases and important for proper regulation of glucose metabolism in mammals at both the hormonal and cellular level. Defective responses of AMPK to leptin may contribute to resistance to leptin action on food intake and energy expenditure in obese states.

Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.

PubMed

Roskoski, Robert

2005-11-11

Signaling by stem cell factor and Kit, its receptor, plays important roles in gametogenesis, hematopoiesis, mast cell development and function, and melanogenesis. Moreover, human and mouse embryonic stem cells express Kit transcripts. Stem cell factor exists as both a soluble and a membrane-bound glycoprotein while Kit is a receptor protein-tyrosine kinase. The complete absence of stem cell factor or Kit is lethal. Deficiencies of either produce defects in red and white blood cell production, hypopigmentation, and sterility. Gain-of-function mutations of Kit are associated with several human neoplasms including acute myelogenous leukemia, gastrointestinal stromal tumors, and mastocytomas. Kit consists of an extracellular domain, a transmembrane segment, a juxtamembrane segment, and a protein kinase domain that contains an insert of about 80 amino acid residues. Binding of stem cell factor to Kit results in receptor dimerization and activation of protein kinase activity. The activated receptor becomes autophosphorylated at tyrosine residues that serve as docking sites for signal transduction molecules containing SH2 domains. The adaptor protein APS, Src family kinases, and Shp2 tyrosyl phosphatase bind to phosphotyrosine 568. Shp1 tyrosyl phosphatase and the adaptor protein Shc bind to phosphotyrosine 570. C-terminal Src kinase homologous kinase and the adaptor Shc bind to both phosphotyrosines 568 and 570. These residues occur in the juxtamembrane segment of Kit. Three residues in the kinase insert domain are phosphorylated and attract the adaptor protein Grb2 (Tyr703), phosphatidylinositol 3-kinase (Tyr721), and phospholipase Cgamma (Tyr730). Phosphotyrosine 900 in the distal kinase domain binds phosphatidylinositol 3-kinase which in turn binds the adaptor protein Crk. Phosphotyrosine 936, also in the distal kinase domain, binds the adaptor proteins APS, Grb2, and Grb7. Kit has the potential to participate in multiple signal transduction pathways as a result of interaction with several enzymes and adaptor proteins.

Implementation Guidance for the Next Generation Leaching ...

EPA Pesticide Factsheets

Poster provides an overview of the purpose and utility of this research, highlights of the research to support the Leaching Environmental Assessment Framework (LEAF), application and translation (including data management and analysis software), intended end users, and lessons learned. The methods are in use by EPRI, industry, academia, and commercial labs and supported by NGOs, National Academy of Sciences, EPA and State regional offices, and academia. Internationally the methods are in use in Europe, Scandinavian countries, Australia, China, Brazil, Israel, New Zealand, and Canada. To provide to the SHC BOSC Review, an overview of research to develop more reliable leaching tests for partitioning of inorganics in our environment from the use or disposal of fly ash and other industrial by-products

Prolonged asymmetric vestibular stimulation induces opposite, long-term effects on self-motion perception and ocular responses.

PubMed

Pettorossi, V E; Panichi, R; Botti, F M; Kyriakareli, A; Ferraresi, A; Faralli, M; Schieppati, M; Bronstein, A M

2013-04-01

Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR.

Prolonged asymmetric vestibular stimulation induces opposite, long-term effects on self-motion perception and ocular responses

PubMed Central

Pettorossi, V E; Panichi, R; Botti, F M; Kyriakareli, A; Ferraresi, A; Faralli, M; Schieppati, M; Bronstein, A M

2013-01-01

Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR. PMID:23318876

Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density.

PubMed

Byström, Sanna; Eklund, Martin; Hong, Mun-Gwan; Fredolini, Claudia; Eriksson, Mikael; Czene, Kamila; Hall, Per; Schwenk, Jochen M; Gabrielson, Marike

2018-02-14

Mammographic breast density is one of the strongest risk factors for breast cancer, but molecular understanding of how breast density relates to cancer risk is less complete. Studies of proteins in blood plasma, possibly associated with mammographic density, are well-suited as these allow large-scale analyses and might shed light on the association between breast cancer and breast density. Plasma samples from 1329 women in the Swedish KARMA project, without prior history of breast cancer, were profiled with antibody suspension bead array (SBA) assays. Two sample sets comprising 729 and 600 women were screened by two different SBAs targeting a total number of 357 proteins. Protein targets were selected through searching the literature, for either being related to breast cancer or for being linked to the extracellular matrix. Association between proteins and absolute area-based breast density (AD) was assessed by quantile regression, adjusting for age and body mass index (BMI). Plasma profiling revealed linear association between 20 proteins and AD, concordant in the two sets of samples (p < 0.05). Plasma levels of seven proteins were positively associated and 13 proteins negatively associated with AD. For eleven of these proteins evidence for gene expression in breast tissue existed. Among these, ABCC11, TNFRSF10D, F11R and ERRF were positively associated with AD, and SHC1, CFLAR, ACOX2, ITGB6, RASSF1, FANCD2 and IRX5 were negatively associated with AD. Screening proteins in plasma indicates associations between breast density and processes of tissue homeostasis, DNA repair, cancer development and/or progression in breast cancer. Further validation and follow-up studies of the shortlisted protein candidates in independent cohorts will be needed to infer their role in breast density and its progression in premenopausal and postmenopausal women.

Microbial characterization of probiotics–Advisory report of the Working Group “8651 Probiotics” of the Belgian Superior Health Council (SHC)

PubMed Central

Huys, Geert; Botteldoorn, Nadine; Delvigne, Frank; Vuyst, Luc De; Heyndrickx, Marc; Pot, Bruno; Dubois, Jean-Jacques; Daube, Georges

2013-01-01

When ingested in sufficient numbers, probiotics are expected to confer one or more proven health benefits on the consumer. Theoretically, the effectiveness of a probiotic food product is the sum of its microbial quality and its functional potential. Whereas the latter may vary much with the body (target) site, delivery mode, human target population, and health benefit envisaged microbial assessment of the probiotic product quality is more straightforward. The range of stakeholders that need to be informed on probiotic quality assessments is extremely broad, including academics, food and biotherapeutic industries, healthcare professionals, competent authorities, consumers, and professional press. In view of the rapidly expanding knowledge on this subject, the Belgian Superior Health Council installed Working Group “8651 Probiotics” to review the state of knowledge regarding the methodologies that make it possible to characterize strains and products with purported probiotic activity. This advisory report covers three main steps in the microbial quality assessment process, i.e. (i) correct species identification and strain-specific typing of bacterial and yeast strains used in probiotic applications, (ii) safety assessment of probiotic strains used for human consumption, and (iii) quality of the final probiotic product in terms of its microbial composition, concentration, stability, authenticity, and labeling. PMID:23801655

A framework for multi-stakeholder decision-making and ...

EPA Pesticide Factsheets

We propose a decision-making framework to compute compromise solutions that balance conflicting priorities of multiple stakeholders on multiple objectives. In our setting, we shape the stakeholder dis-satisfaction distribution by solving a conditional-value-at-risk (CVaR) minimization problem. The CVaR problem is parameterized by a probability level that shapes the tail of the dissatisfaction distribution. The proposed approach allows us to compute a family of compromise solutions and generalizes multi-stakeholder settings previously proposed in the literature that minimize average and worst-case dissatisfactions. We use the concept of the CVaR norm to give a geometric interpretation to this problem +and use the properties of this norm to prove that the CVaR minimization problem yields Pareto optimal solutions for any choice of the probability level. We discuss a broad range of potential applications of the framework that involve complex decision-making processes. We demonstrate the developments using a biowaste facility location case study in which we seek to balance stakeholder priorities on transportation, safety, water quality, and capital costs. This manuscript describes the methodology of a new decision-making framework that computes compromise solutions that balance conflicting priorities of multiple stakeholders on multiple objectives as needed for SHC Decision Science and Support Tools project. A biowaste facility location is employed as the case study

EPA Scientific Knowledge Management Assessment and ...

EPA Pesticide Factsheets

A series of activities have been conducted by a core group of EPA scientists from across the Agency. The activities were initiated in 2012 and the focus was to increase the reuse and interoperability of science software at EPA. The need for increased reuse and interoperability is linked to the increased complexity of environmental assessments in the 21st century. This complexity is manifest in the form of problems that require integrated multi-disciplinary solutions. To enable the means to develop these solutions (i.e., science software systems) it is necessary to integrate software developed by disparate groups representing a variety of science domains. Thus, reuse and interoperability becomes imperative. This report briefly describes the chronology of activities conducted by the group of scientists to provide context for the primary purpose of this report, that is, to describe the proceedings and outcomes of the latest activity, a workshop entitled “Workshop on Advancing US EPA integration of environmental and information sciences”. The EPA has been lagging in digital maturity relative to the private sector and even other government agencies. This report helps begin the process of improving the agency’s use of digital technologies, especially in the areas of efficiency and transparency. This report contributes to SHC 1.61.2.

Sick-leave decisions for patients with severe subjective health complaints presenting in primary care: A cross-sectional study in Norway, Sweden, and Denmark

PubMed Central

2013-01-01

Abstract Objectives The primary objective of this study was to explore whether general practitioners (GPs) in Norway, Sweden, and Denmark make similar or different decisions regarding sick leave for patients with severe subjective health complaints (SHC). The secondary objective was to investigate if patient diagnoses, the reasons attributed for patient complaints, and GP demographics could explain variations in sick leave decisions. Design A cross-sectional study. Method Video vignettes of GP consultations with nine different patients. Subjects 126 GPs in Norway, Sweden, and Denmark. Setting Primary care in Norway, Sweden, and Denmark. Main outcome measure Sick leave decisions made by GPs. Results “Psychological” diagnoses in Sweden were related to lower odds ratio (OR) of granting sick leave than in Norway (OR = 0.07; 95% CI = 0.01–0.83) Assessments of patient health, the risk of deterioration, and their ability to work predicted sick leave decisions. Specialists in general medicine grant significantly fewer sick leaves than non-specialists. Conclusion Sick-leave decisions made by GPs in the three countries were relatively similar. However, Swedish GPs were more reluctant to grant sick leave for patients with “psychological” diagnoses. Assessments regarding health-related factors were more important than diagnoses in sick-leave decisions. Specialist training may be of importance for sick-leave decisions. PMID:24164371

A novel MPL point mutation resulting in thrombopoietin-independent activation.

PubMed

Abe, M; Suzuki, K; Inagaki, O; Sassa, S; Shikama, H

2002-08-01

Thrombopoietin (TPO) and its receptor (MPL) are important regulators of megakaryopoiesis. MPL belongs to a cytokine receptor superfamily. To date, all constitutively active MPL mutants have been artificially constructed with amino acid substitutions in the transmembrane domain or extracellular domain of the protein, and they activate signal transduction pathways in Ba/F3 cells that can also be activated by the normal MPL. In this paper, we report a novel spontaneously occurring mutation of MPL, with an amino acid substitution of Trp(508) to Ser(508) in the intracellular domain of MPL, that induces the factor-independent growth of Ba/F3 cells. Examination of intracellular signaling pathways demonstrated that the mutant MPL protein constitutively activates three distinct signaling pathways, SHC-Ras-Raf-MAPK/JNK, JAK-STAT, and PI3K-Akt-Bad.

Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease.

PubMed

Camici, Giovanni G; Savarese, Gianluigi; Akhmedov, Alexander; Lüscher, Thomas F

2015-12-21

Western societies are aging due to an increasing life span, decreased birth rates, and improving social and health conditions. On the other hand, the prevalence of cardiovascular (CV) and cerebrovascular (CBV) diseases rises with age. Thus, in view of the ongoing aging pandemic, it is appropriate to better understand the molecular pathways of aging as well as age-associated CV and CBV diseases. Oxidative stress contributes to aging of organs and the whole body by an accumulation of reactive oxygen species promoting oxidative damage. Indeed, increased oxidative stress produced in the mitochondria and cytosol of heart and brain is a common denominator to almost all CV and CBV diseases. The mitochondrial adaptor protein p66(Shc) and the family of deacetylase enzymes, the sirtuins, regulate the aging process, determine lifespan of many species and are involved in CV diseases. GDF11, a member of TGFβ superfamily with homology to myostatin also retards the aging process via yet unknown mechanisms. Recent evidence points towards a promising role of this novel 'rejuvenation' factor in reducing age-related heart disease. Finally, telomere length is also involved in aging and the development of age-related CV dysfunction. This review focuses on the latest scientific advances in understanding age-related changes of the CV and CBV system, as well as delineating potential novel therapeutic targets derived from aging research for CV and CBV diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture

PubMed Central

Park, Kyoungmin; Li, Qian

2016-01-01

The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributing risk factors in diabetes. George L. King, MD, of the Section of Vascular Cell Biology and Complications, Dianne Nunnally Hoppes Laboratory for Diabetes Complications, Joslin Diabetes Center, Harvard Medical School, Boston, MA, received the prestigious award at the American Diabetes Association’s 75th Scientific Sessions, 5–9 June 2015, in Boston, MA. He presented the Edwin Bierman Award Lecture, “Selective Insulin Resistance and the Development of Cardiovascular Disease in Diabetes,” on Sunday, 7 June 2015. This review is focused on the factors and potential mechanisms that are causing various cardiovascular pathologies. In diabetes, insulin’s actions on the endothelium and other vascular cells have significant influence on systemic metabolisms and the development of cardiovascular pathologies. Our studies showed that insulin receptors on the endothelium are important for insulin transport across the endothelial barrier and mediate insulin’s actions in muscle, heart, fat, and the brain. Insulin actions on the vascular cells are mediated by two pathways involving the actions of either IRS/PI3K/Akt or Grb/Shc/MAPK. Insulin’s activation of IRS/PI3K/Akt results in mostly antiatherogenic actions, as this pathway induces activation of eNOS, the expressions of HO-1 and VEGF, and the reduction of VCAM-1. In contrast, insulin’s activation of the Grb/Shc/MAPK pathway mediates the expressions of ET-1 and PAI-1 and migration and proliferation of contractile cells, which have proatherogenic actions. Elevated levels of glucose, free fatty acids, and inflammatory cytokines due to diabetes and insulin resistance selectively inhibit insulin’s antiatherogenic actions via the IRS/PI3K/Akt pathway. This review provides evidence to support the importance of insulin actions in preventing cardiovascular pathology that can be selectively inhibited via the IRS/PI3K/Akt cascade in diabetes. PMID:27222390

Left Transsylvian Transcisternal and Transinferior Insular Sulcus Approach for Resection of Uncohippocampal Tumor: 3-Dimensional Operative Video.

PubMed

Fernandez-Miranda, Juan C

2018-06-07

The medial temporal lobe can be divided in anterior, middle, and posterior segments. The anterior segment is formed by the uncus and hippocampal head, and it has extra and intraventricular structures. There are 2 main approaches to the uncohippocampal region, the anteromedial temporal lobectomy (Spencer's technique) and the transsylvian selective amygdalohippocampectomy (Yasargil's technique).In this video, we present the case of a 29-yr-old man with new onset of generalized seizures and a contrast-enhancing lesion in the left anterior segment of the medial temporal lobe compatible with high-grade glioma. He had a medical history of cervical astrocytoma at age 8 requiring craniospinal radiation therapy and ventriculoperitoneal shunt placement.The tumor was approached using a combined transsylvian transcisternal and transinferior insular sulcus approach to the extra and intraventricular aspects of the uncohippocampal region. It was resected completely, and the patient was neurologically intact after resection with no further seizures at 6-mo follow-up. The diagnosis was glioblastoma IDH-wild type, for which he underwent adjuvant therapy.Surgical anatomy and technical nuances of this approach are illustrated using a 3-dimensional video and anatomic dissections. The selective approach, when compared to an anteromedial temporal lobectomy, has the advantage of preserving the anterolateral temporal cortex, which is particularly relevant in dominant-hemisphere lesions, and the related fiber tracts, including the inferior fronto-occipital and inferior longitudinal fascicles, and most of the optic radiation fibers. The transsylvian approach, however, is technically and anatomically more challenging and potentially carries a higher risk of vascular injury and vasospasm.Page 1 and figures from Fernández-Miranda JC et al, Microvascular Anatomy of the Medial Temporal Region: Part 1: Its Application to Arteriovenous Malformation Surgery, Operative Neurosurgery, 2010, Volume 67, issue 3, ons237-ons276, by permission of the Congress of Neurological Surgeons (1:26-1:37 in video).Page 1 from Fernández-Miranda JC et al, Three-Dimensio-nal Microsurgical and Tractographic Anatomy of the White Matter of the Human Brain, Neurosurgery, 2008, Volume 62, issue suppl_3, SHC989-SHC1028, by permission of the Congress of Neurological Surgeons (1:54-1:56 in video).

Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.

PubMed

Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian

2013-01-01

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

PubMed Central

Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Sun, Tao

2014-01-01

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol. PMID:25143940

Subjective Health Complaints Among Workers in the Aftermath of an Oil Tank Explosion.

PubMed

Tjalvin, Gro; Hollund, Bjørg Eli; Lygre, Stein Håkon Låstad; Moen, Bente Elisabeth; Bråtveit, Magne

2015-01-01

The aim of the study was to assess whether exposed workers had more subjective health complaints than controls 1 1/2 years after a chemical explosion involving a mixture of hydrocarbons and sulfurous compounds. A cross-sectional survey based on the Subjective Health Complaints Inventory (SHC) was conducted among 147 exposed workers and 137 controls. A significantly higher total SCH score (linear regression, p=.01) was found for the exposed workers compared with controls when adjusting for gender, age, smoking habits, and educational level. The exposed workers reported significantly more headache, hot flashes, sleep problems, tiredness, dizziness, and sadness/depression. The cause of these complaints is unknown, but health personnel should be aware that health complaints might be related to polluting episodes even when exposure levels are below occupational guideline levels.

Microbial characterization of probiotics--advisory report of the Working Group "8651 Probiotics" of the Belgian Superior Health Council (SHC).

PubMed

Huys, Geert; Botteldoorn, Nadine; Delvigne, Frank; De Vuyst, Luc; Heyndrickx, Marc; Pot, Bruno; Dubois, Jean-Jacques; Daube, Georges

2013-08-01

When ingested in sufficient numbers, probiotics are expected to confer one or more proven health benefits on the consumer. Theoretically, the effectiveness of a probiotic food product is the sum of its microbial quality and its functional potential. Whereas the latter may vary much with the body (target) site, delivery mode, human target population, and health benefit envisaged microbial assessment of the probiotic product quality is more straightforward. The range of stakeholders that need to be informed on probiotic quality assessments is extremely broad, including academics, food and biotherapeutic industries, healthcare professionals, competent authorities, consumers, and professional press. In view of the rapidly expanding knowledge on this subject, the Belgian Superior Health Council installed Working Group "8651 Probiotics" to review the state of knowledge regarding the methodologies that make it possible to characterize strains and products with purported probiotic activity. This advisory report covers three main steps in the microbial quality assessment process, i.e. (i) correct species identification and strain-specific typing of bacterial and yeast strains used in probiotic applications, (ii) safety assessment of probiotic strains used for human consumption, and (iii) quality of the final probiotic product in terms of its microbial composition, concentration, stability, authenticity, and labeling. © 2013 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

G-Quadruplex-based DNAzyme for colorimetric detection of cocaine: using magnetic nanoparticles as the separation and amplification element.

PubMed

Du, Yan; Li, Bingling; Guo, Shaojun; Zhou, Zhixue; Zhou, Ming; Wang, Erkang; Dong, Shaojun

2011-02-07

The appearance of the aptamer provides good recognition elements for small molecules, especially for drugs. In this work, by combining the advantages of magnetic nanoparticles (MNPs) with colorimetric drug detection using hemin-G-quadruplex complex as the sensing element, we report a simple and sensitive DNAzyme-based colorimetric sensor for cocaine detection in a 3,3,5,5-tetramethylbenzidine sulfate (TMB)-H(2)O(2) reaction system. The whole experimental processes are simplified. Cocaine aptamer fragments, SH-C2, are covalently labeled onto the amine-functionalized MNPs. When the target cocaine and another cocaine aptamer fragments (C1) grafted with G-riched strand AG4 (i.e. C1-AG4) are present simultaneously, the C2 layer on MNPs hybridizes partly with C1-AG4 to bind the cocaine. The C1-AG4 can be combinded with hemin to form DNAzyme which can effectively catalyze the H(2)O(2)-mediated oxidation of TMB, giving rise to a change in solution color. Importantly, using MNPs as the separation and amplification elements could effectively reduce the background signal and the interference from the real samples. A linear response from 0.1 μM to 20 μM is obtained for cocaine and a detection limit of 50 nM is achieved, which provides high sensitivity and selectivity to detect cocaine.

NEXT GENERATION LEACHING TESTS FOR EVALUATING ...

EPA Pesticide Factsheets

In the U.S. as in other countries, there is increased interest in using industrial by-products as alternative or secondary materials, helping to conserve virgin or raw materials. The LEAF and associated test methods are being used to develop the source term for leaching or any inorganic constituents of potential concern (COPC) in determining what is environmentally acceptable. The leaching test methods include batch equilibrium, percolation column and semi-dynamic mass transport tests for monolithic and compacted granular materials. By testing over a range of values for pH, liquid/solid ratio, and physical form of the material, this approach allows one data set to be used to evaluate a range of management scenarios for a material, representing different environmental conditions (e.g., disposal or beneficial use). The results from these tests may be interpreted individually or integrated to identify a solid material’s characteristic leaching behavior. Furthermore the LEAF approach provides the ability to make meaningful comparisons of leaching between similar and dissimilar materials from national and worldwide origins. To present EPA's research under SHC to implement validated leaching tests referred to as the Leaching Environmental Assessment Framework (LEAF). The primary focus will be on the guidance for implementation of LEAF describing three case studies for developing source terms for evaluating inorganic constituents.

Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial.

PubMed

Ory, Daniel S; Ottinger, Elizabeth A; Farhat, Nicole Yanjanin; King, Kelly A; Jiang, Xuntian; Weissfeld, Lisa; Berry-Kravis, Elizabeth; Davidson, Cristin D; Bianconi, Simona; Keener, Lee Ann; Rao, Ravichandran; Soldatos, Ariane; Sidhu, Rohini; Walters, Kimberly A; Xu, Xin; Thurm, Audrey; Solomon, Beth; Pavan, William J; Machielse, Bernardus N; Kao, Mark; Silber, Steven A; McKew, John C; Brewer, Carmen C; Vite, Charles H; Walkley, Steven U; Austin, Christopher P; Porter, Forbes D

2017-10-14

Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by progressive neurodegeneration. In preclinical testing, 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delayed cerebellar Purkinje cell loss, slowed progression of neurological manifestations, and increased lifespan in mouse and cat models of NPC1. The aim of this study was to assess the safety and efficacy of lumbar intrathecal HPβCD. In this open-label, dose-escalation phase 1-2a study, we gave monthly intrathecal HPβCD to participants with NPC1 with neurological manifestation at the National Institutes of Health (NIH), Bethesda, MD, USA. To explore the potential effect of 2-week dosing, three additional participants were enrolled in a parallel study at Rush University Medical Center (RUMC), Chicago, IL, USA. Participants from the NIH were non-randomly, sequentially assigned in cohorts of three to receive monthly initial intrathecal HPβCD at doses of 50, 200, 300, or 400 mg per month. A fifth cohort of two participants received initial doses of 900 mg. Participants from RUMC initially received 200 or 400 mg every 2 weeks. The dose was escalated based on tolerance or safety data from higher dose cohorts. Serum and CSF 24(S)-hydroxycholesterol (24[S]-HC), which serves as a biomarker of target engagement, and CSF protein biomarkers were evaluated. NPC Neurological Severity Scores (NNSS) were used to compare disease progression in HPβCD-treated participants relative to a historical comparison cohort of 21 NPC1 participants of similar age range. Between Sept 21, 2013, and Jan 19, 2015, 32 participants with NPC1 were assessed for eligibility at the National Institutes of Health. 18 patients were excluded due to inclusion criteria not met (six patients), declined to participate (three patients), pursued independent expanded access and obtained the drug outside of the study (three patients), enrolled in the RUMC cohort (one patient), or too late for the trial enrolment (five patients). 14 patients were enrolled and sequentially assigned to receive intrathecal HPβCD at a starting dose of 50 mg per month (three patients), 200 mg per month (three patients), 300 mg per month (three patients), 400 mg per month (three patients), or 900 mg per month (two patients). During the first year, two patients had treatment interrupted for one dose, based on grade 1 ototoxicity. All 14 patients were assessed at 12 months. Between 12 and 18 months, one participant had treatment interrupted at 17 months due to hepatocellular carcinoma, one patient had dose interruption for 2 doses based on caregiver hardship and one patient had treatment interrupted for 1 dose for mastoiditis. 11 patients were assessed at 18 months. Between Dec 11, 2013, and June 25, 2014, three participants were assessed for eligibility and enrolled at RUMC, and were assigned to receive intrathecal HPβCD at a starting dose of 200 mg every 2 weeks (two patients), or 400 mg every two weeks (one patient). There were no dropouts in this group and all 3 patients were assessed at 18 months. Biomarker studies were consistent with improved neuronal cholesterol homoeostasis and decreased neuronal pathology. Post-drug plasma 24(S)-HC area under the curve (AUC 8-72 ) values, an indicator of neuronal cholesterol homoeostasis, were significantly higher than post-saline plasma 24(S)-HC AUC 8-72 after doses of 900 mg (p=0·0063) and 1200 mg (p=0·0037). CSF 24(S)-HC concentrations in three participants given either 600 or 900 mg of HPβCD were increased about two fold (p=0·0032) after drug administration. No drug-related serious adverse events were observed. Mid-frequency to high-frequency hearing loss, an expected adverse event, was documented in all participants. When managed with hearing aids, this did not have an appreciable effect on daily communication. The NNSS for the 14 participants treated monthly increased at a rate of 1·22, SEM 0·34 points per year compared with 2·92, SEM 0·27 points per year (p=0·0002) for the 21 patient comparison group. Decreased progression was observed for NNSS domains of ambulation (p=0·0622), cognition (p=0·0040) and speech (p=0·0423). Patients with NPC1 treated with intrathecal HPβCD had slowed disease progression with an acceptable safety profile. These data support the initiation of a multinational, randomised, controlled trial of intrathecal HPβCD. National Institutes of Health, Dana's Angels Research Trust, Ara Parseghian Medical Research Foundation, Hope for Haley, Samantha's Search for the Cure Foundation, National Niemann-Pick Disease Foundation, Support of Accelerated Research for NPC Disease, Vtesse, Janssen Research and Development, a Johnson & Johnson company, and Johnson & Johnson. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phosphorylation of the Activation Loop Tyrosine 823 in c-Kit Is Crucial for Cell Survival and Proliferation*

PubMed Central

Agarwal, Shruti; Kazi, Julhash U.; Rönnstrand, Lars

2013-01-01

The receptor tyrosine kinase c-Kit, also known as the stem cell factor receptor, plays a key role in several developmental processes. Activating mutations in c-Kit lead to alteration of these cellular processes and have been implicated in many human cancers such as gastrointestinal stromal tumors, acute myeloid leukemia, testicular seminomas and mastocytosis. Regulation of the catalytic activity of several kinases is known to be governed by phosphorylation of tyrosine residues in the activation loop of the kinase domain. However, in the case of c-Kit phosphorylation of Tyr-823 has been demonstrated to be a late event that is not required for kinase activation. However, because phosphorylation of Tyr-823 is a ligand-activated event, we sought to investigate the functional consequences of Tyr-823 phosphorylation. By using a tyrosine-to-phenylalanine mutant of tyrosine 823, we investigated the impact of Tyr-823 on c-Kit signaling. We demonstrate here that Tyr-823 is crucial for cell survival and proliferation and that mutation of Tyr-823 to phenylalanine leads to decreased sustained phosphorylation and ubiquitination of c-Kit as compared with the wild-type receptor. Furthermore, the mutated receptor was, upon ligand-stimulation, quickly internalized and degraded. Phosphorylation of the E3 ubiquitin ligase Cbl was transient, followed by a substantial reduction in phosphorylation of downstream signaling molecules such as Akt, Erk, p38, Shc, and Gab2. Thus, we propose that activation loop tyrosine 823 is crucial for activation of both the MAPK and PI3K pathways and that its disruption leads to a destabilization of the c-Kit receptor and decreased survival of cells. PMID:23803604

Polymorphic Variation in Susceptibility and Metabolism of Triclosan-Resistant Mutants of Escherichia coli and Klebsiella pneumoniae Clinical Strains Obtained after Exposure to Biocides and Antibiotics

PubMed Central

Curiao, Tânia; Marchi, Emmanuela; Viti, Carlo; Oggioni, Marco R.; Baquero, Fernando; Martinez, José Luis

2015-01-01

Exposure to biocides may result in cross-resistance to other antimicrobials. Changes in biocide and antibiotic susceptibilities, metabolism, and fitness costs were studied here in biocide-selected Escherichia coli and Klebsiella pneumoniae mutants. E. coli and K. pneumoniae mutants with various degrees of triclosan susceptibility were obtained after exposure to triclosan (TRI), benzalkonium chloride (BKC), chlorhexidine (CHX) or sodium hypochlorite (SHC), and ampicillin or ciprofloxacin. Alterations in antimicrobial susceptibility and metabolism in mutants were tested using Phenotype MicroArrays. The expression of AcrAB pump and global regulators (SoxR, MarA, and RamA) was measured by quantitative reverse transcription-PCR (qRT-PCR), and the central part of the fabI gene was sequenced. The fitness costs of resistance were assessed by a comparison of relative growth rates. Triclosan-resistant (TRIr) and triclosan-hypersusceptible (TRIhs) mutants of E. coli and K. pneumoniae were obtained after selection with biocides and/or antibiotics. E. coli TRIr mutants, including those with mutations in the fabI gene or in the expression of acrB, acrF, and marA, exhibited changes in susceptibility to TRI, CHX, and antibiotics. TRIr mutants for which the TRI MIC was high presented improved metabolism of carboxylic acids, amino acids, and carbohydrates. In TRIr mutants, resistance to one antimicrobial provoked hypersusceptibility to another one(s). TRIr mutants had fitness costs, particularly marA-overexpressing (E. coli) or ramA-overexpressing (K. pneumoniae) mutants. TRI, BKC, and CIP exposure frequently yielded TRIr mutants exhibiting alterations in AraC-like global regulators (MarA, SoxR, and RamA), AcrAB-TolC, and/or FabI, and influencing antimicrobial susceptibility, fitness, and metabolism. These various phenotypes suggest a trade-off of different selective processes shaping the evolution toward antibiotic/biocide resistance and influencing other adaptive traits. PMID:25824225

Polymorphic variation in susceptibility and metabolism of triclosan-resistant mutants of Escherichia coli and Klebsiella pneumoniae clinical strains obtained after exposure to biocides and antibiotics.

PubMed

Curiao, Tânia; Marchi, Emmanuela; Viti, Carlo; Oggioni, Marco R; Baquero, Fernando; Martinez, José Luis; Coque, Teresa M

2015-01-01

Exposure to biocides may result in cross-resistance to other antimicrobials. Changes in biocide and antibiotic susceptibilities, metabolism, and fitness costs were studied here in biocide-selected Escherichia coli and Klebsiella pneumoniae mutants. E. coli and K. pneumoniae mutants with various degrees of triclosan susceptibility were obtained after exposure to triclosan (TRI), benzalkonium chloride (BKC), chlorhexidine (CHX) or sodium hypochlorite (SHC), and ampicillin or ciprofloxacin. Alterations in antimicrobial susceptibility and metabolism in mutants were tested using Phenotype MicroArrays. The expression of AcrAB pump and global regulators (SoxR, MarA, and RamA) was measured by quantitative reverse transcription-PCR (qRT-PCR), and the central part of the fabI gene was sequenced. The fitness costs of resistance were assessed by a comparison of relative growth rates. Triclosan-resistant (TRI(r)) and triclosan-hypersusceptible (TRI(hs)) mutants of E. coli and K. pneumoniae were obtained after selection with biocides and/or antibiotics. E. coli TRI(r) mutants, including those with mutations in the fabI gene or in the expression of acrB, acrF, and marA, exhibited changes in susceptibility to TRI, CHX, and antibiotics. TRI(r) mutants for which the TRI MIC was high presented improved metabolism of carboxylic acids, amino acids, and carbohydrates. In TRI(r) mutants, resistance to one antimicrobial provoked hypersusceptibility to another one(s). TRI(r) mutants had fitness costs, particularly marA-overexpressing (E. coli) or ramA-overexpressing (K. pneumoniae) mutants. TRI, BKC, and CIP exposure frequently yielded TRI(r) mutants exhibiting alterations in AraC-like global regulators (MarA, SoxR, and RamA), AcrAB-TolC, and/or FabI, and influencing antimicrobial susceptibility, fitness, and metabolism. These various phenotypes suggest a trade-off of different selective processes shaping the evolution toward antibiotic/biocide resistance and influencing other adaptive traits. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Pressure sensing of Fabry-Perot interferometer with a microchannel demodulated by a FBG

NASA Astrophysics Data System (ADS)

Yu, Yongqin; Chen, Xue; Huang, Quandong; Du, Chenlin; Ruan, Shuangchen

2015-07-01

A novel and compact fiber-probe pressure sensor was demonstrated based on micro Fabry-Perot interferometer (FPI). The device was fabricated by splicing both ends of a short section simplified hollow-core photonic crystal fiber (SHCPCF) with single mode fibers (SMFs), and then a micro channel was drilled by femtosecond laser micromachining in the SHC-PCF to significantly enhance the pressure sensitivity. The pressure sensing characteristics based on micro-FPI have been investigated by measuring the signals through the demodulation of phase since the external signal imposing on the interferometer will induce the phase change of interference signal. Then a FBG was cascaded to demodulate the signal. A micro FPI demonstrates a maximum pressure sensitivity of 32 dB/MPa, while a low temperature cross-sensitivity of 0.27 KPa/°C. Hence it may have potential for pressure applications in harsh environment.

Sustainability Tools Inventory - Initial Gaps Analysis | Science ...

EPA Pesticide Factsheets

This report identifies a suite of tools that address a comprehensive set of community sustainability concerns. The objective is to discover whether "gaps" exist in the tool suite’s analytic capabilities. These tools address activities that significantly influence resource consumption, waste generation, and hazard generation including air pollution and greenhouse gases. In addition, the tools have been evaluated using four screening criteria: relevance to community decision making, tools in an appropriate developmental stage, tools that may be transferrable to situations useful for communities, and tools with requiring skill levels appropriate to communities. This document provides an initial gap analysis in the area of community sustainability decision support tools. It provides a reference to communities for existing decision support tools, and a set of gaps for those wishing to develop additional needed tools to help communities to achieve sustainability. It contributes to SHC 1.61.4

Enzymatic Addition of Alcohols to Terpenes by Squalene Hopene Cyclase Variants.

PubMed

Kühnel, Lisa C; Nestl, Bettina M; Hauer, Bernhard

2017-11-16

Squalene-hopene cyclases (SHCs) catalyze the polycyclization of squalene into a mixture of hopene and hopanol. Recently, amino-acid residues lining the catalytic cavity of the SHC from Alicyclobacillus acidocaldarius were replaced by small and large hydrophobic amino acids. The alteration of leucine 607 to phenylalanine resulted in increased enzymatic activity towards the formation of an intermolecular farnesyl-farnesyl ether product from farnesol. Furthermore, the addition of small-chain alcohols acting as nucleophiles led to the formation of non-natural ether-linked terpenoids and, thus, to significant alteration of the product pattern relative to that obtained with the wild type. It is proposed that the mutation of leucine at position 607 may facilitate premature quenching of the intermediate by small alcohol nucleophiles. This mutagenesis-based study opens the field for further intermolecular bond-forming reactions and the generation of non-natural products. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The selective and inducible activation of endogenous PI 3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth.

PubMed

Ashcroft, M; Stephens, R M; Hallberg, B; Downward, J; Kaplan, D R

1999-08-12

The Trk/Nerve Growth Factor receptor mediates the rapid activation of a number of intracellular signaling proteins, including phosphatidylinositol 3-kinase (PI 3-kinase). Here, we describe a novel, NGF-inducible system that we used to specifically address the signaling potential of endogenous PI 3-kinase in NGF-mediated neuronal survival and differentiation processes. This system utilizes a Trk receptor mutant (Trk(def)) lacking sequences Y490, Y785 and KFG important for the activation of the major Trk targets; SHC, PLC-gammal, Ras, PI 3-kinase and SNT. Trk(def) was kinase active but defective for NGF-induced responses when stably expressed in PC12nnr5 cells (which lack detectable levels of TrkA and are non-responsive to NGF). The PI 3-kinase consensus binding site, YxxM (YVPM), was introduced into the insert region within the kinase domain of Trk(def). NGF-stimulated tyrosine phosphorylation of the Trk(def)+PI 3-kinase addback receptor, resulted in the direct association and selective activation of PI 3-kinase in vitro and the production of PI(3,4)P2 and PI(3,4,5)P3 in vivo (comparable to wild-type). PC12nnr5 cells stably expressing Trk(def) + PI 3-kinase, initiated neurite outgrowth but failed to stably extend and maintain these neurites in response to NGF as compared to PC12 parental cells, or PC12nnr5 cells overexpressing wild-type Trk. However, Trk(def) + PI 3-kinase was fully competent in mediating NGF-induced survival processes. We propose that while endogenous PI 3-kinase can contribute in part to neurite initiation processes, its selective activation and subsequent signaling to downstream effectors such as Akt, functions mainly to promote cell survival in the PC12 system.

Drainage area characterization for evaluating green infrastructure using the Storm Water Management Model

NASA Astrophysics Data System (ADS)

Lee, Joong Gwang; Nietch, Christopher T.; Panguluri, Srinivas

2018-05-01

Urban stormwater runoff quantity and quality are strongly dependent upon catchment properties. Models are used to simulate the runoff characteristics, but the output from a stormwater management model is dependent on how the catchment area is subdivided and represented as spatial elements. For green infrastructure modeling, we suggest a discretization method that distinguishes directly connected impervious area (DCIA) from the total impervious area (TIA). Pervious buffers, which receive runoff from upgradient impervious areas should also be identified as a separate subset of the entire pervious area (PA). This separation provides an improved model representation of the runoff process. With these criteria in mind, an approach to spatial discretization for projects using the US Environmental Protection Agency's Storm Water Management Model (SWMM) is demonstrated for the Shayler Crossing watershed (SHC), a well-monitored, residential suburban area occupying 100 ha, east of Cincinnati, Ohio. The model relies on a highly resolved spatial database of urban land cover, stormwater drainage features, and topography. To verify the spatial discretization approach, a hypothetical analysis was conducted. Six different representations of a common urbanscape that discharges runoff to a single storm inlet were evaluated with eight 24 h synthetic storms. This analysis allowed us to select a discretization scheme that balances complexity in model setup with presumed accuracy of the output with respect to the most complex discretization option considered. The balanced approach delineates directly and indirectly connected impervious areas (ICIA), buffering pervious area (BPA) receiving impervious runoff, and the other pervious area within a SWMM subcatchment. It performed well at the watershed scale with minimal calibration effort (Nash-Sutcliffe coefficient = 0.852; R2 = 0.871). The approach accommodates the distribution of runoff contributions from different spatial components and flow pathways that would impact green infrastructure performance. A developed SWMM model using the discretization approach is calibrated by adjusting parameters per land cover component, instead of per subcatchment and, therefore, can be applied to relatively large watersheds if the land cover components are relatively homogeneous and/or categorized appropriately in the GIS that supports the model parameterization. Finally, with a few model adjustments, we show how the simulated stream hydrograph can be separated into the relative contributions from different land cover types and subsurface sources, adding insight to the potential effectiveness of planned green infrastructure scenarios at the watershed scale.

Nicotine Enhances High-Fat Diet-Induced Oxidative Stress in the Kidney.

PubMed

Arany, Istvan; Hall, Samuel; Reed, Dustin K; Reed, Caitlyn T; Dixit, Mehul

2016-07-01

Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. Both smoking-through nicotine (NIC)-and obesity-by free fatty acid overload-provoke oxidative stress in the kidney, which ultimately results in development of chronic kidney injury. Their combined renal risk, however, is virtually unknown. We tested the hypothesis that chronic NIC exposure worsens renal oxidative stress in mice on high-fat diet (HFD) by altering the balance between expression of pro-oxidant and antioxidant genes. Nine-week-old male C57Bl/6J mice consumed normal diet (ND) or HFD and received either NIC (200 μg/ml) or vehicle (2% saccharine) in their drinking water. Body weight, plasma clinical parameters, renal lipid deposition, markers of renal oxidative stress and injury, as well as renal expression of the pro-oxidant p66shc and the antioxidant MnSOD were determined after 12 weeks. NIC significantly augmented levels of circulating free fatty acid, as well as lipid deposition, oxidative stress and sublethal injury in the kidneys of mice on HFD. In addition, NIC exposure suppressed HFD-mediated induction of MnSOD while increased expression of p66shc in the kidney. Tobacco smoking or the increasingly popular E-cigarettes-via NIC exposure-could worsen obesity-associated lipotoxicity in the kidney. Hence, our findings could help to develop strategies that mitigate adverse effects of NIC on the obese kidney. Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. NIC-the main component of tobacco smoke, E-cigarettes and replacement therapies-links smoking to renal injury via oxidative stress, which could superimpose renal oxidative stress caused by obesity. Our results substantiate this scenario using a mouse model of diet induced obesity and NIC exposure and imply the augmented long-term renal risk in obese smokers. Also, our study may help to develop strategies that mitigate adverse effects of NIC on the obese kidney. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture.

PubMed

King, George L; Park, Kyoungmin; Li, Qian

2016-06-01

The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributing risk factors in diabetes. George L. King, MD, of the Section of Vascular Cell Biology and Complications, Dianne Nunnally Hoppes Laboratory for Diabetes Complications, Joslin Diabetes Center, Harvard Medical School, Boston, MA, received the prestigious award at the American Diabetes Association's 75th Scientific Sessions, 5-9 June 2015, in Boston, MA. He presented the Edwin Bierman Award Lecture, "Selective Insulin Resistance and the Development of Cardiovascular Disease in Diabetes," on Sunday, 7 June 2015.This review is focused on the factors and potential mechanisms that are causing various cardiovascular pathologies. In diabetes, insulin's actions on the endothelium and other vascular cells have significant influence on systemic metabolisms and the development of cardiovascular pathologies. Our studies showed that insulin receptors on the endothelium are important for insulin transport across the endothelial barrier and mediate insulin's actions in muscle, heart, fat, and the brain. Insulin actions on the vascular cells are mediated by two pathways involving the actions of either IRS/PI3K/Akt or Grb/Shc/MAPK. Insulin's activation of IRS/PI3K/Akt results in mostly antiatherogenic actions, as this pathway induces activation of eNOS, the expressions of HO-1 and VEGF, and the reduction of VCAM-1. In contrast, insulin's activation of the Grb/Shc/MAPK pathway mediates the expressions of ET-1 and PAI-1 and migration and proliferation of contractile cells, which have proatherogenic actions. Elevated levels of glucose, free fatty acids, and inflammatory cytokines due to diabetes and insulin resistance selectively inhibit insulin's antiatherogenic actions via the IRS/PI3K/Akt pathway. This review provides evidence to support the importance of insulin actions in preventing cardiovascular pathology that can be selectively inhibited via the IRS/PI3K/Akt cascade in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system

PubMed Central

2014-01-01

Background Neurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking. Results Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLCγ docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered. Conclusions We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment. PMID:25256039

Results and analysis of saltstone cores taken from saltstone disposal unit cell 2A

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

Reigel, M. M.; Hill, K. A.

2016-03-01

As part of an ongoing Performance Assessment (PA) Maintenance Plan, Savannah River Remediation (SRR) has developed a sampling and analyses strategy to facilitate the comparison of field-emplaced samples (i.e., saltstone placed and cured in a Saltstone Disposal Unit (SDU)) with samples prepared and cured in the laboratory. The primary objectives of the Sampling and Analyses Plan (SAP) are; (1) to demonstrate a correlation between the measured properties of laboratory-prepared, simulant samples (termed Sample Set 3), and the field-emplaced saltstone samples (termed Sample Set 9), and (2) to validate property values assumed for the Saltstone Disposal Facility (SDF) PA modeling. Themore » analysis and property data for Sample Set 9 (i.e. six core samples extracted from SDU Cell 2A (SDU2A)) are documented in this report, and where applicable, the results are compared to the results for Sample Set 3. Relevant properties to demonstrate the aforementioned objectives include bulk density, porosity, saturated hydraulic conductivity (SHC), and radionuclide leaching behavior.« less

LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in atherosclerosis

PubMed Central

Zhou, Li; Plattner, Florian; Liu, Mingxia; Parks, John S; Hammer, Robert E; Boucher, Philippe; Tsai, Shirling

2017-01-01

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGFβ and PDGFRβ in reverse cholesterol transport and the maintenance of vascular wall integrity. Here we used a knockin mouse model to uncover a novel atheroprotective role for LRP1 in macrophages where tyrosine phosphorylation of an NPxY motif in its intracellular domain initiates a signaling cascade along an LRP1/SHC1/PI3K/AKT/PPARγ/LXR axis to regulate and integrate cellular cholesterol homeostasis through the expression of the major cholesterol exporter ABCA1 with apoptotic cell removal and inflammatory responses. PMID:29144234

Use and interest in complementary and alternative medicine among college students seeking healthcare at a university campus student health center.

PubMed

Nguyen, Jannett; Liu, Michael A; Patel, Rohini J; Tahara, Keli; Nguyen, Annie L

2016-08-01

There is growing data on complementary and alternative medicine (CAM) preferences among college students. While several studies have focused on undergraduate students, there is limited data on graduate students. Cross sectional analysis of undergraduate and graduate students seeking medical care at the University of California Irvine's Student Health Center (SHC). The survey assessed previous CAM use and preferences for future CAM use and education. The majority (67.0%) had used CAM within the last year, 27.0% would use CAM for their current health condition, and 51.9% would consider CAM for their current health condition if they were more knowledgeable. Most respondents desired more CAM education and indicated that they would try CAM modalities if covered under insurance. Most college students requested more knowledge to assist in their decisions to use CAM. These findings provide insight for health centers on the preferences of college student patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Skin changes in streptozotocin-induced diabetic rats.

PubMed

Andrade, Thiago Antônio Moretti; Masson-Meyers, Daniela Santos; Caetano, Guilherme Ferreira; Terra, Vânia Aparecida; Ovidio, Paula Payão; Jordão-Júnior, Alceu Afonso; Frade, Marco Andrey Cipriani

2017-09-02

Diabetes can cause serious health complications, which can affect every organ of the body, including the skin. The molecular etiology has not yet been clarified for all diabetic skin conditions. Thus, this study aimed to investigate the changes of diabetes in skin compared to non-diabetic skin in rats. Fifteen days after establishing the diabetic status, skin samples from the dorsum-cervical region were harvested for subsequent analysis of alterations caused by diabetes. Our results demonstrate that diabetes stimulated higher inflammation and oxidative stress in skin, but antioxidant defense levels were lower compared to the non-diabetic group (p < 0.05). This could have been related to a decreased number of blood vessels and low expression of VEGF, eNOS and TGF-β1. Finally, insulin signaling proteins IRS, Akt, Shc and ERK showed a low expression in the diabetic group. Thus, our study shows that the pathology of diabetes induced immunohistopathological and biochemical skin changes compared to non-diabetic skin in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members.

PubMed

Deneka, Alexander; Korobeynikov, Vladislav; Golemis, Erica A

2015-10-01

The CAS (Crk-associated substrate) adaptor protein family consists of four members: CASS1/BCAR1/p130Cas, CASS2/NEDD9/HEF1/Cas-L, CASS3/EFS/Sin and CASS4/HEPL. While CAS proteins lack enzymatic activity, they contain specific recognition and binding sites for assembly of larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes. All family members are intermediates in integrin-dependent signaling pathways mediated at focal adhesions, and associate with FAK and SRC family kinases to activate downstream effectors regulating the actin cytoskeleton. Most studies of CAS proteins to date have been focused on the first two members, BCAR1 and NEDD9, with altered expression of these proteins now appreciated as influencing disease development and prognosis for cancer and other serious pathological conditions. For these family members, additional mechanisms of action have been defined in receptor tyrosine kinase (RTK) signaling, estrogen receptor signaling or cell cycle progression, involving discrete partner proteins such as SHC, NSP proteins, or AURKA. By contrast, EFS and CASS4 have been less studied, although structure-function analyses indicate they conserve many elements with the better-known family members. Intriguingly, a number of recent studies have implicated these proteins in immune system function, and the pathogenesis of developmental disorders, autoimmune disorders including Crohn's disease, Alzheimer's disease, cancer and other diseases. In this review, we summarize the current understanding of EFS and CASS4 protein function in the context of the larger CAS family group. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular mechanisms of ulcer healing.

PubMed

Tarnawski, A

2000-04-01

An ulcer in the gastrointestinal tract is a deep necrotic lesion penetrating the entire mucosal thickness and muscularis mucosae. Ulcer healing is an active process of filling the mucosal defect with proliferating and migrating epithelial and connective tissue cells. At the ulcer margin, epithelial cells proliferate and migrate onto the granulation tissue to cover (reepithelialize) the ulcer and also invade granulation tissue to reconstruct glandular structures within the ulcer scar. The reepithelialization and reconstruction of glandular structures is controlled by growth factors: trefoil peptides, EGF, HGF, bFGF and PDGF; and locally produced cytokines by regenerating cells in an orderly fashion and integrated manner to ensure the quality of mucosal restoration. These growth factors, most notably EGF, trigger cell proliferation via signal transduction pathways involving EGF-R, adapter proteins (Grb2, Shc and Sos), Ras, Raf1 and MAP (Erk1/Erk2) kinases, which, after translocation to nuclei, activate transcription factors and cell proliferation. Cell migration requires cytoskeletal rearrangements and is controlled by growth factors via Rho/Rac and signaling pathways involving PLC-gamma, PI-3 K and phosphorylation of focal adhesion proteins. Granulation tissue develops at the ulcer base. It consists of connective tissue cells: fibroblasts, macrophages and proliferating endothelial cells forming microvessels under the control of angiogenic growth factors: bFGF, VEGF and angiopoietins, which all promote angiogenesiscapillary vessel formation, essential for the restoration of microvascular network in the mucosa and thus crucial for oxygen and nutrient supply. The major mechanism of activation of angiogenic growth factors and their receptor expression appears to be hypoxia, which activates hypoxia-inducible factor, which binds to VEGF promoter.

Tropomyosin-related kinase C (TrkC) enhances podocyte migration by ERK-mediated WAVE2 activation.

PubMed

Gromnitza, Sascha; Lepa, Carolin; Weide, Thomas; Schwab, Albrecht; Pavenstädt, Hermann; George, Britta

2018-03-01

Podocyte malfunction is central to glomerular diseases and is marked by defective podocyte intercellular junctions and actin cytoskeletal dynamics. Podocytes share many morphologic features with neurons, so that similar sets of proteins appear to regulate cell process formation. One such protein is the tropomyosin-related kinase C (TrkC). TrkC deficiency in mice leads to proteinuria as a surrogate of defective kidney filter function. Activation of endogenous TrkC by its ligand neurotrophin-3 resulted in increased podocyte migration-a surrogate of podocyte actin dynamics in vivo. Employing a mutagenesis approach, we found that the Src homologous and collagen-like (Shc) binding site Tyr 516 within the TrkC cytoplasmic domain was necessary for TrkC-induced migration of podocytes. TrkC activation led to a mobility shift of Wiskott-Aldrich syndrome family verprolin-homologous protein (WAVE)-2 which is known to orchestrate Arp2/3 activation and actin polymerization. Chemical inactivation of Erk or mutagenesis of 2 of 4 known Erk target sites within WAVE2, Thr 346 and Ser 351 , abolished the TrkC-induced WAVE2 mobility shift. Knockdown of WAVE2 by shRNA abolished TrkC-induced podocyte migration. In summary, TrkC signals to the podocyte actin cytoskeleton to induce migration by phosphorylating WAVE2 Erk dependently. This signaling mechanism may be important for TrkC-mediated cytoskeletal dynamics in podocyte disease.-Gromnitza, S., Lepa, C., Weide, T., Schwab, A., Pavenstädt, H., George, B. Tropomyosin-related kinase C (TrkC) enhances podocyte migration by ERK-mediated WAVE2 activation.

Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II.

PubMed

Feigelson, Heather Spencer; Teras, Lauren R; Diver, W Ryan; Tang, Weining; Patel, Alpa V; Stevens, Victoria L; Calle, Eugenia E; Thun, Michael J; Bouzyk, Mark

2008-01-01

Obesity has consistently been associated with postmenopausal breast cancer risk. Proteins that are secreted by adipose tissue or are involved in regulating body mass may play a role in breast tumor development. We conducted a nested case-control study among postmenopausal women from the American Cancer Society Cancer Prevention Study II Nutrition Cohort to determine whether genes associated with obesity increase risk for breast cancer. Tagging single nucleotide polymorphisms (SNPs) were selected to capture common variation across seven candidate genes that encode adipose-related proteins: ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1. Thirty-nine SNPs were genotyped in 648 cases and 659 controls. Logistic regression models were used to examine the association between each tagging SNP and risk for breast cancer while adjusting for matching factors and potential confounders. We also examined whether these SNPs were associated with measures of adult adiposity. Two out of five tagging SNPs in HSD11B1 were associated with breast cancer (rs11807619, P = 0.006; rs932335, P = 0.0001). rs11807619 and rs932335 were highly correlated (r2 = 0.74) and, when modeled as a haplotype, only haplotypes containing the rs932335 C allele were associated with breast cancer. The rs932335 C allele was associated with a nearly twofold increased risk for breast cancer (odds ratio = 1.83, 95% confidence interval = 1.01-3.33 for C/C versus G/G). Three of the 11 SNPs for IRS2 were associated with breast cancer (rs4773082, P = 0.007; rs2289046, P = 0.016; rs754204, P = 0.03). When these three SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63-0.92 for TGC versus CAT). IRS2 rs2289046, rs754204, and rs12584136 were also associated with adult weight gain but only among cases. None of the other SNPs in any gene investigated were associated with breast cancer or adiposity. Our findings suggest that these tagging SNPs in HSD11B1 and IRS2 mark regions of the genome that may harbor risk alleles for breast cancer, and these associations are probably independent of adiposity.

Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II

PubMed Central

Feigelson, Heather Spencer; Teras, Lauren R; Diver, W Ryan; Tang, Weining; Patel, Alpa V; Stevens, Victoria L; Calle, Eugenia E; Thun, Michael J; Bouzyk, Mark

2008-01-01

Introduction Obesity has consistently been associated with postmenopausal breast cancer risk. Proteins that are secreted by adipose tissue or are involved in regulating body mass may play a role in breast tumor development. Methods We conducted a nested case-control study among postmenopausal women from the American Cancer Society Cancer Prevention Study II Nutrition Cohort to determine whether genes associated with obesity increase risk for breast cancer. Tagging single nucleotide polymorphisms (SNPs) were selected to capture common variation across seven candidate genes that encode adipose-related proteins: ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1. Thirty-nine SNPs were genotyped in 648 cases and 659 controls. Logistic regression models were used to examine the association between each tagging SNP and risk for breast cancer while adjusting for matching factors and potential confounders. We also examined whether these SNPs were associated with measures of adult adiposity. Results Two out of five tagging SNPs in HSD11B1 were associated with breast cancer (rs11807619, P = 0.006; rs932335, P = 0.0001). rs11807619 and rs932335 were highly correlated (r2 = 0.74) and, when modeled as a haplotype, only haplotypes containing the rs932335 C allele were associated with breast cancer. The rs932335 C allele was associated with a nearly twofold increased risk for breast cancer (odds ratio = 1.83, 95% confidence interval = 1.01–3.33 for C/C versus G/G). Three of the 11 SNPs for IRS2 were associated with breast cancer (rs4773082, P = 0.007; rs2289046, P = 0.016; rs754204, P = 0.03). When these three SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63–0.92 for TGC versus CAT). IRS2 rs2289046, rs754204, and rs12584136 were also associated with adult weight gain but only among cases. None of the other SNPs in any gene investigated were associated with breast cancer or adiposity. Conclusion Our findings suggest that these tagging SNPs in HSD11B1 and IRS2 mark regions of the genome that may harbor risk alleles for breast cancer, and these associations are probably independent of adiposity. PMID:18611262

A systems biology approach to the pathogenesis of obesity-related nonalcoholic fatty liver disease using reverse phase protein microarrays for multiplexed cell signaling analysis.

PubMed

Calvert, Valerie S; Collantes, Rochelle; Elariny, Hazem; Afendy, Arian; Baranova, Ancha; Mendoza, Michael; Goodman, Zachary; Liotta, Lance A; Petricoin, Emanuel F; Younossi, Zobair M

2007-07-01

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Omental adipose tissue, a biologically active organ secreting adipokines and cytokines, may play a role in the development of NAFLD. We tested this hypothesis with reverse-phase protein microarrays (RPA) for multiplexed cell signaling analysis of adipose tissue from patients with NAFLD. Omental adipose tissue was obtained from 99 obese patients. Liver biopsies obtained at the time of surgery were all read by the same hepatopathologist. Adipose tissue was exposed to rapid pressure cycles to extract protein lysates. RPA was used to investigate intracellular signaling. Analysis of 54 different kinase substrates and cell signaling endpoints showed that an insulin signaling pathway is deranged in different locations in NAFLD patients. Furthermore, components of insulin receptor-mediated signaling differentiate most of the conditions on the NAFLD spectrum. For example, PKA (protein kinase A) and AKT/mTOR (protein kinase B/mammalian target of rapamycin) pathway derangement accurately discriminates patients with NASH from those with the non-progressive forms of NAFLD. PKC (protein kinase C) delta, AKT, and SHC phosphorylation changes occur in patients with simple steatosis. Amounts of the FKHR (forkhead factor Foxo1)phosphorylated at S256 residue were significantly correlated with AST/ALT ratio in all morbidly obese patients. Furthermore, amounts of cleaved caspase 9 and pp90RSK S380 were positively correlated in patients with NASH. Specific insulin pathway signaling events are altered in the adipose tissue of patients with NASH compared with patients with nonprogressive forms of NAFLD. These findings provide evidence for the role of omental fat in the pathogenesis, and potentially, the progression of NAFLD.

Paediatric cardiology programs in countries with limited resources: how to bridge the gap.

PubMed

Sulafa, K M Ali

2010-07-01

Establishing paediatric cardiology service in a country with limited resources like Sudan is a challenging task. A paediatric cardiac team was formed then the services in different disciplines were gradually established. Echocardiography (echo) clinics were founded in tertiary and peripheral hospitals. Cardiac catheterization (cath) was established at the Sudan Heart Centre (SHC) in 2004 and over 400 procedures had been performed including interventional catheterization like pulmonary valve dilatation, patent ductus arteriosus and atrial septal defect device closure. Congenital heart surgery started in 2001, currently 200 cases are done each year including closed procedures as well as open heart procedures for patients weighing more than 8 kg. Cardiology-cardiac surgery as well as adult congenital heart disease meetings were held and contributed positively to the services. The cardiology-cardiac surgery scientific club meeting was founded as a forum for academic discussions. A fellowship program was established in 2004 and included seven candidates trained in paediatric cardiology and intensive care. Two training courses had been established: congenital heart disease echo and paediatric electrocardiogram interpretation. Links with regional and international cardiac centres had important roles in consolidating our program. Significant obstacles face our service due to the small number of trained personnel, high cost of procedures, the lack of regular supplies and lack of cardiac intensive care facilities for young infants. Bridging the huge gap needs extensive official as well as non-governmental efforts, training more staff, supporting families and collaboration with regional and international centres.

Cumulus cells surrounding oocytes with high developmental competence exhibit down-regulation of phosphoinositol 1,3 kinase/protein kinase B (PI3K/AKT) signalling genes involved in proliferation and survival

PubMed Central

Artini, P G; Tatone, C; Sperduti, S; D’Aurora, M; Franchi, S; Di Emidio, G; Ciriminna, R; Vento, M; Di Pietro, C; Stuppia, L; Gatta, V

2017-01-01

Abstract STUDY QUESTION Is the phosphoinositol 1,3-kinase/protein kinase B (PI3K/AKT) pathway expression profile in cumulus cells (CCs) a potential marker of oocyte competence and predictive of pregnancy outcome? SUMMARY ANSWER Eleven genes (AKT1, ARHGEF7, BCL2L1, CCND1, E2F1, HRAS, KCNH2, PIK3C2A, SHC1, SOS1 and SPP1) in the PI3K/AKT pathway were significantly down-regulated in CCs from oocytes that went on to produce a pregnancy compared to CCs associated with a negative outcome. WHAT IS KNOWN ALREADY The PI3K/AKT pathway plays a pivotal role in the interdependence and continuous feedback between the oocyte and CCs. STUDY DESIGN SIZE, DURATION The expression analysis of 92 transcripts in the PI3K/AKT pathway in CCs from patients with negative or positive pregnancy outcome, after single embryo transfer, was performed. Mouse CCs target gene expression was conducted to associate the expression profile of PI3K/AKT pathway to oocyte developmental profile. PARTICIPANTS/MATERIALS, SETTING, METHODS Fifty-five good prognosis IVF patients who had been referred to IVF or intracytoplasmic sperm injection treatment for male-factor infertility or tubal disease were enroled. CCs from single cumulus-oocyte complexes (COCs) from 16 patients who underwent a single embryo transfer were analyzed. Twenty-five CD-1 mice were used to assess gene expression in CCs associated with oocytes with different competence in relation to hCG priming. A total 220 human COCs were collected. The RNA extracted from CCs of 16 selected patients was used to analyze PI3K/AKT pathway gene expression employing a 96-well custom TaqMan Array. Expression data of CCs associated to positive IVF outcome were compared to data from negative outcome samples. Mice were sacrificed after 9, 12, 15, 21 and 24 h post-hCG administration to obtain CCs from MII oocytes with different developmental competence. Akt1, Bcl2l2 and Shc1 expression were tested in the collected mouse CCs. In addition, the expression of upstream regulator ESR1, the gene encoding for the oestrogen receptor ERβ, and the downstream effectors of the pathway FOXO1, FOXO3 and FOXO4 was evaluated in human and mouse samples. MAIN RESULTS AND THE ROLE OF CHANCE Transcripts involved in the PI3K Signaling Pathway were selectively modulated according to the IVF/ICSI outcome of the oocyte. Eleven transcripts in this pathway were significantly down-regulated in all samples of CCs from oocytes with positive when compared those with a negative outcome. These outcomes were confirmed in mouse CCs associated with oocytes at different maturation stages. Expression data revealed that the down-regulation of ESR1 could be related to oocyte competence and is likely to be the driver of expression changes highlighted in the PI3K/AKT pathway. LIMITATIONS REASONS FOR CAUTION Small sample size and retrospective design. WIDER IMPLICATIONS OF THE FINDINGS The CCs expression profile of PI3K/AKT signaling genes, disclosed a specific CCs gene signature related to oocyte competence. It could be speculated that CCs associated with competent oocytes have completed their role in sustaining oocyte development and are influencing their fate in response to metabolic and hormonal changes by de-activating anti-apoptotic signals. STUDY FUNDING/COMPETING INTEREST(S) Supported by Merck Serono an affiliate of Merck KGaA, Darmstadt, Germany (research grant for the laboratory session; Merck KGaA reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors). The authors declare no conflict of interest. PMID:29087515

Molecular Basis of Signaling Specificity of Insulin and IGF Receptors: Neglected Corners and Recent Advances

PubMed Central

Siddle, Kenneth

2011-01-01

Insulin and insulin-like growth factor (IGF) receptors utilize common phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase signaling pathways to mediate a broad spectrum of “metabolic” and “mitogenic” responses. Specificity of insulin and IGF action in vivo must in part reflect expression of receptors and responsive pathways in different tissues but it is widely assumed that it is also determined by the ligand binding and signaling mechanisms of the receptors. This review focuses on receptor-proximal events in insulin/IGF signaling and examines their contribution to specificity of downstream responses. Insulin and IGF receptors may differ subtly in the efficiency with which they recruit their major substrates (IRS-1 and IRS-2 and Shc) and this could influence effectiveness of signaling to “metabolic” and “mitogenic” responses. Other substrates (Grb2-associated binder, downstream of kinases, SH2Bs, Crk), scaffolds (RACK1, β-arrestins, cytohesins), and pathways (non-receptor tyrosine kinases, phosphoinositide kinases, reactive oxygen species) have been less widely studied. Some of these components appear to be specifically involved in “metabolic” or “mitogenic” signaling but it has not been shown that this reflects receptor-preferential interaction. Very few receptor-specific interactions have been characterized, and their roles in signaling are unclear. Signaling specificity might also be imparted by differences in intracellular trafficking or feedback regulation of receptors, but few studies have directly addressed this possibility. Although published data are not wholly conclusive, no evidence has yet emerged for signaling mechanisms that are specifically engaged by insulin receptors but not IGF receptors or vice versa, and there is only limited evidence for differential activation of signaling mechanisms that are common to both receptors. Cellular context, rather than intrinsic receptor activity, therefore appears to be the major determinant of whether responses to insulin and IGFs are perceived as “metabolic” or “mitogenic.” PMID:22649417

Dispersant Effectiveness, In-Situ Droplet Size Distribution and ...

EPA Pesticide Factsheets

This report summarizes two projects covered under an Interagency Agreement between the Bureau of Safety and Environmental Enforcement (BSEE) and the U.S. Environmental Protection Agency (EPA) in collaboration with the Bedford Institute of Oceanography, Department of Fisheries and Oceans Canada (BIO DFO), New Jersey Institute of Technology (NJIT) and Dalhousie University. Both projects dovetail together in addressing the ability to differentiate physical from chemical dispersion effectiveness using dispersed oil simulations within a flume tank for improving forensic response monitoring tools. This report is split into separateTasks based upon the two projects funded by BSEE: 1) Dispersant Effectiveness, In-Situ Droplet Size Distribution and Numerical Modeling to Assess Subsurface Dispersant Injection as a Deepwater Blowout Oil Spill Response Option. 2) Evaluation of Oil Fluorescence Characteristics to Improve Forensic Response Tools. This report summarizes 2 collaborative projects funded through an Interagency Agreement with DOI BSEE and a Cooperative Agreement with DFO Canada. BSEE required that the projects be combined into one report as they are both covered under the one Interagency Agreement. Task B (Fluorescence of oils) is an SHC 3.62 FY16 product.

Two dimensional Blue Native-/SDS-PAGE analysis of SLP family adaptor protein complexes.

PubMed

Swamy, Mahima; Kulathu, Yogesh; Ernst, Sandra; Reth, Michael; Schamel, Wolfgang W A

2006-04-15

SH2 domain containing leukocyte protein (SLP) adaptor proteins serve a central role in the antigen-mediated activation of lymphocytes by organizing multiprotein signaling complexes. Here, we use two dimensional native-/SDS-gel electrophoresis to study the number, size and relative abundance of protein complexes containing SLP family proteins. In non-stimulated T cells all SLP-76 proteins are in a approximately 400 kDa complex with the small adaptor protein Grb2-like adaptor protein downstream of Shc (Gads), whereas half of Gads is monomeric. This constitutive SLP-76/Gads complex could be reconstituted in Drosophila S2 cells expressing both components, suggesting that it might not contain additional subunits. In contrast, in B cells SLP-65 exists in a 180 kDa complex as well as in monomeric form. Since the complex was not found in S2 cells expressing only SLP-65, it was not di/trimeric SLP-65. Upon antigen-stimulation only the complexed SLP-65 was phosphorylated. Surprisingly, stimulation-induced alteration of SLP complexes could not be detected, suggesting that active signaling complexes form only transiently, and are of low abundance.

BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius.

PubMed

Goitsuka, R; Fujimura, Y; Mamada, H; Umeda, A; Morimura, T; Uetsuka, K; Doi, K; Tsuji, S; Kitamura, D

1998-12-01

The bursa of Fabricius is a gut-associated lymphoid organ that is essential for the generation of a diversified B cell repertoire in the chicken. We describe here a novel gene preferentially expressed in bursal B cells. The gene encodes an 85-kDa protein, designated BASH (B cell adaptor containing SH2 domain), that contains N-terminal acidic domains with SH2 domain-binding phosphotyrosine-based motifs, a proline-rich domain, and a C-terminal SH2 domain. BASH shows a substantial sequence similarity to SLP-76, an adaptor protein functioning in TCR-signal transduction. BASH becomes tyrosine-phosphorylated with the B cell Ag receptor (BCR) cross-link or by coexpression with Syk and Lyn and associates with signaling molecules including Syk and a putative chicken Shc homologue. Overexpression of BASH results in suppression of the NF-AT activation induced by BCR-cross-linking. These findings suggest that BASH is involved in BCR-mediated signal transduction and could play a critical role in B cell development in the bursa.

Collaboration in Action: Office of Research and Development ...

EPA Pesticide Factsheets

The "Collaboration in Action: US EPA's Office of Research and Develop - Current Wildfire Research Program" was invited by the USDA's US Forest Service's Scientific Executive Committee to provide USFS scientific leadership active and potential future opportunities for cooperation/collaboration. Health impacts of wildfire smoke merit the attention and action of the US EPA and current research is supported in the ACE and SHC Research Programs. Wildland fire smoke research has taken on greater importance because the 1) contribution of wildland fire PM emissions relative to total US PM emissions is increasing, 2) the population health impacts are measurable and costly, 3) vulnerable and sensitive populations at-risk are increasing attendant to our aging U.S. population and the increasing area of the wildland-urban interface, and 4) health impacts of smoke could be minimized by identifying at-risk individuals and reducing their exposures. Examples are provided. The "Collaboration in Action: US EPA's Office of Research and Develop - Current Wildfire Research Program" was invited by the USDA's US Forest Service's Scientific Executive Committee to provide USFS scientific leadership active and potential future opportunities for cooperation/collaboration.

ATM Mediates pRB Function To Control DNMT1 Protein Stability and DNA Methylation

PubMed Central

Suzuki, Misa; Hayashi, Naoyuki; Kobayashi, Masahiko; Sasaki, Nobunari; Nishiuchi, Takumi; Doki, Yuichiro; Okamoto, Takahiro; Kohno, Susumu; Muranaka, Hayato; Kitajima, Shunsuke; Yamamoto, Ken-ichi

2013-01-01

The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression. PMID:23754744

Suppression of Autophagy in Osteocytes Mimics Skeletal Aging*

PubMed Central

Onal, Melda; Piemontese, Marilina; Xiong, Jinhu; Wang, Yiying; Han, Li; Ye, Shiqiao; Komatsu, Masaaki; Selig, Martin; Weinstein, Robert S.; Zhao, Haibo; Jilka, Robert L.; Almeida, Maria; Manolagas, Stavros C.; O'Brien, Charles A.

2013-01-01

Bone mass declines with age but the mechanisms responsible remain unclear. Here we demonstrate that deletion of a conditional allele for Atg7, a gene essential for autophagy, from osteocytes caused low bone mass in 6-month-old male and female mice. Cancellous bone volume and cortical thickness were decreased, and cortical porosity increased, in conditional knock-out mice compared with control littermates. These changes were associated with low osteoclast number, osteoblast number, bone formation rate, and wall width in the cancellous bone of conditional knock-out mice. In addition, oxidative stress was higher in the bones of conditional knock-out mice as measured by reactive oxygen species levels in the bone marrow and by p66shc phosphorylation in L6 vertebra. Each of these changes has been previously demonstrated in the bones of old versus young adult mice. Thus, these results demonstrate that suppression of autophagy in osteocytes mimics, in many aspects, the impact of aging on the skeleton and suggest that a decline in autophagy with age may contribute to the low bone mass associated with aging. PMID:23645674

Different gene expression in human heart tissue and progenitor cells from control and diabetic subjects: relevance to the pathogenesis of human diabetic cardiomyopathy.

PubMed

de Cillis, Emanuela; Leonardini, Anna; Laviola, Luigi; Giorgino, Francesco; Tupputi Schinosa, Luigi de Luca; Bortone, Alessandro Santo

2010-04-01

The The aim of our study is to investigate the molecular mechanisms of diabetic cardiomyopathy through the identification of remarkable genes for the myocardial function that are expressed differently between diabetic and normal subjects. Moreover, we intend to characterize both in human myocardial tissue and in the related cardiac progenitor cells the pattern of gene expression and the levels of expression and protein activation of molecular effectors involved in the regulation of the myocardial function and differentiation to clarify whether in specific human pathological conditions (type 2 diabetes mellitus, cardiac failure, coronary artery disease) specific alterations of the aforementioned factors could take place. Thirty-five patients scheduled for coronary artery bypass grafting (CABG) or for aortic or mitral valve replacement were recruited into the study. There were 13 men and 22 women with a mean age of 64.8 +/- 13.4 years. A list of anamnestic, anthropometric, clinical, and instrumental data required for an optimal phenotypical characterization of the patients is reported. The small cardiac biopsy specimens were placed in the nourishing buffer, in a sterile tube provided the day of the procedure, to maintain the stability of the sample for several hours at room temperature. The cells were isolated by a dedicated protocol and then cultured in vitro. The sample was processed for total RNA extraction and levels of gene expression and protein activation of molecular effectors involved in the regulation of function and differentiation of human myocardium was analyzed. In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed. From a small sample of myocardium cardiac stem cells and cardiomyoblasts were also isolated and characterized. These cells showed a considerable proliferative capacity due to the fact that they demonstrate stability up to the eleventh passage. Analysis of gene expression in a subgroup of subjects showed the trend of a decrease in levels of expression of cardiac-specific transcription genes and oxidative stress-related proteins in tissues of diabetic patients compared with controls subjects. This trend is not confirmed in isolated cells. As for the coronary artery disease, diabetic cardiomyopathy could be associated with a reduction of the cardiac stem and progenitor cells pool. The expansion of the cardiac resident cells pool could be associated with a preservation of cardiac performance, suggesting that a preserved stamina compartment can counteract the impact of diabetes on the myocardium.

Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin beta4 cytoplasmic domain.

PubMed Central

Murgia, C; Blaikie, P; Kim, N; Dans, M; Petrie, H T; Giancotti, F G

1998-01-01

The cytoplasmic domain of the integrin beta4 subunit mediates both association with the hemidesmosomal cytoskeleton and recruitment of the signaling adaptor protein Shc. To examine the significance of these interactions during development, we have generated mice carrying a targeted deletion of the beta4 cytoplasmic domain. Analysis of homozygous mutant mice indicates that the tail-less alpha6beta4 binds efficiently to laminin 5, but is unable to integrate with the cytoskeleton. Accordingly, these mice display extensive epidermal detachment at birth and die immmediately thereafter from a syndrome resembling the human disease junctional epidermolysis bullosa with pyloric atresia (PA-JEB). In addition, we find a significant proliferative defect. Specifically, the number of precursor cells in the intestinal epithelium, which remains adherent to the basement membrane, and in intact areas of the skin is reduced, and post-mitotic enterocytes display increased levels of the cyclin-dependent kinase inhibitor p27(Kip). These findings indicate that the interactions mediated by the beta4 tail are crucial for stable adhesion of stratified epithelia to the basement membrane and for proper cell-cycle control in the proliferative compartments of both stratified and simple epithelia. PMID:9670011

Pseudotargeted MS Method for the Sensitive Analysis of Protein Phosphorylation in Protein Complexes.

PubMed

Lyu, Jiawen; Wang, Yan; Mao, Jiawei; Yao, Yating; Wang, Shujuan; Zheng, Yong; Ye, Mingliang

2018-05-15

In this study, we presented an enrichment-free approach for the sensitive analysis of protein phosphorylation in minute amounts of samples, such as purified protein complexes. This method takes advantage of the high sensitivity of parallel reaction monitoring (PRM). Specifically, low confident phosphopeptides identified from the data-dependent acquisition (DDA) data set were used to build a pseudotargeted list for PRM analysis to allow the identification of additional phosphopeptides with high confidence. The development of this targeted approach is very easy as the same sample and the same LC-system were used for the discovery and the targeted analysis phases. No sample fractionation or enrichment was required for the discovery phase which allowed this method to analyze minute amount of sample. We applied this pseudotargeted MS method to quantitatively examine phosphopeptides in affinity purified endogenous Shc1 protein complexes at four temporal stages of EGF signaling and identified 82 phospho-sites. To our knowledge, this is the highest number of phospho-sites identified from the protein complexes. This pseudotargeted MS method is highly sensitive in the identification of low abundance phosphopeptides and could be a powerful tool to study phosphorylation-regulated assembly of protein complex.

Expression of a functional epidermal growth factor receptor on human adipose-derived mesenchymal stem cells and its signaling mechanism.

PubMed

Baer, Patrick C; Schubert, Ralf; Bereiter-Hahn, Jürgen; Plösser, Michaela; Geiger, Helmut

2009-05-01

Adult stem cells act as a pluripotent source of regenerative cells during tissue injury. Despite expanded research in stem cell biology, understanding how growth and migration of adipose-derived adult mesenchymal stem cells (ASC) are governed by interactions with growth factors is very limited. One important property of ASC is the presence of the epidermal growth factor (EGF) receptor and the cellular response to soluble EGF. Expression of the EGF receptor was proven by PCR and Western blotting. Signal transduction was analyzed by Western blotting and PhosFlow assay. EGF caused robust phosphorylation of SHC and ERK1/2, which could be inhibited by EGF receptor antagonist AG1478 and MEK inhibitor PD98059. ASC proliferation was determined by MTT assay. Stem cell migration was analyzed in a modified Boyden chamber. Incubation with EGF led to cell proliferation and induced cell migration, but did not change the undifferentiated state of the cells. In the kidney, injured renal tubular cells express high amounts of EGF. Therefore, our results may highlight a mechanism underlying renal regeneration. Thus, future in vivo studies that focus on the effects of EGF on recruitment of ASC to sites of injury are necessary.

Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.

PubMed

Li, Jiannong; Bennett, Keiryn; Stukalov, Alexey; Fang, Bin; Zhang, Guolin; Yoshida, Takeshi; Okamoto, Isamu; Kim, Jae-Young; Song, Lanxi; Bai, Yun; Qian, Xiaoning; Rawal, Bhupendra; Schell, Michael; Grebien, Florian; Winter, Georg; Rix, Uwe; Eschrich, Steven; Colinge, Jacques; Koomen, John; Superti-Furga, Giulio; Haura, Eric B

2013-11-05

We hypothesized that elucidating the interactome of epidermal growth factor receptor (EGFR) forms that are mutated in lung cancer, via global analysis of protein-protein interactions, phosphorylation, and systematically perturbing the ensuing network nodes, should offer a new, more systems-level perspective of the molecular etiology. Here, we describe an EGFR interactome of 263 proteins and offer a 14-protein core network critical to the viability of multiple EGFR-mutated lung cancer cells. Cells with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) had differential dependence of the core network proteins based on the underlying molecular mechanisms of resistance. Of the 14 proteins, 9 are shown to be specifically associated with survival of EGFR-mutated lung cancer cell lines. This included EGFR, GRB2, MK12, SHC1, ARAF, CD11B, ARHG5, GLU2B, and CD11A. With the use of a drug network associated with the core network proteins, we identified two compounds, midostaurin and lestaurtinib, that could overcome drug resistance through direct EGFR inhibition when combined with erlotinib. Our results, enabled by interactome mapping, suggest new targets and combination therapies that could circumvent EGFR TKI resistance.

Organizational policy recommendations for control of STI/HIV among female sex workers in China: regular examination of workers in social hygiene clinics.

PubMed

Morisky, Donald E; Urada, Lianne A

2011-06-01

This article aims to address female sex workers at high risk for contracting HIV in China by recommending evidence-based socio-structural interventions and policies at the national level that have yielded effective outcomes in other countries. National governments such as the Philippines and Hong Kong have utilized the Social Hygiene Clinic (SHC) model. A similar national policy can be highly effective in China. Evidence-based research study results indicate significant reductions in STI and consistent condom use among female sex workers in both China and the Philippines. Consistent condom use in both countries continues to be significantly associated with interpersonal- and venue-level factors. Individuals who had higher appointment-keeping ratios in the Philippines had higher rates of consistent condom use (OR = 2.7, 95% CI = 1.6-3.7) and significantly lower rates of STI (OR = 0.43, 95% CI = 0.26-0.57). By beginning with provinces, which already have a good relationship between establishment venues and the local Health Department, China can develop city ordinances and establishment regulations that begin to require regular examinations of female sex workers and entertainers in the local STI clinic.

The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells.

PubMed

Vitagliano, Donata; De Falco, Valentina; Tamburrino, Anna; Coluzzi, Sabrina; Troncone, Giancarlo; Chiappetta, Gennaro; Ciardiello, Fortunato; Tortora, Giampaolo; Fagin, James A; Ryan, Anderson J; Carlomagno, Francesca; Santoro, Massimo

2011-02-01

Oncogenic conversion of the RET tyrosine kinase is a frequent feature of medullary thyroid carcinoma (MTC). ZD6474 (vandetanib) is an ATP-competitive inhibitor of RET, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptors kinases. In this study, we have studied ZD6474 mechanism of action in TT and MZ-CRC-1 human MTC cell lines, carrying cysteine 634 to tryptophan (C634W) and methionine 918 to threonine (M918T) RET mutation respectively. ZD6474 blunted MTC cell proliferation and RET, Shc and p44/p42 mitogen-activated protein kinase (MAPK) phosphorylation. Single receptor knockdown by RNA interference showed that MTC cells depended on RET for proliferation. Adoptive expression of the ZD6474-resistant V804M RET mutant rescued proliferation of TT cells under ZD6474 treatment, showing that RET is a key ZD6474 target in these MTC cells. Upon RET inhibition, adoptive stimulation of EGFR partially rescued TT cell proliferation, MAPK signaling, and expression of cell-cycle-related genes. This suggests that simultaneous inhibition of RET and EGFR by ZD6474 may overcome the risk of MTC cells to escape from RET blockade through compensatory over-activation of EGFR.

Repeated psychosocial stress at night affects the circadian activity rhythm of male mice.

PubMed

Bartlang, Manuela S; Oster, Henrik; Helfrich-Förster, Charlotte

2015-06-01

We have recently shown that molecular rhythms in the murine suprachiasmatic nucleus (SCN) are affected by repeated social defeat (SD) during the dark/active phase (social defeat dark [SDD]), while repeated SD during the light/inactive phase (social defeat light [SDL]) had no influence on PERIOD2::LUCIFERASE explant rhythms in the SCN. Here we assessed the effects of the same stress paradigm by in vivo biotelemetry on 2 output rhythms of the circadian clock (i.e., activity and core body temperature) in wild-type (WT) and clock-deficient Period (Per)1/2 double-mutant mice during and following repeated SDL and SDD. In general, stress had more pronounced effects on activity compared to body temperature rhythms. Throughout the SD procedure, activity and body temperature were markedly increased during the 2 h of stressor exposure at zeitgeber time (ZT) 1 to ZT3 (SDL mice) and ZT13 to ZT15 (SDD mice), which was compensated by decreased activity during the remaining dark phase (SDL and SDD mice) and light phase (SDL mice) in both genotypes. Considerable differences in the activity between SDL and SDD mice were seen in the poststress period. SDD mice exhibited a reduced first activity bout at ZT13, delayed activity onset, and, consequently, a more narrow activity bandwidth compared with single-housed control (SHC) and SDL mice. Given that this effect was absent in Per1/2 mutant SDD mice and persisted under constant darkness conditions in SDD WT mice, it suggests an involvement of the endogenous clock. Taken together, the present findings demonstrate that SDD has long-lasting consequences for the functional output of the biological clock that, at least in part, appear to depend on the clock genes Per1 and Per2. © 2015 The Author(s).

Knowledge, attitude, and preventive practice survey regarding AIDS comparing registered to freelance commercial sex workers in Iloilo City, Philippines.

PubMed

Liu, T I; So, R

1996-12-01

A survey of female commercial sex workers (CSW) in Iloilo City, Philipines, was conducted in October and November 1995 to determine the level of knowledge, attitudes, and preventive practices regarding HIV/AIDS to guide future education programs. CSWs in the Philippines were categorized as registered or freelance. Registered CSWs included "hospitality girls" from licensed bars, night clubs, and massage parlors who have registered with the local social hygiene clinic (SHC). Freelance CSWs are not registered. 110 registered and 46 freelance CSWs were surveyed. We compared demographic data, scores from a basic knowledge test, and preventive practices between registered and freelance CSWs. Demographic data indicate that registered CSWs often originate from provinces outside of the Visayan Islands (25%) and most have never been married (93%). Freelance CSWs included more married (11%) and separated (11%) women from nearby cities. Knowledge test scores of registered and freelance CSWs were not significantly different. 90-96% of CSWs correctly answered questions regarding modes of transmission. However, 25% still believed it is possible to contract AIDS from using a public restroom. Registered and freelance CSWs believed their risks for AIDS to be equally great. However, 38% of freelance CSWs admit to never or almost never using condoms compared to 15% of registered CSWs. Licensed establishments and a support staff at the social hygiene clinic may provide a relatively structured working environment, giving registered CSWs security and confidence to insist on condom use. In most cases, condom use seems to depend on male customer compliance, and CSWs, especially freelancers, cannot afford to insist on condom use. The CSWs indicated that they learned most about AIDS through health personnel and television.

GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2.

PubMed

Zhao, Chunmei; Ma, Hong; Bossy-Wetzel, Ella; Lipton, Stuart A; Zhang, Zhuohua; Feng, Gen-Sheng

2003-09-05

Gab1 and Gab2 are scaffolding proteins acting downstream of cell surface receptors and interact with a variety of cytoplasmic signaling proteins such as Grb2, Shp-2, phosphatidylinositol 3-kinase, Shc, and Crk. To identify new binding partners for GAB proteins and better understand their functions, we performed a yeast two-hybrid screening with hGab2-(120-587) as bait. This work led to identification of a novel GTPase-activating protein (GAP) for Rho family GTPases. The GAP domain shows high similarity to the recently cloned CdGAP and displays activity toward RhoA, Rac1, and Cdc42 in vitro. The protein was named GC-GAP for its ability to interact with GAB proteins and its activity toward Rac and Cdc42. GC-GAP is predominantly expressed in the brain with low levels detected in other tissues. Antibodies directed against GC-GAP recognized a protein of approximately 200 kDa. Expression of GC-GAP in 293T cells led to a reduction in active Rac1 and Cdc42 levels but not RhoA. Suppression of GC-GAP expression by siRNA inhibited proliferation of C6 astroglioma cells. In addition, GC-GAP contains several classic proline-rich motifs, and it interacts with the first SH3 domain of Crk and full-length Nck in vitro. We propose that Gab1 and Gab2 in cooperation with other adapter molecules might regulate the cellular localization of GC-GAP under specific stimuli, acting to regulate precisely Rac and Cdc42 activities. Given that GC-GAP is specifically expressed in the nervous system and that it is localized to the dendritic processes of cultured neurons, GC-GAP may play a role in dendritic morphogenesis and also possibly in neural/glial cell proliferation.

In vivo disruption of T cell development by expression of a dominant-negative polypeptide designed to abolish the SLP-76/Gads interaction.

PubMed

Jordan, Martha S; Maltzman, Jonathan S; Kliche, Stefanie; Shabason, Jacob; Smith, Jennifer E; Obstfeld, Amrom; Schraven, Burkhart; Koretzky, Gary A

2007-10-01

Multi-molecular complexes nucleated by adaptor proteins play a central role in signal transduction. In T cells, one central axis consists of the assembly of several signaling proteins linked together by the adaptors linker of activated T cells (LAT), Src homology 2 domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76), and Grb2-related adaptor downstream of Shc (Gads). Each of these adaptors has been shown to be important for normal T cell development, and their proper sub-cellular localization is critical for optimal function in cell lines. We previously demonstrated in Jurkat T cells and a rat basophilic leukemic cell line that expression of a 50-amino acid polypeptide identical to the site on SLP-76 that binds to Gads blocks proper localization of SLP-76 and SLP-76-dependent signaling events. Here we extend these studies to investigate the ability of this polypeptide to inhibit TCR-induced integrin activity in Jurkat cells and to inhibit in vivo thymocyte development and primary T cell function. These data provide evidence for the in vivo function of a dominant-negative peptide based upon the biology of SLP-76 action and suggest the possibility of therapeutic potential of targeting the SLP-76/Gads interaction.

The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.

PubMed

Rozakis-Adcock, M; Fernley, R; Wade, J; Pawson, T; Bowtell, D

1993-05-06

Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve growth factor and insulin, transmit intracellular signals through Ras proteins. Ligand binding to such receptors stimulates Ras guanine-nucleotide-exchange activity and increases the level of GTP-bound Ras, suggesting that these tyrosine kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans and Drosophila, genetic studies have shown that Ras activation by tyrosine kinases requires the protein Sem-5/drk, which contains a single Src-homology (SH) 2 domain and two flanking SH3 domains. Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain. Here we show that in rodent fibroblasts, the SH3 domains of Grb2 are bound to the proline-rich carboxy-terminal tail of mSos1, a protein homologous to Drosophila Sos. Sos is required for Ras signalling and contains a central domain related to known Ras-GNRPs. EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells.

Development of a Climate Resilience Screening Index (CRSI) ...

EPA Pesticide Factsheets

A Climate Resilience Screening Index is being developed that is applicable at multiple scales for the United States. Those scales include national, state, county and community. The index will be applied at the first three scales and at selected communities. The index was developed in order to explicitly include domains, indicators and metrics addressing environmental, economic and societal aspects of climate resilience. In addition, the index uses indicators and metrics that assess ecosystem, economic, governance and social services at these scales. Finally, we are developing forecasting approaches that can relate intended changes in services and governance to likely levels of changes in the resiliency of communities to climate change impacts. The present challenge is the incorporation of the index, its relationships to governance and the developing forecasting tools into Federal decision-making across US government and into state/county/community decision-making across the US. Governmental acceptance of changes to policies often can be just as challenging as the initial technical acceptance of the index and its relation to climate change. Climate Resilience Index is a requested product by ORD AA and EPA Administrator through SHC Program. Index needed to assess states', counties', and communities' abilities of recovery from climate events. Audience: Internal EPA (Administrator, IO, OLEM, OW and OAR) and external (states, counties and communities). Product

Characterizing light attenuation within Northwest Florida ...

EPA Pesticide Factsheets

Water Quality (WQ) condition is based on ecosystem stressor indicators (e.g. water clarity) which are biogeochemically important and critical when considering the Deepwater Horizon oil spill restoration efforts under the 2012 RESTORE Act. Nearly all of the proposed RESTORE projects list restoring WC as a goal, but 90% neglect water clarity. Here, dynamics of optical constituents impacting clarity are presented from a 2009-2011 study within Pensacola, Choctawhatchee, St. Andrew and St. Joseph estuaries (targeted RESTORE sites) in Northwest Florida. Phytoplankton were the smallest contribution to total absorption (at-wPAR) at 412 nm (5-11%), whereas colored dissolved organic matter was the largest (61-79%). Estuarine at-wPAR was significantly related to light attenuation (KdPAR), where individual contributors to clarity and the influence of climatic events were discerned. Provided are conversion equations demonstrating interoperability of clarity indicators between traditional State-measured WQ measures (e.g. secchi disc), optical constituents, and even satellite remote sensing for obtaining baseline assessments. This paper arose from efforts under SSWR and SHC to utilize water quality data as baseline measures for RESTORE Act monitoring in Florida estuaries. This paper aims to (1) describe dynamics of optical constituents that impact water clarity in four NW Florida estuaries, and (2) make a case for the total absorption coefficient (at-wPAR) as a valuable

Quantitative In Vivo Fluorescence Cross-Correlation Analyses Highlight the Importance of Competitive Effects in the Regulation of Protein-Protein Interactions

PubMed Central

Sadaie, Wakako; Harada, Yoshie; Matsuda, Michiyuki

2014-01-01

Computer-assisted simulation is a promising approach for clarifying complicated signaling networks. However, this approach is currently limited by a deficiency of kinetic parameters determined in living cells. To overcome this problem, we applied fluorescence cross-correlation spectrometry (FCCS) to measure dissociation constant (Kd) values of signaling molecule complexes in living cells (in vivo Kd). Among the pairs of fluorescent molecules tested, that of monomerized enhanced green fluorescent protein (mEGFP) and HaloTag-tetramethylrhodamine was most suitable for the measurement of in vivo Kd by FCCS. Using this pair, we determined 22 in vivo Kd values of signaling molecule complexes comprising the epidermal growth factor receptor (EGFR)–Ras–extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. With these parameters, we developed a kinetic simulation model of the EGFR-Ras-ERK MAP kinase pathway and uncovered a potential role played by stoichiometry in Shc binding to EGFR during the peak activations of Ras, MEK, and ERK. Intriguingly, most of the in vivo Kd values determined in this study were higher than the in vitro Kd values reported previously, suggesting the significance of competitive bindings inside cells. These in vivo Kd values will provide a sound basis for the quantitative understanding of signal transduction. PMID:24958104

Handling of subpixel structures in the application of satellite derived irradiance data for solar energy system analysis - a review

NASA Astrophysics Data System (ADS)

Beyer, Hans Georg

2016-04-01

With the increasing availability of satellite derived irradiance information, this type of data set is more and more in use for the design and operation of solar energy systems, most notably PV- and CSP-systems. By this, the need for data measured on-site is reduced. However, due to basic limitations of the satellite-derived data, several requirements put by the intended application cannot be coped with this data type directly. Traw satellite information has to be enhanced in both space and time resolution by additional information to be fully applicable for all aspects of the modelling od solar energy systems. To cope with this problem, several individual and collaborative projects had been performed in the recent years or are ongoing. Approaches are on one hand based on pasting synthesized high-resolution data into the low-resolution original sets. Pre-requite is an appropriate model, validated against real world data. For the case of irradiance data, these models can be extracted either directly from ground measured data sets or from data referring to the cloud situation as gained from the images of sky cameras or from monte -carlo initialized physical models. The current models refer to the spatial structure of the cloud fields. Dynamics are imposed by moving the cloud structures according to a large scale cloud motion vector, either extracted from the dynamics interfered from consecutive satellite images or taken from a meso-scale meteorological model. Dynamic irradiance information is then derived from the cloud field structure and the cloud motion vector. This contribution, which is linked to subtask A - Solar Resource Applications for High Penetration of Solar Technologies - of IEA SHC task 46, will present the different approaches and discuss examples in view of validation, need for auxiliary information and respective general applicability.

Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats.

PubMed

Laughlin, M Harold; Padilla, Jaume; Jenkins, Nathan T; Thorne, Pamela K; Martin, Jeffrey S; Rector, R Scott; Akter, Sadia; Davis, J Wade

2015-09-15

Using next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of Otsuka Long Evans Tokushima Fatty (OLETF) rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). We hypothesized that the greatest effects of exercise would be in the gastrocnemius arterioles. Results show that EX caused the largest number of changes in gene expression in the soleus and white gastrocnemius 2a arterioles with little to no changes in the feed arteries. In contrast, SPRINT caused substantial changes in gene expression in the feed arteries. IPA canonical pathway analysis revealed 18 pathways with significant changes in gene expression when analyzed across vessels and revealed that EX induces increased expression of the following genes in all arterioles examined: Shc1, desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein binding protein, alpha (Gnat1), and Bcl2l1 and decreased expression of ubiquitin D (Ubd) and cAMP response element modulator (Crem). EX increased expression of endothelin converting enzyme (Ece1), Hsp90b, Fkbp5, and Cdcl4b in four of five arterioles. SPRINT had effects on expression of Crem, Dhh, Bcl2l1, and Ubd that were similar to EX. SPRINT also increased expression of Nfkbia, Hspa5, Tubb 2a and Tubb 2b, and Fkbp5 in all five arterioles and increased expression of Gnat1 in all but the soleus second-order arterioles. Many contractile and/or structural protein genes were increased by SPRINT in the gastrocnemius feed artery, but the same genes exhibited decreased expression in red gastrocnemius arterioles. We conclude that training-induced changes in arteriolar gene expression patterns differ by muscle fiber type composition and along the arteriolar tree.

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins*

PubMed Central

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-01

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. PMID:27927989

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins.

PubMed

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-20

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Reduced Oxidant Stress and Extended Lifespan in Mice Exposed to a Low Glycotoxin Diet

PubMed Central

Cai, Weijing; He, John Cijiang; Zhu, Li; Chen, Xue; Wallenstein, Sylvan; Striker, Gary E.; Vlassara, Helen

2007-01-01

Aging is accompanied by increased oxidative stress (OS) and accumulation of advanced glycation end products (AGEs). AGE formation in food is temperature-regulated, and ingestion of nutrients prepared with excess heat promotes AGE formation, OS, and cardiovascular disease in mice. We hypothesized that sustained exposure to the high levels of pro-oxidant AGEs in normal diets (RegAGE) contributes to aging via an increased AGE load, which causes AGER1 dysregulation and depletion of anti-oxidant capacity, and that an isocaloric, but AGE-restricted (by 50%) diet (LowAGE), would decrease these abnormalities. C57BL6 male mice with a life-long exposure to a LowAGE diet had higher than baseline levels of tissue AGER1 and glutathione/oxidized glutathione and reduced plasma 8-isoprostanes and tissue RAGE and p66shc levels compared with mice pair-fed the regular (RegAGE) diet. This was associated with a reduction in systemic AGE accumulation and amelioration of insulin resistance, albuminuria, and glomerulosclerosis. Moreover, lifespan was extended in LowAGE mice, compared with RegAGE mice. Thus, OS-dependent metabolic and end organ dysfunction of aging may result from life-long exposure to high levels of glycoxidants that exceed AGER1 and anti-oxidant reserve capacity. A reduced AGE diet preserved these innate defenses, resulting in decreased tissue damage and a longer lifespan in mice. PMID:17525257

Quantitative in vivo fluorescence cross-correlation analyses highlight the importance of competitive effects in the regulation of protein-protein interactions.

PubMed

Sadaie, Wakako; Harada, Yoshie; Matsuda, Michiyuki; Aoki, Kazuhiro

2014-09-01

Computer-assisted simulation is a promising approach for clarifying complicated signaling networks. However, this approach is currently limited by a deficiency of kinetic parameters determined in living cells. To overcome this problem, we applied fluorescence cross-correlation spectrometry (FCCS) to measure dissociation constant (Kd) values of signaling molecule complexes in living cells (in vivo Kd). Among the pairs of fluorescent molecules tested, that of monomerized enhanced green fluorescent protein (mEGFP) and HaloTag-tetramethylrhodamine was most suitable for the measurement of in vivo Kd by FCCS. Using this pair, we determined 22 in vivo Kd values of signaling molecule complexes comprising the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. With these parameters, we developed a kinetic simulation model of the EGFR-Ras-ERK MAP kinase pathway and uncovered a potential role played by stoichiometry in Shc binding to EGFR during the peak activations of Ras, MEK, and ERK. Intriguingly, most of the in vivo Kd values determined in this study were higher than the in vitro Kd values reported previously, suggesting the significance of competitive bindings inside cells. These in vivo Kd values will provide a sound basis for the quantitative understanding of signal transduction. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways.

PubMed

Yankee, Thomas M; Solow, Sasha A; Draves, Kevin D; Clark, Edward A

2003-01-01

Adapter proteins play a critical role in regulating signals triggered by Ag receptor cross-linking. These small molecules link receptor proximal events with downstream signaling pathways. In this study, we explore the expression and function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related adaptor downstream of Shc adapter protein in human B cells. GrpL is expressed in naive B cells and is down-regulated following B cell Ag receptor ligation. By contrast, germinal center and memory B cells express little or no GrpL. Using human B cell lines, we detected constitutive interactions between GrpL and B cell linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa, hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2 domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular signal-related kinase and p38 mitogen-activated protein kinase phosphorylation. Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor-mediated signaling events.

Carbon storage in US wetlands | Science Inventory | US EPA

EPA Pesticide Factsheets

This Nature Communications article is a product of legacy work that contributes to Safe and Sustainable Water Resources research on technical support and research on the enhancement of Office of Water’s National Aquatic Resource Surveys (NARS) (SSWR 3.01A). The research is also potentially relevant to SHC and ACE research program questions. The research was conducted under USEPA cooperative agreement number 83422601 with Michigan State University in association with Kenyon College. USEPA 2011 National Wetland Condition Assessment data used for this research are publically available from https://www.epa.gov/national-aquatic-resource-surveys/data-national-aquatic-resource-surveys. ***This is article is clearing for completion ONLY*** The research and conclusions in this article highlight the role of wetland soils in storing carbon and the implications of disturbance to wetlands for climate change. Specifically, we provide unbiased estimates of soil carbon stocks for wetlands at regional and national scales using field data from the 2011 National Wetland Condition Assessment (NWCA). This research also describes how soil carbon stocks vary by wetland type and soil depth, and by anthropogenic disturbance to the wetland. We find that wetlands in the conterminous US store a total of 11.52 PgC – roughly equivalent to four years of annual carbon emissions by the US. Freshwater inland wetlands, in part due to their substantial areal extent, hold nearly ten-fol

gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes.

PubMed

Braun, L; Ghebrehiwet, B; Cossart, P

2000-04-03

InlB is a Listeria monocytogenes protein that promotes entry of the bacterium into mammalian cells by stimulating tyrosine phosphorylation of the adaptor proteins Gab1, Cbl and Shc, and activation of phosphatidyl- inositol (PI) 3-kinase. Using affinity chromatography and enzyme-linked immunosorbent assay, we demonstrate a direct interaction between InlB and the mammalian protein gC1q-R, the receptor of the globular part of the complement component C1q. Soluble C1q or anti-gC1q-R antibodies impair InlB-mediated entry. Transient transfection of GPC16 cells, which are non-permissive to InlB-mediated entry, with a plasmid-expressing human gC1q-R promotes entry of InlB-coated beads. Furthermore, several experiments indicate that membrane recruitment and activation of PI 3-kinase involve an InlB-gC1q-R interaction and that gC1q-R associates with Gab1 upon stimulation of Vero cells with InlB. Thus, gC1q-R constitutes a cellular receptor involved in InlB-mediated activation of PI 3-kinase and tyrosine phosphorylation of the adaptor protein Gab1. After E-cadherin, the receptor for internalin, gC1q-R is the second identified mammalian receptor promoting entry of L. monocytogenes into mammalian cells.

Saccharomyces boulardii Preserves the Barrier Function and Modulates the Signal Transduction Pathway Induced in Enteropathogenic Escherichia coli-Infected T84 Cells

PubMed Central

Czerucka, Dorota; Dahan, Stephanie; Mograbi, Baharia; Rossi, Bernard; Rampal, Patrick

2000-01-01

Use of the nonpathogenic yeast Saccharomyces boulardii in the treatment of infectious diarrhea has attracted growing interest. The present study designed to investigate the effect of this yeast on enteropathogenic Escherichia coli (EPEC)-associated disease demonstrates that S. boulardii abrogated the alterations induced by an EPEC strain on transepithelial resistance, [3H]inulin flux, and ZO-1 distribution in T84 cells. Moreover, EPEC-mediated apoptosis of epithelial cells was delayed in the presence of S. boulardii. The yeast did not modify the number of adherent bacteria but lowered by 50% the number of intracellular bacteria. Infection by EPEC induced tyrosine phosphorylation of several proteins in T84 cells, including p46 and p52 SHC isoforms, that was attenuated in the presence of S. boulardii. Similarly, EPEC-induced activation of the ERK1/2 mitogen-activated protein (MAP) kinase pathway was diminished in the presence of the yeast. Interestingly, inhibition of the ERK1/2 pathway with the specific inhibitor PD 98059 decreased EPEC internalization, suggesting that modulation of the ERK1/2 MAP pathway might account for the lowering of the number of intracellular bacteria observed in the presence of S. boulardii. Altogether, this study demonstrated that S. boulardii exerts a protective effect on epithelial cells after EPEC adhesion by modulating the signaling pathway induced by bacterial infection. PMID:10992512

Non-Ligand-Induced Dimerization is Sufficient to Initiate the Signalling and Endocytosis of EGF Receptor.

PubMed

Kourouniotis, George; Wang, Yi; Pennock, Steven; Chen, Xinmei; Wang, Zhixiang

2016-07-25

The binding of epidermal growth factor (EGF) to EGF receptor (EGFR) stimulates cell mitogenesis and survival through various signalling cascades. EGF also stimulates rapid EGFR endocytosis and its eventual degradation in lysosomes. The immediate events induced by ligand binding include receptor dimerization, activation of intrinsic tyrosine kinase and autophosphorylation. However, in spite of intensified efforts, the results regarding the roles of these events in EGFR signalling and internalization is still very controversial. In this study, we constructed a chimeric EGFR by replacing its extracellular domain with leucine zipper (LZ) and tagged a green fluorescent protein (GFP) at its C-terminus. We showed that the chimeric LZ-EGFR-GFP was constitutively dimerized. The LZ-EGFR-GFP dimer autophosphorylated each of its five well-defined C-terminal tyrosine residues as the ligand-induced EGFR dimer does. Phosphorylated LZ-EGFR-GFP was localized to both the plasma membrane and endosomes, suggesting it is capable of endocytosis. We also showed that LZ-EGFR-GFP activated major signalling proteins including Src homology collagen-like (Shc), extracellular signal-regulated kinase (ERK) and Akt. Moreover, LZ-EGFR-GFP was able to stimulate cell proliferation. These results indicate that non-ligand induced dimerization is sufficient to activate EGFR and initiate cell signalling and EGFR endocytosis. We conclude that receptor dimerization is a critical event in EGF-induced cell signalling and EGFR endocytosis.

Incidence of genital warts among the Hong Kong general adult population

PubMed Central

2010-01-01

Background The objective of this study is to estimate the incidence of genital warts in Hong Kong and explore a way to establish a surveillance system for genital warts among the Hong Kong general population. Methods A total of 170 private doctors and all doctors working in the 5 local Social Hygiene Clinics (SHC) participated in this study. During the 14-day data collection period (January 5 through18, 2009), the participating doctors filled out a log-form on a daily basis to record the number of patients with genital warts. The total number of new cases of genital warts presented to private and public doctors in Hong Kong was projected using the stratification sampling method. Results A total of 721 (0.94%) adults presented with genital warts to the participating doctors during the two-week study period, amongst them 73 (10.1%) were new cases. The projected number of new cases of genital warts among Hong Kong adults was 442 (297 male and 144 female) during the study period. The incidence of genital warts in Hong Kong was estimated to be 203.7 per 100,000 person-years (respectively 292.2 and 124.9 per 100,000 person-years for males and females). Conclusions The incidence of genital warts is high among adults in Hong Kong. The study demonstrates the importance of collecting surveillance data from both private and public sectors. PMID:20849578

Incidence of genital warts among the Hong Kong general adult population.

PubMed

Lin, Chunqing; Lau, Joseph T F; Ho, King-Man; Lau, Man-Chun; Tsui, Hi-Yi; Lo, Kuen-Kong

2010-09-17

The objective of this study is to estimate the incidence of genital warts in Hong Kong and explore a way to establish a surveillance system for genital warts among the Hong Kong general population. A total of 170 private doctors and all doctors working in the 5 local Social Hygiene Clinics (SHC) participated in this study. During the 14-day data collection period (January 5 through 18, 2009), the participating doctors filled out a log-form on a daily basis to record the number of patients with genital warts. The total number of new cases of genital warts presented to private and public doctors in Hong Kong was projected using the stratification sampling method. A total of 721 (0.94%) adults presented with genital warts to the participating doctors during the two-week study period, amongst them 73 (10.1%) were new cases. The projected number of new cases of genital warts among Hong Kong adults was 442 (297 male and 144 female) during the study period. The incidence of genital warts in Hong Kong was estimated to be 203.7 per 100,000 person-years (respectively 292.2 and 124.9 per 100,000 person-years for males and females). The incidence of genital warts is high among adults in Hong Kong. The study demonstrates the importance of collecting surveillance data from both private and public sectors.

Computational identification and validation of alternative splicing in ZSF1 rat RNA-seq data, a preclinical model for type 2 diabetic nephropathy.

PubMed

Zhang, Chi; Dower, Ken; Zhang, Baohong; Martinez, Robert V; Lin, Lih-Ling; Zhao, Shanrong

2018-05-16

Obese ZSF1 rats exhibit spontaneous time-dependent diabetic nephropathy and are considered to be a highly relevant animal model of progressive human diabetic kidney disease. We previously identified gene expression changes between disease and control animals across six time points from 12 to 41 weeks. In this study, the same data were analysed at the isoform and exon levels to reveal additional disease mechanisms that may be governed by alternative splicing. Our analyses identified alternative splicing patterns in genes that may be implicated in disease pathogenesis (such as Shc1, Serpinc1, Epb4.1l5, and Il-33), which would have been overlooked in standard gene-level analysis. The alternatively spliced genes were enriched in pathways related to cell adhesion, cell-cell interactions/junctions, and cytoskeleton signalling, whereas the differentially expressed genes were enriched in pathways related to immune response, G protein-coupled receptor, and cAMP signalling. Our findings indicate that additional mechanistic insights can be gained from exon- and isoform-level data analyses over standard gene-level analysis. Considering alternative splicing is poorly conserved between rodents and humans, it is noted that this work is not translational, but the point holds true that additional insights can be gained from alternative splicing analysis of RNA-seq data.

Constraining the presence and abundance of an excess gas phase prior to the June 1991 eruption of Mt Pinatubo (Philippines) using S-isotopes

NASA Astrophysics Data System (ADS)

Bouvet de Maisonneuve, C.; Fiege, A.; Fabbro, G.; Kubo, A. I.

2016-12-01

Large explosive eruptions typically release orders of magnitude more S to the atmosphere than expected based on degassing of the erupted magma. To explain this, an excess, accumulated vapor phase is often proposed. Resolving the presence, composition, and source of such an exsolved volatile phase is essential, as it will drive eruptions towards increased explosivity. Integration of melt inclusion (MI) volatile contents (H, C, S, Cl, F) with S isotope data on melt inclusions, and sulfur-bearing minerals (anhydrite) can provide information on pre- and syn-eruptive degassing. The June 1991 eruption of Mt Pinatubo is an ideal candidate for such a study as it injected a >17 Mt of SO2 into the stratosphere, corresponding to a S excess release of a factor close to 100. The erupted magma was oxidized (QFM+3) and should therefore yield a clear isotopic trend. Volatile contents in glassy but vesicular quartz-hosted MIs were measured by SIMS and yield <3 wt% H2O and <100 ppm S but up to 1500 ppm CO2, in agreement with previous measurements. The MIs with few but large vapor bubbles (avoided during analysis) have lower H2O and CO2 contents and smaller standard deviations. The MIs with many small bubbles have higher volatile contents and standard deviations because the gas phase was not avoided during analysis. We observed scattered S contents and highly variable S isotope compositions for all MIs, which could be due to the presence of submicron S phases. Thus, we homogenized a batch of MIs under P-T-fO2 conditions that best correspond to pre-eruptive conditions. The δ34S for quartz-hosted MIs ranges from -1 to +14 ‰ and δ34S vs. S-H-C content trends are used to infer open or closed system degassing processes. In the near future, anhydrites and melt inclusions in other mineral hosts (amphibole and plagioclase) will be investigated in order to reconstruct the degassing history of the 1991 Pinatubo magma and to trace the S source.

Pheno- and Genotyping of Hopanoid Production in Acidobacteria

PubMed Central

Damsté, Jaap S. Sinninghe; Rijpstra, W. Irene C.; Dedysh, Svetlana N.; Foesel, Bärbel U.; Villanueva, Laura

2017-01-01

Hopanoids are pentacyclic triterpenoid lipids synthesized by different bacterial groups. Methylated hopanoids were believed to be exclusively synthesized by cyanobacteria and aerobic methanotrophs until the genes encoding for the methylation at the C-2 and C-3 position (hpnP and hpnR) were found to be widespread in the bacterial domain, invalidating their use as specific biomarkers. These genes have been detected in the genome of the Acidobacterium “Ca. Koribacter versatilis,” but our knowledge of the synthesis of hopanoids and the presence of genes of their biosynthetic pathway in other member of the Acidobacteria is limited. We analyzed 38 different strains of seven Acidobacteria subdivisions (SDs 1, 3, 4, 6, 8, 10, and 23) for the presence of C30 hopenes and C30+ bacteriohopane polyols (BHPs) using the Rohmer reaction. BHPs and/or C30 hopenes were detected in all strains of SD1 and SD3 but not in SD4 (excepting Chloracidobacterium thermophilum), 6, 8, 10, and 23. This is in good agreement with the presence of genes required for hopanoid biosynthesis in the 31 available whole genomes of cultivated Acidobacteria. All genomes encode the enzymes involved in the non-mevalonate pathway ultimately leading to farnesyl diphosphate but only SD1 and 3 Acidobacteria and C. thermophilum encode all three enzymes required for the synthesis of squalene, its cyclization (shc), and addition and modification of the extended side chain (hpnG, hpnH, hpnI, hpnJ, hpnO). In almost all strains, only tetrafunctionalized BHPs were detected; three strains contained variable relative abundances (up to 45%) of pentafunctionalized BHPs. Only “Ca. K. versatilis” contained methylated hopanoids (i.e., 2,3-dimethyl bishomohopanol), although in low (<10%) amounts. These genes are not present in any other Acidobacterium, consistent with the absence of methylated BHPs in the other examined strains. These data are in agreement with the scattered occurrence of methylated BHPs in other bacterial phyla such as the Alpha-, Beta-, and Gammaproteobacteria and the Cyanobacteria, limiting their biomarker potential. Metagenomes of Acidobacteria were also examined for the presence of genes required for hopanoid biosynthesis. The complete pathway for BHP biosynthesis was evident in SD2 Acidobacteria and a group phylogenetically related to SD1 and SD3, in line with the limited occurrence of BHPs in acidobacterial cultures. PMID:28642737

Conditional expression of RET/PTC induces a weak oncogenic drive in thyroid PCCL3 cells and inhibits thyrotropin action at multiple levels.

PubMed

Wang, Jianwei; Knauf, Jeffrey A; Basu, Saswata; Puxeddu, Efisio; Kuroda, Hiroaki; Santoro, Massimo; Fusco, Alfredo; Fagin, James A

2003-07-01

Chromosomal rearrangements linking the promoter(s) and N-terminal domain of unrelated gene(s) to the C terminus of RET result in constitutively activated chimeric forms of the receptor in thyroid cells (RET/PTC). RET/PTC rearrangements are thought to be tumor-initiating events; however, the early biological consequences of RET/PTC activation are unknown. To explore this, we generated clonal lines derived from well-differentiated rat thyroid PCCL3 cells with doxycycline-inducible expression of either RET/PTC1 or RET/PTC3. As previously shown in other cell types, RET/PTC1 and RET/PTC3 oligomerized and displayed constitutive tyrosine kinase activity. Neither RET/PTC1 nor RET/PTC3 conferred cells with the ability to grow in the absence of TSH, likely because of concomitant stimulation of both DNA synthesis and apoptosis, resulting in no net growth in the cell population. Effects of RET/PTC on DNA synthesis and apoptosis did not require direct interaction of the oncoprotein with either Shc or phospholipase Cgamma. Acute expression of the oncoprotein decreased TSH-mediated growth stimulation due to interference of TSH signaling by RET/PTC at multiple levels. Taken together, these data indicate that RET/PTC is a weak tumor-initiating event and that TSH action is disrupted by this oncoprotein at several points, and also predict that secondary genetic or epigenetic changes are required for clonal expansion.

Gab1 Is Required for Cell Cycle Transition, Cell Proliferation, and Transformation Induced by an Oncogenic Met Receptor

PubMed Central

Mood, Kathleen; Saucier, Caroline; Bong, Yong-Sik; Lee, Hyun-Shik; Park, Morag

2006-01-01

We have shown previously that either Grb2- or Shc-mediated signaling from the oncogenic Met receptor Tpr-Met is sufficient to trigger cell cycle progression in Xenopus oocytes. However, direct binding of these adaptors to Tpr-Met is dispensable, implying that another Met binding partner mediates these responses. In this study, we show that overexpression of Grb2-associated binder 1 (Gab1) promotes cell cycle progression when Tpr-Met is expressed at suboptimal levels. This response requires that Gab1 possess an intact Met-binding motif, the pleckstrin homology domain, and the binding sites for phosphatidylinositol 3-kinase and tyrosine phosphatase SHP-2, but not the Grb2 and CrkII/phospholipase Cγ binding sites. Importantly, we establish that Gab1-mediated signals are critical for cell cycle transition promoted by the oncogenic Met and fibroblast growth factor receptors, but not by progesterone, the natural inducer of cell cycle transition in Xenopus oocytes. Moreover, Gab1 is essential for Tpr-Met–mediated morphological transformation and proliferation of fibroblasts. This study provides the first evidence that Gab1 is a key binding partner of the Met receptor for induction of cell cycle progression, proliferation, and oncogenic morphological transformation. This study identifies Gab1 and its associated signaling partners as potential therapeutic targets to impair proliferation or transformation of cancer cells in human malignancies harboring a deregulated Met receptor. PMID:16775003

Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood.

PubMed

Pennings, Jeroen L A; Jennen, Danyel G J; Nygaard, Unni C; Namork, Ellen; Haug, Line S; van Loveren, Henk; Granum, Berit

2016-01-01

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds that have widespread use in consumer and industrial applications. PFAS are considered environmental pollutants that have various toxic properties, including effects on the immune system. Recent human studies indicate that prenatal exposure to PFAS leads to suppressed immune responses in early childhood. In this study, data from the Norwegian BraMat cohort was used to investigate transcriptomics profiles in neonatal cord blood and their association with maternal PFAS exposure, anti-rubella antibody levels at 3 years of age and the number of common cold episodes until 3 years. Genes associated with PFAS exposure showed enrichment for immunological and developmental functions. The analyses identified a toxicogenomics profile of 52 PFAS exposure-associated genes that were in common with genes associated with rubella titers and/or common cold episodes. This gene set contains several immunomodulatory genes (CYTL1, IL27) as well as other immune-associated genes (e.g. EMR4P, SHC4, ADORA2A). In addition, this study identified PPARD as a PFAS toxicogenomics marker. These markers can serve as the basis for further mechanistic or epidemiological studies. This study provides a transcriptomics connection between prenatal PFAS exposure and impaired immune function in early childhood and supports current views on PPAR- and NF-κB-mediated modes of action. The findings add to the available evidence that PFAS exposure is immunotoxic in humans and support regulatory policies to phase out these substances.

IGF-1 and PDGF-bb Suppress IL-1β-Induced Cartilage Degradation through Down-Regulation of NF-κB Signaling: Involvement of Src/PI-3K/AKT Pathway

PubMed Central

Mobasheri, Ali; Buhrmann, Constanze; Aldinger, Constance; Rad, Jafar Soleimani; Shakibaei, Mehdi

2011-01-01

Objective Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes. Methods Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy. Results Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling. Conclusion The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects. PMID:22194879

Environmental enrichment reduces chronic psychosocial stress-induced anxiety and ethanol-related behaviors in mice.

PubMed

Bahi, Amine

2017-07-03

Previous research from our laboratory has shown that exposure to chronic psychosocial stress increased voluntary ethanol consumption and preference as well as acquisition of ethanol-induced conditioned place preference (CPP) in mice. This study was done to determine whether an enriched environment could have "curative" effects on chronic psychosocial stress-induced ethanol intake and CPP. For this purpose, experimental mice "intruders" were exposed to the chronic subordinate colony (CSC) housing for 19 consecutive days in the presence of an aggressive "resident" mouse. At the end of that period, mice were tested for their anxiety-like behavior using the elevated plus maze (EPM) test then housed in a standard or enriched environment (SE or EE respectively). Anxiety and ethanol-related behaviors were investigated using the open field (OF) test, a standard two-bottle choice drinking paradigm, and the CPP procedure. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to single housed colony (SHC) controls. In addition, CSC exposure increased voluntary ethanol intake and ethanol-CPP. Interestingly, we found that EE significantly and consistently reduced anxiety and ethanol consumption and preference. However, neither tastants' (saccharin and quinine) intake nor blood ethanol metabolism were affected by EE. Finally, and most importantly, EE reduced the acquisition of CPP induced by 1.5g/kg ethanol. Taken together, these results support the hypothesis that EE can reduce voluntary ethanol intake and ethanol-induced conditioned reward and seems to be one of the strategies to reduce the behavioral deficits and the risk of anxiety-induced alcohol abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of the Ras-ERK pathway in mitotic COS7 cells is due to the inability of EGFR/Raf to transduce EGF signaling to downstream proteins.

PubMed

Shi, Huaiping; Zhang, Tianying; Yi, Yongqing; Ma, Yue

2016-06-01

Although previous studies have shown that Ras-ERK signaling in mitosis is closed due to the inhibition of signal transduction, the events involved in the molecular mechanisms are still unclear. In the present study, we investigated the Ras-ERK signaling pathway in mitotic COS7 cells. The results demonstrated that treatment with epidermal growth factor (EGF) failed to increase the endocytosis of EGF-EGFR (EGF receptor) complexes in mitotic COS7 cells, although a large amount of endosomes were found in asynchronous COS7 cells. Clathrin expression levels in mitotic COS7 cells were inhibited whereas caveolin expression levels in mitotic COS7 cells were almost unaffected. Y1068 and Y1086 residues of EGFR in the mitotic COS7 cells were activated. However, Grb2 and Shc in the mitotic COS7 cells did not bind to activated EGFR. Ras activity was inhibited in the mitotic COS7 cells whereas its downstream protein, Raf, was obviously phosphorylated by EGF in mitosis. Treatment with phorbol 12-myristate 13-acetate (PMA) also increased the phosphorylation levels of Raf in the mitotic COS7 cells. Nevertheless, Raf phosphorylation in mitosis was significantly inhibited by AG1478. Lastly, activation of EGF-mediated MEK and ERK in the mitotic COS7 cells was obviously inhibited. In summary, our results suggest that the Ras-ERK pathway is inhibited in mitotic COS7 cells which may be the dual result of the difficulty in the transduction of EGF signaling by EGFR or Raf to downstream proteins.

Membrane estrogen receptors - is it an alternative way of estrogen action?

PubMed

Soltysik, K; Czekaj, P

2013-04-01

The functions of estrogens are relatively well known, however the molecular mechanism of their action is not clear. The classical pathway of estrogen action is dependent on ERα and ERβ which act as transcription factors. The effects of this pathway occur within hours or days. In addition, so-called, non-classical mechanism of steroid action dependent on membrane estrogen receptors (mER) was described. In this mechanism the effects of estrogen action are observed in a much shorter time. Here we review the structure and cellular localization of mER, molecular basis of non-classical mER action, physiological role of mER as well as implications of mER action for cancer biology. Finally, some concerns about the new estrogen receptor - GPER and candidates for estrogen receptors - ER-X and ERx, are briefly discussed. It seems that mER is a complex containing signal proteins (signalosome), as IGF receptor, EGF receptor, Ras protein, adaptor protein Shc, non-receptor kinase c-Src and PI-3K, what rationalizes production of second messengers. Some features of membrane receptors are almost identical if compared to nuclear receptors. Probably, membrane and nuclear estrogen receptors are not separate units, but rather the components of a complex mechanism in which they both cooperate with each other. We conclude that the image of the estrogen receptor as a simple transcription factor is a far-reaching simplification. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors.

STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family.

PubMed Central

Iwama, A; Yamaguchi, N; Suda, T

1996-01-01

STK/RON tyrosine kinase, a member of the hepatocyte growth factor (HGF) receptor family, is a receptor for macrophage-stimulating protein (MSP). To examine the STK/RON signalling pathway, we generated STK/ RON transfectants showing opposite features in growth. STK/RON-expressing Ba/F3 pro-B cells (BaF/STK) exhibited MSP-dependent growth, whereas STK/ RON-expressing mouse erythroleukaemia cells (MEL/ STK) displayed MSP-induced apoptosis. This apoptosis was accompanied by the prolonged activation of c-Jun N-terminal kinase (JNK), which has recently been implicated in the initiation of apoptosis. Co-immunoprecipitation analyses showed that autophosphorylated STK/RON associated with PLC-gamma, P13-kinase, Shc and Grb2 in both transfectants. However, major tyrosine-phosphorylated proteins, p61 and p65, specifically associated with STK/RON in MEL/STK cells. Mutations at two C-terminal tyrosine residues, Y1330 and Y1337, in the counterpart of the multifunctional docking site of the HGF receptor abolished both MSP-induced growth and apoptosis. Analyses of these mutants and in vitro association revealed that signalling proteins including p61 and p65 directly bound to the phosphotyrosines in the multifunctional docking site. These results demonstrate that positive or negative signals toward cell growth are generated through the multifunctional docking site and suggest the involvement of p61 and p65 as well as JNK in apoptosis. Our findings provide the first evidence for apoptosis via a receptor tyrosine kinase. Images PMID:8918464

Budget impact analysis of chronic kidney disease mass screening test in Japan.

PubMed

Kondo, Masahide; Yamagata, Kunihiro; Hoshi, Shu-Ling; Saito, Chie; Asahi, Koichi; Moriyama, Toshiki; Tsuruya, Kazuhiko; Konta, Tsuneo; Fujimoto, Shouichi; Narita, Ichiei; Kimura, Kenjiro; Iseki, Kunitoshi; Watanabe, Tsuyoshi

2014-12-01

Our recently published cost-effectiveness study on chronic kidney disease mass screening test in Japan evaluated the use of dipstick test, serum creatinine (Cr) assay or both in specific health checkup (SHC). Mandating the use of serum Cr assay additionally, or the continuation of current policy mandating dipstick test only was found cost-effective. This study aims to examine the affordability of previously suggested reforms. Budget impact analysis was conducted assuming the economic model would be good for 15 years and applying a population projection. Costs expended by social insurers without discounting were counted as budgets. Annual budget impacts of mass screening compared with do-nothing scenario were calculated as ¥79-¥-1,067 million for dipstick test only, ¥2,505-¥9,235 million for serum Cr assay only and ¥2,517-¥9,251 million for the use of both during a 15-year period. Annual budget impacts associated with the reforms were calculated as ¥975-¥4,129 million for mandating serum Cr assay in addition to the currently used mandatory dipstick test, and ¥963-¥4,113 million for mandating serum Cr assay only and abandoning dipstick test. Estimated values associated with the reform from ¥963-¥4,129 million per year over 15 years are considerable amounts of money under limited resources. The most impressive finding of this study is the decreasing additional expenditures in dipstick test only scenario. This suggests that current policy which mandates dipstick test only would contain medical care expenditure.

Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination

PubMed Central

Lau, Susanna K. P.; Feng, Yun; Chen, Honglin; Luk, Hayes K. H.; Yang, Wei-Hong; Li, Kenneth S. M.; Zhang, Yu-Zhen; Huang, Yi; Song, Zhi-Zhong; Chow, Wang-Ngai; Fan, Rachel Y. Y.; Ahmed, Syed Shakeel; Yeung, Hazel C.; Lam, Carol S. F.; Cai, Jian-Piao; Wong, Samson S. Y.; Chan, Jasper F. W.; Yuen, Kwok-Yung

2015-01-01

ABSTRACT Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. IMPORTANCE Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination. PMID:26269185

Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination.

PubMed

Lau, Susanna K P; Feng, Yun; Chen, Honglin; Luk, Hayes K H; Yang, Wei-Hong; Li, Kenneth S M; Zhang, Yu-Zhen; Huang, Yi; Song, Zhi-Zhong; Chow, Wang-Ngai; Fan, Rachel Y Y; Ahmed, Syed Shakeel; Yeung, Hazel C; Lam, Carol S F; Cai, Jian-Piao; Wong, Samson S Y; Chan, Jasper F W; Yuen, Kwok-Yung; Zhang, Hai-Lin; Woo, Patrick C Y

2015-10-01

Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a.

PubMed

Schiering, Nikolaus; Knapp, Stefan; Marconi, Marina; Flocco, Maria M; Cui, Jean; Perego, Rita; Rusconi, Luisa; Cristiani, Cinzia

2003-10-28

The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique C-terminal tail of c-Met (supersite). There is a strong link between aberrant c-Met activity and oncogenesis, which makes this kinase an important cancer drug target. The furanosylated indolocarbazole K-252a belongs to a family of microbial alkaloids that also includes staurosporine. It was recently shown to be a potent inhibitor of c-Met. Here we report the crystal structures of an unphosphorylated c-Met kinase domain harboring a human cancer mutation and its complex with K-252a at 1.8-A resolution. The structure follows the well established architecture of protein kinases. It adopts a unique, inhibitory conformation of the activation loop, a catalytically noncompetent orientation of helix alphaC, and reveals the complete C-terminal docking site. The first SH2-binding motif (1349YVHV) adopts an extended conformation, whereas the second motif (1356YVNV), a binding site for Grb2-SH2, folds as a type II Beta-turn. The intermediate portion of the supersite (1353NATY) assumes a type I Beta-turn conformation as in an Shc-phosphotyrosine binding domain peptide complex. K-252a is bound in the adenosine pocket with an analogous binding mode to those observed in previously reported structures of protein kinases in complex with staurosporine.

SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.

PubMed

Anafi, M; Kiefer, F; Gish, G D; Mbamalu, G; Iscove, N N; Pawson, T

1997-10-31

Ste20-related protein kinases have been implicated as regulating a range of cellular responses, including stress-activated protein kinase pathways and the control of cytoskeletal architecture. An important issue involves the identities of the upstream signals and regulators that might control the biological functions of mammalian Ste20-related protein kinases. HPK1 is a protein-serine/threonine kinase that possesses a Ste20-like kinase domain, and in transfected cells activates a protein kinase pathway leading to the stress-activated protein kinase SAPK/JNK. Here we have investigated candidate upstream regulators that might interact with HPK1. HPK1 possesses an N-terminal catalytic domain and an extended C-terminal tail with four proline-rich motifs. The SH3 domains of Grb2 bound in vitro to specific proline-rich motifs in the HPK1 tail and functioned synergistically to direct the stable binding of Grb2 to HPK1 in transfected Cos1 cells. Epidermal growth factor (EGF) stimulation did not affect the binding of Grb2 to HPK1 but induced recruitment of the Grb2.HPK1 complex to the autophosphorylated EGF receptor and to the Shc docking protein. Several activated receptor and cytoplasmic tyrosine kinases, including the EGF receptor, stimulated the tyrosine phosphorylation of the HPK1 serine/threonine kinase. These results suggest that HPK1, a mammalian Ste20-related protein-serine/threonine kinase, can potentially associate with protein-tyrosine kinases through interactions mediated by SH2/SH3 adaptors such as Grb2. Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases.

Mitogenic signals and transforming potential of Nyk, a newly identified neural cell adhesion molecule-related receptor tyrosine kinase.

PubMed Central

Ling, L; Kung, H J

1995-01-01

Nyk/Mer is a recently identified receptor tyrosine kinase with neural cell adhesion molecule-like structure (two immunoglobulin G-like domains and two fibronectin III-like domains) in its extracellular region and belongs to the Ufo/Axl family of receptors. The ligand for Nyk/Mer is presently unknown, as are the signal transduction pathways mediated by this receptor. We constructed and expressed a chimeric receptor (Fms-Nyk) composed of the extracellular domain of the human colony-stimulating factor 1 receptor (Fms) and the transmembrane and cytoplasmic domains of human Nyk/Mer in NIH 3T3 fibroblasts in order to investigate the mitogenic signaling and biochemical properties of Nyk/Mer. Colony-stimulating factor 1 stimulation of the Fms-Nyk chimeric receptor in transfected NIH 3T3 fibroblasts leads to a transformed phenotype and generates a proliferative response in the absence of other growth factors. We show that phospholipase C gamma, phosphatidylinositol 3-kinase/p70 S6 kinase, Shc, Grb2, Raf-1, and mitogen-activated protein kinase are downstream components of the Nyk/Mer signal transduction pathways. In addition, Nyk/Mer weakly activates p90rsk, while stress-activated protein kinase, Ras GTPase-activating protein (GAP), and GAP-associated p62 and p190 proteins are not activated or tyrosine phosphorylated by Nyk/Mer. An analysis comparing the Nyk/Mer signal cascade with that of the epidermal growth factor receptor indicates substrate preferences by these two receptors. Our results provide a detailed description of the Nyk/Mer signaling pathways. Given the structural similarity between the Ufo/Axl family receptors, some of the information may also be applied to other members of this receptor tyrosine kinase family. PMID:8524223

Protein-intrinsic and signaling network-based sources of resistance to EGFR- and ErbB family-targeted therapies in head and neck cancer

PubMed Central

Mehra, Ranee; Serebriiskii, Ilya G.; Dunbrack, Roland L.; Robinson, Matthew K.; Burtness, Barbara; Golemis, Erica A.

2011-01-01

Agents targeting EGFR and related ErbB family proteins are valuable therapies for the treatment of many cancers. For some tumor types, including squamous cell carcinomas of the head and neck (SCCHN), antibodies targeting EGFR were the first protein-directed agents to show clinical benefit, and remain a standard component of clinical strategies for management of the disease. Nevertheless, many patients display either intrinsic or acquired resistance to these drugs; hence, major research goals are to better understand the underlying causes of resistance, and to develop new therapeutic strategies that boost the impact of EGFR/ErbB inhibitors. In this review, we first summarize current standard use of EGFR inhibitors in the context of SCCHN, and described new agents targeting EGFR currently moving through pre-clinical and clinical development. We then discuss how changes in other transmembrane receptors, including IGF1R, c-Met, and TGF-β, can confer resistance to EGFR-targeted inhibitors, and discuss new agents targeting these proteins. Moving downstream, we discuss critical EGFR-dependent effectors, including PLC-γ; PI3K and PTEN; SHC, GRB2, and RAS and the STAT proteins, as factors in resistance to EGFR-directed inhibitors and as alternative targets of therapeutic inhibition. We summarize alternative sources of resistance among cellular changes that target EGFR itself, through regulation of ligand availability, post-translational modification of EGFR, availability of EGFR partners for hetero-dimerization and control of EGFR intracellular trafficking for recycling versus degradation. Finally, we discuss new strategies to identify effective therapeutic combinations involving EGFR-targeted inhibitors, in the context of new system level data becoming available for analysis of individual tumors. PMID:21920801

Characterization of In Vivo Resistance to Osimertinib and JNJ-61186372, an EGFR/Met Bispecific Antibody, Reveals Unique and Consensus Mechanisms of Resistance.

PubMed

Emdal, Kristina B; Dittmann, Antje; Reddy, Raven J; Lescarbeau, Rebecca S; Moores, Sheri L; Laquerre, Sylvie; White, Forest M

2017-11-01

Approximately 10% of non-small cell lung cancer (NSCLC) patients in the United States and 40% of NSCLC patients in Asia have activating epidermal growth factor receptor (EGFR) mutations and are eligible to receive targeted anti-EGFR therapy. Despite an extension of life expectancy associated with this treatment, resistance to EGFR tyrosine kinase inhibitors and anti-EGFR antibodies is almost inevitable. To identify additional signaling routes that can be cotargeted to overcome resistance, we quantified tumor-specific molecular changes that govern resistant cancer cell growth and survival. Mass spectrometry-based quantitative proteomics was used to profile in vivo signaling changes in 41 therapy-resistant tumors from four xenograft NSCLC models. We identified unique and tumor-specific tyrosine phosphorylation rewiring in tumors resistant to treatment with the irreversible third-generation EGFR-inhibitor, osimertinib, or the novel dual-targeting EGFR/Met antibody, JNJ-61186372. Tumor-specific increases in tyrosine-phosphorylated peptides from EGFR family members, Shc1 and Gab1 or Src family kinase (SFK) substrates were observed, underscoring a differential ability of tumors to uniquely escape EGFR inhibition. Although most resistant tumors within each treatment group displayed a marked inhibition of EGFR as well as SFK signaling, the combination of EGFR inhibition (osimertinib) and SFK inhibition (saracatinib or dasatinib) led to further decrease in cell growth in vitro This result suggests that residual SFK signaling mediates therapeutic resistance and that elimination of this signal through combination therapy may delay onset of resistance. Overall, analysis of individual resistant tumors captured unique in vivo signaling rewiring that would have been masked by analysis of in vitro cell population averages. Mol Cancer Ther; 16(11); 2572-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Health care seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia

PubMed Central

Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C.; Farag, Tamer H.; Saha, Debasish; Sow, Samba O.; Alonso, Pedro L.; Breiman, Robert F.; Sur, Dipika; Faruque, Abu S. G.; Zaidi, Anita K. M.; Biswas, Kousick; Van Eijk, Anna Maria; Walker, Damian G.; Levine, Myron M.; Kotloff, Karen L.

2013-01-01

We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0–59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings. PMID:23629939

AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

PubMed

Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

2017-04-04

Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

Urokinase-type plasminogen activator receptor (uPAR) ligation induces a raft-localized integrin signaling switch that mediates the hypermotile phenotype of fibrotic fibroblasts.

PubMed

Grove, Lisa M; Southern, Brian D; Jin, Tong H; White, Kimberly E; Paruchuri, Sailaja; Harel, Efrat; Wei, Ying; Rahaman, Shaik O; Gladson, Candece L; Ding, Qiang; Craik, Charles S; Chapman, Harold A; Olman, Mitchell A

2014-05-02

The urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol-linked membrane protein with no cytosolic domain that localizes to lipid raft microdomains. Our laboratory and others have documented that lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) exhibit a hypermotile phenotype. This study was undertaken to elucidate the molecular mechanism whereby uPAR ligation with its cognate ligand, urokinase, induces a motile phenotype in human lung fibroblasts. We found that uPAR ligation with the urokinase receptor binding domain (amino-terminal fragment) leads to enhanced migration of fibroblasts on fibronectin in a protease-independent, lipid raft-dependent manner. Ligation of uPAR with the amino-terminal fragment recruited α5β1 integrin and the acylated form of the Src family kinase, Fyn, to lipid rafts. The biological consequences of this translocation were an increase in fibroblast motility and a switch of the integrin-initiated signal pathway for migration away from the lipid raft-independent focal adhesion kinase pathway and toward a lipid raft-dependent caveolin-Fyn-Shc pathway. Furthermore, an integrin homologous peptide as well as an antibody that competes with β1 for uPAR binding have the ability to block this effect. In addition, its relative insensitivity to cholesterol depletion suggests that the interactions of α5β1 integrin and uPAR drive the translocation of α5β1 integrin-acylated Fyn signaling complexes into lipid rafts upon uPAR ligation through protein-protein interactions. This signal switch is a novel pathway leading to the hypermotile phenotype of IPF patient-derived fibroblasts, seen with uPAR ligation. This uPAR dependent, fibrotic matrix-selective, and profibrotic fibroblast phenotype may be amenable to targeted therapeutics designed to ameliorate IPF.

Daylighting simulation: methods, algorithms, and resources

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

Carroll, William L.

This document presents work conducted as part of Subtask C, ''Daylighting Design Tools'', Subgroup C2, ''New Daylight Algorithms'', of the IEA SHC Task 21 and the ECBCS Program Annex 29 ''Daylight in Buildings''. The search for and collection of daylighting analysis methods and algorithms led to two important observations. First, there is a wide range of needs for different types of methods to produce a complete analysis tool. These include: Geometry; Light modeling; Characterization of the natural illumination resource; Materials and components properties, representations; and Usability issues (interfaces, interoperability, representation of analysis results, etc). Second, very advantageously, there have beenmore » rapid advances in many basic methods in these areas, due to other forces. They are in part driven by: The commercial computer graphics community (commerce, entertainment); The lighting industry; Architectural rendering and visualization for projects; and Academia: Course materials, research. This has led to a very rich set of information resources that have direct applicability to the small daylighting analysis community. Furthermore, much of this information is in fact available online. Because much of the information about methods and algorithms is now online, an innovative reporting strategy was used: the core formats are electronic, and used to produce a printed form only secondarily. The electronic forms include both online WWW pages and a downloadable .PDF file with the same appearance and content. Both electronic forms include live primary and indirect links to actual information sources on the WWW. In most cases, little additional commentary is provided regarding the information links or citations that are provided. This in turn allows the report to be very concise. The links are expected speak for themselves. The report consists of only about 10+ pages, with about 100+ primary links, but with potentially thousands of indirect links. For purposes of the printed version, a list of the links is explicitly provided. This document exists in HTML form at the URL address: http://eande.lbl.gov/Task21/dlalgorithms.html. An equivalent downloadable PDF version, also with live links, at the URL address: http://eande.lbl.gov/Task21/dlalgorithms.pdf. A printed report can be derived directly from either of the electronic versions by simply printing either of them. In addition to the live links in the electronic forms, all report forms, electronic and paper, also have explicitly listed link addresses so that they can be followed up or referenced manually.« less

Peptidyl-prolyl Cis/Trans Isomerase NIMA-interacting 1 Associates with Insulin Receptor Substrate-1 and Enhances Insulin Actions and Adipogenesis

PubMed Central

Nakatsu, Yusuke; Sakoda, Hideyuki; Kushiyama, Akifumi; Zhang, Jun; Ono, Hiraku; Fujishiro, Midori; Kikuchi, Takako; Fukushima, Toshiaki; Yoneda, Masayasu; Ohno, Haruya; Horike, Nanao; Kanna, Machi; Tsuchiya, Yoshihiro; Kamata, Hideaki; Nishimura, Fusanori; Isobe, Toshiaki; Ogihara, Takehide; Katagiri, Hideki; Oka, Yoshitomo; Takahashi, Shin-ichiro; Kurihara, Hiroki; Uchida, Takafumi; Asano, Tomoichiro

2011-01-01

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a unique enzyme that associates with the pSer/Thr-Pro motif and catalyzes cis-trans isomerization. We identified Pin1 in the immunoprecipitates of overexpressed IRS-1 with myc and FLAG tags in mouse livers and confirmed the association between IRS-1 and Pin1 by not only overexpression experiments but also endogenously in the mouse liver. The analysis using deletion- and point-mutated Pin1 and IRS-1 constructs revealed the WW domain located in the N terminus of Pin1 and Ser-434 in the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 to be involved in their association. Subsequently, we investigated the role of Pin1 in IRS-1 mediation of insulin signaling. The overexpression of Pin1 in HepG2 cells markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events: phosphatidylinositol 3-kinase binding with IRS-1 and Akt phosphorylation. In contrast, the treatment of HepG2 cells with Pin1 siRNA or the Pin1 inhibitor Juglone suppressed these events. In good agreement with these in vitro data, Pin1 knock-out mice exhibited impaired insulin signaling with glucose intolerance, whereas adenoviral gene transfer of Pin1 into the ob/ob mouse liver mostly normalized insulin signaling and restored glucose tolerance. In addition, it was also demonstrated that Pin1 plays a critical role in adipose differentiation, making Pin1 knock-out mice resistant to diet-induced obesity. Importantly, Pin1 expression was shown to be up-regulated in accordance with nutrient conditions such as food intake or a high-fat diet. Taken together, these observations indicate that Pin1 binds to IRS-1 and thereby markedly enhances insulin action, essential for adipogenesis. PMID:21454638

Protein S-sulfhydration by hydrogen sulfide in cardiovascular system.

PubMed

Meng, Guoliang; Zhao, Shuang; Xie, Liping; Han, Yi; Ji, Yong

2018-04-01

Hydrogen sulfide (H 2 S), independently of any specific transporters, has a number of biological effects on the cardiovascular system. However, until now, the detailed mechanism of H 2 S was not clear. Recently, a novel post-translational modification induced by H 2 S, named S-sulfhydration, has been proposed. S-sulfhydration is the chemical modification of specific cysteine residues of target proteins by H 2 S. There are several methods for detecting S-sulfhydration, such as the modified biotin switch assay, maleimide assay with fluorescent thiol modifying regents, tag-switch method and mass spectrometry. H 2 S induces S-sulfhydration on enzymes or receptors (such as p66Shc, phospholamban, protein tyrosine phosphatase 1B, mitogen-activated extracellular signal-regulated kinase 1 and ATP synthase subunit α), transcription factors (such as specific protein-1, kelch-like ECH-associating protein 1, NF-κB and interferon regulatory factor-1), and ion channels (such as voltage-activated Ca 2+ channels, transient receptor potential channels and ATP-sensitive K + channels) in the cardiovascular system. Although significant progress has been achieved in delineating the role of protein S-sulfhydration by H 2 S in the cardiovascular system, more proteins with detailed cysteine sites of S-sulfhydration as well as physiological function need to be investigated in further studies. This review mainly summarizes the role and possible mechanism of S-sulfhydration in the cardiovascular system. The S-sulfhydrated proteins may be potential novel targets for therapeutic intervention and drug design in the cardiovascular system, which may accelerate the development and application of H 2 S-related drugs in the future. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc. © 2017 The British Pharmacological Society.

Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor.

PubMed

Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou; Chmura, Aleksei A; Zhu, Guangjian; Epstein, Jonathan H; Mazet, Jonna K; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu-Ji; Luo, Chu-Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Crameri, Gary; Zhang, Shu-Yi; Wang, Lin-Fa; Daszak, Peter; Shi, Zheng-Li

2013-11-28

The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

Gaps along the HIV care continuum: findings among a population seeking sexual health care services in New York City.

PubMed

Pathela, Preeti; Jamison, Kelly; Braunstein, Sarah L; Schillinger, Julia A; Tymejczyk, Olga; Nash, Denis

2018-03-02

Linkage/re-linkage to HIV care for virally unsuppressed persons with new sexually transmitted infections is critical for ending the HIV epidemic. We quantified HIV care continuum gaps, and viral suppression, among HIV-positive patients attending New York City (NYC) sexual health clinics (SHC). 1,649 HIV-positive patients and a 10% sample of 11,954 patients with unknown HIV status on clinic visit date (DOV) were matched against the NYC HIV registry. Using registry diagnosis dates, we categorized matched HIV-positive patients as "new-positives" (newly diagnosed on DOV), "recent-positives (diagnosed ≤90 days before DOV), "prevalent-positives" (diagnosed >90 days before DOV), and "unknown-positives" (previously diagnosed, but status unknown to clinic on DOV). We assessed HIV care continuum outcomes before and after DOV for new-positives, prevalent-positives, and unknown-positives using registry laboratory data. In addition to 1,626 known HIV-positive patients, 5% of the unknown sample (63/1,196) matched to the registry, signifying that about 630 additional HIV-positive patients attended SHCs. Of new-positives, 65% were linked to care after DOV. Of prevalent-positives, 66% were in care on DOV; 43% of the out-of-care were re-linked after DOV. Of unknown-positives, 40% were in care on DOV; 21% of the out-of-care re-linked after DOV. Viral suppression was achieved by: 88% of in-care unknown-positives, 76% in-care prevalent-positives, 50% new-positives, 42% out-of-care prevalent-positives, and 16% out-of-care unknown-positives. Many HIV-positive persons, including those with uncontrolled HIV infection, attend SHCs and potentially contribute to HIV spread. However, HIV status often is not known to staff, resulting in missed linkage/re-linkage to care opportunities. Better outcomes could be facilitated by real-time ascertainment of HIV status and HIV care status.

Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells.

PubMed

Wadsworth, Teri L; Carroll, Julie M; Mallinson, Rebecca A; Roberts, Charles T; Roselli, Charles E

2004-07-01

A common alternative therapy for benign prostatic hyperplasia (BPH) is the extract from the fruit of saw palmetto (SPE). BPH is caused by nonmalignant growth of epithelial and stromal elements of the prostate. IGF action is important for prostate growth and development, and changes in the IGF system have been documented in BPH tissues. The main signaling pathways activated by the binding of IGF-I to the IGF-I receptor (IGF-IR) are the ERK arm of the MAPK cascade and the phosphoinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) cascade. We tested the hypothesis that SPE suppresses growth and induces apoptosis in the P69 prostate epithelial cell line by inhibiting IGF-I signaling. Treatment with 150 microg/ml SPE for 24 h decreased IGF-I-induced proliferation of P69 cells and induced cleavage of the enzyme poly(ADP-ribose)polymerase (PARP), an index of apoptosis. Treatment of serum-starved P69 cells with 150 microg/ml SPE for 6 h reduced IGF-I-induced phosphorylation of Akt (assessed by Western blot) and Akt activity (assessed by an Akt kinase assay). Western blot analysis showed that SPE reduced IGF-I-induced phosphorylation of the adapter protein insulin receptor substrate-1 and decreased downstream effects of Akt activation, including increased cyclin D1 levels and phosphorylation of glycogen synthase kinase-3 and p70(s6k). There was no effect on IGF-I-induced phosphorylation of MAPK, IGF-IR, or Shc. Treatment of starved cells with SPE alone induced phosphorylation the proapoptotic protein JNK. SPE treatment may relieve symptoms of BPH, in part, by inhibiting specific components of the IGF-I signaling pathway and inducing JNK activation, thus mediating antiproliferative and proapoptotic effects on prostate epithelia.

miR-34a-5p Inhibition Alleviates Intestinal Ischemia/Reperfusion-Induced Reactive Oxygen Species Accumulation and Apoptosis via Activation of SIRT1 Signaling.

PubMed

Wang, Guangzhi; Yao, Jihong; Li, Zhenlu; Zu, Guo; Feng, Dongcheng; Shan, Wen; Li, Yang; Hu, Yan; Zhao, Yongfu; Tian, Xiaofeng

2016-06-10

Reactive oxygen species (ROS) generation and massive epithelial apoptosis are critical in the pathogenesis of intestinal ischemia/reperfusion (I/R) injury. We previously found that the Sirtuin 1 (SIRT1)-mediated antioxidant pathway was impaired in the intestine after I/R. Here, we investigate the potential role of SIRT1-targeting microRNAs (miRNAs) in regulating ROS accumulation and apoptosis in intestinal I/R, and the important role SIRT1 involved in. C57BL/6 mice were subjected to intestinal I/R induced by occlusion of the superior mesenteric artery followed by reperfusion. Caco-2 cells were incubated under hypoxia/reoxygenation condition to mimic I/R in vivo. We find that SIRT1 is gradually repressed during the early reperfusion, and that this repression results in intestinal ROS accumulation and apoptosis. Using bioinformatics analysis and real-time PCR, we demonstrate that miR-34a-5p and miR-495-3p are significantly increased among the 41 putative miRNAs that can target SIRT1. Inhibition of miR-34a-5p, but not miR-495-3p, attenuates intestinal I/R injury, as demonstrated by repressing p66shc upregulation, manganese superoxide dismutase repression, and the caspase-3 activation in vitro and in vivo; it further alleviates systemic injury, as demonstrated by reducing inflammatory cytokine release, attenuating lung and liver lesions, and improving survival. Interestingly, SIRT1 plays an indispensable role in the protection afforded by miR-34a-5p inhibition. This study provides the first evidence of miRNAs in regulating oxidative stress and apoptosis in intestinal I/R. miR-34a-5p knockdown attenuates intestinal I/R injury through promoting SIRT1-mediated suppression of epithelial ROS accumulation and apoptosis. This may represent a novel prophylactic approach to intestinal I/R injury. Antioxid. Redox Signal. 24, 961-973.

Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers

PubMed Central

Ghosh, Ritwik; Narasanna, Archana; Wang, Shizhen Emily; Liu, Shuying; Chakrabarty, Anindita; Balko, Justin M.; González-Angulo, Ana María; Mills, Gordon B.; Penuel, Elicia; Winslow, John; Sperinde, Jeff; Dua, Rajiv; Pidaparthi, Sailaja; Mukherjee, Ali; Leitzel, Kim; Kostler, Wolfgang J.; Lipton, Allan; Bates, Michael; Arteaga, Carlos L.

2011-01-01

In breast cancer cells with HER2 gene amplification, HER2 receptors exist on the cell surface as monomers, homodimers and heterodimers with EGFR/HER3. The therapeutic antibody trastuzumab, an approved therapy for HER2+ breast cancer, cannot block ligand-induced HER2 heterodimers, suggesting it cannot effectively inhibit HER2 signaling. Hence, HER2 oligomeric states may predict the odds of a clinical response to trastuzumab in HER2-driven tumors. To test this hypothesis, we generated non-transformed human MCF10A mammary epithelial cells stably expressing a chimeric HER2-FKBP molecule that could be conditionally induced to homodimerize by adding the FKBP ligand AP1510, or instead induced to heterodimerize with EGFR or HER3 by adding the heterodimer ligands EGF/TGFα or heregulin. AP1510, EGF, and heregulin each induced growth of MCF10A cells expressing HER2-FKBP. As expected, trastuzumab inhibited homodimer-mediated but not heterodimer-mediated cell growth. In contrast, the HER2 antibody pertuzumab, which blocks HER2 heterodimerization, inhibited growth induced by heregulin but not AP1510. Lastly, HER2/EGFR tyrosine kinase inhibitor lapatinib blocked both homodimer- and heterodimer-induced growth. AP1510 triggered phosphorylation of Erk1/2 but not AKT, whereas trastuzumab inhibited AP1510-induced Erk1/2 phosphorylation and Shc-HER2 homodimer binding, but not TGFα-induced AKT phosphorylation. Consistent with these observations, high levels of HER2 homodimers correlated with longer time to progression following trastuzumab therapy in a cohort of HER2-overexpressing patients. Together, our findings corroborate the hypothesis that HER2 oligomeric states regulate HER2 signaling, also arguing that trastuzumab sensitivity of homodimers reflects an inability to activate the PI3K/AKT pathway. One of the most important clinical implications of our results is that high levels of HER2 homodimers may predict a positive response to trastuzumab. PMID:21324925

The role of perceived well-being in the family, school and peer context in adolescents' subjective health complaints: evidence from a Greek cross-sectional study.

PubMed

Petanidou, Dimitra; Daskagianni, Evangelie; Dimitrakaki, Christine; Kolaitis, Gerasimos; Tountas, Yannis

2013-11-28

During adolescence children are usually confronted with an expanding social arena. Apart from families, schools and neighbourhoods, peers, classmates, teachers, and other adult figures gain increasing importance for adolescent socio-emotional adjustment. The aim of the present study was to investigate the extent to which Greek adolescents' perceived well-being in three main social contexts (family, school and peers) predicted self-reported Subjective Health Complaints. Questionnaires were administered to a Greek nation-wide, random, school-based sample of children aged 12-18 years in 2003. Data from 1.087 adolescents were analyzed. A hierarchical regression model with Subjective Health Complaints as the outcome variable was employed in order to i) control for the effects of previously well-established demographic factors (sex, age and subjective economic status) and ii) to identify the unique proportion of variance attributed to each context. Bivariate correlations and multicollinearity were also explored. As hypothesized, adolescents' perceived well-being in each of the three social contexts appeared to hold unique proportions of variance in self-reported Subjective Health Complaints, after controlling for the effects of sex, age and subjective economic status. In addition, our final model confirmed that the explained variance in SHC was accumulated from each social context studied. The regression models were statistically significant and explained a total of approximately 24% of the variance in Subjective Health Complaints. Our study delineated the unique and cumulative contributions of adolescents' perceived well-being in the family, school and peer setting in the explanation of Subjective Health Complaints. Apart from families, schools, teachers and peers appear to have a salient role in adolescent psychosomatic adjustment. A thorough understanding of the relationship between adolescents' Subjective Health Complaints and perceived well-being in their social contexts could not only lead to more effective tailored initiatives, but also to promote a multi- and inter-disciplinary culture in adolescent psychosomatic health.

The role of perceived well-being in the family, school and peer context in adolescents’ subjective health complaints: evidence from a Greek cross-sectional study

PubMed Central

2013-01-01

Background During adolescence children are usually confronted with an expanding social arena. Apart from families, schools and neighbourhoods, peers, classmates, teachers, and other adult figures gain increasing importance for adolescent socio-emotional adjustment. The aim of the present study was to investigate the extent to which Greek adolescents’ perceived well-being in three main social contexts (family, school and peers) predicted self-reported Subjective Health Complaints. Methods Questionnaires were administered to a Greek nation-wide, random, school-based sample of children aged 12–18 years in 2003. Data from 1.087 adolescents were analyzed. A hierarchical regression model with Subjective Health Complaints as the outcome variable was employed in order to i) control for the effects of previously well-established demographic factors (sex, age and subjective economic status) and ii) to identify the unique proportion of variance attributed to each context. Bivariate correlations and multicollinearity were also explored. Results As hypothesized, adolescents’ perceived well-being in each of the three social contexts appeared to hold unique proportions of variance in self-reported Subjective Health Complaints, after controlling for the effects of sex, age and subjective economic status. In addition, our final model confirmed that the explained variance in SHC was accumulated from each social context studied. The regression models were statistically significant and explained a total of approximately 24% of the variance in Subjective Health Complaints. Conclusions Our study delineated the unique and cumulative contributions of adolescents’ perceived well-being in the family, school and peer setting in the explanation of Subjective Health Complaints. Apart from families, schools, teachers and peers appear to have a salient role in adolescent psychosomatic adjustment. A thorough understanding of the relationship between adolescents’ Subjective Health Complaints and perceived well-being in their social contexts could not only lead to more effective tailored initiatives, but also to promote a multi- and inter-disciplinary culture in adolescent psychosomatic health. PMID:24283390

The relation between degree-2160 spectral models of Earth's gravitational and topographic potential: a guide on global correlation measures and their dependency on approximation effects

NASA Astrophysics Data System (ADS)

Hirt, Christian; Rexer, Moritz; Claessens, Sten; Rummel, Reiner

2017-10-01

Comparisons between high-degree models of the Earth's topographic and gravitational potential may give insight into the quality and resolution of the source data sets, provide feedback on the modelling techniques and help to better understand the gravity field composition. Degree correlations (cross-correlation coefficients) or reduction rates (quantifying the amount of topographic signal contained in the gravitational potential) are indicators used in a number of contemporary studies. However, depending on the modelling techniques and underlying levels of approximation, the correlation at high degrees may vary significantly, as do the conclusions drawn. The present paper addresses this problem by attempting to provide a guide on global correlation measures with particular emphasis on approximation effects and variants of topographic potential modelling. We investigate and discuss the impact of different effects (e.g., truncation of series expansions of the topographic potential, mass compression, ellipsoidal versus spherical approximation, ellipsoidal harmonic coefficient versus spherical harmonic coefficient (SHC) representation) on correlation measures. Our study demonstrates that the correlation coefficients are realistic only when the model's harmonic coefficients of a given degree are largely independent of the coefficients of other degrees, permitting degree-wise evaluations. This is the case, e.g., when both models are represented in terms of SHCs and spherical approximation (i.e. spherical arrangement of field-generating masses). Alternatively, a representation in ellipsoidal harmonics can be combined with ellipsoidal approximation. The usual ellipsoidal approximation level (i.e. ellipsoidal mass arrangement) is shown to bias correlation coefficients when SHCs are used. Importantly, gravity models from the International Centre for Global Earth Models (ICGEM) are inherently based on this approximation level. A transformation is presented that enables a transformation of ICGEM geopotential models from ellipsoidal to spherical approximation. The transformation is applied to generate a spherical transform of EGM2008 (sphEGM2008) that can meaningfully be correlated degree-wise with the topographic potential. We exploit this new technique and compare a number of models of topographic potential constituents (e.g., potential implied by land topography, ocean water masses) based on the Earth2014 global relief model and a mass-layer forward modelling technique with sphEGM2008. Different to previous findings, our results show very significant short-scale correlation between Earth's gravitational potential and the potential generated by Earth's land topography (correlation +0.92, and 60% of EGM2008 signals are delivered through the forward modelling). Our tests reveal that the potential generated by Earth's oceans water masses is largely unrelated to the geopotential at short scales, suggesting that altimetry-derived gravity and/or bathymetric data sets are significantly underpowered at 5 arc-min scales. We further decompose the topographic potential into the Bouguer shell and terrain correction and show that they are responsible for about 20 and 25% of EGM2008 short-scale signals, respectively. As a general conclusion, the paper shows the importance of using compatible models in topographic/gravitational potential comparisons and recommends the use of SHCs together with spherical approximation or EHCs with ellipsoidal approximation in order to avoid biases in the correlation measures.

Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations

PubMed Central

Yoneyama, Sachiko; Guo, Yiran; Lanktree, Matthew B.; Barnes, Michael R.; Elbers, Clara C.; Karczewski, Konrad J; Padmanabhan, Sandosh; Bauer, Florianne; Baumert, Jens; Beitelshees, Amber; Berenson, Gerald S.; Boer, Jolanda M.A.; Burke, Gregory; Cade, Brian; Chen, Wei; Cooper-Dehoff, Rhonda M.; Gaunt, Tom R.; Gieger, Christian; Gong, Yan; Gorski, Mathias; Heard-Costa, Nancy; Johnson, Toby; Lamonte, Michael J.; Mcdonough, Caitrin; Monda, Keri L.; Onland-Moret, N. Charlotte; Nelson, Christopher P.; O'Connell, Jeffrey R.; Ordovas, Jose; Peter, Inga; Peters, Annette; Shaffer, Jonathan; Shen, Haiqinq; Smith, Erin; Speilotes, Liz; Thomas, Fridtjof; Thorand, Barbara; Monique Verschuren, W. M.; Anand, Sonia S.; Dominiczak, Anna; Davidson, Karina W.; Hegele, Robert A.; Heid, Iris; Hofker, Marten H.; Huggins, Gordon S.; Illig, Thomas; Johnson, Julie A.; Kirkland, Susan; König, Wolfgang; Langaee, Taimour Y.; Mccaffery, Jeanne; Melander, Olle; Mitchell, Braxton D.; Munroe, Patricia; Murray, Sarah S.; Papanicolaou, George; Redline, Susan; Reilly, Muredach; Samani, Nilesh J.; Schork, Nicholas J.; Van Der Schouw, Yvonne T.; Shimbo, Daichi; Shuldiner, Alan R.; Tobin, Martin D.; Wijmenga, Cisca; Yusuf, Salim; Hakonarson, Hakon; Lange, Leslie A.; Demerath, Ellen W; Fox, Caroline S.; North, Kari E; Reiner, Alex P.; Keating, Brendan; Taylor, Kira C.

2014-01-01

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20–80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10−6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β ± SE, 0.048 ± 0.008, P = 7.7 × 10−9) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10−7) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10−6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10−6) and rs1037575-A in ATBDB4 (β = 0.046 ± 0.01, P = 2.2 × 10−6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue. PMID:24345515

Chimeras of the native form or achondroplasia mutant (G375C) of human fibroblast growth factor receptor 3 induce ligand-dependent differentiation of PC12 cells.

PubMed Central

Thompson, L M; Raffioni, S; Wasmuth, J J; Bradshaw, R A

1997-01-01

Mutations in the gene for human fibroblast growth factor receptor 3 (hFGFR3) cause a variety of skeletal dysplasias, including the most common genetic form of dwarfism, achondroplasia (ACH). Evidence indicates that these phenotypes are not due to simple haploinsufficiency of FGFR3 but are more likely related to a role in negatively regulating skeletal growth. The effects of one of these mutations on FGFR3 signaling were examined by constructing chimeric receptors composed of the extracellular domain of human platelet-derived growth factor receptor beta (hPDGFR beta) and the transmembrane and intracellular domains of hFGFR3 or of an ACH (G375C) mutant. Following stable transfection in PC12 cells, which lack platelet-derived growth factor (PDGF) receptors, all clonal cell lines, with either type of chimera, showed strong neurite outgrowth in the presence of PDGF but not in its absence. Antiphosphotyrosine immunoblots showed ligand-dependent autophosphorylation, and both receptor types stimulated strong phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase, an event associated with the differentiative response of these cells. In addition, ligand-dependent phosphorylation of phospholipase Cgamma and Shc was also observed. All of these responses were comparable to those observed from ligand activation, such as by nerve growth factor, of the native PC12 cells used to prepare the stable transfectants. The cells with the chimera bearing the ACH mutation were more rapidly responsive to ligand with less sustained MAPK activation, indicative of a preactivated or primed condition and consistent with the view that these mutations weaken ligand control of FGFR3 function. However, the full effect of the mutation likely depends in part on structural features of the extracellular domain. Although FGFR3 has been suggested to act as a negative regulator of long-bone growth in chrondrocytes, it produces differentiative signals similar to those of FGFR1, to which only positive effects have been ascribed, in PC12 cells. Therefore, its regulatory effects on bone growth likely result from cellular contexts and not the induction of a unique FGFR3 signaling pathway. PMID:9199352

Direct normal irradiance related definitions and applications: The circumsolar issue

DOE PAGES

Blanc, P.; Espinar, B.; Geuder, N.; ...

2014-10-21

The direct irradiance received on a plane normal to the sun, called direct normal irradiance (DNI), is of particular relevance to concentrated solar technologies, including concentrating solar thermal plants and concentrated photovoltaic systems. Following various standards from the International Organization for Standardization (ISO), the DNI definition is related to the irradiance from a small solid angle of the sky, centered on the position of the sun. Half-angle apertures of pyrheliometers measuring DNI have varied over time, up to ≈10°. The current recommendation of the World Meteorological Organization (WMO) for this half-angle is 2.5°. Solar concentrating collectors have an angular acceptancemore » function that can be significantly narrower, especially for technologies with high concentration ratios. The disagreement between the various interpretations of DNI, from the theoretical definition used in atmospheric physics and radiative transfer modeling to practical definitions corresponding to specific measurements or conversion technologies is significant, especially in the presence of cirrus clouds or large concentration of aerosols. Under such sky conditions, the circumsolar radiation—i.e. the diffuse radiation coming from the vicinity of the sun—contributes significantly to the DNI ground measurement, although some concentrating collectors cannot utilize the bulk of it. These issues have been identified in the EU-funded projects MACC-II (Monitoring Atmospheric Composition and Climate-Interim Implementation) and SFERA (Solar Facilities for the European Research Area), and have been discussed within a panel of international experts in the framework of the Solar Heating and Cooling (SHC) program of the International Energy Agency’s (IEA’s) Task 46 “ Solar Resource Assessment and Forecasting”. In accordance with these discussions, the terms of reference related to DNI are specified here. The important role of circumsolar radiation is evidenced, and its potential contribution is evaluated for typical atmospheric conditions. Thus, thorough analysis of performance of concentrating solar systems, it is recommended that, in addition to the conventional DNI related to 2.5° half-angle of today’s pyrheliometers, solar resource data sets also report the sunshape, the circumsolar contribution or the circumsolar ratio (CSR).« less

Effects of Two Types of Melatonin-Loaded Nanocapsules with Distinct Supramolecular Structures: Polymeric (NC) and Lipid-Core Nanocapsules (LNC) on Bovine Embryo Culture Model.

PubMed

Komninou, Eliza Rossi; Remião, Mariana Härter; Lucas, Caroline Gomes; Domingues, William Borges; Basso, Andrea Cristina; Jornada, Denise Soledade; Deschamps, João Carlos; Beck, Ruy Carlos Ruver; Pohlmann, Adriana Raffin; Bordignon, Vilceu; Seixas, Fabiana Kömmling; Campos, Vinicius Farias; Guterres, Silvia Stanisçuaski; Collares, Tiago

2016-01-01

Melatonin has been used as a supplement in culture medium to improve the efficiency of in vitro produced mammalian embryos. Through its ability to scavenge toxic oxygen derivatives and regulate cellular mRNA levels for antioxidant enzymes, this molecule has been shown to play a protective role against damage by free radicals, to which in vitro cultured embryos are exposed during early development. In vivo and in vitro studies have been performed showing that the use of nanocapsules as active substances carriers increases stability, bioavailability and biodistribution of drugs, such as melatonin, to the cells and tissues, improving their antioxidant properties. These properties can be modulated through the manipulation of formula composition, especially in relation to the supramolecular structures of the nanocapsule core and the surface area that greatly influences drug release mechanisms in biological environments. This study aimed to evaluate the effects of two types of melatonin-loaded nanocapsules with distinct supramolecular structures, polymeric (NC) and lipid-core (LNC) nanocapsules, on in vitro cultured bovine embryos. Embryonic development, apoptosis, reactive oxygen species (ROS) production, and mRNA levels of genes involved in cell apoptosis, ROS and cell pluripotency were evaluated after supplementation of culture medium with non-encapsulated melatonin (Mel), melatonin-loaded polymeric nanocapsules (Mel-NC) and melatonin-loaded lipid-core nanocapsules (Mel-LNC) at 10-6, 10-9, and 10-12 M drug concentrations. The highest hatching rate was observed in embryos treated with 10-9 M Mel-LNC. When compared to Mel and Mel-NC treatments at the same concentration (10-9 M), Mel-LNC increased embryo cell number, decreased cell apoptosis and ROS levels, down-regulated mRNA levels of BAX, CASP3, and SHC1 genes, and up-regulated mRNA levels of CAT and SOD2 genes. These findings indicate that nanoencapsulation with LNC increases the protective effects of melatonin against oxidative stress and cell apoptosis during in vitro embryo culture in bovine species.

Exploring molecular complexity with ALMA (EMoCA): Alkanethiols and alkanols in Sagittarius B2(N2)

NASA Astrophysics Data System (ADS)

Müller, Holger S. P.; Belloche, Arnaud; Xu, Li-Hong; Lees, Ronald M.; Garrod, Robin T.; Walters, Adam; van Wijngaarden, Jennifer; Lewen, Frank; Schlemmer, Stephan; Menten, Karl M.

2016-03-01

Context. Over the past five decades, radio astronomy has shown that molecular complexity is a natural outcome of interstellar chemistry, in particular in star forming regions. However, the pathways that lead to the formation of complex molecules are not completely understood and the depth of chemical complexity has not been entirely revealed. In addition, the sulfur chemistry in the dense interstellar medium is not well understood. Aims: We want to know the relative abundances of alkanethiols and alkanols in the Galactic center source Sagittarius B2(N2), the northern hot molecular core in Sgr B2(N), whose relatively small line widths are favorable for studying the molecular complexity in space. Methods: We investigated spectroscopic parameter sets that were able to reproduce published laboratory rotational spectra of ethanethiol and studied effects that modify intensities in the predicted rotational spectrum of ethanol. We used the Atacama Large Millimeter Array (ALMA) in its Cycles 0 and 1 for a spectral line survey of Sagittarius B2(N) between 84 and 114.4 GHz. These data were analyzed by assuming local thermodynamic equilibrium (LTE) for each molecule. Our observations are supplemented by astrochemical modeling; a new network is used that includes reaction pathways for alkanethiols for the first time. Results: We detected methanol and ethanol in their parent 12C species and their isotopologs with one 12C atom substituted by 13C; the latter were detected for the first time unambiguously in the case of ethanol. The 12C/13C ratio is ~25 for both molecules. In addition, we identified CH318 OH with a 16O/18O ratio of ~180 and a 13CH3OH/CH318 OH ratio of ~7.3. Upper limits were derived for the next larger alkanols normal- and iso-propanol. We observed methanethiol, CH3SH, also known as methyl mercaptan, including torsionally excited transitions for the first time. We also identified transitions of ethanethiol (or ethyl mercaptan), though not enough to claim a secure detection in this source. The ratios CH3SH to C2H5SH and C2H5OH to C2H5SH are ≳21 and ≳125, respectively. In the process of our study, we noted severe discrepancies in the intensities of observed and predicted ethanol transitions and propose a change in the relative signs of the dipole moment components. In addition, we determined alternative sets of spectroscopic parameters for ethanethiol. The astrochemical models indicate that substantial quantities of both CH3SH and C2H5SH may be produced on the surfaces of dust grains, to be later released into the gas phase. The modeled ratio CH3SH/C2H5SH = 3.1 is lower than the observed value of ≳21; the model value appears to be affected most by the underprediction of CH3SH relative to CH3OH and C2H5OH, as judged by a very high CH3OH/CH3SH ratio. Conclusions: The column density ratios involving methanol, ethanol, and methanethiol in Sgr B2(N2) are similar to values reported for Orion KL, but those involving ethanethiol are significantly different and suggest that the detection of ethanethiol reported toward Orion KL is uncertain. Our chemical model presently does not permit the prediction of sufficiently accurate column densities of alkanethiols or their ratios among alkanethiols and alkanols. Therefore, additional observational results are required to establish the level of C2H5SH in the dense and warm interstellar medium with certainty.

Meanings, mechanisms, and measures of holistic processing.

PubMed

Richler, Jennifer J; Palmeri, Thomas J; Gauthier, Isabel

2012-01-01

Few concepts are more central to the study of face recognition than holistic processing. Progress toward understanding holistic processing is challenging because the term "holistic" has many meanings, with different researchers addressing different mechanisms and favoring different measures. While in principle the use of different measures should provide converging evidence for a common theoretical construct, convergence has been slow to emerge. We explore why this is the case. One challenge is that "holistic processing" is often used to describe both a theoretical construct and a measured effect, which may not have a one-to-one mapping. Progress requires more than greater precision in terminology regarding different measures of holistic processing or different hypothesized mechanisms of holistic processing. Researchers also need to be explicit about what meaning of holistic processing they are investigating so that it is clear whether different researchers are describing the same phenomenon or not. Face recognition differs from object recognition, and not all meanings of holistic processing are equally suited to help us understand that important difference.

Individual differences in emotion word processing: A diffusion model analysis.

PubMed

Mueller, Christina J; Kuchinke, Lars

2016-06-01

The exploratory study investigated individual differences in implicit processing of emotional words in a lexical decision task. A processing advantage for positive words was observed, and differences between happy and fear-related words in response times were predicted by individual differences in specific variables of emotion processing: Whereas more pronounced goal-directed behavior was related to a specific slowdown in processing of fear-related words, the rate of spontaneous eye blinks (indexing brain dopamine levels) was associated with a processing advantage of happy words. Estimating diffusion model parameters revealed that the drift rate (rate of information accumulation) captures unique variance of processing differences between happy and fear-related words, with highest drift rates observed for happy words. Overall emotion recognition ability predicted individual differences in drift rates between happy and fear-related words. The findings emphasize that a significant amount of variance in emotion processing is explained by individual differences in behavioral data.

Meanings, Mechanisms, and Measures of Holistic Processing

PubMed Central

Richler, Jennifer J.; Palmeri, Thomas J.; Gauthier, Isabel

2012-01-01

Few concepts are more central to the study of face recognition than holistic processing. Progress toward understanding holistic processing is challenging because the term “holistic” has many meanings, with different researchers addressing different mechanisms and favoring different measures. While in principle the use of different measures should provide converging evidence for a common theoretical construct, convergence has been slow to emerge. We explore why this is the case. One challenge is that “holistic processing” is often used to describe both a theoretical construct and a measured effect, which may not have a one-to-one mapping. Progress requires more than greater precision in terminology regarding different measures of holistic processing or different hypothesized mechanisms of holistic processing. Researchers also need to be explicit about what meaning of holistic processing they are investigating so that it is clear whether different researchers are describing the same phenomenon or not. Face recognition differs from object recognition, and not all meanings of holistic processing are equally suited to help us understand that important difference. PMID:23248611

Uncertainty in age-specific harvest estimates and consequences for white-tailed deer management

USGS Publications Warehouse

Collier, B.A.; Krementz, D.G.

2007-01-01

Age structure proportions (proportion of harvested individuals within each age class) are commonly used as support for regulatory restrictions and input for deer population models. Such use requires critical evaluation when harvest regulations force hunters to selectively harvest specific age classes, due to impact on the underlying population age structure. We used a stochastic population simulation model to evaluate the impact of using harvest proportions to evaluate changes in population age structure under a selective harvest management program at two scales. Using harvest proportions to parameterize the age-specific harvest segment of the model for the local scale showed that predictions of post-harvest age structure did not vary dependent upon whether selective harvest criteria were in use or not. At the county scale, yearling frequency in the post-harvest population increased, but model predictions indicated that post-harvest population size of 2.5 years old males would decline below levels found before implementation of the antler restriction, reducing the number of individuals recruited into older age classes. Across the range of age-specific harvest rates modeled, our simulation predicted that underestimation of age-specific harvest rates has considerable influence on predictions of post-harvest population age structure. We found that the consequence of uncertainty in harvest rates corresponds to uncertainty in predictions of residual population structure, and this correspondence is proportional to scale. Our simulations also indicate that regardless of use of harvest proportions or harvest rates, at either the local or county scale the modeled SHC had a high probability (>0.60 and >0.75, respectively) of eliminating recruitment into >2.5 years old age classes. Although frequently used to increase population age structure, our modeling indicated that selective harvest criteria can decrease or eliminate the number of white-tailed deer recruited into older age classes. Thus, we suggest that using harvest proportions for management planning and evaluation should be viewed with caution. In addition, we recommend that managers focus more attention on estimation of age-specific harvest rates, and modeling approaches which combine harvest rates with information from harvested individuals to further increase their ability to effectively manage deer populations under selective harvest programs. ?? 2006 Elsevier B.V. All rights reserved.

Feature genes in metastatic breast cancer identified by MetaDE and SVM classifier methods.

PubMed

Tuo, Youlin; An, Ning; Zhang, Ming

2018-03-01

The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of P<0.05. Based on the protein‑protein interactions (PPIs) in the Biological General Repository for Interaction Datasets, Human Protein Reference Database and Biomolecular Interaction Network Database, the PPI network of the feature genes was constructed. The feature genes identified by topological characteristics were then used for support vector machine (SVM) classifier training and verification. The accuracy of the SVM classifier was then evaluated using another independent dataset from The Cancer Genome Atlas database. Finally, function and pathway enrichment analyses for genes in the SVM classifier were performed. A total of 541 feature genes were identified between metastatic and non‑metastatic samples. The top 10 genes with the highest betweenness centrality values in the PPI network of feature genes were Nuclear RNA Export Factor 1, cyclin‑dependent kinase 2 (CDK2), myelocytomatosis proto‑oncogene protein (MYC), Cullin 5, SHC Adaptor Protein 1, Clathrin heavy chain, Nucleolin, WD repeat domain 1, proteasome 26S subunit non‑ATPase 2 and telomeric repeat binding factor 2. The cyclin‑dependent kinase inhibitor 1A (CDKN1A), E2F transcription factor 1 (E2F1), and MYC interacted with CDK2. The SVM classifier constructed by the top 30 feature genes was able to distinguish metastatic samples from non‑metastatic samples [correct rate, specificity, positive predictive value and negative predictive value >0.89; sensitivity >0.84; area under the receiver operating characteristic curve (AUROC) >0.96]. The verification of the SVM classifier in an independent dataset (35 metastatic samples and 143 non‑metastatic samples) revealed an accuracy of 94.38% and AUROC of 0.958. Cell cycle associated functions and pathways were the most significant terms of the 30 feature genes. A SVM classifier was constructed to assess the possibility of breast cancer metastasis, which presented high accuracy in several independent datasets. CDK2, CDKN1A, E2F1 and MYC were indicated as the potential feature genes in metastatic breast cancer.

Emotional Picture and Word Processing: An fMRI Study on Effects of Stimulus Complexity

PubMed Central

Schlochtermeier, Lorna H.; Kuchinke, Lars; Pehrs, Corinna; Urton, Karolina; Kappelhoff, Hermann; Jacobs, Arthur M.

2013-01-01

Neuroscientific investigations regarding aspects of emotional experiences usually focus on one stimulus modality (e.g., pictorial or verbal). Similarities and differences in the processing between the different modalities have rarely been studied directly. The comparison of verbal and pictorial emotional stimuli often reveals a processing advantage of emotional pictures in terms of larger or more pronounced emotion effects evoked by pictorial stimuli. In this study, we examined whether this picture advantage refers to general processing differences or whether it might partly be attributed to differences in visual complexity between pictures and words. We first developed a new stimulus database comprising valence and arousal ratings for more than 200 concrete objects representable in different modalities including different levels of complexity: words, phrases, pictograms, and photographs. Using fMRI we then studied the neural correlates of the processing of these emotional stimuli in a valence judgment task, in which the stimulus material was controlled for differences in emotional arousal. No superiority for the pictorial stimuli was found in terms of emotional information processing with differences between modalities being revealed mainly in perceptual processing regions. While visual complexity might partly account for previously found differences in emotional stimulus processing, the main existing processing differences are probably due to enhanced processing in modality specific perceptual regions. We would suggest that both pictures and words elicit emotional responses with no general superiority for either stimulus modality, while emotional responses to pictures are modulated by perceptual stimulus features, such as picture complexity. PMID:23409009

Mechanism of case processing in the brain: an fMRI study.

PubMed

Yokoyama, Satoru; Maki, Hideki; Hashimoto, Yosuke; Toma, Masahiko; Kawashima, Ryuta

2012-01-01

In sentence comprehension research, the case system, which is one of the subsystems of the language processing system, has been assumed to play a crucial role in signifying relationships in sentences between noun phrases (NPs) and other elements, such as verbs, prepositions, nouns, and tense. However, so far, less attention has been paid to the question of how cases are processed in our brain. To this end, the current study used fMRI and scanned the brain activity of 15 native English speakers during an English-case processing task. The results showed that, while the processing of all cases activates the left inferior frontal gyrus and posterior part of the middle temporal gyrus, genitive case processing activates these two regions more than nominative and accusative case processing. Since the effect of the difference in behavioral performance among these three cases is excluded from brain activation data, the observed different brain activations would be due to the different processing patterns among the cases, indicating that cases are processed differently in our brains. The different brain activations between genitive case processing and nominative/accusative case processing may be due to the difference in structural complexity between them.

Global-local processing relates to spatial and verbal processing: implications for sex differences in cognition.

PubMed

Pletzer, Belinda; Scheuringer, Andrea; Scherndl, Thomas

2017-09-05

Sex differences have been reported for a variety of cognitive tasks and related to the use of different cognitive processing styles in men and women. It was recently argued that these processing styles share some characteristics across tasks, i.e. male approaches are oriented towards holistic stimulus aspects and female approaches are oriented towards stimulus details. In that respect, sex-dependent cognitive processing styles share similarities with attentional global-local processing. A direct relationship between cognitive processing and global-local processing has however not been previously established. In the present study, 49 men and 44 women completed a Navon paradigm and a Kimchi Palmer task as well as a navigation task and a verbal fluency task with the goal to relate the global advantage (GA) effect as a measure of global processing to holistic processing styles in both tasks. Indeed participants with larger GA effects displayed more holistic processing during spatial navigation and phonemic fluency. However, the relationship to cognitive processing styles was modulated by the specific condition of the Navon paradigm, as well as the sex of participants. Thus, different types of global-local processing play different roles for cognitive processing in men and women.

What is the source of cultural differences? -- Examining the influence of thinking style on the attribution process.

PubMed

Jen, Chun-Hui; Lien, Yunn-Wen

2010-02-01

The present research is intended to find out whether individuals with analytic or holistic thought have different attribution processes. Cross-cultural research has suggested that East Asians, who tend to have a holistic thought pattern, differ in cognitive process from Westerners, who tend to engage in analytic thought. However, studies that found cultural difference in attribution process may have non-equivalence problems that make it hard to interpret the causal relationship between thinking style and attribution process. The present research extends this by measuring participants' thinking style within a single culture in order to ensure equivalence on potentially confounding variables such as prior knowledge and cognitive capacity. Two experiments demonstrate that both types of thinkers have identical attribution processes and suggest different thinking styles might relate to different tendencies toward situational information, but not to the attribution process itself. Copyright 2009 Elsevier B.V. All rights reserved.

Serial Comparison Processes and Sex Differences in Clerical Speed.

ERIC Educational Resources Information Center

Majeres, Raymond L.

1988-01-01

Three experiments were conducted with 91 male and 91 female university students to assess sex differences in performance on speeded matching tests and theory on same-different judgments. Results are interpreted via the dual-process hypothesis of same-difference judgments with sex differences explained in terms of serial comparison processes rather…

Exploring business process modelling paradigms and design-time to run-time transitions

NASA Astrophysics Data System (ADS)

Caron, Filip; Vanthienen, Jan

2016-09-01

The business process management literature describes a multitude of approaches (e.g. imperative, declarative or event-driven) that each result in a different mix of process flexibility, compliance, effectiveness and efficiency. Although the use of a single approach over the process lifecycle is often assumed, transitions between approaches at different phases in the process lifecycle may also be considered. This article explores several business process strategies by analysing the approaches at different phases in the process lifecycle as well as the various transitions.

The role of rational and experiential processing in influencing the framing effect.

PubMed

Stark, Emily; Baldwin, Austin S; Hertel, Andrew W; Rothman, Alexander J

2017-01-01

Research on individual differences and the framing effect has focused primarily on how variability in rational processing influences choice. However, we propose that measuring only rational processing presents an incomplete picture of how participants are responding to framed options, as orthogonal individual differences in experiential processing might be relevant. In two studies, we utilize the Rational Experiential Inventory, which captures individual differences in rational and experiential processing, to investigate how both processing types influence decisions. Our results show that differences in experiential processing, but not rational processing, moderated the effect of frame on choice. We suggest that future research should more closely examine the influence of experiential processing on making decisions, to gain a broader understanding of the conditions that contribute to the framing effect.

[Influence of different processing methods and mature stages on 3,29-dibenzoyl rarounitriol of Trichosanthes kirilowii seeds].

PubMed

Liu, Jin-Na; Xie, Xiao-Liang; Yang, Tai-Xin; Zhang, Cun-Li; Jia, Dong-Sheng; Liu, Ming; Wen, Chun-Xiu

2014-04-01

To study the different mature stages and the best processing methods on the quality of Trichosanthes kirilowii seeds. The content of 3,29-dibenzoyl rarounitriol in Trichosanthes kirilowii seeds was determined by HPLC. The sample of different mature stages such as immature, near mature and fully mature and processed by different methods were studied. Fully mature Trichosanthes kirilowii seeds were better than the immatured, and the best processing method was dried under 60degrees C, the content of 3,29-dibenzoyl rarounitriol reached up to 131.63microlg/mL. Different processing methods and different mature stages had a significant influence on the quality of Trichosanthes kirilowii seeds.

Cell-assembly coding in several memory processes.

PubMed

Sakurai, Y

1998-01-01

The present paper discusses why the cell assembly, i.e., an ensemble population of neurons with flexible functional connections, is a tenable view of the basic code for information processes in the brain. The main properties indicating the reality of cell-assembly coding are neurons overlaps among different assemblies and connection dynamics within and among the assemblies. The former can be detected as multiple functions of individual neurons in processing different kinds of information. Individual neurons appear to be involved in multiple information processes. The latter can be detected as changes of functional synaptic connections in processing different kinds of information. Correlations of activity among some of the recorded neurons appear to change in multiple information processes. Recent experiments have compared several different memory processes (tasks) and detected these two main properties, indicating cell-assembly coding of memory in the working brain. The first experiment compared different types of processing of identical stimuli, i.e., working memory and reference memory of auditory stimuli. The second experiment compared identical processes of different types of stimuli, i.e., discriminations of simple auditory, simple visual, and configural auditory-visual stimuli. The third experiment compared identical processes of different types of stimuli with or without temporal processing of stimuli, i.e., discriminations of elemental auditory, configural auditory-visual, and sequential auditory-visual stimuli. Some possible features of the cell-assembly coding, especially "dual coding" by individual neurons and cell assemblies, are discussed for future experimental approaches. Copyright 1998 Academic Press.

Behavioral and Physiological Findings of Gender Differences in Global-Local Visual Processing

ERIC Educational Resources Information Center

Roalf, David; Lowery, Natasha; Turetsky, Bruce I.

2006-01-01

Hemispheric asymmetries in global-local visual processing are well-established, as are gender differences in cognition. Although hemispheric asymmetry presumably underlies gender differences in cognition, the literature on gender differences in global-local processing is sparse. We employed event related brain potential (ERP) recordings during…

The Influence of Different Processing Methods on Component Content of Sophora japonica

NASA Astrophysics Data System (ADS)

Ji, Y. B.; Zhu, H. J.; Xin, G. S.; Wei, C.

2017-12-01

The purpose of this experiment is to understand the effect of different processing methods on the content of active ingredients in Sophora japonica, and to determine the content of rutin and quercetin in Sophora japonica under different processing methods by UV spectrophotometry of the content determination. So as to compare the effect of different processing methods on the active ingredient content of Sophora japonica. Experiments can be seen in the rutin content: Fried Sophora japonica>Vinegar sunburn Sophora> Health products Sophora japonica> Charred sophora flower, Vinegar sunburn Sophora and Fried Sophora japonica difference is not obvious; Quercetin content: Charred sophora flower> Fried Sophora japonica> Vinegar sunburn Sophora>Health products Sophora japonica. It is proved that there are some differences in the content of active ingredients in Sophora japonica in different processing methods. The content of rutin increased with the increase of the processing temperature, but the content decreased after a certain temperature; Quercetin content will increase gradually with time.

Potential of different mechanical and thermal treatments to control off-flavour generation in broccoli puree.

PubMed

Koutidou, Maria; Grauwet, Tara; Van Loey, Ann; Acharya, Parag

2017-02-15

The aim of this study was scientifically investigate the impact of the sequence of different thermo-mechanical treatments on the volatile profile of differently processed broccoli puree, and to investigate if any relationship persists between detected off-flavour changes and microstructural changes as a function of selected process conditions. Comparison of the headspace GC-MS fingerprinting of the differently processed broccoli purees revealed that an adequate combination of processing steps allows to reduce the level of off-flavour volatiles. Moreover, applying mechanical processing before or after the thermal processing at 90°C determines the pattern of broccoli tissue disruption, resulting into different microstructures and various enzymatic reactions inducing volatile generation. These results may aid the identification of optimal process conditions generating a reduced level of off-flavour in processed broccoli. In this way, broccoli can be incorporated as a food ingredient into mixed food products with limited implications on sensorial consumer acceptance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Component processes underlying future thinking.

PubMed

D'Argembeau, Arnaud; Ortoleva, Claudia; Jumentier, Sabrina; Van der Linden, Martial

2010-09-01

This study sought to investigate the component processes underlying the ability to imagine future events, using an individual-differences approach. Participants completed several tasks assessing different aspects of future thinking (i.e., fluency, specificity, amount of episodic details, phenomenology) and were also assessed with tasks and questionnaires measuring various component processes that have been hypothesized to support future thinking (i.e., executive processes, visual-spatial processing, relational memory processing, self-consciousness, and time perspective). The main results showed that executive processes were correlated with various measures of future thinking, whereas visual-spatial processing abilities and time perspective were specifically related to the number of sensory descriptions reported when specific future events were imagined. Furthermore, individual differences in self-consciousness predicted the subjective feeling of experiencing the imagined future events. These results suggest that future thinking involves a collection of processes that are related to different facets of future-event representation.

What can individual differences reveal about face processing?

PubMed Central

Yovel, Galit; Wilmer, Jeremy B.; Duchaine, Brad

2014-01-01

Faces are probably the most widely studied visual stimulus. Most research on face processing has used a group-mean approach that averages behavioral or neural responses to faces across individuals and treats variance between individuals as noise. However, individual differences in face processing can provide valuable information that complements and extends findings from group-mean studies. Here we demonstrate that studies employing an individual differences approach—examining associations and dissociations across individuals—can answer fundamental questions about the way face processing operates. In particular these studies allow us to associate and dissociate the mechanisms involved in face processing, tie behavioral face processing mechanisms to neural mechanisms, link face processing to broader capacities and quantify developmental influences on face processing. The individual differences approach we illustrate here is a powerful method that should be further explored within the domain of face processing as well as fruitfully applied across the cognitive sciences. PMID:25191241

Effect of heat treatment On Microstructure of steel AISI 01 Tools

NASA Astrophysics Data System (ADS)

Dyanasari Sebayang, Melya; Yudo, Sesmaro Max; Silitonga, Charlie

2018-03-01

This study discusses the influence of quenching, normalizing, and annealing to changes in hardness, tensile, and microstructure of materials tool steel AISI 01 after the material undergo heat treatment process. This heat treatment process includes an initial warming of 600° C and a 5-minute detention time, followed by heating to an austenisation temperature of 850°C. After that a different cooling process, including annealing process, normalizing and quenching oil SAE 40. Tests performed include tensile, hard, and microstructure with shooting using SEM (Scanning Electron Microscope). This is done to see the effect of different heat treatment and cooling process. The result of this research is difference of tensile test value, hard, and micro structure from influence of difference of each process. The quenching process obtains the highest tensile and hard values followed by the normalizing process, annealing, and the lowest is in the starting material, this is because the initial material does not undergo heat treatment process. The resulting microstructure is pearlit and cementite, the difference seen from the shape and size of the grains. The larger the grain size, the greater the hardness.

Developmental trajectories of children's symbolic numerical magnitude processing skills and associated cognitive competencies.

PubMed

Vanbinst, Kiran; Ceulemans, Eva; Peters, Lien; Ghesquière, Pol; De Smedt, Bert

2018-02-01

Although symbolic numerical magnitude processing skills are key for learning arithmetic, their developmental trajectories remain unknown. Therefore, we delineated during the first 3years of primary education (5-8years of age) groups with distinguishable developmental trajectories of symbolic numerical magnitude processing skills using a model-based clustering approach. Three clusters were identified and were labeled as inaccurate, accurate but slow, and accurate and fast. The clusters did not differ in age, sex, socioeconomic status, or IQ. We also tested whether these clusters differed in domain-specific (nonsymbolic magnitude processing and digit identification) and domain-general (visuospatial short-term memory, verbal working memory, and processing speed) cognitive competencies that might contribute to children's ability to (efficiently) process the numerical meaning of Arabic numerical symbols. We observed minor differences between clusters in these cognitive competencies except for verbal working memory for which no differences were observed. Follow-up analyses further revealed that the above-mentioned cognitive competencies did not merely account for the cluster differences in children's development of symbolic numerical magnitude processing skills, suggesting that other factors account for these individual differences. On the other hand, the three trajectories of symbolic numerical magnitude processing revealed remarkable and stable differences in children's arithmetic fact retrieval, which stresses the importance of symbolic numerical magnitude processing for learning arithmetic. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Chemical Constituents in Scrophulariae Radix Processed by Different Methods based on UFLC-MS Combined with Multivariate Statistical Analysis.

PubMed

Wang, Shengnan; Hua, Yujiao; Zou, Lisi; Liu, Xunhong; Yan, Ying; Zhao, Hui; Luo, Yiyuan; Liu, Juanxiu

2018-02-01

Scrophulariae Radix is one of the most popular traditional Chinese medicines (TCMs). Primary processing of Scrophulariae Radix is an important link which closely related to the quality of products in this TCM. The aim of this study is to explore the influence of different processing methods on chemical constituents in Scrophulariae Radix. The difference of chemical constituents in Scrophulariae Radix processed by different methods was analyzed by using ultra fast liquid chromatography-triple quadrupole-time of flight mass spectrometry coupled with principal component analysis and orthogonal partial least squares discriminant analysis. Furthermore, the contents of 12 index differential constituents in Scrophulariae Radix processed by different methods were simultaneously determined by using ultra fast liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry. Gray relational analysis was performed to evaluate the different processed samples according to the contents of 12 constituents. All of the results demonstrated that the quality of Scrophulariae Radix processed by "sweating" method was better. This study will provide the basic information for revealing the change law of chemical constituents in Scrophulariae Radix processed by different methods and facilitating selection of the suitable processing method of this TCM. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence of Different Container Closure Systems and Capping Process Parameters on Product Quality and Container Closure Integrity (CCI) in GMP Drug Product Manufacturing.

PubMed

Mathaes, Roman; Mahler, Hanns-Christian; Roggo, Yves; Huwyler, Joerg; Eder, Juergen; Fritsch, Kamila; Posset, Tobias; Mohl, Silke; Streubel, Alexander

2016-01-01

Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters (e.g., pre-compression force, capping plate height, turntable rotating speed) contribute to the final residual seal force of a sealed container closure system and its relation to container closure integrity and other drug product quality parameters. Stopper compression measured by computer tomography correlated to residual seal force measurements.In our studies, we used different container closure system configurations from different good manufacturing practice drug product fill & finish facilities to investigate the influence of differences in primary packaging, that is, vial size and rubber stopper design on the capping process and the capped drug product. In addition, we compared two large-scale good manufacturing practice manufacturing capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force.The capping plate to plunger distance had a major influence on the obtained residual seal force values of a sealed vial, whereas the capping pre-compression force and the turntable rotation speed showed only a minor influence on the residual seal force of a sealed vial. Capping process parameters could not easily be transferred from capping equipment of different manufacturers. However, the residual seal force tester did provide a valuable tool to compare capping performance of different capping equipment. No vial showed any leakage greater than 10(-8)mbar L/s as measured by a helium mass spectrometry system, suggesting that container closure integrity was warranted in the residual seal force range tested for the tested container closure systems. Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in the literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters contribute to the final capping result.In this study, we used different container closure system configurations from different good manufacturing process drug product fill & finish facilities to investigate the influence of the vial size and the rubber stopper design on the capping process. In addition, we compared two examples of large-scale good manufacturing process capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force. © PDA, Inc. 2016.

Design, scale-up, Six Sigma in processing different feedstocks in a fixed bed downdraft biomass gasifier

NASA Astrophysics Data System (ADS)

Boravelli, Sai Chandra Teja

This thesis mainly focuses on design and process development of a downdraft biomass gasification processes. The objective is to develop a gasifier and process of gasification for a continuous steady state process. A lab scale downdraft gasifier was designed to develop the process and obtain optimum operating procedure. Sustainable and dependable sources such as biomass are potential sources of renewable energy and have a reasonable motivation to be used in developing a small scale energy production plant for countries such as Canada where wood stocks are more reliable sources than fossil fuels. This thesis addresses the process of thermal conversion of biomass gasification process in a downdraft reactor. Downdraft biomass gasifiers are relatively cheap and easy to operate because of their design. We constructed a simple biomass gasifier to study the steady state process for different sizes of the reactor. The experimental part of this investigation look at how operating conditions such as feed rate, air flow, the length of the bed, the vibration of the reactor, height and density of syngas flame in combustion flare changes for different sizes of the reactor. These experimental results also compare the trends of tar, char and syngas production for wood pellets in a steady state process. This study also includes biomass gasification process for different wood feedstocks. It compares how shape, size and moisture content of different feedstocks makes a difference in operating conditions for the gasification process. For this, Six Sigma DMAIC techniques were used to analyze and understand how each feedstock makes a significant impact on the process.

Holistic processing, contact, and the other-race effect in face recognition.

PubMed

Zhao, Mintao; Hayward, William G; Bülthoff, Isabelle

2014-12-01

Face recognition, holistic processing, and processing of configural and featural facial information are known to be influenced by face race, with better performance for own- than other-race faces. However, whether these various other-race effects (OREs) arise from the same underlying mechanisms or from different processes remains unclear. The present study addressed this question by measuring the OREs in a set of face recognition tasks, and testing whether these OREs are correlated with each other. Participants performed different tasks probing (1) face recognition, (2) holistic processing, (3) processing of configural information, and (4) processing of featural information for both own- and other-race faces. Their contact with other-race people was also assessed with a questionnaire. The results show significant OREs in tasks testing face memory and processing of configural information, but not in tasks testing either holistic processing or processing of featural information. Importantly, there was no cross-task correlation between any of the measured OREs. Moreover, the level of other-race contact predicted only the OREs obtained in tasks testing face memory and processing of configural information. These results indicate that these various cross-race differences originate from different aspects of face processing, in contrary to the view that the ORE in face recognition is due to cross-race differences in terms of holistic processing. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analysis of fingerprints features of infrared spectra of various processed products of Radix Aconiti kusnezoffii

NASA Astrophysics Data System (ADS)

Tu-ya; Yang, Ping; Sun, Su-qin; Zhou, Qun; Bao, Xiao-hua; Noda, Isao

2010-06-01

Fourier-transform infrared spectroscopy (FTIR) and two-dimensional correlation infrared spectroscopy (2D-IR)) are employed to analyze various processed products and ether extracts of Radix Aconiti kusnezoffii. There is a resemblance among the spectra of different processed products. The major difference lies in the absorption peak at 1641 cm -1 in the IR spectra, which reflects the transformation of raw aconite to the processed products. There are distinctive differences in the absorption peaks in the range of 1800-1500 cm -1 in the second derivative spectra, which has better resolution, of different processed products. 2D-IR spectra, which elevate the resolution further, can present even more differences among the products in the range of 1800-800 cm -1. Analysis of ether extracts of various processed products proves that there are alcohols, esters, carboxylic acids or ketones in all of them. However, their contents in different samples have obvious differences. With the advantages of high resolution, high-speed and convenience, IR can quickly and precisely distinguish various processed products of Radix A. kusnezoffii, and can be applied to predict the tendency of transformation of the complicated chemical mixture systems under heat perturbation.

Commercially sterilized mussel meats (Mytilus chilensis): a study on process yield.

PubMed

Almonacid, S; Bustamante, J; Simpson, R; Urtubia, A; Pinto, M; Teixeira, A

2012-06-01

The processing steps most responsible for yield loss in the manufacture of canned mussel meats are the thermal treatments of precooking to remove meats from shells, and thermal processing (retorting) to render the final canned product commercially sterile for long-term shelf stability. The objective of this study was to investigate and evaluate the impact of different combinations of process variables on the ultimate drained weight in the final mussel product (Mytilu chilensis), while verifying that any differences found were statistically and economically significant. The process variables selected for this study were precooking time, brine salt concentration, and retort temperature. Results indicated 2 combinations of process variables producing the widest difference in final drained weight, designated best combination and worst combination with 35% and 29% yield, respectively. Significance of this difference was determined by employing a Bootstrap methodology, which assumes an empirical distribution of statistical error. A difference of nearly 6 percentage points in total yield was found. This represents a 20% increase in annual sales from the same quantity of raw material, in addition to increase in yield, the conditions for the best process included a retort process time 65% shorter than that for the worst process, this difference in yield could have significant economic impact, important to the mussel canning industry. © 2012 Institute of Food Technologists®

The Relationship between Sensory Processing Difficulties and Leisure Activity Preference of Children with Different Types of ADHD

ERIC Educational Resources Information Center

Engel-Yeger, Batya; Ziv-On, Daniella

2011-01-01

Sensory processing difficulties (SPD) are prevalent among children with ADHD. Yet, the question whether different SPD characterize children with different types of ADHD has not received enough attention in the literature. The current study characterized sensory processing difficulties (SPD) of children with different types of ADHD and explored the…

Cleanliness of Ti-bearing Al-killed ultra-low-carbon steel during different heating processes

NASA Astrophysics Data System (ADS)

Guo, Jian-long; Bao, Yan-ping; Wang, Min

2017-12-01

During the production of Ti-bearing Al-killed ultra-low-carbon (ULC) steel, two different heating processes were used when the converter tapping temperature or the molten steel temperature in the Ruhrstahl-Heraeus (RH) process was low: heating by Al addition during the RH decarburization process and final deoxidation at the end of the RH decarburization process (process-I), and increasing the oxygen content at the end of RH decarburization, heating and final deoxidation by one-time Al addition (process-II). Temperature increases of 10°C by different processes were studied; the results showed that the two heating processes could achieve the same heating effect. The T.[O] content in the slab and the refining process was better controlled by process-I than by process-II. Statistical analysis of inclusions showed that the numbers of inclusions in the slab obtained by process-I were substantially less than those in the slab obtained by process-II. For process-I, the Al2O3 inclusions produced by Al added to induce heating were substantially removed at the end of decarburization. The amounts of inclusions were substantially greater for process-II than for process-I at different refining stages because of the higher dissolved oxygen concentration in process-II. Industrial test results showed that process-I was more beneficial for improving the cleanliness of molten steel.

Levels of integration in cognitive control and sequence processing in the prefrontal cortex.

PubMed

Bahlmann, Jörg; Korb, Franziska M; Gratton, Caterina; Friederici, Angela D

2012-01-01

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex.

Levels of Integration in Cognitive Control and Sequence Processing in the Prefrontal Cortex

PubMed Central

Bahlmann, Jörg; Korb, Franziska M.; Gratton, Caterina; Friederici, Angela D.

2012-01-01

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex. PMID:22952762

Remote Sensing Image Quality Assessment Experiment with Post-Processing

NASA Astrophysics Data System (ADS)

Jiang, W.; Chen, S.; Wang, X.; Huang, Q.; Shi, H.; Man, Y.

2018-04-01

This paper briefly describes the post-processing influence assessment experiment, the experiment includes three steps: the physical simulation, image processing, and image quality assessment. The physical simulation models sampled imaging system in laboratory, the imaging system parameters are tested, the digital image serving as image processing input are produced by this imaging system with the same imaging system parameters. The gathered optical sampled images with the tested imaging parameters are processed by 3 digital image processes, including calibration pre-processing, lossy compression with different compression ratio and image post-processing with different core. Image quality assessment method used is just noticeable difference (JND) subject assessment based on ISO20462, through subject assessment of the gathered and processing images, the influence of different imaging parameters and post-processing to image quality can be found. The six JND subject assessment experimental data can be validated each other. Main conclusions include: image post-processing can improve image quality; image post-processing can improve image quality even with lossy compression, image quality with higher compression ratio improves less than lower ratio; with our image post-processing method, image quality is better, when camera MTF being within a small range.

Examining Candidate Information Search Processes: The Impact of Processing Goals and Sophistication.

ERIC Educational Resources Information Center

Huang, Li-Ning

2000-01-01

Investigates how 4 different information-processing goals, varying on the dimensions of effortful versus effortless and impression-driven versus non-impression-driven processing, and individual difference in political sophistication affect the depth at which undergraduate students process candidate information and their decision-making strategies.…

Beyond the initial 140 ms, lexical decision and reading aloud are different tasks: An ERP study with topographic analysis.

PubMed

Mahé, Gwendoline; Zesiger, Pascal; Laganaro, Marina

2015-11-15

Most of our knowledge on the time-course of the mechanisms involved in reading derived from electrophysiological studies is based on lexical decision tasks. By contrast, very few ERP studies investigated the processes involved in reading aloud. It has been suggested that the lexical decision task provides a good index of the processes occurring during reading aloud, with only late processing differences related to task response modalities. However, some behavioral studies reported different sensitivity to psycholinguistic factors between the two tasks, suggesting that print processing could differ at earlier processing stages. The aim of the present study was thus to carry out an ERP comparison between lexical decision and reading aloud in order to determine when print processing differs between these two tasks. Twenty native French speakers performed a lexical decision task and a reading aloud task with the same written stimuli. Results revealed different electrophysiological patterns on both waveform amplitudes and global topography between lexical decision and reading aloud from about 140 ms after stimulus presentation for both words and pseudowords, i.e., as early as the N170 component. These results suggest that only very early, low-level visual processes are common to the two tasks which differ in core processes. Taken together, our main finding questions the use of the lexical decision task as an appropriate paradigm to investigate reading processes and warns against generalizing its results to word reading. Copyright © 2015 Elsevier Inc. All rights reserved.

Individual differences in working memory capacity and dual-process theories of the mind.

PubMed

Barrett, Lisa Feldman; Tugade, Michele M; Engle, Randall W

2004-07-01

Dual-process theories of the mind are ubiquitous in psychology. A central principle of these theories is that behavior is determined by the interplay of automatic and controlled processing. In this article, the authors examine individual differences in the capacity to control attention as a major contributor to differences in working memory capacity (WMC). The authors discuss the enormous implications of this individual difference for a host of dual-process theories in social, personality, cognitive, and clinical psychology. In addition, the authors propose several new areas of investigation that derive directly from applying the concept of WMC to dual-process theories of the mind.

Individual Differences in Working Memory Capacity and Dual-Process Theories of the Mind

PubMed Central

Barrett, Lisa Feldman; Tugade, Michele M.; Engle, Randall W.

2005-01-01

Dual-process theories of the mind are ubiquitous in psychology. A central principle of these theories is that behavior is determined by the interplay of automatic and controlled processing. In this article, the authors examine individual differences in the capacity to control attention as a major contributor to differences in working memory capacity (WMC). The authors discuss the enormous implications of this individual difference for a host of dual-process theories in social, personality, cognitive, and clinical psychology. In addition, the authors propose several new areas of investigation that derive directly from applying the concept of WMC to dual-process theories of the mind. PMID:15250813

Logical-rules and the classification of integral dimensions: individual differences in the processing of arbitrary dimensions

PubMed Central

Blunden, Anthea G.; Wang, Tony; Griffiths, David W.; Little, Daniel R.

2015-01-01

A variety of converging operations demonstrate key differences between separable dimensions, which can be analyzed independently, and integral dimensions, which are processed in a non-analytic fashion. A recent investigation of response time distributions, applying a set of logical rule-based models, demonstrated that integral dimensions are pooled into a single coactive processing channel, in contrast to separable dimensions, which are processed in multiple, independent processing channels. This paper examines the claim that arbitrary dimensions created by factorially morphing four faces are processed in an integral manner. In two experiments, 16 participants completed a categorization task in which either upright or inverted morph stimuli were classified in a speeded fashion. Analyses focused on contrasting different assumptions about the psychological representation of the stimuli, perceptual and decisional separability, and the processing architecture. We report consistent individual differences which demonstrate a mixture of some observers who demonstrate coactive processing with other observers who process the dimensions in a parallel self-terminating manner. PMID:25620941

Simulation analysis of resource flexibility on healthcare processes

PubMed Central

Simwita, Yusta W; Helgheim, Berit I

2016-01-01

Purpose This paper uses discrete event simulation to explore the best resource flexibility scenario and examine the effect of implementing resource flexibility on different stages of patient treatment process. Specifically we investigate the effect of resource flexibility on patient waiting time and throughput in an orthopedic care process. We further seek to explore on how implementation of resource flexibility on patient treatment processes affects patient access to healthcare services. We focus on two resources, namely, orthopedic surgeon and operating room. Methods The observational approach was used to collect process data. The developed model was validated by comparing the simulation output with actual patient data collected from the studied orthopedic care process. We developed different scenarios to identify the best resource flexibility scenario and explore the effect of resource flexibility on patient waiting time, throughput, and future changes in demand. The developed scenarios focused on creating flexibility on service capacity of this care process by altering the amount of additional human resource capacity at different stages of patient care process and extending the use of operating room capacity. Results The study found that resource flexibility can improve responsiveness to patient demand in the treatment process. Testing different scenarios showed that the introduction of resource flexibility reduces patient waiting time and improves throughput. The simulation results show that patient access to health services can be improved by implementing resource flexibility at different stages of the patient treatment process. Conclusion This study contributes to the current health care literature by explaining how implementing resource flexibility at different stages of patient care processes can improve ability to respond to increasing patients demands. This study was limited to a single patient process; studies focusing on additional processes are recommended. PMID:27785046

Simulation analysis of resource flexibility on healthcare processes.

PubMed

Simwita, Yusta W; Helgheim, Berit I

2016-01-01

This paper uses discrete event simulation to explore the best resource flexibility scenario and examine the effect of implementing resource flexibility on different stages of patient treatment process. Specifically we investigate the effect of resource flexibility on patient waiting time and throughput in an orthopedic care process. We further seek to explore on how implementation of resource flexibility on patient treatment processes affects patient access to healthcare services. We focus on two resources, namely, orthopedic surgeon and operating room. The observational approach was used to collect process data. The developed model was validated by comparing the simulation output with actual patient data collected from the studied orthopedic care process. We developed different scenarios to identify the best resource flexibility scenario and explore the effect of resource flexibility on patient waiting time, throughput, and future changes in demand. The developed scenarios focused on creating flexibility on service capacity of this care process by altering the amount of additional human resource capacity at different stages of patient care process and extending the use of operating room capacity. The study found that resource flexibility can improve responsiveness to patient demand in the treatment process. Testing different scenarios showed that the introduction of resource flexibility reduces patient waiting time and improves throughput. The simulation results show that patient access to health services can be improved by implementing resource flexibility at different stages of the patient treatment process. This study contributes to the current health care literature by explaining how implementing resource flexibility at different stages of patient care processes can improve ability to respond to increasing patients demands. This study was limited to a single patient process; studies focusing on additional processes are recommended.

Deeper Processing for Better EFL Reading Comprehension.

ERIC Educational Resources Information Center

Oded, Brenda; Walters, Joel

2001-01-01

Investigates the extent to which tasks involving processing differences in English-as-a-foreign-language (EFL) reading result in differences in performance on comprehension. Processing differences were created by the assignment of two tasks--writing a text summary and listing the examples in the text. (Author/VWL)

Information processing speed and attention in multiple sclerosis: Reconsidering the Attention Network Test (ANT).

PubMed

Roth, Alexandra K; Denney, Douglas R; Lynch, Sharon G

2015-01-01

The Attention Network Test (ANT) assesses attention in terms of discrepancies between response times to items that differ in the burden they place on some facet of attention. However, simple arithmetic difference scores commonly used to capture these discrepancies fail to provide adequate control for information processing speed, leading to distorted findings when patient and control groups differ markedly in the speed with which they process and respond to stimulus information. This study examined attention networks in patients with multiple sclerosis (MS) using simple difference scores, proportional scores, and residualized scores that control for processing speed through statistical regression. Patients with relapsing-remitting (N = 20) or secondary progressive (N = 20) MS and healthy controls (N = 40) of similar age, education, and gender completed the ANT. Substantial differences between patients and controls were found on all measures of processing speed. Patients exhibited difficulties in the executive control network, but only when difference scores were considered. When deficits in information processing speed were adequately controlled using proportional or residualized score, deficits in the alerting network emerged. The effect sizes for these deficits were notably smaller than those for overall information processing speed and were also limited to patients with secondary progressive MS. Deficits in processing speed are more prominent in MS than those involving attention, and when the former are properly accounted for, differences in the latter are confined to the alerting network.

Reasoning strategies modulate gender differences in emotion processing.

PubMed

Markovits, Henry; Trémolière, Bastien; Blanchette, Isabelle

2018-01-01

The dual strategy model of reasoning has proposed that people's reasoning can be understood asa combination of two different ways of processing information related to problem premises: a counterexample strategy that examines information for explicit potential counterexamples and a statistical strategy that uses associative access to generate a likelihood estimate of putative conclusions. Previous studies have examined this model in the context of basic conditional reasoning tasks. However, the information processing distinction that underlies the dual strategy model can be seen asa basic description of differences in reasoning (similar to that described by many general dual process models of reasoning). In two studies, we examine how these differences in reasoning strategy may relate to processing very different information, specifically we focus on previously observed gender differences in processing negative emotions. Study 1 examined the intensity of emotional reactions to a film clip inducing primarily negative emotions. Study 2 examined the speed at which participants determine the emotional valence of sequences of negative images. In both studies, no gender differences were observed among participants using a counterexample strategy. Among participants using a statistical strategy, females produce significantly stronger emotional reactions than males (in Study 1) and were faster to recognize the valence of negative images than were males (in Study 2). Results show that the processing distinction underlying the dual strategy model of reasoning generalizes to the processing of emotions. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of simulated mechanical recycling processes on the structure and properties of poly(lactic acid).

PubMed

Beltrán, F R; Lorenzo, V; Acosta, J; de la Orden, M U; Martínez Urreaga, J

2018-06-15

The aim of this work is to study the effects of different simulated mechanical recycling processes on the structure and properties of PLA. A commercial grade of PLA was melt compounded and compression molded, then subjected to two different recycling processes. The first recycling process consisted of an accelerated ageing and a second melt processing step, while the other recycling process included an accelerated ageing, a demanding washing process and a second melt processing step. The intrinsic viscosity measurements indicate that both recycling processes produce a degradation in PLA, which is more pronounced in the sample subjected to the washing process. DSC results suggest an increase in the mobility of the polymer chains in the recycled materials; however the degree of crystallinity of PLA seems unchanged. The optical, mechanical and gas barrier properties of PLA do not seem to be largely affected by the degradation suffered during the different recycling processes. These results suggest that, despite the degradation of PLA, the impact of the different simulated mechanical recycling processes on the final properties is limited. Thus, the potential use of recycled PLA in packaging applications is not jeopardized. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trait-Treatment Interactions (TTI), Cognitive Processes and Research on Communication Media.

ERIC Educational Resources Information Center

Di Vesta, Francis J.

The Trait Treatment Interaction (TTI) Process approach is particularly adapted to the study of information-processing by receivers of information presented in the media. Differences in people's experiences do lead to different cognitive structures. Different people use the same machinery of perceiving, coding, storing, and retrieving. Neverthless,…

Individual Differences in Depth and Breadth of Processing.

ERIC Educational Resources Information Center

Schmeck, Ronald R.; McCarthy, Patricia

Memory has been defined as traces left behind by past information processing. One approach to the study of everyday memory is to isolate reliable differences between individuals in the ways in which they process information when preparing for test events. The Inventory of Learning Processes, consisting of four scales, i.e., Deep Processing,…

Sex differences in processing printed advertisements.

PubMed

Putrevu, Sanjay

2004-06-01

The success of using biological sex to divide or segment markets requires a thorough understanding of how men and women process and respond to advertisements and other persuasive communications. Toward this end, this research (N=64; 32 men and 32 women) studied how college-age men and women respond to printed advertisements. There were no differences between the sexes in recall and recognition of claims in advertisements, but men and women generated different types of message relevant thoughts-women generated more category thoughts and men generated more attribute thoughts, suggesting that, while women and men might not differ in the depth of processing, they might use different processing styles.

Spatial Mechanisms within the Dorsal Visual Pathway Contribute to the Configural Processing of Faces.

PubMed

Zachariou, Valentinos; Nikas, Christine V; Safiullah, Zaid N; Gotts, Stephen J; Ungerleider, Leslie G

2017-08-01

Human face recognition is often attributed to configural processing; namely, processing the spatial relationships among the features of a face. If configural processing depends on fine-grained spatial information, do visuospatial mechanisms within the dorsal visual pathway contribute to this process? We explored this question in human adults using functional magnetic resonance imaging and transcranial magnetic stimulation (TMS) in a same-different face detection task. Within localized, spatial-processing regions of the posterior parietal cortex, configural face differences led to significantly stronger activation compared to featural face differences, and the magnitude of this activation correlated with behavioral performance. In addition, detection of configural relative to featural face differences led to significantly stronger functional connectivity between the right FFA and the spatial processing regions of the dorsal stream, whereas detection of featural relative to configural face differences led to stronger functional connectivity between the right FFA and left FFA. Critically, TMS centered on these parietal regions impaired performance on configural but not featural face difference detections. We conclude that spatial mechanisms within the dorsal visual pathway contribute to the configural processing of facial features and, more broadly, that the dorsal stream may contribute to the veridical perception of faces. Published by Oxford University Press 2016.

[Preliminary study on correlation between diversity of soluble proteins and producing area of Cordyceps sinensis].

PubMed

Ren, Yan; Qiu, Yi; Wan, De-Guang; Lu, Xian-Ming; Guo, Jin-Lin

2013-05-01

To analyze the content and type of soluble proteins in Cordyceps sinensis from different producing areas and processed with different methods with bradford method and 2-DE technology, in order to discover significant differences in soluble proteins in C. sinensis processed with different methods and from different producing areas. The preliminary study indicated that the content and diversity of soluble proteins were related to producing areas and processing methods to some extent.

Age differences in dual information-processing modes: implications for cancer decision making.

PubMed

Peters, Ellen; Diefenbach, Michael A; Hess, Thomas M; Västfjäll, Daniel

2008-12-15

Age differences in affective/experiential and deliberative processes have important theoretical implications for cancer decision making, as cancer is often a disease of older adulthood. The authors examined evidence for adult age differences in affective and deliberative information processes, reviewed the sparse evidence about age differences in decision making, and introduced how dual process theories and their findings might be applied to cancer decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age, particularly when decisions are unfamiliar and the information is numeric. However, age-related adaptive processes, including an increased focus on emotional goals and greater experience, can influence decision making and potentially offset age-related declines. A better understanding of the mechanisms that underlie cancer decision processes in our aging population should ultimately allow us to help older adults to better help themselves.

Age Differences in Dual Information-Processing Modes: Implications for Cancer Decision Making

PubMed Central

Peters, Ellen; Diefenbach, Michael A.; Hess, Thomas M.; Västfjäll, Daniel

2008-01-01

Age differences in affective/experiential and deliberative processes have important theoretical implications for cancer decision making as cancer is often a disease of older adulthood. We examine evidence for adult age differences in affective and deliberative information processes, review the sparse evidence about age differences in decision making and introduce how dual process theories and their findings might be applied to cancer decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age, particularly when decisions are unfamiliar and the information is numeric. However, age-related adaptive processes, including an increased focus on emotional goals and greater experience, can influence decision making and potentially offset age-related declines. A better understanding of the mechanisms that underlie cancer decision processes in our aging population should ultimately allow us to help older adults to better help themselves. PMID:19058148

Clock-like mutational processes in human somatic cells

DOE PAGES

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; ...

2015-11-09

During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutationmore » rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This paper provides the first survey of clock-like mutational processes operating in human somatic cells.« less

Clock-like mutational processes in human somatic cells

PubMed Central

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; Sale, Julian E.; Campbell, Peter J.; Nik-Zainal, Serena; Stratton, Michael R.

2016-01-01

During the course of a lifetime somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell’s genome. Some processes generate mutations throughout life at a constant rate in all individuals and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operative in human somatic cells. PMID:26551669

Neuro-cognitive foundations of word stress processing - evidence from fMRI

PubMed Central

2011-01-01

Background To date, the neural correlates of phonological word stress processing are largely unknown. Methods In the present study, we investigated the processing of word stress and vowel quality using an identity matching task with pseudowords. Results In line with previous studies, a bilateral fronto-temporal network comprising the superior temporal gyri extending into the sulci as well as the inferior frontal gyri was observed for word stress processing. Moreover, we found differences in the superior temporal gyrus and the superior temporal sulcus, bilaterally, for the processing of different stress patterns. For vowel quality processing, our data reveal a substantial contribution of the left intraparietal cortex. All activations were modulated by task demands, yielding different patterns for same and different pairs of stimuli. Conclusions Our results suggest that the left superior temporal gyrus represents a basic system underlying stress processing to which additional structures including the homologous cortex site are recruited with increasing difficulty. PMID:21575209

Ethnic Differences in Family Stress Processes Among African-Americans and Black Caribbeans

PubMed Central

Caldwell, Cleopatra Howard; Bellatorre, Anna; Jackson, James S.

2012-01-01

Several theories of stress exposure, including the stress process and the family stress model for economically disadvantaged families, suggest that family processes work similarly across race/ethnic groups. Much of this research, however, treats African-Americans as a monolithic group and ignores potential differences in family stress processes within race that may emerge across ethnic groups. This study examines whether family stress processes differ intraracially in African-American and Black Caribbean families. Using data from the National Survey of American Life, a national representative data set of African-American and Black Caribbean families, we assess the extent to which parents’ stress appraisals and psychological adjustment are related to their adolescent children’s stress appraisals, psychological adjustment, and depressive symptoms. Our study illustrates that stress processes differ by ethnicity and operate through varying pathways in African-American and Black Caribbean families. The implications of intraracial variations in stress processes are discussed. PMID:23349643

Continuous counter-current chromatography for capture and polishing steps in biopharmaceutical production.

PubMed

Steinebach, Fabian; Müller-Späth, Thomas; Morbidelli, Massimo

2016-09-01

The economic advantages of continuous processing of biopharmaceuticals, which include smaller equipment and faster, efficient processes, have increased interest in this technology over the past decade. Continuous processes can also improve quality assurance and enable greater controllability, consistent with the quality initiatives of the FDA. Here, we discuss different continuous multi-column chromatography processes. Differences in the capture and polishing steps result in two different types of continuous processes that employ counter-current column movement. Continuous-capture processes are associated with increased productivity per cycle and decreased buffer consumption, whereas the typical purity-yield trade-off of classical batch chromatography can be surmounted by continuous processes for polishing applications. In the context of continuous manufacturing, different but complementary chromatographic columns or devices are typically combined to improve overall process performance and avoid unnecessary product storage. In the following, these various processes, their performances compared with batch processing and resulting product quality are discussed based on a review of the literature. Based on various examples of applications, primarily monoclonal antibody production processes, conclusions are drawn about the future of these continuous-manufacturing technologies. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neural differences in the processing of true and false sentences: insights into the nature of 'truth' in language comprehension.

PubMed

Marques, J Frederico; Canessa, Nicola; Cappa, Stefano

2009-06-01

The inquiry on the nature of truth in language comprehension has a long history of opposite perspectives. These perspectives either consider that there are qualitative differences in the processing of true and false statements, or that these processes are fundamentally the same and only differ in quantitative terms. The present study evaluated the processing nature of true and false statements in terms of patterns of brain activity using event-related functional-Magnetic-Resonance-Imaging (fMRI). We show that when true and false concept-feature statements are controlled for relation strength/ambiguity, their processing is associated to qualitatively different processes. Verifying true statements activates the left inferior parietal cortex and the caudate nucleus, a neural correlate compatible with an extended search and matching process for particular stored information. In contrast, verifying false statements activates the fronto-polar cortex and is compatible with a reasoning process of finding and evaluating a contradiction between the sentence information and stored knowledge.

Recognizing the bank robber and spotting the difference: emotional state and global vs. local attentional set.

PubMed

Pacheco-Unguetti, Antonia Pilar; Acosta, Alberto; Lupiáñez, Juan

2014-01-01

In two experiments (161 participants in total), we investigated how current mood influences processing styles (global vs. local). Participants watched a video of a bank robbery before receiving a positive, negative or neutral induction, and they performed two tasks: a face-recognition task about the bank robber as global processing measure, and a spot-the-difference task using neutral pictures (Experiment-1) or emotional scenes (Experiment-2) as local processing measure. Results showed that positive mood induction favoured a global processing style, enhancing participants' ability to correctly identify a face even when they watched the video before the mood-induction. This shows that, besides influencing encoding processes, mood state can be also related to retrieval processes. On the contrary, negative mood induction enhanced a local processing style, making easier and faster the detection of differences between nearly identical pictures, independently of their valence. This dissociation supports the hypothesis that current mood modulates processing through activation of different cognitive styles.

Processing Intransitive Verbs: How Do Children Differ from Adults?

ERIC Educational Resources Information Center

Koring, Loes; Mak, Pim; Mulders, Iris; Reuland, Eric

2018-01-01

Previous studies have demonstrated that, for adults, differences between unaccusative verbs (e.g., "fall") and unergative verbs (e.g., "dance") lead to a difference in processing. However, so far we don't know whether this effect shows up in children's processing of these verbs as well. This study measures children's processing…

Age-related differences in reaction time task performance in young children.

PubMed

Kiselev, Sergey; Espy, Kimberly Andrews; Sheffield, Tiffany

2009-02-01

Performance of reaction time (RT) tasks was investigated in young children and adults to test the hypothesis that age-related differences in processing speed supersede a "global" mechanism and are a function of specific differences in task demands and processing requirements. The sample consisted of 54 4-year-olds, 53 5-year-olds, 59 6-year-olds, and 35 adults from Russia. Using the regression approach pioneered by Brinley and the transformation method proposed by Madden and colleagues and Ridderinkhoff and van der Molen, age-related differences in processing speed differed among RT tasks with varying demands. In particular, RTs differed between children and adults on tasks that required response suppression, discrimination of color or spatial orientation, reversal of contingencies of previously learned stimulus-response rules, and greater stimulus-response complexity. Relative costs of these RT task differences were larger than predicted by the global difference hypothesis except for response suppression. Among young children, age-related differences larger than predicted by the global difference hypothesis were evident when tasks required color or spatial orientation discrimination and stimulus-response rule complexity, but not for response suppression or reversal of stimulus-response contingencies. Process-specific, age-related differences in processing speed that support heterochronicity of brain development during childhood were revealed.

New analyses of the National Institute of Mental Health Treatment of Depression Collaborative Research Program: do different treatments reflect different processes?

PubMed

Herbert, Gregory L; Callahan, Jennifer; Ruggero, Camilo J; Murrell, Amy R

2013-01-01

To determine whether or not different therapies have distinct patterns of change, it is useful to investigate not only the end result of psychotherapy (outcome) but also the processes by which outcomes are attained. The present study subjected data from the National Institute of Mental Health Treatment of Depression Collaborative Research Program to survival analyses to examine whether the process of psychotherapy, as conceptualized by the phase model, differed between psychotherapy treatment approaches. Few differences in terms of progression through phases of psychotherapy were identified between cognitive behavior therapy and interpersonal therapy. Additionally, results indicate that phases of psychotherapy may not represent discrete, sequentially invariant processes.

10 CFR 74.59 - Quality assurance and accounting requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... occurs which has the potential to affect a measurement result or when program data, generated by tests.../receiver differences, inventory differences, and process differences. (4) Utilize the data generated during... difference (SEID) and the standard error of the process differences. Calibration and measurement error data...

10 CFR 74.59 - Quality assurance and accounting requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... occurs which has the potential to affect a measurement result or when program data, generated by tests.../receiver differences, inventory differences, and process differences. (4) Utilize the data generated during... difference (SEID) and the standard error of the process differences. Calibration and measurement error data...

Effects of drying process on the physicochemical properties of nopal cladodes at different maturity stages.

PubMed

Contreras-Padilla, Margarita; Gutiérrez-Cortez, Elsa; Valderrama-Bravo, María Del Carmen; Rojas-Molina, Isela; Espinosa-Arbeláez, Diego Germán; Suárez-Vargas, Raúl; Rodríguez-García, Mario Enrique

2012-03-01

Chemical proximate analysis was done in order to determine the changes of nutritional characteristics of nopal powders from three different maturity stages 50, 100, and 150 days and obtained by three different drying processes: freeze dried, forced air oven, and tunnel. Results indicate that nopal powder obtained by the process of freeze dried retains higher contents of protein, soluble fiber, and fat than the other two processes. Also, freeze dried process had less effect on color hue variable. No changes were observed in insoluble fiber content, chroma and lightness with the three different drying processes. Furthermore, the soluble fibers decreased with the age of nopal while insoluble fibers and ash content shows an opposite trend. In addition, the luminosity and hue values did not show differences among the maturity stages studied. The high content of dietary fibers of nopal pad powder could to be an interesting source of these important components for human diets and also could be used in food, cosmetics and pharmaceutical industry.

Dietary self-control is related to the speed with which health and taste attributes are processed

PubMed Central

Sullivan, Nicolette; Hutcherson, Cendri; Harris, Alison; Rangel, Antonio

2015-01-01

We propose that self-control failures, and variation across individuals in self-control abilities, are partly due to differences in the speed with which the decision-making circuitry processes basic attributes like taste, versus more abstract attributes such as health. We test these hypotheses by combining a dietary choice task with a novel form of mouse tracking that allows us to pinpoint when different attributes are being integrated into the choice process with millisecond temporal resolution. We find that, on average, taste attributes are processed about 195 ms earlier than health attributes during the choice process. We also find that 13 - 39% of observed individual differences in self-control ability can be explained by differences in the relative speed with which taste and health attributes are processed. PMID:25515527

Dietary self-control is related to the speed with which attributes of healthfulness and tastiness are processed.

PubMed

Sullivan, Nicolette; Hutcherson, Cendri; Harris, Alison; Rangel, Antonio

2015-02-01

We propose that self-control failures, and variation across individuals in self-control abilities, are partly due to differences in the speed with which the decision-making circuitry processes basic attributes, such as tastiness, versus more abstract attributes, such as healthfulness. We tested these hypotheses by combining a dietary-choice task with a novel form of mouse tracking that allowed us to pinpoint when different attributes were being integrated into the choice process with temporal resolution at the millisecond level. We found that, on average, tastiness was processed about 195 ms earlier than healthfulness during the choice process. We also found that 13% to 39% of observed individual differences in self-control ability could be explained by differences in the relative speed with which tastiness and healthfulness were processed. © The Author(s) 2014.

Plastic deformation history in infeed rotary swaging process

NASA Astrophysics Data System (ADS)

Liu, Yang; Herrmann, Marius; Schenck, Christian; Kuhfuss, Bernd

2017-10-01

In bulk forming processes, the net shape of a final product is achieved by plastic deformation as the material flows from the initial shape to the final shape of the workpiece. The material flow during the process is an important issue for its relationship with forging force, heat generation, microstructure transformation and energy consumption. Hence, the final properties of the product are directly influenced. Former researches showed that the material flow in the rotary swaging process is affected by different processing parameters like die angle, feeding velocity and friction condition. Thus, a profound knowledge of detailed material flow during the process is essential for a better understanding of the process. By using FEM, the material flow was investigated by the history of the plastic strain (PEEQ) development. In this study a 2D-axisymmetric model was built by using ABAQUS explicit. Both aluminum alloy (3.3206) and steel (1.0308) are studied with different feeding velocities and coefficients of friction. To achieve the development of PEEQ in different areas, the workpiece was divided into radial layers. The PEEQ history of each layer was tracked during the quasi-static forming process. Based on that, the plastic strain rate (PSR) was calculated and examined in a single stroke of the process. In that way, the material flow in different layers is presented and the material flow on the surface differs from that in the center, just the first 1/4 radial area from the surface is sensitive to different friction conditions.

Information Processing Capabilities in Performers Differing in Levels of Motor Skill

DTIC Science & Technology

1979-01-01

F. I. 1. , ’ Lockhart , R. S. Levels of* processing : A framework for memory research. Journal of Verbal Learning and Verbal Behavior, 1972, 11, 671-684...ARI TECHNICAL REPORT LEVEr.79iA4 Information Processing Capabilities in Performers Differing In Levels of 00 Motor Skill ,4 by Robert N. Singer... PROCESSING CAPABILITIES IN PERFORMERS DIFFERING IN LEVELS OF MOTOR SKILL INTRODUCTION In the human behaving systems model developed by Singer, Gerson, and

Adult Age Differences in Dual Information Processes: Implications for the Role of Affective and Deliberative Processes in Older Adults' Decision Making.

PubMed

Peters, Ellen; Hess, Thomas M; Västfjäll, Daniel; Auman, Corinne

2007-03-01

Age differences in affective/experiential and deliberative processes have important theoretical implications for judgment and decision theory and important pragmatic implications for older-adult decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age. However, age-related adaptive processes, including motivated selectivity in the use of deliberative capacity, an increased focus on emotional goals, and greater experience, predict better or worse decisions for older adults depending on the situation. The aim of the current review is to examine adult age differences in affective and deliberative information processes in order to understand their potential impact on judgments and decisions. We review evidence for the role of these dual processes in judgment and decision making and then review two representative life-span perspectives (based on aging-related changes to cognitive or motivational processes) on the interplay between these processes. We present relevant predictions for older-adult decisions and make note of contradictions and gaps that currently exist in the literature. Finally, we review the sparse evidence about age differences in decision making and how theories and findings regarding dual processes could be applied to decision theory and decision aiding. In particular, we focus on prospect theory (Kahneman & Tversky, 1979) and how prospect theory and theories regarding age differences in information processing can inform one another. © 2007 Association for Psychological Science.

The contribution of local and transport processes to phytoplankton biomass variability over different timescales in the Upper James River, Virginia

NASA Astrophysics Data System (ADS)

Qin, Qubin; Shen, Jian

2017-09-01

Although both local processes (photosynthesis, respiration, grazing, and settling), and transport processes (advective transport and diffusive transport) significantly affect local phytoplankton dynamics, it is difficult to separate their contributions and to investigate the relative importance of each process to the local variability of phytoplankton biomass over different timescales. A method of using the transport rate is introduced to quantify the contribution of transport processes. By combining the time-varying transport rate and high-frequency observed chlorophyll a data, we can explicitly examine the impact of local and transport processes on phytoplankton biomass over a range of timescales from hourly to annually. For the Upper James River, results show that the relative importance of local and transport processes differs on different timescales. Local processes dominate phytoplankton variability on daily to weekly timescales, whereas the contribution of transport processes increases on seasonal to annual timescales and reaches equilibrium with local processes. With the use of the transport rate and high-frequency chlorophyll a data, a method similar to the open water oxygen method for metabolism is also presented to estimate phytoplankton primary production.

Israeli and Palestinian families in the peace process: sources of stress and response patterns.

PubMed

Lavee, Y; Ben-David, A; Azaiza, F

1997-09-01

The Israeli-Palestinian peace process is characterized by its unknown outcomes and consequences for the families involved. The purpose of this study was to identify family processes under conditions of prolonged uncertainty. Data were collected from both Israeli and Palestinian families in the West Bank by means of semi-structured interviews. Qualitative and quantitative analyses showed cross-cultural differences in the perception of the situation; different kinds of concerns and sources of stress; different coping responses; and differences in dyadic interaction patterns and intrafamily processes. The findings are discussed in social-contextual terms, particularly the ways in which political and cultural contexts shape the perception of the situation and family processes under prolonged stressful conditions.

Individual Differences in Working Memory Capacity and Dual-Process Theories of the Mind

ERIC Educational Resources Information Center

Barrett, Lisa Feldman; Tugade, Michele M.; Engle, Randall W.

2004-01-01

Dual-process theories of the mind are ubiquitous in psychology. A central principle of these theories is that behavior is determined by the interplay of automatic and controlled processing. In this article, the authors examine individual differences in the capacity to control attention as a major contributor to differences in working memory…

Effects of orthographic consistency on eye movement behavior: German and English children and adults process the same words differently.

PubMed

Rau, Anne K; Moll, Kristina; Snowling, Margaret J; Landerl, Karin

2015-02-01

The current study investigated the time course of cross-linguistic differences in word recognition. We recorded eye movements of German and English children and adults while reading closely matched sentences, each including a target word manipulated for length and frequency. Results showed differential word recognition processes for both developing and skilled readers. Children of the two orthographies did not differ in terms of total word processing time, but this equal outcome was achieved quite differently. Whereas German children relied on small-unit processing early in word recognition, English children applied small-unit decoding only upon rereading-possibly when experiencing difficulties in integrating an unfamiliar word into the sentence context. Rather unexpectedly, cross-linguistic differences were also found in adults in that English adults showed longer processing times than German adults for nonwords. Thus, although orthographic consistency does play a major role in reading development, cross-linguistic differences are detectable even in skilled adult readers. Copyright © 2014 Elsevier Inc. All rights reserved.

Top-down and bottom-up competition in visual stimuli processing.

PubMed

Ligeza, Tomasz S; Tymorek, Agnieszka D; Wyczesany, Mirosław

2017-01-01

Limited attention capacity results that not all the stimuli present in the visual field are equally processed. While processing of salient stimuli is automatically boosted by bottom‑up attention, processing of task‑relevant stimuli can be boosted volitionally by top‑down attention. Usually, both top‑down and bottom‑up influences are present simultaneously, which creates a competition between these two types of attention. We examined this competition using both behavioral and electrophysiological measures. Participants responded to letters superimposed on background pictures. We assumed that responding to different conditions of the letter task engages top‑down attention to different extent, whereas processing of background pictures of varying salience engages bottom‑up attention to different extent. To check how manipulation of top‑down attention influences bottom‑up processing, we measured evoked response potentials (ERPs) in response to pictures (engaging mostly bottom‑up attention) during three conditions of a letter task (different levels of top‑down engagement). Conversely, to check how manipulation of bottom‑up attention influences top‑down processing, we measured ERP responses for letters (engaging mostly top‑down attention) while manipulating the salience of background pictures (different levels of bottom‑up engagement). The correctness and reaction times in response to letters were also analyzed. As expected, most of the ERPs and behavioral measures revealed a trade‑off between both types of processing: a decrease of bottom‑up processing was associated with an increase of top‑down processing and, similarly, a decrease of top‑down processing was associated with an increase in bottom‑up processing. Results proved competition between the two types of attentions.

A pixellated γ-camera based on CdTe detectors clinical interests and performances

NASA Astrophysics Data System (ADS)

Chambron, J.; Arntz, Y.; Eclancher, B.; Scheiber, Ch; Siffert, P.; Hage Hali, M.; Regal, R.; Kazandjian, A.; Prat, V.; Thomas, S.; Warren, S.; Matz, R.; Jahnke, A.; Karman, M.; Pszota, A.; Nemeth, L.

2000-07-01

A mobile gamma camera dedicated to nuclear cardiology, based on a 15 cm×15 cm detection matrix of 2304 CdTe detector elements, 2.83 mm×2.83 mm×2 mm, has been developed with a European Community support to academic and industrial research centres. The intrinsic properties of the semiconductor crystals - low-ionisation energy, high-energy resolution, high attenuation coefficient - are potentially attractive to improve the γ-camera performances. But their use as γ detectors for medical imaging at high resolution requires production of high-grade materials and large quantities of sophisticated read-out electronics. The decision was taken to use CdTe rather than CdZnTe, because the manufacturer (Eurorad, France) has a large experience for producing high-grade materials, with a good homogeneity and stability and whose transport properties, characterised by the mobility-lifetime product, are at least 5 times greater than that of CdZnTe. The detector matrix is divided in 9 square units, each unit is composed of 256 detectors shared in 16 modules. Each module consists in a thin ceramic plate holding a line of 16 detectors, in four groups of four for an easy replacement, and holding a special 16 channels integrated circuit designed by CLRC (UK). A detection and acquisition logic based on a DSP card and a PC has been programmed by Eurorad for spectral and counting acquisition modes. Collimators LEAP and LEHR from commercial design, mobile gantry and clinical software were provided by Siemens (Germany). The γ-camera head housing, its general mounting and the electric connections were performed by Phase Laboratory (CNRS, France). The compactness of the γ-camera head, thin detectors matrix, electronic readout and collimator, facilitates the detection of close γ sources with the advantage of a high spatial resolution. Such an equipment is intended to bedside explorations. There is a growing clinical requirement in nuclear cardiology to early assess the extent of an infarct in intensive care units, as well as in neurology to detect the grade of a cerebral vascular insult, in pregnancy to detect a pulmonary capillary embolism, or in presurgical oncology to identify sentinel lymph nodes. The physical tests and the clinical imaging capabilities of the experimental device which have been performed by IPB (France) and SHC (Hungary), agree with the expected performances better than those of a cardiac conventional γ- camera except for dynamic studies.

Challenge of representing entropy at different levels of resolution in molecular simulation.

PubMed

Huang, Wei; van Gunsteren, Wilfred F

2015-01-22

The role of entropic contributions in processes involving biomolecules is illustrated using the process of vaporization or condensation of the solvents water and methanol and the process of polypeptide folding in solution using molecular models at different levels of resolution: subatomic, atomic, supra-atomic, and supramolecular. For the folding process, a β-hexapeptide that adopts, as inferred from NMR experiments, both a right-handed 2.710/12-helical fold and a left-handed 314-helical fold in methanol, is used to illustrate the challenge of modeling thermodynamically driven processes at different levels of resolution.

Study on Silicon Microstructure Processing Technology Based on Porous Silicon

NASA Astrophysics Data System (ADS)

Shang, Yingqi; Zhang, Linchao; Qi, Hong; Wu, Yalin; Zhang, Yan; Chen, Jing

2018-03-01

Aiming at the heterogeneity of micro - sealed cavity in silicon microstructure processing technology, the technique of preparing micro - sealed cavity of porous silicon is proposed. The effects of different solutions, different substrate doping concentrations, different current densities, and different etching times on the rate, porosity, thickness and morphology of the prepared porous silicon were studied. The porous silicon was prepared by different process parameters and the prepared porous silicon was tested and analyzed. For the test results, optimize the process parameters and experiments. The experimental results show that the porous silicon can be controlled by optimizing the parameters of the etching solution and the doping concentration of the substrate, and the preparation of porous silicon with different porosity can be realized by different doping concentration, so as to realize the preparation of silicon micro-sealed cavity, to solve the sensor sensitive micro-sealed cavity structure heterogeneous problem, greatly increasing the application of the sensor.

Cultural variation in the focus on goals versus processes of actions.

PubMed

Miyamoto, Yuri; Knoepfler, Christopher A; Ishii, Keiko; Ji, Li-Jun

2013-06-01

Everyday actions (e.g., riding a bike) can be described in ways that emphasize either the goals of the action by adapting a higher level identification (e.g., getting exercise) or the processes of the action by adapting a lower level identification (e.g., pedaling). In Studies 1 and 2, we demonstrate cultural differences in focusing on the process or goal of actions at the individual level: Americans are more likely than Japanese to focus on the goal (rather than the process) of actions. Study 3 recruited Chinese participants in addition to American and Japanese participants and found that cultural differences in action identification are partly explained by cultural differences in self-consistency. Study 4 further showed cultural differences at the collective level: American media presents more goal-oriented information and less process-oriented information than does Japanese media. These findings highlight the role of culture in shaping how people attend to different aspects of actions.

Health technology assessment process of a cardiovascular medical device in four different settings.

PubMed

Olry de Labry Lima, Antonio; Espín Balbino, Jaime; Lemgruber, Alexandre; Caro Martínez, Araceli; García-Mochón, Leticia; Martín Ruiz, Eva; Lessa, Fernanda

2017-10-01

Health technology assessment (HTA) is a tool to help the decision-making process. The aim is to describe methods and processes used in the reimbursement decision making for drug-eluting stents (DES) in four different settings. DES as a technology under study was selected according to different criteria, all of them agreed by a working group. A survey of key informants was designed. DES was evaluated following well-structured HTA processes. Nonetheless, scope for improvement was observed in relation to the data considered for the final decision, the transparency and inclusiveness of the process as well as in the methods employed. An attempt to describe the HTA processes of a well-known medical device.

Qualitative Differences in Real-Time Solution of Standardized Figural Analogies.

ERIC Educational Resources Information Center

Schiano, Diane J.; And Others

Performance on standardized figural analogy tests is considered highly predictive of academic success. While information-processing models of analogy solution attribute performance differences to quantitative differences in processing parameters, the problem-solving literature suggests that qualitative differences in problem representation and…

Second-order relational face processing is applied to faces of different race and photographic contrast.

PubMed

Matheson, H E; Bilsbury, T G; McMullen, P A

2012-03-01

A large body of research suggests that faces are processed by a specialized mechanism within the human visual system. This specialized mechanism is made up of subprocesses (Maurer, LeGrand, & Mondloch, 2002). One subprocess, called second- order relational processing, analyzes the metric distances between face parts. Importantly, it is well established that other-race faces and contrast-reversed faces are associated with impaired performance on numerous face processing tasks. Here, we investigated the specificity of second-order relational processing by testing how this process is applied to faces of different race and photographic contrast. Participants completed a feature displacement discrimination task, directly measuring the sensitivity to second-order relations between face parts. Across three experiments we show that, despite absolute differences in sensitivity in some conditions, inversion impaired performance in all conditions. The presence of robust inversion effects for all faces suggests that second-order relational processing can be applied to faces of different race and photographic contrast.

Distinct conflict resolution deficits related to different facets of Schizophrenia.

PubMed

Kerns, John G

2009-11-01

An important issue in understanding the nature of conflict processing is whether it is a unitary or multidimensional construct. One way to examine this is to study whether people with impaired conflict processing exhibit a general pattern of deficits or whether they exhibit impairments in distinct aspects of conflict processing. One group who might exhibit conflict deficits are people with schizophrenia. Schizophrenia is a heterogeneous disorder, with one way to break down the heterogeneity of schizophrenia is to examine specific symptoms. Previous research has found that specific symptoms of schizophrenia are associated with specific deficits in conflict processing. In particular, disorganization is associated with increased response conflict, alogia is associated with increased retrieval conflict, and anhedonia is associated with increased emotional conflict. Moreover, there is evidence that different types of conflict processing are unassociated with each other. This evidence suggests that conflict processing is a multidimensional construct and that different aspects of schizophrenia are associated with impairments in processing different types of conflict.

The combined impact of vineyard origin and processing winery on the elemental profile of red wines.

PubMed

Hopfer, Helene; Nelson, Jenny; Collins, Thomas S; Heymann, Hildegarde; Ebeler, Susan E

2015-04-01

The combined effects of vineyard origin and winery processing have been studied in 65 red wines samples. Grapes originating from five different vineyards within 40 miles of each other were processed in at least two different wineries. Sixty-three different elements were determined with inductively coupled-plasma mass spectrometry (ICP-MS), and wines were classified according to vineyard origin, processing winery, and the combination of both factors. Vineyard origin as well as winery processing have an impact on the elemental composition of wine, but each winery and each vineyard change the composition to a different degree. For some vineyards, wines showed a characteristic elemental pattern, independent of the processing winery, but the same was found for some wineries, with similar elemental pattern for all grapes processed in these wineries, independent of the vineyard origin. Studying the combined effects of grapegrowing and winemaking provides insight into the determination of geographical origin of red wines. Copyright © 2014 Elsevier Ltd. All rights reserved.

In-depth analysis and characterization of a dual damascene process with respect to different CD

NASA Astrophysics Data System (ADS)

Krause, Gerd; Hofmann, Detlef; Habets, Boris; Buhl, Stefan; Gutsch, Manuela; Lopez-Gomez, Alberto; Kim, Wan-Soo; Thrun, Xaver

2018-03-01

In a 200 mm high volume environment, we studied data from a dual damascene process. Dual damascene is a combination of lithography, etch and CMP that is used to create copper lines and contacts in one single step. During these process steps, different metal CD are measured by different measurement methods. In this study, we analyze the key numbers of the different measurements after different process steps and develop simple models to predict the electrical behavior* . In addition, radial profiles have been analyzed of both inline measurement parameters and electrical parameters. A matching method was developed based on inline and electrical data. Finally, correlation analysis for radial signatures is presented that can be used to predict excursions in electrical signatures.

Lexical Familiarity and Processing Efficiency: Individual Differences in Naming, Lexical Decision, and Semantic Categorization

PubMed Central

Lewellen, Mary Jo; Goldinger, Stephen D.; Pisoni, David B.; Greene, Beth G.

2012-01-01

College students were separated into 2 groups (high and low) on the basis of 3 measures: subjective familiarity ratings of words, self-reported language experiences, and a test of vocabulary knowledge. Three experiments were conducted to determine if the groups also differed in visual word naming, lexical decision, and semantic categorization. High Ss were consistently faster than low Ss in naming visually presented words. They were also faster and more accurate in making difficult lexical decisions and in rejecting homophone foils in semantic categorization. Taken together, the results demonstrate that Ss who differ in lexical familiarity also differ in processing efficiency. The relationship between processing efficiency and working memory accounts of individual differences in language processing is also discussed. PMID:8371087

The Development of Verbal and Visual Working Memory Processes: A Latent Variable Approach

ERIC Educational Resources Information Center

Koppenol-Gonzalez, Gabriela V.; Bouwmeester, Samantha; Vermunt, Jeroen K.

2012-01-01

Working memory (WM) processing in children has been studied with different approaches, focusing on either the organizational structure of WM processing during development (factor analytic) or the influence of different task conditions on WM processing (experimental). The current study combined both approaches, aiming to distinguish verbal and…

The Processing on Different Types of English Formulaic Sequences

ERIC Educational Resources Information Center

Qian, Li

2015-01-01

Formulaic sequences are found to be processed faster than their matched novel phrases in previous studies. Given the variety of formulaic types, few studies have compared processing on different types of formulaic sequences. The present study explored the processing among idioms, speech formulae and written formulae. It has been found that in…

Neural processing of reward in adolescent rodents.

PubMed

Simon, Nicholas W; Moghaddam, Bita

2015-02-01

Immaturities in adolescent reward processing are thought to contribute to poor decision making and increased susceptibility to develop addictive and psychiatric disorders. Very little is known; however, about how the adolescent brain processes reward. The current mechanistic theories of reward processing are derived from adult models. Here we review recent research focused on understanding of how the adolescent brain responds to rewards and reward-associated events. A critical aspect of this work is that age-related differences are evident in neuronal processing of reward-related events across multiple brain regions even when adolescent rats demonstrate behavior similar to adults. These include differences in reward processing between adolescent and adult rats in orbitofrontal cortex and dorsal striatum. Surprisingly, minimal age related differences are observed in ventral striatum, which has been a focal point of developmental studies. We go on to discuss the implications of these differences for behavioral traits affected in adolescence, such as impulsivity, risk-taking, and behavioral flexibility. Collectively, this work suggests that reward-evoked neural activity differs as a function of age and that regions such as the dorsal striatum that are not traditionally associated with affective processing in adults may be critical for reward processing and psychiatric vulnerability in adolescents. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

High-impact strength acrylic denture base material processed by autoclave.

PubMed

Abdulwahhab, Salwan Sami

2013-10-01

To investigate the effect of two different cycles of autoclave processing on the transverse strength, impact strength, surface hardness and the porosity of high-impact strength acrylic denture base material. High Impact Acryl was the heat-cured acrylic denture base material included in the study. A total of 120 specimens were prepared, the specimens were grouped into: control groups in which high-impact strength acrylic resins processed by conventional water-bath processing technique (74°C for 1.5 h then boil for 30 min) and experimental groups in which high-impact strength acrylic resins processed by autoclave at 121°C, 210 kPa .The experimental groups were divided into (fast) groups for 15 min, and (slow) groups for 30 min. To study the effect of the autoclave processing (Tuttnauer 2540EA), four tests were conducted transverse strength (Instron universal testing machine), impact strength (Charpy tester), surface hardness (shore D), and porosity test. The results were analyzed to ANOVA and LSD test. In ANOVA test, there were highly significant differences between the results of the processing techniques in transverse, impact, hardness, and porosity test. The LSD test showed a significant difference between control and fast groups in transverse and hardness tests and a non-significant difference in impact test and a highly significant difference in porosity test; while, there were a highly significant differences between control and slow groups in all examined tests; finally, there were a non-significant difference between fast and slow groups in transverse and porosity tests and a highly significant difference in impact and hardness tests. In the autoclave processing technique, the slow (long) curing cycle improved the tested physical and mechanical properties as compared with the fast (short) curing cycle. The autoclave processing technique improved the tested physical and mechanical properties of High Impact Acryl. Copyright © 2013 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Preparation and physicochemical characterization of matrix pellets containing APIs with different solubility via extrusion process.

PubMed

Hegyesi, Diána; Thommes, Markus; Kleinebudde, Peter; Sovány, Tamás; Kása, Péter; Kelemen, András; Pintye-Hódi, Klára; Regdon, Géza

2017-03-01

In this study, a multiparticulate matrix system was produced, containing two different active pharmaceutical ingredients (APIs): enalapril-maleate and hydrochlorothiazide. The critical control points of the process were investigated by means of factorial design. Beside the generally used microcrystalline cellulose, ethylcellulose was used as matrix former to achieve modified drug release ensured by diffusion. The matrix pellets were made by extrusion-spheronization using a twin-screw extruder. Some pellet properties (aspect ratio, 10% interval fraction, hardness, deformation process) were determined. The aim of our study was to investigate how the two different APIs with different solubility and particle size influence the process. The amount of the granulation liquid plays a key role in the pellet shaping. A higher liquid feed rate is preferred in the pelletization process.

Similarities and Differences Between Working Memory and Long-Term Memory: Evidence From the Levels-of-Processing Span Task

PubMed Central

Rose, Nathan S.; Myerson, Joel; Roediger, Henry L.; Hale, Sandra

2010-01-01

Two experiments compared the effects of depth of processing on working memory (WM) and long-term memory (LTM) using a levels-of-processing (LOP) span task, a newly developed WM span procedure that involves processing to-be-remembered words based on their visual, phonological, or semantic characteristics. Depth of processing had minimal effect on WM tests, yet subsequent memory for the same items on delayed tests showed the typical benefits of semantic processing. Although the difference in LOP effects demonstrates a dissociation between WM and LTM, we also found that the retrieval practice provided by recalling words on the WM task benefited long-term retention, especially for words initially recalled from supraspan lists. The latter result is consistent with the hypothesis that WM span tasks involve retrieval from secondary memory, but the LOP dissociation suggests the processes engaged by WM and LTM tests may differ. Therefore, similarities and differences between WM and LTM depend on the extent to which retrieval from secondary memory is involved and whether there is a match (or mismatch) between initial processing and subsequent retrieval, consistent with transfer-appropriate-processing theory. PMID:20192543

Patterns of linguistic and numerical performance in aphasia.

PubMed

Rath, Dajana; Domahs, Frank; Dressel, Katharina; Claros-Salinas, Dolores; Klein, Elise; Willmes, Klaus; Krinzinger, Helga

2015-02-04

Empirical research on the relationship between linguistic and numerical processing revealed inconsistent results for different levels of cognitive processing (e.g., lexical, semantic) as well as different stimulus materials (e.g., Arabic digits, number words, letters, non-number words). Information of dissociation patterns in aphasic patients was used in order to investigate the dissociability of linguistic and numerical processes. The aim of the present prospective study was a comprehensive, specific, and systematic investigation of relationships between linguistic and numerical processing, considering the impact of asemantic vs. semantic processing and the type of material employed (numbers compared to letters vs. words). A sample of aphasic patients (n = 60) was assessed with a battery of linguistic and numerical tasks directly comparable for their cognitive processing levels (e.g., perceptual, morpho-lexical, semantic). Mean performance differences and frequencies of (complementary) dissociations in individual patients revealed the most prominent numerical advantage for asemantic tasks when comparing the processing of numbers vs. letters, whereas the least numerical advantage was found for semantic tasks when comparing the processing of numbers vs. words. Different patient subgroups showing differential dissociation patterns were further analysed and discussed. A comprehensive model of linguistic and numerical processing should take these findings into account.

Organizational Conflict Management as Disputing Process: The Problem of Social Escalation.

ERIC Educational Resources Information Center

Morrill, Calvin; Thomas, Cheryl King

1992-01-01

Develops an instrument to study organizational conflict management as a disputing process involving the social escalation from grievance to conflict and dispute stages. Finds differences in dispute process according to different strengths of informal relations. (SR)

Ant-mediated ecosystem processes are driven by trophic community structure but mainly by the environment.

PubMed

Salas-Lopez, Alex; Mickal, Houadria; Menzel, Florian; Orivel, Jérôme

2017-01-01

The diversity and functional identity of organisms are known to be relevant to the maintenance of ecosystem processes but can be variable in different environments. Particularly, it is uncertain whether ecosystem processes are driven by complementary effects or by dominant groups of species. We investigated how community structure (i.e., the diversity and relative abundance of biological entities) explains the community-level contribution of Neotropical ant communities to different ecosystem processes in different environments. Ants were attracted with food resources representing six ant-mediated ecosystem processes in four environments: ground and vegetation strata in cropland and forest habitats. The exploitation frequencies of the baits were used to calculate the taxonomic and trophic structures of ant communities and their contribution to ecosystem processes considered individually or in combination (i.e., multifunctionality). We then investigated whether community structure variables could predict ecosystem processes and whether such relationships were affected by the environment. We found that forests presented a greater biodiversity and trophic complementarity and lower dominance than croplands, but this did not affect ecosystem processes. In contrast, trophic complementarity was greater on the ground than on vegetation and was followed by greater resource exploitation levels. Although ant participation in ecosystem processes can be predicted by means of trophic-based indices, we found that variations in community structure and performance in ecosystem processes were best explained by environment. We conclude that determining the extent to which the dominance and complementarity of communities affect ecosystem processes in different environments requires a better understanding of resource availability to different species.

Changes to Serum Sample Tube and Processing Methodology Does Not Cause Inter-Individual Variation in Automated Whole Serum N-Glycan Profiling in Health and Disease

PubMed Central

Shubhakar, Archana; Kalla, Rahul; Nimmo, Elaine R.; Fernandes, Daryl L.; Satsangi, Jack; Spencer, Daniel I. R.

2015-01-01

Introduction Serum N-glycans have been identified as putative biomarkers for numerous diseases. The impact of different serum sample tubes and processing methods on N-glycan analysis has received relatively little attention. This study aimed to determine the effect of different sample tubes and processing methods on the whole serum N-glycan profile in both health and disease. A secondary objective was to describe a robot automated N-glycan release, labeling and cleanup process for use in a biomarker discovery system. Methods 25 patients with active and quiescent inflammatory bowel disease and controls had three different serum sample tubes taken at the same draw. Two different processing methods were used for three types of tube (with and without gel-separation medium). Samples were randomised and processed in a blinded fashion. Whole serum N-glycan release, 2-aminobenzamide labeling and cleanup was automated using a Hamilton Microlab STARlet Liquid Handling robot. Samples were analysed using a hydrophilic interaction liquid chromatography/ethylene bridged hybrid(BEH) column on an ultra-high performance liquid chromatography instrument. Data were analysed quantitatively by pairwise correlation and hierarchical clustering using the area under each chromatogram peak. Qualitatively, a blinded assessor attempted to match chromatograms to each individual. Results There was small intra-individual variation in serum N-glycan profiles from samples collected using different sample processing methods. Intra-individual correlation coefficients were between 0.99 and 1. Unsupervised hierarchical clustering and principal coordinate analyses accurately matched samples from the same individual. Qualitative analysis demonstrated good chromatogram overlay and a blinded assessor was able to accurately match individuals based on chromatogram profile, regardless of disease status. Conclusions The three different serum sample tubes processed using the described methods cause minimal inter-individual variation in serum whole N-glycan profile when processed using an automated workstream. This has important implications for N-glycan biomarker discovery studies using different serum processing standard operating procedures. PMID:25831126

Changes to serum sample tube and processing methodology does not cause Intra-Individual [corrected] variation in automated whole serum N-glycan profiling in health and disease.

PubMed

Ventham, Nicholas T; Gardner, Richard A; Kennedy, Nicholas A; Shubhakar, Archana; Kalla, Rahul; Nimmo, Elaine R; Fernandes, Daryl L; Satsangi, Jack; Spencer, Daniel I R

2015-01-01

Serum N-glycans have been identified as putative biomarkers for numerous diseases. The impact of different serum sample tubes and processing methods on N-glycan analysis has received relatively little attention. This study aimed to determine the effect of different sample tubes and processing methods on the whole serum N-glycan profile in both health and disease. A secondary objective was to describe a robot automated N-glycan release, labeling and cleanup process for use in a biomarker discovery system. 25 patients with active and quiescent inflammatory bowel disease and controls had three different serum sample tubes taken at the same draw. Two different processing methods were used for three types of tube (with and without gel-separation medium). Samples were randomised and processed in a blinded fashion. Whole serum N-glycan release, 2-aminobenzamide labeling and cleanup was automated using a Hamilton Microlab STARlet Liquid Handling robot. Samples were analysed using a hydrophilic interaction liquid chromatography/ethylene bridged hybrid(BEH) column on an ultra-high performance liquid chromatography instrument. Data were analysed quantitatively by pairwise correlation and hierarchical clustering using the area under each chromatogram peak. Qualitatively, a blinded assessor attempted to match chromatograms to each individual. There was small intra-individual variation in serum N-glycan profiles from samples collected using different sample processing methods. Intra-individual correlation coefficients were between 0.99 and 1. Unsupervised hierarchical clustering and principal coordinate analyses accurately matched samples from the same individual. Qualitative analysis demonstrated good chromatogram overlay and a blinded assessor was able to accurately match individuals based on chromatogram profile, regardless of disease status. The three different serum sample tubes processed using the described methods cause minimal inter-individual variation in serum whole N-glycan profile when processed using an automated workstream. This has important implications for N-glycan biomarker discovery studies using different serum processing standard operating procedures.

The time course of attentional modulation on emotional conflict processing.

PubMed

Zhou, Pingyan; Yang, Guochun; Nan, Weizhi; Liu, Xun

2016-01-01

Cognitive conflict resolution is critical to human survival in a rapidly changing environment. However, emotional conflict processing seems to be particularly important for human interactions. This study examined whether the time course of attentional modulation on emotional conflict processing was different from cognitive conflict processing during a flanker task. Results showed that emotional N200 and P300 effects, similar to colour conflict processing, appeared only during the relevant task. However, the emotional N200 effect preceded the colour N200 effect, indicating that emotional conflict can be identified earlier than cognitive conflict. Additionally, a significant emotional N100 effect revealed that emotional valence differences could be perceived during early processing based on rough aspects of input. The present data suggest that emotional conflict processing is modulated by top-down attention, similar to cognitive conflict processing (reflected by N200 and P300 effects). However, emotional conflict processing seems to have more time advantages during two different processing stages.

Analysis of fingerprints features of infrared spectra of various processed products of Rhizoma Coptidis and their different extracts

NASA Astrophysics Data System (ADS)

Xu, Beilei; Zhang, Guijun; Xu, Changhua; Sun, Suqin

2015-09-01

Fourier transform infrared spectroscopy (FT-IR) associated with second derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2D-IR) are employed to analyze various processed products and different extracts of Rhizoma Coptidis. There is a shift of the peak of 1641 cm-1 of raw Rhizoma Coptidis after processed, which drifts to lower wave number. Peaks at 1508, 1387, 1363, 1332, 1274 and 1234 cm-1 barely change in most samples, except an obvious enhancement of these peaks after processed, suggesting that processed Rhizoma Coptidis may have higher content of berberine than raw material, which is corresponding to the results of correlation coefficients analysis. There are some differences in the absorption peaks in the range of 1800-1000 cm-1 in the SD-IR spectra, which have better resolution, of different processed products. 2D-IR spectra, which elevate the resolution further, can present more differences among the products in the range of 1300-800 cm-1 and 1800-1300 cm-1. Analysis of aqueous, ethanol and petroleum ether extracts of various processed products proves that there are distinctive differences of all auto-peaks in shapes and intensities in all of them. With the advantages of high resolution, high speed and convenience, FT-IR combined with 2D-IR can quickly and precisely distinguish various processed products of Rhizoma Coptidis and can be applied to predict the tendency of transformation of the complicated chemical mixture systems under heat perturbation.

Human Evoked Cortical Activity to Silent Gaps in Noise: Effects of Age, Attention, and Cortical Processing Speed

PubMed Central

Harris, Kelly C.; Wilson, Sara; Eckert, Mark A.; Dubno, Judy R.

2011-01-01

Objectives The goal of this study was to examine the degree to which age-related differences in early or automatic levels of auditory processing and attention-related processes explain age-related differences in auditory temporal processing. We hypothesized that age-related differences in attention and cognition compound age-related differences at automatic levels of processing, contributing to the robust age effects observed during challenging listening tasks. Design We examined age-related and individual differences in cortical event-related potential (ERP) amplitudes and latencies, processing speed, and gap detection from twenty-five younger and twenty-five older adults with normal hearing. ERPs were elicited by brief silent periods (gaps) in an otherwise continuous broadband noise and were measured under two listening conditions, passive and active. During passive listening, participants ignored the stimulus and read quietly. During active listening, participants button pressed each time they detected a gap. Gap detection (percent detected) was calculated for each gap duration during active listening (3, 6, 9, 12 and 15 ms). Processing speed was assessed using the Purdue Pegboard test and the Connections Test. Repeated measures ANOVAs assessed effects of age on gap detection, processing speed, and ERP amplitudes and latencies. An “attention modulation” construct was created using linear regression to examine the effects of attention while controlling for age-related differences in auditory processing. Pearson correlation analyses assessed the extent to which attention modulation, ERPs, and processing speed predicted behavioral gap detection. Results: Older adults had significantly poorer gap detection and slower processing speed than younger adults. Even after adjusting for poorer gap detection, the neurophysiological response to gap onset was atypical in older adults with reduced P2 amplitudes and virtually absent N2 responses. Moreover, individual differences in attention modulation of P2 response latencies and N2 amplitudes predicted gap detection and processing speed in older adults. That is, older adults with P2 latencies that decreased and N2 amplitudes that increased with active listening had faster processing speed and better gap detection than those older adults whose P2 latencies increased and N2 amplitudes decreased with attention Conclusions Results from the current study are broadly consistent with previous findings that older adults exhibit significantly poorer gap detection than younger adults in challenging tasks. Even after adjusting for poorer gap detection, older and younger adults showed robust differences in their electrophysiological responses to sound offset. Furthermore, the degree to which attention modulated the ERP was associated with individual variation in measures of processing speed and gap detection. Taken together, these results suggests an age-related deficit in early or automatic levels of auditory temporal processing and that some older adults may be less able to compensate for declines in processing by attending to the stimulus. These results extend our previous findings and support the hypothesis that age-related differences in cognitive or attention-related processing, including processing speed, contribute to an age-related decrease in gap detection. PMID:22374321

Subjective workload and individual differences in information processing abilities

NASA Technical Reports Server (NTRS)

Damos, D. L.

1984-01-01

This paper describes several experiments examining the source of individual differences in the experience of mental workload. Three sources of such differences were examined: information processing abilities, timesharing abilities, and personality traits/behavior patterns. On the whole, there was little evidence that individual differences in information processing abilities or timesharing abilities are related to perceived differences in mental workload. However, individuals with strong Type A coronary prone behavior patterns differed in both single- and multiple-task performance from individuals who showed little evidence of such a pattern. Additionally, individuals with a strong Type A pattern showed some dissociation between objective performance and the experience of mental workload.

Evaluating Web accessibility at different processing phases

NASA Astrophysics Data System (ADS)

Fernandes, N.; Lopes, R.; Carriço, L.

2012-09-01

Modern Web sites use several techniques (e.g. DOM manipulation) that allow for the injection of new content into their Web pages (e.g. AJAX), as well as manipulation of the HTML DOM tree. This has the consequence that the Web pages that are presented to users (i.e. after browser processing) are different from the original structure and content that is transmitted through HTTP communication (i.e. after browser processing). This poses a series of challenges for Web accessibility evaluation, especially on automated evaluation software. This article details an experimental study designed to understand the differences posed by accessibility evaluation after Web browser processing. We implemented a Javascript-based evaluator, QualWeb, that can perform WCAG 2.0 based accessibility evaluations in the two phases of browser processing. Our study shows that, in fact, there are considerable differences between the HTML DOM trees in both phases, which have the consequence of having distinct evaluation results. We discuss the impact of these results in the light of the potential problems that these differences can pose to designers and developers that use accessibility evaluators that function before browser processing.

Image quality and dose differences caused by vendor-specific image processing of neonatal radiographs.

PubMed

Sensakovic, William F; O'Dell, M Cody; Letter, Haley; Kohler, Nathan; Rop, Baiywo; Cook, Jane; Logsdon, Gregory; Varich, Laura

2016-10-01

Image processing plays an important role in optimizing image quality and radiation dose in projection radiography. Unfortunately commercial algorithms are black boxes that are often left at or near vendor default settings rather than being optimized. We hypothesize that different commercial image-processing systems, when left at or near default settings, create significant differences in image quality. We further hypothesize that image-quality differences can be exploited to produce images of equivalent quality but lower radiation dose. We used a portable radiography system to acquire images on a neonatal chest phantom and recorded the entrance surface air kerma (ESAK). We applied two image-processing systems (Optima XR220amx, by GE Healthcare, Waukesha, WI; and MUSICA(2) by Agfa HealthCare, Mortsel, Belgium) to the images. Seven observers (attending pediatric radiologists and radiology residents) independently assessed image quality using two methods: rating and matching. Image-quality ratings were independently assessed by each observer on a 10-point scale. Matching consisted of each observer matching GE-processed images and Agfa-processed images with equivalent image quality. A total of 210 rating tasks and 42 matching tasks were performed and effective dose was estimated. Median Agfa-processed image-quality ratings were higher than GE-processed ratings. Non-diagnostic ratings were seen over a wider range of doses for GE-processed images than for Agfa-processed images. During matching tasks, observers matched image quality between GE-processed images and Agfa-processed images acquired at a lower effective dose (11 ± 9 μSv; P < 0.0001). Image-processing methods significantly impact perceived image quality. These image-quality differences can be exploited to alter protocols and produce images of equivalent image quality but lower doses. Those purchasing projection radiography systems or third-party image-processing software should be aware that image processing can significantly impact image quality when settings are left near default values.

Occupational Differences between Hispanics and Non-Hispanics. A Rand Note.

ERIC Educational Resources Information Center

Stolzenberg, Ross M.

A study examined the occupational differences between Hispanics and non-Hispanics. The study focused on the determinants of Hispanic occupational achievement; differences in the process of occupational achievement among different Hispanic ethnic subgroups; variations in the process of occupational achievement across geographic areas; and…

Welding parameter optimization of alloy material by friction stir welding using Taguchi approach and design of experiments

NASA Astrophysics Data System (ADS)

Karwande, Amit H.; Rao, Seeram Srinivasa

2018-04-01

Friction stir welding (FSW) a welding process in which metals are joint by melting them at their solid state. In different engineering areas such as civil, mechanical, naval and aeronautical engineering beams are widely used of the magnesium alloys for different applications and that are joined by conventional inert gas welding process. Magnesium metal has less density and low melting point for that reason large heat generation in the common welding process so its necessity to adapt new welding process. FSW process increases the weld quality which observed under various mechanical testing by using different tool size.

Oleochemical industry future through biotechnology.

PubMed

Abdelmoez, Wael; Mustafa, Ahmad

2014-01-01

Lipases are the most widely used class of enzymes in organic synthesis. Enzymatic processes have been implemented in a broad range of industries as they are specific, save raw materials, energy and chemicals, environmentally friendly and fast in action compared to conventional processes. The most notable benefit is the moderate process temperature and pressure with no unwanted side reactions. In the past two decades, intensive research was carried out towards enzymatic synthesis of oleochemicals. This review has a sharp focus on the current implemented enzymatic processes for producing different oleochemicals such as fatty acids, glycerin, biodiesel, biolubricant and different alkyl esters via different processes including hydrolysis, esterification, transesterification and intraesterification.

Gender Differences in Processing Speed: A Review of Recent Research

ERIC Educational Resources Information Center

Roivainen, Eka

2011-01-01

A review of recent large-scale studies on gender differences in processing speed and on the cognitive factors assumed to affect processing speed was performed. It was found that females have an advantage in processing speed tasks involving digits and alphabets as well as in rapid naming tasks while males are faster on reaction time tests and…

When a Dog Has a Pen for a Tail: The Time Course of Creative Object Processing

ERIC Educational Resources Information Center

Wang, Botao; Duan, Haijun; Qi, Senqing; Hu, Weiping; Zhang, Huan

2017-01-01

Creative objects differ from ordinary objects in that they are created by human beings to contain novel, creative information. Previous research has demonstrated that ordinary object processing involves both a perceptual process for analyzing different features of the visual input and a higher-order process for evaluating the relevance of this…

The Influence of Schema and Cultural Difference on L1 and L2 Reading

ERIC Educational Resources Information Center

Yang, Shi-sheng

2010-01-01

Reading in L1 shares numerous basic elements with reading in L2, and the processes also differ greatly. Intriguing questions involve whether there are two parallel cognitive processes at work, or whether there are processing strategies that accommodate both L1 and L2. This paper examines how reading in L1 is different from and similar to reading…

The Different Role of Working Memory in Open-Ended versus Closed-Ended Creative Problem Solving: A Dual-Process Theory Account

ERIC Educational Resources Information Center

Lin, Wei-Lun; Lien, Yunn-Wen

2013-01-01

This study examined how working memory plays different roles in open-ended versus closed-ended creative problem-solving processes, as represented by divergent thinking tests and insight problem-solving tasks. With respect to the analysis of different task demands and the framework of dual-process theories, the hypothesis was that the idea…

Pursuing the method of multiple working hypotheses to understand differences in process-based snow models

NASA Astrophysics Data System (ADS)

Clark, Martyn; Essery, Richard

2017-04-01

When faced with the complex and interdisciplinary challenge of building process-based land models, different modelers make different decisions at different points in the model development process. These modeling decisions are generally based on several considerations, including fidelity (e.g., what approaches faithfully simulate observed processes), complexity (e.g., which processes should be represented explicitly), practicality (e.g., what is the computational cost of the model simulations; are there sufficient resources to implement the desired modeling concepts), and data availability (e.g., is there sufficient data to force and evaluate models). Consequently the research community, comprising modelers of diverse background, experience, and modeling philosophy, has amassed a wide range of models, which differ in almost every aspect of their conceptualization and implementation. Model comparison studies have been undertaken to explore model differences, but have not been able to meaningfully attribute inter-model differences in predictive ability to individual model components because there are often too many structural and implementation differences among the different models considered. As a consequence, model comparison studies to date have provided limited insight into the causes of differences in model behavior, and model development has often relied on the inspiration and experience of individual modelers rather than on a systematic analysis of model shortcomings. This presentation will summarize the use of "multiple-hypothesis" modeling frameworks to understand differences in process-based snow models. Multiple-hypothesis frameworks define a master modeling template, and include a a wide variety of process parameterizations and spatial configurations that are used in existing models. Such frameworks provide the capability to decompose complex models into the individual decisions that are made as part of model development, and evaluate each decision in isolation. It is hence possible to attribute differences in system-scale model predictions to individual modeling decisions, providing scope to mimic the behavior of existing models, understand why models differ, characterize model uncertainty, and identify productive pathways to model improvement. Results will be presented applying multiple hypothesis frameworks to snow model comparison projects, including PILPS, SnowMIP, and the upcoming ESM-SnowMIP project.

Process for manufacturing bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene

DOEpatents

Rasmussen, Paul George; Lawton, Richard Graham

2014-06-03

A process to manufacture substituted tetracyano-hexaazatricyclics with the substitutions occurring at the 9 and 10 hydrogens. The process begins with 2,3-dichloro-5,6-dicyanopyrazine, which is reacted to form the desired tetracyano-hexaazatricyclic. Different process embodiments enable different reaction paths to the desired tetracyano-hexaazatricyclic. Different tetracyano-hexaazatricyclic embodiments include bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene and bis(2-methoxyethoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracen- e.

Individual differences and predictors of forgetting in old age: the role of processing speed and working memory.

PubMed

Zimprich, Daniel; Kurtz, Tanja

2013-01-01

The goal of the present study was to examine whether individual differences in basic cognitive abilities, processing speed, and working memory, are reliable predictors of individual differences in forgetting rates in old age. The sample for the present study comprised 364 participants aged between 65 and 80 years from the Zurich Longitudinal Study on Cognitive Aging. The impact of basic cognitive abilities on forgetting was analyzed by modeling working memory and processing speed as predictors of the amount of forgetting of 27 words, which had been learned across five trials. Forgetting was measured over a 30-minute interval by using parceling and a latent change model, in which the latent difference between recall performance after five learning trials and a delayed recall was modeled. Results implied reliable individual differences in forgetting. These individual differences in forgetting were strongly related to processing speed and working memory. Moreover, an age-related effect, which was significantly stronger for forgetting than for learning, emerged even after controlling effects of processing speed and working memory.

Using sex differences in the developing brain to identify nodes of influence for seizure susceptibility and epileptogenesis.

PubMed

Kight, Katherine E; McCarthy, Margaret M

2014-12-01

Sexual differentiation of the developing brain organizes the neural architecture differently between males and females, and the main influence on this process is exposure to gonadal steroids during sensitive periods of prenatal and early postnatal development. Many molecular and cellular processes are influenced by steroid hormones in the developing brain, including gene expression, cell birth and death, neurite outgrowth and synaptogenesis, and synaptic activity. Perturbations in these processes can alter neuronal excitability and circuit activity, leading to increased seizure susceptibility and the promotion of pathological processes that constitute epileptogenesis. In this review, we will provide a general overview of sex differences in the early developing brain that may be relevant for altered seizure susceptibility in early life, focusing on limbic areas of the brain. Sex differences that have the potential to alter the progress of epileptogenesis are evident at molecular and cellular levels in the developing brain, and include differences in neuronal excitability, response to environmental insult, and epigenetic control of gene expression. Knowing how these processes differ between the sexes can help us understand fundamental mechanisms underlying gender differences in seizure susceptibility and epileptogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Color categories only affect post-perceptual processes when same- and different-category colors are equally discriminable.

PubMed

He, Xun; Witzel, Christoph; Forder, Lewis; Clifford, Alexandra; Franklin, Anna

2014-04-01

Prior claims that color categories affect color perception are confounded by inequalities in the color space used to equate same- and different-category colors. Here, we equate same- and different-category colors in the number of just-noticeable differences, and measure event-related potentials (ERPs) to these colors on a visual oddball task to establish if color categories affect perceptual or post-perceptual stages of processing. Category effects were found from 200 ms after color presentation, only in ERP components that reflect post-perceptual processes (e.g., N2, P3). The findings suggest that color categories affect post-perceptual processing, but do not affect the perceptual representation of color.

Developing Cultural Differences in Face Processing

ERIC Educational Resources Information Center

Kelly, David J.; Liu, Shaoying; Rodger, Helen; Miellet, Sebastien; Ge, Liezhong; Caldara, Roberto

2011-01-01

Perception and eye movements are affected by culture. Adults from Eastern societies (e.g. China) display a disposition to process information "holistically," whereas individuals from Western societies (e.g. Britain) process information "analytically." Recently, this pattern of cultural differences has been extended to face…

Microstructure and Texture of Al-2.5wt.%Mg Processed by Combining Accumulative Roll Bonding and Conventional Rolling

NASA Astrophysics Data System (ADS)

Gatti, J. R.; Bhattacharjee, P. P.

2014-12-01

Evolution of microstructure and texture during severe deformation and annealing was studied in Al-2.5%Mg alloy processed by two different routes, namely, monotonic Accumulative Roll Bonding (ARB) and a hybrid route combining ARB and conventional rolling (CR). For this purpose Al-2.5%Mg sheets were subjected to 5 cycles of monotonic ARB (equivalent strain (ɛeq) = 4.0) processing while in the hybrid route (ARB + CR) 3 cycle ARB-processed sheets were further deformed by conventional rolling to 75% reduction in thickness (ɛeq = 4.0). Although formation of ultrafine structure was observed in the two processing routes, the monotonic ARB—processed material showed finer microstructure but weak texture as compared to the ARB + CR—processed material. After complete recrystallization, the ARB + CR-processed material showed weak cube texture ({001}<100>) but the cube component was almost negligible in the monotonic ARB-processed material-processed material. However, the ND-rotated cube components were stronger in the monotonic ARB-processed material-processed material. The observed differences in the microstructure and texture evolution during deformation and annealing could be explained by the characteristic differences of the two processing routes.

Oscillatory mechanisms of process binding in memory.

PubMed

Klimesch, Wolfgang; Freunberger, Roman; Sauseng, Paul

2010-06-01

A central topic in cognitive neuroscience is the question, which processes underlie large scale communication within and between different neural networks. The basic assumption is that oscillatory phase synchronization plays an important role for process binding--the transient linking of different cognitive processes--which may be considered a special type of large scale communication. We investigate this question for memory processes on the basis of different types of oscillatory synchronization mechanisms. The reviewed findings suggest that theta and alpha phase coupling (and phase reorganization) reflect control processes in two large memory systems, a working memory and a complex knowledge system that comprises semantic long-term memory. It is suggested that alpha phase synchronization may be interpreted in terms of processes that coordinate top-down control (a process guided by expectancy to focus on relevant search areas) and access to memory traces (a process leading to the activation of a memory trace). An analogous interpretation is suggested for theta oscillations and the controlled access to episodic memories. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Quality assessment of baby food made of different pre-processed organic raw materials under industrial processing conditions.

PubMed

Seidel, Kathrin; Kahl, Johannes; Paoletti, Flavio; Birlouez, Ines; Busscher, Nicolaas; Kretzschmar, Ursula; Särkkä-Tirkkonen, Marjo; Seljåsen, Randi; Sinesio, Fiorella; Torp, Torfinn; Baiamonte, Irene

2015-02-01

The market for processed food is rapidly growing. The industry needs methods for "processing with care" leading to high quality products in order to meet consumers' expectations. Processing influences the quality of the finished product through various factors. In carrot baby food, these are the raw material, the pre-processing and storage treatments as well as the processing conditions. In this study, a quality assessment was performed on baby food made from different pre-processed raw materials. The experiments were carried out under industrial conditions using fresh, frozen and stored organic carrots as raw material. Statistically significant differences were found for sensory attributes among the three autoclaved puree samples (e.g. overall odour F = 90.72, p < 0.001). Samples processed from frozen carrots show increased moisture content and decrease of several chemical constituents. Biocrystallization identified changes between replications of the cooking. Pre-treatment of raw material has a significant influence on the final quality of the baby food.

Some opinions on the review process of research papers destined for publication.

PubMed

Roohi, Ehsan; Mahian, Omid

2015-06-01

The current paper discusses the peer review process in journals that publish research papers purveying new science and understandings (scientific journals). Different aspects of peer review including the selection of reviewers, the review process and the decision policy of editor are discussed in details. Here, the pros and cons of different conventional methods of review processes are mentioned. Finally, a suggestion is presented for the review process of scientific papers.

Neural Correlates of Sex/Gender Differences in Humor Processing for Different Joke Types.

PubMed

Chan, Yu-Chen

2016-01-01

Humor operates through a variety of techniques, which first generate surprise and then amusement and laughter once the unexpected incongruity is resolved. As different types of jokes use different techniques, the corresponding humor processes also differ. The present study builds on the framework of the 'tri-component theory of humor,' which details the mechanisms involved in cognition (comprehension), affect (appreciation), and laughter (expression). This study seeks to identify differences among joke types and between sexes/genders in the neural mechanisms underlying humor processing. Three types of verbal jokes, bridging-inference jokes (BJs), exaggeration jokes (EJs), and ambiguity jokes (AJs), were used as stimuli. The findings revealed differences in brain activity for an interaction between sex/gender and joke type. For BJs, women displayed greater activation in the temporoparietal-mesocortical-motor network than men, demonstrating the importance of the temporoparietal junction (TPJ) presumably for 'theory of mind' processing, the orbitofrontal cortex for motivational functions and reward coding, and the supplementary motor area for laughter. Women also showed greater activation than men in the frontal-mesolimbic network associated with EJs, including the anterior (frontopolar) prefrontal cortex (aPFC, BA 10) for executive control processes, and the amygdala and midbrain for reward anticipation and salience processes. Conversely, AJs elicited greater activation in men than women in the frontal-paralimbic network, including the dorsal prefrontal cortex (dPFC) and parahippocampal gyrus. All joke types elicited greater activation in the aPFC of women than of men, whereas men showed greater activation than women in the dPFC. To confirm the findings related to sex/gender differences, random group analysis and within group variance analysis were also performed. These findings help further establish the mechanisms underlying the processing of different joke types for the sexes/genders and provide a neural foundation for a theory of sex/gender differences in humor.

Neural Correlates of Sex/Gender Differences in Humor Processing for Different Joke Types

PubMed Central

Chan, Yu-Chen

2016-01-01

Humor operates through a variety of techniques, which first generate surprise and then amusement and laughter once the unexpected incongruity is resolved. As different types of jokes use different techniques, the corresponding humor processes also differ. The present study builds on the framework of the ‘tri-component theory of humor,’ which details the mechanisms involved in cognition (comprehension), affect (appreciation), and laughter (expression). This study seeks to identify differences among joke types and between sexes/genders in the neural mechanisms underlying humor processing. Three types of verbal jokes, bridging-inference jokes (BJs), exaggeration jokes (EJs), and ambiguity jokes (AJs), were used as stimuli. The findings revealed differences in brain activity for an interaction between sex/gender and joke type. For BJs, women displayed greater activation in the temporoparietal–mesocortical-motor network than men, demonstrating the importance of the temporoparietal junction (TPJ) presumably for ‘theory of mind’ processing, the orbitofrontal cortex for motivational functions and reward coding, and the supplementary motor area for laughter. Women also showed greater activation than men in the frontal-mesolimbic network associated with EJs, including the anterior (frontopolar) prefrontal cortex (aPFC, BA 10) for executive control processes, and the amygdala and midbrain for reward anticipation and salience processes. Conversely, AJs elicited greater activation in men than women in the frontal-paralimbic network, including the dorsal prefrontal cortex (dPFC) and parahippocampal gyrus. All joke types elicited greater activation in the aPFC of women than of men, whereas men showed greater activation than women in the dPFC. To confirm the findings related to sex/gender differences, random group analysis and within group variance analysis were also performed. These findings help further establish the mechanisms underlying the processing of different joke types for the sexes/genders and provide a neural foundation for a theory of sex/gender differences in humor. PMID:27199791

Executive functioning and processing speed in age-related differences in memory: contribution of a coding task.

PubMed

Baudouin, Alexia; Clarys, David; Vanneste, Sandrine; Isingrini, Michel

2009-12-01

The aim of the present study was to examine executive dysfunctioning and decreased processing speed as potential mediators of age-related differences in episodic memory. We compared the performances of young and elderly adults in a free-recall task. Participants were also given tests to measure executive functions and perceptual processing speed and a coding task (the Digit Symbol Substitution Test, DSST). More precisely, we tested the hypothesis that executive functions would mediate the age-related differences observed in the free-recall task better than perceptual speed. We also tested the assumption that a coding task, assumed to involve both executive processes and perceptual speed, would be the best mediator of age-related differences in memory. Findings first confirmed that the DSST combines executive processes and perceptual speed. Secondly, they showed that executive functions are a significant mediator of age-related differences in memory, and that DSST performance is the best predictor.

Gender differences in identity processes and self-esteem in middle and later adulthood.

PubMed

Skultety, Karyn M; Krauss Whitbourne, Susan

2004-01-01

Gender differences were examined in the identity processes of identity assimilation (maintaining identity despite age changes), identity accommodation (changing identity) and balance (using both processes) and in the relationship of these processes to self-esteem. We tested a community sample of 222 adults (131 females and 91 males) ranging from 40 to 84 years of age (M = 57.5, SD = 12.1). Analysis of variance yielded evidence showing greater use of identity accommodation for women. Identity accommodation was negatively associated with self-esteem for both genders, while identity assimilation was positively associated with self-esteem for women only. For both men and women, identity balance was positively related to self-esteem. Women's use of the identity processes in relation to self-esteem is discussed. Societal views on aging are suggested to impact women, such that they engage in identity accommodation while benefiting from identity assimilation. From these findings, it appears that examining the processes contributing to the maintenance of self-esteem may be a more useful approach to characterizing the aging process and gender differences than focusing on mean differences alone.

Age-related differences in brain activity during implicit and explicit processing of fearful facial expressions.

PubMed

Zsoldos, Isabella; Cousin, Emilie; Klein-Koerkamp, Yanica; Pichat, Cédric; Hot, Pascal

2016-11-01

Age-related differences in neural correlates underlying implicit and explicit emotion processing are unclear. Within the framework of the Frontoamygdalar Age-related Differences in Emotion model (St Jacques et al., 2009), our objectives were to examine the behavioral and neural modifications that occur with age for both processes. During explicit and implicit processing of fearful faces, we expected to observe less amygdala activity in older adults (OA) than in younger adults (YA), associated with poorer recognition performance in the explicit task, and more frontal activity during implicit processing, suggesting compensation. At a behavioral level, explicit recognition of fearful faces was impaired in OA compared with YA. We did not observe any cerebral differences between OA and YA during the implicit task, whereas in the explicit task, OA recruited more frontal, parietal, temporal, occipital, and cingulate areas. Our findings suggest that automatic processing of emotion may be preserved during aging, whereas deliberate processing is impaired. Additional neural recruitment in OA did not appear to compensate for their behavioral deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

Conflict Tasks of Different Types Divergently Affect the Attentional Processing of Gaze and Arrow.

PubMed

Fan, Lingxia; Yu, Huan; Zhang, Xuemin; Feng, Qing; Sun, Mengdan; Xu, Mengsi

2018-01-01

The present study explored the attentional processing mechanisms of gaze and arrow cues in two different types of conflict tasks. In Experiment 1, participants performed a flanker task in which gaze and arrow cues were presented as central targets or bilateral distractors. The congruency between the direction of the target and the distractors was manipulated. Results showed that arrow distractors greatly interfered with the attentional processing of gaze, while the processing of arrow direction was immune to conflict from gaze distractors. Using a spatial compatibility task, Experiment 2 explored the conflict effects exerted on gaze and arrow processing by their relative spatial locations. When the direction of the arrow was in conflict with its spatial layout on screen, response times were slowed; however, the encoding of gaze was unaffected by spatial location. In general, processing to an arrow cue is less influenced by bilateral gaze cues but is affected by irrelevant spatial information, while processing to a gaze cue is greatly disturbed by bilateral arrows but is unaffected by irrelevant spatial information. Different effects on gaze and arrow cues by different types of conflicts may reflect two relatively distinct specific modes of the attentional process.

Differences in Low and High Working-Memory Capacity Readers' Cognitive and Metacognitive Processing Patterns as a Function of Reading for Different Purposes

ERIC Educational Resources Information Center

Linderholm, Tracy; Cong, Xiaosi; Zhao, Qin

2008-01-01

Differences in cognitive and metacognitive processing patterns as a function of working-memory capacity and reading for different purposes were examined in college-aged readers by collecting reading times and calculating absolute monitoring accuracy, which is the difference between estimated and actual comprehension test performance. Readers read…

International Students Decision-Making Process

ERIC Educational Resources Information Center

Cubillo, Jose Maria; Sanchez, Joaquin; Cervino, Julio

2006-01-01

Purpose--The purpose of this paper is to propose a theoretical model that integrates the different groups of factors which influence the decision-making process of international students, analysing different dimensions of this process and explaining those factors which determine students' choice. Design/methodology/approach--A hypothetical model…

Cultural differences in human brain activity: a quantitative meta-analysis.

PubMed

Han, Shihui; Ma, Yina

2014-10-01

Psychologists have been trying to understand differences in cognition and behavior between East Asian and Western cultures within a single cognitive framework such as holistic versus analytic or interdependent versus independent processes. However, it remains unclear whether cultural differences in multiple psychological processes correspond to the same or different neural networks. We conducted a quantitative meta-analysis of 35 functional MRI studies to examine cultural differences in brain activity engaged in social and non-social processes. We showed that social cognitive processes are characterized by stronger activity in the dorsal medial prefrontal cortex, lateral frontal cortex and temporoparietal junction in East Asians but stronger activity in the anterior cingulate, ventral medial prefrontal cortex and bilateral insula in Westerners. Social affective processes are associated with stronger activity in the right dorsal lateral frontal cortex in East Asians but greater activity in the left insula and right temporal pole in Westerners. Non-social processes induce stronger activity in the left inferior parietal cortex, left middle occipital and left superior parietal cortex in East Asians but greater activations in the right lingual gyrus, right inferior parietal cortex and precuneus in Westerners. The results suggest that cultural differences in social and non-social processes are mediated by distinct neural networks. Moreover, East Asian cultures are associated with increased neural activity in the brain regions related to inference of others' mind and emotion regulation whereas Western cultures are associated with enhanced neural activity in the brain areas related to self-relevance encoding and emotional responses during social cognitive/affective processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Ensemble analyses improve signatures of tumour hypoxia and reveal inter-platform differences

PubMed Central

2014-01-01

Background The reproducibility of transcriptomic biomarkers across datasets remains poor, limiting clinical application. We and others have suggested that this is in-part caused by differential error-structure between datasets, and their incomplete removal by pre-processing algorithms. Methods To test this hypothesis, we systematically assessed the effects of pre-processing on biomarker classification using 24 different pre-processing methods and 15 distinct signatures of tumour hypoxia in 10 datasets (2,143 patients). Results We confirm strong pre-processing effects for all datasets and signatures, and find that these differ between microarray versions. Importantly, exploiting different pre-processing techniques in an ensemble technique improved classification for a majority of signatures. Conclusions Assessing biomarkers using an ensemble of pre-processing techniques shows clear value across multiple diseases, datasets and biomarkers. Importantly, ensemble classification improves biomarkers with initially good results but does not result in spuriously improved performance for poor biomarkers. While further research is required, this approach has the potential to become a standard for transcriptomic biomarkers. PMID:24902696

Quantification of chemical transport processes from the soil to surface runoff.

PubMed

Tian, Kun; Huang, Chi-Hua; Wang, Guang-Qian; Fu, Xu-Dong; Parker, Gary

2013-01-01

There is a good conceptual understanding of the processes that govern chemical transport from the soil to surface runoff, but few studies have actually quantified these processes separately. Thus, we designed a laboratory flow cell and experimental procedures to quantify the chemical transport from soil to runoff water in the following individual processes: (i) convection with a vertical hydraulic gradient, (ii) convection via surface flow or the Bernoulli effect, (iii) diffusion, and (iv) soil loss. We applied different vertical hydraulic gradients by setting the flow cell to generate different seepage or drainage conditions. Our data confirmed the general form of the convection-diffusion equation. However, we now have additional quantitative data that describe the contribution of each individual chemical loading process in different surface runoff and soil hydrological conditions. The results of this study will be useful for enhancing our understanding of different geochemical processes in the surface soil mixing zone. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Disentangling the Dyadic Dance: Theoretical, Methodological and Outcomes Systematic Review of Mother-Infant Dyadic Processes.

PubMed

Provenzi, Livio; Scotto di Minico, Giunia; Giusti, Lorenzo; Guida, Elena; Müller, Mitho

2018-01-01

Background: During the last decades, the research on mother-infant dyad has produced a great amount of data, methods and theories, which largely contributed to set a revolution in the way we look at developmental changes during infancy and childhood. Very different constructs depict the different aspects of the "dyadic dance" occurring between a mother and her infant; nonetheless, a comprehensive and consistent systematization of these concepts in a coherent theoretical landscape is still lacking. Aim: In the present work, we aim at disentangling the different theoretical and methodological definitions of 9 dyadic constructs and we highlight their effects on infants' and children developmental outcomes. Methods: A literature search has been conducted on three databases-PubMed, Scopus, Web of Science. Three different reviews are reported here: (1) a review on the theoretical definitions of dyadic constructs; (2) a review of operational definitions, settings and methods of dyadic processes; (3) a systematic review of dyadic processes' outcomes for infants' and children developmental trajectories. Results: Two constructs emerged as wide meta-theoretical concepts (reciprocity and mutuality) and seven described specific processes (attunement, contingency, coordination, matching, mirroring, reparation, synchrony). A global model resuming the relationships among different processes is reported, which highlights the emergence of two specific cycles of dyadic functioning (i.e., matching-mismatching-reparation-synchrony; contingency, coordination, attunement, mirroring). A comprehensive review of the adopted measures is also provided. Finally, all the processes provided significant contributions to infants' behavioral, cognitive, and socio-emotional development during the first 3 years of age, but limited research has been conducted on specific processes (e.g. reparation and mirroring). Conclusion: The present study provides an original research-grounded framework to consider the different nature of mother-infant dyadic processes within a unified dyadic eco-system. Different levels of evidence emerged for the role of diverse mother-infant dyadic processes on infants' and children development. Open questions and future research directions are highlighted.

Disentangling the Dyadic Dance: Theoretical, Methodological and Outcomes Systematic Review of Mother-Infant Dyadic Processes

PubMed Central

Provenzi, Livio; Scotto di Minico, Giunia; Giusti, Lorenzo; Guida, Elena; Müller, Mitho

2018-01-01

Background: During the last decades, the research on mother-infant dyad has produced a great amount of data, methods and theories, which largely contributed to set a revolution in the way we look at developmental changes during infancy and childhood. Very different constructs depict the different aspects of the “dyadic dance” occurring between a mother and her infant; nonetheless, a comprehensive and consistent systematization of these concepts in a coherent theoretical landscape is still lacking. Aim: In the present work, we aim at disentangling the different theoretical and methodological definitions of 9 dyadic constructs and we highlight their effects on infants' and children developmental outcomes. Methods: A literature search has been conducted on three databases—PubMed, Scopus, Web of Science. Three different reviews are reported here: (1) a review on the theoretical definitions of dyadic constructs; (2) a review of operational definitions, settings and methods of dyadic processes; (3) a systematic review of dyadic processes' outcomes for infants' and children developmental trajectories. Results: Two constructs emerged as wide meta-theoretical concepts (reciprocity and mutuality) and seven described specific processes (attunement, contingency, coordination, matching, mirroring, reparation, synchrony). A global model resuming the relationships among different processes is reported, which highlights the emergence of two specific cycles of dyadic functioning (i.e., matching-mismatching-reparation-synchrony; contingency, coordination, attunement, mirroring). A comprehensive review of the adopted measures is also provided. Finally, all the processes provided significant contributions to infants' behavioral, cognitive, and socio-emotional development during the first 3 years of age, but limited research has been conducted on specific processes (e.g. reparation and mirroring). Conclusion: The present study provides an original research-grounded framework to consider the different nature of mother-infant dyadic processes within a unified dyadic eco-system. Different levels of evidence emerged for the role of diverse mother-infant dyadic processes on infants' and children development. Open questions and future research directions are highlighted. PMID:29615947

Study on the Property Change of Rhizoma Coptidis and Its Ginger Juice Processed Products Based on 5-Ht Level and Brain Tissues Morphology of Rats

NASA Astrophysics Data System (ADS)

Zhong, Lingyun; Tong, Hengli; Lv, Mu; Deng, Yufen

2017-09-01

According to the theory of traditional Chinese Medicine (TCM), all Chinese materia medica need to be processed using Pao zhi which is a processing technology before being used in clinic. Ginger juice, made from dried or fresh ginger, is one of the main TCM processing accessories and always used to help change some Chinese materia medica’s properties for its warm or hot nature. The purpose of this paper is to discuss the influence of ginger juice on Rhizoma Coptidis (RC) by determining 5-hydroxytryptamine (5-HT) content and observing morphological changes in the harns tissue of rats. Raw Rhizoma Coptidis (RRC), fresh ginger juice processed Rhizoma Coptidis (FGJPRC), dried juice processed Rhizoma Coptidis (DGJPRC), dried ginger juice (DGJ) and fresh ginger juice (FGJ) were prepared using appropriate methods. Immunohistochemical staining was used to observe the distribution of 5-HT and fluorescence spectrophotometry was applied to determine 5-hydroxytryptamine content in the brain tissue of rats. 5 - HT in brain tissue of the rats of RRC group was distributed most densely, with the highest content. Compared to the blank group, RRC and different ginger processed RC groups could lead to increasing content of 5-HT in rat encephalon, and significant differences in RRC. Compared with the RRC, the 5-HT content in rat encephalon in DGJPRC, FGJPRC, FGJ and DGJ groups reduced, and DGJPRC, FGJPRC groups showed significant difference, FGJ and DGJ groups showed extreme significant differences. The research showed that processing with hot, warm accessories would moderate the cold nature of RC. The cold and hot nature of Traditional Chinese Materia Medica could be expressed by the difference of 5-HT contents and morphological changes of rats’ brain tissue. Simultaneously, the research showed the different excipient of ginger juice would have different effects on the processing of RC.

Different processing of CAPA and pyrokinin precursors in the giant mealworm beetle Zophobas atratus (Tenebrionidae) and the boll weevil Anthonomus grandis grandis (Curculionidae).

PubMed

Neupert, Susanne; Marciniak, Pawel; Köhler, Rene; Nachman, Ronald J; Suh, Charles P-C; Predel, Reinhard

2018-03-01

Capa and pyrokinin (pk) genes in hexapods share a common evolutionary origin. Using transcriptomics and peptidomics, we analyzed products of these genes in two beetles, the giant mealworm beetle (Zophobas atratus; Tenebrionidae) and the boll weevil (Anthonomus grandis grandis; Curculionidae). Our data revealed that even within Coleoptera, which represents a very well-defined group of insects, highly different evolutionary developments occurred in the neuropeptidergic system. These differences, however, primarily affect the general structure of the precursors and differential processing of mature peptides and, to a lesser degree, the sequences of the active core motifs. With the differential processing of the CAPA-precursor in Z. atratus we found a perfect example of completely different products cleaved from a single neuropeptide precursor in different cells. The CAPA precursor in abdominal ganglia of this species yields primarily periviscerokinins (PVKs) whereas processing of the same precursor in neurosecretory cells of the subesophageal ganglion results in CAPA-tryptoPK and a novel CAPA-PK. Particularly important was the detection of that CAPA-PK which has never been observed in the CNS of insects before. The three different types of CAPA peptides (CAPA-tryptoPK, CAPA-PK, PVK) each represent potential ligands which activate different receptors. In contrast to the processing of the CAPA precursor from Z. atratus, no indications of a differential processing of the CAPA precursor were found in A. g. grandis. These data suggest that rapid evolutionary changes regarding the processing of CAPA precursors were still going on when the different beetle lineages diverged. The sequence of the single known PVK of A. g. grandis occupies a special position within the known PVKs of insects and might serve asa basis to develop lineage-specific peptidomimetics capable of disrupting physiological processes regulated by PVKs. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-Evaluation Processes in Life Satisfaction: Uncovering Measurement Non-Equivalence and Age-Related Differences

ERIC Educational Resources Information Center

Heidemeier, Heike; Staudinger, Ursula M.

2012-01-01

This study demonstrates how self-evaluation processes explain subgroup differences in ratings of life satisfaction (population heterogeneity). Life domains differ with regard to the constraints they impose on beliefs in internal control. We hypothesized that these differences are linked with cognitive biases in ratings of life satisfaction. In…

Modelling of additive manufacturing processes: a review and classification

NASA Astrophysics Data System (ADS)

Stavropoulos, Panagiotis; Foteinopoulos, Panagis

2018-03-01

Additive manufacturing (AM) is a very promising technology; however, there are a number of open issues related to the different AM processes. The literature on modelling the existing AM processes is reviewed and classified. A categorization of the different AM processes in process groups, according to the process mechanism, has been conducted and the most important issues are stated. Suggestions are made as to which approach is more appropriate according to the key performance indicator desired to be modelled and a discussion is included as to the way that future modelling work can better contribute to improving today's AM process understanding.

What is a good public participation process? Five perspectives from the public.

PubMed

Webler, T; Tuler, S; Krueger, R

2001-03-01

It is now widely accepted that members of the public should be involved in environmental decision-making. This has inspired many to search for principles that characterize good public participation processes. In this paper we report on a study that identifies discourses about what defines a good process. Our case study was a forest planning process in northern New England and New York. We employed Q methodology to learn how participants characterize a good process differently, by selecting, defining, and privileging different principles. Five discourses, or perspectives, about good process emerged from our study. One perspective emphasizes that a good process acquires and maintains popular legitimacy. A second sees a good process as one that facilitates an ideological discussion. A third focuses on the fairness of the process. A fourth perspective conceptualizes participatory processes as a power struggle--in this instance a power play between local land-owning interests and outsiders. A fifth perspective highlights the need for leadership and compromise. Dramatic differences among these views suggest an important challenge for those responsible for designing and carrying out public participation processes. Conflicts may emerge about process designs because people disagree about what is good in specific contexts.

An Application of X-Ray Fluorescence as Process Analytical Technology (PAT) to Monitor Particle Coating Processes.

PubMed

Nakano, Yoshio; Katakuse, Yoshimitsu; Azechi, Yasutaka

2018-06-01

An attempt to apply X-Ray Fluorescence (XRF) analysis to evaluate small particle coating process as a Process Analytical Technologies (PAT) was made. The XRF analysis was used to monitor coating level in small particle coating process with at-line manner. The small particle coating process usually consists of multiple coating processes. This study was conducted by a simple coating particles prepared by first coating of a model compound (DL-methionine) and second coating by talc on spherical microcrystalline cellulose cores. The particles with two layered coating are enough to demonstrate the small particle coating process. From the result by the small particle coating process, it was found that the XRF signal played different roles, resulting that XRF signals by first coating (layering) and second coating (mask coating) could demonstrate the extent with different mechanisms for the coating process. Furthermore, the particle coating of the different particle size has also been investigated to evaluate size effect of these coating processes. From these results, it was concluded that the XRF could be used as a PAT in monitoring particle coating processes and become powerful tool in pharmaceutical manufacturing.

Control Strategies for Drug Product Continuous Direct Compression-State of Control, Product Collection Strategies, and Startup/Shutdown Operations for the Production of Clinical Trial Materials and Commercial Products.

PubMed

Almaya, Ahmad; De Belder, Lawrence; Meyer, Robert; Nagapudi, Karthik; Lin, Hung-Ren Homer; Leavesley, Ian; Jayanth, Jayanthy; Bajwa, Gurjit; DiNunzio, James; Tantuccio, Anthony; Blackwood, Dan; Abebe, Admassu

2017-04-01

Continuous manufacturing (CM) has emerged in the pharmaceutical industry as a paradigm shift with significant advantages related to cost, efficiency, flexibility, and higher assurance of quality. The inherent differences from batch processes justify examining the CM control strategy more holistically. This article describes the current thinking for the control and implementation of CM, using the example of a direct compression process and taking into consideration the ICH Q10 definition of "state of control" and process validation requirements. Statistical process control using control charts, sources of variation, process capability, and process performance is explained as a useful concept that can help assess the impact of variation within a batch and indicates if a process is in state of control. The potential for time-variant nature of startup and shutdown with CM is discussed to assure product quality while minimizing waste as well as different options for detection and isolation of non-conforming materials due to process upsets. While different levels of control are possible with CM, an appropriate balance between process control and end product testing is needed depending on the level of process understanding at the different stages of development from the production of clinical supplies through commercialization. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Processing maize flour and corn meal food products

PubMed Central

Gwirtz, Jeffrey A; Garcia-Casal, Maria Nieves

2014-01-01

Corn is the cereal with the highest production worldwide and is used for human consumption, livestock feed, and fuel. Various food technologies are currently used for processing industrially produced maize flours and corn meals in different parts of the world to obtain precooked refined maize flour, dehydrated nixtamalized flour, fermented maize flours, and other maize products. These products have different intrinsic vitamin and mineral contents, and their processing follows different pathways from raw grain to the consumer final product, which entail changes in nutrient composition. Dry maize mechanical processing creates whole or fractionated products, separated by anatomical features such as bran, germ, and endosperm. Wet maize processing separates by chemical compound classification such as starch and protein. Various industrial processes, including whole grain, dry milling fractionation, and nixtamalization, are described. Vitamin and mineral losses during processing are identified and the nutritional impacts outlined. Also discussed are the vitamin and mineral contents of corn. PMID:24329576

Towards a multi-level approach to the emergence of meaning processes in living systems.

PubMed

Queiroz, João; El-Hani, Charbel Niño

2006-09-01

Any description of the emergence and evolution of different types of meaning processes (semiosis, sensu C.S.Peirce) in living systems must be supported by a theoretical framework which makes it possible to understand the nature and dynamics of such processes. Here we propose that the emergence of semiosis of different kinds can be understood as resulting from fundamental interactions in a triadically-organized hierarchical process. To grasp these interactions, we develop a model grounded on Stanley Salthe's hierarchical structuralism. This model can be applied to establish, in a general sense, a set of theoretical constraints for explaining the instantiation of different kinds of meaning processes (iconic, indexical, symbolic) in semiotic systems. We use it to model a semiotic process in the immune system, namely, B-cell activation, in order to offer insights into the heuristic role it can play in the development of explanations for specific semiotic processes.

Self-tuning regulator for an interacting CSTR process

NASA Astrophysics Data System (ADS)

Rajendra Mungale, Niraj; Upadhyay, Akshay; Jaganatha Pandian, B.

2017-11-01

In the paper we have laid emphasis on STR that is Self Tuning Regulator and its application for an interacting process. CSTR has a great importance in Chemical Process when we deal with controlling different parameters of a process using CSTR. Basically CSTR is used to maintain a constant liquid temperature in the process. The proposed method called self-tuning regulator, is a different scheme where process parameters are updated and the controller parameters are obtained from the solution of a design problem. The paper deals with STR and methods associated with it.

Biosimilarity Versus Manufacturing Change: Two Distinct Concepts.

PubMed

Declerck, Paul; Farouk-Rezk, Mourad; Rudd, Pauline M

2016-02-01

As products of living cells, biologics are far more complicated than small molecular-weight drugs not only with respect to size and structural complexity but also their sensitivity to manufacturing processes and post-translational changes. Most of the information on the manufacturing process of biotherapeutics is proprietary and hence not fully accessible to the public. This information gap represents a key challenge for biosimilar developers and plays a key role in explaining the differences in regulatory pathways required to demonstrate biosimilarity versus those required to ensure that a change in manufacturing process did not have implications on safety and efficacy. Manufacturing process changes are frequently needed for a variety of reasons including response to regulatory requirements, up scaling production, change in facility, change in raw materials, improving control of quality (consistency) or optimising production efficiency. The scope of the change is usually a key indicator of the scale of analysis required to evaluate the quality. In most cases, where the scope of the process change is limited, only quality and analytical studies should be sufficient while comparative clinical studies can be required in case of major changes (e.g., cell line changes). Biosimilarity exercises have been addressed differently by regulators on the understanding that biosimilar developers start with fundamental differences being a new cell line and also a knowledge gap of the innovator's processes, including culture media, purification processes, and potentially different formulations, and are thus required to ensure that differences from innovators do not result in differences in efficacy and safety.

Neural correlates of processing facial identity based on features versus their spacing.

PubMed

Maurer, D; O'Craven, K M; Le Grand, R; Mondloch, C J; Springer, M V; Lewis, T L; Grady, C L

2007-04-08

Adults' expertise in recognizing facial identity involves encoding subtle differences among faces in the shape of individual facial features (featural processing) and in the spacing among features (a type of configural processing called sensitivity to second-order relations). We used fMRI to investigate the neural mechanisms that differentiate these two types of processing. Participants made same/different judgments about pairs of faces that differed only in the shape of the eyes and mouth, with minimal differences in spacing (featural blocks), or pairs of faces that had identical features but differed in the positions of those features (spacing blocks). From a localizer scan with faces, objects, and houses, we identified regions with comparatively more activity for faces, including the fusiform face area (FFA) in the right fusiform gyrus, other extrastriate regions, and prefrontal cortices. Contrasts between the featural and spacing conditions revealed distributed patterns of activity differentiating the two conditions. A region of the right fusiform gyrus (near but not overlapping the localized FFA) showed greater activity during the spacing task, along with multiple areas of right frontal cortex, whereas left prefrontal activity increased for featural processing. These patterns of activity were not related to differences in performance between the two tasks. The results indicate that the processing of facial features is distinct from the processing of second-order relations in faces, and that these functions are mediated by separate and lateralized networks involving the right fusiform gyrus, although the FFA as defined from a localizer scan is not differentially involved.

Processing of visually presented clock times.

PubMed

Goolkasian, P; Park, D C

1980-11-01

The encoding and representation of visually presented clock times was investigated in three experiments utilizing a comparative judgment task. Experiment 1 explored the effects of comparing times presented in different formats (clock face, digit, or word), and Experiment 2 examined angular distance effects created by varying positions of the hands on clock faces. In Experiment 3, encoding and processing differences between clock faces and digitally presented times were directly measured. Same/different reactions to digitally presented times were faster than to times presented on a clock face, and this format effect was found to be a result of differences in processing that occurred after encoding. Angular separation also had a limited effect on processing. The findings are interpreted within the framework of theories that refer to the importance of representational codes. The applicability to the data of Bank's semantic-coding theory, Paivio's dual-coding theory, and the levels-of-processing view of memory are discussed.

Isoflavone profile in soymilk as affected by soybean variety, grinding, and heat-processing methods.

PubMed

Zhang, Yan; Chang, Sam K C; Liu, Zhisheng

2015-05-01

Isoflavones impart health benefits and their overall content and profile in foods are greatly influenced at each step during processing. In this study, 2 soybean varieties (Prosoy and black soybean) were processed with 3 different grinding (ambient, cold, and hot grinding) and heating methods (traditional stove cooking, 1-phase UHT, and 2-phase UHT) for soymilk making. The results showed after cold, ambient, and hot grinding, the total isoflavones were 3917, 5013, and 5949 nmol/g for Prosoy; the total isoflavones were 4073, 3966, and 4284 nmol/g for black soybean. Grinding could significantly increase isoflavone extraction. The grinding process had a destructive effect on isoflavones and this effect varied with grinding temperature. Different heating methods had different effects on different isoflavone forms. Two soybean varieties showed distinct patterns with respect to the change of isoflavone profile during processing. © 2015 Institute of Food Technologists®

Processing data base information having nonwhite noise

DOEpatents

Gross, Kenneth C.; Morreale, Patricia

1995-01-01

A method and system for processing a set of data from an industrial process and/or a sensor. The method and system can include processing data from either real or calculated data related to an industrial process variable. One of the data sets can be an artificial signal data set generated by an autoregressive moving average technique. After obtaining two data sets associated with one physical variable, a difference function data set is obtained by determining the arithmetic difference between the two pairs of data sets over time. A frequency domain transformation is made of the difference function data set to obtain Fourier modes describing a composite function data set. A residual function data set is obtained by subtracting the composite function data set from the difference function data set and the residual function data set (free of nonwhite noise) is analyzed by a statistical probability ratio test to provide a validated data base.

The Vanderbilt Holistic Face Processing Test: A short and reliable measure of holistic face processing

PubMed Central

Richler, Jennifer J.; Floyd, R. Jackie; Gauthier, Isabel

2014-01-01

Efforts to understand individual differences in high-level vision necessitate the development of measures that have sufficient reliability, which is generally not a concern in group studies. Holistic processing is central to research on face recognition and, more recently, to the study of individual differences in this area. However, recent work has shown that the most popular measure of holistic processing, the composite task, has low reliability. This is particularly problematic for the recent surge in interest in studying individual differences in face recognition. Here, we developed and validated a new measure of holistic face processing specifically for use in individual-differences studies. It avoids some of the pitfalls of the standard composite design and capitalizes on the idea that trial variability allows for better traction on reliability. Across four experiments, we refine this test and demonstrate its reliability. PMID:25228629

Early and late brain signatures of emotional prosody among individuals with high versus low power.

PubMed

Paulmann, Silke; Uskul, Ayse K

2017-04-01

Using ERPs, we explored the relationship between social power and emotional prosody processing. In particular, we investigated differences at early and late processing stages between individuals primed with high or low power. Comparable to previously published findings from nonprimed participants, individuals primed with low power displayed differentially modulated P2 amplitudes in response to different emotional prosodies, whereas participants primed with high power failed to do so. Similarly, participants primed with low power showed differentially modulated amplitudes in response to different emotional prosodies at a later processing stage (late ERP component), whereas participants primed with high power did not. These ERP results suggest that high versus low power leads to emotional prosody processing differences at the early stage associated with emotional salience detection and at a later stage associated with more in-depth processing of emotional stimuli. © 2016 Society for Psychophysiological Research.

The Effect of Keyboard-Based Word Processing on Students with Different Working Memory Capacity during the Process of Academic Writing

ERIC Educational Resources Information Center

Van Der Steen, Steffie; Samuelson, Dianne; Thomson, Jennifer M.

2017-01-01

This study addresses the current debate about the beneficial effects of text processing software on students with different working memory (WM) during the process of academic writing, especially with regard to the ability to display higher-level conceptual thinking. A total of 54 graduate students (15 male, 39 female) wrote one essay by hand and…

Efficient multitasking: parallel versus serial processing of multiple tasks

PubMed Central

Fischer, Rico; Plessow, Franziska

2015-01-01

In the context of performance optimizations in multitasking, a central debate has unfolded in multitasking research around whether cognitive processes related to different tasks proceed only sequentially (one at a time), or can operate in parallel (simultaneously). This review features a discussion of theoretical considerations and empirical evidence regarding parallel versus serial task processing in multitasking. In addition, we highlight how methodological differences and theoretical conceptions determine the extent to which parallel processing in multitasking can be detected, to guide their employment in future research. Parallel and serial processing of multiple tasks are not mutually exclusive. Therefore, questions focusing exclusively on either task-processing mode are too simplified. We review empirical evidence and demonstrate that shifting between more parallel and more serial task processing critically depends on the conditions under which multiple tasks are performed. We conclude that efficient multitasking is reflected by the ability of individuals to adjust multitasking performance to environmental demands by flexibly shifting between different processing strategies of multiple task-component scheduling. PMID:26441742

Efficient multitasking: parallel versus serial processing of multiple tasks.

PubMed

Fischer, Rico; Plessow, Franziska

2015-01-01

In the context of performance optimizations in multitasking, a central debate has unfolded in multitasking research around whether cognitive processes related to different tasks proceed only sequentially (one at a time), or can operate in parallel (simultaneously). This review features a discussion of theoretical considerations and empirical evidence regarding parallel versus serial task processing in multitasking. In addition, we highlight how methodological differences and theoretical conceptions determine the extent to which parallel processing in multitasking can be detected, to guide their employment in future research. Parallel and serial processing of multiple tasks are not mutually exclusive. Therefore, questions focusing exclusively on either task-processing mode are too simplified. We review empirical evidence and demonstrate that shifting between more parallel and more serial task processing critically depends on the conditions under which multiple tasks are performed. We conclude that efficient multitasking is reflected by the ability of individuals to adjust multitasking performance to environmental demands by flexibly shifting between different processing strategies of multiple task-component scheduling.

Comparison of the sensitivity to change of the Functional Independence Measure with the Assessment of Motor and Process Skills within different rehabilitation populations.

PubMed

Choo, Silvana X; Stratford, Paul; Richardson, Julie; Bosch, Jackie; Pettit, Susan M; Ansley, Barbara J; Harris, Jocelyn E

2017-09-10

To determine whether there was a difference in the sensitivity to change of the subscales of the Functional Independence Measure and the Assessment of Motor and Process Skills within three different post-acute inpatient rehabilitation populations. We conducted retrospective chart review of patients consecutively admitted to inpatient rehabilitation units, with both admission and discharge Functional Independence Measure and Assessment of Motor and Process Skills scores. A total of 276 participants were included and categorized into diagnostic groups (orthopedic, oncology, and geriatric). Within group, sensitivity to change was evaluated for the subscales of each measure by calculating the difference in standardized response means (SRM) and 95% confidence intervals (CI). The Functional Independence Measure motor subscale was more sensitive to change than the Assessment of Motor and Process Skills in the orthopedic and geriatric groups (SRM difference  = 1.53 [95% CI 0.93, 2.3] and 0.65 [95% CI 0.3, 1.02], respectively) but not in the oncology group (SRM difference  = 0.42 [95% CI -0.2, 1.04]). For the cognitive subscales, the Assessment of Motor and Process Skills was more sensitive to change than the Functional Independence Measure in all three groups (SRM difference  = 0.38 [95% CI 004, 0.74], 0.65 [95% CI 0.45, 0.90], and 1.15 [95% CI 0.77, 1.69] for orthopedic, geriatric, and oncology, respectively). The Functional Independence Measure is a mandated measure for all rehabilitation units in Canada. As the cognitive subscale of the Assessment of Motor and Process Skills is more sensitive to change than the Functional Independence Measure, we recommend also administering the Assessment of Motor and Process Skills to better detect changes in the cognitive aspect of function. Implications for rehabilitation When deciding between the Functional Independence Measure or the Assessment of Motor and Process Skills, it is important to consider whether patients' functional status is expected to change similarly or differently. The difference in sensitivity to change between the subscales of the two outcome measures varies with the characteristics of change (similar or different) in patients' functional status. We recommend using the Assessment of Motor and Process Skills, along with the Functional Independence Measure, for patients who are expected to make similar amounts of change in functional status, as the cognitive subscale of the Assessment of Motor and Process Skills is more sensitive to change and can better detect changes in the cognitive aspect of functioning. For patients whose functional status are expected to change differently (diverse diagnoses), the Functional Independence Measure may be more useful as the motor subscale was more sensitive to change when comparing between rehabilitation populations.

Structural organization of parallel information processing within the tectofugal visual system of the pigeon.

PubMed

Hellmann, B; Güntürkün, O

2001-01-01

Visual information processing within the ascending tectofugal pathway to the forebrain undergoes essential rearrangements between the mesencephalic tectum opticum and the diencephalic nucleus rotundus of birds. The outer tectal layers constitute a two-dimensional map of the visual surrounding, whereas nucleus rotundus is characterized by functional domains in which different visual features such as movement, color, or luminance are processed in parallel. Morphologic correlates of this reorganization were investigated by means of focal injections of the neuronal tracer choleratoxin subunit B into different regions of the nuclei rotundus and triangularis of the pigeon. Dependent on the thalamic injection site, variations in the retrograde labeling pattern of ascending tectal efferents were observed. All rotundal projecting neurons were located within the deep tectal layer 13. Five different cell populations were distinguished that could be differentiated according to their dendritic ramifications within different retinorecipient laminae and their axons projecting to different subcomponents of the nucleus rotundus. Because retinorecipient tectal layers differ in their input from distinct classes of retinal ganglion cells, each tectorotundal cell type probably processes different aspects of the visual surrounding. Therefore, the differential input/output connections of the five tectorotundal cell groups might constitute the structural basis for spatially segregated parallel information processing of different stimulus aspects within the tectofugal visual system. Because two of five rotundal projecting cell groups additionally exhibited quantitative shifts along the dorsoventral extension of the tectum, data also indicate visual field-dependent alterations in information processing for particular visual features. Copyright 2001 Wiley-Liss, Inc.

A Contextual View of Adult Learning and Memory.

ERIC Educational Resources Information Center

Glynn, Shawn M.

Explanations of age-related differences in adult memory usually assume two forms: processing deficits and structural deficits. Processing deficit explanations attribute recall differences to a failure of older adults to effectively use the processes of attention, organization, mediation (the use of such devices as visual images and verbal images…

Exciton-dominant Electroluminescence from a Diode of Monolayer MoS2

DTIC Science & Technology

2014-05-14

caused by a phonon-assisted nonradiative process, as the two peaks display different current dependencies. We pro- pose this is a different effect...monolayer MoS2. The Auger process opens up a nonradiative recombination channel for electron-hole pair recombination. If the Auger process is

Children's Incidental Memory for Pictures: Item Processing Versus List Organizations.

ERIC Educational Resources Information Center

Ghatala, Elizabeth S.; Levin, Joel R.

1981-01-01

Two experiments which tested recall differences among young children indicated: (1) organizational factors, not item processing per se, influenced previously found differences in children's recall of pictures following semantic and physical orienting tasks; and (2) physical orienting tasks may effectively inhibit subjects' processing of words, but…

Human Cognition and Information Processing: Potential Problems for a Field Dependent Human Sequential Information Processor.

ERIC Educational Resources Information Center

Shaughnessy, M.; And Others

Numerous cognitive psychologists have validated the hypothesis, originally advanced by the Russian physician, A. Luria, that different individuals process information in two distinctly different manners: simultaneously and sequentially. The importance of recognizing the existence of these two distinct styles of processing information and selecting…

An Individual Differences Analysis of Double-Aspect Stimulus Perception.

ERIC Educational Resources Information Center

Forsyth, G. Alfred; Huber, R. John

Any theory of information processing must address both what is processed and how that processing takes place. Most studies investigating variables which alter physical dimension utilization have ignored the large individual differences in selective attention or cue utilization. A paradigm was developed using an individual focus on information…

Nitrous oxide and methane emissions from different treatment processes in full-scale municipal wastewater treatment plants.

PubMed

Rena, Y G; Wang, J H; Li, H F; Zhang, J; Qi, P Y; Hu, Z

2013-01-01

Nitrous oxide (N2O) and methane (CH4) are two important greenhouse gases (GHG) emitted from biological nutrient removal (BNR) processes in municipal wastewater treatment plants (WWTP). In this study, three typical biological wastewater treatment processes were studied in WWTP of Northern China: pre-anaerobic carrousel oxidation ditch (A+OD) process, pre-anoxic anaerobic-anoxic-oxic (A-A/ A/O) process and reverse anaerobic-anoxic-oxic (r-A/ A/O) process. The N2O and CH4 emissions from these three different processes were measured in every processing unit of each WWTP. Results showed that N2O and CH4 were mainly discharged during the nitrification/denitrification process and the anaerobic/anoxic treatment process, respectively and the amounts of their formation and release were significantly influenced by different BNR processes implemented in these WWTP. The N2O conversion ratio of r-A/ A/O process was the lowest among the three WWTP, which were 10.9% and 18.6% lower than that of A-A/A/O process and A+OD process, respectively. Similarly, the CH4 conversion ratio of r-A/ A/O process was the lowest among the three WWTP, which were 89. I% and 80.8% lower than that of A-A/ A/O process and A+OD process, respectively. The factors influencing N2O and CH4 formation and emission in the three WWTP were investigated to explain the difference between these processes. The nitrite concentration and oxidation-reduction potential (ORP) value were found to be the dominant influencing factors affecting N2O and CH4 production, respectively. The flow-based emission factors of N2O and CH4 of the WWTP were figured out for better quantification of GHG emissions and further technical assessments of mitigation options.

Illumina MiSeq sequencing reveals microbial community in HA process for dyeing wastewater treatment fed with different co-substrates.

PubMed

Xie, Xuehui; Liu, Na; Ping, Jing; Zhang, Qingyun; Zheng, Xiulin; Liu, Jianshe

2018-06-01

In present study, a hydrolysis acidification (HA) reactor was used for simulated dyeing wastewater treatment. Co-substrates included starch, glucose, sucrose, yeast extract (YE) and peptone were fed sequentially into the HA reactor to enhance the HA process effects. The performance of the HA reactor and the microbial community structure in HA process were investigated under different co-substrates conditions. Results showed that different co-substrates had different influences on the performance of HA reactor. The highest decolorization (50.64%) and COD removal rate (60.73%) of the HA reactor were obtained when sucrose was as the co-substrate. And it found that carbon co-substrates starch, glucose and sucrose exhibited better decolorization and higher COD removal efficiency of the HA reactor than the nitrogen co-substrates YE and peptone. Microbial community structure in the HA process was analyzed by Illumina MiSeq sequencing. Results revealed different co-substrates had different influences on the community structure and microbial diversity in HA process. It was considered that sucrose could enrich the species such as Raoultella, Desulfovibrio, Tolumonas, Clostridium, which might be capable of degrading the dyes. Sucrose was considered to be the best co-substrate of enhancing the HA reactor's performance in this study. This work would provide deep insight into the influence of many different co-substrates on HA reactor performance and microbial communities in HA process. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Process management in the hospital pharmacy for the improvement of the patient safety].

PubMed

Govindarajan, R; Perelló-Juncá, A; Parès-Marimòn, R M; Serrais-Benavente, J; Ferrandez-Martí, D; Sala-Robinat, R; Camacho-Calvente, A; Campabanal-Prats, C; Solà-Anderiu, I; Sanchez-Caparrós, S; Gonzalez-Estrada, J; Martinez-Olalla, P; Colomer-Palomo, J; Perez-Mañosas, R; Rodríguez-Gallego, D

2013-01-01

To define a process management model for a hospital pharmacy in order to measure, analyse and make continuous improvements in patient safety and healthcare quality. In order to implement process management, Igualada Hospital was divided into different processes, one of which was the Hospital Pharmacy. A multidisciplinary management team was given responsibility for each process. For each sub-process one person was identified to be responsible, and a working group was formed under his/her leadership. With the help of each working group, a risk analysis using failure modes and effects analysis (FMEA) was performed, and the corresponding improvement actions were implemented. Sub-process indicators were also identified, and different process management mechanisms were introduced. The first risk analysis with FMEA produced more than thirty preventive actions to improve patient safety. Later, the weekly analysis of errors, as well as the monthly analysis of key process indicators, permitted us to monitor process results and, as each sub-process manager participated in these meetings, also to assume accountability and responsibility, thus consolidating the culture of excellence. The introduction of different process management mechanisms, with the participation of people responsible for each sub-process, introduces a participative management tool for the continuous improvement of patient safety and healthcare quality. Copyright © 2012 SECA. Published by Elsevier Espana. All rights reserved.

Purification processes of xenogeneic bone substitutes and their impact on tissue reactions and regeneration.

PubMed

Perić Kačarević, Zeljka; Kavehei, Faraz; Houshmand, Alireza; Franke, Jörg; Smeets, Ralf; Rimashevskiy, Denis; Wenisch, Sabine; Schnettler, Reinhard; Jung, Ole; Barbeck, Mike

2018-04-01

Xenogeneic bone substitute materials are widely used in oral implantology. Prior to their clinical use, purification of the former bone tissue has to be conducted to ensure the removal of immunogenic components and pathogens. Different physicochemical methods are applied for purification of the donor tissue, and temperature treatment is one of these methods. Differences in these methods and especially the application of different temperatures for purification may lead to different material characteristics, which may influence the tissue reactions to these materials and the related (bone) healing process. However, little is known about the different material characteristics and their influences on the healing process. Thus, the aim of this mini-review is to summarize the preparation processes and the related material characteristics, safety aspects, tissue reactions, resorbability and preclinical and clinical data of two widely used xenogeneic bone substitutes that mainly differ in the temperature treatment: sintered (cerabone ® ) and non-sintered (Bio-Oss ® ) bovine-bone materials. Based on the summarized data from the literature, a connection between the material-induced tissue reactions and the consequences for the healing processes are presented with the aim of translation into their clinical application.

Gender differences in memory processing of female facial attractiveness: evidence from event-related potentials.

PubMed

Zhang, Yan; Wei, Bin; Zhao, Peiqiong; Zheng, Minxiao; Zhang, Lili

2016-06-01

High rates of agreement in the judgment of facial attractiveness suggest universal principles of beauty. This study investigated gender differences in recognition memory processing of female facial attractiveness. Thirty-four Chinese heterosexual participants (17 females, 17 males) aged 18-24 years (mean age 21.63 ± 1.51 years) participated in the experiment which used event-related potentials (ERPs) based on a study-test paradigm. The behavioral data results showed that both men and women had significantly higher accuracy rates for attractive faces than for unattractive faces, but men reacted faster to unattractive faces. Gender differences on ERPs showed that attractive faces elicited larger early components such as P1, N170, and P2 in men than in women. The results indicated that the effects of recognition bias during memory processing modulated by female facial attractiveness are greater for men than women. Behavioral and ERP evidences indicate that men and women differ in their attentional adhesion to attractive female faces; different mating-related motives may guide the selective processing of attractive men and women. These findings establish a contribution of gender differences on female facial attractiveness during memory processing from an evolutionary perspective.

A Novel Scale Up Model for Prediction of Pharmaceutical Film Coating Process Parameters.

PubMed

Suzuki, Yasuhiro; Suzuki, Tatsuya; Minami, Hidemi; Terada, Katsuhide

2016-01-01

In the pharmaceutical tablet film coating process, we clarified that a difference in exhaust air relative humidity can be used to detect differences in process parameters values, the relative humidity of exhaust air was different under different atmospheric air humidity conditions even though all setting values of the manufacturing process parameters were the same, and the water content of tablets was correlated with the exhaust air relative humidity. Based on this experimental data, the exhaust air relative humidity index (EHI), which is an empirical equation that includes as functional parameters the pan coater type, heated air flow rate, spray rate of coating suspension, saturated water vapor pressure at heated air temperature, and partial water vapor pressure at atmospheric air pressure, was developed. The predictive values of exhaust relative humidity using EHI were in good correlation with the experimental data (correlation coefficient of 0.966) in all datasets. EHI was verified using the date of seven different drug products of different manufacturing scales. The EHI model will support formulation researchers by enabling them to set film coating process parameters when the batch size or pan coater type changes, and without the time and expense of further extensive testing.

Information theoretic analysis of edge detection in visual communication

NASA Astrophysics Data System (ADS)

Jiang, Bo; Rahman, Zia-ur

2010-08-01

Generally, the designs of digital image processing algorithms and image gathering devices remain separate. Consequently, the performance of digital image processing algorithms is evaluated without taking into account the artifacts introduced into the process by the image gathering process. However, experiments show that the image gathering process profoundly impacts the performance of digital image processing and the quality of the resulting images. Huck et al. proposed one definitive theoretic analysis of visual communication channels, where the different parts, such as image gathering, processing, and display, are assessed in an integrated manner using Shannon's information theory. In this paper, we perform an end-to-end information theory based system analysis to assess edge detection methods. We evaluate the performance of the different algorithms as a function of the characteristics of the scene, and the parameters, such as sampling, additive noise etc., that define the image gathering system. The edge detection algorithm is regarded to have high performance only if the information rate from the scene to the edge approaches the maximum possible. This goal can be achieved only by jointly optimizing all processes. People generally use subjective judgment to compare different edge detection methods. There is not a common tool that can be used to evaluate the performance of the different algorithms, and to give people a guide for selecting the best algorithm for a given system or scene. Our information-theoretic assessment becomes this new tool to which allows us to compare the different edge detection operators in a common environment.

Growth Control and Disease Mechanisms in Computational Embryogeny

NASA Technical Reports Server (NTRS)

Shapiro, Andrew A.; Yogev, Or; Antonsson, Erik K.

2008-01-01

This paper presents novel approach to applying growth control and diseases mechanisms in computational embryogeny. Our method, which mimics fundamental processes from biology, enables individuals to reach maturity in a controlled process through a stochastic environment. Three different mechanisms were implemented; disease mechanisms, gene suppression, and thermodynamic balancing. This approach was integrated as part of a structural evolutionary model. The model evolved continuum 3-D structures which support an external load. By using these mechanisms we were able to evolve individuals that reached a fixed size limit through the growth process. The growth process was an integral part of the complete development process. The size of the individuals was determined purely by the evolutionary process where different individuals matured to different sizes. Individuals which evolved with these characteristics have been found to be very robust for supporting a wide range of external loads.

Implementation of a Web-Based Collaborative Process Planning System

NASA Astrophysics Data System (ADS)

Wang, Huifen; Liu, Tingting; Qiao, Li; Huang, Shuangxi

Under the networked manufacturing environment, all phases of product manufacturing involving design, process planning, machining and assembling may be accomplished collaboratively by different enterprises, even different manufacturing stages of the same part may be finished collaboratively by different enterprises. Based on the self-developed networked manufacturing platform eCWS(e-Cooperative Work System), a multi-agent-based system framework for collaborative process planning is proposed. In accordance with requirements of collaborative process planning, share resources provided by cooperative enterprises in the course of collaboration are classified into seven classes. Then a reconfigurable and extendable resource object model is built. Decision-making strategy is also studied in this paper. Finally a collaborative process planning system e-CAPP is developed and applied. It provides strong support for distributed designers to collaboratively plan and optimize product process though network.

Antioxidants, mechanisms, and recovery by membrane processes.

PubMed

Bazinet, Laurent; Doyen, Alain

2017-03-04

Antioxidants molecules have a great interest for bio-food and nutraceutical industries since they play a vital role for their capacity to reduce oxidative processes. Consequently, these molecules, generally present in complex matrices, have to be fractionated and purified to characterize them and to test their antioxidant activity. However, as natural or synthetics antioxidant molecules differ in terms of structural composition and physico-chemical properties, appropriate separation technologies must be selected. Different fractionation technologies are available but the most commonly used are filtration processes. Indeed, these technologies allow fractionation according to molecular size (pressure-driven processes), charge, or both size and charge (electrically driven processes). In this context, and after summarizing the reaction mechanisms of the different classes and nature of antioxidants as well as membrane fractionation technologies, this manuscript presents the specific applications of these membranes processes for the recovery of antioxidant molecules.

Individual and Developmental Differences in Cognitive-Processing Components of Mental Ability

ERIC Educational Resources Information Center

Keating, Daniel P.; Bobbitt, Bruce L.

1978-01-01

Three experiments (simple versus choice reaction time, Posner letter identification, and Sternberg memory scanning) attempted to determine whether reliable individual differences in cognitive processing exist in children and, if so, whether these differences are systematically related to age and ability. (Author/JMB)

Influence of different positive emotions on persuasion processing: a functional evolutionary approach.

PubMed

Griskevicius, Vladas; Shiota, Michelle N; Neufeld, Samantha L

2010-04-01

Much research has found that positive affect facilitates increased reliance on heuristics in cognition. However, theories proposing distinct evolutionary fitness-enhancing functions for specific positive emotions also predict important differences among the consequences of different positive emotion states. Two experiments investigated how six positive emotions influenced the processing of persuasive messages. Using different methods to induce emotions and assess processing, we showed that the positive emotions of anticipatory enthusiasm, amusement, and attachment love tended to facilitate greater acceptance of weak persuasive messages (consistent with previous research), whereas the positive emotions of awe and nurturant love reduced persuasion by weak messages. In addition, a series of mediation analyses suggested that the effects distinguishing different positive emotions from a neutral control condition were best accounted for by different mediators rather than by one common mediator. These findings build upon approaches that link affective valence to certain types of processing, documenting emotion-specific effects on cognition that are consistent with functional evolutionary accounts of discrete positive emotions. Copyright 2010 APA, all rights reserved.