Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

PubMed

Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

2014-12-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

Overexpression of EMMPRIN Isoform 2 Is Associated with Head and Neck Cancer Metastasis

PubMed Central

Guo, Weijie; Wang, Lili; Li, Haigang; Zhang, Tianyu; Liu, Xiaojia; Xu, Qin; Li, Jinsong; Guo, Zhongmin

2014-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a plasma membrane protein of the immunoglobulin (Ig) superfamily, has been reported to promote cancer cell invasion and metastasis in several human malignancies. However, the roles of the different EMMPRIN isoforms and their associated mechanisms in head and neck cancer progression remain unknown. Using quantitative real-time PCR, we found that EMMPRIN isoform 2 (EMMPRIN-2) was the only isoform that was overexpressed in both head and neck cancer tissues and cell lines and that it was associated with head and neck cancer metastasis. To determine the effects of EMMPRIN-2 on head and neck cancer progression, we transfected head and neck cancer cells with an EMMPRIN-2 expression vector and EMMPRIN-2 siRNA to exogenously modulate EMMPRIN-2 expression and examined the functional importance of EMMPRIN-2 in head and neck cancer invasion and metastasis. We found that EMMPRIN-2 promoted head and neck cancer cell invasion, migration, and adhesion in vitro and increased lung metastasis in vivo. Mechanistic studies revealed that EMMPRIN-2 overexpression promoted the secretion of extracellular signaling molecules, including matrix metalloproteinases-2(MMP-2), urokinase-type plasminogen activator(uPA) and Cathepsin B, in head and neck cancer cells. While MMP-2 and uPA have been demonstrated to be important mediators of EMMPRIN signaling, the role of Cathepsin B in EMMPRIN-mediated molecular cascades and tumorigenesis has not been established. We found that EMMPRIN-2 overexpression and Cathepsin B down-regulation significantly inhibited the invasion, migration and adhesion of Tca8133 cells, suggesting that Cathepsin B is required for EMMPRIN-2 enhanced cell migration and invasion in head and neck cancer. The results of our study demonstrate the important role of EMMPRIN-2 in head and neck cancer progression for the first time and reveal that increased extracellular secretion of Cathepsin B may be a novel mechanism underlying EMMPRIN-2 enhanced tumor progression in head and neck cancer. PMID:24705283

Overexpression of EMMPRIN isoform 2 is associated with head and neck cancer metastasis.

PubMed

Huang, Zhiquan; Tan, Ning; Guo, Weijie; Wang, Lili; Li, Haigang; Zhang, Tianyu; Liu, Xiaojia; Xu, Qin; Li, Jinsong; Guo, Zhongmin

2014-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a plasma membrane protein of the immunoglobulin (Ig) superfamily, has been reported to promote cancer cell invasion and metastasis in several human malignancies. However, the roles of the different EMMPRIN isoforms and their associated mechanisms in head and neck cancer progression remain unknown. Using quantitative real-time PCR, we found that EMMPRIN isoform 2 (EMMPRIN-2) was the only isoform that was overexpressed in both head and neck cancer tissues and cell lines and that it was associated with head and neck cancer metastasis. To determine the effects of EMMPRIN-2 on head and neck cancer progression, we transfected head and neck cancer cells with an EMMPRIN-2 expression vector and EMMPRIN-2 siRNA to exogenously modulate EMMPRIN-2 expression and examined the functional importance of EMMPRIN-2 in head and neck cancer invasion and metastasis. We found that EMMPRIN-2 promoted head and neck cancer cell invasion, migration, and adhesion in vitro and increased lung metastasis in vivo. Mechanistic studies revealed that EMMPRIN-2 overexpression promoted the secretion of extracellular signaling molecules, including matrix metalloproteinases-2(MMP-2), urokinase-type plasminogen activator(uPA) and Cathepsin B, in head and neck cancer cells. While MMP-2 and uPA have been demonstrated to be important mediators of EMMPRIN signaling, the role of Cathepsin B in EMMPRIN-mediated molecular cascades and tumorigenesis has not been established. We found that EMMPRIN-2 overexpression and Cathepsin B down-regulation significantly inhibited the invasion, migration and adhesion of Tca8133 cells, suggesting that Cathepsin B is required for EMMPRIN-2 enhanced cell migration and invasion in head and neck cancer. The results of our study demonstrate the important role of EMMPRIN-2 in head and neck cancer progression for the first time and reveal that increased extracellular secretion of Cathepsin B may be a novel mechanism underlying EMMPRIN-2 enhanced tumor progression in head and neck cancer.

The mediator complex in genomic and non-genomic signaling in cancer.

PubMed

Weber, Hannah; Garabedian, Michael J

2018-05-01

Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Mediator structure and rearrangements required for holoenzyme formation.

PubMed

Tsai, Kuang-Lei; Yu, Xiaodi; Gopalan, Sneha; Chao, Ti-Chun; Zhang, Ying; Florens, Laurence; Washburn, Michael P; Murakami, Kenji; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2017-04-13

The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 Å resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 Å resolution cryo-electron microscopy map of a Mediator-RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.

Mediator Recruitment to Heat Shock Genes Requires Dual Hsf1 Activation Domains and Mediator Tail Subunits Med15 and Med16*

PubMed Central

Kim, Sunyoung; Gross, David S.

2013-01-01

The evolutionarily conserved Mediator complex is central to the regulation of gene transcription in eukaryotes because it serves as a physical and functional interface between upstream regulators and the Pol II transcriptional machinery. Nonetheless, its role appears to be context-dependent, and the detailed mechanism by which it governs the expression of most genes remains unknown. Here we investigate Mediator involvement in HSP (heat shock protein) gene regulation in the yeast Saccharomyces cerevisiae. We find that in response to thermal upshift, subunits representative of each of the four Mediator modules (Head, Middle, Tail, and Kinase) are rapidly, robustly, and selectively recruited to the promoter regions of HSP genes. Their residence is transient, returning to near-background levels within 90 min. Hsf1 (heat shock factor 1) plays a central role in recruiting Mediator, as indicated by the fact that truncation of either its N- or C-terminal activation domain significantly reduces Mediator occupancy, whereas removal of both activation domains abolishes it. Likewise, ablation of either of two Mediator Tail subunits, Med15 or Med16, reduces Mediator recruitment to HSP promoters, whereas deletion of both abolishes it. Accompanying the loss of Mediator, recruitment of RNA polymerase II is substantially diminished. Interestingly, Mediator antagonizes Hsf1 occupancy of non-induced promoters yet facilitates enhanced Hsf1 association with activated ones. Collectively, our observations indicate that Hsf1, via its dual activation domains, recruits holo-Mediator to HSP promoters in response to acute heat stress through cooperative physical and/or functional interactions with the Tail module. PMID:23447536

Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase.

PubMed

Hensler, Thorsten; Sauerland, Stefan; Bouillon, Bertil; Raum, Marcus; Rixen, Dieter; Helling, Hanns-J; Andermahr, Jonas; Neugebauer, Edmund A M

2002-05-01

Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.

Eye-Pursuit and Reafferent Head Movement Signals Carried by Pursuit Neurons in the Caudal Part of the Frontal Eye Fields during Head-Free Pursuit

PubMed Central

Kasahara, Satoshi; Akao, Teppei; Kurkin, Sergei; Peterson, Barry W.

2009-01-01

Eye and head movements are coordinated during head-free pursuit. To examine whether pursuit neurons in frontal eye fields (FEF) carry gaze-pursuit commands that drive both eye-pursuit and head-pursuit, monkeys whose heads were free to rotate about a vertical axis were trained to pursue a juice feeder with their head and a target with their eyes. Initially the feeder and target moved synchronously with the same visual angle. FEF neurons responding to this gaze-pursuit were tested for eye-pursuit of target motion while the feeder was stationary and for head-pursuit while the target was stationary. The majority of pursuit neurons exhibited modulation during head-pursuit, but their preferred directions during eye-pursuit and head-pursuit were different. Although peak modulation occurred during head movements, the onset of discharge usually was not aligned with the head movement onset. The minority of neurons whose discharge onset was so aligned discharged after the head movement onset. These results do not support the idea that the head-pursuit–related modulation reflects head-pursuit commands. Furthermore, modulation similar to that during head-pursuit was obtained by passive head rotation on stationary trunk. Our results suggest that FEF pursuit neurons issue gaze or eye movement commands during gaze-pursuit and that the head-pursuit–related modulation primarily reflects reafferent signals resulting from head movements. PMID:18483002

Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo.

PubMed

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2017-07-12

The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo.

Reconstitution of active human core Mediator complex reveals a pivotal role of the MED14 subunit

PubMed Central

Cevher, Murat A.; Shi, Yi; Li, Dan; Chait, Brian T.; Malik, Sohail; Roeder, Robert G.

2014-01-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here, we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to mass spectrometry (CX-MS). Whereas the reconstituted head and middle modules can stably associate, only with incorporation of MED14 into the bi-modular complex does it acquire basal and coactivator functions. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematically dissecting the multiple layers of functionalities associated with the Mediator complex. PMID:25383669

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

Fury, Matthew G.; Department of Medicine, Weill Cornell Medical College, New York, New York; Lee, Nancy Y.

Purpose: Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation. Methods and Materials: This was single-institution phase 1 study to establish the maximum tolerated dose of daily everolimus given with fixed dose cisplatin (30 mg/m{sup 2} weekly × 6) and concurrent intensity modulated radiation therapy for patients with locally and/or regionally advanced head-and-neckmore » cancer. The study had a standard 3 + 3 dose-escalation design. Results: Tumor primary sites were oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), and neck node with occult primary (1). In 4 of 4 cases in which resected HNSCC surgical pathology specimens were available for immunohistochemistry, elevated expression of eIF4E was observed in the cancer-free margins. The most common grade ≥3 treatment-related adverse event was lymphopenia (92%), and dose-limiting toxicities (DLTs) were mucositis (n=2) and failure to thrive (n=1). With a median follow up of 19.4 months, 2 patients have experienced recurrent disease. The maximum tolerated dose was everolimus 5 mg/day. Conclusions: Head-and-neck cancer patients tolerated everolimus at therapeutic doses (5 mg/day) given with weekly cisplatin and intensity modulated radiation therapy. The regimen merits further evaluation, especially among patients who are status post resection of HNSCCs that harbor mTORC1-mediated activation of eIF4E in histologically negative surgical margins.« less

Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo.

PubMed

Fossat, Nicolas; Ip, Chi Kin; Jones, Vanessa J; Studdert, Joshua B; Khoo, Poh-Lynn; Lewis, Samara L; Power, Melinda; Tourle, Karin; Loebel, David A F; Kwan, Kin Ming; Behringer, Richard R; Tam, Patrick P L

2015-06-01

Lhx1 encodes a LIM homeobox transcription factor that is expressed in the primitive streak, mesoderm and anterior mesendoderm of the mouse embryo. Using a conditional Lhx1 flox mutation and three different Cre deleters, we demonstrated that LHX1 is required in the anterior mesendoderm, but not in the mesoderm, for formation of the head. LHX1 enables the morphogenetic movement of cells that accompanies the formation of the anterior mesendoderm, in part through regulation of Pcdh7 expression. LHX1 also regulates, in the anterior mesendoderm, the transcription of genes encoding negative regulators of WNT signalling, such as Dkk1, Hesx1, Cer1 and Gsc. Embryos carrying mutations in Pcdh7, generated using CRISPR-Cas9 technology, and embryos without Lhx1 function specifically in the anterior mesendoderm displayed head defects that partially phenocopied the truncation defects of Lhx1-null mutants. Therefore, disruption of Lhx1-dependent movement of the anterior mesendoderm cells and failure to modulate WNT signalling both resulted in the truncation of head structures. Compound mutants of Lhx1, Dkk1 and Ctnnb1 show an enhanced head truncation phenotype, pointing to a functional link between LHX1 transcriptional activity and the regulation of WNT signalling. Collectively, these results provide comprehensive insight into the context-specific function of LHX1 in head formation: LHX1 enables the formation of the anterior mesendoderm that is instrumental for mediating the inductive interaction with the anterior neuroectoderm and LHX1 also regulates the expression of factors in the signalling cascade that modulate the level of WNT activity. © 2015. Published by The Company of Biologists Ltd.

Cubilin, a high affinity receptor for fibroblast growth factor 8, is required for cell survival in the developing vertebrate head.

PubMed

Cases, Olivier; Perea-Gomez, Aitana; Aguiar, Diego P; Nykjaer, Anders; Amsellem, Sabine; Chandellier, Jacqueline; Umbhauer, Muriel; Cereghini, Silvia; Madsen, Mette; Collignon, Jérôme; Verroust, Pierre; Riou, Jean-François; Creuzet, Sophie E; Kozyraki, Renata

2013-06-07

Cubilin (Cubn) is a multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption. During mouse development, Cubn is expressed in both embryonic and extra-embryonic tissues, and Cubn gene inactivation results in early embryo lethality most likely due to the impairment of the function of extra-embryonic Cubn. Here, we focus on the developmental role of Cubn expressed in the embryonic head. We report that Cubn is a novel, interspecies-conserved Fgf receptor. Epiblast-specific inactivation of Cubn in the mouse embryo as well as Cubn silencing in the anterior head of frog or the cephalic neural crest of chick embryos show that Cubn is required during early somite stages to convey survival signals in the developing vertebrate head. Surface plasmon resonance analysis reveals that fibroblast growth factor 8 (Fgf8), a key mediator of cell survival, migration, proliferation, and patterning in the developing head, is a high affinity ligand for Cubn. Cell uptake studies show that binding to Cubn is necessary for the phosphorylation of the Fgf signaling mediators MAPK and Smad1. Although Cubn may not form stable ternary complexes with Fgf receptors (FgfRs), it acts together with and/or is necessary for optimal FgfR activity. We propose that plasma membrane binding of Fgf8, and most likely of the Fgf8 family members Fgf17 and Fgf18, to Cubn improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity.

Addition of glycosylation to influenza A virus hemagglutinin modulates antibody-mediated recognition of H1N1 2009 pandemic viruses.

PubMed

Job, Emma R; Deng, Yi-Mo; Barfod, Kenneth K; Tate, Michelle D; Caldwell, Natalie; Reddiex, Scott; Maurer-Stroh, Sebastian; Brooks, Andrew G; Reading, Patrick C

2013-03-01

Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the viral hemagglutinin (HA). Glycans on the head of HA promote virus survival by shielding antigenic sites, but highly glycosylated seasonal IAV are inactivated by soluble lectins of the innate immune system. In 2009, human strains of pandemic H1N1 [A(H1N1)pdm] expressed a single glycosylation site (Asn(104)) on the head of HA. Since then, variants with additional glycosylation sites have been detected, and the location of these sites has been distinct to those of recent seasonal H1N1 strains. We have compared wild-type and reverse-engineered A(H1N1)pdm IAV with differing potential glycosylation sites on HA for sensitivity to collectins and to neutralizing Abs. Addition of a glycan (Asn(136)) to A(H1N1)pdm HA was associated with resistance to neutralizing Abs but did not increase sensitivity to collectins. Moreover, variants expressing Asn(136) showed enhanced growth in A(H1N1)pdm-vaccinated mice, consistent with evasion of Ab-mediated immunity in vivo. Thus, a fine balance exists regarding the optimal pattern of HA glycosylation to facilitate evasion of Ab-mediated immunity while maintaining resistance to lectin-mediated defenses of the innate immune system.

Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo

PubMed Central

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2017-01-01

The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo. DOI: http://dx.doi.org/10.7554/eLife.28447.001 PMID:28699889

Correlation between number of type 2 serotonin receptors in the frontal cortex and intensity of serotonin-induced head jerks in mice

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

Popova, N.K.; Kulikov, A.V.; Pak, D.F.

This paper shows interlinear differences discovered in the number of S2 receptors in the cerebral cortex and they are compared with the intensity of 5-HT-induced head jerking in mice of inbred lines. The number of S2 receptors was estimated from the quantity of tritium-spiperone, which is specifically bound by brain membrane preparations. Specific binding was assessed as the difference between the quantity of label bound in the absence and in the presence of methylsergide, a drug which specificably blocks S2 receptors. The presence of high correlation be= tween the number of S2 receptors and the number of head jerkings inmore » mice reflects a genetic connection between this form of behavior and the serotonin system, and it in no way signifies that this phenomenon is controlled purely by the serotonin system and cannot be modulated by other mediator systems, for example, the adrenergic system.« less

Photovoltaic module kit including connector assembly for non-penetrating array installation

DOEpatents

Botkin, Jonathan; Graves, Simon; Danning, Matt; Culligan, Matthew

2013-12-31

A PV module kit for non-penetrating rooftop installation, including a plurality of PV modules and a plurality of connectors. Each of the PV modules includes a PV laminate and a frame forming a mounting region assembled thereto. The connectors include a male connector having a male fastener extending from a head, and a female connector having a female fastener assempbled within a head. The heads are entirely formed of plastic. The kit provides a mounted array state including a junction at which the mounting regions of at least two of the PV modules are aligned and interconnected by engagement of the male connector with the female connector. The so-formed junction is substantially electrically insulated. The plurality of connectors can further include a spacer connector including a head forming a bore sized slidably receive the male fastener, with all of the connector heads being identical.

Photovoltaic module kit including connector assembly for non-penetrating array installation

DOEpatents

Botkin, Jonathan [El Cerrito, CA; Graves, Simon [Berkeley, CA; Danning, Matt [Oakland, CA; Culligan, Matthew [Berkeley, CA

2011-11-22

A PV module kit for non-penetrating rooftop installation, including a plurality of PV modules and a plurality of connectors. Each of the PV modules includes a PV laminate and a frame forming a mounting region assembled thereto. The connectors include a male connector having a male fastener extending from a head, and a female connector having a female fastener assembled within a head. The heads are entirely formed of plastic. The kit provides a mounted array state including a junction at which the mounting region of at least two of the PV modules are aligned and interconnected by engagement of the male connector with the female connector. The so-formed junction is substantially electrically insulated. The plurality of connectors can further include a spacer connector including a head forming a bore sized to slidably receive the male fastener, with all of the connector heads being identical.

Photovoltaic module kit including connector assembly for non-penetrating array installation

DOEpatents

Botkin, Jonathan; Graves, Simon; Danning, Matt; Culligan, Matthew

2012-10-23

A PV module kit for non-penetrating rooftop installation, including a plurality of PV modules and a plurality of connectors. Each of the PV modules includes a PV laminate and a frame forming a mounting region assembled thereto. The connectors include a male connector having a male fastener extending from a head, and a female connector having a female fastener assembled within a head. The heads are entirely formed of plastic. The kit provides a mounted array state including a junction at which the mounting region of at least two of the PV modules are aligned and interconnected by engagement of the male connector with the female connector. The so-formed junction is substantially electrically insulated. The plurality of connectors can further include a spacer connector including a head forming a bore sized to slidably receive the male fastener, with all of the connector heads being identical.

A conserved genetic module that encodes the major virion components in both the coliphage T4 and the marine cyanophage S-PM2

PubMed Central

Hambly, Emma; Tétart, Francoise; Desplats, Carine; Wilson, William H.; Krisch, Henry M.; Mann, Nicholas H.

2001-01-01

Sequence analysis of a 10-kb region of the genome of the marine cyanomyovirus S-PM2 reveals a homology to coliphage T4 that extends as a contiguous block from gene (g)18 to g23. The order of the S-PM2 genes in this region is similar to that of T4, but there are insertions and deletions of small ORFs of unknown function. In T4, g18 codes for the tail sheath, g19, the tail tube, g20, the head portal protein, g21, the prohead core protein, g22, a scaffolding protein, and g23, the major capsid protein. Thus, the entire module that determines the structural components of the phage head and contractile tail is conserved between T4 and this cyanophage. The significant differences in the morphology of these phages must reflect the considerable divergence of the amino acid sequence of their homologous virion proteins, which uniformly exceeds 50%. We suggest that their enormous diversity in the sea could be a result of genetic shuffling between disparate phages mediated by such commonly shared modules. These conserved sequences could facilitate genetic exchange by providing partially homologous substrates for recombination between otherwise divergent phage genomes. Such a mechanism would thus expand the pool of phage genes accessible by recombination to all those phages that share common modules. PMID:11553768

Modulation of Atlantic salmon miRNome response to sea louse infestation.

PubMed

Valenzuela-Muñoz, Valentina; Novoa, Beatriz; Figueras, Antonio; Gallardo-Escárate, Cristian

2017-11-01

MicroRNAs are non-coding RNA that plays a crucial role in post-transcriptional regulation and immune system regulation. On other hand, sea lice are prevalent parasites that affect salmon farming, generating different degrees of immune suppression depending on the salmon and sea louse species. Caligus rogercresseyi for example, which affects the salmon industry in Chile, decreases Th1 response, macrophage activation, TLR-mediated response and iron regulation in infected fish. In this study, we explore Atlantic salmon miRNome during infestation by C. rogercresseyi. Using small RNA sequencing, we annotated 1718 miRNAs for skin and head kidney from infected Atlantic salmon. The most abundant families identified were mir-10, mir-21, mir-30, mir-181 and let7. Significant differences were found between tissue, with 1404 annotated miRNA in head kidney and 529 in skin. Differential analysis of transcript expression indicated that at an early stage of infestation miRNA expression was higher in head kidney than in skin tissue, revealing tissue-specific expression patterns. In parallel, miRNA target prediction using 3'UTRs from highly regulated immune-related genes and iron metabolism showed that mir-140-4 and mir-181a-2-5 modulate the expression of TLR22 and Aminolevulinic acid synthase, respectively. This study contributes knowledge about the immune response of Atlantic salmon during infestation with sea lice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments

PubMed Central

Kampourakis, Thomas; Sun, Yin-Biao; Irving, Malcolm

2016-01-01

Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease. PMID:27162358

Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments.

PubMed

Kampourakis, Thomas; Sun, Yin-Biao; Irving, Malcolm

2016-05-24

Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease.

DIPA-family coiled-coils bind conserved isoform-specific head domain of p120-catenin family: potential roles in hydrocephalus and heterotopia.

PubMed

Markham, Nicholas O; Doll, Caleb A; Dohn, Michael R; Miller, Rachel K; Yu, Huapeng; Coffey, Robert J; McCrea, Pierre D; Gamse, Joshua T; Reynolds, Albert B

2014-09-01

p120-catenin (p120) modulates adherens junction (AJ) dynamics by controlling the stability of classical cadherins. Among all p120 isoforms, p120-3A and p120-1A are the most prevalent. Both stabilize cadherins, but p120-3A is preferred in epithelia, whereas p120-1A takes precedence in neurons, fibroblasts, and macrophages. During epithelial-to-mesenchymal transition, E- to N-cadherin switching coincides with p120-3A to -1A alternative splicing. These isoforms differ by a 101-amino acid "head domain" comprising the p120-1A N-terminus. Although its exact role is unknown, the head domain likely mediates developmental and cancer-associated events linked to p120-1A expression (e.g., motility, invasion, metastasis). Here we identified delta-interacting protein A (DIPA) as the first head domain-specific binding partner and candidate mediator of isoform 1A activity. DIPA colocalizes with AJs in a p120-1A- but not 3A-dependent manner. Moreover, all DIPA family members (Ccdc85a, Ccdc85b/DIPA, and Ccdc85c) interact reciprocally with p120 family members (p120, δ-catenin, p0071, and ARVCF), suggesting significant functional overlap. During zebrafish neural tube development, both knockdown and overexpression of DIPA phenocopy N-cadherin mutations, an effect bearing functional ties to a reported mouse hydrocephalus phenotype associated with Ccdc85c. These studies identify a novel, highly conserved interaction between two protein families that may participate either individually or collectively in N-cadherin-mediated development. © 2014 Markham et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Biochip scanner device

DOEpatents

Perov, Alexander; Belgovskiy, Alexander I.; Mirzabekov, Andrei D.

2001-01-01

A biochip scanner device used to detect and acquire fluorescence signal data from biological microchips or biochips and method of use are provided. The biochip scanner device includes a laser for emitting a laser beam. A modulator, such as an optical chopper modulates the laser beam. A scanning head receives the modulated laser beam and a scanning mechanics coupled to the scanning head moves the scanning head relative to the biochip. An optical fiber delivers the modulated laser beam to the scanning head. The scanning head collects the fluorescence light from the biochip, launches it into the same optical fiber, which delivers the fluorescence into a photodetector, such as a photodiode. The biochip scanner device is used in a row scanning method to scan selected rows of the biochip with the laser beam size matching the size of the immobilization site.

Highly preserved consensus gene modules in human papilloma virus 16 positive cervical cancer and head and neck cancers.

PubMed

Zhang, Xianglan; Cha, In-Ho; Kim, Ki-Yeol

2017-12-26

In this study, we investigated the consensus gene modules in head and neck cancer (HNC) and cervical cancer (CC). We used a publicly available gene expression dataset, GSE6791, which included 42 HNC, 14 normal head and neck, 20 CC and 8 normal cervical tissue samples. To exclude bias because of different human papilloma virus (HPV) types, we analyzed HPV16-positive samples only. We identified 3824 genes common to HNC and CC samples. Among these, 977 genes showed high connectivity and were used to construct consensus modules. We demonstrated eight consensus gene modules for HNC and CC using the dissimilarity measure and average linkage hierarchical clustering methods. These consensus modules included genes with significant biological functions, including ATP binding and extracellular exosome. Eigengen network analysis revealed the consensus modules were highly preserved with high connectivity. These findings demonstrate that HPV16-positive head and neck and cervical cancers share highly preserved consensus gene modules with common potentially therapeutic targets.

Highly preserved consensus gene modules in human papilloma virus 16 positive cervical cancer and head and neck cancers

PubMed Central

Zhang, Xianglan; Cha, In-Ho; Kim, Ki-Yeol

2017-01-01

In this study, we investigated the consensus gene modules in head and neck cancer (HNC) and cervical cancer (CC). We used a publicly available gene expression dataset, GSE6791, which included 42 HNC, 14 normal head and neck, 20 CC and 8 normal cervical tissue samples. To exclude bias because of different human papilloma virus (HPV) types, we analyzed HPV16-positive samples only. We identified 3824 genes common to HNC and CC samples. Among these, 977 genes showed high connectivity and were used to construct consensus modules. We demonstrated eight consensus gene modules for HNC and CC using the dissimilarity measure and average linkage hierarchical clustering methods. These consensus modules included genes with significant biological functions, including ATP binding and extracellular exosome. Eigengen network analysis revealed the consensus modules were highly preserved with high connectivity. These findings demonstrate that HPV16-positive head and neck and cervical cancers share highly preserved consensus gene modules with common potentially therapeutic targets. PMID:29371966

EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition.

PubMed

Kim, Song Hee; Lee, Won Hyeok; Kim, Seong Who; Je, Hyoung Uk; Lee, Jong Cheol; Chang, Hyo Won; Kim, Young Min; Kim, Kyungbin; Kim, Sang Yoon; Han, Myung Woul

2018-07-01

Radiotherapy is a well-established therapeutic modality used in the treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after radiation treatment. Thus, many studies have attempted to identify effective radiosensitizers. Eph receptor functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains unclear. In the current study, we established a stable radioresistant head and neck cancer cell line (AMC HN3R cell line) and found that EphA3 was expressed predominantly in the radioresistant head and neck cancer cell line through DNA microarray, real time PCR and Western blotting. Additionally, we found that EphA3 was overexpressed in recurrent laryngeal cancer specimens after radiation therapy. EphA3 mediated the tumor invasiveness and migration in radioresistant head and neck cancer cell lines and epithelial mesenchymal transition- related protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN 3R cell line in vitro and in vivo study. In conclusion, our results suggest that EphA3 is overexpressed in radioresistant head and neck cancer and plays a crucial role in the development of radioresistance in head and neck cancers by regulating the epithelial mesenchymal transition pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

Measuring quality of life in patients with head and neck cancer: Update of the EORTC QLQ-H&N Module, Phase III.

PubMed

Singer, Susanne; Araújo, Cláudia; Arraras, Juan Ignacio; Baumann, Ingo; Boehm, Andreas; Brokstad Herlofson, Bente; Castro Silva, Joaquim; Chie, Wei-Chu; Fisher, Sheila; Guntinas-Lichius, Orlando; Hammerlid, Eva; Irarrázaval, María Elisa; Jensen Hjermstad, Marianne; Jensen, Kenneth; Kiyota, Naomi; Licitra, Lisa; Nicolatou-Galitis, Ourania; Pinto, Monica; Santos, Marcos; Schmalz, Claudia; Sherman, Allen C; Tomaszewska, Iwona M; Verdonck de Leeuw, Irma; Yarom, Noam; Zotti, Paola; Hofmeister, Dirk

2015-09-01

The objective of this study was to pilot test an updated version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N60). Patients with head and neck cancer were asked to complete a list of 60 head and neck cancer-specific items comprising the updated EORTC head and neck module and the core questionnaire EORTC QLQ-C30. Debriefing interviews were conducted to identify any irrelevant items and confusing or upsetting wording. Interviews were performed with 330 patients from 17 countries, representing different head and neck cancer sites and treatments. Forty-one of the 60 items were retained according to the predefined EORTC criteria for module development, for another 2 items the wording was refined, and 17 items were removed. The preliminary EORTC QLQ-H&N43 can now be used in academic research. Psychometrics will be tested in a larger field study. © 2014 Wiley Periodicals, Inc.

Characterization of Triticum aestivum Abscisic Acid Receptors and a Possible Role for These in Mediating Fusairum Head Blight Susceptibility in Wheat

PubMed Central

Gordon, Cameron S.; Rajagopalan, Nandhakishore; Risseeuw, Eddy P.; Surpin, Marci; Ball, Fraser J.; Barber, Carla J.; Buhrow, Leann M.; Clark, Shawn M.; Page, Jonathan E.; Todd, Chris D.; Abrams, Suzanne R.; Loewen, Michele C.

2016-01-01

Abscisic acid (ABA) is a well-characterized plant hormone, known to mediate developmental aspects as well as both abiotic and biotic stress responses. Notably, the exogenous application of ABA has recently been shown to increase susceptibility to the fungal pathogen Fusarium graminearum, the causative agent of Fusarium head blight (FHB) in wheat and other cereals. However roles and mechanisms associated with ABA’s modulation of pathogen responses remain enigmatic. Here the identification of putative ABA receptors from available genomic databases for Triticum aestivum (bread wheat) and Brachypodium distachyon (a model cereal) are reported. A number of these were cloned for recombinant expression and their functionality as ABA receptors confirmed by in vitro assays against protein phosphatases Type 2Cs. Ligand selectivity profiling of one of the wheat receptors (Ta_PYL2DS_FL) highlighted unique activities compared to Arabidopsis AtPYL5. Mutagenic analysis showed Ta_PYL2DS_FL amino acid D180 as being a critical contributor to this selectivity. Subsequently, a virus induced gene silencing (VIGS) approach was used to knockdown wheat Ta_PYL4AS_A (and similar) in planta, yielding plants with increased early stage resistance to FHB progression and decreased mycotoxin accumulation. Together these results confirm the existence of a family of ABA receptors in wheat and Brachypodium and present insight into factors modulating receptor function at the molecular level. That knockdown of Ta_PYL4AS_A (and similar) leads to early stage FHB resistance highlights novel targets for investigation in the future development of disease resistant crops. PMID:27755583

Characterization of Triticum aestivum Abscisic Acid Receptors and a Possible Role for These in Mediating Fusairum Head Blight Susceptibility in Wheat.

PubMed

Gordon, Cameron S; Rajagopalan, Nandhakishore; Risseeuw, Eddy P; Surpin, Marci; Ball, Fraser J; Barber, Carla J; Buhrow, Leann M; Clark, Shawn M; Page, Jonathan E; Todd, Chris D; Abrams, Suzanne R; Loewen, Michele C

2016-01-01

Abscisic acid (ABA) is a well-characterized plant hormone, known to mediate developmental aspects as well as both abiotic and biotic stress responses. Notably, the exogenous application of ABA has recently been shown to increase susceptibility to the fungal pathogen Fusarium graminearum, the causative agent of Fusarium head blight (FHB) in wheat and other cereals. However roles and mechanisms associated with ABA's modulation of pathogen responses remain enigmatic. Here the identification of putative ABA receptors from available genomic databases for Triticum aestivum (bread wheat) and Brachypodium distachyon (a model cereal) are reported. A number of these were cloned for recombinant expression and their functionality as ABA receptors confirmed by in vitro assays against protein phosphatases Type 2Cs. Ligand selectivity profiling of one of the wheat receptors (Ta_PYL2DS_FL) highlighted unique activities compared to Arabidopsis AtPYL5. Mutagenic analysis showed Ta_PYL2DS_FL amino acid D180 as being a critical contributor to this selectivity. Subsequently, a virus induced gene silencing (VIGS) approach was used to knockdown wheat Ta_PYL4AS_A (and similar) in planta, yielding plants with increased early stage resistance to FHB progression and decreased mycotoxin accumulation. Together these results confirm the existence of a family of ABA receptors in wheat and Brachypodium and present insight into factors modulating receptor function at the molecular level. That knockdown of Ta_PYL4AS_A (and similar) leads to early stage FHB resistance highlights novel targets for investigation in the future development of disease resistant crops.

Remembering the past and imagining the future

PubMed Central

Byrne, Patrick; Becker, Suzanna; Burgess, Neil

2009-01-01

The neural mechanisms underlying spatial cognition are modelled, integrating neuronal, systems and behavioural data, and addressing the relationships between long-term memory, short-term memory and imagery, and between egocentric and allocentric and visual and idiothetic representations. Long-term spatial memory is modeled as attractor dynamics within medial-temporal allocentric representations, and short-term memory as egocentric parietal representations driven by perception, retrieval and imagery, and modulated by directed attention. Both encoding and retrieval/ imagery require translation between egocentric and allocentric representations, mediated by posterior parietal and retrosplenial areas and utilizing head direction representations in Papez’s circuit. Thus hippocampus effectively indexes information by real or imagined location, while Papez’s circuit translates to imagery or from perception according to the direction of view. Modulation of this translation by motor efference allows “spatial updating” of representations, while prefrontal simulated motor efference allows mental exploration. The alternating temporo-parietal flows of information are organized by the theta rhythm. Simulations demonstrate the retrieval and updating of familiar spatial scenes, hemispatial neglect in memory, and the effects on hippocampal place cell firing of lesioned head direction representations and of conflicting visual and ideothetic inputs. PMID:17500630

Temporary inactivation of the anterior part of the bed nucleus of the stria terminalis blocks alarm pheromone-induced defensive behavior in rats

PubMed Central

Breitfeld, Tino; Bruning, Johann E. A.; Inagaki, Hideaki; Takeuchi, Yukari; Kiyokawa, Yasushi; Fendt, Markus

2015-01-01

Rats emit an alarm pheromone in threatening situations. Exposure of rats to this alarm pheromone induces defensive behaviors, such as head out behavior, and increases c-Fos expression in brain areas involved in the mediation of defensive behaviors. One of these brain areas is the anterior bed nucleus of the stria terminalis (aBNST). The goal of the present study was to investigate if pharmacological inactivation of the aBNST by local microinjections of the GABAA receptor-agonist muscimol modulates alarm pheromone-induced defensive behaviors. We first established the behavioral paradigm of alarm pheromone-induced defensive behaviors in Sprague-Dawley rats in our laboratory. In a second experiment, we inactivated the aBNST, then exposed rats to one of four different odors (neck odor, female urine, alarm pheromone, fox urine) and tested the effects of the aBNST inactivation on the behavior in response to these odors. Our data show that temporary inactivation of the aBNST blocked head out behavior in response to the alarm pheromone. This indicates that the aBNST plays an important role in the mediation of the alarm pheromone-induced defensive behavior in rats. PMID:26441496

Adjustment of saccade characteristics during head movements.

NASA Technical Reports Server (NTRS)

Morasso, P.; Bizzi, E.; Dichgans, J.

1973-01-01

Saccade characteristics have been studied during coordinated eye-head movements in monkeys. Amplitude, duration, and peak velocity of saccades with head turning were compared with saccades executed while the head was artificially restrained. The results indicate that the saccade characteristics are modulated as a function of head movement, hence the gaze movement (eye+head) exactly matches saccades with head fixed. Saccade modulation is achieved by way of negative vestibulo-ocular feedback. The neck proprioceptors, because of their longer latency, are effective only if the head starts moving prior to the onset of saccade. It is concluded that saccades make with head turning are not 'ballistic' movements because their trajectory is not entirely predetermined by a central command.

Nutrition in Head Start: A Comprehensive Plan for Quality Improvement. Module One--Staff Development: Training To Meet the Nutritional Needs of Children and Families. Module Two--Community Awareness: Educating Local Businesses on the Mission of Head Start Nutrition. Module Three--Children and Families: Nutrition Education for Health and Employment.

ERIC Educational Resources Information Center

Riedel-Lester, Priscilla

Three modules address the objectives and services of the nutrition part of the health services component of the Head Start program. The planning of the nutrition services involves the following issues: (1) identifying the nutritional needs and problems of the children and the families; (2) meeting the daily nutritional needs of the children; (3)…

Advances in endonasal low intensity laser irradiation therapy

NASA Astrophysics Data System (ADS)

Jiao, Jian-Ling; Liu, Timon C.; Liu, Jiang; Cui, Li-Ping; Liu, Song-hao

2005-07-01

Endonasal low intensity laser therapy (ELILT) began in China in 1998. Now in China it is widely applied to treat hyperlipidemia and brain diseases such as Alzheimer's disease, Parkinson's disease, insomnia, poststroke depression, intractable headache, ache in head or face, cerebral thrombosis, acute ischemic cerebrovascular disease, migraine, brain lesion and mild cognitive impairment. There are four pathways mediating EILILT, Yangming channel, autonomic nervous systems and blood cells. Two unhealth acupoints of Yangming channal inside nose might mediate the one as is low intensity laser acupuncture. Unbalance autonomic nervous systems might be modulated. Blood cells might mediate the one as is intravascular low intensity laser therapy. These three pathways are integrated in ELILT so that serum amyloid β protein, malformation rate of erythrocyte, CCK-8, the level of viscosity at lower shear rates and hematocrit, or serum lipid might decrease, and melanin production/SOD activity or β endorphin might increase after ELILT treatment. These results indicate ELILT might work, but it need to be verified by randomized placebo-controlled trial.

Treatment for intranasal synechiae by CO2 laser under endoscopic visualization

NASA Astrophysics Data System (ADS)

Feng, Yunhai; Yin, Shankai

2005-07-01

Endonasal low intensity laser therapy (ELILT) began in China in 1998. Now in China it is widely applied to treat hyperlipidemia and brain diseases such as Alzheimer's disease, Parkinson's disease, insomnia, poststroke depression, intractable headache, ache in head or face, cerebral thrombosis, acute ischemic cerebrovascular disease, migraine, brain lesion and mild cognitive impairment. There are four pathways mediating EILILT, Yangming channel, autonomic nervous systems and blood cells. Two unhealth acupoints of Yangming channal inside nose might mediate the one as is low intensity laser acupuncture. Unbalance autonomic nervous systems might be modulated. Blood cells might mediate the one as is intravascular low intensity laser therapy. These three pathways are integrated in ELILT so that serum amyloid β protein, malformation rate of erythrocyte, CCK-8, the level of viscosity at lower shear rates and hematocrit, or serum lipid might decrease, and melanin production/SOD activity or β endorphin might increase after ELILT treatment. These results indicate ELILT might work, but it need to be verified by randomized placebo-controlled trial.

Support arrangement for core modules of nuclear reactors

DOEpatents

Bollinger, Lawrence R.

1987-01-01

A support arrangement is provided for the core modules of a nuclear reactor which provides support access through the control drive mechanisms of the reactor. This arrangement provides axial support of individual reactor core modules from the pressure vessel head in a manner which permits attachment and detachment of the modules from the head to be accomplished through the control drive mechanisms after their leadscrews have been removed. The arrangement includes a module support nut which is suspended from the pressure vessel head and screw threaded to the shroud housing for the module. A spline lock prevents loosening of the screw connection. An installation tool assembly, including a cell lifting and preloading tool and a torquing tool, fits through the control drive mechanism and provides lifting of the shroud housing while disconnecting the spline lock, as well as application of torque to the module support nut.

Support arrangements for core modules of nuclear reactors. [PWR

DOEpatents

Bollinger, L.R.

1983-11-03

A support arrangement is provided for the core modules of a nuclear reactor which provides support access through the control drive mechanisms of the reactor. This arrangement provides axial support of individual reactor core modules from the pressure vessel head in a manner which permits attachment and detachment of the modules from the head to be accomplished through the control drive mechanisms after their leadscrews have been removed. The arrangement includes a module support nut which is suspended from the pressure vessel head and screw threaded to the shroud housing for the module. A spline lock prevents loosening of the screw connection. An installation tool assembly, including a cell lifting and preloading tool and a torquing tool, fits through the control drive mechanism and provides lifting of the shroud housing while disconnecting the spline lock, as well as application of torque to the module support nut.

AUTOMOTIVE DIESEL MAINTENANCE 1. UNIT VIII. ENGINE COMPONENTS--PART I.

ERIC Educational Resources Information Center

Human Engineering Inst., Cleveland, OH.

THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF THE CONSTRUCTION AND MAINTENANCE OF DIESEL ENGINE CYLINDER HEADS AND CYLINDER ASSEMBLIES. TOPICS ARE CYLINDER ASSEMBLY (LINERS), CYLINDER HEADS, VALVES AND VALVE MECHANISMS, AND PISTON AND PISTON RINGS. THE MODULE CONSISTS OF A SELF-INSTRUCTIONAL BRANCH PROGRAMED TRAINING…

Father Beliefs as a Mediator between Contextual Barriers and Father Involvement

ERIC Educational Resources Information Center

Freeman, Harry; Newland, Lisa A.; Coyl, Diana D.

2008-01-01

Fathers' beliefs were examined as mediators between multiple risk factors and involvement practices with children age zero to five enrolled in Head Start or Early Head Start. A diverse sample of 101 fathers, living in rural Midwestern communities of the USA completed questionnaires assessing "mediators" (i.e. parenting efficacy, role beliefs, and…

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis.

PubMed

Ohkawara, Bisei; Glinka, Andrei; Niehrs, Christof

2011-03-15

The R-Spondin (Rspo) family of secreted Wnt modulators is involved in development and disease and holds therapeutic promise as stem cell growth factors. Despite growing biological importance, their mechanism of action is poorly understood. Here, we show that Rspo3 binds syndecan 4 (Sdc4) and that together they activate Wnt/PCP signaling. In Xenopus embryos, Sdc4 and Rspo3 are essential for two Wnt/PCP-driven processes-gastrulation movements and head cartilage morphogenesis. Rspo3/PCP signaling during gastrulation requires Wnt5a and is transduced via Fz7, Dvl, and JNK. Rspo3 functions by inducing Sdc4-dependent, clathrin-mediated endocytosis. We show that this internalization is essential for PCP signal transduction, suggesting that endocytosis of Wnt-receptor complexes is a key mechanism by which R-spondins promote Wnt signaling. Copyright © 2011 Elsevier Inc. All rights reserved.

Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

PubMed

Beste, Christian; Ness, Vanessa; Lukas, Carsten; Hoffmann, Rainer; Stüwe, Sven; Falkenstein, Michael; Saft, Carsten

2012-08-01

Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict monitoring and flexible adaptation of actions. Copyright © 2012 Elsevier Inc. All rights reserved.

Behavioral effects of diazepam in the murine plus-maze: flumazenil antagonism of enhanced head dipping but not the disinhibition of open-arm avoidance.

PubMed

Dalvi, A; Rodgers, R J

1999-04-01

Although it is widely believed that benzodiazepines reduce anxiety through positive allosteric modulation of the GABA(A)-chloride channel complex, this is not the only mechanism through which agents of this class can modify CNS function. Furthermore, a significant number of reports of apparent flumazenil blockade of diazepam anxiolysis in animal models have paid limited attention to possible intrinsic behavioral actions of the antagonist per se. In the present study, ethological methods were employed to assess in detail the effects of diazepam, flumazenil, and their combination on the behavior of male DBA/2 mice in the elevated plus-maze paradigm. In two experiments, diazepam (1.5 mg/kg) alone reduced open-arm avoidance and increased head dipping, whereas flumazenil (10-40 mg/kg) alone was without significant behavioral effect. However, with the sole exception of head dipping, prior administration of flumazenil (10 and 40 mg/kg) failed to block the behavioral effects of diazepam under present test conditions. These findings imply that the anxiolytic effects of diazepam in the mouse plus-maze are not mediated through flumazenil-sensitive benzodiazepine receptors and that alternate mechanisms must be considered.

G protein-coupled receptors Flop1 and Flop2 inhibit Wnt/β-catenin signaling and are essential for head formation in Xenopus.

PubMed

Miyagi, Asuka; Negishi, Takefumi; Yamamoto, Takamasa S; Ueno, Naoto

2015-11-01

Patterning of the vertebrate anterior-posterior axis is regulated by the coordinated action of growth factors whose effects can be further modulated by upstream and downstream mediators and the cross-talk of different intracellular pathways. In particular, the inhibition of the Wnt/β-catenin signaling pathway by various factors is critically required for anterior specification. Here, we report that Flop1 and Flop2 (Flop1/2), G protein-coupled receptors related to Gpr4, contribute to the regulation of head formation by inhibiting Wnt/β-catenin signaling in Xenopus embryos. Using whole-mount in situ hybridization, we showed that flop1 and flop2 mRNAs were expressed in the neural ectoderm during early gastrulation. Both the overexpression and knockdown of Flop1/2 resulted in altered embryonic head phenotypes, while the overexpression of either Flop1/2 or the small GTPase RhoA in the absence of bone morphogenetic protein (BMP) signaling resulted in ectopic head induction. Examination of the Flops' function in Xenopus embryo animal cap cells showed that they inhibited Wnt/β-catenin signaling by promoting β-catenin degradation through both RhoA-dependent and -independent pathways in a cell-autonomous manner. These results suggest that Flop1 and Flop2 are essential regulators of Xenopus head formation that act as novel inhibitory components of the Wnt/β-catenin signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Modification of Eye Movements and Motion Perception during Off-Vertical Axis Rotation

NASA Technical Reports Server (NTRS)

Wood, S. J.; Reschke, M. F.; Denise, P.; CLement, G.

2006-01-01

Constant velocity Off-Vertical Axis Rotation (OVAR) imposes a continuously varying orientation of the head and body relative to gravity. The ensuing ocular reflexes include modulation of both torsional and horizontal eye movements as a function of the varying linear acceleration along the lateral plane, and modulation of vertical and vergence eye movements as a function of the varying linear acceleration along the sagittal plane. Previous studies have demonstrated that tilt and translation otolith-ocular responses, as well as motion perception, vary as a function of stimulus frequency during OVAR. The purpose of this study is to examine normative OVAR responses in healthy human subjects, and examine adaptive changes in astronauts following short duration space flight at low (0.125 Hz) and high (0.5 Hz) frequencies. Data was obtained on 24 normative subjects (14 M, 10 F) and 14 (13 M, 1F) astronaut subjects. To date, astronauts have participated in 3 preflight sessions (n=14) and on R+0/1 (n=7), R+2 (n= 13) and R+4 (n= 13) days after landing. Subjects were rotated in darkness about their longitudinal axis 20 deg off-vertical at constant rates of 45 and 180 deg/s, corresponding to 0.125 and 0.5 Hz. Binocular responses were obtained with video-oculography. Perceived motion was evaluated using verbal reports and a two-axis joystick (pitch and roll tilt) mounted on top of a two-axis linear stage (anterior-posterior and medial-lateral translation). Eye responses were obtained in ten of the normative subjects with the head and trunk aligned, and then with the head turned relative to the trunk 40 deg to the right or left of center. Sinusoidal curve fits were used to derive amplitude, phase and bias of the responses over several cycles at each stimulus frequency. Eye responses during 0.125 Hz OVAR were dominated by modulation of torsional and vertical eye position, compensatory for tilt relative to gravity. While there is a bias horizontal slow phase velocity (SPV), the modulation of horizontal and vergence SPV is negligible at this lower stimulus frequency. Eye responses during 0.5 Hz OVAR; however, are characterized by modulation of horizontal and vergence SPV, compensatory for translation in the lateral and sagittal planes, respectively. Neither amplitude nor bias velocities were significantly altered by head-on-trunk position. The phases of the ocular reflexes, on the other hand, shifted towards alignment with the head. During the lower frequency OVAR, subjects reported the perception of progressing along the edge of a cone. During higher frequency OVAR, subjects reported the perception of progressing along the edge of an upright cylinder. In contrast to the eye movements, the phase of both perceived tilt and translation motion is not altered by stimulus frequency. Preliminary results from astronaut data suggest that the ocular responses are not substantially altered by short-duration spaceflight. However, compared to preflight averages, astronauts reported greater amplitude of both perceived tilt and translation at low and high frequency, respectively, during early post-flight testing. We conclude that the neural processing to distinguish tilt and translation linear acceleration stimuli differs between eye movements and motion perception. The results from modifying head-on-trunk position are consistent with the modulation of ocular reflexes during OVAR being primarily mediated by the otoliths in response to the sinusoidally varying linear acceleration along the interaural and naso-occipital head axis. While the tilt and translation ocular reflexes appear to operate in an independent fashion, the timing of perceived tilt and translation influence each other. We conclude that the perceived motion path during linear acceleration in darkness results from a composite representation of tilt and translation inputs from both vestibular and somatosensory systems.

Effect of the tubular-fan drum shapes on the performance of cleaning head module

NASA Astrophysics Data System (ADS)

Hong, C. K.; Y Cho, M.; Kim, Y. J.

2013-12-01

The geometrical effects of a tubular-fan drum on the performance improvement of the cleaning head module of a vacuum cleaner were investigated. In this study, the number of blades and the width of the blade were selected as the design parameters. Static pressure, eccentric vortex, turbulence kinetic energy (TKE) and suction efficiency were analysed and tabulated. Three-dimensional computational fluid dynamics method was used with an SST (Shear Stress Transfer) turbulence model to simulate the flow field at the suction of the cleaning head module using the commercial code ANSYS-CFX. Suction pressure distributions were graphically depicted for different values of the design parameters.

Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers

PubMed Central

Bhide, S A; Newbold, K L; Harrington, K J; Nutting, C M

2012-01-01

Radiotherapy and surgery are the principal curative modalities in treatment of head and neck cancer. Conventional two-dimensional and three-dimensional conformal radiotherapy result in significant side effects and altered quality of life. Intensity-modulated radiotherapy (IMRT) can spare the normal tissues, while delivering a curative dose to the tumour-bearing tissues. This article reviews the current role of IMRT in head and neck cancer from the point of view of normal tissue sparing, and also reviews the current published literature by individual head and neck cancer subsites. In addition, we briefly discuss the role of image guidance in head and neck IMRT, and future directions in this area. PMID:22556403

GlyCAM1 negatively regulates monocyte entry into the optic nerve head and contributes to radiation-based protection in glaucoma.

PubMed

Williams, Pete A; Braine, Catherine E; Foxworth, Nicole E; Cochran, Kelly E; John, Simon W M

2017-04-26

We previously reported a profound long-term neuroprotection subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma. This neuroprotection prevents entry of monocyte-like immune cells into the optic nerve head during glaucoma. Gene expression studies in radiation-treated mice implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for L-selectin and is an excellent candidate to modulate immune cell entry into the eye. Here, we experimentally test the hypothesis that radiation-induced over-expression of Glycam1 is a key component of the neuroprotection. We generated a null allele of Glycam1 on a DBA/2J background. Gene and protein expression of Glycam1, monocyte entry into the optic nerve head, retinal ganglion cell death, and axon loss in the optic nerve were assessed. Radiation therapy potently inhibits monocyte entry into the optic nerve head and prevents retinal ganglion cell death and axon loss. DBA/2J mice carrying a null allele of Glycam1 show increased monocyte entry and increased retinal ganglion cell death and axon loss following radiation therapy, but the majority of optic nerves were still protected by radiation therapy. Although GlyCAM1 is an L-selectin ligand, its roles in immunity are not yet fully defined. The current study demonstrates a partial role for GlyCAM1 in radiation-mediated protection. Furthermore, our results clearly show that GlyCAM1 levels modulate immune cell entry from the vasculature into neural tissues. As Glycam1 deficiency has a more profound effect on cell entry than on neurodegeneration, further experiments are needed to precisely define the role of monocyte entry in DBA/2J glaucoma. Nevertheless, GlyCAM1's function as a negative regulator of extravasation may lead to novel therapeutic strategies for an array of common conditions involving inflammation.

Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling.

PubMed

Fetoni, A R; Paciello, F; Mezzogori, D; Rolesi, R; Eramo, S L M; Paludetti, G; Troiani, D

2015-11-17

In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo. The effects of curcumin and/or cisplatin treatment have been evaluated in head and neck squamous cell carcinoma as well as in a rat model of cisplatin-induced ototoxicity by using immunofluorescence, western blot, and functional and morphological analysis. This study demonstrates that curcumin attenuates all stages of tumour progression (survival, proliferation) and, by targeting pSTAT3 and Nrf-2 signalling pathways, provides chemosensitisation to cisplatin in vitro and protection from its ototoxic adverse effects in vivo. These results indicate that curcumin can be used as an efficient adjuvant to cisplatin cancer therapy. This treatment strategy in head and neck cancer could mediate cisplatin chemoresistance by modulating therapeutic targets (STAT3 and Nrf2) and, at the same time, reduce cisplatin-related ototoxic adverse effects.

Artist's concept of Apollo 8 command/service module heading for the moon

NASA Technical Reports Server (NTRS)

1968-01-01

North American Rockwell artist's concept illustrating a phase of the scheduled Apollo 8 lunar orbit mission. Here, the Apollo 8 spacecraft command and service modules, still attached to the Satury V third (S-IVB) stage, heads for the moon at a speed of about 24,300 miles an hour.

Review of the Modular Administrative Structure.

ERIC Educational Resources Information Center

Grand Valley State Colleges, Allendale, MI. Office of Institutional Analysis.

The modular administrative structure implemented at Grand Valley State Colleges in 1973 is described as a system in which administrative affairs are divided into functional self-contained units called modules, each of which has a head or acting head who is responsible for the management of the functions contained within the module. A long-range…

Computations underlying the visuomotor transformation for smooth pursuit eye movements

PubMed Central

Murdison, T. Scott; Leclercq, Guillaume; Lefèvre, Philippe

2014-01-01

Smooth pursuit eye movements are driven by retinal motion and enable us to view moving targets with high acuity. Complicating the generation of these movements is the fact that different eye and head rotations can produce different retinal stimuli but giving rise to identical smooth pursuit trajectories. However, because our eyes accurately pursue targets regardless of eye and head orientation (Blohm G, Lefèvre P. J Neurophysiol 104: 2103–2115, 2010), the brain must somehow take these signals into account. To learn about the neural mechanisms potentially underlying this visual-to-motor transformation, we trained a physiologically inspired neural network model to combine two-dimensional (2D) retinal motion signals with three-dimensional (3D) eye and head orientation and velocity signals to generate a spatially correct 3D pursuit command. We then simulated conditions of 1) head roll-induced ocular counterroll, 2) oblique gaze-induced retinal rotations, 3) eccentric gazes (invoking the half-angle rule), and 4) optokinetic nystagmus to investigate how units in the intermediate layers of the network accounted for different 3D constraints. Simultaneously, we simulated electrophysiological recordings (visual and motor tunings) and microstimulation experiments to quantify the reference frames of signals at each processing stage. We found a gradual retinal-to-intermediate-to-spatial feedforward transformation through the hidden layers. Our model is the first to describe the general 3D transformation for smooth pursuit mediated by eye- and head-dependent gain modulation. Based on several testable experimental predictions, our model provides a mechanism by which the brain could perform the 3D visuomotor transformation for smooth pursuit. PMID:25475344

A comparative study of standard intensity-modulated radiotherapy and RapidArc planning techniques for ipsilateral and bilateral head and neck irradiation

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

Pursley, Jennifer, E-mail: jpursley@mgh.harvard.edu; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Damato, Antonio L.

The purpose of this study was to investigate class solutions using RapidArc volumetric-modulated arc therapy (VMAT) planning for ipsilateral and bilateral head and neck (H&N) irradiation, and to compare dosimetric results with intensity-modulated radiotherapy (IMRT) plans. A total of 14 patients who received ipsilateral and 10 patients who received bilateral head and neck irradiation were retrospectively replanned with several volumetric-modulated arc therapy techniques. For ipsilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the contralateral parotid, two 260° or 270° arcs, and two 210° arcs. For bilateral neck irradiation, themore » volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the shoulders, and 3 arcs. All patients had a sliding-window-delivery intensity-modulated radiotherapy plan that was used as the benchmark for dosimetric comparison. For ipsilateral neck irradiation, a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid was dosimetrically comparable to intensity-modulated radiotherapy, with improved conformity (conformity index = 1.22 vs 1.36, p < 0.04) and lower contralateral parotid mean dose (5.6 vs 6.8 Gy, p < 0.03). For bilateral neck irradiation, 3-arc volumetric-modulated arc therapy techniques were dosimetrically comparable to intensity-modulated radiotherapy while also avoiding irradiation through the shoulders. All volumetric-modulated arc therapy techniques required fewer monitor units than sliding-window intensity-modulated radiotherapy to deliver treatment, with an average reduction of 35% for ipsilateral plans and 67% for bilateral plans. Thus, for ipsilateral head and neck irradiation a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid is recommended. For bilateral neck irradiation, 2- or 3-arc techniques are dosimetrically comparable to intensity-modulated radiotherapy, but more work is needed to determine the optimal approaches by disease site.« less

A comparative study of standard intensity-modulated radiotherapy and RapidArc planning techniques for ipsilateral and bilateral head and neck irradiation.

PubMed

Pursley, Jennifer; Damato, Antonio L; Czerminska, Maria A; Margalit, Danielle N; Sher, David J; Tishler, Roy B

2017-01-01

The purpose of this study was to investigate class solutions using RapidArc volumetric-modulated arc therapy (VMAT) planning for ipsilateral and bilateral head and neck (H&N) irradiation, and to compare dosimetric results with intensity-modulated radiotherapy (IMRT) plans. A total of 14 patients who received ipsilateral and 10 patients who received bilateral head and neck irradiation were retrospectively replanned with several volumetric-modulated arc therapy techniques. For ipsilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the contralateral parotid, two 260° or 270° arcs, and two 210° arcs. For bilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the shoulders, and 3 arcs. All patients had a sliding-window-delivery intensity-modulated radiotherapy plan that was used as the benchmark for dosimetric comparison. For ipsilateral neck irradiation, a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid was dosimetrically comparable to intensity-modulated radiotherapy, with improved conformity (conformity index = 1.22 vs 1.36, p < 0.04) and lower contralateral parotid mean dose (5.6 vs 6.8Gy, p < 0.03). For bilateral neck irradiation, 3-arc volumetric-modulated arc therapy techniques were dosimetrically comparable to intensity-modulated radiotherapy while also avoiding irradiation through the shoulders. All volumetric-modulated arc therapy techniques required fewer monitor units than sliding-window intensity-modulated radiotherapy to deliver treatment, with an average reduction of 35% for ipsilateral plans and 67% for bilateral plans. Thus, for ipsilateral head and neck irradiation a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid is recommended. For bilateral neck irradiation, 2- or 3-arc techniques are dosimetrically comparable to intensity-modulated radiotherapy, but more work is needed to determine the optimal approaches by disease site. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Enhancing Children's Growth and Development. Training Guides for the Head Start Learning Community.

ERIC Educational Resources Information Center

Aspen Systems Corp., Rockville, MD.

This training guide is designed to enhance the skills of Head Start education staff in applying knowledge of how children grow and develop to planning, implementing, and evaluating activities and experiences in the center, at home, and during group socialization sessions. Each of the guide's modules details module outcomes, key concepts, and…

Antagonistic Self-Organizing Patterning Systems Control Maintenance and Regeneration of the Anteroposterior Axis in Planarians.

PubMed

Stückemann, Tom; Cleland, James Patrick; Werner, Steffen; Thi-Kim Vu, Hanh; Bayersdorf, Robert; Liu, Shang-Yun; Friedrich, Benjamin; Jülicher, Frank; Rink, Jochen Christian

2017-02-06

Planarian flatworms maintain their body plan in the face of constant internal turnover and can regenerate from arbitrary tissue fragments. Both phenomena require self-maintaining and self-organizing patterning mechanisms, the molecular mechanisms of which remain poorly understood. We show that a morphogenic gradient of canonical Wnt signaling patterns gene expression along the planarian anteroposterior (A/P) axis. Our results demonstrate that gradient formation likely occurs autonomously in the tail and that an autoregulatory module of Wnt-mediated Wnt expression both shapes the gradient at steady state and governs its re-establishment during regeneration. Functional antagonism between the tail Wnt gradient and an unknown head patterning system further determines the spatial proportions of the planarian A/P axis and mediates mutually exclusive molecular fate choices during regeneration. Overall, our results suggest that the planarian A/P axis is patterned by self-organizing patterning systems deployed from either end that are functionally coupled by mutual antagonism. Copyright © 2017 Elsevier Inc. All rights reserved.

High-throughput transcriptome analysis of ISAV-infected Atlantic salmon Salmo salar unravels divergent immune responses associated to head-kidney, liver and gills tissues.

PubMed

Valenzuela-Miranda, Diego; Boltaña, Sebastian; Cabrejos, Maria E; Yáñez, José M; Gallardo-Escárate, Cristian

2015-08-01

Infectious salmon anaemia virus (ISAV) is an orthomyxovirus causing high mortality in farmed Atlantic salmon (Salmo salar). The collective data from the Atlantic salmon-ISAV interactions, performed "in vitro" using various salmon cell lines and "in vivo" fish infected with different ISAV isolates, have shown a strong regulation of immune related transcripts during the infection. Despite this strong defence response, the majority of fish succumb to infections with ISAV. The deficient protection of the host against ISAV is in part due to virulence factors of the virus, which allow evade the host-defence machinery. As such, the viral replication is uninhibited and viral loads quickly spread to several tissues causing massive cellular damage before the host can develop an effective cell-mediated and humoral outcome. To interrogate the correlation of the viral replication with the host defence response, we used fish that have been infected by cohabitation with ISAV-injected salmons. Whole gene expression patterns were measured with RNA-seq using RNA extracted from Head-kidney, Liver and Gills. The results show divergent mRNA abundance of functional modules related to interferon pathway, adaptive/innate immune response and cellular proliferation/differentiation. Furthermore, gene regulation in distinct tissues during the infection process was independently controlled within the each tissue and the observed mRNA expression suggests high modulation of the ISAV-segment transcription. Importantly this is the first time that strong correlations between functional modules containing significant immune process with protein-protein affinities and viral-segment transcription have been made between different tissues of ISAV-infected fish. Copyright © 2015 Elsevier Ltd. All rights reserved.

Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1.

PubMed

Lee, Hyeyoon; Cheong, Seong-Moon; Han, Wonhee; Koo, Youngmu; Jo, Saet-Byeol; Cho, Gun-Sik; Yang, Jae-Seong; Kim, Sanguk; Han, Jin-Kwan

2018-04-10

Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether the antagonism of Wnt signaling that is necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here, we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in the prospective head region of Xenopus We further found that March2 acquires regional and functional specificities for head formation from the Dsh-interacting protein Dapper1 (Dpr1). Dpr1 stabilizes the interaction between March2 and Dsh in order to mediate ubiquitylation and the subsequent degradation of Dsh protein only in the dorso-animal region of Xenopus embryo. These results suggest that March2 restricts cytosolic pools of Dsh protein and reduces the need for Wnt signaling in precise vertebrate head development. © 2018. Published by The Company of Biologists Ltd.

Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification.

PubMed

Yasuoka, Yuuri; Suzuki, Yutaka; Takahashi, Shuji; Someya, Haruka; Sudou, Norihiro; Haramoto, Yoshikazu; Cho, Ken W; Asashima, Makoto; Sugano, Sumio; Taira, Masanori

2014-07-09

Head specification by the head-selector gene, orthodenticle (otx), is highly conserved among bilaterian lineages. However, the molecular mechanisms by which Otx and other transcription factors (TFs) interact with the genome to direct head formation are largely unknown. Here we employ ChIP-seq and RNA-seq approaches in Xenopus tropicalis gastrulae and find that occupancy of the corepressor, TLE/Groucho, is a better indicator of tissue-specific cis-regulatory modules (CRMs) than the coactivator p300, during early embryonic stages. On the basis of TLE binding and comprehensive CRM profiling, we define two distinct types of Otx2- and TLE-occupied CRMs. Using these devices, Otx2 and other head organizer TFs (for example, Lim1/Lhx1 (activator) or Goosecoid (repressor)) are able to upregulate or downregulate a large battery of target genes in the head organizer. An underlying principle is that Otx marks target genes for head specification to be regulated positively or negatively by partner TFs through specific types of CRMs.

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN-depleted head and neck cancer tumor cells.

PubMed

Liu, Zhiyong; Hartman, Yolanda E; Warram, Jason M; Knowles, Joseph A; Sweeny, Larissa; Zhou, Tong; Rosenthal, Eben L

2011-08-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma-mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer, there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here, we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were cocultured with fibroblasts or inoculated with fibroblasts into severe combined immunodeficient mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Coculture experiments showed fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN-silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN-silenced cells compared with control vector-transfected cells, whereas inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast coculture, suggesting the importance of FGFR2 signaling in fibroblast-mediated tumor growth. Analysis of xenografted tumors revealed that EMMPRIN-silenced tumors had a larger stromal compartment compared with control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast-independent tumor growth.

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN depleted head and neck cancer tumor cells

PubMed Central

Liu, Zhiyong; Hartman, Yolanda E.; Warram, Jason M.; Knowles, Joseph A.; Sweeny, Larrisa; Zhou, Tong; Rosenthal, Eben L.

2011-01-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were co-cultured with fibroblasts or inoculated with fibroblasts into SCID mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Co-culture experiments demonstrated fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN silenced cells compared to control vector transfected cells, while inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast co-culture, suggesting the importance of FGFR2 signaling in fibroblast mediated tumor growth. Analysis of xenografted tumors revealed EMMPRIN silenced tumors had a larger stromal compartment compared to control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast independent tumor growth. PMID:21665938

Intensity Modulated Radiotherapy (IMRT) in head and neck cancers - an overview.

PubMed

Nutting, C M

2012-07-01

Radiotherapy (RT) is effective in head and neck cancers. Following RT, dryness and dysphagia are the 2 major sequelae which alter the quality of life (QOL) significantly in these patients. There is randomized evidence that Intensity Modulated Radiotherapy (IMRT) effectively spares the parotid glands. IMRT has been attempted in all head and neck subsites with encouraging results (discussed below). Role of IMRT in swallowing structure (constrictor muscles) sparing is less clear.Further improvement in results may be possible by using functional imaging at the time of RT planning and by image guidance/verification at the time of treatment delivery. The following text discusses these issues in detail. Head and neck cancer, IMRT.

Neural correlates for angular head velocity in the rat dorsal tegmental nucleus

NASA Technical Reports Server (NTRS)

Bassett, J. P.; Taube, J. S.; Oman, C. M. (Principal Investigator)

2001-01-01

Many neurons in the rat lateral mammillary nuclei (LMN) fire selectively in relation to the animal's head direction (HD) in the horizontal plane independent of the rat's location or behavior. One hypothesis of how this representation is generated and updated is via subcortical projections from the dorsal tegmental nucleus (DTN). Here we report the type of activity in DTN neurons. The majority of cells (75%) fired as a function of the rat's angular head velocity (AHV). Cells exhibited one of two types of firing patterns: (1) symmetric, in which the firing rate was positively correlated with AHV during head turns in both directions, and (2) asymmetric, in which the firing rate was positively correlated with head turns in one direction and correlated either negatively or not at all in the opposite direction. In addition to modulation by AHV, some of the AHV cells (40.1%) were weakly modulated by the rat's linear velocity, and a smaller number were modulated by HD (11%) or head pitch (15.9%). Autocorrelation analyses indicated that with the head stationary, AHV cells displayed irregular discharge patterns. Because afferents from the DTN are the major source of information projecting to the LMN, these results suggest that AHV information from the DTN plays a significant role in generating the HD signal in LMN. A model is proposed showing how DTN AHV cells can generate and update the LMN HD cell signal.

Emerging Insights into Wnt/β-catenin Signaling in Head and Neck Cancer.

PubMed

Alamoud, K A; Kukuruzinska, M A

2018-06-01

Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits. A central component of canonical Wnt signaling is β-catenin, which balances its role as a structural component of E-cadherin junctions with its function as a transcriptional coactivator of numerous target genes. Recent genomic characterization of head and neck cancer revealed that while β-catenin is not frequently mutated in HNSCC, its activity is unchecked by more common mutations in genes encoding upstream regulators of β-catenin, NOTCH1, FAT1, and AJUBA. Wnt/β-catenin signaling affects a wide range epigenetic and transcriptional activities, mediated by the interaction of β-catenin with different transcription factors and transcriptional coactivators and corepressors. Furthermore, Wnt/β-catenin functions in a network with many signaling and metabolic pathways that modulate its activity. In addition to its effects on tumor epithelia, β-catenin activity regulates the tumor microenvironment by regulating extracellular matrix remodeling, fibrotic processes, and immune response. These multifunctional oncogenic effects of β-catenin make it an attractive bona fide target for HNSCC therapy.

Mediator directs co-transcriptional heterochromatin assembly by RNA interference-dependent and -independent pathways.

PubMed

Oya, Eriko; Kato, Hiroaki; Chikashige, Yuji; Tsutsumi, Chihiro; Hiraoka, Yasushi; Murakami, Yota

2013-01-01

Heterochromatin at the pericentromeric repeats in fission yeast is assembled and spread by an RNAi-dependent mechanism, which is coupled with the transcription of non-coding RNA from the repeats by RNA polymerase II. In addition, Rrp6, a component of the nuclear exosome, also contributes to heterochromatin assembly and is coupled with non-coding RNA transcription. The multi-subunit complex Mediator, which directs initiation of RNA polymerase II-dependent transcription, has recently been suggested to function after initiation in processes such as elongation of transcription and splicing. However, the role of Mediator in the regulation of chromatin structure is not well understood. We investigated the role of Mediator in pericentromeric heterochromatin formation and found that deletion of specific subunits of the head domain of Mediator compromised heterochromatin structure. The Mediator head domain was required for Rrp6-dependent heterochromatin nucleation at the pericentromere and for RNAi-dependent spreading of heterochromatin into the neighboring region. In the latter process, Mediator appeared to contribute to efficient processing of siRNA from transcribed non-coding RNA, which was required for efficient spreading of heterochromatin. Furthermore, the head domain directed efficient transcription in heterochromatin. These results reveal a pivotal role for Mediator in multiple steps of transcription-coupled formation of pericentromeric heterochromatin. This observation further extends the role of Mediator to co-transcriptional chromatin regulation.

The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering

PubMed Central

Ellis, Stephanie J.; Lostchuck, Emily; Goult, Benjamin T.; Bouaouina, Mohamed; Fairchild, Michael J.; López-Ceballos, Pablo; Calderwood, David A.; Tanentzapf, Guy

2014-01-01

Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex. In addition, the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands, a process known as inside-out activation. We previously showed that in Drosophila, mutating the integrin binding site in the talin head domain resulted in weakened adhesion to the ECM. Intriguingly, subsequent studies showed that canonical inside-out activation of integrin might not take place in flies. Consistent with this, a mutation in talin that specifically blocks its ability to activate mammalian integrins does not significantly impinge on talin function during fly development. Here, we describe results suggesting that the talin head domain reinforces and stabilizes the integrin adhesion complex by promoting integrin clustering distinct from its ability to support inside-out activation. Specifically, we show that an allele of talin containing a mutation that disrupts intramolecular interactions within the talin head attenuates the assembly and reinforcement of the integrin adhesion complex. Importantly, we provide evidence that this mutation blocks integrin clustering in vivo. We propose that the talin head domain is essential for regulating integrin avidity in Drosophila and that this is crucial for integrin-mediated adhesion during animal development. PMID:25393120

A Dyadic Analysis of Head Start Parents' Depressive Symptoms and Parent Involvement: Sense of Mastery as a Mediator

ERIC Educational Resources Information Center

Meng, Christine; Cheng, Ya-Fang

2017-01-01

This study used the actor-partner interdependence mediation model to examine the association among parents' depressive symptoms, sense of mastery, and parent involvement. To address the research goal, this study conducted secondary analysis using the cross-sectional data collected from the 2000 cohort of the Head Start Family and Child Experiences…

Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients

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

Penoncello, Gregory P.; Ding, George X., E-mail: george.ding@vanderbilt.edu

The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, andmore » 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2 cm{sup 3} for head and neck plans and brain plans and a contiguous volume of 5 cm{sup 3} for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.« less

Design of the PET-MR system for head imaging of the DREAM Project

NASA Astrophysics Data System (ADS)

González, A. J.; Conde, P.; Hernández, L.; Herrero, V.; Moliner, L.; Monzó, J. M.; Orero, A.; Peiró, A.; Rodríguez-Álvarez, M. J.; Ros, A.; Sánchez, F.; Soriano, A.; Vidal, L. F.; Benlloch, J. M.

2013-02-01

In this paper we describe the overall design of a PET-MR system for head imaging within the framework of the DREAM Project as well as the first detector module tests. The PET system design consists of 4 rings of 16 detector modules each and it is expected to be integrated in a head dedicated radio frequency coil of an MR scanner. The PET modules are based on monolithic LYSO crystals coupled by means of optical devices to an array of 256 Silicon Photomultipliers. These types of crystals allow to preserve the scintillation light distribution and, thus, to recover the exact photon impact position with the proper characterization of such a distribution. Every module contains 4 Application Specific Integrated Circuits (ASICs) which return detailed information of several light statistical momenta. The preliminary tests carried out on this design and controlled by means of ASICs have shown promising results towards the suitability of hybrid PET-MR systems.

Joint representation of translational and rotational components of optic flow in parietal cortex

PubMed Central

Sunkara, Adhira; DeAngelis, Gregory C.; Angelaki, Dora E.

2016-01-01

Terrestrial navigation naturally involves translations within the horizontal plane and eye rotations about a vertical (yaw) axis to track and fixate targets of interest. Neurons in the macaque ventral intraparietal (VIP) area are known to represent heading (the direction of self-translation) from optic flow in a manner that is tolerant to rotational visual cues generated during pursuit eye movements. Previous studies have also reported that eye rotations modulate the response gain of heading tuning curves in VIP neurons. We tested the hypothesis that VIP neurons simultaneously represent both heading and horizontal (yaw) eye rotation velocity by measuring heading tuning curves for a range of rotational velocities of either real or simulated eye movements. Three findings support the hypothesis of a joint representation. First, we show that rotation velocity selectivity based on gain modulations of visual heading tuning is similar to that measured during pure rotations. Second, gain modulations of heading tuning are similar for self-generated eye rotations and visually simulated rotations, indicating that the representation of rotation velocity in VIP is multimodal, driven by both visual and extraretinal signals. Third, we show that roughly one-half of VIP neurons jointly represent heading and rotation velocity in a multiplicatively separable manner. These results provide the first evidence, to our knowledge, for a joint representation of translation direction and rotation velocity in parietal cortex and show that rotation velocity can be represented based on visual cues, even in the absence of efference copy signals. PMID:27095846

The Role of Classroom Quality in Explaining Head Start Impacts

ERIC Educational Resources Information Center

Connors, Maia C.; Friedman-Krauss, Allison H.; Morris, Pamela A.; Page, Lindsay C.; Feller, Avi

2014-01-01

This study seeks to answer the following question: Are impacts on Head Start classroom quality associated with impacts of Head Start on children's learning and development? This study employs a variety of descriptive and quasi-experimental methods to explore the role of classroom quality as a mediator or mechanism of Head Start impacts. This…

43 CFR 17.332 - Mediation.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., and Enforcement Procedures § 17.332 Mediation. (a) Referral of complaints for mediation. DOI will... it. The FMCS shall send the agreement to DOI. DOI, however, retains the right to monitor the... process without prior approval of the head of the mediation agency. (e) DOI will use the mediation process...

An evaluation to design high performance pinhole array detector module for four head SPECT: a simulation study

NASA Astrophysics Data System (ADS)

Rahman, Tasneem; Tahtali, Murat; Pickering, Mark R.

2014-09-01

The purpose of this study is to derive optimized parameters for a detector module employing an off-the-shelf X-ray camera and a pinhole array collimator applicable for a range of different SPECT systems. Monte Carlo simulations using the Geant4 application for tomographic emission (GATE) were performed to estimate the performance of the pinhole array collimators and were compared to that of low energy high resolution (LEHR) parallel-hole collimator in a four head SPECT system. A detector module was simulated to have 48 mm by 48 mm active area along with 1mm, 1.6mm and 2 mm pinhole aperture sizes at 0.48 mm pitch on a tungsten plate. Perpendicular lead septa were employed to verify overlapping and non-overlapping projections against a proper acceptance angle without lead septa. A uniform shape cylindrical water phantom was used to evaluate the performance of the proposed four head SPECT system of the pinhole array detector module. For each head, 100 pinhole configurations were evaluated based on sensitivity and detection efficiency for 140 keV γ-rays, and compared to LEHR parallel-hole collimator. SPECT images were reconstructed based on filtered back projection (FBP) algorithm where neither scatter nor attenuation corrections were performed. A better reconstruction algorithm development for this specific system is in progress. Nevertheless, activity distribution was well visualized using the backprojection algorithm. In this study, we have evaluated several quantitative and comparative analyses for a pinhole array imaging system providing high detection efficiency and better system sensitivity over a large FOV, comparing to the conventional four head SPECT system. The proposed detector module is expected to provide improved performance in various SPECT imaging.

Intensity-Modulated Radiation Therapy (IMRT) for Head and Neck Surgeons

PubMed Central

Gutiontov, Stanley I.; Shin, Edward J.; Lok, Benjamin; Lee, Nancy Y.; Cabanillas, Ruben

2016-01-01

The development of intensity-modulated radiation therapy has played a major role in improving outcomes and decreasing morbidity in head and neck cancer patients. This review addresses this vital modality with a focus on the important role of the head and neck surgeon. The technique as well as its benefits and points of caution are outlined, the definitions of tumor and treatment volumes are discussed, and the dose and fractionation are detailed. Following this are several sections dedicated to the role of the head and neck surgeon in the planning of both definitive and post-operative radiation therapy to the primary site and neck. There is a focus throughout on anatomic and surgical considerations; commonly encountered situations are illustrated. With a deeper understanding of this technique and their own pivotal contribution to target delineation, head and neck surgeons will be poised to expand their role and improve cancer care for their patients. PMID:26705685

Industrial and biomedical use of aerospace personal cooling garments

NASA Technical Reports Server (NTRS)

Williams, B. A.; Mcewen, G. N., Jr.; Montgomery, L. D.; Elkins, W. E.

1975-01-01

Liquid-cooled garments (LCG) have been developed which utilize liquid-cooled modules rather than the network of tygon tubing typical of Apollo LCG's. The ultra-thin, heat-sealed, polyurethane modules are situated over the body to cover 50 percent of the body surface area with special emphasis on the 'working' muscles and the head-neck area. These garments are being designed specifically for industrial and biomedical uses, such as: a head-neck cooling system which is being tested for race-car drivers, tractor drivers, truck drivers, or a head-neck cooling system tested for the reduction of the scalp hair loss which normally accompanies cancer treatments. A combined head-neck and thorax unit is being developed for use during mine distaster rescue operations, and for other hazardous hot applications. Finally applications for head-neck and partitional cooling are anticipated for military pilots, tank drivers, and heavy equipment operations.

Frames of reference for gaze saccades evoked during stimulation of lateral intraparietal cortex.

PubMed

Constantin, A G; Wang, H; Martinez-Trujillo, J C; Crawford, J D

2007-08-01

Previous studies suggest that stimulation of lateral intraparietal cortex (LIP) evokes saccadic eye movements toward eye- or head-fixed goals, whereas most single-unit studies suggest that LIP uses an eye-fixed frame with eye-position modulations. The goal of our study was to determine the reference frame for gaze shifts evoked during LIP stimulation in head-unrestrained monkeys. Two macaques (M1 and M2) were implanted with recording chambers over the right intraparietal sulcus and with search coils for recording three-dimensional eye and head movements. The LIP region was microstimulated using pulse trains of 300 Hz, 100-150 microA, and 200 ms. Eighty-five putative LIP sites in M1 and 194 putative sites in M2 were used in our quantitative analysis throughout this study. Average amplitude of the stimulation-evoked gaze shifts was 8.67 degrees for M1 and 7.97 degrees for M2 with very small head movements. When these gaze-shift trajectories were rotated into three coordinate frames (eye, head, and body), gaze endpoint distribution for all sites was most convergent to a common point when plotted in eye coordinates. Across all sites, the eye-centered model provided a significantly better fit compared with the head, body, or fixed-vector models (where the latter model signifies no modulation of the gaze trajectory as a function of initial gaze position). Moreover, the probability of evoking a gaze shift from any one particular position was modulated by the current gaze direction (independent of saccade direction). These results provide causal evidence that the motor commands from LIP encode gaze command in eye-fixed coordinates but are also subtly modulated by initial gaze position.

Mediator kinase module and human tumorigenesis.

PubMed

Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

2015-01-01

Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

Mediator kinase module and human tumorigenesis

PubMed Central

Clark, Alison D.; Oldenbroek, Marieke; Boyer, Thomas G.

2016-01-01

Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit “kinase” module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways. PMID:26182352

The Impact of Parent Involvement in Head Start on Parents and Children. Final Report [and] Executive Summary.

ERIC Educational Resources Information Center

Parker, Faith Lamb; Piotrkowski, Chaya S.; Kessler-Sklar, Susan; Baker, Amy J. L.; Peay, Lenore; Clark, Beryl

From its inception, Head Start's legislative mandate called for "maximum feasible participation" of parents in all programmatic efforts and policy decisions. Nevertheless, there has been little research done on the benefits of Head Start to parents and on the role of parents as mediators of child and family outcomes. The Head Start…

Inhibition of Hsp27 Radiosensitizes Head-and-Neck Cancer by Modulating Deoxyribonucleic Acid Repair

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

Guttmann, David M.; Hart, Lori; Du, Kevin

Purpose: To present a novel method of tumor radiosensitization through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair. Methods and Materials: Clonogenic survival assays, immunoblotting, the proximity ligation assay, and γH2AX foci analysis were conducted in SQ20B and FaDu human head-and-neck cancer cell lines treated with Hsp27 LNA and Hsp27 short hairpin RNA (shRNA). Additionally, nude mice with FaDu flank tumors were treated with fractionated radiation therapy after pretreatment with Hsp27 LNA and monitored for tumor growth. Results: Hsp27 LNA and Hsp27 shRNA radiosensitized head-and-neck cancer cellmore » lines in an Hsp27-dependent manner. Ataxia-Telangectasia Mutated-mediated DNA repair signaling was impaired in irradiated cells with Hsp27 knockdown. ATM kinase inhibition abrogated the radiosensitizing effect of Hsp27. Furthermore, Hsp27 LNA and shRNA both attenuated DNA repair kinetics after radiation, and Hsp27 was found to colocalize with ATM in both untreated and irradiated cells. Last, combined radiation and Hsp27 LNA treatment in tumor xenografts in nude mice suppressed tumor growth compared with either treatment alone. Conclusions: These results support a radiosensitizing property of Hsp27 LNA in vitro and in vivo, implicate Hsp27 in double strand break repair, and suggest that Hsp27 LNA might eventually serve as an effective clinical agent in the radiotherapy of head-and-neck cancer.« less

Inhibition of Hsp27 radiosensitizes head-and-neck cancer by modulating deoxyribonucleic acid repair.

PubMed

Guttmann, David M; Hart, Lori; Du, Kevin; Seletsky, Andrew; Koumenis, Constantinos

2013-09-01

To present a novel method of tumor radiosensitization through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair. Clonogenic survival assays, immunoblotting, the proximity ligation assay, and γH2AX foci analysis were conducted in SQ20B and FaDu human head-and-neck cancer cell lines treated with Hsp27 LNA and Hsp27 short hairpin RNA (shRNA). Additionally, nude mice with FaDu flank tumors were treated with fractionated radiation therapy after pretreatment with Hsp27 LNA and monitored for tumor growth. Hsp27 LNA and Hsp27 shRNA radiosensitized head-and-neck cancer cell lines in an Hsp27-dependent manner. Ataxia-Telangectasia Mutated-mediated DNA repair signaling was impaired in irradiated cells with Hsp27 knockdown. ATM kinase inhibition abrogated the radiosensitizing effect of Hsp27. Furthermore, Hsp27 LNA and shRNA both attenuated DNA repair kinetics after radiation, and Hsp27 was found to colocalize with ATM in both untreated and irradiated cells. Last, combined radiation and Hsp27 LNA treatment in tumor xenografts in nude mice suppressed tumor growth compared with either treatment alone. These results support a radiosensitizing property of Hsp27 LNA in vitro and in vivo, implicate Hsp27 in double strand break repair, and suggest that Hsp27 LNA might eventually serve as an effective clinical agent in the radiotherapy of head-and-neck cancer. Copyright © 2013. Published by Elsevier Inc.

Visualizing Simulated Electrical Fields from Electroencephalography and Transcranial Electric Brain Stimulation: A Comparative Evaluation

PubMed Central

Eichelbaum, Sebastian; Dannhauer, Moritz; Hlawitschka, Mario; Brooks, Dana; Knösche, Thomas R.; Scheuermann, Gerik

2014-01-01

Electrical activity of neuronal populations is a crucial aspect of brain activity. This activity is not measured directly but recorded as electrical potential changes using head surface electrodes (electroencephalogram - EEG). Head surface electrodes can also be deployed to inject electrical currents in order to modulate brain activity (transcranial electric stimulation techniques) for therapeutic and neuroscientific purposes. In electroencephalography and noninvasive electric brain stimulation, electrical fields mediate between electrical signal sources and regions of interest (ROI). These fields can be very complicated in structure, and are influenced in a complex way by the conductivity profile of the human head. Visualization techniques play a central role to grasp the nature of those fields because such techniques allow for an effective conveyance of complex data and enable quick qualitative and quantitative assessments. The examination of volume conduction effects of particular head model parameterizations (e.g., skull thickness and layering), of brain anomalies (e.g., holes in the skull, tumors), location and extent of active brain areas (e.g., high concentrations of current densities) and around current injecting electrodes can be investigated using visualization. Here, we evaluate a number of widely used visualization techniques, based on either the potential distribution or on the current-flow. In particular, we focus on the extractability of quantitative and qualitative information from the obtained images, their effective integration of anatomical context information, and their interaction. We present illustrative examples from clinically and neuroscientifically relevant cases and discuss the pros and cons of the various visualization techniques. PMID:24821532

Planning comparison between intensity modulated radiation therapy and intensity modulated proton therapy in a case of head and neck cancer

NASA Astrophysics Data System (ADS)

Nguyen, T. T. C.; Nguyen, B. T.; Mai, N. V.

2018-03-01

In this work, we made the comparison between IMRT plan and IMPT plan for a head and neck case. We used Prowess Panther to perform IMRT plan and LAP- CERR for IMPT plan. The result showed that IMPT plan had better coverage than IMRT plan. In the IMRT plan, normal structures received higher dose with higher volume. Especially, the maximum dose of spinal cord is 31.5 Gy (RBE) using IMRT technique compared to 13.5 Gy (RBE) using IMPT technique. These results showed that IMPT is beneficial for head and neck cancer compared to IMRT technique.

Dynamic modulation of ocular orientation during visually guided saccades and smooth-pursuit eye movements

NASA Technical Reports Server (NTRS)

Hess, Bernhard J M.; Angelaki, Dora E.

2003-01-01

Rotational disturbances of the head about an off-vertical yaw axis induce a complex vestibuloocular reflex pattern that reflects the brain's estimate of head angular velocity as well as its estimate of instantaneous head orientation (at a reduced scale) in space coordinates. We show that semicircular canal and otolith inputs modulate torsional and, to a certain extent, also vertical ocular orientation of visually guided saccades and smooth-pursuit eye movements in a similar manner as during off-vertical axis rotations in complete darkness. It is suggested that this graviceptive control of eye orientation facilitates rapid visual spatial orientation during motion.

The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

PubMed Central

Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

2014-01-01

Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

PubMed

Carbonaro, Theresa M; Eshleman, Amy J; Forster, Michael J; Cheng, Kejun; Rice, Kenner C; Gatch, Michael B

2015-01-01

Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients.

PubMed

Penoncello, Gregory P; Ding, George X

2016-01-01

The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2cm(3) for head and neck plans and brain plans and a contiguous volume of 5cm(3) for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

15 CFR 930.112 - Request for Secretarial mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Request for Secretarial mediation. 930... RESOURCE MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.112 Request for Secretarial mediation. (a) The Secretary or other head of a Federal agency, or the...

Challenges of Roll Orientation with Respect to Vehicle Heading at Touchdown for the Orion Command Module

NASA Technical Reports Server (NTRS)

Gay, Robert S.; Bihari, Brian D.

2008-01-01

Due to mass constraints, the Orion Command Module landing attention system requires that the capsule be oriented in a specific direction with respect to the horizontal surface-relative velocity (Heading) at touchdown in order to keep crew and vehicle loads within specifications. These constraints apply to both land and water landings. In fact, water landings are even more constrained with the addition of impact angle requirements necessary to slice through the water. There are two primary challenges with achieving this touchdown orientation: 1. Navigation knowledge of velocity (needed to determine Heading) with and without GPS, including the effects of the Heading angle itself becoming undefined as horizontal velocity decreases, and 2. Controlling to the desired orientation in the presences of chute torque and wind gusts that may change the Heading just prior to touchdown. This paper will discuss the design and performance of the current Orion navigation and control system used to achieve the desired orientation at touchdown.

Cognitive Flexibility, Approaches to Learning, and Academic School Readiness in Head Start Preschool Children

ERIC Educational Resources Information Center

Vitiello, Virginia E.; Greenfield, Daryl B.; Munis, Pelin; George, J'Lene

2011-01-01

Research Findings: The purpose of this study was to examine whether approaches to learning significantly mediated relations between cognitive flexibility (a component of executive functions) and school readiness in Head Start preschoolers. A total of 191 children from 22 Head Start classrooms were directly assessed on cognitive flexibility and…

Kinematic principles of primate rotational vestibulo-ocular reflex. II. Gravity-dependent modulation of primary eye position

NASA Technical Reports Server (NTRS)

Hess, B. J.; Angelaki, D. E.

1997-01-01

The kinematic constraints of three-dimensional eye positions were investigated in rhesus monkeys during passive head and body rotations relative to gravity. We studied fast and slow phase components of the vestibulo-ocular reflex (VOR) elicited by constant-velocity yaw rotations and sinusoidal oscillations about an earth-horizontal axis. We found that the spatial orientation of both fast and slow phase eye positions could be described locally by a planar surface with torsional variation of <2.0 +/- 0.4 degrees (displacement planes) that systematically rotated and/or shifted relative to Listing's plane. In supine/prone positions, displacement planes pitched forward/backward; in left/right ear-down positions, displacement planes were parallel shifted along the positive/negative torsional axis. Dynamically changing primary eye positions were computed from displacement planes. Torsional and vertical components of primary eye position modulated as a sinusoidal function of head orientation in space. The torsional component was maximal in ear-down positions and approximately zero in supine/prone orientations. The opposite was observed for the vertical component. Modulation of the horizontal component of primary eye position exhibited a more complex dependence. In contrast to the torsional component, which was relatively independent of rotational speed, modulation of the vertical and horizontal components of primary position depended strongly on the speed of head rotation (i.e., on the frequency of oscillation of the gravity vector component): the faster the head rotated relative to gravity, the larger was the modulation. Corresponding results were obtained when a model based on a sinusoidal dependence of instantaneous displacement planes (and primary eye position) on head orientation relative to gravity was fitted to VOR fast phase positions. When VOR fast phase positions were expressed relative to primary eye position estimated from the model fits, they were confined approximately to a single plane with a small torsional standard deviation ( approximately 1.4-2.6 degrees). This reduced torsional variation was in contrast to the large torsional spread (well >10-15 degrees ) of fast phase positions when expressed relative to Listing's plane. We conclude that primary eye position depends dynamically on head orientation relative to space rather than being fixed to the head. It defines a gravity-dependent coordinate system relative to which the torsional variability of eye positions is minimized even when the head is moved passively and vestibulo-ocular reflexes are evoked. In this general sense, Listing's law is preserved with respect to an otolith-controlled reference system that is defined dynamically by gravity.

Method and system for compact efficient laser architecture

DOEpatents

Bayramian, Andrew James; Erlandson, Alvin Charles; Manes, Kenneth Rene; Spaeth, Mary Louis; Caird, John Allyn; Deri, Robert J.

2015-09-15

A laser amplifier module having an enclosure includes an input window, a mirror optically coupled to the input window and disposed in a first plane, and a first amplifier head disposed along an optical amplification path adjacent a first end of the enclosure. The laser amplifier module also includes a second amplifier head disposed along the optical amplification path adjacent a second end of the enclosure and a cavity mirror disposed along the optical amplification path.

Optical-fiber-connected 300-GHz FM-CW radar system

NASA Astrophysics Data System (ADS)

Kanno, Atsushi; Sekine, Norihiko; Kasamatsu, Akifumi; Yamamoto, Naokatsu; Kawanishi, Tetsuya

2017-05-01

300-GHz frequency-modulated continuous-wave (FM-CW) radar system operated by radio over fiber technologies is configured and demonstrated. Centralized signal generator, which is based on an optical frequency comb generation, provides high-precise FM-CW radar signal. The optical signal is easy to be transported to radar heads through an optical fiber network. Optical-modulator-based optical frequency comb generator is utilized as an optical frequency multiplier from a microwave signal to a 300-GHz terahertz signal by an optical modulation technique. In the study, we discuss the configuration of the network, signal generator and remote radar head for terahertz-wave multi-static radar system.

Development of a Meso-Scale Fiberoptic Rotation Sensor for a Torsion Actuator.

PubMed

Sheng, Jun; Desai, Jaydev P

2018-01-01

This paper presents the development of a meso-scale fiberoptic rotation sensor for a shape memory alloy (SMA) torsion actuator for neurosurgical applications. Within the sensor, a rotary head with a reflecting surface is capable of modulating the light intensity collected by optical fibers when the rotary head is coupled to the torsion actuator. The mechanism of light intensity modulation is modeled, followed by experimental model verification. Meanwhile, working performances for different rotary head designs, optical fibers, and fabrication materials are compared. After the calibration of the fiberoptic rotation sensor, the sensor is capable of precisely measuring rotary motion and controlling the SMA torsion actuator with feedback control.

Juvenile hormone mediates developmental integration between exaggerated traits and supportive traits in the horned flour beetle Gnatocerus cornutus.

PubMed

Okada, Yasukazu; Gotoh, Hiroki; Miura, Toru; Miyatake, Takahisa; Okada, Kensuke

2012-07-01

Sexually selected exaggerated traits are often coupled with modifications in other nontarget traits. In insects with weapons, enlargements of nontarget characters that functionally support the weapon often occur (i.e. supportive traits). The support of sexual traits requires developmental coordination among functionally related multiple traits-an explicit example of morphological integration. The genetic theory predicts that developmental integration among different body modules, for which development is regulated via different sets of genes, is likely to be coordinated by pleiotropic factors. However, the developmental backgrounds of morphological integrations are largely unknown. We tested the hypothesis that the juvenile hormone (JH), as a pleiotropic factor, mediates the integration between exaggerated and supportive traits in an armed beetle Gnatocerus cornutus. During combat, males of this beetle use exaggerated mandibles to lift up their opponents with the supportive traits, that is, the head and prothoracic body parts. Application of methoprene, a JH analog (JHA), during the larval to prepupal period, induced the formation of large mandibles relative to the body sizes in males. Morphometric examination of nontarget traits elucidated an increase in the relative sizes of supportive traits, including the head and prothoracic body parts. In addition, reductions in the hind wing area and elytra length, which correspond to flight and reproductive abilities, were detected. Our findings are consistent with the genetic theory and support the idea that JH is a key pleiotropic factor that coordinates the developmental integration of exaggerated traits and supportive characters, as well as resource allocation trade-offs. © 2012 Wiley Periodicals, Inc.

Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of the Med3 coactivator.

PubMed

Gonzalez, Deyarina; Hamidi, Nurul; Del Sol, Ricardo; Benschop, Joris J; Nancy, Thomas; Li, Chao; Francis, Lewis; Tzouros, Manuel; Krijgsveld, Jeroen; Holstege, Frank C P; Conlan, R Steven

2014-02-18

Mediator, an evolutionary conserved large multisubunit protein complex with a central role in regulating RNA polymerase II-transcribed genes, serves as a molecular switchboard at the interface between DNA binding transcription factors and the general transcription machinery. Mediator subunits include the Cdk8 module, which has both positive and negative effects on activator-dependent transcription through the activity of the cyclin-dependent kinase Cdk8, and the tail module, which is required for positive and negative regulation of transcription, correct preinitiation complex formation in basal and activated transcription, and Mediator recruitment. Currently, the molecular mechanisms governing Mediator function remain largely undefined. Here we demonstrate an autoregulatory mechanism used by Mediator to repress transcription through the activity of distinct components of different modules. We show that the function of the tail module component Med3, which is required for transcription activation, is suppressed by the kinase activity of the Cdk8 module. Med3 interacts with, and is phosphorylated by, Cdk8; site-specific phosphorylation triggers interaction with and degradation by the Grr1 ubiquitin ligase, thereby preventing transcription activation. This active repression mechanism involving Grr1-dependent ubiquitination of Med3 offers a rationale for the substoichiometric levels of the tail module that are found in purified Mediator and the corresponding increase in tail components seen in cdk8 mutants.

Promoting Mental Health. Training Guides for the Head Start Learning Community.

ERIC Educational Resources Information Center

Bowman (James) Associates, San Francisco, CA.

This training guide is intended to help Head Start staff promote mental health for all members of the Head Start Community, by means of activities that build skills in creating responsive, respectful relationships with co-workers, parents, and children. The guide has five working sections, the first three of which are training modules. Each of the…

The role of the proline-rich domain of Ssdp1 in the modular architecture of the vertebrate head organizer

PubMed Central

Enkhmandakh, Badam; Makeyev, Alexandr V.; Bayarsaihan, Dashzeveg

2006-01-01

Lim1, Ssdp1, and Ldb1 proteins are components of the Ldb1-associated transcriptional complex, which is important in the head-organizing activity during early mouse development. Depletion of each individual protein alone causes a headless phenotype. To explore in more detail the modular architecture of the complex, we have generated two different gene-trapped mouse lines that express truncated forms of Ssdp1. Embryos derived from the gene-trapped line that encodes a truncated Ssdp1 lacking the proline-rich sequence exhibit a lethal abnormal head-development phenotype, resembling mouse embryos deficient for Lim1, Ssdp1, or Otx2 genes. Embryos derived from the second gene-trapped line, in which most of the proline-rich domain of Ssdp1 is retained, did not show abnormalities in head development. Our data demonstrate that components of the Ldb1-dependent module can be subdivided further into discrete functional domains and that the proline-rich stretch of Ssdp1 is critical for embryonic head development. Furthermore, phylogenetic comparisons revealed that in Caenorhabditis elegans, a similar proline-rich sequence is absent in Ssdp but present in Ldb1. We conclude that although the overall architecture of the Ldb1-dependent module has been preserved, the genetic specification of its individual components has diversified during evolution, without compromising the function of the module. PMID:16864769

The role of the proline-rich domain of Ssdp1 in the modular architecture of the vertebrate head organizer.

PubMed

Enkhmandakh, Badam; Makeyev, Alexandr V; Bayarsaihan, Dashzeveg

2006-08-01

Lim1, Ssdp1, and Ldb1 proteins are components of the Ldb1-associated transcriptional complex, which is important in the head-organizing activity during early mouse development. Depletion of each individual protein alone causes a headless phenotype. To explore in more detail the modular architecture of the complex, we have generated two different gene-trapped mouse lines that express truncated forms of Ssdp1. Embryos derived from the gene-trapped line that encodes a truncated Ssdp1 lacking the proline-rich sequence exhibit a lethal abnormal head-development phenotype, resembling mouse embryos deficient for Lim1, Ssdp1, or Otx2 genes. Embryos derived from the second gene-trapped line, in which most of the proline-rich domain of Ssdp1 is retained, did not show abnormalities in head development. Our data demonstrate that components of the Ldb1-dependent module can be subdivided further into discrete functional domains and that the proline-rich stretch of Ssdp1 is critical for embryonic head development. Furthermore, phylogenetic comparisons revealed that in Caenorhabditis elegans, a similar proline-rich sequence is absent in Ssdp but present in Ldb1. We conclude that although the overall architecture of the Ldb1-dependent module has been preserved, the genetic specification of its individual components has diversified during evolution, without compromising the function of the module.

Malleable machines in transcription regulation: the mediator complex.

PubMed

Tóth-Petróczy, Agnes; Oldfield, Christopher J; Simon, István; Takagi, Yuichiro; Dunker, A Keith; Uversky, Vladimir N; Fuxreiter, Monika

2008-12-01

The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs) to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs) distinguished by a high protein-protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the arrangements of the disordered regions and their embedded interaction sites are quite similar in the two organisms. All of these data suggest an integral role for intrinsic disorder in Mediator's function.

Introduction to Industry Services. Self-Paced Instructional Module. Module Number I-A.

ERIC Educational Resources Information Center

Brooks, Kent

One of 33 self-paced instructional modules categorized under 13 major headings, which have been prepared for training industry services leaders to provide guidance in the performance of industry service tasks, this module is an introduction for those who need basic information about the concepts and activities of industry services programs.…

Modulation of head movement control in humans during treadmill walking

NASA Technical Reports Server (NTRS)

Mulavara, Ajitkumar P.; Verstraete, Mary C.; Bloomberg, Jacob J.

2002-01-01

The purpose of this study was to investigate the coordination of the head relative to the trunk within a gait cycle during gaze fixation. Nine normal subjects walked on a motorized treadmill driven at 1.79 m/s (20 s trials) while fixing their gaze on a centrally located earth-fixed target positioned at a distance of 2 m from their eyes. The net and relative angular motions of the head about the three axes of rotations, as well as the corresponding values for the moments acting on it relative to the trunk during the gait cycle were quantified and used as measures of coordination. The average net moment, as well as the average moments about the different axes were significantly different (P<0.01) between the high impact and low/no impact phases of the gait cycle. However, the average net angular displacement as well as the average angular displacement about the axial rotation axis of the head relative to the trunk was maintained uniform (P>0.01) throughout the gait cycle. The average angular displacement about the lateral bending axis was significantly increased (P<0.01) during the high impact phase while that about the flexion-extension axis was significantly decreased (P<0.01) throughout the gait cycle. Thus, the coordination of the motion of the head relative to the trunk during walking is dynamically modulated depending on the behavioral events occurring in the gait cycle. This modulation may serve to aid stabilization of the head by counteracting the force variations acting on the upper body that may aid in the visual fixation of targets during walking.

Mediator Undergoes a Compositional Change during Transcriptional Activation.

PubMed

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2016-11-03

Mediator is a transcriptional co-activator recruited to enhancers by DNA-binding activators, and it also interacts with RNA polymerase (Pol) II as part of the preinitiation complex (PIC). We demonstrate that a single Mediator complex associates with the enhancer and core promoter in vivo, indicating that it can physically bridge these transcriptional elements. However, the Mediator kinase module associates strongly with the enhancer, but not with the core promoter, and it dissociates from the enhancer upon depletion of the TFIIH kinase. Severing the kinase module from Mediator by removing the connecting subunit Med13 does not affect Mediator association at the core promoter but increases occupancy at enhancers. Thus, Mediator undergoes a compositional change in which the kinase module, recruited via Mediator to the enhancer, dissociates from Mediator to permit association with Pol II and the PIC. As such, Mediator acts as a dynamic bridge between the enhancer and core promoter. Copyright © 2016 Elsevier Inc. All rights reserved.

Electro-optic voltage sensor head

DOEpatents

Crawford, T.M.; Davidson, J.R.; Woods, G.K.

1999-08-17

The invention is an electro-optic voltage sensor head designed for integration with existing types of high voltage transmission and distribution apparatus. The sensor head contains a transducer, which comprises a transducing material in which the Pockels electro-optic effect is observed. In the practice of the invention at least one beam of electromagnetic radiation is routed into the transducing material of the transducer in the sensor head. The beam undergoes an electro-optic effect in the sensor head when the transducing material is subjected to an E-field. The electro-optic effect is observed as a differential phase a shift, also called differential phase modulation, of the beam components in orthogonal planes of the electromagnetic radiation. In the preferred embodiment the beam is routed through the transducer along an initial axis and then reflected by a retro-reflector back substantially parallel to the initial axis, making a double pass through the transducer for increased measurement sensitivity. The preferred embodiment of the sensor head also includes a polarization state rotator and at least one beam splitter for orienting the beam along major and minor axes and for splitting the beam components into two signals which are independent converse amplitude-modulated signals carrying E-field magnitude and hence voltage information from the sensor head by way of optic fibers. 6 figs.

Electro-optic voltage sensor head

DOEpatents

Crawford, Thomas M.; Davidson, James R.; Woods, Gregory K.

1999-01-01

The invention is an electro-optic voltage sensor head designed for integration with existing types of high voltage transmission and distribution apparatus. The sensor head contains a transducer, which comprises a transducing material in which the Pockels electro-optic effect is observed. In the practice of the invention at least one beam of electromagnetic radiation is routed into the transducing material of the transducer in the sensor head. The beam undergoes an electro-optic effect in the sensor head when the transducing material is subjected to an E-field. The electro-optic effect is observed as a differential phase a shift, also called differential phase modulation, of the beam components in orthogonal planes of the electromagnetic radiation. In the preferred embodiment the beam is routed through the transducer along an initial axis and then reflected by a retro-reflector back substantially parallel to the initial axis, making a double pass through the transducer for increased measurement sensitivity. The preferred embodiment of the sensor head also includes a polarization state rotator and at least one beam splitter for orienting the beam along major and minor axes and for splitting the beam components into two signals which are independent converse amplitude-modulated signals carrying E-field magnitude and hence voltage information from the sensor head by way of optic fibers.

Research studies on advanced optical module/head designs for optical devices

NASA Technical Reports Server (NTRS)

Burke, James J.

1991-01-01

A summary is presented of research in optical data storage materials and of research at the center. The first section contains summary reports under the general headings of: (1) Magnetooptic media: modeling, design, fabrication, characterization, and testing; (2) Optical heads: holographic optical elements; and (3) Optical heads: integrated optics. The second section consist of a proposal entitled, Signal Processing Techniques for Optical Data Storage. And section three presents various publications prepared by the center.

Research Studies on Advanced Optical Module/Head Designs for Optical Disk Recording Devices

NASA Technical Reports Server (NTRS)

Burke, James J.; Seery, Bernard D.

1993-01-01

The Annual Report of the Optical Data Storage Center of the University of Arizona is presented. Summary reports on continuing projects are presented. Research areas include: magneto-optic media, optical heads, and signal processing.

V-Assembly Dual-Head Efficient Resonator (VADER) for Remote Sensing Applications

NASA Technical Reports Server (NTRS)

Coyle, D. Barry; Kay, Richard B.; Stysley, Paul R.; Clark, Greg; Poulios, Demetrios; Frederickson, Robert; Blalock, Gordon; Arnold, Ed; Cory, Ken

2011-01-01

The V-Assembly Dual-head Efficient Resonator (VADER) is a diode pumped, Nd:YAG, Q-switched, positive branch unstable resonator that employs a split laser gain module designed for optimal efficiency and thermal lensing compensation.

Soft-information flipping approach in multi-head multi-track BPMR systems

NASA Astrophysics Data System (ADS)

Warisarn, C.; Busyatras, W.; Myint, L. M. M.

2018-05-01

Inter-track interference is one of the most severe impairments in bit-patterned media recording system. This impairment can be effectively handled by a modulation code and a multi-head array jointly processing multiple tracks; however, such a modulation constraint has never been utilized to improve the soft-information. Therefore, this paper proposes the utilization of modulation codes with an encoded constraint defined by the criteria for soft-information flipping during a three-track data detection process. Moreover, we also investigate the optimal offset position of readheads to provide the most improvement in system performance. The simulation results indicate that the proposed systems with and without position jitter are significantly superior to uncoded systems.

Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.

PubMed

Romano, Anthony G; Quinn, Jennifer L; Li, Luchuan; Dave, Kuldip D; Schindler, Emmanuelle A; Aloyo, Vincent J; Harvey, John A

2010-10-01

Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

Bisphosphonate-modified gold nanoparticles: a useful vehicle to study the treatment of osteonecrosis of the femoral head

NASA Astrophysics Data System (ADS)

Fanord, Fedena; Fairbairn, Korie; Kim, Harry; Garces, Amanda; Bhethanabotla, Venkat; Gupta, Vinay K.

2011-01-01

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that presents in children aged 2-14 years. To date, there is no effective medical therapy for treating LCPD largely due to an inability to modulate the repair process, including the predominance of bone resorption. This investigation aims to evaluate the feasibility of using gold nanoparticles (GNPs) that are surface modified with a bisphosphonate compound for the treatment of osteonecrosis at the cellular level. Studies have found osteoclast-mediated resorption to be a process that contributes significantly to the pathogenesis of femoral head deformities arising from Perthes disease. Our in vitro model was designed to elucidate the effect of alendronate-(a bisphosphonate) modified GNPs, on osteoclastogenesis and osteoclast function. RAW 264.7 macrophage cells were cultured with recombinant mouse receptor activator of NF-κB ligand (RANKL), which stimulates osteoclastogenesis, and were then treated with alendronate-modified GNPs for 24, 48, and 72 h. Cell proliferation, osteoclast function, and osteoclast morphology were evaluated by trypan blue dye exclusion assay, tartrate-resistant acid phosphatase (TRAP) staining, and transmission electron microscopy (TEM) imaging. Comparative studies were performed with GNPs that were only stabilized with citrate ions and with alendronate alone. Neither osteoclastogenesis nor osteoclast function were adversely affected by the presence of the citrate-GNP. Alendronate-modified GNPs had an enhanced effect on inducing osteoclast apoptosis and impairing osteoclast function when compared to unbound alendronate populations.

Kinematic principles of primate rotational vestibulo-ocular reflex. I. Spatial organization of fast phase velocity axes

NASA Technical Reports Server (NTRS)

Hess, B. J.; Angelaki, D. E.

1997-01-01

The spatial organization of fast phase velocity vectors of the vestibulo-ocular reflex (VOR) was studied in rhesus monkeys during yaw rotations about an earth-horizontal axis that changed continuously the orientation of the head relative to gravity ("barbecue spit" rotation). In addition to a velocity component parallel to the rotation axis, fast phases also exhibited a velocity component that invariably was oriented along the momentary direction of gravity. As the head rotated through supine and prone positions, torsional components of fast phase velocity axes became prominent. Similarly, as the head rotated through left and right ear-down positions, fast phase velocity axes exhibited prominent vertical components. The larger the speed of head rotation the greater the magnitude of this fast phase component, which was collinear with gravity. The main sequence properties of VOR fast phases were independent of head position. However, peak amplitude as well as peak velocity of fast phases were both modulated as a function of head orientation, exhibiting a minimum in prone position. The results suggest that the fast phases of vestibulo-ocular reflexes not only redirect gaze and reposition the eye in the direction of head motion but also reorient the eye with respect to earth-vertical when the head moves relative to gravity. As further elaborated in the companion paper, the underlying mechanism could be described as a dynamic, gravity-dependent modulation of the coordinates of ocular rotations relative to the head.

Responses to vertical vestibular stimulation of neurons in the nucleus reticularis gigantocellularis in rabbits.

PubMed

Fagerson, M H; Barmack, N H

1995-06-01

1. Because the nucleus reticularis gigantocellularis (NRGc) receives a substantial descending projection from the caudal vestibular nuclei, we used extracellular single-unit recording combined with natural vestibular stimulation to examine the possible peripheral origins of the vestibularly modulated activity of caudal NRGc neurons located within 500 microns of the midline. Chloralose-urethan anesthetized rabbits were stimulated with an exponential "step" and/or static head-tilt stimulus, as well as sinusoidal rotation about the longitudinal or interaural axes providing various combinations of roll or pitch, respectively. Recording sites were reconstructed from electrolytic lesions confirmed histologically. 2. More than 85% of the 151 neurons, in the medial aspect of the caudal NRGc, responded to vertical vestibular stimulation. Ninety-six percent of these responded to rotation onto the contralateral side (beta responses). Only a few also responded to horizontal stimulation. Seventy-eight percent of the neurons that responded to vestibular stimulation responded during static roll-tilt. One-half of these neurons also responded transiently to the change in head position during exponential "step" stimulation, suggesting input mediated by otolith and semicircular canal receptors or tonic-phasic otolith neurons. 3. Seventy-five percent of the responsive neurons had a "null plane." The planes of stimulation resulting in maximal responses, for cells that responded to static stimulation, were distributed throughout 150 degrees in both roll and pitch quadrants. Five of these cells responded only transiently during exponential "step" stimulation and responded maximally when stimulated in the plane of one of the vertical semicircular canals. 4. The phase of the response of the 25% of medial NRGc neurons that lacked "null planes" gradually shifted approximately 180 degrees during sinusoidal vestibular stimulation as the plane of stimulation was shifted about the vertical axis. These neurons likely received convergent input with differing spatial and temporal properties. 5. The activity of neurons in the medial aspect of the caudal NRGc of rabbits was modulated by both otolithic macular and vertical semicircular canal receptor stimulation. This vestibular information may be important for controlling the intensity of the muscle activity in muscles such as neck muscles where the load on the muscle is affected by the position of the head with respect to gravity. Some of these neurons may also shift muscle function from an agonist to an antagonist as the direction of head tilt changes.

HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

PubMed

Cox, Freek; Kwaks, Ted; Brandenburg, Boerries; Koldijk, Martin H; Klaren, Vincent; Smal, Bastiaan; Korse, Hans J W M; Geelen, Eric; Tettero, Lisanne; Zuijdgeest, David; Stoop, Esther J M; Saeland, Eirikur; Vogels, Ronald; Friesen, Robert H E; Koudstaal, Wouter; Goudsmit, Jaap

2016-01-01

Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the in vivo protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies. We used a panel of anti-stem and anti-head influenza A and B monoclonal antibodies with identical human IgG1 Fc domains and investigated their ability to mediate ADCC-associated FcγRIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate FcγRIIIa activation. However, the FcγRIIIa activation was inhibited when a mutant HA, unable to bind sialic acids, was used. Antibodies which block sialic acid receptor interactions of HA interfered with FcγRIIIa activation. The inhibition of FcγRIIIa activation by HA head-binding and sialic acid receptor-blocking antibodies was confirmed in plasma samples of H5N1 vaccinated human subjects. Together, these results suggest that in addition to Fc-FcγR binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. I. Linear acceleration responses during off-vertical axis rotation

NASA Technical Reports Server (NTRS)

Angelaki, D. E.; Hess, B. J.

1996-01-01

1. The dynamic properties of otolith-ocular reflexes elicited by sinusoidal linear acceleration along the three cardinal head axes were studied during off-vertical axis rotations in rhesus monkeys. As the head rotates in space at constant velocity about an off-vertical axis, otolith-ocular reflexes are elicited in response to the sinusoidally varying linear acceleration (gravity) components along the interaural, nasooccipital, or vertical head axis. Because the frequency of these sinusoidal stimuli is proportional to the velocity of rotation, rotation at low and moderately fast speeds allows the study of the mid-and low-frequency dynamics of these otolith-ocular reflexes. 2. Animals were rotated in complete darkness in the yaw, pitch, and roll planes at velocities ranging between 7.4 and 184 degrees/s. Accordingly, otolith-ocular reflexes (manifested as sinusoidal modulations in eye position and/or slow-phase eye velocity) were quantitatively studied for stimulus frequencies ranging between 0.02 and 0.51 Hz. During yaw and roll rotation, torsional, vertical, and horizontal slow-phase eye velocity was sinusoidally modulated as a function of head position. The amplitudes of these responses were symmetric for rotations in opposite directions. In contrast, mainly vertical slow-phase eye velocity was modulated during pitch rotation. This modulation was asymmetric for rotations in opposite direction. 3. Each of these response components in a given rotation plane could be associated with an otolith-ocular response vector whose sensitivity, temporal phase, and spatial orientation were estimated on the basis of the amplitude and phase of sinusoidal modulations during both directions of rotation. Based on this analysis, which was performed either for slow-phase eye velocity alone or for total eye excursion (including both slow and fast eye movements), two distinct response patterns were observed: 1) response vectors with pronounced dynamics and spatial/temporal properties that could be characterized as the low-frequency range of "translational" otolith-ocular reflexes; and 2) response vectors associated with an eye position modulation in phase with head position ("tilt" otolith-ocular reflexes). 4. The responses associated with two otolith-ocular vectors with pronounced dynamics consisted of horizontal eye movements evoked as a function of gravity along the interaural axis and vertical eye movements elicited as a function of gravity along the vertical head axis. Both responses were characterized by a slow-phase eye velocity sensitivity that increased three- to five-fold and large phase changes of approximately 100-180 degrees between 0.02 and 0.51 Hz. These dynamic properties could suggest nontraditional temporal processing in utriculoocular and sacculoocular pathways, possibly involving spatiotemporal otolith-ocular interactions. 5. The two otolith-ocular vectors associated with eye position responses in phase with head position (tilt otolith-ocular reflexes) consisted of torsional eye movements in response to gravity along the interaural axis, and vertical eye movements in response to gravity along the nasooccipital head axis. These otolith-ocular responses did not result from an otolithic effect on slow eye movements alone. Particularly at high frequencies (i.e., high speed rotations), saccades were responsible for most of the modulation of torsional and vertical eye position, which was relatively large (on average +/- 8-10 degrees/g) and remained independent of frequency. Such reflex dynamics can be simulated by a direct coupling of primary otolith afferent inputs to the oculomotor plant. (ABSTRACT TRUNCATED).

Genome-wide association of mediator and RNA polymerase II in wild-type and mediator mutant yeast.

PubMed

Paul, Emily; Zhu, Z Iris; Landsman, David; Morse, Randall H

2015-01-01

Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genome-Wide Association of Mediator and RNA Polymerase II in Wild-Type and Mediator Mutant Yeast

PubMed Central

Paul, Emily; Zhu, Z. Iris

2014-01-01

Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences. PMID:25368384

Metabotropic Glutamate2 Receptors Play a Key Role in Modulating Head Twitches Induced by a Serotonergic Hallucinogen in Mice

PubMed Central

Benvenga, Mark J.; Chaney, Stephen F.; Baez, Melvyn; Britton, Thomas C.; Hornback, William J.; Monn, James A.; Marek, Gerard J.

2018-01-01

There is substantial evidence that glutamate can modulate the effects of 5-hydroxytryptamine2A (5-HT2A) receptor activation through stimulation of metabotropic glutamate2/3 (mGlu2/3) receptors in the prefrontal cortex. Here we show that constitutive deletion of the mGlu2 gene profoundly attenuates an effect of 5-HT2A receptor activation using the mouse head twitch response (HTR). MGlu2 and mGlu3 receptor knockout (KO) as well as age-matched ICR (CD-1) wild type (WT) mice were administered (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and observed for head twitch activity. DOI failed to produce significant head twitches in mGlu2 receptor KO mice at a dose 10-fold higher than the peak effective dose in WT or mGlu3 receptor KO mice. In addition, the mGlu2/3 receptor agonist LY379268, and the mGlu2 receptor positive allosteric modulator (PAM) CBiPES, potently blocked the HTR to DOI in WT and mGlu3 receptor KO mice. Conversely, the mGlu2/3 receptor antagonist LY341495 (10 mg/kg) increased the HTR produced by DOI (3 mg/kg) in mGlu3 receptor KO mice. Finally, the mGlu2 receptor potentiator CBiPES was able to attenuate the increase in the HTR produced by LY341495 in mGlu3 receptor KO mice. Taken together, all of these results are consistent with the hypothesis that that DOI-induced head twitches are modulated by mGlu2 receptor activation. These results also are in keeping with a critical autoreceptor function for mGlu2 receptors in the prefrontal cortex with differential effects of acute vs. chronic perturbation (e.g., constitutive mGlu2 receptor KO mice). The robust attenuation of DOI-induced head twitches in the mGlu2 receptor KO mice appears to reflect the critical role of glutamate in ongoing regulation of 5-HT2A receptors in the prefrontal cortex. Future experiments with inducible knockouts for the mGlu2 receptor and/or selective mGlu3 receptor agonists/PAMs/antagonists could provide an important tools in understanding glutamatergic modulation of prefrontal cortical 5-HT2A receptor function. PMID:29599719

Head temperature modulates thermal behavior in the cold in humans

PubMed Central

Mündel, Toby; Raman, Aaron; Schlader, Zachary J.

2016-01-01

ABSTRACT We tested the hypothesis that skin temperature, specifically of the head, is capable of modulating thermal behavior during exercise in the cold. Following familiarization 8 young, healthy, recreationally active males completed 3 trials, each consisting of 30 minutes of self-paced cycle ergometry in 6°C. Participants were instructed to control their exercise work rate to achieve and maintain thermal comfort. On one occasion participants wore only shorts and shoes (Control) and on the 2 other occasions their head was either warmed (Warming) or cooled (Cooling). Work rate, rate of metabolic heat production, thermal perceptions, rectal, mean weighted skin and head temperatures were measured. Exercise work rate was reduced during Warming and augmented during Cooling after the first and second minutes of exercise, respectively (P ≤ 0.04), with the rate of metabolic heat production mirroring work rate. At this early stage of exercise (≤5 min) the changes over time for rectal temperature were negligible and similar (0.1 ± 0.1°C, P = 0.51), while the decrease in mean skin temperature was not different between all trials (1.7 ± 0.6°C, P = 0.13). Mean head temperature was either decreased (Control: 1.5 ± 1.1°C, Cooling: 2.9 ± 0.8°C, both P < 0.01) or increased (Warming: 1.7 ± 0.9°C, P < 0.01). Head thermal perception was warmer and more comfortable in Warming and cooler and less comfortable in Cooling (P < 0.01). Participants achieved thermal comfort similarly in all trials (P > 0.09) after 10 ± 7 min and this was maintained until the end of exercise. These results indicate that peripheral temperatures modulate thermal behavior in the cold. PMID:27857959

Eye position modulates the electromyographic responses of neck muscles to electrical stimulation of the superior colliculus in the alert cat.

PubMed

Hadjidimitrakis, K; Moschovakis, A K; Dalezios, Y; Grantyn, A

2007-05-01

Rapid gaze shifts are often accomplished with coordinated movements of the eyes and head, the relative amplitude of which depends on the starting position of the eyes. The size of gaze shifts is determined by the superior colliculus (SC) but additional processing in the lower brain stem is needed to determine the relative contributions of eye and head components. Models of eye-head coordination often assume that the strength of the command sent to the head controllers is modified by a signal indicative of the eye position. Evidence in favor of this hypothesis has been recently obtained in a study of phasic electromyographic (EMG) responses to stimulation of the SC in head-restrained monkeys (Corneil et al. in J Neurophysiol 88:2000-2018, 2002b). Bearing in mind that the patterns of eye-head coordination are not the same in all species and because the eye position sensitivity of phasic EMG responses has not been systematically investigated in cats, in the present study we used cats to address this issue. We stimulated electrically the intermediate and deep layers of the caudal SC in alert cats and recorded the EMG responses of neck muscles with horizontal and vertical pulling directions. Our data demonstrate that phasic, short latency EMG responses can be modulated by the eye position such that they increase as the eye occupies more and more eccentric positions in the pulling direction of the muscle tested. However, the influence of the eye position is rather modest, typically accounting for only 10-50% of the variance of EMG response amplitude. Responses evoked from several SC sites were not modulated by the eye position.

Advanced Mathematics. Training Module 1.303.3.77.

ERIC Educational Resources Information Center

Kirkwood Community Coll., Cedar Rapids, IA.

This document is an instructional module prepared in objective form for use by an instructor familiar with mathematics as applied to water and wastewater treatment plant operation. Included are objectives, instructor guides and student handouts. This is the third level of a three module series and is concerned with statistics, total head, steady…

Catalytic metathesis of carbon dioxide with heterocumulenes mediated by titanium isopropoxide.

PubMed

Ghosh, Rajshekhar; Samuelson, Ashoka G

2005-04-21

The insertion of an isopropoxide ligand of titanium isopropoxide into heterocumulenes gives a product that carries out metathesis at elevated temperatures by undergoing insertion of a second heterocumulene in a head to head fashion, followed by an extrusion reaction.

Defensive peripersonal space: the blink reflex evoked by hand stimulation is increased when the hand is near the face.

PubMed

Sambo, C F; Liang, M; Cruccu, G; Iannetti, G D

2012-02-01

Electrical stimulation of the median nerve at the wrist may elicit a blink reflex [hand blink reflex (HBR)] mediated by a neural circuit at brain stem level. As, in a Sherringtonian sense, the blink reflex is a defensive response, in a series of experiments we tested, in healthy volunteers, whether and how the HBR is modulated by the proximity of the stimulated hand to the face. Electromyographic activity was recorded from the orbicularis oculi, bilaterally. We observed that the HBR is enhanced when the stimulated hand is inside the peripersonal space of the face, compared with when it is outside, irrespective of whether the proximity of the hand to the face is manipulated by changing the position of the arm (experiment 1) or by rotating the head while keeping the arm position constant (experiment 3). Experiment 2 showed that such HBR enhancement has similar magnitude when the participants have their eyes closed. Experiments 4 and 5 showed, respectively, that the blink reflex elicited by the electrical stimulation of the supraorbital nerve, as well as the N20 wave of the somatosensory evoked potentials elicited by the median nerve stimulation, are entirely unaffected by hand position. Taken together, our results provide compelling evidence that the brain stem circuits mediating the HBR in humans undergo tonic and selective top-down modulation from higher order cortical areas responsible for encoding the location of somatosensory stimuli in external space coordinates. These findings support the existence of a "defensive" peripersonal space, representing a safety margin advantageous for survival.

Attention to affective pictures in closed head injury: event-related brain potentials and cardiac responses.

PubMed

Solbakk, Anne-Kristin; Reinvang, Ivar; Svebak, Sven; Nielsen, Christopher S; Sundet, Kjetil

2005-02-01

We examined whether closed head injury patients show altered patterns of selective attention to stimulus categories that naturally evoke differential responses in healthy people. Self-reported rating and electrophysiological (event-related potentials [ERPs], heart rate [HR]) responses to affective pictures were studied in patients with mild head injury (n = 20; CT/MRI negative), in patients with predominantly frontal brain lesions (n = 12; CT/MRI confirmed), and in healthy controls (n = 20). Affective valence similarly modulated HR and ERP responses in all groups, but group differences occurred that were independent of picture valence. The attenuation of P3-slow wave amplitudes in the mild head injury group indicates a reduction in the engagement of attentional resources to the task. In contrast, the general enhancement of ERP amplitudes at occipital sites in the group with primarily frontal brain injury may reflect disinhibition of input at sensory receptive areas, possibly due to a deficit in top-down modulation performed by anterior control systems.

Curcumin Induces Apoptosis of Upper Aerodigestive Tract Cancer Cells by Targeting Multiple Pathways

PubMed Central

Amin, A. R. M. Ruhul; Haque, Abedul; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Khuri, Fadlo Raja; Shin, Dong Moon

2015-01-01

Curcumin, a natural compound isolated from the Indian spice "Haldi" or "curry powder", has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the related protein p73 in head and neck and lung cancer cell lines. Inactivation of p73 by dominant negative p73 significantly protected cells from curcumin-induced apoptosis, whereas ablation of p53 by shRNA had no effect. Curcumin treatment also strongly inhibited p-AKT and Bcl-2 and overexpression of constitutively active AKT or Bcl-2 significantly inhibited curcumin-induced apoptosis. Taken together, our findings suggest that curcumin-induced apoptosis is mediated via activating tumor suppressor p73 and inhibiting p-AKT and Bcl-2. PMID:25910231

Head position modulates optokinetic nystagmus

PubMed Central

Ferraresi, A.; Botti, F. M.; Panichi, R.; Barmack, N. H.

2011-01-01

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior → anterior (P → A) direction, slow phase eye velocity (SPEV) increased by 3.5–5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A → P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, “open loop.” Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during “closed loop” HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement. PMID:21735244

Head position modulates optokinetic nystagmus.

PubMed

Pettorossi, V E; Ferraresi, A; Botti, F M; Panichi, R; Barmack, N H

2011-08-01

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior → anterior (P → A) direction, slow phase eye velocity (SPEV) increased by 3.5-5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A → P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during "closed loop" HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement.

Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering General Rules for Motor Activity.

PubMed

Jana, Biman; Onuchic, José N

2016-08-01

A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities.

Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering General Rules for Motor Activity

PubMed Central

Jana, Biman; Onuchic, José N.

2016-01-01

A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities. PMID:27494025

Executive functions and school readiness intervention: Impact, moderation, and mediation in the Head Start REDI program

PubMed Central

BIERMAN, KAREN L.; NIX, ROBERT L.; GREENBERG, MARK T.; BLAIR, CLANCY; DOMITROVICH, CELENE E.

2011-01-01

Despite their potentially central role in fostering school readiness, executive function (EF) skills have received little explicit attention in the design and evaluation of school readiness interventions for socioeconomically disadvantaged children. The present study examined a set of five EF measures in the context of a randomized-controlled trial of a research-based intervention integrated into Head Start programs (Head Start REDI). Three hundred fifty-six 4-year-old children (17% Hispanic, 25% African American; 54% girls) were followed over the course of the prekindergarten year. Initial EF predicted gains in cognitive and social–emotional skills and moderated the impact of the Head Start REDI intervention on some outcomes. The REDI intervention promoted gains on two EF measures, which partially mediated intervention effects on school readiness. We discuss the importance of further study of the neurobiological bases of school readiness, the implications for intervention design, and the value of incorporating markers of neurobiological processes into school readiness interventions. PMID:18606033

Artist's concept of Apollo 14 Command/Service Modules circling Moon

NASA Image and Video Library

1971-01-11

S71-16574 (11 Jan. 1971) --- An artist's concept depicting the Apollo 14 Command and Service Modules (CSM) circling the moon as the Lunar Module (LM) heads toward a lunar landing. While astronaut Stuart A. Roosa, command module pilot, remains with the CSM in lunar orbit, astronauts Alan B. Shepard Jr., commander; and Edgar D. Mitchell, lunar module pilot, will descend in the LM to explore an area in the rugged Fra Mauro highlands.

Effect of Helmet Pads on the Load Transfer to Head under Blast Loadings

DTIC Science & Technology

2015-06-01

0.15 0.2 X  St re ss  (K Pa ) Time (ms) Foam  L Foam  M Foam  R 6 its much smaller acoustic impedance. The stress amplitude increases as it reflects...understood for the helmet/ foam pads. The pads between the helmet and head can not only absorb energy, but also produce more comfort to the head. The gap...to investigate the effects of foam pads on the load transmitted to the head under blast loading. The ALE module in the commercial code, LSDYNA was

Drosophila nemo is an essential gene involved in the regulation of programmed cell death.

PubMed

Mirkovic, Ivana; Charish, Kristi; Gorski, Sharon M; McKnight, Kristen; Verheyen, Esther M

2002-11-01

Nemo-like kinases define a novel family of serine/threonine kinases that are involved in integrating multiple signaling pathways. They are conserved regulators of Wnt/Wingless pathways, which may coordinate Wnt with TGFbeta-mediated signaling. Drosophila nemo was identified through its involvement in epithelial planar polarity, a process regulated by a non-canonical Wnt pathway. We have previously found that ectopic expression of Nemo using the Gal4-UAS system resulted in embryonic lethality associated with defects in patterning and head development. In this study we present our analyses of the phenotypes of germline clone-derived embryos. We observe lethality associated with head defects and reduction of programmed cell death and conclude that nmo is an essential gene. We also present data showing that nmo is involved in regulating apoptosis during eye development, based on both loss of function phenotypes and on genetic interactions with the pro-apoptotic gene reaper. Finally, we present genetic data from the adult wing that suggest the activity of ectopically expressed Nemo can be modulated by Jun N-terminal kinase (JNK) signaling. Such an observation supports the model that there is cross-talk between Wnt, TGFbeta and JNK signaling at multiple stages of development. Copyright 2002 Elsevier Science Ireland Ltd.

Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

PubMed

Möbius, Patrick; Preidl, Raimund H M; Weber, Manuel; Amann, Kerstin; Neukam, Friedrich W; Wehrhan, Falk

2017-11-01

Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

Inhibition of miR-92d-3p enhances inflammation responses in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) with Streptococcus iniae infection by modulating complement C3.

PubMed

Qiang, Jun; Tao, Yi-Fan; He, Jie; Li, Hong-Xia; Xu, Pao; Bao, Jin-Wen; Sun, Yi-Lan

2017-04-01

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate target gene expression by binding to the 3'-untranslated regions (3'-UTRs) of their target mRNAs. The miR-92 family is an important miRNA family, which was discovered to be related to regulation of tumor proliferation, apoptosis, invasion, and metastasis. Inhibition of miR-92d-3p was found previously in head kidney of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to Streptococcus iniae infection. In this study, we found that miR-92d-3p regulated complement C3 mRNA levels by binding to its 3'-UTR by 3'-UTR luciferase reporter assay, and reduced miR-92d-3p expression resulted in increased C3 mRNA levels. We detected a negative relationship between the expression levels of miR-92d-3p and C3 in GIFT injected with miRNA antagomir. We performed in vivo functional analysis by miR-92d-3p silencing. Inhibition of miR-92d-3p levels in GIFT head kidney caused a significant increase in C3 expression, which consequently increased the white blood cell counts and interleukin-1β, tumor necrosis factor-α, and interferon-γ mRNA levels, all of which may help to activate the inflammatory response in GIFT post-infection with S. iniae. Our findings indicate that miR-92d-3p regulated C3 levels by binding with the C3 mRNA 3'-UTR, and this interaction affected S. iniae infection induction and the immune response in GIFT. We concluded that miR-92d-3p plays an important role in modulating the inflammatory response in GIFT head kidney. Our findings may contribute to understanding the mechanisms of miRNA-mediated gene regulation in tilapia in response to S. iniae infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psychiatric risk factor ANK3/Ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses

PubMed Central

Smith, Katharine R.; Kopeikina, Katherine J.; Fawcett-Patel, Jessica M.; Leaderbrand, Katherine; Gao, Ruoqi; Schürmann, Britta; Myczek, Kristoffer; Radulovic, Jelena; Swanson, Geoffrey T.; Penzes, Peter

2014-01-01

Summary Recent evidence implicates glutamatergic synapses as key pathogenic sites in psychiatric disorders. Common and rare variants in the ANK3 gene, encoding ankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism. Here we demonstrate that ankyrin-G is integral to AMPAR-mediated synaptic transmission and maintenance of spine morphology. Using super-resolution microscopy we find that ankyrin-G forms distinct nanodomain structures within the spine head and neck. At these sites, it modulates mushroom spine structure and function, likely as a perisynaptic scaffold and barrier within the spine neck. Neuronal activity promotes ankyrin-G accumulation in distinct spine subdomains, where it differentially regulates NMDA receptor-dependent plasticity. These data implicate subsynaptic nanodomains containing a major psychiatric risk molecule, ankyrin-G, as having location-specific functions, and opens directions for basic and translational investigation of psychiatric risk molecules. PMID:25374361

Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature

PubMed Central

Sarlos, Patricia; Kovesdi, Erzsebet; Magyari, Lili; Banfai, Zsolt; Szabo, Andras; Javorhazy, Andras; Melegh, Bela

2014-01-01

Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammation-related genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility. PMID:25133031

Vision and air flow combine to streamline flying honeybees

PubMed Central

Taylor, Gavin J.; Luu, Tien; Ball, David; Srinivasan, Mandyam V.

2013-01-01

Insects face the challenge of integrating multi-sensory information to control their flight. Here we study a ‘streamlining' response in honeybees, whereby honeybees raise their abdomen to reduce drag. We find that this response, which was recently reported to be mediated by optic flow, is also strongly modulated by the presence of air flow simulating a head wind. The Johnston's organs in the antennae were found to play a role in the measurement of the air speed that is used to control the streamlining response. The response to a combination of visual motion and wind is complex and can be explained by a model that incorporates a non-linear combination of the two stimuli. The use of visual and mechanosensory cues increases the strength of the streamlining response when the stimuli are present concurrently. We propose this multisensory integration will make the response more robust to transient disturbances in either modality. PMID:24019053

Histones: Controlling Tumor Signaling Circuitry

PubMed Central

Martins, Manoela D.; Castilho, Rogerio M.

2014-01-01

Epigenetic modifications constitute the next frontier in tumor biology research. Post-translation modification of histones dynamically influences gene expression independent of alterations to the DNA sequence. These mechanisms are often mediated by histone linkers or by proteins associated with the recruitment of DNA-binding proteins, HDAC I and II interacting proteins and transcriptional activators, coactivators or corepressors. Early evidence suggested that histones and their modifiers are involved in sophisticated processes that modulate tumor behavior and cellular phenotype. In this review, we discuss how recent discoveries about chromatin modifications, particularly histone acetylation, are shaping our knowledge of cell biology and our understanding of the molecular circuitry governing tumor progression and consider whether recent insights may extend to novel therapeutic approaches. Furthermore, we discuss the latest oncogenomic findings in Head and Neck Squamous Cell Carcinoma (HNSCC) from studies using Next Generation Sequencing (NGS) technology and highlight the impact of mutations identified in histones and their modifiers. PMID:25177526

Transition by head-on collision: mechanically mediated manoeuvres in cockroaches and small robots.

PubMed

Jayaram, Kaushik; Mongeau, Jean-Michel; Mohapatra, Anand; Birkmeyer, Paul; Fearing, Ronald S; Full, Robert J

2018-02-01

Exceptional performance is often considered to be elegant and free of 'errors' or missteps. During the most extreme escape behaviours, neural control can approach or exceed its operating limits in response time and bandwidth. Here we show that small, rapid running cockroaches with robust exoskeletons select head-on collisions with obstacles to maintain the fastest escape speeds possible to transition up a vertical wall. Instead of avoidance, animals use their passive body shape and compliance to negotiate challenging environments. Cockroaches running at over 1 m or 50 body lengths per second transition from the floor to a vertical wall within 75 ms by using their head like an automobile bumper, mechanically mediating the manoeuvre. Inspired by the animal's behaviour, we demonstrate a passive, high-speed, mechanically mediated vertical transitions with a small, palm-sized legged robot. By creating a collision model for animal and human materials, we suggest a size dependence favouring mechanical mediation below 1 kg that we term the 'Haldane limit'. Relying on the mechanical control offered by soft exoskeletons represents a paradigm shift for understanding the control of small animals and the next generation of running, climbing and flying robots where the use of the body can off-load the demand for rapid sensing and actuation. © 2018 The Authors.

Transition by head-on collision: mechanically mediated manoeuvres in cockroaches and small robots

PubMed Central

Mongeau, Jean-Michel; Mohapatra, Anand; Birkmeyer, Paul; Fearing, Ronald S.; Full, Robert J.

2018-01-01

Exceptional performance is often considered to be elegant and free of ‘errors’ or missteps. During the most extreme escape behaviours, neural control can approach or exceed its operating limits in response time and bandwidth. Here we show that small, rapid running cockroaches with robust exoskeletons select head-on collisions with obstacles to maintain the fastest escape speeds possible to transition up a vertical wall. Instead of avoidance, animals use their passive body shape and compliance to negotiate challenging environments. Cockroaches running at over 1 m or 50 body lengths per second transition from the floor to a vertical wall within 75 ms by using their head like an automobile bumper, mechanically mediating the manoeuvre. Inspired by the animal's behaviour, we demonstrate a passive, high-speed, mechanically mediated vertical transitions with a small, palm-sized legged robot. By creating a collision model for animal and human materials, we suggest a size dependence favouring mechanical mediation below 1 kg that we term the ‘Haldane limit’. Relying on the mechanical control offered by soft exoskeletons represents a paradigm shift for understanding the control of small animals and the next generation of running, climbing and flying robots where the use of the body can off-load the demand for rapid sensing and actuation. PMID:29445036

The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.

PubMed

Fierro-González, Juan Carlos; Cornils, Astrid; Alcedo, Joy; Miranda-Vizuete, Antonio; Swoboda, Peter

2011-01-27

Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.

The Thioredoxin TRX-1 Modulates the Function of the Insulin-Like Neuropeptide DAF-28 during Dauer Formation in Caenorhabditis elegans

PubMed Central

Fierro-González, Juan Carlos; Cornils, Astrid; Alcedo, Joy

2011-01-01

Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions. PMID:21304598

Development of cryogenic Yb:YAG ceramics amplifier for over 100 J DPSSL

NASA Astrophysics Data System (ADS)

Sekine, T.; Takeuchi, Y.; Kurita, T.; Hatano, Y.; Muramatsu, Y.; Mizuta, Y.; Kabeya, Y.; Tamaoki, Y.; Kato, Y.

2017-02-01

A high gain cryogenic Yb:YAG ceramics laser amplifier for a high energy laser amplification system has been developed. The laser system consists of a fiber oscillator and two stage LD pumped cryogenic Yb:YAG ceramic amplifiers. The preamplifier stage has a 5-pass laser amplifier head and the main amplifier stage has a 2-pass laser amplifier head, respectively. The preamplifier obtained an average stored energy density of 0.836 J/cc and small-signal gain (SSG) of 60 with 33 J of stored energy. Then about 1 μJ of input energy from the oscillator was amplified to 3.6 J. The main amplifier head had four pumping LD modules which irradiated the Yb:YAG ceramics directly. This original angular pumping scheme ideally increases irradiation intensity and homogenizes irradiation pattern on the Yb:YAG ceramics due to superposition effect of all of the LD modules. A maximum peak power of over 100 kW was generated by one LD module. When the output energy of the LD modules was 450 J, a 20 of SSG at single pass was obtained. Stored energy density was evaluated to 0.429 J/cc when 148 J energy was stored in 346 cc of Yb:YAG ceramics. As a result, a 55-J output energy with 10 ns pulse duration was demonstrated at a pumping energy of 450 J. The optical-tooptical conversion efficiency which includes transmissivity of the LD modules was 12 %. The extraction efficiency was estimated to 37%.

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

Meagher, Martin; Enemark, Eric J.

The crystal structure of the N-terminal domain of thePyrococcus furiosusminichromosome maintenance (MCM) protein as a double hexamer is described. The MCM complex is a ring-shaped helicase that unwinds DNA at the replication fork of eukaryotes and archaea. Prior to replication initiation, the MCM complex assembles as an inactive double hexamer at specific sites of DNA. The presented structure is highly consistent with previous MCM double-hexamer structures and shows two MCM hexamers with a head-to-head interaction mediated by the N-terminal domain. Minor differences include a diminished head-to-head interaction and a slightly reduced inter-hexamer rotation.

STS-55 German payload specialist Schlegel and MS3 Harris work in SL-D2 module

NASA Technical Reports Server (NTRS)

1993-01-01

STS-55 German Payload Specialist 2 Ulrich Walter, wearing special head gear, finds plenty of room to 'spread out' (head to the floor, feet at the ceiling) while conducting Tissue Thickness and Compliance Along Body Axis salt-water balance experiment in the Spacelab Deutsche 2 (SL-D2) science module aboard the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. Schlegel represents the German Aerospace Research Establishment (DLR). In the background, Mission Specialist 3 (MS3) Bernard A. Harris, Jr monitors an experiment in Rack 11, an experiment rack.

A direct modulated optical link for MRI RF receive coil interconnection.

PubMed

Yuan, Jing; Wei, Juan; Shen, G X

2007-11-01

Optical glass fiber is a promising alternative to traditional coaxial cables for MRI RF receive coil interconnection to avoid any crosstalk and electromagnetic interference between multiple channels. A direct modulated optical link is proposed for MRI coil interconnection in this paper. The link performances of power gain, frequency response and dynamic range are measured. Phantom and in vivo human head images have been demonstrated by the connection of this direct modulated optical link to a head coil on a 0.3T MRI scanner for the first time. Comparable image qualities to coaxial cable link verify the feasibility of using the optical link for imaging with minor modification on the existing scanners. This optical link could also be easily extended for multi-channel array interconnections at high field of 1.5 T.

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

PubMed Central

Tsai, Kuang-Lei; Sato, Shigeo; Tomomori-Sato, Chieri; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2013-01-01

The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a preeminent complex in eukaryotic transcription regulation. We used macromolecular electron microscopy and biochemistry to investigate the subunit organization, structure, and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator’s Middle module interferes with CTD-dependent RNAPII binding to a previously unknown Middle module CTD-binding site targeted early on in a multi-step holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD, and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the Mediator mechanism. PMID:23563140

Place recognition and heading retrieval are mediated by dissociable cognitive systems in mice.

PubMed

Julian, Joshua B; Keinath, Alexander T; Muzzio, Isabel A; Epstein, Russell A

2015-05-19

A lost navigator must identify its current location and recover its facing direction to restore its bearings. We tested the idea that these two tasks--place recognition and heading retrieval--might be mediated by distinct cognitive systems in mice. Previous work has shown that numerous species, including young children and rodents, use the geometric shape of local space to regain their sense of direction after disorientation, often ignoring nongeometric cues even when they are informative. Notably, these experiments have almost always been performed in single-chamber environments in which there is no ambiguity about place identity. We examined the navigational behavior of mice in a two-chamber paradigm in which animals had to both recognize the chamber in which they were located (place recognition) and recover their facing direction within that chamber (heading retrieval). In two experiments, we found that mice used nongeometric features for place recognition, but simultaneously failed to use these same features for heading retrieval, instead relying exclusively on spatial geometry. These results suggest the existence of separate systems for place recognition and heading retrieval in mice that are differentially sensitive to geometric and nongeometric cues. We speculate that a similar cognitive architecture may underlie human navigational behavior.

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

Kalavagunta, C; Lin, M; Snider, J

Purpose: To quantify the factors leading to thermoplastic mask bolus-associated-increased skin dose in head and neck IMRT/VMAT using EBT2 film. Methods: EBT2 film placed beneath a dual layer 3-point ORFIT head, neck and shoulder mask was used to test the effect of mask thickness, beam modulation, air gap, and beam obliquity on bolus effect. Mask thickness was varied based on the distribution of 1.6mm Orfilight layer on top of 2 mm Efficast layer. Beam modulation was varied by irradiating the film with an open field (no beam modulation) and a step and shoot field (beam modulation). Air gap between maskmore » and film was varied from 0 to 5mm. Beam obliquity was varied by irradiating the film at gantry angles of 0°, 35°, and 70°.Finally, film strips placed on a Rando phantom under an Orfit mask, in regions of expected high dose, were irradiated using 5 IMRT and 5 VMAT plans with various modulation levels (modulation factor 2 to 5) and the results were compared with those obtained placing OSLDs at the same locations. Results: An 18–34% increase in mask bolus effect was observed for three factors where the effect of beam obliquity ≥ beam modulation > mask thickness. No increase in mask bolus effect was observed for change in air gap. A 6–13% increase in dose due to mask bolus effect was observed on film strips. Conclusion: This work underlines the role of beam obliquity and beam modulation combined with thermoplastic mask thickness in increasing mask bolus-associated skin dose in head and neck IMRT/VMAT. One possible method of dose reduction, based on knowledge gained from this work, is inclusion of skin as an avoidance structure in treatment planning. Another approach is to design a mask with the least amount of thermoplastic material necessary for immobilization.« less

Anterior visceral endoderm SMAD4 signaling specifies anterior embryonic patterning and head induction in mice.

PubMed

Li, Cuiling; Li, Yi-Ping; Fu, Xin-Yuan; Deng, Chu-Xia

2010-09-27

SMAD4 serves as a common mediator for signaling of TGF-β superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.5) due to failure of mesoderm induction and extraembryonic defects; however, functions of SMAD4 in each germ layer remain elusive. To investigate this, we disrupted SMAD4 in the visceral endoderm and epiblast, respectively, using a Cre-loxP mediated approach. We showed that mutant embryos lack of SMAD4 in the visceral endoderm (Smad4(Co/Co);TTR-Cre) died at E7.5-E9.5 without head-fold and anterior embryonic structures. We demonstrated that TGF-β regulates expression of several genes, such as Hex1, Cer1, and Lim1, in the anterior visceral endoderm (AVE), and the failure of anterior embryonic development in Smad4(Co/Co);TTR-Cre embryos is accompanied by diminished expression of these genes. Consistent with this finding, SMAD4-deficient embryoid bodies showed impaired responsiveness to TGF-β-induced gene expression and morphological changes. On the other hand, embryos carrying Cre-loxP mediated disruption of SMAD4 in the epiblasts exhibited relatively normal mesoderm and head-fold induction although they all displayed profound patterning defects in the later stages of gastrulation. Cumulatively, our data indicate that SMAD4 signaling in the epiblasts is dispensable for mesoderm induction although it remains critical for head patterning, which is significantly different from SMAD4 signaling in the AVE, where it specifies anterior embryonic patterning and head induction.

Anterior Visceral Endoderm SMAD4 Signaling Specifies Anterior Embryonic Patterning and Head Induction in Mice

PubMed Central

Li, Cuiling; Li, Yi-Ping; Fu, Xin-Yuan; Deng, Chu-Xia

2010-01-01

SMAD4 serves as a common mediator for signaling of TGF-β superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.5) due to failure of mesoderm induction and extraembryonic defects; however, functions of SMAD4 in each germ layer remain elusive. To investigate this, we disrupted SMAD4 in the visceral endoderm and epiblast, respectively, using a Cre-loxP mediated approach. We showed that mutant embryos lack of SMAD4 in the visceral endoderm (Smad4Co/Co;TTR-Cre) died at E7.5-E9.5 without head-fold and anterior embryonic structures. We demonstrated that TGF-β regulates expression of several genes, such as Hex1, Cer1, and Lim1, in the anterior visceral endoderm (AVE), and the failure of anterior embryonic development in Smad4Co/Co;TTR-Cre embryos is accompanied by diminished expression of these genes. Consistent with this finding, SMAD4-deficient embryoid bodies showed impaired responsiveness to TGF-β-induced gene expression and morphological changes. On the other hand, embryos carrying Cre-loxP mediated disruption of SMAD4 in the epiblasts exhibited relatively normal mesoderm and head-fold induction although they all displayed profound patterning defects in the later stages of gastrulation. Cumulatively, our data indicate that SMAD4 signaling in the epiblasts is dispensable for mesoderm induction although it remains critical for head patterning, which is significantly different from SMAD4 signaling in the AVE, where it specifies anterior embryonic patterning and head induction. PMID:20941375

Travelling for treatment; does distance and deprivation affect travel for intensity-modulated radiotherapy in the rural setting for head and neck cancer?

PubMed

Cosway, B; Douglas, L; Armstrong, N; Robson, A

2017-06-01

NHS England has commissioned intensity-modulated radiotherapy for head and neck cancers from Newcastle hospitals for patients in North Cumbria. This study assessed whether travel distances affected the decision to travel to Newcastle (to receive intensity-modulated radiotherapy) or Carlisle (to receive conformal radiotherapy). All patients for whom the multidisciplinary team recommended intensity-modulated radiotherapy between December 2013 and January 2016 were included. Index of multiple deprivation scores and travel distances were calculated. Patients were also asked why they chose their treating centre. Sixty-nine patients were included in this study. There were no significant differences in travel distance (p = 0.53) or index of multiple deprivation scores (p = 0.47) between patients opting for treatment in Carlisle or Newcastle. However, 29 of the 33 patients gave travel distance as their main reason for not travelling for treatment. Quantitatively, travel distance and deprivation does not impact on whether patients accept intensity-modulated radiotherapy. However, patients say distance is a major barrier for access. Future research should explore how to reduce this.

In search of rules behind environmental framing; the case of head pitch.

PubMed

Wilson, Gwendoline Ixia; Norman, Brad; Walker, James; Williams, Hannah J; Holton, M D; Clarke, D; Wilson, Rory P

2015-01-01

Whether, and how, animals move requires them to assess their environment to determine the most appropriate action and trajectory, although the precise way the environment is scanned has been little studied. We hypothesized that head attitude, which effectively frames the environment for the eyes, and the way it changes over time, would be modulated by the environment. To test this, we used a head-mounted device (Human-Interfaced Personal Observation platform - HIPOP) on people moving through three different environments; a botanical garden ('green' space), a reef ('blue' space), and a featureless corridor, to examine if head movement in the vertical axis differed between environments. Template matching was used to identify and quantify distinct behaviours. The data on head pitch from all subjects and environments over time showed essentially continuous clear waveforms with varying amplitude and wavelength. There were three stylised behaviours consisting of smooth, regular peaks and troughs in head pitch angle and variable length fixations during which the head pitch remained constant. These three behaviours accounted for ca. 40 % of the total time, with irregular head pitch changes accounting for the rest. There were differences in rates of manifestation of behaviour according to environment as well as environmentally different head pitch values of peaks, troughs and fixations. Finally, although there was considerable variation in head pitch angles, the peak and trough values bounded most of the variation in the fixation pitch values. It is suggested that the constant waveforms in head pitch serve to inform people about their environment, providing a scanning mechanism. Particular emphasis to certain sectors is manifest within the peak and trough limits and these appear modulated by the distribution of the points where fixation, interpreted as being due to objects of interest, occurs. This behaviour explains how animals allocate processing resources to the environment and shows promise for movement studies attempting to elucidate which parts of the environment affect movement trajectories.

Clinical challenges in the implementation of a tomotherapy service for head and neck cancer patients in a regional UK radiotherapy centre.

PubMed

Chatterjee, S; Mott, J H; Smyth, G; Dickson, S; Dobrowsky, W; Kelly, C G

2011-04-01

Intensity-modulated radiotherapy (IMRT) is increasingly being used to treat head and neck cancer cases. We discuss the clinical challenges associated with the setting up of an image guided intensity modulated radiotherapy service for a subset of head and neck cancer patients, using a recently commissioned helical tomotherapy (HT) Hi Art (Tomotherapy Inc, WI) machine in this article. We also discuss the clinical aspects of the tomotherapy planning process, treatment and image guidance experiences for the first 10 head and neck cancer cases. The concepts of geographical miss along with tomotherapy-specific effects, including that of field width and megavoltage CT (MVCT) imaging strategy, have been highlighted using the first 10 head and neck cases treated. There is a need for effective streamlining of all aspects of the service to ensure compliance with cancer waiting time targets. We discuss how patient toxicity audits are crucial to guide refinement of the newly set-up planning dose constraints. This article highlights the important clinical issues one must consider when setting up a head and neck IMRT, image-guided radiotherapy service. It shares some of the clinical challenges we have faced during the setting up of a tomotherapy service. Implementation of a clinical tomotherapy service requires a multidisciplinary team approach and relies heavily on good team working and effective communication between different staff groups.

Recognition of VLSI Module Isomorphism

DTIC Science & Technology

1990-03-01

forthforth->next; 6.5 else{ prev4=prev4->next; forth=forth->next; if (header-. nenI ->tai==third){ header-.nevrI->tail=prev3; prev3->next=NULL; end...end=TRUE; if (header-. nenI ->head=third){ header-.newn->head=third->next; I if((third!=prev3)&&(finished!=TRUE)){ prev3->next=prev3->next->next; third

Sensory and motor properties of the cerebellar uvula and modulus

NASA Technical Reports Server (NTRS)

Robinson, F. R.

1985-01-01

The uvula and nodulus (vermal lobules 9 and 10) of the vestibulocerebellum are implicated by behavioral evidence in the control of eye and head movements and in the production of motion sickness. The uvula and nodulus could play a role in these functions through known output pathways. Purkinje cells in both structures project via the fastigial and vestibular nuceli to the ventral horn of the cervical spin cord, to oculomotor neurons, and to the emetic region of the reticular formation (ablation of which abolishes susceptability to motion sickness). Uvula and nodulus Purkinje cells will be analyzed in cats trained to make controlled head movements. The activity of these neurons is expected to modulate well during head and/or eye movements because the uvula and nodulus receive heavy projections from sources of visual, vestibular and neck proprioceptive information. How neuron activity contributes to movement and how different sensory inputs converge to influence this contribution may be determined by characterizing movement related properties of these neurons. A population of neurons that modulates powerfully to the conflict between different head movement signals that can cause motion sickness may be identified.

Comparison of intensity-modulated radiotherapy and volumetric-modulated arc therapy dose measurement for head and neck cancer using optical stimulated luminescence dosimeter

NASA Astrophysics Data System (ADS)

Lai, Lu-Han; Chuang, Keh-Shih; Lin, Hsin-Hon; Liu, Yi-Chi; Kuo, Chiung-Wen; Lin, Jao-Perng

2017-11-01

The in-vivo dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), a newly developed technique, for head and neck cancer have been investigated for several years. The present study used a head-and-neck RANDO phantom to simulate the clinical conditions of nasopharyngeal carcinoma and compare the radiation doses between VMAT and IMRT. Three types of planning target volume (PTV) profiles were targeted by reducing the PTV surface margin by 0, 3, and 5 mm. An optically stimulated luminescence dosimeter was used to measure the surface doses. The results revealed that VMAT provided on average 16.8-13.8% lower surface doses within the PTV target areas than IMRT. When the PTV margin was reduced by 0 mm, the surface doses for IMRT reached their maximum value, accounting for 75.1% of its prescribed dose (Dp); however, the Dp value of VMAT was only 61.1%. When the PTV margin was reduced by 3 or 5 mm, the surface doses decreased considerably. The observed surface doses were insufficient when the tumours invaded the body surface; however, VMAT exerted larger skin-sparing effects than IMRT when the tumours away from the skin. These results suggest that the skin doses for these two techniques are insufficient for surface tumours. Notably, VMAT can provide lower skin doses for deep tumours.

Control of synaptic function by endocannabinoid-mediated retrograde signaling.

PubMed

Kano, Masanobu

2014-01-01

Since the first reports in 2001, great advances have been made towards the understanding of endocannabinoid-mediated synaptic modulation. Electrophysiological studies have revealed that one of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), is produced from membrane lipids upon postsynaptic Ca(2+) elevation and/or activation of Gq/11-coupled receptors, and released from postsynaptic neurons. The released 2-AG then acts retrogradely onto presynaptic cannabinoid CB1 receptors and induces suppression of neurotransmitter release either transiently or persistently. These forms of 2-AG-mediated retrograde synaptic modulation are functional throughout the brain. The other major endocannabinoid, anandamide, mediates a certain form of endocannabinoid-mediated long-term depression (LTD). Anandamide also functions as an agonist for transient receptor potential vanilloid receptor type 1 (TRPV1) and mediates endocannabinoid-independent and TRPV1-dependent forms of LTD. It has also been demonstrated that the endocannabinoid system itself is plastic, which can be either up- or down-regulated by experimental or environmental conditions. In this review, I will make an overview of the mechanisms underlying endocannabinoid-mediated synaptic modulation.

Control of synaptic function by endocannabinoid-mediated retrograde signaling

PubMed Central

KANO, Masanobu

2014-01-01

Since the first reports in 2001, great advances have been made towards the understanding of endocannabinoid-mediated synaptic modulation. Electrophysiological studies have revealed that one of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), is produced from membrane lipids upon postsynaptic Ca2+ elevation and/or activation of Gq/11-coupled receptors, and released from postsynaptic neurons. The released 2-AG then acts retrogradely onto presynaptic cannabinoid CB1 receptors and induces suppression of neurotransmitter release either transiently or persistently. These forms of 2-AG-mediated retrograde synaptic modulation are functional throughout the brain. The other major endocannabinoid, anandamide, mediates a certain form of endocannabinoid-mediated long-term depression (LTD). Anandamide also functions as an agonist for transient receptor potential vanilloid receptor type 1 (TRPV1) and mediates endocannabinoid-independent and TRPV1-dependent forms of LTD. It has also been demonstrated that the endocannabinoid system itself is plastic, which can be either up- or down-regulated by experimental or environmental conditions. In this review, I will make an overview of the mechanisms underlying endocannabinoid-mediated synaptic modulation. PMID:25169670

Inertial Orientation Trackers with Drift Compensation

NASA Technical Reports Server (NTRS)

Foxlin, Eric M.

2008-01-01

A class of inertial-sensor systems with drift compensation has been invented for use in measuring the orientations of human heads (and perhaps other, similarly sized objects). These systems can be designed to overcome some of the limitations of prior orientation-measuring systems that are based, variously, on magnetic, optical, mechanical-linkage, and acoustical principles. The orientation signals generated by the systems of this invention could be used for diverse purposes, including controlling head-orientation-dependent virtual reality visual displays or enabling persons whose limbs are paralyzed to control machinery by means of head motions. The inventive concept admits to variations too numerous to describe here, making it necessary to limit this description to a typical system, the selected aspects of which are illustrated in the figure. A set of sensors is mounted on a bracket on a band or a cap that gently but firmly grips the wearer s head to be tracked. Among the sensors are three drift-sensitive rotationrate sensors (e.g., integrated-circuit angular- rate-measuring gyroscopes), which put out DC voltages nominally proportional to the rates of rotation about their sensory axes. These sensors are mounted in mutually orthogonal orientations for measuring rates of rotation about the roll, pitch, and yaw axes of the wearer s head. The outputs of these rate sensors are conditioned and digitized, and the resulting data are fed to an integrator module implemented in software in a digital computer. In the integrator module, the angular-rate signals are jointly integrated by any of several established methods to obtain a set of angles that represent approximately the orientation of the head in an external, inertial coordinate system. Because some drift is always present as a component of an angular position computed by integrating the outputs of angular-rate sensors, the orientation signal is processed further in a drift-compensator software module.

Psychometric Validation of the M. D. Anderson Symptom Inventory-Head and Neck Module in the Spanish Language.

PubMed

Sánchez, Daniel; Chala, Andrés; Alvarez, Andrés; Payan, Catalina; Mendoza, Tito; Cleeland, Charles; Sanabria, Alvaro

2016-06-01

The assessment of cancer-related symptoms requires culturally adapted and psychometrically validated symptom assessment tools. The M. D. Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) is a useful instrument for measuring symptom burden that was specifically developed for head and neck cancer patients. To validate the Spanish version of the MDASI-HN. We evaluated the psychometric features of the MDASI-HN in patients with head and neck cancer. We evaluated the item-scale correlations and the internal consistency. We conducted principal axis factoring to identify the underlying dimensions as a measure of construct validity. The convergence/concurrent validity was assessed with the University of Washington Quality of Life Questionnaire for Head and Neck Patients, and known-group validity and test-retest reliability also were assessed. One hundred thirty patients were included. The mean ± SD age was 60.5 ± 13.6 years; 68% of patients were male, 42% had laryngeal tumors, and 45.9% had Stage III tumors. Forty-seven percent of the patients underwent surgery, 55% underwent radiotherapy, and 36% underwent chemotherapy. The global Cronbach alpha for the HN module was 0.81. The factor analysis identified two factors (Factor 1: speech, mucus, coughing, and constipation; Factor 2: teeth, taste, sores, swallowing, and skin). The correlation with the global score of the University of Washington Quality of Life was -0.68. The difference in the MDASI-HN scores according to Eastern Cooperative Oncology Group performance status was statistically significant (2.72 vs. 4.01, P = 0.006). The intraclass test-retest correlation was 0.62. The Spanish version of the MDASI-HN is reliable and valid for evaluating cancer-related symptoms in head and neck cancer patients. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Head and neck mucosal melanoma: a review.

PubMed

Lourenço, Silvia V; Fernandes, Juliana D; Hsieh, Ricardo; Coutinho-Camillo, Claudia M; Bologna, Sheyla; Sangueza, Martin; Nico, Marcello M S

2014-07-01

Head and neck mucosal melanoma (MM) is an aggressive and rare neoplasm of melanocytic origin. To date, few retrospective series and case reports have been reported on MM. This article reviews the current evidence on head and neck MM and the molecular pathways that mediate the pathogenesis of this disease. Head and neck MM accounts for 0.7%-3.8% of all melanomas and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus. Although many studies have examined MM of the head and neck and the underlying molecular pathways, individual genetic and molecular alterations were less investigated. Further studies are needed to complement existing data and to increase our understanding of melanocytes tumorigenesis.

Intimacy processes and psychological distress among couples coping with head and neck or lung cancers.

PubMed

Manne, Sharon; Badr, Hoda

2010-09-01

Couples coping with head and neck and lung cancers are at increased risk for psychological and relationship distress given patients' poor prognosis and aggressive and sometimes disfiguring treatments. The relationship intimacy model of couples' psychosocial adaptation proposes that relationship intimacy mediates associations between couples' cancer-related support communication and psychological distress. Because the components of this model have not yet been evaluated in the same study, we examined associations between three types of cancer-related support communication (self-disclosure, perceived partner disclosure, and protective buffering), intimacy (global and cancer-specific), and global distress among patients coping with either head and neck or lung cancer and their partners. One hundred and nine patients undergoing active treatment and their partners whose average time since diagnosis was 15 months completed cross-sectional surveys. For both patients and their partners, multilevel analyses using the actor-partner interdependence model showed that global and cancer-specific intimacy fully mediated associations between self- and perceived partner disclosure and distress; global intimacy partially mediated the association between protective buffering and distress. Evidence for moderated mediation was found; specifically, lower levels of distress were reported as a function of global and cancer-specific intimacy, but these associations were stronger for partners than for patients. Enhancing relationship intimacy by disclosing cancer-related concerns may facilitate both partners' adjustment to these illnesses. (c) 2010 John Wiley & Sons, Ltd.

Intimacy Processes and Psychological Distress among Couples Coping with Head and Neck or Lung Cancers

PubMed Central

Manne, Sharon; Badr, Hoda

2009-01-01

Objective Couples coping with head and neck and lung cancers are at increased risk for psychological and relationship distress given patients’ poor prognosis and aggressive and sometimes disfiguring treatments. The relationship intimacy model of couples’ psychosocial adaptation proposes that relationship intimacy mediates associations between couples’ cancer-related support communication and psychological distress. Because the components of this model have not yet been evaluated in the same study, we examined associations between three types of cancer-related support communication (self-disclosure, perceived partner disclosure, and protective buffering), intimacy (global and cancer-specific), and global distress among patients coping with either head and neck or lung cancer and their partners. Method One hundred and nine patients undergoing active treatment and their partners whose average time since diagnosis was 15 months completed cross-sectional surveys. Results For both patients and their partners, multilevel analyses using the Actor-Partner Interdependence Model showed that global and cancer-specific intimacy fully mediated associations between self- and perceived partner disclosure and distress; global intimacy partially mediated the association between protective buffering and distress. Evidence for moderated mediation was found; specifically, lower levels of distress were reported as a function of global and cancer-specific intimacy, but these associations were stronger for partners than for patients. Conclusions Enhancing relationship intimacy by disclosing cancer-related concerns may facilitate both partners’ adjustment to these illnesses. PMID:19885852

Development of a Hybrid Atomic Force Microscopic Measurement System Combined with White Light Scanning Interferometry

PubMed Central

Guo, Tong; Wang, Siming; Dorantes-Gonzalez, Dante J.; Chen, Jinping; Fu, Xing; Hu, Xiaotang

2012-01-01

A hybrid atomic force microscopic (AFM) measurement system combined with white light scanning interferometry for micro/nanometer dimensional measurement is developed. The system is based on a high precision large-range positioning platform with nanometer accuracy on which a white light scanning interferometric module and an AFM head are built. A compact AFM head is developed using a self-sensing tuning fork probe. The head need no external optical sensors to detect the deflection of the cantilever, which saves room on the head, and it can be directly fixed under an optical microscopic interferometric system. To enhance the system’s dynamic response, the frequency modulation (FM) mode is adopted for the AFM head. The measuring data can be traceable through three laser interferometers in the system. The lateral scanning range can reach 25 mm × 25 mm by using a large-range positioning platform. A hybrid method combining AFM and white light scanning interferometry is proposed to improve the AFM measurement efficiency. In this method, the sample is measured firstly by white light scanning interferometry to get an overall coarse morphology, and then, further measured with higher resolution by AFM. Several measuring experiments on standard samples demonstrate the system’s good measurement performance and feasibility of the hybrid measurement method. PMID:22368463

Development of a hybrid atomic force microscopic measurement system combined with white light scanning interferometry.

PubMed

Guo, Tong; Wang, Siming; Dorantes-Gonzalez, Dante J; Chen, Jinping; Fu, Xing; Hu, Xiaotang

2012-01-01

A hybrid atomic force microscopic (AFM) measurement system combined with white light scanning interferometry for micro/nanometer dimensional measurement is developed. The system is based on a high precision large-range positioning platform with nanometer accuracy on which a white light scanning interferometric module and an AFM head are built. A compact AFM head is developed using a self-sensing tuning fork probe. The head need no external optical sensors to detect the deflection of the cantilever, which saves room on the head, and it can be directly fixed under an optical microscopic interferometric system. To enhance the system's dynamic response, the frequency modulation (FM) mode is adopted for the AFM head. The measuring data can be traceable through three laser interferometers in the system. The lateral scanning range can reach 25 mm × 25 mm by using a large-range positioning platform. A hybrid method combining AFM and white light scanning interferometry is proposed to improve the AFM measurement efficiency. In this method, the sample is measured firstly by white light scanning interferometry to get an overall coarse morphology, and then, further measured with higher resolution by AFM. Several measuring experiments on standard samples demonstrate the system's good measurement performance and feasibility of the hybrid measurement method.

Hypothesis: Leukocyte Endogenous Mediator/Endogenous Pyrogen/Lymphocyte-Activating Factor Modulates the Development of Nonspecific and Specific Immunity and Affects Nutritional Status

DTIC Science & Technology

1982-04-01

Hypothesis: leukocyte endogenous mediator/ endogenous pyrogen /lymphocyte-activating factor modulates the development of nonspecific and specific... endogenous pyrogen /lympho- NI cyte-activating factor (LEM/EP/LAF) integrates the host’s nonspecific and specific immune responses to infection by...mediator/ endogenous pyrogen /lymphocyte-activating factor, nonspecific and specific immunity, infection, metabolism, nutrition. Introduction LAF which lead

Directional plasticity rapidly improves 3D vestibulo-ocular reflex alignment in monkeys using a multichannel vestibular prosthesis.

PubMed

Dai, Chenkai; Fridman, Gene Y; Chiang, Bryce; Rahman, Mehdi A; Ahn, Joong Ho; Davidovics, Natan S; Della Santina, Charles C

2013-12-01

Bilateral loss of vestibular sensation can be disabling. We have shown that a multichannel vestibular prosthesis (MVP) can partly restore vestibular sensation as evidenced by improvements in the 3-dimensional angular vestibulo-ocular reflex (3D VOR). However, a key challenge is to minimize misalignment between the axes of eye and head rotation, which is apparently caused by current spread beyond each electrode's targeted nerve branch. We recently reported that rodents wearing a MVP markedly improve 3D VOR alignment during the first week after MVP activation, probably through the same central nervous system adaptive mechanisms that mediate cross-axis adaptation over time in normal individuals wearing prisms that cause visual scene movement about an axis different than the axis of head rotation. We hypothesized that rhesus monkeys would exhibit similar improvements with continuous prosthetic stimulation over time. We created bilateral vestibular deficiency in four rhesus monkeys via intratympanic injection of gentamicin. A MVP was mounted to the cranium, and eye movements in response to whole-body passive rotation in darkness were measured repeatedly over 1 week of continuous head motion-modulated prosthetic electrical stimulation. 3D VOR responses to whole-body rotations about each semicircular canal axis were measured on days 1, 3, and 7 of chronic stimulation. Horizontal VOR gain during 1 Hz, 50 °/s peak whole-body rotations before the prosthesis was turned on was <0.1, which is profoundly below normal (0.94 ± 0.12). On stimulation day 1, VOR gain was 0.4-0.8, but the axis of observed eye movements aligned poorly with head rotation (misalignment range ∼30-40 °). Substantial improvement of axis misalignment was observed after 7 days of continuous motion-modulated prosthetic stimulation under normal diurnal lighting. Similar improvements were noted for all animals, all three axes of rotation tested, for all sinusoidal frequencies tested (0.05-5 Hz), and for high-acceleration transient rotations. VOR asymmetry changes did not reach statistical significance, although they did trend toward slight improvement over time. Prior studies had already shown that directional plasticity reduces misalignment when a subject with normal labyrinths views abnormal visual scene movement. Our results show that the converse is also true: individuals receiving misoriented vestibular sensation under normal viewing conditions rapidly adapt to restore a well-aligned 3D VOR. Considering the similarity of VOR physiology across primate species, similar effects are likely to occur in humans using a MVP to treat bilateral vestibular deficiency.

Mother's educational level and fetal growth: the genesis of health inequalities.

PubMed

Silva, Lindsay M; Jansen, Pauline W; Steegers, Eric A P; Jaddoe, Vincent W V; Arends, Lidia R; Tiemeier, Henning; Verhulst, Frank C; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

2010-10-01

Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P < 0.0001). This effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts.

Head motion in humans alternating between straight and curved walking path: combination of stabilizing and anticipatory orienting mechanisms.

PubMed

Hicheur, Halim; Vieilledent, Stéphane; Berthoz, Alain

Anticipatory head orientation relative to walking direction was investigated in humans. Subjects were asked to walk along a 20 m perimeter, figure of eight. The geometry of this path required subjects to steer their body according to both curvature variations (alternate straight with curved walking) and walking direction (clock wise and counter clock wise). In agreement with previous results obtained during different locomotor tasks [R. Grasso, S. Glasauer, Y. Takei, A. Berthoz, The predictive brain: anticipatory control of head direction for the steering of locomotion, NeuroReport 7 (1996) 1170-1174; R. Grasso, P. Prevost, Y.P. Ivanenko, A. Berthoz, Eye-head coordination for the steering of locomotion in humans: an anticipatory synergy, Neurosci. Lett. 253 (2) (1998) 115-118; T. Imai, S.T. Moore, T. Raphan, B. Cohen, Interaction of body, head, and eyes during walking and turning, Exp. Brain Res. 136 (2001) 1-18; P. Prevost, Y. Ivanenko, R. Grasso, A. Berthoz, Spatial invariance in anticipatory orienting behaviour during human navigation, Neurosci. Lett. 339 (2002) 243-247; G. Courtine, M. Schieppati, Human walking along a curved path. I. Body trajectory, segment orientation and the effect of vision, Eur. J. Neurosci. 18 (2003) 177-190], the head turned toward the future walking direction. This anticipatory head behaviour was continuously modulated by the geometrical variations of the path. Two main components were observed in the anticipatory head behaviour. One was related to the geometrical form of the path, the other to the transfer of body mass from one foot to the other during stepping. A clear modulation of the head deviation pattern was observed between walking on curved versus straight parts of the path: head orientation was influenced to a lesser extent by step alternation for curved path where a transient head fixation was observed. We also observed good symmetry in the head deviation profile, i.e. the head tended to anticipate the future walking direction with the same amplitude when turning to the left (29.75 +/- 7.41 degrees of maximum head deviation) or to the right (30.86 +/- 9.92 degrees ). These findings suggest a combination of motor strategies underlying head stabilization in space and more global orienting mechanisms for steering the whole body in the desired direction.

In utero Head Circumference is Associated with Childhood Allergy.

PubMed

Eviston, David P; Minasyan, Anna; Mann, Kristy P; Campbell, Dianne E; Nanan, Ralph K

2015-01-01

Altered fetal growth is known to be associated with allergic disease. Specifically, increased head circumference at birth has been linked to asthma and elevated IgE. However, few studies have examined a link between early fetal anthropometry and allergic disease. The aim of this study was to examine head circumference at mid-gestation in children diagnosed with allergy. This was a retrospective cohort study, comprising pregnancies delivered between 10/2006 and 9/2010 at Nepean Hospital, Australia. Exclusion criteria were illegal drug use, alcohol consumption, gestation <35 weeks, and gestational hypertension. Pregnancy data were sourced from the Nepean Obstetric Database. Atopic diseases (asthma, atopic dermatitis, and IgE-mediated food allergy) were assessed by questionnaire at age 1-5 years. Infants from pregnancies with completed questionnaires, who also had a mid-gestation ultrasound scan, were included (N = 121). Multiple logistic regression techniques were used to model head circumference against the development of allergies. Smaller head circumference at mid-gestation was associated with increased odds of allergic disease in children aged 1-5 years. A 1 mm smaller head circumference was associated with a 7% increased chance of allergies being later diagnosed, adjusted for gestation (95% CI: 1-14%, p = 0.036). Head circumference at mid-gestation was also inversely correlated with the presence of multiple atopic disease. Smaller mid-gestational head circumference is associated with early childhood allergic disease, which suggests that fetal programing of allergic disease occurs before mid-gestation. This suggests that mediators such as brain-derived neurotrophic factor may be dysregulated early in utero in a milieu, which also predisposes to atopic disease.

Leading the Way: Disabilities Services and the Management Team. Training Guides for the Head Start Learning Community.

ERIC Educational Resources Information Center

Education Development Center, Inc., Newton, MA.

This guide is designed to provide Head Start managers with the skills and knowledge needed to plan and implement integrated services for children with disabilities and their families. Module 1, "Identifying Shared Responsibilities," assists participants in identifying how current roles and collaboration practices as a team affect…

The Potential for Tumor Suppressor Gene Therapy in Head and Neck Cancer

PubMed Central

Birkeland, Andrew C.; Ludwig, Megan L.; Spector, Matthew E.; Brenner, J. Chad

2016-01-01

Head and neck squamous cell carcinoma remains a highly morbid and fatal disease. Importantly, genomic sequencing of head and neck cancers has identified frequent mutations in tumor suppressor genes. While targeted therapeutics increasingly are being investigated in head and neck cancer, the majority of these agents are against overactive/overexpressed oncogenes. Therapy to restore lost tumor suppressor gene function remains a key and under-addressed niche in trials for head and neck cancer. Recent advances in gene editing have captured the interest of both the scientific community and the public. As our technology for gene editing and gene expression modulation improves, addressing lost tumor suppressor gene function in head and neck cancers is becoming a reality. This review will summarize new techniques, challenges to implementation, future directions, and ethical ramifications of gene therapy in head and neck cancer. PMID:26896601

Biomolecular Modulation of Neurodegenerative Events during Ageing

PubMed Central

Scarsella, Gianfranco; Librando, Aloisa; Pescosolido, Nicola

2015-01-01

The objective is to assess the modulation of retinal and optic nerve degenerative events induced by the combination of α-lipoic acid (ALA) and superoxide dismutase (SOD) in an animal model of ageing. For this study, 24 male Wistar-Harlan strain rats were left to age for up to 24 months. One group of rats was subjected to a diet supplemented with ALA and SOD for 8 weeks, while another group was used as a positive control and not subjected to any dietary treatment. To assess the cytoprotective effects of the antioxidants, a morphological analysis was carried out on sections of retina and optic nerve head, stained with haematoxylin-eosin, followed by an analysis of the modifications to nuclear DNA detected by the TUNEL technique. The lipid peroxidation assay was used to assess the damage induced by oxidative stress at cell membrane level. The molecules involved in apoptosis mediated by oxidative stress, such as caspase-3 and inducible nitric oxide synthase, were also assayed by immunolocalization and western blot. ALA and SOD are able to counteract senile neurodegenerative deterioration to the retina and optic nerve. Indeed, the combination of these antioxidant molecules can reduce oxidative stress levels and thus prevent both nuclear degradation and subsequent cell death. PMID:26583065

Cell polarity proteins and spermatogenesis.

PubMed

Gao, Ying; Xiao, Xiang; Lui, Wing-Yee; Lee, Will M; Mruk, Dolores; Cheng, C Yan

2016-11-01

When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are notably polarized cells. For instance, Sertoli cell nuclei are found near the basement membrane. On the other hand, tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific actin-rich anchoring junction), gap junction (GJ) and desmosome that constitute the blood-testis barrier (BTB) are also located near the basement membrane. The BTB, in turn, divides the epithelium into the basal and the adluminal (apical) compartments. Within the epithelium, undifferentiated spermatogonia and preleptotene spermatocytes restrictively reside in the basal compartment whereas spermatocytes and post-meiotic spermatids reside in the adluminal compartment. Furthermore, the heads of elongating/elongated spermatids point toward the basement membrane with their elongating tails toward the tubule lumen. However, the involvement of polarity proteins in this unique cellular organization, in particular the underlying molecular mechanism(s) by which polarity proteins confer cellular polarity in the seminiferous epithelium is virtually unknown until recent years. Herein, we discuss latest findings regarding the role of different polarity protein complexes or modules and how these protein complexes are working in concert to modulate Sertoli cell and spermatid polarity. These findings also illustrate polarity proteins exert their effects through the actin-based cytoskeleton mediated by actin binding and regulatory proteins, which in turn modulate adhesion protein complexes at the cell-cell interface since TJ, basal ES and GJ utilize F-actin for attachment. We also propose a hypothetical model which illustrates the antagonistic effects of these polarity proteins. This in turn provides a unique mechanism to modulate junction remodeling in the testis to support germ cell transport across the epithelium in particular the BTB during the epithelial cycle of spermatogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection of eQTL modules mediated by activity levels of transcription factors.

PubMed

Sun, Wei; Yu, Tianwei; Li, Ker-Chau

2007-09-01

Studies of gene expression quantitative trait loci (eQTL) in different organisms have shown the existence of eQTL hot spots: each being a small segment of DNA sequence that harbors the eQTL of a large number of genes. Two questions of great interest about eQTL hot spots arise: (1) which gene within the hot spot is responsible for the linkages, i.e. which gene is the quantitative trait gene (QTG)? (2) How does a QTG affect the expression levels of many genes linked to it? Answers to the first question can be offered by available biological evidence or by statistical methods. The second question is harder to address. One simple situation is that the QTG encodes a transcription factor (TF), which regulates the expression of genes linked to it. However, previous results have shown that TFs are not overrepresented in the eQTL hot spots. In this article, we consider the scenario that the propagation of genetic perturbation from a QTG to other linked genes is mediated by the TF activity. We develop a procedure to detect the eQTL modules (eQTL hot spots together with linked genes) that are compatible with this scenario. We first detect 27 eQTL modules from a yeast eQTL data, and estimate TF activity profiles using the method of Yu and Li (2005). Then likelihood ratio tests (LRTs) are conducted to find 760 relationships supporting the scenario of TF activity mediation: (DNA polymorphism --> cis-linked gene --> TF activity --> downstream linked gene). They are organized into 4 eQTL modules: an amino acid synthesis module featuring a cis-linked gene LEU2 and the mediating TF Leu3; a pheromone response module featuring a cis-linked gene GPA1 and the mediating TF Ste12; an energy-source control module featuring two cis-linked genes, GSY2 and HAP1, and the mediating TF Hap1; a mitotic exit module featuring four cis-linked genes, AMN1, CSH1, DEM1 and TOS1, and the mediating TF complex Ace2/Swi5. Gene Ontology is utilized to reveal interesting functional groups of the downstream genes in each module. Our methods are implemented in an R package: eqtl.TF, which includes source codes and relevant data. It can be freely downloaded at http://www.stat.ucla.edu/~sunwei/software.htm. http://www.stat.ucla.edu/~sunwei/yeast_eQTL_TF/supplementary.pdf.

Egocentric and allocentric representations in auditory cortex

PubMed Central

Brimijoin, W. Owen; Bizley, Jennifer K.

2017-01-01

A key function of the brain is to provide a stable representation of an object’s location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system, and auditory cortex is necessary for sound localization. However, the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects; here we recorded spatial receptive fields in the auditory cortex of freely moving ferrets. We found that most spatially tuned neurons represented sound source location relative to the head across changes in head position and direction. In addition, we also recorded a small number of neurons in which sound location was represented in a world-centered coordinate frame. We used measurements of spatial tuning across changes in head position and direction to explore the influence of sound source distance and speed of head movement on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas, for both populations, modulation was stronger at faster movement speeds. Our findings suggest that early auditory cortex primarily represents sound source location relative to ourselves but that a minority of cells can represent sound location in the world independent of our own position. PMID:28617796

Preschool Interactive Peer Play Mediates Problem Behavior and Learning for Low-Income Children

ERIC Educational Resources Information Center

Bulotsky-Shearer, Rebecca J.; Bell, Elizabeth R.; Romero, Sandy L.; Carter, Tracy M.

2012-01-01

The study employed a developmental, ecological, and resiliency framework to examine whether interactive peer play competencies mediated associations between teacher reported problem behavior and learning outcomes for a representative sample of urban low-income children (N = 507 across 46 Head Start classrooms). Structural equation models provided…

Does gall midge larvae cause pre-dispersal seed mortality and limit cornflower population growth?

NASA Astrophysics Data System (ADS)

Koprdova, Stanislava; Bellanger, Solène; Skuhrovec, Jiří; Darmency, Henri

2015-11-01

Many kinds of pests can reduce seed production. Some directly attack seeds before they are released, and some are hosted by the fruit and impact seed ripening and viability indirectly. Pre-dispersal seed mortality may have strong effects on plant population dynamics and evolution. Our goals were to determine to what extent insect-mediated pre-dispersal seed mortality contributes to population-level declines of cornflower, Centaurea cyanus L. We recorded occurrence and abundance of seed-feeding insects on flower heads in twelve cornflower populations. We measured flower head size, number of disc florets, seed production, and seed viability and germination. Larger flower heads had proportionally fewer healthy seeds. Although we observed no visible damage to the C. cyanus seed, the presence of gall midge (Cecidomyiidae) larvae inside the flower head correlated with four times fewer viable seeds. It seems that gall midges could have a significant impact on ovule fertilization, seed abortion and viability of fully developed cornflower seeds. The higher rate of aborted seeds in the presence of gall midge larvae could have been because the larvae extracted resources from the seeds, or because the larvae repelled pollinators. The viability of apparently healthy seeds was 40% lower in flower heads that contained larvae and/or aborted seed. Insect-mediated pre-dispersal mortality could select against evolution toward larger flower head, and have detrimental consequences on seed number, viability and germination, all of which could limit the spread of C. cyanus populations.

Value of Intensity-Modulated Radiotherapy in Stage IV Head-and-Neck Squamous Cell Carcinoma

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

Dirix, Piet, E-mail: piet.dirix@uzleuven.b; Nuyts, Sandra

2010-12-01

Purpose: To review outcome and toxicity of Stage IVa and IVb head-and-neck squamous cell carcinoma patients treated with concomitant chemotherapy and intensity-modulated radiotherapy (IMRT) according to a hybrid fractionation schedule. Methods and Materials: Between 2006 and 2008, 42 patients with Stage IV head-and-neck squamous cell carcinoma were irradiated according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily), followed by 20 fractions of 1.6 Gy (twice daily), to a total dose of 72 Gy. Chemotherapy (cisplatinum, 100mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively comparedmore » with a previous patient group (n = 55), treated according to the same schedule, but without intensity modulation. Results: Locoregional control (LRC) and overall survival were 81% and 56% after 2 years, respectively. In comparison with the previous cohort, no significant differences were observed regarding either LRC (66%, p = 0.38) or overall survival (73%, p = 0.29). No Grade 4 or 5 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of late Grade 2 or 3 xerostomia (52.9% vs. 90.2%, p < 0.001). No difference was observed regarding late Grade 2 or 3 dysphagia (p = 0.66). Conclusions: Intensity-modulated chemoradiotherapy does not compromise LRC and significantly reduces late toxicity, especially regarding xerostomia.« less

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

PubMed

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Swallowing performance and tube feeding status in patients treated with parotid-sparing intensity-modulated radiotherapy for head and neck cancer.

PubMed

Roe, Justin W G; Carding, Paul N; Drinnan, Michael J; Harrington, Kevin J; Nutting, Christopher M

2016-04-01

The purpose of this prospective study was to evaluate the swallowing performance of patients with head and neck cancer treated with parotid-sparing intensity-modulated radiotherapy (IMRT). Sixty-two patients were recruited. Data were collected before and up to 12 months after treatment. Measures included the Performance Status Scale for head and neck cancer (PSS-HN Normalcy of Diet and Eating in Public subscales), tube feeding status, and 100 mL water swallow test (WST) volume and capacity scores. There was a significant reduction in PSS-HN and WST scores from baseline to 3 months (p < .001). Significant improvements were observed up to 12 months on the PSS-HN. Swallowing volume and capacity scores recovered but did not reach statistical significance. Tube feeding was not required in 47% of the patients. IMRT significantly impacts on swallowing performance, although there is a trend for improvement up to 12 months after treatment. Our data support a case-by-case approach to tube feeding. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1436-E1444, 2016. © 2015 Wiley Periodicals, Inc.

Contact rate modulates foraging efficiency in leaf cutting ants.

PubMed

Bouchebti, S; Ferrere, S; Vittori, K; Latil, G; Dussutour, A; Fourcassié, V

2015-12-21

Lane segregation is rarely observed in animals that move in bidirectional flows. Consequently, these animals generally experience a high rate of head-on collisions during their journeys. Although these collisions have a cost (each collision induces a delay resulting in a decrease of individual speed), they could also have a benefit by promoting information transfer between individuals. Here we explore the impact of head-on collisions in leaf-cutting ants moving on foraging trails by artificially decreasing the rate of head-on collisions between individuals. We show that head-on collisions do not influence the rate of recruitment in these ants but do influence foraging efficiency, i.e. the proportion of ants returning to the nest with a leaf fragment. Surprisingly, both unladen and laden ants returning to the nest participate in the modulation of foraging efficiency: foraging efficiency decreases when the rate of contacts with both nestbound laden or unladen ants decreases. These results suggest that outgoing ants are able to collect information from inbound ants even when these latter do not carry any leaf fragment and that this information can influence their foraging decisions when reaching the end of the trail.

The working mechanism of manual therapy in participants with chronic tension-type headache.

PubMed

Castien, René; Blankenstein, Annette; van der Windt, Daniëlle; Heymans, Martijn W; Dekker, Joost

2013-10-01

Prospective longitudinal study. To explore the working mechanism of manual therapy, we investigated whether 3 cervical spine variables were mediators of the effect of manual therapy on headache frequency. Background Manual therapy has been shown to reduce headache frequency in participants with chronic tension-type headache (CTTH). To what extent specific elements of treatment contribute to the effectiveness of manual therapy in CTTH is unknown. One hundred eighty-two participants with CTTH participated in a prospective longitudinal study: 142 underwent manual therapy and 40 participants received usual care by their general practitioner. Regression analysis was performed according to the steps described by Baron and Kenny, and the proportion of mediated effect was estimated for 3 potential mediators: (1) cervical range of motion, (2) neck flexor endurance, and (3) forward head posture. Outcome was defined as a 50% or greater reduction in headache days. Neck flexor endurance mediated 24.5% of the effect of manual therapy. Cervical range of motion and forward head posture showed no mediated effect. Increased neck flexor endurance appears to be a working mechanism of manual therapy. This finding supports isometric training of neck flexors in participants with CTTH. Trial registered with Netherlands Trial Register (TR 1074).

The Features of Effective Online Professional Development for Early Childhood Educators

ERIC Educational Resources Information Center

Ascetta, Kate Elisabeth

2017-01-01

The purpose of this current study was to examine the effect of a preschool teacher intervention around the use self-monitoring and the online learning modules. The interventions were delivered online using: online learning modules that provided exemplars of the operationally defined instructional language supports. The study included 12 Head Start…

Promoting Evidence-Based Practices: New Teaching Module for Early Childhood Teacher Educators

ERIC Educational Resources Information Center

Young Children, 2009

2009-01-01

Linda Halgunseth, head of NAEYC's Office of Applied Research (OAR), tells readers about Child Care and Early Education Research Connections, a Web site (www.researchconnections.org/teaching_modules) to help teacher educators integrate knowledge about evidence-based practices into teacher education programs. In addition, the article touts the…

Simultaneous exposure to concentrated ambient particles and acrolein causes cardiac effects mediated by parasympathetic modulation in mice

EPA Science Inventory

This study shows that exposure to CAPs and acrolein causes an increase in HRV that is mediated by the parasympathetic nervous system. Numerous studies show that short-term air pollution exposure modulates heart rate variability (HRV), which is an indicator of autonomic influence...

Prostanoids and their receptors that modulate dendritic cell-mediated immunity.

PubMed

Gualde, Norbert; Harizi, Hedi

2004-08-01

Dendritic cells (DC) are essential for the initiation of immune responses by capturing, processing and presenting antigens to T cells. In addition to their important role as professional APC, they are able to produce immunosuppressive and pro-inflammatory prostanoids from arachidonic acid (AA) by the action of cyclooxygenase (COX) enzymes. In an autocrine and paracrine fashion, the secreted lipid mediators subsequently modulate the maturation, cytokine production, Th-cell polarizing ability, chemokine receptor expression, migration, and apoptosis of these extremely versatile APC. The biological actions of prostanoids, including their effects on APC-mediated immunity and acute inflammatory responses, are exerted by G protein-coupled receptors on plasma membrane. Some COX metabolites act as anti-inflammatory lipid mediators by binding to nuclear receptors and modulating DC functions. Although the role of cytokines in DC function has been studied extensively, the effects of prostanoids on DC biology have only recently become the focus of investigation. This review summarizes the current knowledge about the role of prostanoids and their receptors in modulating DC function and the subsequent immune responses.

Initiating head development in mouse embryos: integrating signalling and transcriptional activity.

PubMed

Arkell, Ruth M; Tam, Patrick P L

2012-03-01

The generation of an embryonic body plan is the outcome of inductive interactions between the progenitor tissues that underpin their specification, regionalization and morphogenesis. The intercellular signalling activity driving these processes is deployed in a time- and site-specific manner, and the signal strength must be precisely controlled. Receptor and ligand functions are modulated by secreted antagonists to impose a dynamic pattern of globally controlled and locally graded signals onto the tissues of early post-implantation mouse embryo. In response to the WNT, Nodal and Bone Morphogenetic Protein (BMP) signalling cascades, the embryo acquires its body plan, which manifests as differences in the developmental fate of cells located at different positions in the anterior-posterior body axis. The initial formation of the anterior (head) structures in the mouse embryo is critically dependent on the morphogenetic activity emanating from two signalling centres that are juxtaposed with the progenitor tissues of the head. A common property of these centres is that they are the source of antagonistic factors and the hub of transcriptional activities that negatively modulate the function of WNT, Nodal and BMP signalling cascades. These events generate the scaffold of the embryonic head by the early-somite stage of development. Beyond this, additional tissue interactions continue to support the growth, regionalization, differentiation and morphogenesis required for the elaboration of the structure recognizable as the embryonic head.

LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling.

PubMed

Sheu, J J-C; Lee, C-C; Hua, C-H; Li, C-I; Lai, M-T; Lee, S-C; Cheng, J; Chen, C-M; Chan, C; Chao, S C-C; Chen, J-Y; Chang, J-Y; Lee, C-H

2014-03-13

EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers.

Ethnic Group Differences in Early Head Start Parents Parenting Beliefs and Practices and Links to Children's Early Cognitive Development

ERIC Educational Resources Information Center

Keels, Micere

2009-01-01

Data from the Early Head Start Research and Evaluation study were used to examine the extent to which several factors mediate between- and within-ethnic-group differences in parenting beliefs and behaviors, and children's early cognitive development (analysis sample of 1198 families). The findings indicate that Hispanic-, European-, and…

Dissociation of eye and head components of gaze shifts by stimulation of the omnipause neuron region.

PubMed

Gandhi, Neeraj J; Sparks, David L

2007-07-01

Natural movements often include actions integrated across multiple effectors. Coordinated eye-head movements are driven by a command to shift the line of sight by a desired displacement vector. Yet because extraocular and neck motoneurons are separate entities, the gaze shift command must be separated into independent signals for eye and head movement control. We report that this separation occurs, at least partially, at or before the level of pontine omnipause neurons (OPNs). Stimulation of the OPNs prior to and during gaze shifts temporally decoupled the eye and head components by inhibiting gaze and eye saccades. In contrast, head movements were consistently initiated before gaze onset, and ongoing head movements continued along their trajectories, albeit with some characteristic modulations. After stimulation offset, a gaze shift composed of an eye saccade, and a reaccelerated head movement was produced to preserve gaze accuracy. We conclude that signals subject to OPN inhibition produce the eye-movement component of a coordinated eye-head gaze shift and are not the only signals involved in the generation of the head component of the gaze shift.

Lens dose in routine head CT: comparison of different optimization methods with anthropomorphic phantoms.

PubMed

Nikupaavo, Ulla; Kaasalainen, Touko; Reijonen, Vappu; Ahonen, Sanna-Mari; Kortesniemi, Mika

2015-01-01

The purpose of this study was to study different optimization methods for reducing eye lens dose in head CT. Two anthropomorphic phantoms were scanned with a routine head CT protocol for evaluation of the brain that included bismuth shielding, gantry tilting, organ-based tube current modulation, or combinations of these techniques. Highsensitivity metal oxide semiconductor field effect transistor dosimeters were used to measure local equivalent doses in the head region. The relative changes in image noise and contrast were determined by ROI analysis. The mean absorbed lens doses varied from 4.9 to 19.7 mGy and from 10.8 to 16.9 mGy in the two phantoms. The most efficient method for reducing lens dose was gantry tilting, which left the lenses outside the primary radiation beam, resulting in an approximately 75% decrease in lens dose. Image noise decreased, especially in the anterior part of the brain. The use of organ-based tube current modulation resulted in an approximately 30% decrease in lens dose. However, image noise increased as much as 30% in the posterior and central parts of the brain. With bismuth shields, it was possible to reduce lens dose as much as 25%. Our results indicate that gantry tilt, when possible, is an effective method for reducing exposure of the eye lenses in CT of the brain without compromising image quality. Measurements in two different phantoms showed how patient geometry affects the optimization. When lenses can only partially be cropped outside the primary beam, organ-based tube current modulation or bismuth shields can be useful in lens dose reduction.

Impact of Asynchronous Training on Radiology Learning Curve among Emergency Medicine Residents and Clerkship Students

PubMed Central

Pourmand, Ali; Woodward, Christina; Shokoohi, Hamid; King, Jordan B; Taheri, M Reza; King, Jackson; Lawrence, Christopher

2018-01-01

Context Web-based learning (WBL) modules are effectively used to improve medical education curriculum; however, they have not been evaluated to improve head computed tomography (CT) scan interpretation in an emergency medicine (EM) setting. Objective To evaluate the effectiveness of a WBL module to aid identification of cranial structures on CT and to improve ability to distinguish between normal and abnormal findings. Design Prospective, before-and-after trial in the Emergency Department of an academic center. Baseline head CT knowledge was assessed via a standardized test containing ten head CT scans, including normal scans and those showing hemorrhagic stroke, trauma, and infection (abscess). All trainees then participated in a WBL intervention. Three weeks later, they were given the same ten CT scans to evaluate in a standardized posttest. Main Outcome Measures Improvement in test scores. Results A total of 131 EM clerkship students and 32 EM residents were enrolled. Pretest scores correlated with stage of training, with students and first-year residents demonstrating the lowest scores. Overall, there was a significant improvement in percentage of correctly classified CT images after the training intervention from a mean pretest score of 32% ± 12% to posttest score of 67% ± 13% (mean improvement = 35% ± 13%, p < 0.001). Among subsets by training level, all subgroups except first-year residents demonstrated a statistically significant increase in scores after the training. Conclusion Incorporating asynchronous WBL modules into EM clerkship and residency curriculum provides early radiographic exposure in their clinical training and can enhance diagnostic head CT scan interpretation. PMID:29272248

Performance evaluation of a novel high performance pinhole array detector module using NEMA NU-4 image quality phantom for four head SPECT Imaging

NASA Astrophysics Data System (ADS)

Rahman, Tasneem; Tahtali, Murat; Pickering, Mark R.

2015-03-01

Radiolabeled tracer distribution imaging of gamma rays using pinhole collimation is considered promising for small animal imaging. The recent availability of various radiolabeled tracers has enhanced the field of diagnostic study and is simultaneously creating demand for high resolution imaging devices. This paper presents analyses to represent the optimized parameters of a high performance pinhole array detector module using two different characteristics phantoms. Monte Carlo simulations using the Geant4 application for tomographic emission (GATE) were executed to assess the performance of a four head SPECT system incorporated with pinhole array collimators. The system is based on a pixelated array of NaI(Tl) crystals coupled to an array of position sensitive photomultiplier tubes (PSPMTs). The detector module was simulated to have 48 mm by 48 mm active area along with different pinhole apertures on a tungsten plate. The performance of this system has been evaluated using a uniform shape cylindrical water phantom along with NEMA NU-4 image quality (IQ) phantom filled with 99mTc labeled radiotracers. SPECT images were reconstructed where activity distribution is expected to be well visualized. This system offers the combination of an excellent intrinsic spatial resolution, good sensitivity and signal-to-noise ratio along with high detection efficiency over an energy range between 20-160 keV. Increasing number of heads in a stationary system configuration offers increased sensitivity at a spatial resolution similar to that obtained with the current SPECT system design with four heads.

[The interactive neuroanatomical simulation and practical application of frontotemporal transsylvian exposure in neurosurgery].

PubMed

Balogh, Attila; Czigléczki, Gábor; Papal, Zsolt; Preul, Mark C; Banczerowski, Péter

2014-11-30

There is an increased need for new digital education tools in neurosurgical training. Illustrated textbooks offer anatomic and technical reference but do not substitute hands-on experience provided by surgery or cadaver dissection. Due to limited availability of cadaver dissections the need for development of simulation tools has been augmented. We explored simulation technology for producing virtual reality-like reconstructions of simulated surgical approaches on cadaver. Practical application of the simulation tool has been presented through frontotemporal transsylvian exposure. The dissections were performed on two cadaveric heads. Arteries and veins were prepared and injected with colorful silicon rubber. The heads were rigidly fixed in Mayfield headholder. A robotic microscope with two digital cameras in inverted cone method of image acquisition was used to capture images around a pivot point in several phases of dissections. Multilayered, high-resolution images have been built into interactive 4D environment by custom developed software. We have developed the simulation module of the frontotemporal transsylvian approach. The virtual specimens can be rotated or tilted to any selected angles and examined from different surgical perspectives at any stage of dissections. Important surgical issues such as appropriate head positioning or surgical maneuvers to expose deep situated neuroanatomic structures can be simulated and studied by using the module. The simulation module of the frontotemporal transsylvian exposure helps to examine effect of head positioning on the visibility of deep situated neuroanatomic structures and study surgical maneuvers required to achieve optimal exposure of deep situated anatomic structures. The simulation program is a powerful tool to study issues of preoperative planning and well suited for neurosurgical training.

Electrical stimulation of acupuncture points and blood pressure responses to postural changes: a pilot study.

PubMed

Jones, Alice Y M; Kwan, Y L; Leung, Nathan T F; Yu, Rachel P W; Wu, Cindy M Y; Warburton, Darren E R

2011-05-01

Application of transcutaneous electrical stimulation over acupuncture points (Acu-TENS) facilitates heart rate recovery after exercise and restores hemodynamic stability after open heart surgery. The role of Acu-TENS on cardiovascular parameters in response to postural changes has not been reported. To investigate (1) the effect of Acu-TENS on blood pressure responses to -10º head-down postural change and (2) whether such effects were associated with modulation by the autonomic nervous system. Sixteen healthy volunteers, mean age 22.8 (SD, 3.1) years, were subjected to a -10º head-down tilt from the supine position on 3 separate occasions and received in random order the following 3 intervention protocols for 40 minutes before the postural change: Acu-TENS (over bilateral acupuncture points, PC6), sham-TENS (TENS applied to the skin over the patellae), and control (no electrical output from the TENS device applied at PC6). Mean arterial pressure, large artery elasticity index, cardiac output, and heart rate were recorded and compared at different stimulation protocols in the supine and -10º head-down tilt positions. Spectral analysis of heart rate variability was used to determine any modulation by the autonomic nervous system. Change in large artery elasticity index was observed only in the Acu-TENS group (P < .05) and mean arterial pressure appeared most stable during Acu-TENS. Autonomic nervous system modulation was not apparent with spectral analysis, irrespective of intervention. Sympathetic activity predominated in all positions. Acu-TENS seems to reduce blood pressure changes with -10º head-down tilt with concomitant changes in arterial vessel tone.

Calcium accelerates SNARE-mediated lipid mixing through modulating α-synuclein membrane interaction.

PubMed

Zhang, Zeting; Jiang, Xin; Xu, Danrui; Zheng, Wenwen; Liu, Maili; Li, Conggang

2018-04-04

α-Synuclein is involved in Parkinson's disease, and its interaction with cell membrane is vital to its pathological and physiological functions. We have shown that Ca 2+ can regulate α-synuclein membrane interaction, but the physiological role of Ca 2+ in modulating α-synuclein membrane interaction is still unexplored. Based on the previous findings that α-synuclein inhibits membrane fusion and its inhibitory effect is highly related to its membrane binding, here we employed solution state Nuclear Magnetic Resonance (NMR) spectroscopy and the ensemble fluorescence fusion assay to show that Ca 2+ can modulate the inhibitory effect of α-synuclein on SNARE-mediated membrane fusion through disrupting α-synuclein membrane interaction, resulting in acceleration of SNARE-mediated membrane fusion. These results suggest a modulatory effect of Ca 2+ on membrane mediated normal function of α-synuclein, which of importance for the study of the Parkinson's disease. Copyright © 2018 Elsevier B.V. All rights reserved.

SU-E-T-449: Hippocampal Sparing Radiotherapy Using Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy

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

Moon, S; Kyung Hee University Hospital at Gangdong, Gangdong-gu; Kim, D

2015-06-15

Purpose: The hippocampus sparing during the cranial irradiation has become interesting because it may mitigate radiation-induced neurocognitive toxicity. Herein we report our preliminary study for sparing the hippocampus with and without tilling condition for patient with brain metastases. Methods: Ten patients previously treated with whole brain were reviewed. Five patients tilted the head to around 30 degrees and others were treated without tilting. Treatment plans of linear accelerator (Linac)-based volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) were generated for prescription dose of 30 Gy in 15 fractions. Hippocampal avoidance regions were created with 5-mm volumetric expansion aroundmore » the hippocampus. Whole brain, hippocampus and hippocampal avoidance volume were 1372cm3, 6cm3 and 30cm3 and hippocampal avoidance volume was 2.2% of the whole brain planned target volume in average. Organs at risk (OARs) are hippocampus, eyes, lens, and cochleae. Coverage index (CVI), conformity index (CI), homogeneity index (HI) and mean dose to OARs were used to compare dose characteristic of tilted and non-tilted cases. Results: In IMRT, when CI, CVI and HI of whole brain were 0.88, 0.09 and 0.98 in both tilted and non-tilted cases, absorbed dose of hippocampal avoidance volume in tilted cases were 10% lower than non-tilted cases. Doses in other OARs such as eyes, lens, and cochleae were also decreased about 20% when tilting the head. When CI, HI and CVI in VMAT were 0.9, 0.08 and 0.99, the dose-decreased ratio of OARs in both with and without tilting cases were almost the same with IMRT. But absolute dose of hippocampal avoidance volume in VMAT was 30% lower than IMRT. Conclusion: This study confirms that dose to hippocampus decreases if patients tilt the head. When treating the whole brain with head tilted, patients can acquire the same successful treatment Result and also preserve their valuable memory.« less

Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

PubMed

LeBouder, Emmanuel; Rey-Nores, Julia E; Raby, Anne-Catherine; Affolter, Michael; Vidal, Karine; Thornton, Catherine A; Labéta, Mario O

2006-03-15

The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

Specific detection of the wheat blast pathogen (Magnaporthe oryzae Triticum) by loop-mediated isothermal amplification

USDA-ARS?s Scientific Manuscript database

Wheat blast, caused by Magnaporthe oryzae Triticum (MoT) pathotype, is an economically important fungal disease of wheat. Wheat blast symptoms are similar to Fusarium head scab and can cause confusion in the field. Currently, no in-field diagnostic exists for MoT. Loop-mediated isothermal amplificat...

A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.

PubMed

Reynolds, Kerry Lynn; Bedard, Philippe L; Lee, Se-Hoon; Lin, Chia-Chi; Tabernero, Josep; Alsina, Maria; Cohen, Ezra; Baselga, José; Blumenschein, George; Graham, Donna M; Garrido-Laguna, Ignacio; Juric, Dejan; Sharma, Sunil; Salgia, Ravi; Seroutou, Abdelkader; Tian, Xianbin; Fernandez, Rose; Morozov, Alex; Sheng, Qing; Ramkumar, Thiruvamoor; Zubel, Angela; Bang, Yung-Jue

2017-09-12

Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. Clinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice.

PubMed

Malik, Maninder; Rangel-Barajas, Claudia; Mach, Robert H; Luedtke, Robert R

2016-09-01

Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds. Copyright © 2016. Published by Elsevier Inc.

Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

PubMed

Arosarena, Oneida A; Barr, Eric W; Thorpe, Ryan; Yankey, Hilary; Tarr, Joseph T; Safadi, Fayez F

2018-01-01

Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion. © 2017 Wiley Periodicals, Inc.

Avian orientation: the pulse effect is mediated by the magnetite receptors in the upper beak

PubMed Central

Wiltschko, Wolfgang; Munro, Ursula; Ford, Hugh; Wiltschko, Roswitha

2009-01-01

Migratory silvereyes treated with a strong magnetic pulse shift their headings by approximately 90°, indicating an involvement of magnetite-based receptors in the orientation process. Structures containing superparamagnetic magnetite have been described in the inner skin at the edges of the upper beak of birds, while single-domain magnetite particles are indicated in the nasal cavity. To test which of these structures mediate the pulse effect, we subjected migratory silvereyes, Zosterops l. lateralis, to a strong pulse, and then tested their orientation, while the skin of their upper beak was anaesthetized with a local anaesthetic to temporarily deactivate the magnetite-containing structures there. After the pulse, birds without anaesthesia showed the typical shift, whereas when their beak was anaesthetized, they maintained their original headings. This indicates that the superparamagnetic magnetite-containing structures in the skin of the upper beak are most likely the magnetoreceptors that cause the change in headings observed after pulse treatment. PMID:19324756

A functional portrait of Med7 and the mediator complex in Candida albicans.

PubMed

Tebbji, Faiza; Chen, Yaolin; Richard Albert, Julien; Gunsalus, Kearney T W; Kumamoto, Carol A; Nantel, André; Sellam, Adnane; Whiteway, Malcolm

2014-11-01

Mediator is a multi-subunit protein complex that regulates gene expression in eukaryotes by integrating physiological and developmental signals and transmitting them to the general RNA polymerase II machinery. We examined, in the fungal pathogen Candida albicans, a set of conditional alleles of genes encoding Mediator subunits of the head, middle, and tail modules that were found to be essential in the related ascomycete Saccharomyces cerevisiae. Intriguingly, while the Med4, 8, 10, 11, 14, 17, 21 and 22 subunits were essential in both fungi, the structurally highly conserved Med7 subunit was apparently non-essential in C. albicans. While loss of CaMed7 did not lead to loss of viability under normal growth conditions, it dramatically influenced the pathogen's ability to grow in different carbon sources, to form hyphae and biofilms, and to colonize the gastrointestinal tracts of mice. We used epitope tagging and location profiling of the Med7 subunit to examine the distribution of the DNA sites bound by Mediator during growth in either the yeast or the hyphal form, two distinct morphologies characterized by different transcription profiles. We observed a core set of 200 genes bound by Med7 under both conditions; this core set is expanded moderately during yeast growth, but is expanded considerably during hyphal growth, supporting the idea that Mediator binding correlates with changes in transcriptional activity and that this binding is condition specific. Med7 bound not only in the promoter regions of active genes but also within coding regions and at the 3' ends of genes. By combining genome-wide location profiling, expression analyses and phenotyping, we have identified different Med7p-influenced regulons including genes related to glycolysis and the Filamentous Growth Regulator family. In the absence of Med7, the ribosomal regulon is de-repressed, suggesting Med7 is involved in central aspects of growth control.

A Functional Portrait of Med7 and the Mediator Complex in Candida albicans

PubMed Central

Tebbji, Faiza; Chen, Yaolin; Richard Albert, Julien; Gunsalus, Kearney T. W.; Kumamoto, Carol A.; Nantel, André; Sellam, Adnane; Whiteway, Malcolm

2014-01-01

Mediator is a multi-subunit protein complex that regulates gene expression in eukaryotes by integrating physiological and developmental signals and transmitting them to the general RNA polymerase II machinery. We examined, in the fungal pathogen Candida albicans, a set of conditional alleles of genes encoding Mediator subunits of the head, middle, and tail modules that were found to be essential in the related ascomycete Saccharomyces cerevisiae. Intriguingly, while the Med4, 8, 10, 11, 14, 17, 21 and 22 subunits were essential in both fungi, the structurally highly conserved Med7 subunit was apparently non-essential in C. albicans. While loss of CaMed7 did not lead to loss of viability under normal growth conditions, it dramatically influenced the pathogen's ability to grow in different carbon sources, to form hyphae and biofilms, and to colonize the gastrointestinal tracts of mice. We used epitope tagging and location profiling of the Med7 subunit to examine the distribution of the DNA sites bound by Mediator during growth in either the yeast or the hyphal form, two distinct morphologies characterized by different transcription profiles. We observed a core set of 200 genes bound by Med7 under both conditions; this core set is expanded moderately during yeast growth, but is expanded considerably during hyphal growth, supporting the idea that Mediator binding correlates with changes in transcriptional activity and that this binding is condition specific. Med7 bound not only in the promoter regions of active genes but also within coding regions and at the 3′ ends of genes. By combining genome-wide location profiling, expression analyses and phenotyping, we have identified different Med7p-influenced regulons including genes related to glycolysis and the Filamentous Growth Regulator family. In the absence of Med7, the ribosomal regulon is de-repressed, suggesting Med7 is involved in central aspects of growth control. PMID:25375174

Maternal pelvic dimensions and neonatal size: Implications for growth plasticity in early life as adaptation.

PubMed

Wells, Jonathan C K; Figueiroa, José N; Alves, Joao G

2017-01-01

Patterns of fetal growth predict non-communicable disease risk in adult life, but fetal growth variability appears to have a relatively weak association with maternal nutritional dynamics during pregnancy. This challenges the interpretation of fetal growth variability as 'adaptation'. We hypothesized that associations of maternal size and nutritional status with neonatal size are mediated by the dimensions of the maternal pelvis. We analysed data on maternal height, body mass index (BMI) and pelvic dimensions (conjugate, inter-spinous and inter-cristal diameters) and neonatal gestational age, weight, length, thorax girth and head girth ( n = 224). Multiple regression analysis was used to identify independent maternal predictors of neonatal size, and the mediating role of neonatal head girth in these associations. Pelvic dimensions displaced maternal BMI as a predictor of birth weight, explaining 11.6% of the variance. Maternal conjugate and inter-spinous diameters predicted neonatal length, thorax girth and head girth, whereas inter-cristal diameter only predicted neonatal length. Associations of pelvic dimensions with birth length, but not birth weight, were mediated by neonatal head girth. Pelvic dimensions predicted neonatal size better than maternal BMI, and these associations were mostly independent of maternal height. Sensitivity of fetal growth to pelvic dimensions reduces the risk of cephalo-pelvic disproportion, potentially a strong selective pressure during secular trends in height. Selection on fetal adaptation to relatively inflexible components of maternal phenotype, rather than directly to external ecological conditions, may help explain high levels of growth plasticity during late fetal life and early infancy.

Cerebellar re-encoding of self-generated head movements

PubMed Central

Dugué, Guillaume P; Tihy, Matthieu; Gourévitch, Boris; Léna, Clément

2017-01-01

Head movements are primarily sensed in a reference frame tied to the head, yet they are used to calculate self-orientation relative to the world. This requires to re-encode head kinematic signals into a reference frame anchored to earth-centered landmarks such as gravity, through computations whose neuronal substrate remains to be determined. Here, we studied the encoding of self-generated head movements in the rat caudal cerebellar vermis, an area essential for graviceptive functions. We found that, contrarily to peripheral vestibular inputs, most Purkinje cells exhibited a mixed sensitivity to head rotational and gravitational information and were differentially modulated by active and passive movements. In a subpopulation of cells, this mixed sensitivity underlay a tuning to rotations about an axis defined relative to gravity. Therefore, we show that the caudal vermis hosts a re-encoded, gravitationally polarized representation of self-generated head kinematics in freely moving rats. DOI: http://dx.doi.org/10.7554/eLife.26179.001 PMID:28608779

Presentation and assessment of rideability of a novel single-track vehicle: the Anaconda

NASA Astrophysics Data System (ADS)

Verlinden, O.; Kabeya, P.

2012-08-01

In this paper, a new single-track vehicle, the Anaconda, is presented and modelled according to a multibody theory. This articulated vehicle begins with a traditional bicycle, called the head module, followed by a succession of so-called pedal modules (PMs) equipped with one rear-steered wheel. Each module is connected to the preceding one by a spherical joint. To assess its dynamic behaviour, the model of an Anaconda with two PMs is simulated under the EasyDyn framework, a multibody library based on the minimal coordinates approach. The simulation of such a vehicle cannot be performed without the riders' action, consisting of the torques applied on the handlebars. The latter is implemented through controllers designed by optimal control, from the out-of-plane dynamics of the vehicle going straight ahead at 20 km/h. First, two optimal controllers are determined separately for the Head Module alone on one hand and for the Pedal Module alone on the other hand. They are then implemented on the Anaconda and it appears that the vehicle is close to instability and that the handling of the pedal modules is delicate but humanly possible. Finally, the difficulty in riding the Anaconda is evaluated through the so-called rideability index, which increases, as expected, with the amount of PMs, and shows that good psycho-motor skills will be needed to drive the Anaconda.

Concussion Awareness Education: A Design and Development Research Study

ERIC Educational Resources Information Center

Pilbeam, Renee M.

2016-01-01

This research study looks at the design and development of an online concussion awareness education module. The Keep Your Head in the Game: Concussion Awareness Training for High School Athletes, or Brainbook, is a stand-alone e-learning module designed to run for fifty minutes and to be highly interactive using short video clips with associated…

Continuation of Programmatic Research on Curricular Modules for Early Childhood Education and Parent Participation. Final Report.

ERIC Educational Resources Information Center

Adkins, Dorothy C.; O'Malley, J. Michael

Four projects, conducted as part of an ongoing programmatic research effort to develop and evaluate curricular modules for Head Start classes, are presented. Project A was an attempt to identify the effectiveness of an intervention approach that involved the introduction into two classes of curricula in language, mathematics, motivation, and…

Performance Evaluation and Software Design for EVA Robotic Assistant Stereo Vision Heads

NASA Technical Reports Server (NTRS)

DiPaolo, Daniel

2003-01-01

The purpose of this project was to aid the EVA Robotic Assistant project by evaluating and designing the necessary interfaces for two stereo vision heads - the TracLabs Biclops pan-tilt-verge head, and the Helpmate Zebra pan-tilt-verge head. The first half of the project consisted of designing the necessary software interface so that the other modules of the EVA Robotic Assistant had proper access to all of the functionalities offered by each of the stereovision heads. This half took most of the project time, due to a lack of ready-made CORBA drivers for either of the heads. Once this was overcome, the evaluation stage of the project began. The second half of the project was to take these interfaces and to evaluate each of the stereo vision heads in terms of usefulness to the project. In the key project areas such as stability and reliability, the Zebra pan-tilt-verge head came out on top. However, the Biclops did have many more advantages over the Zebra, such as: lower power consumption, faster communications, and a simpler, cleaner API. Overall, the Biclops pan-tilt-verge head outperformed the Zebra pan-tilt-verge head.

The tae-miR408-Mediated Control of TaTOC1 Genes Transcription Is Required for the Regulation of Heading Time in Wheat1[OPEN

PubMed Central

Zhao, Xiang Yu; Hong, Po; Chen, Xiang Bin; Ye, Xing Guo; Pan, Yan You; Wang, Jian

2016-01-01

Timing of flowering is not only an interesting topic in developmental biology, but it also plays a significant role in agriculture for its effects on the maturation time of seed. The hexaploid wheat (Triticum aestivum) is one of the most important crop species whose flowering time, i.e. heading time, greatly influences yield. However, it remains unclear whether and how microRNAs regulate heading time in it. In our current study, we identified the tae-miR408 in wheat and its targets in vivo, including Triticum aestivum TIMING OF CAB EXPRESSION-A1 (TaTOC-A1), TaTOC-B1, and TaTOC-D1. The tae-miR408 levels were reciprocal to those of TaTOC1s under long-day and short-day conditions. Wheat plants with a knockdown of TaTOC1s via RNA interference and overexpression of tae-miR408 showed early-heading phenotype. Furthermore, TaTOC1s expression was down-regulated by the tae-miR408 in the hexaploid wheat. In addition, other important agronomic traits in wheat, such as plant height and flag leaf angle, were regulated by both tae-miR408 and TaTOC1s. Thus, our results suggested that the tae-miR408 functions in the wheat heading time by mediating TaTOC1s expression, and the study provides important new information on the mechanism underlying heading time regulation in wheat. PMID:26768600

The tae-miR408-Mediated Control of TaTOC1 Genes Transcription Is Required for the Regulation of Heading Time in Wheat.

PubMed

Zhao, Xiang Yu; Hong, Po; Wu, Ji Yun; Chen, Xiang Bin; Ye, Xing Guo; Pan, Yan You; Wang, Jian; Zhang, Xian Sheng

2016-03-01

Timing of flowering is not only an interesting topic in developmental biology, but it also plays a significant role in agriculture for its effects on the maturation time of seed. The hexaploid wheat (Triticum aestivum) is one of the most important crop species whose flowering time, i.e. heading time, greatly influences yield. However, it remains unclear whether and how microRNAs regulate heading time in it. In our current study, we identified the tae-miR408 in wheat and its targets in vivo, including Triticum aestivum TIMING OF CAB EXPRESSION-A1 (TaTOC-A1), TaTOC-B1, and TaTOC-D1. The tae-miR408 levels were reciprocal to those of TaTOC1s under long-day and short-day conditions. Wheat plants with a knockdown of TaTOC1s via RNA interference and overexpression of tae-miR408 showed early-heading phenotype. Furthermore, TaTOC1s expression was down-regulated by the tae-miR408 in the hexaploid wheat. In addition, other important agronomic traits in wheat, such as plant height and flag leaf angle, were regulated by both tae-miR408 and TaTOC1s. Thus, our results suggested that the tae-miR408 functions in the wheat heading time by mediating TaTOC1s expression, and the study provides important new information on the mechanism underlying heading time regulation in wheat. © 2016 American Society of Plant Biologists. All Rights Reserved.

Regulation of Membrane-Type 4 Matrix Metalloproteinase by SLUG Contributes to Hypoxia-Mediated Metastasis12

PubMed Central

Huang, Chi-Hung; Yang, Wen-Hao; Chang, Shyue-Yih; Tai, Shyh-Kuan; Tzeng, Cheng-Hwei; Kao, Jung-Yie; Wu, Kou-Juey; Yang, Muh-Hwa

2009-01-01

The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT), and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1α was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1α and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis. PMID:20019845

Context Modulates Congruency Effects in Selective Attention to Social Cues.

PubMed

Ravagli, Andrea; Marini, Francesco; Marino, Barbara F M; Ricciardelli, Paola

2018-01-01

Head and gaze directions are used during social interactions as essential cues to infer where someone attends. When head and gaze are oriented toward opposite directions, we need to extract socially meaningful information despite stimulus conflict. Recently, a cognitive and neural mechanism for filtering-out conflicting stimuli has been identified while performing non-social attention tasks. This mechanism is engaged proactively when conflict is anticipated in a high proportion of trials and reactively when conflict occurs infrequently. Here, we investigated whether a similar mechanism is at play for limiting distraction from conflicting social cues during gaze or head direction discrimination tasks in contexts with different probabilities of conflict. Results showed that, for the gaze direction task only (Experiment 1), inverse efficiency (IE) scores for distractor-absent trials (i.e., faces with averted gaze and centrally oriented head) were larger (indicating worse performance) when these trials were intermixed with congruent/incongruent distractor-present trials (i.e., faces with averted gaze and tilted head in the same/opposite direction) relative to when the same distractor-absent trials were shown in isolation. Moreover, on distractor-present trials, IE scores for congruent (vs. incongruent) head-gaze pairs in blocks with rare conflict were larger than in blocks with frequent conflict, suggesting that adaptation to conflict was more efficient than adaptation to infrequent events. However, when the task required discrimination of head orientation while ignoring gaze direction, performance was not impacted by both block-level and current trial congruency (Experiment 2), unless the cognitive load of the task was increased by adding a concurrent task (Experiment 3). Overall, our study demonstrates that during attention to social cues proactive cognitive control mechanisms are modulated by the expectation of conflicting stimulus information at both the block- and trial-sequence level, and by the type of task and cognitive load. This helps to clarify the inherent differences in the distracting potential of head and gaze cues during speeded social attention tasks.

Flexibility of the Head-Stalk Linker Domain of Paramyxovirus HN Glycoprotein Is Essential for Triggering Virus Fusion.

PubMed

Adu-Gyamfi, Emmanuel; Kim, Lori S; Jardetzky, Theodore S; Lamb, Robert A

2016-10-15

The Paramyxoviridae comprise a large family of enveloped, negative-sense, single-stranded RNA viruses with significant economic and public health implications. For nearly all paramyxoviruses, infection is initiated by fusion of the viral and host cell plasma membranes in a pH-independent fashion. Fusion is orchestrated by the receptor binding protein hemagglutinin-neuraminidase (HN; also called H or G depending on the virus type) protein and a fusion (F) protein, the latter undergoing a major refolding process to merge the two membranes. Mechanistic details regarding the coupling of receptor binding to F activation are not fully understood. Here, we have identified the flexible loop region connecting the bulky enzymatically active head and the four-helix bundle stalk to be essential for fusion promotion. Proline substitution in this region of HN of parainfluenza virus 5 (PIV5) and Newcastle disease virus HN abolishes cell-cell fusion, whereas HN retains receptor binding and neuraminidase activity. By using reverse genetics, we engineered recombinant PIV5-EGFP viruses with mutations in the head-stalk linker region of HN. Mutations in this region abolished virus recovery and infectivity. In sum, our data suggest that the loop region acts as a "hinge" around which the bulky head of HN swings to-and-fro to facilitate timely HN-mediate F-triggering, a notion consistent with the stalk-mediated activation model of paramyxovirus fusion. Paramyxovirus fusion with the host cell plasma membrane is essential for virus infection. Membrane fusion is orchestrated via interaction of the receptor binding protein (HN, H, or G) with the viral fusion glycoprotein (F). Two distinct models have been suggested to describe the mechanism of fusion: these include "the clamp" and the "provocateur" model of activation. By using biochemical and reverse genetics tools, we have obtained strong evidence in favor of the HN stalk-mediated activation of paramyxovirus fusion. Specifically, our data strongly support the notion that the short linker between the head and stalk plays a role in "conformational switching" of the head group to facilitate F-HN interaction and triggering. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Flexibility of the Head-Stalk Linker Domain of Paramyxovirus HN Glycoprotein Is Essential for Triggering Virus Fusion

PubMed Central

Adu-Gyamfi, Emmanuel; Kim, Lori S.; Jardetzky, Theodore S.

2016-01-01

ABSTRACT The Paramyxoviridae comprise a large family of enveloped, negative-sense, single-stranded RNA viruses with significant economic and public health implications. For nearly all paramyxoviruses, infection is initiated by fusion of the viral and host cell plasma membranes in a pH-independent fashion. Fusion is orchestrated by the receptor binding protein hemagglutinin-neuraminidase (HN; also called H or G depending on the virus type) protein and a fusion (F) protein, the latter undergoing a major refolding process to merge the two membranes. Mechanistic details regarding the coupling of receptor binding to F activation are not fully understood. Here, we have identified the flexible loop region connecting the bulky enzymatically active head and the four-helix bundle stalk to be essential for fusion promotion. Proline substitution in this region of HN of parainfluenza virus 5 (PIV5) and Newcastle disease virus HN abolishes cell-cell fusion, whereas HN retains receptor binding and neuraminidase activity. By using reverse genetics, we engineered recombinant PIV5-EGFP viruses with mutations in the head-stalk linker region of HN. Mutations in this region abolished virus recovery and infectivity. In sum, our data suggest that the loop region acts as a “hinge” around which the bulky head of HN swings to-and-fro to facilitate timely HN-mediate F-triggering, a notion consistent with the stalk-mediated activation model of paramyxovirus fusion. IMPORTANCE Paramyxovirus fusion with the host cell plasma membrane is essential for virus infection. Membrane fusion is orchestrated via interaction of the receptor binding protein (HN, H, or G) with the viral fusion glycoprotein (F). Two distinct models have been suggested to describe the mechanism of fusion: these include “the clamp” and the “provocateur” model of activation. By using biochemical and reverse genetics tools, we have obtained strong evidence in favor of the HN stalk-mediated activation of paramyxovirus fusion. Specifically, our data strongly support the notion that the short linker between the head and stalk plays a role in “conformational switching” of the head group to facilitate F-HN interaction and triggering. PMID:27489276

Intraspecific divergence in sperm morphology of the green sea urchin, Strongylocentrotus droebachiensis: implications for selection in broadcast spawners

PubMed Central

2008-01-01

Background Sperm morphology can be highly variable among species, but less is known about patterns of population differentiation within species. Most studies of sperm morphometric variation are done in species with internal fertilization, where sexual selection can be mediated by complex mating behavior and the environment of the female reproductive tract. Far less is known about patterns of sperm evolution in broadcast spawners, where reproductive dynamics are largely carried out at the gametic level. We investigated variation in sperm morphology of a broadcast spawner, the green sea urchin (Strongylocentrotus droebachiensis), within and among spawnings of an individual, among individuals within a population, and among populations. We also examined population-level variation between two reproductive seasons for one population. We then compared among-population quantitative genetic divergence (QST) for sperm characters to divergence at neutral microsatellite markers (FST). Results All sperm traits except total length showed strong patterns of high diversity among populations, as did overall sperm morphology quantified using multivariate analysis. We also found significant differences in almost all traits among individuals in all populations. Head length, axoneme length, and total length had high within-male repeatability across multiple spawnings. Only sperm head width had significant within-population variation across two reproductive seasons. We found signatures of directional selection on head length and head width, with strong selection possibly acting on head length between the Pacific and West Atlantic populations. We also discuss the strengths and limitations of the QST-FST comparison. Conclusion Sperm morphology in S. droebachiensis is highly variable, both among populations and among individuals within populations, and has low variation within an individual across multiple spawnings. Selective pressures acting among populations may differ from those acting within, with directional selection implicated in driving divergence among populations and balancing selection as a possible mechanism for producing variability among males. Sexual selection in broadcast spawners may be mediated by different processes from those acting on internal fertilizers. Selective divergence in sperm head length among populations is associated with ecological differences among populations that may play a large role in mediating sexual selection in this broadcast spawner. PMID:18851755

Prospective Trial of High-Dose Reirradiation Using Daily Image Guidance With Intensity-Modulated Radiotherapy for Recurrent and Second Primary Head-and-Neck Cancer

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

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Farwell, D. Gregory; Luu, Quang

2011-07-01

Purpose: To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and Materials: Twenty-one consecutive patients were prospectively treated with intensity-modulated radiotherapy from February 2006 to March 2009 to a median dose of 66 Gy (range, 60-70 Gy). None of these patients received concurrent chemotherapy. Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment. Results: The 1- and 2-year estimates of in-field control were 72% and 65%, respectively. A total of 651more » daily megavoltage CT scans were obtained. The mean systematic shift to account for interfraction motion was 1.38 {+-} 1.25 mm, 1.79 {+-} 1.45 mm, and 1.98 {+-} 1.75 mm for the medial-lateral, superior-inferior, and anterior-posterior directions, respectively. Pretreatment shifts of >3 mm occurred in 19% of setups in the medial-lateral, 27% in the superior-inferior, and 33% in the anterior-posterior directions, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis, naso-lacrimal duct stenosis, and brachial plexopathy. Conclusions: Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck.« less

Protons in head-and-neck cancer: bridging the gap of evidence.

PubMed

Ramaekers, Bram L T; Grutters, Janneke P C; Pijls-Johannesma, Madelon; Lambin, Philippe; Joore, Manuela A; Langendijk, Johannes A

2013-04-01

To use Normal Tissue Complication Probability (NTCP) models and comparative planning studies to explore the (cost-)effectiveness of swallowing sparing intensity modulated proton radiotherapy (IMPT) compared with swallowing sparing intensity modulated radiotherapy with photons (IMRT) in head and neck cancer (HNC). A Markov model was constructed to examine and compare the costs and quality-adjusted life years (QALYs) of the following strategies: (1) IMPT for all patients; (2) IMRT for all patients; and (3) IMPT if efficient. The assumption of equal survival for IMPT and IMRT in the base case analysis was relaxed in a sensitivity analysis. Intensity modulated proton radiation therapy and IMRT for all patients yielded 6.620 and 6.520 QALYs and cost €50,989 and €41,038, respectively. Intensity modulated proton radiation therapy if efficient yielded 6.563 QALYs and cost €43,650. The incremental cost-effectiveness ratio of IMPT if efficient versus IMRT for all patients was €60,278 per QALY gained. In the sensitivity analysis, IMRT was more effective (0.967 QALYs) and less expensive (€8218) and thus dominated IMPT for all patients. Cost-effectiveness analysis based on normal tissue complication probability models and planning studies proved feasible and informative and enables the analysis of individualized strategies. The increased effectiveness of IMPT does not seem to outweigh the higher costs for all head-and-neck cancer patients. However, when assuming equal survival among both modalities, there seems to be value in identifying those patients for whom IMPT is cost-effective. Copyright © 2013 Elsevier Inc. All rights reserved.

Monoamines and neuropeptides interact to inhibit aversive behaviour in Caenorhabditis elegans.

PubMed

Mills, Holly; Wragg, Rachel; Hapiak, Vera; Castelletto, Michelle; Zahratka, Jeffrey; Harris, Gareth; Summers, Philip; Korchnak, Amanda; Law, Wenjing; Bamber, Bruce; Komuniecki, Richard

2012-02-01

Pain modulation is complex, but noradrenergic signalling promotes anti-nociception, with α(2)-adrenergic agonists used clinically. To better understand the noradrenergic/peptidergic modulation of nociception, we examined the octopaminergic inhibition of aversive behaviour initiated by the Caenorhabditis elegans nociceptive ASH sensory neurons. Octopamine (OA), the invertebrate counterpart of norepinephrine, modulates sensory-mediated reversal through three α-adrenergic-like OA receptors. OCTR-1 and SER-3 antagonistically modulate ASH signalling directly, with OCTR-1 signalling mediated by Gα(o). In contrast, SER-6 inhibits aversive responses by stimulating the release of an array of 'inhibitory' neuropeptides that activate receptors on sensory neurons mediating attraction or repulsion, suggesting that peptidergic signalling may integrate multiple sensory inputs to modulate locomotory transitions. These studies highlight the complexity of octopaminergic/peptidergic interactions, the role of OA in activating global peptidergic signalling cascades and the similarities of this modulatory network to the noradrenergic inhibition of nociception in mammals, where norepinephrine suppresses chronic pain through inhibitory α(2)-adrenoreceptors on afferent nociceptors and stimulatory α(1)-receptors on inhibitory peptidergic interneurons.

Monoamines and neuropeptides interact to inhibit aversive behaviour in Caenorhabditis elegans

PubMed Central

Mills, Holly; Wragg, Rachel; Hapiak, Vera; Castelletto, Michelle; Zahratka, Jeffrey; Harris, Gareth; Summers, Philip; Korchnak, Amanda; Law, Wenjing; Bamber, Bruce; Komuniecki, Richard

2012-01-01

Pain modulation is complex, but noradrenergic signalling promotes anti-nociception, with α2-adrenergic agonists used clinically. To better understand the noradrenergic/peptidergic modulation of nociception, we examined the octopaminergic inhibition of aversive behaviour initiated by the Caenorhabditis elegans nociceptive ASH sensory neurons. Octopamine (OA), the invertebrate counterpart of norepinephrine, modulates sensory-mediated reversal through three α-adrenergic-like OA receptors. OCTR-1 and SER-3 antagonistically modulate ASH signalling directly, with OCTR-1 signalling mediated by Gαo. In contrast, SER-6 inhibits aversive responses by stimulating the release of an array of ‘inhibitory' neuropeptides that activate receptors on sensory neurons mediating attraction or repulsion, suggesting that peptidergic signalling may integrate multiple sensory inputs to modulate locomotory transitions. These studies highlight the complexity of octopaminergic/peptidergic interactions, the role of OA in activating global peptidergic signalling cascades and the similarities of this modulatory network to the noradrenergic inhibition of nociception in mammals, where norepinephrine suppresses chronic pain through inhibitory α2-adrenoreceptors on afferent nociceptors and stimulatory α1-receptors on inhibitory peptidergic interneurons. PMID:22124329

A protein interaction mechanism for suppressing the mechanosensitive Piezo channels.

PubMed

Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

2017-11-27

Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residue-constituted intracellular linker connecting the pore-module and mechanotransduction-module. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels.

Current status of EVA degradation in Si modules and interface stability in CdTe/CdS modules

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

Czanderna, A.W.

1994-06-30

The goals, objectives, background, technical approach, status, and accomplishments on the PV Module Reliability Research Task are summarized for FY 1993. The accomplishments are reported in two elements, ethylene vinyl acetate (EVA) degradation and stability in CdTe/CdS modules. The EVA results are presented under the headings modified EVA and potential EVA replacements, degradation mechanisms, efficiency losses from yellowed EVA, and equipment acquisitions. The results on CdTe/CdS modules are presented under subheadings of stability of the SnO[sub 2]/CdS interface and degradation at the CdTe/CdS interface.

Anti-cancer effects of curcumin on head and neck cancers.

PubMed

Gao, Wei; Chan, Jimmy Yu-Wai; Wei, William Ignance; Wong, Thian-Sze

2012-11-01

Head and neck cancer is the sixth large type of cancer in the world. The treatment regimens for head and neck cancer encompass surgery, radiotherapy and chemotherapy. However, all current treatment regimens for head and neck cancer have adverse effects. Therefore, continuing investigations have been undertaken to seek less toxic therapies to reduce treatment morbidity for head and neck cancer. Substantial evidence has demonstrated that curcumin inhibited proliferation, migration, invasion and metastasis and induced apoptosis via modulating multiple signaling pathways in head and neck cancer. Curcumin also suppressed the growth of xenograft derived from head and neck cancer in vivo in animal models. This review summarizes the evidence demonstrating potential use of curcumin as a single chemotherapeutic agent or in combination with other chemotherapeutic agents and radiation to minimize their toxicity in head and neck cancer. Although curcumin has been shown to be safe at doses of 8 g/d in both phase I and phase II clinical trials, its bioavailability is poor. Overcoming the poor bioavailability of curcumin in the near future would facilitate its clinical use.

Automated IMRT planning in Pinnacle : A study in head-and-neck cancer.

PubMed

Kusters, J M A M; Bzdusek, K; Kumar, P; van Kollenburg, P G M; Kunze-Busch, M C; Wendling, M; Dijkema, T; Kaanders, J H A M

2017-12-01

This study evaluates the performance and planning efficacy of the Auto-Planning (AP) module in the clinical version of Pinnacle 9.10 (Philips Radiation Oncology Systems, Fitchburg, WI, USA). Twenty automated intensity-modulated radiotherapy (IMRT) plans were compared with the original manually planned clinical IMRT plans from patients with oropharyngeal cancer. Auto-Planning with IMRT offers similar coverage of the planning target volume as the original manually planned clinical plans, as well as better sparing of the contralateral parotid gland, contralateral submandibular gland, larynx, mandible, and brainstem. The mean dose of the contralateral parotid gland and contralateral submandibular gland could be reduced by 2.5 Gy and 1.7 Gy on average. The number of monitor units was reduced with an average of 143.9 (18%). Hands-on planning time was reduced from 1.5-3 h to less than 1 h. The Auto-Planning module was able to produce clinically acceptable head and neck IMRT plans with consistent quality.

Silencing of OsGRX17 in rice improves drought stress tolerance by modulating ROS accumulation and stomatal closure

USDA-ARS?s Scientific Manuscript database

Glutaredoxins (GRXs) have emerged as key mediators in plant responses to environmental stimuli by modulating redox-dependent signaling pathways. Here, we report that RNAi-mediated suppression of the rice gene OsGRXS17, encoding a monothiol GRX with a CGFS-type active site motif, elevates H2O2 produc...

Dkk1 and noggin cooperate in mammalian head induction

PubMed Central

del Barco Barrantes, Ivan; Davidson, Gary; Gröne, Hermann-Josef; Westphal, Heiner; Niehrs, Christof

2003-01-01

Growth factor antagonists play important roles in mediating the inductive effects of the Spemann organizer in amphibian embryos and its equivalents in other vertebrates. Dual inhibition of Wnt and BMP signals has been proposed to confer head organizer activity. We tested the requirement of this coinhibition in Xenopus and mice. In Xenopus, simultaneous reduction of the BMP antagonists chordin and noggin, and the Wnt antagonist dickkopf1 (dkk1) leads to anterior truncations. In mice, compound mutants for dkk1 and noggin display severe head defects, with deletion of all head structures anterior to the mid-hindbrain boundary. These defects arise as a result of a failure in anterior specification at the gastrula stage. The results provide genetic evidence for the dual inhibition model and indicate that dkk1 and noggin functionally cooperate in the head organizer. PMID:12952897

The COMPASS-Like Complex Promotes Flowering and Panicle Branching in Rice1[OPEN

PubMed Central

Wang, Shiliang; Jiang, Haiyang; Cheng, Beijiu

2018-01-01

Flowering time (heading date) and panicle branch number are important agronomic traits that determine yield in rice (Oryza sativa). The activation of flowering requires histone methylation, but the roles of trimethylation of Lys 4 of histone 3 (H3K4me3) in modulating heading date and panicle development are unclear. Here, we showed that the COMPASS-like complex promotes flowering and panicle branching. The rice (Oryza sativa) WD40 protein OsWDR5a interacts with the TRITHORAX-like protein OsTrx1/SET domain group protein 723 (SDG723) to form the core components of the COMPASS-like complex. Plants in which OsWDR5a or OsTrx1 expression was decreased by RNA interference produced fewer secondary branches and less grain and exhibited a delayed heading date under long-day and short-day conditions, whereas loss of OsWDR5a function resulted in embryo lethality. OsWDR5a binds to Early heading date 1 to regulate its H3K4me3 and expression levels. Together, our results show that the COMPASS-like complex promotes flowering and panicle development and suggest that modulation of H3K4me3 levels by the COMPASS-like complex is critical for rice development. PMID:29440594

Oculomotor control of primary eye position discriminates between translation and tilt

NASA Technical Reports Server (NTRS)

Hess, B. J.; Angelaki, D. E.

1999-01-01

We have previously shown that fast phase axis orientation and primary eye position in rhesus monkeys are dynamically controlled by otolith signals during head rotations that involve a reorientation of the head relative to gravity. Because of the inherent ambiguity associated with primary otolith afferent coding of linear accelerations during head translation and tilts, a similar organization might also underlie the vestibulo-ocular reflex (VOR) during translation. The ability of the oculomotor system to correctly distinguish translational accelerations from gravity in the dynamic control of primary eye position has been investigated here by comparing the eye movements elicited by sinusoidal lateral and fore-aft oscillations (0.5 Hz +/- 40 cm, equivalent to +/- 0.4 g) with those during yaw rotations (180 degrees/s) about a vertically tilted axis (23.6 degrees). We found a significant modulation of primary eye position as a function of linear acceleration (gravity) during rotation but not during lateral and fore-aft translation. This modulation was enhanced during the initial phase of rotation when there was concomitant semicircular canal input. These findings suggest that control of primary eye position and fast phase axis orientation in the VOR are based on central vestibular mechanisms that discriminate between gravity and translational head acceleration.

Gaze pursuit responses in nucleus reticularis tegmenti pontis of head-unrestrained macaques.

PubMed

Suzuki, David A; Betelak, Kathleen F; Yee, Robert D

2009-01-01

Eye-head gaze pursuit-related activity was recorded in rostral portions of the nucleus reticularis tegmenti pontis (rNRTP) in alert macaques. The head was unrestrained in the horizontal plane, and macaques were trained to pursue a moving target either with their head, with the eyes stationary in the orbits, or with their eyes, with their head voluntarily held stationary in space. Head-pursuit-related modulations in rNRTP activity were observed with some cells exhibiting increases in firing rate with increases in head-pursuit frequency. For many units, this head-pursuit response appeared to saturate at higher frequencies (>0.6 Hz). The response phase re:peak head-pursuit velocity formed a continuum, containing cells that could encode head-pursuit velocity and those encoding head-pursuit acceleration. The latter cells did not exhibit head position-related activity. Sensitivities were calculated with respect to peak head-pursuit velocity and averaged 1.8 spikes/s/deg/s. Of the cells that were tested for both head- and eye-pursuit-related activity, 86% exhibited responses to both head- and eye-pursuit and therefore carried a putative gaze-pursuit signal. For these gaze-pursuit units, the ratio of head to eye response sensitivities averaged approximately 1.4. Pursuit eccentricity seemed to affect head-pursuit response amplitude even in the absence of a head position response per se. The results indicated that rNRTP is a strong candidate for the source of an active head-pursuit signal that projects to the cerebellum, specifically to the target-velocity and gaze-velocity Purkinje cells that have been observed in vermal lobules VI and VII.

Local control after intensity-modulated radiotherapy for head-and-neck rhabdomyosarcoma.

PubMed

Curtis, Amarinthia E; Okcu, M Fatih; Chintagumpala, Murali; Teh, Bin S; Paulino, Arnold C

2009-01-01

To examine the patterns of failure in patients treated with intensity-modulated radiotherapy (IMRT) for head-and-neck rhabdomyosarcoma (RMS). Between 1998 and 2005, 19 patients with a diagnosis of head-and-neck RMS received IMRT at The Methodist Hospital. There were 11 male and 8 female patients, with a median age of 6 years at time of irradiation. Tumor location was parameningeal in 7, orbital in 6, and other head-and-neck RMS in 6. Chemotherapy was given to all patients, with vincristine, actinomycin D, and cyclophosphamide being the most common regimen (n = 18). The median prescribed dose was 5040 cGy. The clinical target volume included the gross tumor volume with a 1.5-cm margin. The median duration of follow-up for surviving patients was 56 months. The 4-year overall survival and local control rates were 76% and 92.9%, respectively. One patient developed a local failure in the high-dose region of the radiation field; there were no marginal failures. Distant metastasis was seen in 4 patients. Overall survival was 42.9% for parameningeal sites and 100% for other sites (p < 0.01). Late toxicities were seen in 7 patients. Two secondary malignancies occurred in 1 child with embryonal RMS of the face and a p53 mutation. Local control was excellent in patients receiving IMRT for head-and-neck RMS. Patterns of local failure reveal no marginal failures in this group of patients.

The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans.

PubMed

Grants, Jennifer M; Ying, Lisa T L; Yoda, Akinori; You, Charlotte C; Okano, Hideyuki; Sawa, Hitoshi; Taubert, Stefan

2016-02-01

Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinase-dependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals. Copyright © 2016 by the Genetics Society of America.

Intensity- and energy-modulated electron radiotherapy by means of an xMLC for head and neck shallow tumors

NASA Astrophysics Data System (ADS)

Salguero, Francisco Javier; Arráns, Rafael; Atriana Palma, Bianey; Leal, Antonio

2010-03-01

The purpose of this paper is to assess the feasibility of delivering intensity- and energy-modulated electron radiation treatment (MERT) by a photon multileaf collimator (xMLC) and to evaluate the improvements obtained in shallow head and neck (HN) tumors. Four HN patient cases covering different clinical situations were planned by MERT, which used an in-house treatment planning system that utilized Monte Carlo dose calculation. The cases included one oronasal, two parotid and one middle ear tumors. The resulting dose-volume histograms were compared with those obtained from conventional photon and electron treatment techniques in our clinic, which included IMRT, electron beam and mixed beams, most of them using fixed-thickness bolus. Experimental verification was performed with plane-parallel ionization chambers for absolute dose verification, and a PTW ionization chamber array and radiochromic film for relative dosimetry. A MC-based treatment planning system for target with compromised volumes in depth and laterally has been validated. A quality assurance protocol for individual MERT plans was launched. Relative MC dose distributions showed a high agreement with film measurements and absolute ion chamber dose measurements performed at a reference point agreed with MC calculations within 2% in all cases. Clinically acceptable PTV coverage and organ-at-risk sparing were achieved by using the proposed MERT approach. MERT treatment plans, based on delivery of intensity-modulated electron beam using the xMLC, for superficial head and neck tumors, demonstrated comparable or improved PTV dose homogeneity with significantly lower dose to normal tissues. The clinical implementation of this technique will be able to offer a viable alternative for the treatment of shallow head and neck tumors.

Metrology Arrangement for Measuring the Positions of Mirrors of a Submillimeter Telescope

NASA Technical Reports Server (NTRS)

Abramovici, Alex; Bartman, Randall K.

2011-01-01

The position of the secondary mirror of a submillimeter telescope with respect to the primary mirror needs to be known .0.03 mm in three dimensions. At the time of this reporting, no convenient, reasonably priced arrangement that offers this capability exists. The solution proposed here relies on measurement devices developed and deployed for the GeoSAR mission, and later adapted for the ISAT (Innovative Space Based Radar Antenna Technology) demonstration. The measurement arrangement consists of four metrology heads, located on an optical bench, attached to the secondary mirror. Each metrology head has a dedicated target located at the edge of the primary mirror. One laser beam, launched from the head and returned by the target, is used to measure distance. Another beam, launched from a beacon on the target, is monitored by the metrology head and generates a measurement of the target position in the plane perpendicular to the laser beam. A 100-MHz modulation is carried by a collimated laser beam. The relevant wavelength is the RF one, 3 m, divided by two, because the light carries it to the target and back. The phase change due to travel to the target and back is measured by timing the zero-crossing of the RF modulation, using a 100-MHz clock. In order to obtain good resolution, the 100-MHz modulation signal is down-converted to 1 kHz. Then, the phase change corresponding to the round-trip to the target is carried by a 1-kHz signal. Since the 100-MHz clock beats 100,000 times during one period of the 1-kHz signal, the least-significant-bit (LSB) resolution is LSB = 0.015 mm.

Vestibulospinal control of reflex and voluntary head movement

NASA Technical Reports Server (NTRS)

Boyle, R.; Peterson, B. W. (Principal Investigator)

2001-01-01

Secondary canal-related vestibulospinal neurons respond to an externally applied movement of the head in the form of a firing rate modulation that encodes the angular velocity of the movement, and reflects in large part the input "head velocity in space" signal carried by the semicircular canal afferents. In addition to the head velocity signal, the vestibulospinal neurons can carry a more processed signal that includes eye position or eye velocity, or both (see Boyle on ref. list). To understand the control signals used by the central vestibular pathways in the generation of reflex head stabilization, such as the vestibulocollic reflex (VCR), and the maintenance of head posture, it is essential to record directly from identified vestibulospinal neurons projecting to the cervical spinal segments in the alert animal. The present report discusses two key features of the primate vestibulospinal system. First, the termination morphology of vestibulospinal axons in the cervical segments of the spinal cord is described to lay the structural basis of vestibulospinal control of head/neck posture and movement. And second, the head movement signal content carried by the same class of secondary vestibulospinal neurons during the actual execution of the VCR and during self-generated, or active, rapid head movements is presented.

Locoregional Control and Toxicity in Head and Neck Carcinoma Patients following Helical Tomotherapy-Delivered Intensity-Modulated Radiation Therapy Compared with 3D-CRT Data.

PubMed

Santa Cruz, Olalla; Tsoutsou, Pelagia; Castella, Cyril; Khanfir, Kaouthar; Anchisi, Sandro; Bouayed, Salim; Matzinger, Oscar; Ozsahin, Mahmut

2018-06-12

To assess the feasibility and efficacy of intensity-modulated radiation implemented with helical tomotherapy image-guided with daily megavoltage computed tomography for head and neck cancer. Between May 2010 and May 2013, 72 patients were treated with curative intent. The median age was 64 years, with 57% undergoing definitive and 43% postoperative radiotherapy. Primary tumour sites were oral cavity (21%), oropharynx (26%), hypopharynx (20%), larynx (22%), and others (11%). Staging included 4% stage I, 15% II, 26% III, 48% IVa, and 7% IVb. Radiotherapy was combined with chemotherapy in 64%. Primary endpoint was locoregional control, and secondary endpoints survival and toxicity. Median follow-up was 20 months, with 11 locoregional recurrences. Three-year disease-free survival was 58% and overall survival 57%. In the multivariate analysis, age under 64 years, no extracapsular extension, postoperative radiotherapy, induction chemotherapy, and non-oral cavity tumour were significant favourable prognostic factors for disease-free-survival. The overall incidence of acute grade ≥3 toxicities were mucositis 32%, pain 11%, xerostomia 7%, dysphagia 53%, radiodermatitis 44%, and osteonecrosis 1%. Late grade ≥3 toxicities were fibrosis 6%, dysphagia 21%, fistula 1%, and skin necrosis 1%. Intensity-modulated radiation with helical tomotherapy achieved respectable locoregional control and overall survival, with acceptable toxicity, in head and neck cancer patients. © 2018 S. Karger AG, Basel.

Prosodic expectations in silent reading: ERP evidence from rhyme scheme and semantic congruence in classic Chinese poems.

PubMed

Chen, Qingrong; Zhang, Jingjing; Xu, Xiaodong; Scheepers, Christoph; Yang, Yiming; Tanenhaus, Michael K

2016-09-01

In an ERP study, classic Chinese poems with a well-known rhyme scheme were used to generate an expectation of a rhyme in the absence of an expectation for a specific character. Critical characters were either consistent or inconsistent with the expected rhyme scheme and semantically congruent or incongruent with the content of the poem. These stimuli allowed us to examine whether a top-down rhyme scheme expectation would affect relatively early components of the ERP associated with character-to-sound mapping (P200) and lexically-mediated semantic processing (N400). The ERP data revealed that rhyme scheme congruence, but not semantic congruence modulated the P200: rhyme-incongruent characters elicited a P200 effect across the head demonstrating that top-down expectations influence early phonological coding of the character before lexical-semantic processing. Rhyme scheme incongruence also produced a right-lateralized N400-like effect. Moreover, compared to semantically congruous poems, semantically incongruous poems produced a larger N400 response only when the character was consistent with the expected rhyme scheme. The results suggest that top-down prosodic expectations can modulate early phonological processing in visual word recognition, indicating that prosodic expectations might play an important role in silent reading. They also suggest that semantic processing is influenced by general knowledge of text genre. Copyright © 2016 Elsevier B.V. All rights reserved.

Expression of osteoprotegerin, RNAK and RANKL genes in femoral head avascular necrosis and related signaling pathway.

PubMed

Miao, Qingtang; Hao, Sibin; Li, Hongmei; Sun, Fang; Wang, Xueling

2015-01-01

Femoral head avascular necrosis (AVN) causes the damage of hip joint and related dysfunctions, thus consisting of a clinical challenge. Osteoprotegerin (OPG), receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) all regulate the formation of bones via gene transcriptional regulation for the balance between osteoblasts and osteoclasts. This study thus investigated the expressional profiles of OPG, RANK and RANKL genes in AVN patients, and explored related molecular mediating pathways. Real-time qPCR was used to measure the gene expression of OPG, RANK and RANKL genes in AVN femoral head tissue samples from 42 patients, along with normal tissues. Western blotting analysis was performed to quantify protein levels of OPG and RANKL. There was a trend but not statistically significant elevation of mRNA levels of OPG in femoral head AVN tissues compared to normal tissues (P>0.05). The expression of RNAK and RNAKL, however, was significantly elevated in necrotic tissues (P<0.05). No significant difference in protein levels of OPG or RANKL between groups. The expression of OPG, RANK and RANKL genes exert a crucial role in the progression of AVN, suggesting their roles in mediating bone homeostasis and potential effects on bone destruction.

Is sub-nutrition necessary for a poor outcome following early institutional deprivation?

PubMed

Sonuga-Barke, Edmund J S; Beckett, Celia; Kreppner, Jana; Castle, Jenny; Colvert, Emma; Stevens, Suzanne; Hawkins, Amanda; Rutter, Michael

2008-09-01

Institutional deprivation is multifaceted and includes adverse psychosocial and nutrition-related components. In this study we partitioned these risks in relation to cognitive impairment and mental ill health, and explored the mediating role of reduced head/brain size. There were 138 participants (61 males, 77 females) in the study. Participants were Romanian adoptees who had experienced at least 2 weeks of early institutional deprivation. The sample was stratified on the basis of duration of deprivation (high risk >6 mo in institutions) and sub-nutrition (i.e. 1.5 SD below UK age-related norms for weight at UK entry). UK children adopted before 6 months of age and a group of non-institutionally deprived Romanian children constituted the comparison groups. Duration of deprivation was associated with smaller head circumference, lowered IQ, and increased mental heath problems, independently of effects found for sub-nutrition on head circumference and IQ. The mediating role of head circumference was limited to either sub-nourished (IQ) or non-sub-nourished (inattention/overactivity and disinhibited attachment) subgroups. Many negative effects of early deprivation, including stunted brain growth, occur without sub-nutrition: psychosocial deprivation plays a major role in neurodevelopmental effects of deprivation. Further studies of functional and structural neuroanatomy following institutional deprivation are required to delineate the role of brain development in its effects.

Cell Adhesions: Actin-Based Modules that Mediate Cell-Extracellular Matrix and Cell-Cell Interactions

PubMed Central

Bachir, Alexia; Horwitz, Alan Rick; Nelson, W. James; Bianchini, Julie M.

2018-01-01

Cell adhesions link cells to the extracellular matrix (ECM) and to each other, and depend on interactions with the actin cytoskeleton. Both cell-ECM and cell-cell adhesion sites contain discrete, yet overlapping functional modules. These modules establish physical association with the actin cytoskeleton, locally modulate actin organization and dynamics, and trigger intracellular signaling pathways. Interplay between these modules generates distinct actin architectures that underlie different stages, types, and functions of cell-ECM and cell-cell adhesions. Actomyosin contractility is required to generate mature, stable adhesions, as well as sense and translate the mechanical properties of the cellular environment to changes in cell organization and behavior. In this chapter we discuss the organization and function of different adhesion modules and how they interact with the actin cytoskeleton. We highlight the molecular mechanisms of mechanotransduction in adhesions, and how adhesion molecules mediate crosstalk between cell-ECM and cell-cell adhesion sites. PMID:28679638

Strong G-Protein-Mediated Inhibition of Sodium Channels.

PubMed

Mattheisen, Glynis B; Tsintsadze, Timur; Smith, Stephen M

2018-05-29

Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs and modestly modulated via second messenger pathways. Here, we report that the allosteric modulators of the calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, and NPS 2143 completely inhibit VGSC current in the vast majority of cultured mouse neocortical neurons. This form of VGSC current block persisted in CaSR-deficient neurons, indicating a CaSR-independent mechanism. Cinacalcet-mediated blockade of VGSCs was prevented by the guanosine diphosphate (GDP) analog GDPβs, indicating that G-proteins mediated this effect. Cinacalcet inhibited VGSCs by increasing channel inactivation, and block was reversed by prolonged hyperpolarization. Strong cinacalcet inhibition of VGSC currents was also present in acutely isolated mouse cortical neurons. These data identify a dynamic signaling pathway by which G-proteins regulate VGSC current to indirectly modulate central neuronal excitability. Published by Elsevier Inc.

Comparison of the extent of hippocampal sparing according to the tilt of a patient's head during WBRT using linear accelerator-based IMRT and VMAT.

PubMed

Moon, Sun Young; Yoon, Myonggeun; Chung, Mijoo; Chung, Weon Kuu; Kim, Dong Wook

2016-05-01

In this paper, we report the results of our investigation into whole brain radiotherapy (WBRT) using linear accelerator-based intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in lung cancer patients with a high risk of metastasis to the brain. Specifically, we assessed the absorbed dose and the rate of adverse effects for several organs at risk (OAR), including the hippocampus, according to the tilt of a patient's head. We arbitrarily selected five cases where measurements were made with the patients' heads tilted forward and five cases without such tilt. We set the entire brain as the planning target volume (PTV), and the hippocampi, the lenses, the eyes, and the cochleae as the main OAR, and formulated new plans for IMRT (coplanar, non-coplanar) and VMAT (coplanar, non-coplanar). Using the dose-volume histogram (DVH), we calculated and compared the effective uniform dose (EUD), normal tissue complication probability (NTCP) of the OAR and the mean and the maximum doses of hippocampus. As a result, if the patient tilted the head forward when receiving the Linac-based treatment, for the same treatment effect in the PTV, we confirmed that a lower dose entered the OAR, such as the hippocampus, eye, lens, and cochlea. Moreover, the damage to the hippocampus was expected to be the least when receiving coplanar VMAT with the head tilted forward. Accordingly, if patients tilt their heads forward when undergoing Linac-based WBRT, we anticipate that a smaller dose would be transmitted to the OAR, resulting in better quality of life following treatment. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Cachexia induces head and neck changes in locally advanced oropharyngeal carcinoma during definitive cisplatin and image-guided volumetric-modulated arc radiation therapy.

PubMed

Mazzola, R; Ricchetti, F; Fiorentino, A; Di Paola, G; Fersino, S; Giaj Levra, N; Ruggieri, R; Alongi, F

2016-06-01

Cancer cachexia is a syndrome characterized by weight loss (WL) and sarcopenia. Aim of the study was to assess the impact of cachexia on head and neck changes during definitive cisplatin and image-guided volumetric-modulated arc radiation therapy in a series of locally advanced oropharyngeal cancer. Volume variations of sternocleidomastoid muscle (SCM) were considered as surrogate of muscle changes related to sarcopenia. Two head and neck diameters, encompassing the cranial limits of II and III nodal levels (defined as 'head diameter' and 'neck diameter', respectively), were measured. All parameters were defined retrospectively by means of on-board cone beam computed tomography images at 1-8th to 15-22th and at last fraction (fx) of radiotherapy (RT). Cachexia was defined as WL >5% during treatment. Analysis was conducted correlating the parameter changes with three WL ranges: <5, 5-9 and>10%. Thirty patients were evaluated. One hundred and fifty contoured SCMs and three hundred diameters were collected. Median WL was 6.5% (range, 0-16%). The most significant SCM shrinkage was recorded at 15th fx (mean 1.6 cc) related to WL 5-9% and WL >10% (P 0.001). For 'head diameter', the peak reduction was recorded at the 15th fx (mean 8 mm), statistically correlated to WL >10% (P 0.001). The peak reduction in 'neck diameter' was registered at the 22th fx (mean 6 mm), with a gradual reduction until the end of treatment for WL >5%. In a homogeneous cohort of patients, present study quantified the impact of cachexia on head and neck changes. Present data could provide adaptive RT implications for further investigations.

Evaluation of Robustness to Setup and Range Uncertainties for Head and Neck Patients Treated With Pencil Beam Scanning Proton Therapy

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

Malyapa, Robert; Lowe, Matthew; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester

Purpose: To evaluate the robustness of head and neck plans for treatment with intensity modulated proton therapy to range and setup errors, and to establish robustness parameters for the planning of future head and neck treatments. Methods and Materials: Ten patients previously treated were evaluated in terms of robustness to range and setup errors. Error bar dose distributions were generated for each plan, from which several metrics were extracted and used to define a robustness database of acceptable parameters over all analyzed plans. The patients were treated in sequentially delivered series, and plans were evaluated for both the first seriesmore » and for the combined error over the whole treatment. To demonstrate the application of such a database in the head and neck, for 1 patient, an alternative treatment plan was generated using a simultaneous integrated boost (SIB) approach and plans of differing numbers of fields. Results: The robustness database for the treatment of head and neck patients is presented. In an example case, comparison of single and multiple field plans against the database show clear improvements in robustness by using multiple fields. A comparison of sequentially delivered series and an SIB approach for this patient show both to be of comparable robustness, although the SIB approach shows a slightly greater sensitivity to uncertainties. Conclusions: A robustness database was created for the treatment of head and neck patients with intensity modulated proton therapy based on previous clinical experience. This will allow the identification of future plans that may benefit from alternative planning approaches to improve robustness.« less

The mediating effects of social support and self-efficacy on the relationship between social distress and emotional distress in head and neck cancer outpatients with facial disfigurement.

PubMed

Deno, Minako; Tashiro, Mie; Miyashita, Mitsunori; Asakage, Takahiro; Takahashi, Koji; Saito, Kenich; Busujima, Yasunobu; Mori, Yoshiyuki; Saito, Hiroto; Ichikawa, Yuji

2012-02-01

Although social support has been recognized as an important factor in the quality of life of head and neck cancer patients, there has been little investigation of the buffering effect of social support on these patients' social distress or of the coping skill of self-efficacy. The aim of this study was to examine how social support and self-efficacy mediate the relationship between social distress and emotional distress in head and neck cancer patients. Two hundred twenty-five head and neck cancer patients completed our questionnaire (effective response rate, 92.2%). Of these, 129 (57.3%) had facial disfigurement. These participants responded to questions about perception of social distress, social support, self-efficacy, and emotional distress (depression and anxiety). We used structural equation modeling for statistical analysis. The fit indices of this model were excellent (χ2 (7) = 9.147, p = 0.242, goodness of fit index (GFI) = 0.981, adjusted goodness of fit index (AGFI) = 0.922, comparative fit index (CFI) = 0.993, root mean square error of approximation (RMSEA) = 0.049). Self-efficacy strongly buffered the negative influence of social distress on emotional distress. Social support from family members did not have a direct or indirect influence on emotional distress. Social support from friends was related to lower social distress and higher emotional distress. Our findings suggest that self-efficacy might confound the relationship between social support and emotional distress, and that different sources of social support might play different roles in the mediation of social distress on emotional distress. Copyright © 2010 John Wiley & Sons, Ltd.

A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does not suppress alpha 6 beta 4-mediated cell adhesion to laminins

PubMed Central

1995-01-01

To examine the function of the alpha 6 beta 4 integrin we have determined its ligand-binding ability and overexpressed two potentially dominant negative mutant beta 4 subunits, lacking either the cytoplasmic or extracellular domain, in bladder epithelial 804G cells. The results of cell adhesion and radioligand-binding assays showed that alpha 6 beta 4 is a receptor for several laminin isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or head-less mutant beta 4 subunit did not suppress alpha 6 beta 4-mediated adhesion to laminins, as both types of transfectants adhered to these ligands in the presence of blocking anti-beta 1 antibodies as well as the controls. However, immunofluorescence experiments indicated that the endogenous alpha 6 beta 4 integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes in cells overexpressing tail- less beta 4, while the distribution of these molecules was not altered in cells overexpressing the head-less subunit. Electron microscopic studies confirmed that cells overexpressing tail-less beta 4 had a drastically reduced number of hemidesmosomes, while cells expressing the head-less subunit had a normal number of these structures. Thus, expression of a tail-less, but not a head-less mutant beta 4 subunit leads to a dominant negative effect on hemidesmosome assembly without suppressing initial adhesion to laminins. We conclude that the alpha 6 beta 4 integrin binds to several laminins and plays an essential role in the assembly and/or stability of hemidesmosomes, that alpha 6 beta 4- mediated adhesion and hemidesmosome assembly have distinct requirements, and that it is possible to use a dominant negative approach to selectively interfere with a specific function of an integrin. PMID:7721947

Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma

PubMed Central

Zhang, H; Su, L; Müller, S; Tighiouart, M; Xu, Z; Zhang, X; Shin, H J C; Hunt, J; Sun, S-Y; Shin, D M; Chen, Z(G)

2008-01-01

Caveolin-1 (Cav-1) plays an important role in modulating cellular signalling, but its role in metastasis is not well defined. A significant reduction in Cav-1 levels was detected in lymph node metastases as compared with primary tumour of head and neck squamous cell carcinoma (HNSCC) specimens (P<0.0001), confirming the downregulation of Cav-1 observed in a highly metastatic M4 cell lines derived from our orthotopic xenograft model. To investigate the function of Cav-1 in metastasis of HNSCC, we compared stable clones of M4 cells carrying human cav-1 cDNA (CavS) with cells expressing an empty vector (EV) in vitro and in the orthotopic xenograft model. Overexpression of Cav-1 suppressed growth of the CavS tumours compared with the EV tumours. The incidence of lung metastases was significantly lower in animals carrying CavS tumours than those with EV tumours (P=0.03). In vitro, CavS cells displayed reduced cell growth, invasion, and increased anoikis compared with EV cells. In CavS cells, Cav-1 formed complex with integrin β1 and Src. Further application of integrin β1 neutralising antibody or Src inhibitor PP2 to EV cells illustrated similar phenotypes as CavS cells, suggesting that Cav-1 may play an inhibitory role in tumorigenesis and lung metastasis through regulating integrin β1- and Src-mediated cell–cell and cell–matrix interactions. PMID:19002186

Glutamate Receptor GluA1 Subunit Is Implicated in Capsaicin Induced Modulation of Amygdala LTP but Not LTD

ERIC Educational Resources Information Center

Gebhardt, Christine; Albrecht, Doris

2018-01-01

Capsaicin has been shown to modulate synaptic plasticity in various brain regions including the amygdala. Whereas in the lateral amygdala the modulatory effect of capsaicin on long-term potentiation (LA-LTP) is mediated by TRPV1 channels, we have recently shown that capsaicin-induced enhancement of long term depression (LA-LTD) is mediated by…

Effective connectivity during processing of facial affect: evidence for multiple parallel pathways.

PubMed

Dima, Danai; Stephan, Klaas E; Roiser, Jonathan P; Friston, Karl J; Frangou, Sophia

2011-10-05

The perception of facial affect engages a distributed cortical network. We used functional magnetic resonance imaging and dynamic causal modeling to characterize effective connectivity during explicit (conscious) categorization of affective stimuli in the human brain. Specifically, we examined the modulation of connectivity from posterior regions of the face-processing network to the lateral ventral prefrontal cortex (VPFC) during affective categorization and we tested for a potential role of the amygdala (AMG) in mediating this modulation. We found that explicit processing of facial affect led to prominent modulation (increase) in the effective connectivity from the inferior occipital gyrus (IOG) to the VPFC, while there was less evidence for modulation of the afferent connections from fusiform gyrus and AMG to VPFC. More specifically, the forward connection from IOG to the VPFC exhibited a selective increase under anger (as opposed to fear or sadness). Furthermore, Bayesian model comparison suggested that the modulation of afferent connections to the VPFC was mediated directly by facial affect, as opposed to an indirect modulation mediated by the AMG. Our results thus suggest that affective information is conveyed to the VPFC along multiple parallel pathways and that AMG activity is not sufficient to account for the gating of information transfer to the VPFC during explicit emotional processing.

Panoramic attitude sensor for Radio Astronomy Explorer B

NASA Technical Reports Server (NTRS)

Thomsen, R.

1973-01-01

An instrument system to acquire attitude determination data for the RAE-B spacecraft was designed and built. The system consists of an electronics module and two optical scanner heads. Each scanner head has an optical scanner with a field of view of 0.7 degrees diameter which scans the sky and measures the position of the moon, earth and sun relative to the spacecraft. This scanning is accomplished in either of two modes. When the spacecraft is spinning, the scanner operates in spherical mode, with the spacecraft spin providing the slow sweep of lattitude to scan the entire sky. After the spacecraft is placed in lunar orbit and despun, the scanner will operate in planar mode, advancing at a rate of 5.12 seconds per revolution in a fixed plane parallel to the spacecraft Z axis. This scan will cross and measure the moon horizons with every revolution. Each scanner head also has a sun slit which is aligned parallel to the spin axis of the spacecraft and which provides a sun pulse each revolution of the spacecraft. The electronics module provides the command and control, data processing and housekeeping functions.

Pretreatment risk stratification of feeding tube use in patients treated with intensity-modulated radiotherapy for head and neck cancer.

PubMed

Anderson, Nigel J; Jackson, James E; Smith, Jennifer G; Wada, Morikatsu; Schneider, Michal; Poulsen, Michael; Rolfo, Maureen; Fahandej, Maziar; Gan, Hui; Joon, Daryl Lim; Khoo, Vincent

2018-05-13

The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use. © 2018 Wiley Periodicals, Inc.

Comparison of smooth pursuit and combined eye-head tracking in human subjects with deficient labyrinthine function

NASA Technical Reports Server (NTRS)

Leigh, R. J.; Thurston, S. E.; Sharpe, J. A.; Ranalli, P. J.; Hamid, M. A.

1987-01-01

The effects of deficient labyrinthine function on smooth visual tracking with the eyes and head were investigated, using ten patients with bilateral peripheral vestibular disease and ten normal controls. Active, combined eye-head tracking (EHT) was significantly better in patients than smooth pursuit with the eyes alone, whereas normal subjects pursued equally well in both cases. Compensatory eye movements during active head rotation in darkness were always less in patients than in normal subjects. These data were used to examine current hypotheses that postulate central cancellation of the vestibulo-ocular reflex (VOR) during EHT. A model that proposes summation of an integral smooth pursuit command and VOR/compensatory eye movements is consistent with the findings. Observation of passive EHT (visual fixation of a head-fixed target during en bloc rotation) appears to indicate that in this mode parametric gain changes contribute to modulation of the VOR.

Amsacrine as a Topoisomerase II Poison: Importance of Drug-DNA Interactions†

PubMed Central

Ketron, Adam C.; Denny, William A.; Graves, David E.; Osheroff, Neil

2012-01-01

Amsacrine (m-AMSA) is an anticancer agent that displays activity against refractory acute leukemias as well as Hodgkin’s and non-Hodgkin’s lymphomas. The drug is comprised of an intercalative acridine moiety coupled to a 4’-amino-methanesulfon-m-anisidide head group. m-AMSA is historically significant in that it was the first drug demonstrated to function as a topoisomerase II poison. Although m-AMSA was designed as a DNA binding agent, the ability to intercalate does not appear to be the sole determinant of drug activity. Therefore, to more fully analyze structure-function relationships and the role of DNA binding in the action of m-AMSA, we analyzed a series of derivatives for the ability to enhance DNA cleavage mediated by human topoisomerase IIα and topoisomerase IIβ and to intercalate DNA. Results indicate that the 3’-methoxy (m-AMSA) positively affects drug function, potentially by restricting the rotation of the head group in a favorable orientation. Shifting the methoxy to the 2’-position (o-AMSA), which abrogates drug function, appears to increase rotational freedom of the head group and may impair interactions of the 1’-substituent or other portions of the head group within the ternary complex. Finally, the non-intercalative m-AMSA head group enhanced enzyme-mediated DNA cleavage when it was detached from the acridine moiety, albeit with 100-fold lower affinity. Taken together, our results suggest that much of the activity and specificity of m-AMSA as a topoisomerase II poison is embodied in the head group, while DNA intercalation is used primarily to increase the affinity of m-AMSA for the topoisomerase II-DNA cleavage complex. PMID:22304499

Building an open academic environment - a new approach to empowering students in their learning of anatomy through 'Shadow Modules'.

PubMed

Scott, Jonathan L; Moxham, Bernard J; Rutherford, Stephen M

2014-03-01

Teaching and learning in anatomy is undertaken by a variety of methodologies, yet all of these pedagogies benefit from students discussing and reflecting upon their learning activities. An approach of particular potency is peer-mediated learning, through either peer-teaching or collaborative peer-learning. Collaborative, peer-mediated, learning activities help promote deep learning approaches and foster communities of practice in learning. Students generally flourish in collaborative learning settings but there are limitations to the benefits of collaborative learning undertaken solely within the confines of modular curricula. We describe the development of peer-mediated learning through student-focused and student-led study groups we have termed 'Shadow Modules'. The 'Shadow Module' takes place parallel to the formal academically taught module and facilitates collaboration between students to support their learning for that module. In 'Shadow Module' activities, students collaborate towards curating existing online open resources as well as developing learning resources of their own to support their study. Through the use of communication technologies and Web 2.0 tools these resources are able to be shared with their peers, thus enhancing the learning experience of all students following the module. The Shadow Module activities have the potential to lead to participants feeling a greater sense of engagement with the subject material, as well as improving their study and group-working skills and developing digital literacy. The outputs from Shadow Module collaborative work are open-source and may be utilised by subsequent student cohorts, thus building up a repository of learning resources designed by and for students. Shadow Module activities would benefit all pedagogies in the study of anatomy, and support students moving from being passive consumers to active participants in learning. © 2013 Anatomical Society.

Realization of a CORDIC-Based Plug-In Accelerometer Module for PSG System in Head Position Monitoring for OSAS Patients

PubMed Central

Chou, Wen-Cheng; Shiao, Tsu-Hui; Shiao, Guang-Ming; Luo, Chin-Shan

2017-01-01

Overnight polysomnography (PSG) is currently the standard diagnostic procedure for obstructive sleep apnea (OSA). It has been known that monitoring of head position in sleep is crucial not only for the diagnosis (positional sleep apnea) but also for the management of OSA (positional therapy). However, there are no sensor systems available clinically to hook up with PSG for accurate head position monitoring. In this paper, an accelerometer-based sensing system for accurate head position monitoring is developed and realized. The core CORDIC- (COordinate Rotation DIgital Computer-) based tilting sensing algorithm is realized in the system to quickly and accurately convert accelerometer raw data into the desired head position tilting angles. The system can hook up with PSG devices for diagnosis to have head position information integrated with other PSG-monitored signals. It has been applied in an IRB test in Taipei Veterans General Hospital and has been proved that it can meet the medical needs of accurate head position monitoring for PSG diagnosis. PMID:29065608

Gaze Pursuit Responses in Nucleus Reticularis Tegmenti Pontis of Head-Unrestrained Macaques

PubMed Central

Suzuki, David A.; Betelak, Kathleen F.; Yee, Robert D.

2009-01-01

Eye-head gaze pursuit–related activity was recorded in rostral portions of the nucleus reticularis tegmenti pontis (rNRTP) in alert macaques. The head was unrestrained in the horizontal plane, and macaques were trained to pursue a moving target either with their head, with the eyes stationary in the orbits, or with their eyes, with their head voluntarily held stationary in space. Head-pursuit–related modulations in rNRTP activity were observed with some cells exhibiting increases in firing rate with increases in head-pursuit frequency. For many units, this head-pursuit response appeared to saturate at higher frequencies (>0.6 Hz). The response phase re:peak head-pursuit velocity formed a continuum, containing cells that could encode head-pursuit velocity and those encoding head-pursuit acceleration. The latter cells did not exhibit head position–related activity. Sensitivities were calculated with respect to peak head-pursuit velocity and averaged 1.8 spikes/s/deg/s. Of the cells that were tested for both head- and eye-pursuit–related activity, 86% exhibited responses to both head- and eye-pursuit and therefore carried a putative gaze-pursuit signal. For these gaze-pursuit units, the ratio of head to eye response sensitivities averaged ∼1.4. Pursuit eccentricity seemed to affect head-pursuit response amplitude even in the absence of a head position response per se. The results indicated that rNRTP is a strong candidate for the source of an active head-pursuit signal that projects to the cerebellum, specifically to the target-velocity and gaze-velocity Purkinje cells that have been observed in vermal lobules VI and VII. PMID:18987125

Influence of jaw tracking in intensity-modulated and volumetric-modulated arc radiotherapy for head and neck cancers: a dosimetric study.

PubMed

Mani, Karthick Raj; Upadhayay, Sagar; Das, K J Maria

2017-03-01

To Study the dosimetric advantage of the Jaw tracking technique in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for Head and Neck Cancers. We retrospectively selected 10 previously treated head and neck cancer patients stage (T1/T2, N1, M0) in this study. All the patients were planned for IMRT and VMAT with simultaneous integrated boost technique. IMRT and VMAT plans were performed with jaw tracking (JT) and with static jaw (SJ) technique by keeping the same constraints and priorities for a particular patient. Target conformity, dose to the critical structures and low dose volumes were recorded and analyzed for IMRT and VMAT plans with and without JT for all the patients. The conformity index average of all patients followed by standard deviation ([Formula: see text] ± [Formula: see text]) of the JT-IMRT, SJ-IMRT, JT-VMAT, and SJ-VMAT were 1.72 ± 0.56, 1.67 ± 0.57, 1.83 ± 0.65, and 1.85 ± 0.64, and homogeneity index were 0.059 ± 0.05, 0.064 ± 0.05, 0.064 ± 0.04, and 0.064 ± 0.05. JT-IMRT shows significant mean reduction in right parotid and left parotid shows of 7.64% (p < 0.001) and 7.45% (p < 0.001) compare to SJ-IMRT. JT-IMRT plans also shows considerable dose reduction to thyroid, inferior constrictors, spinal cord and brainstem compared to the SJ-IMRT plans. Significant dose reductions were observed for critical structure in the JT-IMRT compared to SJ-IMRT technique. In JT-VMAT plans dose reduction to the critical structure were not significant compared to the SJ-IMRT due to relatively lesser monitor units.

Automation of radiation treatment planning : Evaluation of head and neck cancer patient plans created by the Pinnacle3 scripting and Auto-Planning functions.

PubMed

Speer, Stefan; Klein, Andreas; Kober, Lukas; Weiss, Alexander; Yohannes, Indra; Bert, Christoph

2017-08-01

Intensity-modulated radiotherapy (IMRT) techniques are now standard practice. IMRT or volumetric-modulated arc therapy (VMAT) allow treatment of the tumor while simultaneously sparing organs at risk. Nevertheless, treatment plan quality still depends on the physicist's individual skills, experiences, and personal preferences. It would therefore be advantageous to automate the planning process. This possibility is offered by the Pinnacle 3 treatment planning system (Philips Healthcare, Hamburg, Germany) via its scripting language or Auto-Planning (AP) module. AP module results were compared to in-house scripts and manually optimized treatment plans for standard head and neck cancer plans. Multiple treatment parameters were scored to judge plan quality (100 points = optimum plan). Patients were initially planned manually by different physicists and re-planned using scripts or AP. Script-based head and neck plans achieved a mean of 67.0 points and were, on average, superior to manually created (59.1 points) and AP plans (62.3 points). Moreover, they are characterized by reproducibility and lower standard deviation of treatment parameters. Even less experienced staff are able to create at least a good starting point for further optimization in a short time. However, for particular plans, experienced planners perform even better than scripts or AP. Experienced-user input is needed when setting up scripts or AP templates for the first time. Moreover, some minor drawbacks exist, such as the increase of monitor units (+35.5% for scripted plans). On average, automatically created plans are superior to manually created treatment plans. For particular plans, experienced physicists were able to perform better than scripts or AP; thus, the benefit is greatest when time is short or staff inexperienced.

Low heart rate variability in unemployed men: The possible mediating effects of life satisfaction.

PubMed

Jandackova, V K; Jackowska, M

2015-01-01

Unemployment has consistently been associated with increased risk of cardiovascular disease and premature mortality, and impaired autonomic modulation of the heart might be one mechanism partly explaining this. This study examined whether the possible effect of unemployment on cardiac autonomic modulation is in part mediated by lower psychological well-being. The sample comprised of 15 job-seeking men aged 30-49 years matched with 15 employed men on age, type of job, smoking habits, alcohol intake, frequency of physical activity, and body mass index. Heart rate variability (HRV) during a modified orthostatic test was the measure of cardiac autonomic modulation, and life satisfaction was the measure of psychological well-being. Unemployed men had significantly lower overall HRV (p = .040) than controls. This association was partially mediated through lower general life satisfaction, and in particular, by low financial satisfaction, independently of demographic and/or behavioral factors that influence HRV. These findings suggest that seeking a job is a potential stressor that may reduce overall HRV and contribute towards disturbance of cardiac autonomic modulation in men. Financial difficulties could be one mechanism through which the effects of unemployment are translated into impaired autonomic modulation.

MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

PubMed Central

Stiller, Jiri; Davoine, Celine; Björklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

2017-01-01

The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways. PMID:28441405

Research Studies on Advanced Optical Module/Head Designs for Optical Data Storage

NASA Technical Reports Server (NTRS)

1992-01-01

Preprints are presented from the recent 1992 Optical Data Storage meeting in San Jose. The papers are divided into the following topical areas: Magneto-optical media (Modeling/design and fabrication/characterization/testing); Optical heads (holographic optical elements); and Optical heads (integrated optics). Some representative titles are as follow: Diffraction analysis and evaluation of several focus and track error detection schemes for magneto-optical disk systems; Proposal for massively parallel data storage system; Transfer function characteristics of super resolving systems; Modeling and measurement of a micro-optic beam deflector; Oxidation processes in magneto-optic and related materials; and A modal analysis of lamellar diffraction gratings in conical mountings.

DNA packaging and the pathway of bacteriophage T4 head assembly.

PubMed Central

Hsiao, C L; Black, L W

1977-01-01

A cold-sensitive mutation in the structural gene for a minor phage T4 capsid protein (p20) leads to formation of heads containing p20 and cleaved head proteins and empty of DNA. Such heads can be filled with DNA and converted to active phages in vivo uponshift to high temperature. It appears that p20 has two distinct roles in head assembly: first, in construction of the prehead shell (blocked by ts and am mutation) and, second,in DNA packaging (blocked by cs mutation). The latter function is closely associated with gene 17 product, previously known to be required for DNA packagaing. Temperature shift studies of cs-ts double mutants and other observations allow determination of phage function required for DNA packaging. Contrary to previous proposals, we find that T4 DNA packaging is not directly coupled to and can follow DNA synthesis, protein cleavage, prehead core removal, and gene 21-mediated cleavage-induced increase in head volume. Our evidence suggests that an altered head assembly pathway exists and that DNA packaging is probably initiated by DNA-capsid (p20) interaction. Images PMID:269421

Romanenko looks through a Rodnik Tank in the SM

NASA Image and Video Library

2012-12-31

ISS034-E-010446 (31 Dec. 2012) --- Russian cosmonaut Roman Romanenko, Expedition 34 flight engineer, looks through a Rodnik tank in the Zvezda Service Module of the International Space Station. Romanenko performed a water transfer from a Rodnik tank in the Progress to a Rodnik tank in the Zvezda Service Module. Note the multiple refractions of the cosmonaut?s head and shoulders in the bubbles.

Pedestrian Detection in Far-Infrared Daytime Images Using a Hierarchical Codebook of SURF

PubMed Central

Besbes, Bassem; Rogozan, Alexandrina; Rus, Adela-Maria; Bensrhair, Abdelaziz; Broggi, Alberto

2015-01-01

One of the main challenges in intelligent vehicles concerns pedestrian detection for driving assistance. Recent experiments have showed that state-of-the-art descriptors provide better performances on the far-infrared (FIR) spectrum than on the visible one, even in daytime conditions, for pedestrian classification. In this paper, we propose a pedestrian detector with on-board FIR camera. Our main contribution is the exploitation of the specific characteristics of FIR images to design a fast, scale-invariant and robust pedestrian detector. Our system consists of three modules, each based on speeded-up robust feature (SURF) matching. The first module allows generating regions-of-interest (ROI), since in FIR images of the pedestrian shapes may vary in large scales, but heads appear usually as light regions. ROI are detected with a high recall rate with the hierarchical codebook of SURF features located in head regions. The second module consists of pedestrian full-body classification by using SVM. This module allows one to enhance the precision with low computational cost. In the third module, we combine the mean shift algorithm with inter-frame scale-invariant SURF feature tracking to enhance the robustness of our system. The experimental evaluation shows that our system outperforms, in the FIR domain, the state-of-the-art Haar-like Adaboost-cascade, histogram of oriented gradients (HOG)/linear SVM (linSVM) and MultiFtrpedestrian detectors, trained on the FIR images. PMID:25871724

The Efficacy of IRIS "STAR Legacy" Modules under Different Instructional Conditions

ERIC Educational Resources Information Center

Sayeski, Kristin L.; Hamilton-Jones, Bethany; Oh, Susan

2015-01-01

The vast majority of special education teacher preparation programs in the United States incorporate the IRIS Center's "STAR Legacy" modules into their coursework. Given the diversity of module content and ways in which the modules are employed, the purpose of this study was to explore the potential mediating effects of instructional…

Behavioral and Nondirective Guided Self-Help for Parents of Children with Externalizing Behavior: Mediating Mechanisms in a Head-To-Head Comparison.

PubMed

Katzmann, Josepha; Hautmann, Christopher; Greimel, Lisa; Imort, Stephanie; Pinior, Julia; Scholz, Kristin; Döpfner, Manfred

2017-05-01

Parent training (PT) delivered as a guided self-help intervention may be a cost- and time-effective intervention in the treatment of children with externalizing disorders. In face-to-face PT, parenting strategies have repeatedly been identified as mediating mechanisms for the decrease of children's problem behavior. Few studies have examined possible mediating effects in guided self-help interventions for parents. The present study aimed to investigate possible mediating variables of a behaviorally oriented guided self-help program for parents of children with externalizing problems compared to a nondirective intervention in a clinical sample. A sample of 110 parents of children with externalizing disorders (80 % boys) were randomized to either a behaviorally oriented or a nondirective guided self-help program. Four putative mediating variables were examined simultaneously in a multiple mediation model using structural equation modelling. The outcomes were child symptoms of ADHD and ODD as well as child externalizing problems, assessed at posttreatment. Analyses showed a significant indirect effect for dysfunctional parental attributions in favor of the group receiving the behavioral program, and significant effects of the behavioral program on positive and negative parenting and parental self-efficacy, compared to the nondirective intervention. Our results indicate that a decrease of dysfunctional parental attributions leads to a decrease of child externalizing problems when parents take part in a behaviorally oriented guided self-help program. However, none of the putative mediating variables could explain the decrease in child externalizing behavior problems in the nondirective group. A change in dysfunctional parental attributions should be considered as a possible mediator in the context of PT.

Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans

PubMed Central

Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D.; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G.; Joyner, Michael J.; Cortelli, Pietro

2017-01-01

The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBRS with the sequence technique in healthy male subjects during passive head-up tilt test (HUTT, n = 58), during supine wakefulness, supine slow-wave sleep (SWS), and in the seated and active standing positions (n = 8), and during progressive loss of 1 L blood (n = 8) to decrease central venous pressure in the supine position. HUTT, SWS, the seated, and the standing positions, but not blood loss, entailed significant increases in the positive correlation between HP and the previous SAP values, which is the expected result of arterial baroreflex control, compared with baseline recordings in the supine position during wakefulness. These increases were mirrored by increases in the low-frequency variability of SAP in each condition but SWS. cBRS decreased significantly during HUTT, in the seated and standing positions, and after blood loss compared with baseline during wakefulness. These decreases were mirrored by decreases in the RMSSD index, which reflects cardiac vagal modulation. These results support the view that the cBRS decrease associated with the upright posture is a byproduct of decreased cardiac vagal modulation, triggered by the arterial baroreflex in response to central hypovolemia. Conversely, the greater baroreflex contribution to cardiac control associated with upright posture may be explained, at least in part, by enhanced fluctuations of SAP, which elicit a more effective entrainment of HP fluctuations by the arterial baroreflex. These SAP fluctuations may result from enhanced fluctuations of vascular resistance specific to the upright posture, and not be driven by the accompanying central hypovolemia. PMID:28396638

Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans.

PubMed

Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G; Joyner, Michael J; Cortelli, Pietro

2017-01-01

The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBRS with the sequence technique in healthy male subjects during passive head-up tilt test (HUTT, n = 58), during supine wakefulness, supine slow-wave sleep (SWS), and in the seated and active standing positions ( n = 8), and during progressive loss of 1 L blood ( n = 8) to decrease central venous pressure in the supine position. HUTT, SWS, the seated, and the standing positions, but not blood loss, entailed significant increases in the positive correlation between HP and the previous SAP values, which is the expected result of arterial baroreflex control, compared with baseline recordings in the supine position during wakefulness. These increases were mirrored by increases in the low-frequency variability of SAP in each condition but SWS. cBRS decreased significantly during HUTT, in the seated and standing positions, and after blood loss compared with baseline during wakefulness. These decreases were mirrored by decreases in the RMSSD index, which reflects cardiac vagal modulation. These results support the view that the cBRS decrease associated with the upright posture is a byproduct of decreased cardiac vagal modulation, triggered by the arterial baroreflex in response to central hypovolemia. Conversely, the greater baroreflex contribution to cardiac control associated with upright posture may be explained, at least in part, by enhanced fluctuations of SAP, which elicit a more effective entrainment of HP fluctuations by the arterial baroreflex. These SAP fluctuations may result from enhanced fluctuations of vascular resistance specific to the upright posture, and not be driven by the accompanying central hypovolemia.

Nanoparticle-based targeted therapeutics in head-and-neck cancer.

PubMed

Wu, Ting-Ting; Zhou, Shui-Hong

2015-01-01

Head-and-neck cancer is a major form of the disease worldwide. Treatment consists of surgery, radiation therapy and chemotherapy, but these have not resulted in improved survival rates over the past few decades. Versatile nanoparticles, with selective tumor targeting, are considered to have the potential to improve these poor outcomes. Application of nanoparticle-based targeted therapeutics has extended into many areas, including gene silencing, chemotherapeutic drug delivery, radiosensitization, photothermal therapy, and has shown much promise. In this review, we discuss recent advances in the field of nanoparticle-mediated targeted therapeutics for head-and-neck cancer, with an emphasis on the description of targeting points, including future perspectives.

Modulation of high-frequency vestibuloocular reflex during visual tracking in humans

NASA Technical Reports Server (NTRS)

Das, V. E.; Leigh, R. J.; Thomas, C. W.; Averbuch-Heller, L.; Zivotofsky, A. Z.; Discenna, A. O.; Dell'Osso, L. F.

1995-01-01

1. Humans may visually track a moving object either when they are stationary or in motion. To investigate visual-vestibular interaction during both conditions, we compared horizontal smooth pursuit (SP) and active combined eye-head tracking (CEHT) of a target moving sinusoidally at 0.4 Hz in four normal subjects while the subjects were either stationary or vibrated in yaw at 2.8 Hz. We also measured the visually enhanced vestibuloocular reflex (VVOR) during vibration in yaw at 2.8 Hz over a peak head velocity range of 5-40 degrees/s. 2. We found that the gain of the VVOR at 2.8 Hz increased in all four subjects as peak head velocity increased (P < 0.001), with minimal phase changes, such that mean retinal image slip was held below 5 degrees/s. However, no corresponding modulation in vestibuloocular reflex gain occurred with increasing peak head velocity during a control condition when subjects were rotated in darkness. 3. During both horizontal SP and CEHT, tracking gains were similar, and the mean slip speed of the target's image on the retina was held below 5.5 degrees/s whether subjects were stationary or being vibrated at 2.8 Hz. During both horizontal SP and CEHT of target motion at 0.4 Hz, while subjects were vibrated in yaw, VVOR gain for the 2.8-Hz head rotations was similar to or higher than that achieved during fixation of a stationary target. This is in contrast to the decrease of VVOR gain that is reported while stationary subjects perform CEHT.(ABSTRACT TRUNCATED AT 250 WORDS).

Pathway and network-based analysis of genome-wide association studies and RT-PCR validation in polycystic ovary syndrome

PubMed Central

Shen, Haoran; Liang, Zhou; Zheng, Saihua; Li, Xuelian

2017-01-01

The purpose of this study was to identify promising candidate genes and pathways in polycystic ovary syndrome (PCOS). Microarray dataset GSE345269 obtained from the Gene Expression Omnibus database includes 7 granulosa cell samples from PCOS patients, and 3 normal granulosa cell samples. Differentially expressed genes (DEGs) were screened between PCOS and normal samples. Pathway enrichment analysis was conducted for DEGs using ClueGO and CluePedia plugin of Cytoscape. A Reactome functional interaction (FI) network of the DEGs was built using ReactomeFIViz, and then network modules were extracted, followed by pathway enrichment analysis for the modules. Expression of DEGs in granulosa cell samples was measured using quantitative RT-PCR. A total of 674 DEGs were retained, which were significantly enriched with inflammation and immune-related pathways. Eight modules were extracted from the Reactome FI network. Pathway enrichment analysis revealed significant pathways of each module: module 0, Regulation of RhoA activity and Signaling by Rho GTPases pathways shared ARHGAP4 and ARHGAP9; module 2, GlycoProtein VI-mediated activation cascade pathway was enriched with RHOG; module 3, Thromboxane A2 receptor signaling, Chemokine signaling pathway, CXCR4-mediated signaling events pathways were enriched with LYN, the hub gene of module 3. Results of RT-PCR confirmed the finding of the bioinformatic analysis that ARHGAP4, ARHGAP9, RHOG and LYN were significantly upregulated in PCOS. RhoA-related pathways, GlycoProtein VI-mediated activation cascade pathway, ARHGAP4, ARHGAP9, RHOG and LYN may be involved in the pathogenesis of PCOS. PMID:28949383

Marshall Space Flight Center head development program

NASA Technical Reports Server (NTRS)

Harrer, Jim

1994-01-01

This report summarizes the results of the candidate head evaluation for the new long-life magnetic head per the SOW of Contract No. NAS8-39407, MSFC Head Development Program. The original program plans were to test a candidate head, fabricate a new head, then qualify the new head. These activities were scheduled to be carried out between March 1993 and March 1994. The program was halted after the evaluation of the candidate head by NAS8-39407 Amendment No. 4. MSFC has provided and authorized the use the MARS-2000 SRB QUAL Recorder PN 10400-0677-801 - Serial Number 200004 (Datatape PN 591000 - Serial Number 1004), Reproduce Amplifier Module (RAM) Datatape PN 533040 - Serial Number 2006, associated cables, and magnetic tape on special SRB/DFI tapered reels to Datatape for this program. All the testing that has been done for the candidate head evaluation was done at Datatape's facility in Pasadena,CA. The testing was performed in a Class 100,000 particle counts clean room at ambient temperature, except for the thermal testing which was conducted in a different area at Datatape. The Performance Verification Test Procedure PVT-11004-4 (PVT) and Acceptance Test Procedure ATP-11004-09 (ATP) procedures were used when tests were conducted on the recorder.

Boeing CST-100 Starliner Processing

NASA Image and Video Library

2018-04-26

Boeing’s CST-100 Pad Abort Test Vehicle is almost ready to head to White Sands, New Mexico, to test the launch abort engines. During that test, the four abort engines will prove that the vehicle can safely perform an abort maneuver in the event of an emergency on the launchpad or during flight. The vehicle is mated to the service module for a fit check, and then the two will be taken apart for final preparations before heading to the desert.

Radiotherapy after surgical resection for head and neck mucosal melanoma.

PubMed

Wu, Abraham J; Gomez, Jennifer; Zhung, Joanne E; Chan, Kelvin; Gomez, Daniel R; Wolden, Suzanne L; Zelefsky, Michael J; Wolchok, Jedd D; Carvajal, Richard D; Chapman, Paul B; Wong, Richard J; Shaha, Ashok R; Kraus, Dennis H; Shah, Jatin P; Lee, Nancy Y

2010-06-01

To present our single-institution experience with postoperative radiotherapy for mucosal melanoma of the head and neck. Between 1992 and 2007, 27 patients with mucosal melanoma of the head and neck underwent surgical resection followed by postoperative radiotherapy. Median age was 68 years (range: 45-89 years). Sites included were sinonasal in 24 patients, oral cavity in 2, and oropharynx in 1. All but 2 patients had stage I disease. Twenty-two patients received hypofractionated radiation. Radiation techniques were intensity-modulated radiation therapy in 13, 3-dimensional conformal in 4, and conventional in 10. The median follow-up for living patients was 45 months (range: 24-122 months). The 3- and 5-year estimates of local progression-free, loco-regional progression-free, distant metastasis-free, and overall survival were: 47% and 35%; 34% and 22%; 30% and 24%; and 40% and 33%, respectively. Median time to local failure and distant metastasis was 32 and 14 months, respectively. Acute toxicities included 19% with grade 2 or higher mucositis. No late complications related to the optic structures were seen. Modern radiotherapeutic techniques including intensity-modulated radiation therapy appear feasible and well-tolerated in the postoperative treatment of head and neck mucosal melanoma. Unusual or serious late complications have not been observed despite extensive use of hypofractionated regimens. However, rates of local and distant failure remain high.

Image-Based 3D Face Modeling System

NASA Astrophysics Data System (ADS)

Park, In Kyu; Zhang, Hui; Vezhnevets, Vladimir

2005-12-01

This paper describes an automatic system for 3D face modeling using frontal and profile images taken by an ordinary digital camera. The system consists of four subsystems including frontal feature detection, profile feature detection, shape deformation, and texture generation modules. The frontal and profile feature detection modules automatically extract the facial parts such as the eye, nose, mouth, and ear. The shape deformation module utilizes the detected features to deform the generic head mesh model such that the deformed model coincides with the detected features. A texture is created by combining the facial textures augmented from the input images and the synthesized texture and mapped onto the deformed generic head model. This paper provides a practical system for 3D face modeling, which is highly automated by aggregating, customizing, and optimizing a bunch of individual computer vision algorithms. The experimental results show a highly automated process of modeling, which is sufficiently robust to various imaging conditions. The whole model creation including all the optional manual corrections takes only 2[InlineEquation not available: see fulltext.]3 minutes.

Bitter Melon Reduces Head and Neck Squamous Cell Carcinoma Growth by Targeting c-Met Signaling

PubMed Central

Nerurkar, Pratibha; Gonzalez, Juan G.; Crawford, Susan; Varvares, Mark; Ray, Ratna B.

2013-01-01

Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC. PMID:24147107

Regional modulation of the response to glutathione in Hydra vulgaris.

PubMed

Pierobon, Paola

2015-07-01

In the presence of prey, or upon exposure to reduced glutathione (GSH), Hydra polyps open a mouth to ingest the captured prey and close it after feeding; at rest the mouth is not evident. In previous papers we have shown that GABA, glycine and NMDA modulate the mechanisms of mouth closure through ligand-gated-ion-channel receptors that are similar to their mammalian analogues in terms of biochemical and pharmacological properties. In order to study the regional distribution of these receptors, we have applied the GSH assay to polyps amputated at different levels of the body column. The response to 1-10 µmol l(-1) GSH of polyps lacking either peduncle and foot or the entire body columns (heads) was not different from control, whole animals. In the presence of GABA or muscimol, duration of the response was significantly decreased in heads; the decrease was suppressed by the GABA antagonists gabazine and bicuculline. By contrast, in animals lacking peduncle and foot, duration of the response did not vary upon GABA administration. Conversely, in the presence of glycine, duration of the response in heads preparations was similar to control, whereas in footless polyps, it was significantly reduced. The decrease was mimicked by the glycine agonists taurine and β-alanine, and counteracted by strychnine. These results suggest a regional distribution of receptors to GABA and glycine in the neuromuscular circuitry modulating the feeding behaviour. © 2015. Published by The Company of Biologists Ltd.

Modulation of NMDA and AMPA-Mediated Synaptic Transmission by CB1 Receptors in Frontal Cortical Pyramidal Cells

PubMed Central

Li, Qiang; Yan, Haidun; Wilson, Wilkie A.; Swartzwelder, H. Scott

2010-01-01

Although the endogenous cannabinoid system modulates a variety of physiological and pharmacological processes, the specific role of cannabinoid CB1 receptors in the modulation of glutamatergic neurotransmission and neural plasticity is not well understood. Using whole-cell patch clamp recording techniques, evoked or spontaneous excitatory postsynaptic currents (eEPSCs or sEPSCs) were recorded from visualized, layer II/III pyramidal cells in frontal cortical slices from rat brain. Bath application of the CB1 receptor agonist, WIN 55212-2 (WIN), reduced the amplitude of NMDA receptor-mediated EPSCs in a concentration-dependent manner. When co-applied with the specific CB1 antagonists, AM251 or AM281, WIN did not suppress NMDA receptor mediated EPSCs. WIN also reduced the amplitude of evoked AMPA receptor-mediated EPSCs, an effect that was also reversed by AM251. Both the frequency and amplitude of spontaneous AMPA receptor-mediated EPSCs were significantly reduced by WIN. In contrast, WIN reduced the frequency, but not the amplitude of miniature EPSCs, suggesting that the suppression of glutmatergic activity by CB1 receptors in the frontal neocortex is mediated by a pre-synaptic mechanism. Taken together, these data indicate a critical role for endocannabinoid signaling in the regulation of excitatory synaptic transmission in frontal neocortex, and suggest a possible neuronal mechanism whereby THC regulates cortical function. PMID:20420813

Long non-coding RNA UCA1/miR-182/PFKFB2 axis modulates glioblastoma-associated stromal cells-mediated glycolysis and invasion of glioma cells.

PubMed

He, Zongze; You, Chao; Zhao, Dongdong

2018-06-07

Glioblastoma (GB) is the most common and deadliest malignant primary brain tumor with a high recurrence. In this study, lncRNA UCA1/miR-182 axis has been regarded as a nodal driver of glioma invasion mediated by GB-associated stromal cells (GASCs) and GASC-secreted chemokine CXCL14. In clinical specimens, CXCL14 upregulation in GASCs also correlated with poor prognosis. Notably, CXCL14-high GASCs mediated lncRNA UCA1 upregulation and miR-182 downregulation in glioma cells. Moreover, miR-182 directly bound to the fructose-2,6-biphosphatase PFKFB2; UCA1/miR-182 axis thereby modulated GASC-induced glycolysis in glioma cells. Overall, UCA1/miR-182/PFKFB2 axis modulates chemokine CXCL14 secretion, glycolysis and invasion of glioma cells in GASCs. Copyright © 2018 Elsevier Inc. All rights reserved.

Actin-Based Adhesion Modules Mediate Cell Interactions with the Extracellular Matrix and Neighboring Cells.

PubMed

Bachir, Alexia I; Horwitz, Alan Rick; Nelson, W James; Bianchini, Julie M

2017-07-05

Cell adhesions link cells to the extracellular matrix (ECM) and to each other and depend on interactions with the actin cytoskeleton. Both cell-ECM and cell-cell adhesion sites contain discrete, yet overlapping, functional modules. These modules establish physical associations with the actin cytoskeleton, locally modulate actin organization and dynamics, and trigger intracellular signaling pathways. Interplay between these modules generates distinct actin architectures that underlie different stages, types, and functions of cell-ECM and cell-cell adhesions. Actomyosin contractility is required to generate mature, stable adhesions, as well as to sense and translate the mechanical properties of the cellular environment into changes in cell organization and behavior. Here, we review the organization and function of different adhesion modules and how they interact with the actin cytoskeleton. We highlight the molecular mechanisms of mechanotransduction in adhesions and how adhesion molecules mediate cross talk between cell-ECM and cell-cell adhesion sites. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Firing properties of rat lateral mammillary single units: head direction, head pitch, and angular head velocity.

PubMed

Stackman, R W; Taube, J S

1998-11-01

Many neurons in the rat anterodorsal thalamus (ADN) and postsubiculum (PoS) fire selectively when the rat points its head in a specific direction in the horizontal plane, independent of the animal's location and ongoing behavior. The lateral mammillary nuclei (LMN) are interconnected with both the ADN and PoS and, therefore, are in a pivotal position to influence ADN/PoS neurophysiology. To further understand how the head direction (HD) cell signal is generated, we recorded single neurons from the LMN of freely moving rats. The majority of cells discharged as a function of one of three types of spatial correlates: (1) directional heading, (2) head pitch, or (3) angular head velocity (AHV). LMN HD cells exhibited higher peak firing rates and greater range of directional firing than that of ADN and PoS HD cells. LMN HD cells were modulated by angular head velocity, turning direction, and anticipated the rat's future HD by a greater amount of time (approximately 95 msec) than that previously reported for ADN HD cells (approximately 25 msec). Most head pitch cells discharged when the rostrocaudal axis of the rat's head was orthogonal to the horizontal plane. Head pitch cell firing was independent of the rat's location, directional heading, and its body orientation (i.e., the cell discharged whenever the rat pointed its head up, whether standing on all four limbs or rearing). AHV cells were categorized as fast or slow AHV cells depending on whether their firing rate increased or decreased in proportion to angular head velocity. These data demonstrate that LMN neurons code direction and angular motion of the head in both horizontal and vertical planes and support the hypothesis that the LMN play an important role in processing both egocentric and allocentric spatial information.

Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks.

PubMed

Hojo, Yasushi; Munetomo, Arisa; Mukai, Hideo; Ikeda, Muneki; Sato, Rei; Hatanaka, Yusuke; Murakami, Gen; Komatsuzaki, Yoshimasa; Kimoto, Tetsuya; Kawato, Suguru

2015-08-01

This article is part of a Special Issue "Estradiol and cognition". Estradiol (E2) is locally synthesized within the hippocampus and the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. The molecular mechanisms of modulation through the synaptic estrogen receptor (ER) and its downstream signaling, however, are largely unknown in the dentate gyrus (DG). We investigated the E2-induced modulation of dendritic spines in male adult rat hippocampal slices by imaging Lucifer Yellow-injected DG granule cells. Treatments with 1 nM E2 increased the density of spines by approximately 1.4-fold within 2h. Spine head diameter analysis showed that the density of middle-head spines (0.4-0.5 μm) was significantly increased. The E2-induced spine density increase was suppressed by blocking Erk MAPK, PKA, PKC and LIMK. These suppressive effects by kinase inhibitors are not non-specific ones because the GSK-3β antagonist did not inhibit E2-induced spine increase. The ER antagonist ICI 182,780 also blocked the E2-induced spine increase. Taken together, these results suggest that E2 rapidly increases the density of spines through kinase networks that are driven by synaptic ER. Copyright © 2015 Elsevier Inc. All rights reserved.

Automatic exposure control in CT: the effect of patient size, anatomical region and prescribed modulation strength on tube current and image quality.

PubMed

Papadakis, Antonios E; Perisinakis, Kostas; Damilakis, John

2014-10-01

To study the effect of patient size, body region and modulation strength on tube current and image quality on CT examinations that use automatic tube current modulation (ATCM). Ten physical anthropomorphic phantoms that simulate an individual as neonate, 1-, 5-, 10-year-old and adult at various body habitus were employed. CT acquisition of head, neck, thorax and abdomen/pelvis was performed with ATCM activated at weak, average and strong modulation strength. The mean modulated mAs (mAsmod) values were recorded. Image noise was measured at selected anatomical sites. The mAsmod recorded for neonate compared to 10-year-old increased by 30 %, 14 %, 6 % and 53 % for head, neck, thorax and abdomen/pelvis, respectively, (P < 0.05). The mAsmod was lower than the preselected mAs with the exception of the 10-year-old phantom. In paediatric and adult phantoms, the mAsmod ranged from 44 and 53 for weak to 117 and 93 for strong modulation strength, respectively. At the same exposure parameters image noise increased with body size (P < 0.05). The ATCM system studied here may affect dose differently for different patient habitus. Dose may decrease for overweight adults but increase for children older than 5 years old. Care should be taken when implementing ATCM protocols to ensure that image quality is maintained. • ATCM efficiency is related to the size of the patient's body. • ATCM should be activated without caution in overweight adult individuals. • ATCM may increase radiation dose in children older than 5 years old. • ATCM efficiency depends on the protocol selected for a specific anatomical region. • Modulation strength may be appropriately tuned to enhance ATCM efficiency.

Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction.

PubMed

Arshad, Q; Roberts, R E; Ahmad, H; Lobo, R; Patel, M; Ham, T; Sharp, D J; Seemungal, B M

2017-04-01

We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted. We report the results of a retrospective analysis of both the comprehensive clinical and vestibular laboratory testing of 20 consecutive THI patients with prominent and persisting vestibular symptoms still present at least 6months post THI. Individual THI patients typically had multiple vestibular diagnoses and unique to this group of vestibular patients, often displayed both peripheral and central vestibular dysfunction. Despite expert neuro-otological management, at two years 20% of patients still had persisting vestibular symptoms. In summary, chronic vestibular dysfunction in THI could relate to: (i) the presence of multiple vestibular diagnoses, increasing the risk of 'missed' vestibular diagnoses leading to persisting symptoms; (ii) the impact of brain trauma which may impair brain plasticity mediated repair mechanisms. Apart from alerting physicians to the potential for multiple vestibular diagnoses in THI, future work to identify the specific deficits in brain function mediating poor recovery from post-THI vestibular dysfunction could provide the rationale for developing new therapy for head injury patients whose vestibular symptoms are resistant to treatment. Copyright © 2017. Published by Elsevier B.V.

Transformational leadership and safety performance among nurses: the mediating role of knowledge-related job characteristics.

PubMed

Lievens, Ilse; Vlerick, Peter

2014-03-01

To report the impact of transformational leadership on two dimensions of nurses' safety performance (i.e. safety compliance and safety participation) and to study the mediating role of knowledge-related job characteristics in this relationship. Safety performance refers to the behaviours that employees exhibit to adhere to safety guidelines and to promote health and safety at their workplace. Nurses' safety performance is a major challenge for healthcare settings, urging the need to identify the key determinants and psychological mechanisms that influence it. A cross-sectional survey study. The study was carried out in September 2010 in a large Belgian hospital. We used self-administered questionnaires; 152 nurses participated. The hypotheses were tested using hierarchical regression analyses. In line with our first hypothesis, the results show that transformational leadership exerted a significant positive impact on both dimensions of nurses' safety performance. This positive relation was mediated by knowledge-related job characteristics, supporting our second hypothesis. Head nurses' transformational leadership can enhance nurses' compliance with and participation in safety. Furthermore, transformational head nurses are able to influence the perception that their nurses have about the kind and amount of knowledge in their job, which can also lead to increases in both dimensions of nurses' safety performance. This study therefore demonstrates the key impact that transformational head nurses have, both directly and indirectly, on the safety performance of their nurses. © 2013 John Wiley & Sons Ltd.

CT dose modulation using automatic exposure control in whole-body PET/CT: effects of scout imaging direction and arm positioning.

PubMed

Inoue, Yusuke; Nagahara, Kazunori; Kudo, Hiroko; Itoh, Hiroyasu

2018-01-01

Automatic exposure control (AEC) modulates tube current and consequently X-ray exposure in CT. We investigated the behavior of AEC systems in whole-body PET/CT. CT images of a whole-body phantom were acquired using AEC on two scanners from different manufactures. The effects of scout imaging direction and arm positioning on dose modulation were evaluated. Image noise was assessed in the chest and upper abdomen. On one scanner, AEC using two scout images in the posteroanterior (PA) and lateral (Lat) directions provided relatively constant image noise along the z-axis with the arms at the sides. Raising the arms increased tube current in the head and neck and decreased it in the body trunk. Image noise increased in the upper abdomen, suggesting excessive reduction in radiation exposure. AEC using the PA scout alone strikingly increased tube current and reduced image noise in the shoulder. Raising the arms did not substantially influence dose modulation and decreased noise in the abdomen. On the other scanner, AEC using the PA scout alone or Lat scout alone resulted in similar dose modulation. Raising the arms increased tube current in the head and neck and decreased it in the trunk. Image noise was higher in the upper abdomen than in the middle and lower chest, and was not influenced by arm positioning. CT dose modulation using AEC may vary greatly depending on scout direction. Raising the arms tended to decrease radiation exposure; however, the effect depends on scout direction and the AEC system.

WHSC1L1-mediated EGFR mono-methylation enhances the cytoplasmic and nuclear oncogenic activity of EGFR in head and neck cancer

PubMed Central

Saloura, Vassiliki; Vougiouklakis, Theodore; Zewde, Makda; Deng, Xiaolan; Kiyotani, Kazuma; Park, Jae-Hyun; Matsuo, Yo; Lingen, Mark; Suzuki, Takehiro; Dohmae, Naoshi; Hamamoto, Ryuji; Nakamura, Yusuke

2017-01-01

While multiple post-translational modifications have been reported to regulate the function of epidermal growth factor receptor (EGFR), the effect of protein methylation on its function has not been well characterized. In this study, we show that WHSC1L1 mono-methylates lysine 721 in the tyrosine kinase domain of EGFR, and that this methylation leads to enhanced activation of its downstream ERK cascade without EGF stimulation. We also show that EGFR K721 mono-methylation not only affects the function of cytoplasmic EGFR, but also that of nuclear EGFR. WHSC1L1-mediated methylation of EGFR in the nucleus enhanced its interaction with PCNA in squamous cell carcinoma of the head and neck (SCCHN) cells and resulted in enhanced DNA synthesis and cell cycle progression. Overall, our study demonstrates the multifaceted oncogenic function of the protein lysine methyltransferase WHSC1L1 in SCCHN, which is mediated through direct non-histone methylation of the EGFR protein with effects both in its cytoplasmic and nuclear functions. PMID:28102297

A Step Towards Developing Adaptive Robot-Mediated Intervention Architecture (ARIA) for Children With Autism

PubMed Central

Bekele, Esubalew T; Lahiri, Uttama; Swanson, Amy R.; Crittendon, Julie A.; Warren, Zachary E.; Sarkar, Nilanjan

2013-01-01

Emerging technology, especially robotic technology, has been shown to be appealing to children with autism spectrum disorders (ASD). Such interest may be leveraged to provide repeatable, accurate and individualized intervention services to young children with ASD based on quantitative metrics. However, existing robot-mediated systems tend to have limited adaptive capability that may impact individualization. Our current work seeks to bridge this gap by developing an adaptive and individualized robot-mediated technology for children with ASD. The system is composed of a humanoid robot with its vision augmented by a network of cameras for real-time head tracking using a distributed architecture. Based on the cues from the child’s head movement, the robot intelligently adapts itself in an individualized manner to generate prompts and reinforcements with potential to promote skills in the ASD core deficit area of early social orienting. The system was validated for feasibility, accuracy, and performance. Results from a pilot usability study involving six children with ASD and a control group of six typically developing (TD) children are presented. PMID:23221831

A key role for foxQ2 in anterior head and central brain patterning in insects

PubMed Central

Kitzmann, Peter; Weißkopf, Matthias; Schacht, Magdalena Ines

2017-01-01

ABSTRACT Anterior patterning of animals is based on a set of highly conserved transcription factors but the interactions within the protostome anterior gene regulatory network (aGRN) remain enigmatic. Here, we identify the red flour beetle Tribolium castaneum ortholog of foxQ2 (Tc-foxQ2) as a novel upstream component of the aGRN. It is required for the development of the labrum and higher order brain structures, namely the central complex and the mushroom bodies. We reveal Tc-foxQ2 interactions by RNAi and heat shock-mediated misexpression. Surprisingly, Tc-foxQ2 and Tc-six3 mutually activate each other, forming a novel regulatory module at the top of the aGRN. Comparisons of our results with those of sea urchins and cnidarians suggest that foxQ2 has acquired more upstream functions in the aGRN during protostome evolution. Our findings expand the knowledge on foxQ2 gene function to include essential roles in epidermal development and central brain patterning. PMID:28811313

Vergence-mediated changes in the axis of eye rotation during the human vestibulo-ocular reflex can occur independent of eye position.

PubMed

Migliaccio, Americo A; Cremer, Phillip D; Aw, Swee T; Halmagyi, G Michael; Curthoys, Ian S; Minor, Lloyd B; Todd, Michael J

2003-07-01

The aim of this study was to determine whether vergence-mediated changes in the axis of eye rotation in the human vestibulo-ocular reflex (VOR) would obey Listing's Law (normally associated with saccadic eye movements) independent of the initial eye position. We devised a paradigm for disassociating the saccadic velocity axis from eye position by presenting near and far targets that were centered with respect to one eye. We measured binocular 3-dimensional eye movements using search coils in ten normal subjects and 3-dimensional linear head acceleration using Optotrak in seven normal subjects. The stimuli consisted of passive, unpredictable, pitch head rotations with peak acceleration of approximately 2000 degrees /s(2 )and amplitude of approximately 20 degrees. During the pitch head rotation, each subject fixated straight ahead with one eye, whereas the other eye was adducted 4 degrees during far viewing (94 cm) and 25 degrees during near viewing (15 cm). Our data showed expected compensatory pitch rotations in both eyes, and a vergence-mediated horizontal rotation only in the adducting eye. In addition, during near viewing we observed torsional eye rotations not only in the adducting eye but also in the eye looking straight ahead. In the straight-ahead eye, the change in torsional eye velocity between near and far viewing, which began approximately 40 ms after the start of head rotation, was 10+/-6 degrees /s (mean +/- SD). This change in torsional eye velocity resulted in a 2.4+/-1.5 degrees axis tilt toward Listing's plane in that eye. In the adducting eye, the change in torsional eye velocity between near and far viewing was 16+/-6 degrees /s (mean +/- SD) and resulted in a 4.1+/-1.4 degrees axis tilt. The torsional eye velocities were conjugate and both eyes partially obeyed Listing's Law. The axis of eye rotation tilted in the direction of the line of sight by approximately one-third of the angle between the line of sight and a line orthogonal to Listing's plane. This tilt was higher than predicted by the one-quarter rule. The translational acceleration component of the pitch head rotation measured 0.5 g and may have contributed to the increased torsional component observed during near viewing. Our data show that vergence-mediated eye movements obey a VOR/Listing's Law compromise strategy independent of the initial eye position.

A new perspective on how humans assess their surroundings; derivation of head orientation and its role in ‘framing’ the environment

PubMed Central

Wilson, Gwendoline Ixia; Holton, Mark D.; Walker, James; Jones, Mark W.; Grundy, Ed; Davies, Ian M.; Clarke, David; Luckman, Adrian; Russill, Nick; Wilson, Vianney; Plummer, Rosie

2015-01-01

Understanding the way humans inform themselves about their environment is pivotal in helping explain our susceptibility to stimuli and how this modulates behaviour and movement patterns. We present a new device, the Human Interfaced Personal Observation Platform (HIPOP), which is a head-mounted (typically on a hat) unit that logs magnetometry and accelerometry data at high rates and, following appropriate calibration, can be used to determine the heading and pitch of the wearer’s head. We used this device on participants visiting a botanical garden and noted that although head pitch ranged between −80° and 60°, 25% confidence limits were restricted to an arc of about 25° with a tendency for the head to be pitched down (mean head pitch ranged between −43° and 0°). Mean rates of change of head pitch varied between −0.00187°/0.1 s and 0.00187°/0.1 s, markedly slower than rates of change of head heading which varied between −0.3141°/0.1 s and 0.01263°/0.1 s although frequency distributions of both parameters showed them to be symmetrical and monomodal. Overall, there was considerable variation in both head pitch and head heading, which highlighted the role that head orientation might play in exposing people to certain features of the environment. Thus, when used in tandem with accurate position-determining systems, the HIPOP can be used to determine how the head is orientated relative to gravity and geographic North and in relation to geographic position, presenting data on how the environment is being ‘framed’ by people in relation to environmental content. PMID:26157643

Implications of Mediated Instruction to Remote Learning in Mathematics.

ERIC Educational Resources Information Center

Matthews-Lopez, Joy L.; Lopez-Permouth, Sergio R.; Keck, David

Mediated learning utilizes multimedia-based instructional modules to provide students with individualized access to information in alignment with their individual learning styles (Kinser, Morris, & Hewitt). In contrast with traditional pedagogy, the mission of the instructor in a mediated learning environment is to facilitate learning rather than…

Development of a Flyable Acousto-Optic Laser Beam Deflection System for a Head Up Display of the Future.

DTIC Science & Technology

Rayleigh criteria). The system was designed for stroke writing but was demonstrated with lissajous writing. The acousto - optic deflectors employed...The report describes a laser display which is to be used in a Head-Up Display of the future. The uniqueness of the display is that it uses acousto ... optic components for the modulation and deflection of the laser beam. As a result, there are no moving parts, which increases the reliability and life

Lock and Dam Number 8 Hydropower Study; Mississippi River Near LaCrosse, Wisconsin. Supplement.

DTIC Science & Technology

1985-01-01

unit used in scheme 3 is a standardized module consisting of an axial flow turbine , a speed increasing gear set, and a generator combined in a short...the flow and generating head ranges associated with specific turbine generator sizes, the program produces annual and monthly flow -duration curves and...open flume turbine passing a rated flow of 14O0 eta at a rated head of 9.75 feat. Cost estimates were made for two and four unit plants having

Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses.

PubMed

Chiurchiù, Valerio; Leuti, Alessandro; Dalli, Jesmond; Jacobsson, Anders; Battistini, Luca; Maccarrone, Mauro; Serhan, Charles N

2016-08-24

Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naïve CD4(+) T cell differentiation into TH1 and TH17 by down-regulating their signature transcription factors, T-bet and Rorc, in a mechanism mediated by the GPR32 and ALX/FPR2 receptors; they concomitantly enhanced de novo generation and function of Foxp3(+) regulatory T (Treg) cells via the GPR32 receptor. These results were also supported in vivo in a mouse deficient for DHA synthesis (Elovl2(-/-)) that showed an increase in TH1/TH17 cells and a decrease in Treg cells compared to wild-type mice. Additionally, either DHA supplementation in Elovl2(-/-) mice or in vivo administration of resolvin D1 significantly reduced cytokine production upon specific stimulation of T cells. These findings demonstrate actions of specific SPMs on adaptive immunity and provide a new avenue for SPM-based approaches to modulate chronic inflammation. Copyright © 2016, American Association for the Advancement of Science.

Folic acid-decorated polyamidoamine dendrimer mediates selective uptake and high expression of genes in head and neck cancer cells.

PubMed

Xu, Leyuan; Kittrell, Shannon; Yeudall, W Andrew; Yang, Hu

2016-11-01

Folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) was synthesized and studied for targeted delivery of genes to head and neck cancer cells expressing high levels of folate receptors (FRs). Cellular uptake, targeting specificity, cytocompatibility and transfection efficiency were evaluated. G4-FA competes with free FA for the same binding site. G4-FA facilitates the cellular uptake of DNA plasmids in a FR-dependent manner and selectively delivers plasmids to FR-high cells, leading to enhanced gene expression. G4-FA is a suitable vector to deliver genes selectively to head and neck cancer cells. The fundamental understandings of G4-FA as a vector and its encouraging transfection results for head and neck cancer cells provided support for its further testing in vivo.

MHC class I loci of the Bar-Headed goose (Anser indicus)

PubMed Central

2010-01-01

MHC class I proteins mediate functions in anti-pathogen defense. MHC diversity has already been investigated by many studies in model avian species, but here we chose the bar-headed goose, a worldwide migrant bird, as a non-model avian species. Sequences from exons encoding the peptide-binding region (PBR) of MHC class I molecules were isolated from liver genomic DNA, to investigate variation in these genes. These are the first MHC class I partial sequences of the bar-headed goose to be reported. A preliminary analysis suggests the presence of at least four MHC class I genes, which share great similarity with those of the goose and duck. A phylogenetic analysis of bar-headed goose, goose and duck MHC class I sequences using the NJ method supports the idea that they all cluster within the anseriforms clade. PMID:21637434

Two-photon microscopy and spectroscopy based on a compact confocal scanning head

NASA Astrophysics Data System (ADS)

Diaspro, Alberto; Chirico, Giberto; Federici, Federico; Cannone, Fabio; Beretta, Sabrina; Robello, Mauro; Olivini, Francesca; Ramoino, Paola

2001-07-01

We have combined a confocal laser scanning head modified for TPE (two-photon excitation) microscopy with some spectroscopic modules to study single molecules and molecular aggregates. The behavior of the TPE microscope unit has been characterized by means of point spread function measurements and of the demonstration of its micropatterning abilities. One-photon and two-photon mode can be simply accomplished by switching from a mono-mode optical fiber (one-photon) coupled to conventional laser sources to an optical module that allows IR laser beam (two- photon/TPE) delivery to the confocal laser scanning head. We have then described the characterization of the two-photon microscope for spectroscopic applications: fluorescence correlation, lifetime and fluorescence polarization anisotropy measurements. We describe the measurement of the response of the two-photon microscope to the light polarization and discuss fluorescence polarization anisotropy measurements on Rhodamine 6G as a function of the viscosity and on a globular protein, the Beta-lactoglobulin B labeled with Alexa 532 at very high dilutions. The average rotational and translational diffusion coefficients measured with fluorescence polarization anisotropy and fluorescence correlation methods are in good agreement with the protein size, therefore validating the use of the microscope for two-photon spectroscopy on biomolecules.

Beta receptor-mediated modulation of the late positive potential in humans.

PubMed

de Rover, Mischa; Brown, Stephen B R E; Boot, Nathalie; Hajcak, Greg; van Noorden, Martijn S; van der Wee, Nic J A; Nieuwenhuis, Sander

2012-02-01

Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has shown that the LPP reflects the modulation of activity in extrastriate visual cortical structures, but little is known about the source of that modulation. The present study investigated whether beta-adrenergic receptors are involved in the generation of the LPP. We used a genetic individual differences approach (experiment 1) and a pharmacological manipulation (experiment 2) to test the hypothesis that the LPP is modulated by the activation of β-adrenergic receptors. In experiment 1, we found that LPP amplitude depends on allelic variation in the β1-receptor gene polymorphism. In experiment 2, we found that LPP amplitude was modulated by the β-blocker propranolol in a direction dependent on subjects' level of trait anxiety: In participants with lower trait anxiety, propranolol led to a (nonsignificant) decrease in the LPP modulation; in participants with higher trait anxiety, propranolol increased the emotion-related LPP modulation. These results provide initial support for the hypothesis that the LPP reflects the downstream effects, in visual cortical areas, of β-receptor-mediated activation of the amygdala.

Renal intercalated cells and blood pressure regulation.

PubMed

Wall, Susan M

2017-12-01

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl - absorption and HCO 3 - secretion largely through pendrin-dependent Cl - /HCO 3 - exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO 3 administration. In some rodent models, pendrin-mediated HCO 3 - secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl - absorption, but also by modulating the aldosterone response for epithelial Na + channel (ENaC)-mediated Na + absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

Pathway and network-based analysis of genome-wide association studies and RT-PCR validation in polycystic ovary syndrome.

PubMed

Shen, Haoran; Liang, Zhou; Zheng, Saihua; Li, Xuelian

2017-11-01

The purpose of this study was to identify promising candidate genes and pathways in polycystic ovary syndrome (PCOS). Microarray dataset GSE345269 obtained from the Gene Expression Omnibus database includes 7 granulosa cell samples from PCOS patients, and 3 normal granulosa cell samples. Differentially expressed genes (DEGs) were screened between PCOS and normal samples. Pathway enrichment analysis was conducted for DEGs using ClueGO and CluePedia plugin of Cytoscape. A Reactome functional interaction (FI) network of the DEGs was built using ReactomeFIViz, and then network modules were extracted, followed by pathway enrichment analysis for the modules. Expression of DEGs in granulosa cell samples was measured using quantitative RT-PCR. A total of 674 DEGs were retained, which were significantly enriched with inflammation and immune-related pathways. Eight modules were extracted from the Reactome FI network. Pathway enrichment analysis revealed significant pathways of each module: module 0, Regulation of RhoA activity and Signaling by Rho GTPases pathways shared ARHGAP4 and ARHGAP9; module 2, GlycoProtein VI-mediated activation cascade pathway was enriched with RHOG; module 3, Thromboxane A2 receptor signaling, Chemokine signaling pathway, CXCR4-mediated signaling events pathways were enriched with LYN, the hub gene of module 3. Results of RT-PCR confirmed the finding of the bioinformatic analysis that ARHGAP4, ARHGAP9, RHOG and LYN were significantly upregulated in PCOS. RhoA-related pathways, GlycoProtein VI-mediated activation cascade pathway, ARHGAP4, ARHGAP9, RHOG and LYN may be involved in the pathogenesis of PCOS.

Calibration methods and tools for KM3NeT

NASA Astrophysics Data System (ADS)

Kulikovskiy, Vladimir

2016-04-01

The KM3NeT detectors, ARCA and ORCA, composed of several thousands digital optical modules, are in the process of their realization in the Mediterranean Sea. Each optical module contains 31 3-inch photomultipliers. Readout of the optical modules and other detector components is synchronized at the level of sub-nanoseconds. The position of the module is measured by acoustic piezo detectors inside the module and external acoustic emitters installed on the bottom of the sea. The orientation of the module is obtained with an internal attitude and heading reference system chip. Detector calibration, i.e. timing, positioning and sea-water properties, is overviewed in this talk and discussed in detail in this conference. Results of the procedure applied to the first detector unit ready for installation in the deep sea will be shown.

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

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

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

Usability study of the EduMod eLearning Program for contouring nodal stations of the head and neck.

PubMed

Deraniyagala, Rohan; Amdur, Robert J; Boyer, Arthur L; Kaylor, Scott

2015-01-01

A major strategy for improving radiation oncology education and competence evaluation is to develop eLearning programs that reproduce the real work environment. A valuable measure of the quality of an eLearning program is "usability," which is a multidimensional endpoint defined from the end user's perspective. The gold standard for measuring usability is the Software Usability Measurement Inventory (SUMI). The purpose of this study is to use the SUMI to measure usability of an eLearning course that uses innovative software to teach and test contouring of nodal stations of the head and neck. This is a prospective institutional review board-approved study in which all participants gave written informed consent. The study population was radiation oncology residents from 8 different programs across the United States. The subjects had to pass all sections of the same 2 eLearning modules and then complete the SUMI usability evaluation instrument. We reached the accrual goal of 25 participants. Usability results for the EduMod eLearning course, "Nodal Stations of the Head and Neck," were compared with a large database of scores of other major software programs. Results were evaluated in 5 domains: Affect, Helpfulness, Control, Learnability, and Global Usability. In all 5 domains, usability scores for the study modules were higher than the database mean and statistically superior in 4 domains. This is the first study to evaluate usability of an eLearning program related to radiation oncology. Usability of 2 representative modules related to contouring nodal stations of the head and neck was highly favorable, with scores that were superior to the industry standard in multiple domains. These results support the continued development of this type of eLearning program for teaching and testing radiation oncology technical skills. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Relative plan robustness of step-and-shoot vs rotational intensity–modulated radiotherapy on repeat computed tomographic simulation for weight loss in head and neck cancer

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

Thomson, David J.; The University of Manchester, Manchester Academic Health Science Centre, Institute of Cancer Sciences, Manchester; Beasley, William J.

Introduction: Interfractional anatomical alterations may have a differential effect on the dose delivered by step-and-shoot intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). The increased degrees of freedom afforded by rotational delivery may increase plan robustness (measured by change in target volume coverage and doses to organs at risk [OARs]). However, this has not been evaluated for head and neck cancer. Materials and methods: A total of 10 patients who required repeat computed tomography (CT) simulation and replanning during head and neck IMRT were included. Step-and-shoot IMRT and VMAT plans were generated from the original planning scan. The initial andmore » second CT simulation scans were fused and targets/OAR contours transferred, reviewed, and modified. The plans were applied to the second CT scan and doses recalculated without repeat optimization. Differences between step-and-shoot IMRT and VMAT for change in target volume coverage and doses to OARs between first and second CT scans were compared by Wilcoxon signed rank test. Results: There were clinically relevant dosimetric changes between the first and the second CT scans for both the techniques (reduction in mean D{sub 95%} for PTV2 and PTV3, D{sub min} for CTV2 and CTV3, and increased mean doses to the parotid glands). However, there were no significant differences between step-and-shoot IMRT and VMAT for change in any target coverage parameter (including D{sub 95%} for PTV2 and PTV3 and D{sub min} for CTV2 and CTV3) or dose to any OARs (including parotid glands) between the first and the second CT scans. Conclusions: For patients with head and neck cancer who required replanning mainly due to weight loss, there were no significant differences in plan robustness between step-and-shoot IMRT and VMAT. This information is useful with increased clinical adoption of VMAT.« less

Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

PubMed

Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

2015-03-01

A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Pyrrolo-dC Metal-Mediated Base Pairs in the Reverse Watson-Crick Double Helix: Enhanced Stability of Parallel DNA and Impact of 6-Pyridinyl Residues on Fluorescence and Silver-Ion Binding.

PubMed

Yang, Haozhe; Mei, Hui; Seela, Frank

2015-07-06

Reverse Watson-Crick DNA with parallel-strand orientation (ps DNA) has been constructed. Pyrrolo-dC (PyrdC) nucleosides with phenyl and pyridinyl residues linked to the 6 position of the pyrrolo[2,3-d]pyrimidine base have been incorporated in 12- and 25-mer oligonucleotide duplexes and utilized as silver-ion binding sites. Thermal-stability studies on the parallel DNA strands demonstrated extremely strong silver-ion binding and strongly enhanced duplex stability. Stoichiometric UV and fluorescence titration experiments verified that a single (2py) PyrdC-(2py) PyrdC pair captures two silver ions in ps DNA. A structure for the PyrdC silver-ion base pair that aligns 7-deazapurine bases head-to-tail instead of head-to-head, as suggested for canonical DNA, is proposed. The silver DNA double helix represents the first example of a ps DNA structure built up of bidentate and tridentate reverse Watson-Crick base pairs stabilized by a dinuclear silver-mediated PyrdC pair. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-motion perception and vestibulo-ocular reflex during whole body yaw rotation in standing subjects: the role of head position and neck proprioception.

PubMed

Panichi, Roberto; Botti, Fabio Massimo; Ferraresi, Aldo; Faralli, Mario; Kyriakareli, Artemis; Schieppati, Marco; Pettorossi, Vito Enrico

2011-04-01

Self-motion perception and vestibulo-ocular reflex (VOR) were studied during whole body yaw rotation in the dark at different static head positions. Rotations consisted of four cycles of symmetric sinusoidal and asymmetric oscillations. Self-motion perception was evaluated by measuring the ability of subjects to manually track a static remembered target. VOR was recorded separately and the slow phase eye position (SPEP) was computed. Three different head static yaw deviations (active and passive) relative to the trunk (0°, 45° to right and 45° to left) were examined. Active head deviations had a significant effect during asymmetric oscillation: the movement perception was enhanced when the head was kept turned toward the side of body rotation and decreased in the opposite direction. Conversely, passive head deviations had no effect on movement perception. Further, vibration (100 Hz) of the neck muscles splenius capitis and sternocleidomastoideus remarkably influenced perceived rotation during asymmetric oscillation. On the other hand, SPEP of VOR was modulated by active head deviation, but was not influenced by neck muscle vibration. Through its effects on motion perception and reflex gain, head position improved gaze stability and enhanced self-motion perception in the direction of the head deviation. Copyright © 2010 Elsevier B.V. All rights reserved.

The effects of elevated endogenous GABA levels on movement-related network oscillations.

PubMed

Muthukumaraswamy, S D; Myers, J F M; Wilson, S J; Nutt, D J; Lingford-Hughes, A; Singh, K D; Hamandi, K

2013-02-01

The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation-inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15-30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60-90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated. Copyright © 2012 Elsevier Inc. All rights reserved.

Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation of β-catenin.

PubMed

Shin, Yoo Seob; Kang, Sung Un; Park, Ju Kyeong; Kim, Yang Eun; Kim, Yeon Soo; Baek, Seung Joon; Lee, Seong-Ho; Kim, Chul-Ho

2016-11-15

Aberrant expression of β-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of β-catenin. In vitro effects of EGCG on the transcription, translation, or degradation of β-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and β-catenin expression was checked in HNC patients' samples. β-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of β-catenin signaling. Knockdown of β-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of β-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of β-catenin. The suppression of β-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits β-catenin expression through multiple mechanisms including decreased transcription and increased ubiquitin-mediated 26S proteasomal degradation. This study proposes a novel molecular rationale for antitumor activities of green tea in HNCs. Copyright © 2016 Elsevier GmbH. All rights reserved.

Summary report of mission acceleration measurements for Spacehab-01, STS-57 launched 21 June 1993

NASA Technical Reports Server (NTRS)

Finley, Brian; Grodsinsky, Carlos; Delombard, Richard

1994-01-01

The maiden voyage of the commercial Spacehab laboratory module onboard the STS-57 mission was integrated with several accelerometer packages, one of which was the Space Acceleration Measurement System (SAMS). The June 21st 1993, launch was the seventh successful mission for the Office of Life and Microgravity Sciences and Application's (OLMSA) SAMS unit. This flight was also complemented by a second accelerometer system. The Three Dimensional Microgravity Accelerometer (3-DMA), a Code C funded acceleration measurement system, offering an on-orbit residual calibration as a reference for the unit's four triaxial accelerometers. The SAMS accelerometer unit utilized three remote triaxial sensor heads mounted on the forward Spacehab module bulkhead and on one centrally located experiment locker door. These triaxial heads had filter cut-offs set to 5, 50, and 1000 Hz. The mission also included other experiment specific accelerometer packages in various locations.

Human vertical eye movement responses to earth horizontal pitch

NASA Technical Reports Server (NTRS)

Wall, C. 3rd; Petropoulos, A. E.

1993-01-01

The vertical eye movements in humans produced in response to head-over-heels constant velocity pitch rotation about a horizontal axis resemble those from other species. At 60 degrees/s these are persistent and tend to have non-reversing slow components that are compensatory to the direction of rotation. In most, but not all subjects, the slow component velocity was well characterized by a rapid build-up followed by an exponential decay to a non-zero baseline. Super-imposed was a cyclic or modulation component whose frequency corresponded to the time for one revolution and whose maximum amplitude occurred during a specific head orientation. All response components (exponential decay, baseline and modulation) were larger during pitch backward compared to pitch forward runs. Decay time constants were shorter during the backward runs, thus, unlike left to right yaw axis rotation, pitch responses display significant asymmetries between paired forward and backward runs.

The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells

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

Dowejko, Albert, E-mail: Albert.Dowejko@klinik.uni-regensburg.de; Bauer, Richard; Bauer, Karin

2012-03-10

There is a growing evidence that the human homologue of the Drosophila headcase (HECA) plays an important role in human carcinogenesis. So far specific protein interaction partners and affected signaling pathways of HECA are still elusive. In a recent study we showed that HECA overexpression in oral squamous-cell carcinoma (OSCC) keratinocytes has tumor suppressive effects resulting in a recuperation of cell cycle control concerning the entry and progression of S-phase, G2- and M-phase. Currently, quantitative RT-PCR and immunohistochemical analysis of primary tumor tissue from OSCC patients demonstrate that HECA expression is markedly decreased compared to normal control patients with abundantmore » HECA expression. Additionally, there is nearly no HECA expression in OSCC metastases. Here, we show that HECA expression is negatively controlled by the Wnt-pathway and TCF4, a Wnt related transcription factor, binds to the HECA promoter. Furthermore, immunocytochemistry reveals colocalization of HECA with the cyclin dependent kinase CDK9. Immunoprecipitation experiments and proximity ligation assays further reveal an interaction of HECA with CDK2, CDK9, Cyclin A and Cyclin K, a direct transcriptional target of the p53 tumor suppressor. Silencing HECA in OSCC cell lines leads to a significant increase of cell division and a markedly increased resistance against the chemotherapeutic cisplatin. On the contrary, HECA overexpressing OSCC cell lines show decreased resistance of OSCC cells against cisplatin. Therefore, HECA could be considered as future therapeutic agent against Wnt-dependent tumor progression. -- Highlights: Black-Right-Pointing-Pointer HECA is a new cell cycle regulator with anti-tumor features in head and neck cancer. Black-Right-Pointing-Pointer During tumor progression HECA mRNA and protein expression decrease. Black-Right-Pointing-Pointer The HECA promotor is a direct target of the Wnt/beta-catenin/TCF-pathway. Black-Right-Pointing-Pointer The HECA protein antagonizes Wnt-mediated cell proliferation through interaction with major cell cycle factors. Black-Right-Pointing-Pointer Modulating HECA level confers benefits for engaging tumor cells with cisplatin.« less

GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986.

PubMed

Gupta, S K; Mishra, R; Kusum, S; Spedding, M; Meiri, K F; Gressens, P; Mani, S

2009-04-01

Positive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators include benzamide compounds that allosterically modulate AMPA glutamate receptors. These small molecules that cross the blood-brain barrier have been shown to act as a neuroprotectant by increasing the levels of endogenous brain-derived neurotrophic factor (BDNF). Positive AMPA receptor modulators have also been shown to increase the levels of growth-associated protein-43 (GAP-43). GAP-43 plays a major role in many aspects of neuronal function in vertebrates. The goal of this study was to determine whether GAP-43 was important in mediating the actions of positive AMPA receptor modulator (S18986) and BDNF. Using cortical cultures from GAP-43 knockout and control mice, we show that (1) GAP-43 is upregulated in response to S18986 and BDNF in control cultures; (2) this upregulation of GAP-43 is essential for mediating the neuroprotective effects of S18986 and BDNF; (3) administration of S18986 and BDNF leads to an increase in the expression of the glutamate transporters GLT-1 and GLAST that are key to limiting excitotoxic cell death and this increase in GLT-1 and GLAST expression is completely blocked in the absence of GAP-43. Taken together this study concludes that GAP-43 is an important mediator of the neurotrophic effects of S18986 and BDNF on neuronal survival and plasticity, and is essential for the success of positive AMPA receptor modulator-BDNF-based neurotrophin therapy.

Behavioral effects of β-phenylethylamine and various monomethylated and monohalogenated analogs in mice are mediated by catecholaminergic mechanisms.

PubMed

Mosnaim, Aron D; Hudzik, Thomas; Wolf, Marion E

2015-01-01

The effects of the administration [intraperitoneally, 15 and 75 mg/kg, except α-MePEA (amphetamine, AMPH) at 5 and 10 mg/kg] of β-phenylethylamine (PEA), its methylated (o-Me-, p-Me-, α-Me-, β-Me-, N-Me-, p-OMe-, N,N-di-Me-, and 3,4-diOH-N-Me-), para-halogenated (Br-, Cl-, F-, and I-), and other derivatives for example, p-OHPEA (p-tyramine), on Swiss male albino mice caged behavior fall into 3 broad categories. (1) N,N-diMe-, 3,4-diOH-N-Me-, and o-MePEA tend to reduce the behavioral activity, (2) p-OH and p-IPEA were without noticeable effects, and (3) the remaining compounds increased locomotor activity, produced hyperexcitability and fighting, jumping and vocalization, and convulsion in a graded manner (listed in increasing order p-OMe-, β-Me-, p-Cl-, p-Br-, p-F-, p-Me-, and N-MePEA, PEA itself and α-MePEA). The latter compound (amphetamine) being the most potent among them; equieffective but with lower potency were p-MePEA, N-MePEA, and PEA itself. The effects of PEAs upon group cage behavior were increased by pretreatment with pargyline (1.5 hours; 15 mg/kg) and decreased after reserpine or haloperidol [4 hours and/or 24 hours (2.5 and/or 2.5 mg/kg) and 1 hour (1 mg/kg), respectively], reaching full suppression with the double-dose regimen of reserpine and single dose of haloperidol. As expected, none of these substances by themselves were noticeable changed group mice activity or stereotypic behavior. The effects of test amines and catecholamine-modulating agents on stereotypy were assessed by rating the sequentially occurring behaviors: increased exploratory behavior with increased sniffing; occasional side-to-side head weaving; paw-licking and other grooming; gnawing, fighting and continuous side-to-side head weaving, and periodic episodes of "popcorn" behavior, during which all mice in the cage ran, jumped, and vocalized. In general, rank efficacy in eliciting stereotype aligned with rank efficacy in affecting group cage behavior. Our results show that a number of as yet little studied monomethylated and monohalogenated PEA analogs share a similar behavioral profile with PEA and AMPH. Behavioral changes observed appear to be, at least in part, mediated by catecholaminergic mechanism as they are modulated by drugs known to influence catecholamine activity. PEA analogs provide a large number of clinically useful drugs; whether further studies on these novel amines will lead to the rational design of newer, safer, and effective PEA-class drugs remains to be seen.

Myeloid-derived suppressor cells modulate B-cell responses.

PubMed

Lelis, Felipe J N; Jaufmann, Jennifer; Singh, Anurag; Fromm, Katja; Teschner, Annkathrin Chiara; Pöschel, Simone; Schäfer, Iris; Beer-Hammer, Sandra; Rieber, Nikolaus; Hartl, Dominik

2017-08-01

Myeloid-derived suppressor cells (MDSCs) are key regulators of adaptive immunity by suppressing T-cell functions. However, their potential action on or interaction with B cells remained poorly understood. Here we demonstrate that human polymorphonuclear MDSCs differentially modulate B-cell function by suppressing B-cell proliferation and antibody production. We further demonstrate that this MDSC-mediated effect is cell contact dependent and involves established mediators such as arginase-1, nitric oxide (NO), reactive oxygen species (ROS) as well as B-cell death. Collectively, our studies provide novel evidence that human MDSCs modulate B cells, which could have future implications for immunotherapy approaches. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor

PubMed Central

Anandhakumar, Jayamani; Moustafa, Yara W.; Chowdhary, Surabhi; Kainth, Amoldeep S.

2016-01-01

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the “anchor away” (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. PMID:27185874

Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Beckham, Jean C; Vujanovic, Anka A; Schmidt, Norman B

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association.

Trauma Exposure and Cigarette Smoking: The Impact of Negative Affect and Affect-Regulatory Smoking Motives

PubMed Central

Farris, Samantha G.; Zvolensky, Michael J.; Beckham, Jean C.; Vujanovic, Anka A.; Schmidt, Norman B.

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association. PMID:25299617

Dopamine does double duty in motivating cognitive effort

PubMed Central

Westbrook, Andrew; Braver, Todd S.

2015-01-01

Cognitive control is subjectively costly, suggesting that engagement is modulated in relationship to incentive state. Dopamine appears to play key roles. In particular, dopamine may mediate cognitive effort by two broad classes of functions: 1) modulating the functional parameters of working memory circuits subserving effortful cognition, and 2) mediating value-learning and decision-making about effortful cognitive action. Here we tie together these two lines of research, proposing how dopamine serves “double duty”, translating incentive information into cognitive motivation. PMID:26889810

Dietary change mediates relationships between stress during pregnancy and infant head circumference measures: the QF2011 study.

PubMed

Dancause, Kelsey N; Mutran, Dima; Elgbeili, Guillaume; Laplante, David P; Kildea, Sue; Stapleton, Helen; McIntyre, David; King, Suzanne

2017-07-01

Prenatal maternal stress can adversely affect birth outcomes, likely reflecting effects of maternal stress hormones on fetal development. Maternal stress might also induce behavioural changes, such as dietary change, that might influence fetal development. Few studies have documented relationships between stress and dietary change in pregnancy. We analysed stress and dietary change among 222 pregnant women exposed to the 2011 Queensland Floods. We assessed women's objective hardship, subjective distress and cognitive appraisal of the disaster; changes in their diets and their associations with infants' gestational age, weight, length and head circumference at birth, head circumference to birth length ratio (HC/BL) and ponderal index. Greater objective hardship was correlated with more negative dietary change, skipped meals and skipped multivitamins. There were no direct effects of stress or dietary change on birth outcomes. However, we observed an interactive effect of dietary change and exposure timing on head circumference for gestational age (HC for GA) (p = 0.010) and a similar trend for HC/BL (p = 0.064). HC for GA and HC/BL were larger among children whose mothers experienced negative changes to their diet in early pregnancy compared with later pregnancy, consistent with a 'head-sparing' response with early gestation exposure. Further analyses indicated that dietary change mediates the relationship between objective hardship because of the floods and these outcomes. This is the first report of relationships among an independent stressor, dietary change and birth outcomes. It highlights another possible mechanism in the relationship between prenatal maternal stress and child development that could guide future research and interventions. © 2016 John Wiley & Sons Ltd.

Reirradiation of head and neck cancer using modern highly conformal techniques.

PubMed

Ho, Jennifer C; Phan, Jack

2018-04-23

Locoregional disease recurrence or development of a second primary cancer after definitive radiotherapy for head and neck cancers remains a treatment challenge. Reirradiation utilizing traditional techniques has been limited by concern for serious toxicity. With the advent of newer, more precise radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT), proton radiotherapy, and stereotactic body radiotherapy (SBRT), there has been renewed interest in curative-intent head and neck reirradiation. However, as most studies were retrospective, single-institutional experiences, the optimal modality is not clear. We provide a comprehensive review of the outcomes of relevant studies using these 3 head and neck reirradiation techniques, followed by an analysis and comparison of the toxicity, tumor control, concurrent systemic therapy, and prognostic factors. Overall, there is evidence that IMRT, proton therapy, and SBRT reirradiation are feasible treatment options that offer a chance for durable local control and survival. Prospective studies, particularly randomized trials, are needed. © 2018 Wiley Periodicals, Inc.

Viscosity-adjusted estimation of pressure head and pump flow with quasi-pulsatile modulation of rotary blood pump for a total artificial heart.

PubMed

Yurimoto, Terumi; Hara, Shintaro; Isoyama, Takashi; Saito, Itsuro; Ono, Toshiya; Abe, Yusuke

2016-09-01

Estimation of pressure and flow has been an important subject for developing implantable artificial hearts. To realize real-time viscosity-adjusted estimation of pressure head and pump flow for a total artificial heart, we propose the table estimation method with quasi-pulsatile modulation of rotary blood pump in which systolic high flow and diastolic low flow phased are generated. The table estimation method utilizes three kinds of tables: viscosity, pressure and flow tables. Viscosity is estimated from the characteristic that differential value in motor speed between systolic and diastolic phases varies depending on viscosity. Potential of this estimation method was investigated using mock circulation system. Glycerin solution diluted with salty water was used to adjust viscosity of fluid. In verification of this method using continuous flow data, fairly good estimation could be possible when differential pulse width modulation (PWM) value of the motor between systolic and diastolic phases was high. In estimation under quasi-pulsatile condition, inertia correction was provided and fairly good estimation was possible when the differential PWM value was high, which was not different from the verification results using continuous flow data. In the experiment of real-time estimation applying moving average method to the estimated viscosity, fair estimation could be possible when the differential PWM value was high, showing that real-time viscosity-adjusted estimation of pressure head and pump flow would be possible with this novel estimation method when the differential PWM value would be set high.

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

PubMed

Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur

2012-01-01

Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

Assessment of Computer-Mediated Module Intervention in a Pharmacy Calculations Course

ERIC Educational Resources Information Center

Bell, Edward C.; Fike, David S.; Liang, Dong; Lockman, Paul R.; McCall, Kenneth L.

2017-01-01

Computer module intervention is the process of exposing students to a series of discrete exercises for the purpose of strengthening students' familiarity with conceptual material. The method has been suggested as a remedy to student under-preparedness. This study was conducted to determine the effectiveness of module intervention in improving and…

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

NASA Astrophysics Data System (ADS)

Weinberg, Rebecca

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity.

Regulating the ethylene response of a plant by modulation of F-box proteins

DOEpatents

Guo, Hongwei [Beijing, CN; Ecker, Joseph R [Carlsbad, CA

2014-01-07

The relationship between F-box proteins and proteins invovled in the ethylene response in plants is described. In particular, F-box proteins may bind to proteins involved in the ethylene response and target them for degradation by the ubiquitin/proteasome pathway. The transcription factor EIN3 is a key transcription factor mediating ethylne-regulated gene expression and morphological responses. EIN3 is degraded through a ubiquitin/proteasome pathway mediated by F-box proteins EBF1 and EBF2. The link between F-box proteins and the ethylene response is a key step in modulating or regulating the response of a plant to ethylene. Described herein are transgenic plants having an altered sensitivity to ethylene, and methods for making transgenic plant haing an althered sensitivity to ethylene by modulating the level of activity of F-box proteins. Methods of altering the ethylene response in a plant by modulating the activity or expression of an F-box protein are described. Also described are methods of identifying compounds that modulate the ethylene response in plants by modulating the level of F-box protein expression or activity.

The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress.

PubMed

Corcoran, Louise; Roche, Michelle; Finn, David P

2015-01-01

Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor. The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli. The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein. We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain's endocannabinoid system modulates pain. We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia. Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders. © 2015 Elsevier Inc. All rights reserved.

IgE-mediated sensitization to malassezia in atopic dermatitis: more common in male patients and in head and neck type.

PubMed

Brodská, Petra; Panzner, Petr; Pizinger, Karel; Schmid-Grendelmeier, Peter

2014-01-01

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate AD, especially in a subset of patients with head and neck type AD (HNAD). In the present study, the relationship between AD and sensitization to Malassezia antigens was investigated. We assessed 173 patients with AD. The severity of eczema was determined with Eczema Area and Severity Index (EASI); the type of AD, namely, head and neck type, was reported as well. The total serum IgE and specific IgE to Malassezia were determined and correlated with clinical picture of AD, sex, age, and the EASI. Total IgE was elevated in 77.7% of patients. Specific IgE to Malassezia was positive (≥0.35 kU/L) in 49.1% of patients. Men were significantly more often sensitized to Malassezia antigen (58% of men vs 42% of women; P value, 0.04). Concurrently, 58% of patients with HNAD versus 42% non-HNAD patients had higher levels of specific IgE to Malassezia, this difference being nearly significant (P value, 0.06). Patients with atopy were also more frequently sensitized to Malassezia. No significant relationship between EASI and the level of total IgE or specific IgE to Malassezia was observed. In our population, IgE-mediated sensitization was found in up to 49% of all patients with AD, most common in men and in head and neck type.

Objective measurement of head movement differences in children with and without autism spectrum disorder.

PubMed

Martin, Katherine B; Hammal, Zakia; Ren, Gang; Cohn, Jeffrey F; Cassell, Justine; Ogihara, Mitsunori; Britton, Jennifer C; Gutierrez, Anibal; Messinger, Daniel S

2018-01-01

Deficits in motor movement in children with autism spectrum disorder (ASD) have typically been characterized qualitatively by human observers. Although clinicians have noted the importance of atypical head positioning (e.g. social peering and repetitive head banging) when diagnosing children with ASD, a quantitative understanding of head movement in ASD is lacking. Here, we conduct a quantitative comparison of head movement dynamics in children with and without ASD using automated, person-independent computer-vision based head tracking (Zface). Because children with ASD often exhibit preferential attention to nonsocial versus social stimuli, we investigated whether children with and without ASD differed in their head movement dynamics depending on stimulus sociality. The current study examined differences in head movement dynamics in children with ( n  = 21) and without ASD ( n  = 21). Children were video-recorded while watching a 16-min video of social and nonsocial stimuli. Three dimensions of rigid head movement-pitch (head nods), yaw (head turns), and roll (lateral head inclinations)-were tracked using Zface. The root mean square of pitch, yaw, and roll was calculated to index the magnitude of head angular displacement (quantity of head movement) and angular velocity (speed). Compared with children without ASD, children with ASD exhibited greater yaw displacement, indicating greater head turning, and greater velocity of yaw and roll, indicating faster head turning and inclination. Follow-up analyses indicated that differences in head movement dynamics were specific to the social rather than the nonsocial stimulus condition. Head movement dynamics (displacement and velocity) were greater in children with ASD than in children without ASD, providing a quantitative foundation for previous clinical reports. Head movement differences were evident in lateral (yaw and roll) but not vertical (pitch) movement and were specific to a social rather than nonsocial condition. When presented with social stimuli, children with ASD had higher levels of head movement and moved their heads more quickly than children without ASD. Children with ASD may use head movement to modulate their perception of social scenes.

Caveolae: a regulatory platform for nutritional modulation of inflammatory diseases

PubMed Central

Layne, Joseph; Majkova, Zuzana; Smart, Eric J.; Toborek, Michal; Hennig, Bernhard

2010-01-01

Dietary intervention strategies have proven to be an effective means of decreasing several risk factors associated with the development of atherosclerosis. Endothelial cell dysfunction influences vascular inflammation and is involved in promoting the earliest stages of lesion formation. Caveolae are lipid raft microdomains abundant within the plasma membrane of endothelial cells and are responsible for mediating receptor-mediated signal transduction. Caveolae have been implicated in the regulation of enzymes associated with several key signaling pathways capable of determining intracellular redox status. Diet and plasma-derived nutrients may modulate an inflammatory outcome by interacting with and altering caveolae-associated cellular signaling. For example, omega-3 fatty acids and several polyphenolics have been shown to improve endothelial cell function by decreasing the formation of ROS and increasing NO bioavailability, events associated with altered caveolae composition. Thus, nutritional modulation of caveolae-mediated signaling events may provide an opportunity to ameliorate inflammatory signaling pathways capable of promoting the formation of vascular diseases, including atherosclerosis. PMID:21292468

Optimization by Molecular Fine Tuning of Dihydro-β-agarofuran Sesquiterpenoids as Reversers of P-Glycoprotein-Mediated Multidrug Resistance.

PubMed

Callies, Oliver; Sánchez-Cañete, María P; Gamarro, Francisco; Jiménez, Ignacio A; Castanys, Santiago; Bazzocchi, Isabel L

2016-03-10

P-glycoprotein (P-gp) plays a crucial role in the development of multidrug resistance (MDR), a major obstacle for successful chemotherapy in cancer. Herein, we report on the development of a natural-product-based library of 81 dihydro-β-agarofuran sesquiterpenes (2-82) by optimization of the lead compound 1. The compound library was evaluated for its ability to inhibit P-gp-mediated daunomycin efflux in MDR cells. Selected analogues were further analyzed for their P-gp inhibition constant, intrinsic toxicity, and potency to reverse daunomycin and vinblastine resistances. Analogues 6, 24, 28, 59, and 66 were identified as having higher potency than compound 1 and verapamil, a first-generation P-gp modulator. SAR analysis revealed the size of the aliphatic chains and presence of nitrogen atoms are important structural characteristics to modulate reversal activity. The present study highlights the potential of these analogues as modulators of P-gp mediated MDR in cancer cells.

The impact of odor–reward memory on chemotaxis in larval Drosophila

PubMed Central

Schleyer, Michael; Reid, Samuel F.; Pamir, Evren; Saumweber, Timo; Paisios, Emmanouil; Davies, Alexander

2015-01-01

How do animals adaptively integrate innate with learned behavioral tendencies? We tackle this question using chemotaxis as a paradigm. Chemotaxis in the Drosophila larva largely results from a sequence of runs and oriented turns. Thus, the larvae minimally need to determine (i) how fast to run, (ii) when to initiate a turn, and (iii) where to direct a turn. We first report how odor-source intensities modulate these decisions to bring about higher levels of chemotactic performance for higher odor-source intensities during innate chemotaxis. We then examine whether the same modulations are responsible for alterations of chemotactic performance by learned odor “valence” (understood throughout as level of attractiveness). We find that run speed (i) is neither modulated by the innate nor by the learned valence of an odor. Turn rate (ii), however, is modulated by both: the higher the innate or learned valence of the odor, the less often larvae turn whenever heading toward the odor source, and the more often they turn when heading away. Likewise, turning direction (iii) is modulated concordantly by innate and learned valence: turning is biased more strongly toward the odor source when either innate or learned valence is high. Using numerical simulations, we show that a modulation of both turn rate and of turning direction is sufficient to account for the empirically found differences in preference scores across experimental conditions. Our results suggest that innate and learned valence organize adaptive olfactory search behavior by their summed effects on turn rate and turning direction, but not on run speed. This work should aid studies into the neural mechanisms by which memory impacts specific aspects of behavior. PMID:25887280

Calpain cleavage within dysferlin exon 40a releases a synaptotagmin-like module for membrane repair

PubMed Central

Redpath, G. M. I.; Woolger, N.; Piper, A. K.; Lemckert, F. A.; Lek, A.; Greer, P. A.; North, K. N.; Cooper, S. T.

2014-01-01

Dysferlin and calpain are important mediators of the emergency response to repair plasma membrane injury. Our previous research revealed that membrane injury induces cleavage of dysferlin to release a synaptotagmin-like C-terminal module we termed mini-dysferlinC72. Here we show that injury-activated cleavage of dysferlin is mediated by the ubiquitous calpains via a cleavage motif encoded by alternately spliced exon 40a. An exon 40a–specific antibody recognizing cleaved mini-dysferlinC72 intensely labels the circumference of injury sites, supporting a key role for dysferlinExon40a isoforms in membrane repair and consistent with our evidence suggesting that the calpain-cleaved C-terminal module is the form specifically recruited to injury sites. Calpain cleavage of dysferlin is a ubiquitous response to membrane injury in multiple cell lineages and occurs independently of the membrane repair protein MG53. Our study links calpain and dysferlin in the calcium-activated vesicle fusion of membrane repair, placing calpains as upstream mediators of a membrane repair cascade that elicits cleaved dysferlin as an effector. Of importance, we reveal that myoferlin and otoferlin are also cleaved enzymatically to release similar C-terminal modules, bearing two C2 domains and a transmembrane domain. Evolutionary preservation of this feature highlights its functional importance and suggests that this highly conserved C-terminal region of ferlins represents a functionally specialized vesicle fusion module. PMID:25143396

Combat cueing

NASA Astrophysics Data System (ADS)

Kachejian, Kerry C.; Vujcic, Doug

1998-08-01

The combat cueing (CBT-Q) research effort will develop and demonstrate a portable tactical information system that will enhance the effectiveness of small unit military operations by providing real-time target cueing information to individual warfighters and teams. CBT-Q consists of a network of portable radio frequency (RF) 'modules' and is controlled by a body-worn 'user station' utilizing a head mounted display . On the battlefield, CBT-Q modules will detect an enemy transmitter and instantly provide the warfighter with an emitter's location. During the 'fog of battle', CBT-Q would tell the warfighter, 'Look here, right now individuals into the RF spectrum, resulting in faster target engagement times, increased survivability, and reduce the potential for fratricide. CBT-Q technology can support both mounted and dismounted tactical forces involved in land, sea and air warfighting operations. The CBT-Q system combines robust geolocation and signal sorting algorithms with hardware and software modularity to offer maximum utility to the warfighter. A single CBT-Q module can provide threat RF detection. Three networked CBT-Q modules can provide emitter positions using a time difference of arrival (TDOA) technique. The TDOA approach relies on timing and positioning data derived from a global positioning systems. The information will be displayed on a variety of displays, including a flat-panel head mounted display. The end results of the program will be the demonstration of the system with US Army Scouts in an operational environment.

Parabrachial nucleus neuronal responses to off-vertical axis rotation in macaques

PubMed Central

McCandless, Cyrus H.; Balaban, Carey D.

2010-01-01

The caudal aspect of the parabrachial nucleus (PBN) contains neurons responsive to whole body, periodic rotational stimulation in alert monkeys. This study characterizes the angular and linear motion-sensitive response properties of PBN unit responses during off-vertical axis rotation (OVAR) and position trapezoid stimulation. The OVAR responses displayed a constant firing component which varied from the firing rate at rest. Nearly two-thirds of the units also modulated their discharges with respect to head orientation (re: gravity) during constant velocity OVAR stimulation. The modulated response magnitudes were equal during ipsilateral and contralateral OVARs, indicative of a one-dimensional accelerometer. These response orientations during OVAR divided the units into three spatially tuned populations, with peak modulation responses centered in the ipsilateral ear down, contralateral anterior semicircular canal down, and occiput down orientations. Because the orientation of the OVAR modulation response was opposite in polarity to the orientation of the static tilt component of responses to position trapezoids for the majority of units, the linear acceleration responses were divided into colinear dynamic linear and static tilt components. The orientations of these unit responses formed two distinct population response axes: (1) units with an interaural linear response axis and (2) units with an ipsilateral anterior semicircular canal-contralateral posterior semicircular canal plane linear response axis. The angular rotation sensitivity of these units is in a head-vertical plane that either contains the linear acceleration response axis or is perpendicular to the linear acceleration axis. Hence, these units behave like head-based (‘strap-down’) inertial guidance sensors. Because the PBN contributes to sensory and interoceptive processing, it is suggested that vestibulo-recipient caudal PBN units may detect potentially dangerous anomalies in control of postural stability during locomotion. In particular, these signals may contribute to the range of affective and emotional responses that include panic associated with falling, malaise associated with motion sickness and mal-de-debarquement, and comorbid balance and anxiety disorders. PMID:20039027

Houttuynia cordata modulates oral innate immune mediators: potential role of herbal plant on oral health.

PubMed

Satthakarn, S; Chung, W O; Promsong, A; Nittayananta, W

2015-05-01

Epithelial cells play an active role in oral innate immunity by producing various immune mediators. Houttuynia cordata Thunb (H. cordata), a herbal plant found in Asia, possesses many activities. However, its impacts on oral innate immunity have never been reported. The aim of this study was to determine the effects of H. cordata extract on the expression of innate immune mediators produced by oral epithelial cells. Primary gingival epithelial cells (GECs) were treated with various concentrations of the extract for 18 h. The gene expression of hBD2, SLPI, cytokines, and chemokines was measured using quantitative real-time RT-PCR. The secreted proteins in the culture supernatants were detected by ELISA or Luminex assay. Cytotoxicity of the extract was assessed using CellTiter-Blue Assay. H. cordata significantly induced the expression of hBD2, SLPI, IL-8, and CCL20 in a dose-dependent manner without cytotoxicity. The secreted hBD2 and SLPI proteins were modulated, and the levels of IL-2, IL-6, IL-8, and IFN-γ were significantly induced by the extract. Our data indicated that H. cordata can modulate oral innate immune mediators. These findings may lead to the development of new topical agents from H. cordata for the prevention and treatment of immune-mediated oral diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early Head Start, Pediatric Dental Use, and Oral Health–Related Quality of Life

PubMed Central

Burgette, J.M.; Preisser, J.S.; Weinberger, M.; King, R.S.; Rozier, R.G.

2017-01-01

The objective of the study was to examine the mediating effect of child dental use on the effectiveness of North Carolina Early Head Start (EHS) in improving oral health–related quality of life (OHRQoL). In total, 479 parents of children enrolled in EHS and 699 parents of Medicaid-matched children were interviewed at baseline when children were approximately 10 mo old and 24 mo later. In this quasi-experimental study, mediation analysis was performed using the counterfactual framework analysis, which employed 2 logit models with random effects: 1) for the mediator as a function of the treatment and covariates and 2) for the outcome as a function of the treatment, mediator, and covariates. The covariates were baseline dental OHRQoL, dental need, survey language, and a propensity score. We used in-person computer-assisted, structured interviews to collect information on demographic characteristics and dental use and to administer the Early Childhood Oral Health Impact Scale, a measure of OHRQoL. Dental use had a mediation effect in the undesired direction with a 2–percentage point increase in the probability of any negative impact to OHRQoL (95% confidence interval [CI], 0.3%–3.9%). Even with higher dental use by EHS participants, the probability of any negative impact to OHRQoL was approximately 8 percentage points lower if an individual were moved from the non-EHS group to the EHS group (95% CI, −13.9% to −1.2%). EHS increases child dental use, which worsens family OHRQoL. However, EHS is associated with improved OHRQoL overall. Knowledge Transfer Statement: Study results can inform policy makers that comprehensive early childhood education programs improve oral health–related quality of life (OHRQoL) for disadvantaged families with young children in pathways outside of clinical dental care. This awareness and its promotion can lead to greater resource investments in early childhood education programs. Information about the negative impacts of dental use on OHRQoL should lead to the development and testing of strategies in dentistry and Early Head Start to improve dental care experiences. PMID:28944292

A score for the differential diagnosis of bradykinin- and histamine-induced head and neck swellings.

PubMed

Lenschow, M; Bas, M; Johnson, F; Wirth, M; Strassen, U

2018-05-02

Acute edema of the head and neck region may lead to life-threatening dyspnea and require quick and targeted treatment. They can be subdivided in bradykinin- and histamine-mediated swellings, which require treatment with different classes of pharmaceuticals. Clinical pathways for differential diagnoses do not exist so far, although it is known that early treatment is decisive for faster symptom relief and reduced expression of the swellings. Aim of the study was the creation of a clinical algorithm for identification of bradykinin-mediated angioedema. 188 patients that presented to our outpatient department between 2010 and 2016 with an acute, non-inflammatory swelling of the head and neck region were included in our retrospective study. All available anamnestic and clinical parameters were obtained from patient files. Parameters showing significant differences between the two groups were included in our score. Utilization of the Youden's index allowed determination of an optimal cut-off value. 76 patients could be assigned to the histamine and 112 patients to bradykinin group. The following parameters were included in our score: age, dyspnea, itching or erythema, glucocorticoid response and intake of ACEi/AT-II blockers. The cut-off value is set at three points. The proposed score yielded a sensitivity for identification of bradykinin-mediated angioedema of 96%, a specificity of 84%, a positive predictive value of 91% and a negative predictive value of 93%. Utilization of the proposed score allows quick and reliable assignment of patients to the correct subgroup and thereby reduces time for treatment.

Wind noise in hearing aids: I. Effect of wide dynamic range compression and modulation-based noise reduction.

PubMed

Chung, King

2012-01-01

The objectives of this study were: (1) to examine the effect of wide dynamic range compression (WDRC) and modulation-based noise reduction (NR) algorithms on wind noise levels at the hearing aid output; and (2) to derive effective strategies for clinicians and engineers to reduce wind noise in hearing aids. Three digital hearing aids were fitted to KEMAR. The noise output was recorded at flow velocities of 0, 4.5, 9.0, and 13.5 m/s in a wind tunnel as the KEMAR head was turned from 0° to 360°. Flow noise levels were compared between the 1:1 linear and 3:1 WDRC conditions, and between NR-activated and NR-deactivated conditions when the hearing aid was programmed to the directional and omnidirectional modes. The results showed that: (1) WDRC increased low-level noise and reduced high-level noise; and (2) different noise reduction algorithms provided different amounts of wind noise reduction in different microphone modes, frequency regions, flow velocities, and head angles. Wind noise can be reduced by decreasing the gain for low-level inputs, increasing the compression ratio for high-level inputs, and activating modulation-based noise reduction algorithms.

Vestibuloocular reflex of rhesus monkeys after spaceflight

NASA Technical Reports Server (NTRS)

Cohen, Bernard; Kozlovskaia, Inessa; Raphan, Theodore; Solomon, David; Helwig, Denice; Cohen, Nathaniel; Sirota, Mikhail; Iakushin, Sergei

1992-01-01

The vestibuloocular reflex (VOR) of two rhesus monkeys was recorded before and after 14 days of spaceflight. The gain (eye velocity/head velocity) of the horizontal VOR, tested 15 and 18 h after landing, was approximately equal to preflight values. The dominant time constant of the animal tested 15 h after landing was equivalent to that before flight. During nystagmus induced by off-vertical axis rotation (OVAR), the latency, rising time constant, steady-state eye velocity, and phase of modulation in eye velocity and eye position with respect to head position were similar in both monkeys before and after flight. There were changes in the amplitude of modulation of horizontal eye velocity during steady-state OVAR and in the ability to discharge stored activity rapidly by tilting during postrotatory nystagmus (tilt dumping) after flight: OVAR modulations were larger, and tilt dumping was lost in the one animal tested on the day of landing and for several days thereafter. If the gain and time constant of the horizontal VOR exchange in microgravity, they must revert to normal soon after landing. The changes that were observed suggest that adaptation to microgravity had caused alterations in way that the central nervous system processes otolith input.

Growth parameters at birth mediate the relationship between prenatal manganese exposure and cognitive test scores among a cohort of 2- to 3-year-old Bangladeshi children.

PubMed

Lee, Jane J; Valeri, Linda; Kapur, Kush; Ibne Hasan, Md Omar Sharif; Quamruzzaman, Quazi; Wright, Robert O; Bellinger, David C; Christiani, David C; Mazumdar, Maitreyi

2018-05-03

Our previous study demonstrated that prenatal manganese exposure is associated with cognitive test scores among a cohort of 2- to 3-year-old Bangladeshi children. This study tested the hypothesis that the adverse effects of manganese are mediated through poor prenatal growth. Pregnant mothers were enrolled in a birth cohort in Bangladesh between 2008 and 2011, and children were followed at birth and age 20-40 months. Manganese concentration was measured in umbilical cord blood. Anthropometric measurements (weight, length, head circumference) were assessed at delivery. Children's cognitive development was assessed at age 20-40 months using the Bayley Scales of Infant and Toddler Development-Third Edition. Using recently developed statistical approaches that estimate mediation and interaction effects simultaneously, we evaluated whether the association between cord blood manganese and cognitive score was mediated through anthropometric measures at birth. This analysis included 764 mother-child pairs. Higher manganese concentration was associated with lower cognitive score [β=-0.61, standard error (SE)=0.23, p = 0.009]. Among the birth measures, we found a significant indirect effect only through birth length (β =-0.10, SE = 0.03, p = 0.001). We also found evidence of mediated interaction (both mediation and interaction, β =-0.03, SE = 0.01, p = 0.01) with birth length in the association between cord blood manganese and cognitive score. The overall proportion mediated by birth length was 33% (p = 0.02) and the proportion attributed to interaction was 11% (p = 0.04). We did not find evidence of a mediating effect through birth weight or head circumference. Our findings confirm that prenatal growth, particularly birth length, contributes to the overall effect of environmental manganese exposure on a child's cognitive development.

Renal intercalated cells and blood pressure regulation

PubMed Central

Wall, Susan M.

2017-01-01

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl− absorption and HCO3− secretion largely through pendrin-dependent Cl−/HCO3− exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO3 administration. In some rodent models, pendrin-mediated HCO3− secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl− absorption, but also by modulating the aldosterone response for epithelial Na+ channel (ENaC)-mediated Na+ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure. PMID:29285423

An Allosteric Coagonist Model for Propofol Effects on α1β2γ2L γ-Aminobutyric Acid Type A Receptors

PubMed Central

Ruesch, Dirk; Neumann, Elena; Wulf, Hinnerk; Forman, Stuart A.

2011-01-01

Background Propofol produces its major actions via γ-aminobutyric acid type A (GABAA) receptors. At low concentrations, propofol enhances agonist-stimulated GABAA receptor activity, and high propofol concentrations directly activate receptors. Etomidate produces similar effects, and there is convincing evidence that a single class of etomidate sites mediate both agonist modulation and direct GABAA receptor activation. It is unknown if the propofol binding site(s) on GABAA receptors that modulate agonist-induced activity also mediate direct activation. Methods GABAA α1β2γ2L receptors were heterologously expressed in Xenopus oocytes and activity was quantified using voltage clamp electrophysiology. We tested whether propofol and etomidate display the same linkage between agonist modulation and direct activation of GABAA receptors by identifying equi-efficacious drug solutions for direct activation. We then determined whether these drug solutions produce equal modulation of GABA-induced receptor activity. We also measured propofol-dependent direct activation and modulation of low GABA responses. Allosteric coagonist models similar to that established for etomidate, but with variable numbers of propofol sites, were fitted to combined data. Results Solutions of 19 μM propofol and 10 μM etomidate were found to equally activate GABAA receptors. These two drug solutions also produced indistinguishable modulation of GABA-induced receptor activity. Combined electrophysiological data behaved in a manner consistent with allosteric co-agonist models with more than one propofol site. The best fit was observed when the model assumed three equivalent propofol sites. Conclusions Our results support the hypothesis that propofol, like etomidate, acts at GABAA receptor sites mediating both GABA modulation and direct activation. PMID:22104494

Metabotropic glutamate receptor modulation of dopamine release in the nucleus accumbens shell is unaffected by phencyclidine pretreatment: In vitro assessment using fast-scan cyclic voltammetry rat brain slices.

PubMed

Gupta, Ishan; Young, Andrew M J

2018-05-15

The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the drug treatment causes long-term changes in the physiology and/or chemistry of the brain. There is evidence that this may occur through glutamatergic modulation of mesolimbic dopamine release, perhaps involving metabotropic glutamate receptors (mGluR). This study sought to investigate the effect of sub-chronic phencyclidine pretreatment on modulation of dopamine neurotransmission by metabotropic glutamate receptors 2 and 5 (mGluR2 and mGluR5) in the nucleus accumbens shell in vitro, with the hypothesis that phencyclidine pretreatment would disrupt the mGluR-mediated modulation of dopamine release. We showed that the orthosteric mGluR2 agonist LY379268 (0.1 µM, 1 µM and 10 µM) and mGluR5 positive allosteric modulator CDPPB (1 µM and 10 µM) both attenuated potassium-evoked dopamine release, underscoring their role in modulating dopamine neurotransmission in the nucleus accumbens. Sub-chronic PCP treatment, which caused cognitive deficits measured by performance in the novel object recognition task, modelling aspects of behavioral deficits seen in schizophrenia, induced neurobiological changes that enhanced dopamine release in the nucleus accumbens, but had no effect on mGluR2 or mGluR5 mediated changes in dopamine release. Therefore it is unlikely that schizophrenia-related behavioural changes seen after sub-chronic phencyclidine pre-treatment are mediated through mGluR modulation of dopamine release. Copyright © 2018 Elsevier B.V. All rights reserved.

A comparison of radioisotope Brayton and Stirling system for lunar surface mobile power

NASA Astrophysics Data System (ADS)

Harty, Richard B.

1991-01-01

A study was performed by the Rocketdyne Division of Rockwell 2.5-kWe modular dynamic isotope power system (DIPS) using a Stirling power conversion system. The results of this study were compared with similar results performed under the DIPS program using a Brayton power conversion system. The study indicated that the Stirling power module has 20% lower mass and 40% lower radiator area than the Brayton module. However, the study also revealed that because the Stirling power module requires a complex heat pipe arrangment to transport heat from the isotope to the Stirling heater head and a pumped NaK heat rejection loop, the Stirling module is much more difficult to integrate with the isotope heat source and heat rejection system.

Head and Neck Cancers: Advantages of Advanced Radiation Therapy and Importance of Supportive Care.

PubMed

Spencer, Sharon

2018-05-01

For more than a decade, the incidence of head and neck cancers has been increasing in the United States. Worldwide, they are the ninth most common cancer. Today, newer advances in radiotherapy (RT), such as fractionation, 4-dimensional cone-beam CT, and intensity-modulated RT, have provided clinicians with the opportunity for improved patient outcomes. At the NCCN 23rd Annual Conference, Sharon Spencer, MD, described the advantages of advances in RT and the means to mitigate untoward side effects. Copyright © 2018 by the National Comprehensive Cancer Network.

Cyborg mini-trainer.

PubMed

Mosso, José L; Nieto, Jesus J; Carbajal, Manuel F; Marmolejo, Jorge; Ochoa, Enrique; De La Fuente, Mireya; Almazan, Andrew; Obrador, Tomas

2009-01-01

We present the smallest surgical trainer with a total weight of 400 gr, built in aluminum of 25 cm large and 24 cm wide, and 23 cm high. It's a system integrated by a small and open module, a lamp and a microcamera connected to a Head Mounted display. It holds two endoscopic instruments, and items to make knots or sutures and enhance visual-motor coordination. The vision we got is by a small microcamera displayed to a Head Mounted Display HMD. This surgical trainer is the smallest in the worldwide, easy to install, and easy to carry.

U.S. Commercial Cargo Craft Heads to the Space Station

NASA Image and Video Library

2018-05-21

The remotely piloted Orbital ATK Cygnus cargo spacecraft launched May 21 from NASA's Wallops Flight Facility, Virginia atop an Antares rocket, headed for a rendezvous with the International Space Station to deliver several tons of scientific experiments and supplies for the station residents. Dubbed the SS “J.R. Thompson” in honor of the late spacefaring manager for both NASA and Orbital ATK, Cygnus will be robotically captured and installed to the earth-facing port of the station’s Unity module for a two-month stay at the orbital outpost.

Emergency Multiengine Aircraft System for Lateral Control Using Differential Thrust Control of Wing Engines

NASA Technical Reports Server (NTRS)

Burken, John J. (Inventor); Burcham, Frank W., Jr. (Inventor); Bull, John (Inventor)

2000-01-01

Development of an emergency flight control system is disclosed for lateral control using only differential engine thrust modulation of multiengine aircraft is currently underway. The multiengine has at least two engines laterally displaced to the left and right from the axis of the aircraft. In response to a heading angle command psi(sub c) is to be tracked. By continually sensing the heading angle psi of the aircraft and computing a heading error signal psi(sub e) as a function of the difference between the heading angle command psi(sub c) and the sensed heading angle psi, a track control signal is developed with compensation as a function of sensed bank angle phi. Bank angle rate phi, or roll rate p, yaw rate tau, and true velocity produce an aircraft thrust control signal ATC(sub psi(L,R)). The thrust control signal is differentially applied to the left and right engines, with equal amplitude and opposite sign, such that a negative sign is applied to the control signal on the side of the aircraft. A turn is required to reduce the error signal until the heading feedback reduces the error to zero.

Why Do We Move Our Head to Look at an Object in Our Peripheral Region? Lateral Viewing Interferes with Attentive Search

PubMed Central

Nakashima, Ryoichi; Shioiri, Satoshi

2014-01-01

Why do we frequently fixate an object of interest presented peripherally by moving our head as well as our eyes, even when we are capable of fixating the object with an eye movement alone (lateral viewing)? Studies of eye-head coordination for gaze shifts have suggested that the degree of eye-head coupling could be determined by an unconscious weighing of the motor costs and benefits of executing a head movement. The present study investigated visual perceptual effects of head direction as an additional factor impacting on a cost-benefit organization of eye-head control. Three experiments using visual search tasks were conducted, manipulating eye direction relative to head orientation (front or lateral viewing). Results show that lateral viewing increased the time required to detect a target in a search for the letter T among letter L distractors, a serial attentive search task, but not in a search for T among letter O distractors, a parallel preattentive search task (Experiment 1). The interference could not be attributed to either a deleterious effect of lateral gaze on the accuracy of saccadic eye movements, nor to potentially problematic optical effects of binocular lateral viewing, because effect of head directions was obtained under conditions in which the task was accomplished without saccades (Experiment 2), and during monocular viewing (Experiment 3). These results suggest that a difference between the head and eye directions interferes with visual processing, and that the interference can be explained by the modulation of attention by the relative positions of the eyes and head (or head direction). PMID:24647634

The origin and diversification of the developmental mechanisms that pattern the vertebrate head skeleton.

PubMed

Square, Tyler; Jandzik, David; Romášek, Marek; Cerny, Robert; Medeiros, Daniel Meulemans

2017-07-15

The apparent evolvability of the vertebrate head skeleton has allowed a diverse array of shapes, sizes, and compositions of the head in order to better adapt species to their environments. This encompasses feeding, breathing, sensing, and communicating: the head skeleton somehow participated in the evolution of all these critical processes for the last 500 million years. Through evolution, present head diversity was made possible via developmental modifications to the first head skeletal genetic program. Understanding the development of the vertebrate common ancestor's head skeleton is thus an important step in identifying how different lineages have respectively achieved their many innovations in the head. To this end, cyclostomes (jawless vertebrates) are extremely useful, having diverged from jawed vertebrates approximately 400 million years ago, at the deepest node within living vertebrates. From this ancestral vantage point (that is, the node connecting cyclostomes and gnathostomes) we can best identify the earliest major differences in development between vertebrate classes, and start to address how these might translate onto morphology. In this review we survey what is currently known about the cell biology and gene expression during head development in modern vertebrates, allowing us to better characterize the developmental genetics driving head skeleton formation in the most recent common ancestor of all living vertebrates. By pairing this vertebrate composite with information from fossil chordates, we can also deduce how gene regulatory modules might have been arranged in the ancestral vertebrate head. Together, we can immediately begin to understand which aspects of head skeletal development are the most conserved, and which are divergent, informing us as to when the first differences appear during development, and thus which pathways or cell types might be involved in generating lineage specific shape and structure. Copyright © 2017 Elsevier Inc. All rights reserved.

Trial-to-Trial Modulations of the Simon Effect in Conditions of Attentional Limitations : Evidence from Dual Tasks

ERIC Educational Resources Information Center

Fischer, Rico; Plessow, Franziska; Kunde, Wilfried; Kiesel, Andrea

2010-01-01

Interference effects are reduced after trials including response conflict. This sequential modulation has often been attributed to a top-down mediated adaptive control mechanism and/or to feature repetition mechanisms. In the present study we tested whether mechanisms responsible for such sequential modulations are subject to attentional…

Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications

PubMed Central

Cui, Jiuwei; Yang, Guozi; Pan, Zhenyu; Zhao, Yuguang; Liang, Xinyue; Li, Wei; Cai, Lu

2017-01-01

The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications. PMID:28134809

Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma.

PubMed

Koch, Raphael; Demant, Martin; Aung, Thiha; Diering, Nina; Cicholas, Anna; Chapuy, Bjoern; Wenzel, Dirk; Lahmann, Marlen; Güntsch, Annemarie; Kiecke, Christina; Becker, Sabrina; Hupfeld, Timo; Venkataramani, Vivek; Ziepert, Marita; Opitz, Lennart; Klapper, Wolfram; Trümper, Lorenz; Wulf, Gerald G

2014-04-03

Tumors are composed of phenotypically heterogeneous cell populations. The nongenomic mechanisms underlying transitions and interactions between cell populations are largely unknown. Here, we show that diffuse large B-cell lymphomas possess a self-organized infrastructure comprising side population (SP) and non-SP cells, where transitions between clonogenic states are modulated by exosome-mediated Wnt signaling. DNA methylation modulated SP-non-SP transitions and was correlated with the reciprocal expressions of Wnt signaling pathway agonist Wnt3a in SP cells and the antagonist secreted frizzled-related protein 4 in non-SP cells. Lymphoma SP cells exhibited autonomous clonogenicity and exported Wnt3a via exosomes to neighboring cells, thus modulating population equilibrium in the tumor.

Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

NASA Technical Reports Server (NTRS)

Whitson, P. A.; Cintron, N. M.; Pietrzyk, R. A.; Scotto, P.; Loeppky, J. A.

1994-01-01

In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

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.

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

PubMed

Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

2016-07-15

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

STS-55 German payload specialists Walter and Schlegel work in SL-D2 module

NASA Technical Reports Server (NTRS)

1993-01-01

STS-55 German Payload Specialist 1 Ulrich Walter, wearing special head gear, conducts Tissue Thickness and Compliance Along Body Axis salt-water balance experiment in the Spacelab Deutsche 2 (SL-D2) science module aboard the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. Walter's activities in front of Rack 9 Anthrorack (AR) are monitored by German Payload Specialist 2 Hans Schlegel. Walter uses intravehicular activity (IVA) foot restraints. Walter and Schlegel represent the German Aerospace Research Establishment (DLR).

Virtual environment architecture for rapid application development

NASA Technical Reports Server (NTRS)

Grinstein, Georges G.; Southard, David A.; Lee, J. P.

1993-01-01

We describe the MITRE Virtual Environment Architecture (VEA), a product of nearly two years of investigations and prototypes of virtual environment technology. This paper discusses the requirements for rapid prototyping, and an architecture we are developing to support virtual environment construction. VEA supports rapid application development by providing a variety of pre-built modules that can be reconfigured for each application session. The modules supply interfaces for several types of interactive I/O devices, in addition to large-screen or head-mounted displays.

SKYLAB (SL)-2 - LAUNCH - KSC

NASA Image and Video Library

1973-05-31

S73-27095 (25 May 1973) --- The Skylab 2 crew, consisting of astronauts Charles Conrad Jr., Joseph P. Kerwin and Paul J. Weitz, inside the command module atop a Saturn IB launch vehicle, heads toward the Skylab space station in Earth orbit. The command module was inserted into Earth orbit approximately 10 minutes after liftoff. The three represent the first of three crews who will spend record-setting durations for human beings in space, while performing a variety of experiments. Photo credit: NASA

SKYLAB (SL)-2 - LAUNCH - KSC

NASA Image and Video Library

1973-05-31

S73-27096 (25 May 1973) --- The Skylab 2 crew, consisting of astronauts Charles Conrad Jr., Joseph P. Kerwin and Paul J. Weitz, inside the command module atop a Saturn IB launch vehicle, heads toward the Skylab space station in Earth orbit. The command module was inserted into Earth orbit approximately 10 minutes after liftoff. The three represent the first of three crews who will spend record-setting durations for human beings in space, while performing a variety of experiments. Photo credit: NASA

SU-F-J-205: Effect of Cone Beam Factor On Cone Beam CT Number Accuracy

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

Yao, W; Hua, C; Farr, J

Purpose: To examine the suitability of a Catphan™ 700 phantom for image quality QA of a cone beam computed tomography (CBCT) system deployed for proton therapy. Methods: Catphan phantoms, particularly Catphan™ 504, are commonly used in image quality QA for CBCT. As a newer product, Catphan™ 700 offers more tissue equivalent inserts which may be useful for generating the electron density – CT number curve for CBCT based treatment planning. The sensitometry-and-geometry module used in Catphan™ 700 is located at the end of the phantom and after the resolution line pair module. In Catphan™ 504 the line pair module ismore » located at the end of the phantom and after the sensitometry-and-geometry module. To investigate the effect of difference in location on CT number accuracy due to the cone beam factor, we scanned the Catphan™ 700 with the central plane of CBCT at the center of the phantom, line pair and sensitometry-andgeometry modules of the phantom, respectively. The protocol head and thorax scan modes were used. For each position, scans were repeated 4 times. Results: For the head scan mode, the standard deviation (SD) of the CT numbers of each insert under 4 repeated scans was up to 20 HU, 11 HU, and 11 HU, respectively, for the central plane of CBCT located at the center of the phantom, line pair, and sensitometry-and-geometry modules of the phantom. The mean of the SD was 9.9 HU, 5.7 HU, and 5.9 HU, respectively. For the thorax mode, the mean of the SD was 4.5 HU, 4.4 HU, and 4.4 HU, respectively. The assessment of image quality based on resolution and spatial linearity was not affected by imaging location changes. Conclusion: When the Catphan™ 700 was aligned to the center of imaging region, the CT number accuracy test may not meet expectations. We recommend reconfiguration of the modules.« less

Does the vestibular system contribute to head direction cell activity in the rat?

NASA Technical Reports Server (NTRS)

Brown, J. E.; Yates, B. J.; Taube, J. S.; Oman, C. M. (Principal Investigator)

2002-01-01

Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus (ADN), postsubiculum (PoS), and lateral mammillary nuclei (LMN), provide the neural substrate for the determination of head direction. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. However, vestibular inputs must be transformed considerably in order to signal head direction, and the neuronal circuitry that accomplishes this signal processing has not been fully established. Furthermore, it is unclear why the removal of vestibular inputs abolishes the directional sensitivity of HDC, as visual and other sensory inputs and motor feedback signals strongly affect the firing of these neurons and would be expected to maintain their directional-related activity. Further physiological studies will be required to establish the role of vestibular system in producing HDC responses, and anatomical studies are needed to determine the neural circuitry that mediates vestibular influences on determination of head direction.

Internally versus externally mediated triggers in the acquisition of visual targets in the horizontal plane.

PubMed

Kolev, Ognyan I; Reschke, Millard F

2014-06-01

In an operational setting acquisition of visual targets using both head and eye movements can be driven by memorized sequence of commands - internal triggering (IT) or by commands issued through secondary operator - external triggering (ET). The primary objective of our research was to examine differences in target acquisition using IT compared with ET. Using a forced time optimal strategy eight subjects were required to acquire targets with angular offsets of ±20°, 30° and 60° along the horizontal plane in both IT and ET conditions. The data showed that the eye/head latency difference in IT condition is longer than that for ET, the target acquisition time is also longer for IT commands. Consistent with this finding were similar results when examining the peak head velocity and peak head acceleration. Under IT protocol head amplitude is higher than when using ET. In conclusion, the study demonstrates that the pattern of performance of target acquisition task is influenced by the way of command triggering. Copyright © 2014 Elsevier B.V. All rights reserved.

Psychosocial consequences of head injury in children and adolescents: implications for rehabilitation.

PubMed

Livingston, M G; McCabe, R J

1990-01-01

Studies measuring psychosocial outcome in children and adolescents have shown that head injury leads to cognitive impairment which is directly related to the severity of injury in those with very severe head injury. Psychiatric disorders are also related to the severity of injury but here the relationship suggests that mediating factors are involved. No specific pattern of post-traumatic psychological/psychiatric dysfunction emerges from the studies, but it is clear that, as with adults, psychosocial recovery lags behind physical. Head injury affects the functioning of the young person in the family, at school, and within the wider community, often resulting in a secondary handicap of low self-esteem. The multitude of deficits which are a consequence of severe head injury present a challenge for rehabilitation specialists. A multi-disciplinary, multi-specialist, and multi-agency response is required. As a result, families are often presented with a bewildering array of treatments and programmes at different agencies. A case manager can be helpful in ensuring the appropriate use of available resources and can be the one professional in charge of a coordinating case record.

Payload Specialist Byron K. Lichtenberg working in the Spacelab

NASA Image and Video Library

1983-11-28

STS009-125-427 (28 Nov 1983) --- Payload Specialist Byron K. Lichtenberg carries out an experiment at the fluid physics module on the busy materials science double rack facility. Two beverage containers can be seen just above the biomedical engineer's head.

A longitudinal analysis of intimacy processes and psychological distress among couples coping with head and neck or lung cancers.

PubMed

Manne, Sharon; Badr, Hoda; Kashy, Deborah A

2012-06-01

Individuals diagnosed with lung and head and neck (HN) cancers and their spouses are at increased risk for distress. This study assessed whether the way couples communicate about cancer and their perceptions of relationship intimacy influenced both partners' adjustment. One-hundred thirty-nine patients and their spouses [For purposes of clarity, we refer to the patients' intimate partner as the spouse, regardless of actual marital status and we reserve the term partner to refer to the other person in the couple (i.e., the patient's partner is the spouse and the spouse's partner is the patient)] completed measures of spousal communication, intimacy, and distress at three time points over 6 months. Using multilevel modeling, an over-time actor-partner interdependence model was specified that examined whether intimacy mediated associations between one's own and one's partner's reports of communication at baseline and later distress. Patients and spouses who reported greater baseline distress reported more negative baseline communication as well as lower levels of intimacy and greater distress over time. Mediation analyses showed patients' and spouses' reports of positive spousal communication were associated with less subsequent distress largely through their effects on intimacy. Clinicians working with head and neck or lung cancer patients should assess communication and intimacy because both impact couples' distress.

Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium.

PubMed

Smith, I M; Baker, A; Arneborg, N; Jespersen, L

2015-11-01

The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast-mediated epithelial cell barrier protection from Salmonella invasion, thus encouraging future efforts aimed at confirming the observed effects in vivo and driving further strain development towards novel yeast probiotics. © 2015 The Society for Applied Microbiology.

Real-time characterization of cannabinoid receptor 1 (CB1 ) allosteric modulators reveals novel mechanism of action.

PubMed

Cawston, Erin E; Redmond, William J; Breen, Courtney M; Grimsey, Natasha L; Connor, Mark; Glass, Michelle

2013-10-01

The cannabinoid receptor type 1 (CB1 ) has an allosteric binding site. The drugs ORG27569 {5-chloro-3-ethyl-N-[2-[4-(1-piperidinyl)phenyl]ethyl]-1H-indole-2-carboxamide} and PSNCBAM-1 {1-(4-chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea} have been extensively characterized with regard to their effects on signalling of the orthosteric ligand CP55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol}, and studies have suggested that these allosteric modulators increase binding affinity but act as non-competitive antagonists in functional assays. To gain a deeper understanding of allosteric modulation of CB1 , we examined real-time signalling and trafficking responses of the receptor in the presence of allosteric modulators. Studies of CB1 signalling were carried out in HEK 293 and AtT20 cells expressing haemagglutinin-tagged human and rat CB1 . We measured real-time accumulation of cAMP, activation and desensitization of potassium channel-mediated cellular hyperpolarization and CB1 internalization. ORG27569 and PSNCBAM-1 produce a complex, concentration and time-dependent modulation of agonist-mediated regulation of cAMP levels, as well as an increased rate of desensitization of CB1 -mediated cellular hyperpolarization and a decrease in agonist-induced receptor internalization. Contrary to previous studies characterizing allosteric modulators at CB1, this study suggests that the mechanism of action is not non-competitive antagonism of signalling, but rather that enhanced binding results in an increased rate of receptor desensitization and reduced internalization, which results in time-dependent modulation of cAMP signalling. The observed effect of the allosteric modulators is therefore dependent on the time frame over which the signalling response occurs. This finding may have important consequences for the potential therapeutic application of these compounds. © 2013 The British Pharmacological Society.

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

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

Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de; Bandurska-Luque, Anna; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based onmore » primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.« less

Quality of life in head and neck cancer survivors: a cross-sectional survey.

PubMed

Chaukar, Devendra A; Walvekar, Rohan R; Das, Ashok K; Deshpande, Mandar S; Pai, Prathamesh S; Chaturvedi, Pankaj; Kakade, Anagha; D'Cruz, Anil K

2009-01-01

Head and neck cancer (HNC) survivors have substantial psychological distress in addition to treatment-related side effects. This study examines the long-term quality of life (QOL) of HNC survivors in a busy tertiary care center. A prospective, cross-sectional survey was conducted studying 212 HNC survivors 1 year after completion of their treatment at a tertiary cancer center. Quality of life assessments were performed using the 2 standardized health-related QOL questionnaires: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and The Quality of Life Questionnaire Head and Neck Cancer Module. The overall global QOL rating for the study cohort was satisfactory. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 scores showed that the domains where most patients faired poorly included financial difficulties (54%), appetite loss (36%), fatigue (33%), and cough (30%). The Quality of Life Questionnaire Head and Neck Cancer Module scale identified the domains with poor scores to be dry mouth (64%), dental problems (42%), sticky saliva (40%), cough (39%), and problems with mouth opening (32%). Patients with early-stage tumors and those treated with surgery alone had significantly better QOL scores when compared with advanced stage tumors and patients receiving either radiation alone or multimodality treatment, respectively. Quality of life questionnaires provide a medium for patients to effectively communicate with their physician in a busy tertiary care facility and provide an insight into the physical, psychological, and social problems affecting our patients which can then direct future interventions.

Variable Conductance Heat Pipes for Radioisotope Stirling Systems

NASA Astrophysics Data System (ADS)

Anderson, William G.; Tarau, Calin

2008-01-01

In a Stirling radioisotope system, heat must continually be removed from the GPHS modules, to maintain the GPHS modules and surrounding insulation at acceptable temperatures. Normally, the Stirling convertor provides this cooling. If the Stirling engine stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS, but also ending the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) was designed to allow multiple stops and restarts of the Stirling engine. A VCHP was designed for the Advanced Stirling Radioisotope Generator, with a 850 °C heater head temperature. The VCHP turns on with a ΔT of 30 °C, which is high enough to not risk standard ASRG operation but low enough to save most heater head life. This VCHP has a low mass, and low thermal losses for normal operation. In addition to the design, a proof-of-concept NaK VCHP was fabricated and tested. While NaK is normally not used in heat pipes, it has an advantage in that it is liquid at the reservoir operating temperature, while Na or K alone would freeze. The VCHP had two condensers, one simulating the heater head, and the other simulating the radiator. The experiments successfully demonstrated operation with the simulated heater head condenser off and on, while allowing the reservoir temperature to vary over 40 to 120 °C, the maximum range expected. In agreement with previous NaK heat pipe tests, the evaporator ΔT was roughly 70 °C, due to distillation of the NaK in the evaporator.

Dosimetric Factors Associated With Long-Term Dysphagia After Definitive Radiotherapy for Squamous Cell Carcinoma of the Head and Neck

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

Caudell, Jimmy J.; Schaner, Philip E.; Desmond, Renee A.

2010-02-01

Purpose: Intensification of radiotherapy and chemotherapy for head-and-neck cancer may lead to increased rates of dysphagia. Dosimetric predictors of objective findings of long-term dysphagia were sought. Methods and Materials: From an institutional database, 83 patients were identified who underwent definitive intensity-modulated radiotherapy for squamous cell carcinoma of the head and neck, after exclusion of those who were treated for a second or recurrent head-and-neck primary lesion, had locoregional recurrence at any time, had less than 12 months of follow-up, or had postoperative radiotherapy. Dosimetric parameters were analyzed relative to three objective endpoints as a surrogate for severe long-term dysphagia: percutaneousmore » endoscopic gastrostomy (PEG) tube dependence at 12 months, aspiration on modified barium swallow, or pharyngoesophageal stricture requiring dilation. Results: Mean dose greater than 41 Gy and volume receiving 60 Gy (V{sub 60}) greater than 24% to the larynx were significantly associated with PEG tube dependence and aspiration. V{sub 60} greater than 12% to the inferior pharyngeal constrictor was also significantly associated with increased PEG tube dependence and aspiration. V{sub 65} greater than 33% to the superior pharyngeal constrictor or greater than 75% to the middle pharyngeal constrictor was associated with pharyngoesophageal stricture requiring dilation. Conclusions: Doses to the larynx and pharyngeal constrictors predicted long-term swallowing complications, even when controlled for other clinical factors. The addition of these structures to intensity-modulated radiotherapy optimization may reduce the incidence of dysphagia, although cautious clinical validation is necessary.« less

A visible Chinese human-combined Monte Carlo simulation study on low-level light therapy of stroke

NASA Astrophysics Data System (ADS)

Wang, Pengbo; Pan, Boan; Zhong, Fulin; Li, Ting

2017-02-01

Stroke is a devastating disease, which is the third leading cause of death and disability worldwide. Although the incidence of stroke increases progressively with age, morbidity among young and middle-aged adults is increasing annually. Medications nevertheless remain the bulwarks of stroke. The treatment is ineffective, speculative and has a long treatment cycle. The function of acupuncture and moxibustion, which are potential therapeutic tools for stroke, is still controversial. Recently, Low-level light therapy (LLLT) has been demonstrated potent in vivo efficacy for treatment of ischemic conditions of acute myocardial infraction and stroke in multiple validated animal models. Optimum LLLT treatment has a dominant influence on therapy of stroke. While more than a thousand clinical trials have been halted, only a few trials on animals have been reported. We addressed this issue by simulating near-infrared light propagation with accurate visible Chinese human head by Monte Carlo modeling. The visible human head embody region of atherosclerotic plaques in head. Through comparing the light propagation of different light illumination, we can get a precise, optimized and straightforward treatment. Here, we developed a LLLT helmet for treating stroke depend on near-infrared light. There are more than 30 LED arrays in in multi-layered 3D printed helmet. Each LED array has independent water-cooling module and can be adjusted to touch the head of different subjects based on Electro pneumatic module. Moreover, the software provides the setup of illumination parameters and 3D distribution of light fluence rate distribution in human brain.

Effect of visuospatial neglect on spatial navigation and heading after stroke.

PubMed

Aravind, Gayatri; Lamontagne, Anouk

2017-06-09

Visuospatial neglect (VSN) impairs the control of locomotor heading in post-stroke individuals, which may affect their ability to safely avoid moving objects while walking. We aimed to compare VSN+ and VSN- stroke individuals in terms of changes in heading and head orientation in space while avoiding obstacles approaching from different directions and reorienting toward the final target. Stroke participants with VSN (VSN+) and without VSN (VSN-) walked in a virtual environment avoiding obstacles that approached contralesionally, head-on or ipsilesionally. Measures of obstacle avoidance (onset-of-heading change, maximum mediolateral deviation) and target alignment (heading and head-rotation errors with respect to target) were compared across groups and obstacle directions. In total, 26 participants with right-hemisphere stroke participated (13 VSN+ and 13 VSN-; 24 males; mean age 60.3 years, range 48 to 72 years). A larger proportion of VSN+ (75%) than VSN- (38%) participants collided with contralesional and head-on obstacles. For VSN- participants, deviating to the same side as the obstacle was a safe strategy to avoid diagonal obstacles and deviating to the opposite-side led to occasional collisions. VSN+ participants deviated ipsilesionally, displaying same-side and opposite-side strategies for ipsilesional and contralesional obstacles, respectively. Overall, VSN+ participants showed greater distances at onset-of-heading change, smaller maximum mediolateral deviation and larger errors in target alignment as compared with VSN- participants. The ipsilesional bias arising from VSN influences the modulation of heading in response to obstacles and, along with the adoption of the "riskier" strategies, contribute to the higher number colliders and poor goal-directed walking abilities in stroke survivors with VSN. Future research should focus on developing assessment and training tools for complex locomotor tasks such as obstacle avoidance in this population. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cyclin-dependent kinase 8 module expression profiling reveals requirement of mediator subunits 12 and 13 for transcription of Serpent-dependent innate immunity genes in Drosophila.

PubMed

Kuuluvainen, Emilia; Hakala, Heini; Havula, Essi; Sahal Estimé, Michelle; Rämet, Mika; Hietakangas, Ville; Mäkelä, Tomi P

2014-06-06

The Cdk8 (cyclin-dependent kinase 8) module of Mediator integrates regulatory cues from transcription factors to RNA polymerase II. It consists of four subunits where Med12 and Med13 link Cdk8 and cyclin C (CycC) to core Mediator. Here we have investigated the contributions of the Cdk8 module subunits to transcriptional regulation using RNA interference in Drosophila cells. Genome-wide expression profiling demonstrated separation of Cdk8-CycC and Med12-Med13 profiles. However, transcriptional regulation by Cdk8-CycC was dependent on Med12-Med13. This observation also revealed that Cdk8-CycC and Med12-Med13 often have opposite transcriptional effects. Interestingly, Med12 and Med13 profiles overlapped significantly with that of the GATA factor Serpent. Accordingly, mutational analyses indicated that GATA sites are required for Med12-Med13 regulation of Serpent-dependent genes. Med12 and Med13 were also found to be required for Serpent-activated innate immunity genes in defense to bacterial infection. The results reveal a novel role for the Cdk8 module in Serpent-dependent transcription and innate immunity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of glia phenotype modulators based on select glial function regulatory signaling pathways.

PubMed

Lee, Sun-Hwa; Suk, Kyoungho

2018-04-20

Despite the considerable social and economic burden on the healthcare system worldwide due to neurodegenerative diseases, there are currently few disease-altering treatment options for many of these conditions. Therefore, new approaches for both prevention and intervention for neurodegenerative diseases are urgently required. Microglia-mediated neurotoxicity is one of the pathologic hallmarks common to Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Current therapeutic approaches to target microglia-mediated neurotoxicity are focused on the identification of glia phenotype modulators (GPMs), which can inhibit the 'classical' pro-inflammatory and neurotoxic phenotypes of microglia. Areas covered: This article reviews selected microglial molecular targets and pathways involved in either neurotoxicity or neuroprotection and how their identification. Expert opinion: Microglial activation and their signaling pathways have important implications in the neurotoxicity and brain disorders. Pharmacological modulation of microglial activation may serve as a potential therapeutic approach for targeting microglia-mediated neurotoxicity. However, given that microglia change their activation states depending on the timing, stage, and severity of disease, and even aging, the appropriate window should be considered for this approach to be clinically effective. In the future, the identification of unknown extracellular signals and intracellular molecular switches that control phenotypic shifts may facilitate the development of novel therapeutics targeting microglia-mediated neurotoxicity.

Biomedical Potential of mTOR Modulation by Nanoparticles.

PubMed

Hulea, Laura; Markovic, Zoran; Topisirovic, Ivan; Simmet, Thomas; Trajkovic, Vladimir

2016-05-01

Modulation of the mammalian target of rapamycin (mTOR), the principal regulator of cellular homeostasis, underlies the biological effects of engineered nanoparticles, including regulation of cell death/survival and metabolic responses. Understanding the mechanisms and biological actions of nanoparticle-mediated mTOR modulation may help in developing safe and efficient nanotherapeutics to fight human disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

PubMed

Avaritt, Brittany R; Swaan, Peter W

2014-09-01

Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

Molecular imaging of drug-modulated protein-protein interactions in living subjects.

PubMed

Paulmurugan, Ramasamy; Massoud, Tarik F; Huang, Jing; Gambhir, Sanjiv S

2004-03-15

Networks of protein interactions mediate cellular responses to environmental stimuli and direct the execution of many different cellular functional pathways. Small molecules synthesized within cells or recruited from the external environment mediate many protein interactions. The study of small molecule-mediated interactions of proteins is important to understand abnormal signal transduction pathways in cancer and in drug development and validation. In this study, we used split synthetic renilla luciferase (hRLUC) protein fragment-assisted complementation to evaluate heterodimerization of the human proteins FRB and FKBP12 mediated by the small molecule rapamycin. The concentration of rapamycin required for efficient dimerization and that of its competitive binder ascomycin required for dimerization inhibition were studied in cell lines. The system was dually modulated in cell culture at the transcription level, by controlling nuclear factor kappaB promoter/enhancer elements using tumor necrosis factor alpha, and at the interaction level, by controlling the concentration of the dimerizer rapamycin. The rapamycin-mediated dimerization of FRB and FKBP12 also was studied in living mice by locating, quantifying, and timing the hRLUC complementation-based bioluminescence imaging signal using a cooled charged coupled device camera. This split reporter system can be used to efficiently screen small molecule drugs that modulate protein-protein interactions and also to assess drugs in living animals. Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells.

TMV-Cg Coat Protein stabilizes DELLA proteins and in turn negatively modulates salicylic acid-mediated defense pathway during Arabidopsis thaliana viral infection.

PubMed

Rodriguez, Maria Cecilia; Conti, Gabriela; Zavallo, Diego; Manacorda, Carlos Augusto; Asurmendi, Sebastian

2014-08-03

Plant viral infections disturb defense regulatory networks during tissue invasion. Emerging evidence demonstrates that a significant proportion of these alterations are mediated by hormone imbalances. Although the DELLA proteins have been reported to be central players in hormone cross-talk, their role in the modulation of hormone signaling during virus infections remains unknown. This work revealed that TMV-Cg coat protein (CgCP) suppresses the salicylic acid (SA) signaling pathway without altering defense hormone SA or jasmonic acid (JA) levels in Arabidopsis thaliana. Furthermore, it was observed that the expression of CgCP reduces plant growth and delays the timing of floral transition. Quantitative RT-qPCR analysis of DELLA target genes showed that CgCP alters relative expression of several target genes, indicating that the DELLA proteins mediate transcriptional changes produced by CgCP expression. Analyses by fluorescence confocal microscopy showed that CgCP stabilizes DELLA proteins accumulation in the presence of gibberellic acid (GA) and that the DELLA proteins are also stabilized during TMV-Cg virus infections. Moreover, DELLA proteins negatively modulated defense transcript profiles during TMV-Cg infection. As a result, TMV-Cg accumulation was significantly reduced in the quadruple-DELLA mutant Arabidopsis plants compared to wild type plants. Taken together, these results demonstrate that CgCP negatively regulates the salicylic acid-mediated defense pathway by stabilizing the DELLA proteins during Arabidopsis thaliana viral infection, suggesting that CgCP alters the stability of DELLAs as a mechanism of negative modulation of antiviral defense responses.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

HIV Nef-mediated cellular phenotypes are differentially expressed as a function of intracellular Nef concentrations.

PubMed

Liu, X; Schrager, J A; Lange, G D; Marsh, J W

2001-08-31

Nef is a regulatory protein encoded by the genome of both human and simian immunodeficiency virus. Its expression in T cells leads to CD4 and major histocompatibility complex class I modulation and either enhancement or suppression of T cell activation. How this viral protein achieves multiple and at times opposing activities has been unclear. Through direct measurements of Nef and the Nef-GFP fusion protein, we find that these events are mediated by different Nef concentrations. Relative to the intracellular concentration that down-modulates surface CD4, an order of magnitude increase in Nef-GFP expression is required for a comparable modulation of major histocompatibility complex class I, and a further 3-fold increase is necessary to suppress T cell activation.

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis.

PubMed

Aranda-Orgilles, Beatriz; Saldaña-Meyer, Ricardo; Wang, Eric; Trompouki, Eirini; Fassl, Anne; Lau, Stephanie; Mullenders, Jasper; Rocha, Pedro P; Raviram, Ramya; Guillamot, María; Sánchez-Díaz, María; Wang, Kun; Kayembe, Clarisse; Zhang, Nan; Amoasii, Leonela; Choudhuri, Avik; Skok, Jane A; Schober, Markus; Reinberg, Danny; Sicinski, Piotr; Schrewe, Heinrich; Tsirigos, Aristotelis; Zon, Leonard I; Aifantis, Iannis

2016-12-01

Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality. Deleting other members of the Mediator kinase module does not affect HSC function, suggesting kinase-independent roles of MED12. MED12 deletion destabilizes P300 binding at lineage-specific enhancers, resulting in H3K27Ac depletion, enhancer de-activation, and consequent loss of HSC stemness signatures. As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Perceived discrimination, psychological distress, and current smoking status: results from the Behavioral Risk Factor Surveillance System Reactions to Race module, 2004-2008.

PubMed

Purnell, Jason Q; Peppone, Luke J; Alcaraz, Kassandra; McQueen, Amy; Guido, Joseph J; Carroll, Jennifer K; Shacham, Enbal; Morrow, Gary R

2012-05-01

We examined the association between perceived discrimination and smoking status and whether psychological distress mediated this relationship in a large, multiethnic sample. We used 2004 through 2008 data from the Behavioral Risk Factor Surveillance System Reactions to Race module to conduct multivariate logistic regression analyses and tests of mediation examining associations between perceived discrimination in health care and workplace settings, psychological distress, and current smoking status. Regardless of race/ethnicity, perceived discrimination was associated with increased odds of current smoking. Psychological distress was also a significant mediator of the discrimination-smoking association. Our results indicate that individuals who report discriminatory treatment in multiple domains may be more likely to smoke, in part, because of the psychological distress associated with such treatment.

Locomotor activity modulates associative learning in mouse cerebellum.

PubMed

Albergaria, Catarina; Silva, N Tatiana; Pritchett, Dominique L; Carey, Megan R

2018-05-01

Changes in behavioral state can profoundly influence brain function. Here we show that behavioral state modulates performance in delay eyeblink conditioning, a cerebellum-dependent form of associative learning. Increased locomotor speed in head-fixed mice drove earlier onset of learning and trial-by-trial enhancement of learned responses that were dissociable from changes in arousal and independent of sensory modality. Eyelid responses evoked by optogenetic stimulation of mossy fiber inputs to the cerebellum, but not at sites downstream, were positively modulated by ongoing locomotion. Substituting prolonged, low-intensity optogenetic mossy fiber stimulation for locomotion was sufficient to enhance conditioned responses. Our results suggest that locomotor activity modulates delay eyeblink conditioning through increased activation of the mossy fiber pathway within the cerebellum. Taken together, these results provide evidence for a novel role for behavioral state modulation in associative learning and suggest a potential mechanism through which engaging in movement can improve an individual's ability to learn.

Apollo 16 lunar module "Orion" photographed from distance during EVA

NASA Image and Video Library

1972-04-23

AS16-116-18678 (23 April 1972) --- A view from the moving Apollo 16 Lunar Roving Vehicle (LRV) as the crew men headed "home" at the end of the mission's third and final extravehicular activity (EVA). Astronaut John W. Young called attention to the series of block fields between the Lunar Module (LM) and LRV. Young also noted that, "The LM was obviously sitting in the only flat place around." Stone Mountain stretches about half way across the background. The high gain antenna and the RCA television camera on the LRV are in the foreground. While astronauts Young, commander; and Charles M. Duke Jr., lunar module pilot; descended in the Apollo 16 LM "Orion" to explore the Descartes highlands landing site on the moon, astronaut Thomas K. Mattingly II, command module pilot, remained with the Command and Service Modules (CSM) "Casper" in lunar orbit.

mTHPC mediated photodynamic therapy (PDT) of squamous cell carcinoma in the head and neck: a systematic review.

PubMed

de Visscher, S A H J; Dijkstra, P U; Tan, I B; Roodenburg, J L N; Witjes, M J H

2013-03-01

Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC). To evaluate available evidence on the use of mTHPC (Foscan®) mediated PDT, we conducted a review of the literature. A systematic review was performed by searching seven bibliographic databases on database specific mesh terms and free text words in the categories; "head and neck neoplasms", "Photodynamic Therapy" and "Foscan". Papers identified were assessed on several criteria by two independent reviewers. The search identified 566 unique papers. Twelve studies were included for our review. Six studies reported PDT with curative intent and six studies reported PDT with palliative intent, of which three studies used interstitial PDT. The studies did not compare PDT to other treatments and none exceeded level 3 using the Oxford levels of evidence. Pooling of data (n=301) was possible for four of the six studies with curative intent. T1 tumors showed higher complete response rates compared to T2 (86% vs 63%). PDT with palliative intent was predominantly used in patients unsuitable for further conventional treatment. After PDT, substantial tumor response and increase in quality of life was observed. Complications of PDT were mostly related to non-compliance to light restriction guidelines. The studies on mTHPC mediated PDT for HNSCC are not sufficient for adequate assessment of the efficacy for curative intent. To assess efficacy of PDT with curative intent, high quality comparative, randomized studies are needed. Palliative treatment with PDT seems to increase the quality of life in otherwise untreatable patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Surface dose measurement with Gafchromic EBT3 film for intensity modulated radiotherapy technique

NASA Astrophysics Data System (ADS)

Akbas, Ugur; Kesen, Nazmiye Donmez; Koksal, Canan; Okutan, Murat; Demir, Bayram; Becerir, Hatice Bilge

2017-09-01

Accurate dose measurement in the buildup region is extremely difficult. Studies have reported that treatment planning systems (TPS) cannot calculate surface dose accurately. The aim of the study was to compare the film measurements and TPS calculations for surface dose in head and neck cancer treatment using intensity modulated radiation therapy (IMRT). IMRT plans were generated for 5 head and neck cancer patients by using Varian Eclipse TPS. Quality assurance (QA) plans of these IMRT plans were created on rando phantoms for surface dose measurements. EBT3 films were cut in size of 2.5 x 2.5 cm2 and placed on the left side, right side and the center of larynx and then the films were irradiated with 6 MV photon beams. The measured doses were compared with TPS. The results of TPS calculations were found to be lower compared to the EBT3 film measurements at all selected points. The lack of surface dose calculation in TPS should be considered while evaluating the radiotherapy plans.

View of the Lunar Portable Magnetometer (LPM)

NASA Image and Video Library

1970-12-21

S70-56721 (December 1970) --- A close-up view of the Lunar Portable Magnetometer (LPM), which will be used by the crew of the Apollo 14 lunar landing mission during the second extravehicular activity (EVA). The LPM's components, a tripod-mounted flux-gate magnetometer sensor head and an electronics data package, connected by a 50-feet flat cable, function together to measure variations in the lunar magnetic field at several points on the geological traverse. Data gathered will be used to determine the location, strength and dimensions of magnetic sources, as well as knowledge of the local and total selenological structure. The LPM will be carried on the Modular Equipment Transporter (MET), and deployed by the lunar module pilot, who will align the sensor head at least 35 feet from the data package. The LM pilot will then return to the MET and verbally relay the LPM readouts to Earth. Astronaut Edgar D. Mitchell is the lunar module pilot for the Apollo 14 lunar landing mission.

A Model of Self-Organizing Head-Centered Visual Responses in Primate Parietal Areas

PubMed Central

Mender, Bedeho M. W.; Stringer, Simon M.

2013-01-01

We present a hypothesis for how head-centered visual representations in primate parietal areas could self-organize through visually-guided learning, and test this hypothesis using a neural network model. The model consists of a competitive output layer of neurons that receives afferent synaptic connections from a population of input neurons with eye position gain modulated retinal receptive fields. The synaptic connections in the model are trained with an associative trace learning rule which has the effect of encouraging output neurons to learn to respond to subsets of input patterns that tend to occur close together in time. This network architecture and synaptic learning rule is hypothesized to promote the development of head-centered output neurons during periods of time when the head remains fixed while the eyes move. This hypothesis is demonstrated to be feasible, and each of the core model components described is tested and found to be individually necessary for successful self-organization. PMID:24349064

Design and development of a Space Station proximity operations research and development mockup

NASA Technical Reports Server (NTRS)

Haines, Richard F.

1986-01-01

Proximity operations (Prox-Ops) on-orbit refers to all activities taking place within one km of the Space Station. Designing a Prox-Ops control station calls for a comprehensive systems approach which takes into account structural constraints, orbital dynamics including approach/departure flight paths, myriad human factors and other topics. This paper describes a reconfigurable full-scale mock-up of a Prox-Ops station constructed at Ames incorporating an array of windows (with dynamic star field, target vehicle(s), and head-up symbology), head-down perspective display of manned and unmanned vehicles, voice- actuated 'electronic checklist', computer-generated voice system, expert system (to help diagnose subsystem malfunctions), and other displays and controls. The facility is used for demonstrations of selected Prox-Ops approach scenarios, human factors research (work-load assessment, determining external vision envelope requirements, head-down and head-up symbology design, voice synthesis and recognition research, etc.) and development of engineering design guidelines for future module interiors.

A smart checkpointing scheme for improving the reliability of clustering routing protocols.

PubMed

Min, Hong; Jung, Jinman; Kim, Bongjae; Cho, Yookun; Heo, Junyoung; Yi, Sangho; Hong, Jiman

2010-01-01

In wireless sensor networks, system architectures and applications are designed to consider both resource constraints and scalability, because such networks are composed of numerous sensor nodes with various sensors and actuators, small memories, low-power microprocessors, radio modules, and batteries. Clustering routing protocols based on data aggregation schemes aimed at minimizing packet numbers have been proposed to meet these requirements. In clustering routing protocols, the cluster head plays an important role. The cluster head collects data from its member nodes and aggregates the collected data. To improve reliability and reduce recovery latency, we propose a checkpointing scheme for the cluster head. In the proposed scheme, backup nodes monitor and checkpoint the current state of the cluster head periodically. We also derive the checkpointing interval that maximizes reliability while using the same amount of energy consumed by clustering routing protocols that operate without checkpointing. Experimental comparisons with existing non-checkpointing schemes show that our scheme reduces both energy consumption and recovery latency.

A Smart Checkpointing Scheme for Improving the Reliability of Clustering Routing Protocols

PubMed Central

Min, Hong; Jung, Jinman; Kim, Bongjae; Cho, Yookun; Heo, Junyoung; Yi, Sangho; Hong, Jiman

2010-01-01

In wireless sensor networks, system architectures and applications are designed to consider both resource constraints and scalability, because such networks are composed of numerous sensor nodes with various sensors and actuators, small memories, low-power microprocessors, radio modules, and batteries. Clustering routing protocols based on data aggregation schemes aimed at minimizing packet numbers have been proposed to meet these requirements. In clustering routing protocols, the cluster head plays an important role. The cluster head collects data from its member nodes and aggregates the collected data. To improve reliability and reduce recovery latency, we propose a checkpointing scheme for the cluster head. In the proposed scheme, backup nodes monitor and checkpoint the current state of the cluster head periodically. We also derive the checkpointing interval that maximizes reliability while using the same amount of energy consumed by clustering routing protocols that operate without checkpointing. Experimental comparisons with existing non-checkpointing schemes show that our scheme reduces both energy consumption and recovery latency. PMID:22163389

The role of proteosome-mediated proteolysis in modulating potentially harmful transcription factor activity in Saccharomyces cerevisiae

PubMed Central

Bonzanni, Nicola; Zhang, Nianshu; Oliver, Stephen G.; Fisher, Jasmin

2011-01-01

Motivation: The appropriate modulation of the stress response to variable environmental conditions is necessary to maintain sustained viability in Saccharomyces cerevisiae. Particularly, controlling the abundance of proteins that may have detrimental effects on cell growth is crucial for rapid recovery from stress-induced quiescence. Results: Prompted by qualitative modeling of the nutrient starvation response in yeast, we investigated in vivo the effect of proteolysis after nutrient starvation showing that, for the Gis1 transcription factor at least, proteasome-mediated control is crucial for a rapid return to growth. Additional bioinformatics analyses show that potentially toxic transcriptional regulators have a significantly lower protein half-life, a higher fraction of unstructured regions and more potential PEST motifs than the non-detrimental ones. Furthermore, inhibiting proteasome activity tends to increase the expression of genes induced during the Environmental Stress Response more than those in the rest of the genome. Our combined results suggest that proteasome-mediated proteolysis of potentially toxic transcription factors tightly modulates the stress response in yeast. Contact: jasmin.fisher@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21685082

The Anti-Helminthic Niclosamide Inhibits Wnt/Frizzled1 Signaling†

PubMed Central

Chen, Minyong; Wang, Jiangbo; Lu, Jiuyi; Bond, Michael C.; Ren, Xiu-Rong; Lyerly, H. Kim; Barak, Larry S.; Chen, Wei

2009-01-01

Wnt proteins bind to seven-transmembrane Frizzled receptors to mediate the important developmental, morphogenetic, and tissue-regenerative effects of Wnt signaling. Dysregulated Wnt signaling is associated with many cancers. Currently there exist no drug candidates, or even tool compounds that modulate Wnt-mediated receptor trafficking, and subsequent Wnt signaling. We examined libraries of FDA-approved drugs for their utility as Frizzled internalization modulators, employing a primary imaged-based GFP-fluorescence assay that uses Frizzled1 endocytosis as the readout. We now report that the anti-helminthic niclosamide, a drug used for the treatment of tapeworm, promotes Frizzled1 endocytosis, down regulates Dishevelled-2 protein, and inhibits Wnt3A-stimulated β-catenin stabilization and LEF/TCF reporter activity. Additionally, following niclosamide mediated internalization, the Frizzled1 receptor co-localizes in vesicles containing Transferrin and agonist-activated β2-adrenergic receptor. Therefore, niclosamide may serve as a negative modulator of Wnt/Frizzled1 signaling by depleting up-stream signaling molecules (i.e. Frizzled and Dishevelled), and moreover may provide a valuable means to study the physiological consequences of Wnt signaling. PMID:19772353

Characterization of C1q in Teleosts

PubMed Central

Hu, Yu-Lan; Pan, Xin-Min; Xiang, Li-Xin; Shao, Jian-Zhong

2010-01-01

C1qs are key components of the classical complement pathway. They have been well documented in human and mammals, but little is known about their molecular and functional characteristics in fish. In the present study, full-length cDNAs of c1qA, c1qB, and c1qC from zebrafish (Danio rerio) were cloned, revealing the conservation of their chromosomal synteny and organization between zebrafish and other species. For functional analysis, the globular heads of C1qA (ghA), C1qB (ghB), and C1qC (ghC) were expressed in Escherichia coli as soluble proteins. Hemolytic inhibitory assays showed that hemolytic activity in carp serum can be inhibited significantly by anti-C1qA, -C1qB, and -C1qC of zebrafish, respectively, indicating that C1qA, C1qB, and C1qC are involved in the classical pathway and are conserved functionally from fish to human. Zebrafish C1qs also could specifically bind to heat-aggregated zebrafish IgM, human IgG, and IgM. The involvement of globular head modules in the C1q-dependent classical pathway demonstrates the structural and functional conservation of these molecules in the classical pathway and their IgM or IgG binding sites during evolution. Phylogenetic analysis revealed that c1qA, c1qB, and c1qC may be formed by duplications of a single copy of c1qB and that the C1q family is, evolutionarily, closely related to the Emu family. This study improves current understanding of the evolutionary history of the C1q family and C1q-mediated immunity. PMID:20615881

Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation

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

Limesand, Kirsten H., E-mail: limesank@u.arizona.ed; Department of Nutritional Sciences, University of Arizona, Tucson, AZ; Avila, Jennifer L.

Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVBmore » mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.« less

CD137 Stimulation Enhances Cetuximab-Induced Natural Killer: Dendritic Cell Priming of Antitumor T-Cell Immunity in Patients with Head and Neck Cancer.

PubMed

Srivastava, Raghvendra M; Trivedi, Sumita; Concha-Benavente, Fernando; Gibson, Sandra P; Reeder, Carly; Ferrone, Soldano; Ferris, Robert L

2017-02-01

Cetuximab, an EGFR-specific antibody (mAb), modestly improves clinical outcome in patients with head and neck cancer (HNC). Cetuximab mediates natural killer (NK) cell:dendritic cell (DC) cross-talk by cross-linking FcγRIIIa, which is important for inducing antitumor cellular immunity. Cetuximab-activated NK cells upregulate the costimulatory receptor CD137 (4-1BB), which, when triggered by agonistic mAb urelumab, might enhance NK-cell functions, to promote T-cell-based immunity. CD137 expression on tumor-infiltrating lymphocytes was evaluated in a prospective cetuximab neoadjuvant trial, and CD137 stimulation was evaluated in a phase Ib trial, in combining agonistic urelumab with cetuximab. Flow cytometry and cytokine release assays using NK cells and DC were used in vitro, testing the addition of urelumab to cetuximab-activated NK, DC, and cross presentation to T cells. CD137 agonist mAb urelumab enhanced cetuximab-activated NK-cell survival, DC maturation, and tumor antigen cross-presentation. Urelumab boosted DC maturation markers, CD86 and HLA DR, and antigen-processing machinery (APM) components TAP1/2, leading to increased tumor antigen cross-presentation. In neoadjuvant cetuximab-treated patients with HNC, upregulation of CD137 by intratumoral, cetuximab-activated NK cells correlated with FcγRIIIa V/F polymorphism and predicted clinical response. Moreover, immune biomarker modulation was observed in an open label, phase Ib clinical trial, of patients with HNC treated with cetuximab plus urelumab. These results suggest a beneficial effect of combination immunotherapy using cetuximab and CD137 agonist in HNC. Clin Cancer Res; 23(3); 707-16. ©2016 AACR. ©2016 American Association for Cancer Research.

Virus Infection and Death Receptor-Mediated Apoptosis.

PubMed

Zhou, Xingchen; Jiang, Wenbo; Liu, Zhongshun; Liu, Shuai; Liang, Xiaozhen

2017-10-27

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis.

Virus Infection and Death Receptor-Mediated Apoptosis

PubMed Central

Zhou, Xingchen; Jiang, Wenbo; Liu, Zhongshun; Liu, Shuai; Liang, Xiaozhen

2017-01-01

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis. PMID:29077026

Loss of actomyosin regulation in distal arthrogryposis myopathy due to mutant myosin binding protein-C slow.

PubMed

Ackermann, Maegen A; Patel, Puja D; Valenti, Jane; Takagi, Yasuharu; Homsher, Earl; Sellers, James R; Kontrogianni-Konstantopoulos, Aikaterini

2013-08-01

Myosin binding protein C (MyBP-C) is expressed in striated muscles, where it plays key roles in the modulation of actomyosin cross-bridges. Slow MyBP-C (sMyBP-C) consists of multiple variants sharing common domains but also containing unique segments within the NH2 and COOH termini. Two missense mutations in the NH2 terminus (W236R) and COOH terminus (Y856H) of sMyBP-C have been causally linked to the development of distal arthrogryposis-1 (DA-1), a severe skeletal muscle disorder. Using a combination of in vitro binding and motility assays, we show that the COOH terminus mediates binding of sMyBP-C to thick filaments, while the NH2 terminus modulates the formation of actomyosin cross-bridges in a variant-specific manner. Consistent with this, a recombinant NH2-terminal peptide that excludes residues 34-59 reduces the sliding velocity of actin filaments past myosin heads from 9.0 ± 1.3 to 5.7 ± 1.0 μm/s at 0.1 μM, while a recombinant peptide that excludes residues 21-59 fails to do so. Notably, the actomyosin regulatory properties of sMyBP-C are completely abolished by the presence of the DA-1 mutations. In summary, our studies are the first to show that the NH2 and COOH termini of sMyBP-C have distinct functions, which are regulated by differential splicing, and are compromized by the presence of missense point mutations linked to muscle disease.

Novel insights into the response of Atlantic salmon (Salmo salar) to Piscirickettsia salmonis: Interplay of coding genes and lncRNAs during bacterial infection.

PubMed

Valenzuela-Miranda, Diego; Gallardo-Escárate, Cristian

2016-12-01

Despite the high prevalence and impact to Chilean salmon aquaculture of the intracellular bacterium Piscirickettsia salmonis, the molecular underpinnings of host-pathogen interactions remain unclear. Herein, the interplay of coding and non-coding transcripts has been proposed as a key mechanism involved in immune response. Therefore, the aim of this study was to evidence how coding and non-coding transcripts are modulated during the infection process of Atlantic salmon with P. salmonis. For this, RNA-seq was conducted in brain, spleen, and head kidney samples, revealing different transcriptional profiles according to bacterial load. Additionally, while most of the regulated genes annotated for diverse biological processes during infection, a common response associated with clathrin-mediated endocytosis and iron homeostasis was present in all tissues. Interestingly, while endocytosis-promoting factors and clathrin inductions were upregulated, endocytic receptors were mainly downregulated. Furthermore, the regulation of genes related to iron homeostasis suggested an intracellular accumulation of iron, a process in which heme biosynthesis/degradation pathways might play an important role. Regarding the non-coding response, 918 putative long non-coding RNAs were identified, where 425 were newly characterized for S. salar. Finally, co-localization and co-expression analyses revealed a strong correlation between the modulations of long non-coding RNAs and genes associated with endocytosis and iron homeostasis. These results represent the first comprehensive study of putative interplaying mechanisms of coding and non-coding RNAs during bacterial infection in salmonids. Copyright © 2016 Elsevier Ltd. All rights reserved.

3-dimensional telepresence system for a robotic environment

DOEpatents

Anderson, Matthew O.; McKay, Mark D.

2000-01-01

A telepresence system includes a camera pair remotely controlled by a control module affixed to an operator. The camera pair provides for three dimensional viewing and the control module, affixed to the operator, affords hands-free operation of the camera pair. In one embodiment, the control module is affixed to the head of the operator and an initial position is established. A triangulating device is provided to track the head movement of the operator relative to the initial position. A processor module receives input from the triangulating device to determine where the operator has moved relative to the initial position and moves the camera pair in response thereto. The movement of the camera pair is predetermined by a software map having a plurality of operation zones. Each zone therein corresponds to unique camera movement parameters such as speed of movement. Speed parameters include constant speed, or increasing or decreasing. Other parameters include pan, tilt, slide, raise or lowering of the cameras. Other user interface devices are provided to improve the three dimensional control capabilities of an operator in a local operating environment. Such other devices include a pair of visual display glasses, a microphone and a remote actuator. The pair of visual display glasses are provided to facilitate three dimensional viewing, hence depth perception. The microphone affords hands-free camera movement by utilizing voice commands. The actuator allows the operator to remotely control various robotic mechanisms in the remote operating environment.

Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study.

PubMed

Hartford, Alan C; Davis, Thomas H; Buckey, Jay C; Foote, Robert L; Sinesi, Mark S; Williams, Benjamin B; Fariss, Anna K; Schaner, Philip E; Claus, Paul L; Okuno, Scott H; Hussey, James R; Clarke, Richard E

2017-03-01

To explore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy >6 months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4 atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiation therapy began within 15 minutes after HBO. Patients were followed for 2 years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+ years for local recurrence, distant metastases, disease-specific survival, and overall survival. Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14 weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5 minutes, with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per-protocol 5-year overall survival was 100%, local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO. While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-F-T-186: A Treatment Planning Study of Normal Tissue Sparing with Robustness Optimized IMPT, 4Pi IMRT, and VMAT for Head and Neck Cases

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

Zhang, J; Li, X; Ding, X

Purpose: We performed a retrospective dosimetric comparison study between the robustness optimized Intensity Modulated Proton Therapy (RO-IMPT), volumetric-modulated arc therapy (VMAT), and the non-coplanar 4? intensity modulated radiation therapy (IMRT). These methods represent the most advanced radiation treatment methods clinically available. We compare their dosimetric performance for head and neck cancer treatments with special focus on the OAR sparing near the tumor volumes. Methods: A total of 11 head and neck cases, which include 10 recurrent cases and one bilateral case, were selected for the study. Different dose levels were prescribed to tumor target depending on disease and location. Threemore » treatment plans were created on commercial TPS systems for a novel noncoplanar 4π method (20 beams), VMAT, and RO-IMPT technique (maximum 4 fields). The maximum patient positioning error was set to 3 mm and the maximum proton range uncertainty was set to 3% for the robustness optimization. Line dose profiles were investigated for OARs close to tumor volumes. Results: All three techniques achieved 98% coverage of the CTV target and most photon plans had less than 110% of the hot spots. The RO-IMPT plans show superior tumor dose homogeneity than 4? and VMAT plans. Although RO-IMPT has greater R50 dose spillage to the surrounding normal tissue than 4π and VMAT, the RO-IMPT plans demonstrate better or comparable OAR (parotid, mandible, carotid, oral cavity, pharynx, and etc.) sparing for structures closely abutting tumor targets. Conclusion: The RO-IMPT’s ability of OAR sparing is benchmarked against the C-arm linac based non-coplanar 4π technique and the standard VMAT method. RO-IMPT consistently shows better or comparable OAR sparing even for tissue structures closely abutting treatment target volume. RO-IMPT further reduces treatment uncertainty associated with proton therapy and delivers robust treatment plans to both unilateral and bilateral head and neck cancer patients with desirable treatment time.« less

The leukotriene B4-leukotriene B4 receptor axis promotes cisplatin-induced acute kidney injury by modulating neutrophil recruitment.

PubMed

Deng, Bo; Lin, Yuli; Ma, Shuai; Zheng, Yin; Yang, Xuguang; Li, Bingji; Yu, Wenyan; Xu, Qingqing; Liu, Tingyan; Hao, Chuanming; He, Rui; Ding, Feng

2017-07-01

Cisplatin is an effective chemotherapeutic agent and widely used in treatment of various solid organ malignancies, including head and neck, ovarian, and testicular cancers. However, the induction of acute kidney injury (AKI) is one of its main side effects. Leukotriene B 4 receptor 1 (BLT1) mediates the majority of physiological effects of leukotriene B 4 (LTB 4 ), a potent lipid chemoattractant generated at inflammation sites, but the role of the LTB 4 -BLT1 axis in cisplatin-induced AKI remains unknown. Here we found upregulated LTB 4 synthesis and BLT1 expression in the kidney after cisplatin administration. Cisplatin was found to directly upregulate gene expression of leukotriene A 4 hydrolase and stimulate LTB 4 production in renal tubular epithelial cells. Reduced kidney structural/functional damage, inflammation, and apoptosis were observed in BLT1 -/- mice, as well as in wild-type mice treated with the LTA4H inhibitor SC-57461A and the BLT1 antagonist U-75302. Neutrophils were likely the target of this pathway, as BLT1 absence induced a significant decrease in infiltrating neutrophils in the kidney. Adoptive transfer of neutrophils from wild-type mice restored kidney injury in BLT1 -/- mice following cisplatin challenge. Thus, the LTB 4 -BLT1 axis contributes to cisplatin-induced AKI by mediating kidney recruitment of neutrophils, which induce inflammation and apoptosis in the kidney. Hence, the LTB 4 -BLT1 axis could be a potential therapeutic target in cisplatin-induced AKI. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Beyond solicitousness: a comprehensive review on informal pain-related social support.

PubMed

Bernardes, Sónia F; Forgeron, Paula; Fournier, Karine; Reszel, Jessica

2017-11-01

Adults with chronic pain cite social support (SS) as an important resource. Research has mostly focused on general SS or pain-specific solicitousness, resulting in a limited understanding of the role of SS in pain experiences. Drawing on SS theoretical models, this review aimed to understand how pain-related SS has been conceptualized and measured and how its relationship with pain experiences has been investigated. Arksey and O'Malley scoping review framework guided the study. A database search (2000-2015) was conducted in PsycINFO, CINAHL, MEDLINE, and EMBASE using a combination of subject headings/keywords on pain and SS; 3864 citations were screened; 101 full texts were assessed for eligibility; references of 52 papers were hand searched. Fifty-three studies were included. Most studies were either a-theoretical or drew upon the operant conditioning model. There are several self-report measures and observational systems to operationalize pain-related SS. However, the Multidimensional Pain Inventory remains the most often used, accounting for the centrality of the concept of solicitousness in the literature. Most studies focused on individuals with chronic pain self-report of spousal pain-related SS and investigated its main effects on pain outcomes. Only a minority investigated the role of pain SS within the stress and coping process (as a buffer or mediator). Little is known about mediating pathways, contextual modulation of the effectiveness of SS exchanges, and there are practically no SS-based intervention studies. Drawing on general SS models, the main gaps in pain-related SS research are discussed and research directions for moving this literature beyond solicitousness are proposed.

Development of new immunotherapy treatments in different cancer types.

PubMed

Stanculeanu, D L; Daniela, Zob; Lazescu, A; Bunghez, R; Anghel, R

2016-01-01

Cancer immunotherapy involves the use of therapeutic modalities that determine a manipulation of the immune system by using immune agents such as cytokines, vaccines, cell therapies and humoral, transfection agents. Immunotherapy of cancer has to stimulate the host's anti-tumor response by increasing the effector cell number and the production of soluble mediators and decrease the host's suppressor mechanisms by inducing tumor killing environment and by modulating immune checkpoints. Immunotherapy seems to work better in more immunogenic tumors. Making a review of literature, the article presents the new immunologic treatments in cancers less presented in the latest conferences, cancers in which, immunotherapy is still under investigation. Bladder cancer was the first indication for which immunotherapy was used in 1970. A promising clinical research in bladder cancer is the use of immune checkpoint inhibitors. Although breast cancer is considered immunologically silent, several preclinical and clinical studies suggested that immunotherapy has the potential to improve the clinical outcomes for patients with breast cancer. Cervical cancer, brain cancer, head and neck cancer and colorectal and esophageal cancers are cancer types for which new immune-based cancer treatments are currently under development. Recent agents used in clinical trials will be described in before mentioned cancers.

The Role of Hedgehog Signaling in Tumor Induced Bone Disease

PubMed Central

Cannonier, Shellese A.; Sterling, Julie A.

2015-01-01

Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

Development of new immunotherapy treatments in different cancer types

PubMed Central

Stanculeanu, DL; Daniela, Zob; Lazescu, A; Bunghez, R; Anghel, R

2016-01-01

Cancer immunotherapy involves the use of therapeutic modalities that determine a manipulation of the immune system by using immune agents such as cytokines, vaccines, cell therapies and humoral, transfection agents. Immunotherapy of cancer has to stimulate the host’s anti-tumor response by increasing the effector cell number and the production of soluble mediators and decrease the host’s suppressor mechanisms by inducing tumor killing environment and by modulating immune checkpoints. Immunotherapy seems to work better in more immunogenic tumors. Making a review of literature, the article presents the new immunologic treatments in cancers less presented in the latest conferences, cancers in which, immunotherapy is still under investigation. Bladder cancer was the first indication for which immunotherapy was used in 1970. A promising clinical research in bladder cancer is the use of immune checkpoint inhibitors. Although breast cancer is considered immunologically silent, several preclinical and clinical studies suggested that immunotherapy has the potential to improve the clinical outcomes for patients with breast cancer. Cervical cancer, brain cancer, head and neck cancer and colorectal and esophageal cancers are cancer types for which new immune-based cancer treatments are currently under development. Recent agents used in clinical trials will be described in before mentioned cancers. PMID:27974927

Building an open academic environment – a new approach to empowering students in their learning of anatomy through ‘Shadow Modules’

PubMed Central

Scott, Jonathan L; Moxham, Bernard J; Rutherford, Stephen M

2014-01-01

Teaching and learning in anatomy is undertaken by a variety of methodologies, yet all of these pedagogies benefit from students discussing and reflecting upon their learning activities. An approach of particular potency is peer-mediated learning, through either peer-teaching or collaborative peer-learning. Collaborative, peer-mediated, learning activities help promote deep learning approaches and foster communities of practice in learning. Students generally flourish in collaborative learning settings but there are limitations to the benefits of collaborative learning undertaken solely within the confines of modular curricula. We describe the development of peer-mediated learning through student-focused and student-led study groups we have termed ‘Shadow Modules’. The ‘Shadow Module’ takes place parallel to the formal academically taught module and facilitates collaboration between students to support their learning for that module. In ‘Shadow Module’ activities, students collaborate towards curating existing online open resources as well as developing learning resources of their own to support their study. Through the use of communication technologies and web 2.0 tools these resources are able to be shared with their peers, thus enhancing the learning experience of all students following the module. The Shadow Module activities have the potential to lead to participants feeling a greater sense of engagement with the subject material, as well as improving their study and group-working skills and developing digital literacy. The outputs from Shadow Module collaborative work are open-source and may be utilised by subsequent student cohorts, thus building up a repository of learning resources designed by and for students. Shadow Module activities would benefit all pedagogies in the study of anatomy, and support students moving from being passive consumers to active participants in learning. PMID:24117249

Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells

PubMed Central

Vogel, Stephanie; Grabski, Elena; Buschjäger, Daniela; Klawonn, Frank; Döring, Marius; Wang, Junxi; Fletcher, Erika; Bechmann, Ingo; Witte, Torsten; Durisin, Martin; Schraven, Burkhart; Mangsbo, Sara M.; Schönfeld, Kurt; Czeloth, Niklas; Kalinke, Ulrich

2015-01-01

Treatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fcγ receptor mediated cell-cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64+ monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients’ inflamed joints that comprised enhanced numbers of CD64+ cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64+ cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64+ cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single FcγR, but also the immunological environment that is appropriate to support such interactions. PMID:26670584

Mediator Tail Module Is Required for Tac1-Activated CDR1 Expression and Azole Resistance in Candida albicans.

PubMed

Liu, Zhongle; Myers, Lawrence C

2017-11-01

The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1 and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C terminus of Tac1. GOF mutations within the Tac1 TAD, outside the context of full-length Tac1, generally do not enhance its absolute potential as a transcriptional activator. Negative regulation of the Tac1 TAD by the Tac1 middle region is necessary for the activating effect of GOF mutations or fluphenazine to be realized. We have found that full-length Tac1, when hyperactivated by xenobiotics or GOF mutations, facilitates the recruitment of the Mediator coactivator complex to the CDR1 promoter. Azole resistance and the activation of Tac1 target genes, such as CDR1 , are dependent on the Tac1 TAD and subunits of the Mediator tail module. The dependence of different Tac1 target promoters on the Mediator tail module, however, varies widely. Lastly, we show that hyperactivation of Tac1 is correlated with its Mediator-dependent phosphorylation, a potentially useful biomarker for Tac1 hyperactivation. The role of Mediator in events downstream of Tac1 hyperactivation in fluconazole-resistant clinical isolates is complex and provides opportunities and challenges for therapeutic intervention. Copyright © 2017 American Society for Microbiology.

Design and implementation of a head-and-neck phantom for system audit and verification of intensity-modulated radiation therapy.

PubMed

Webster, Gareth J; Hardy, Mark J; Rowbottom, Carl G; Mackay, Ranald I

2008-04-16

The head and neck is a challenging anatomic site for intensity-modulated radiation therapy (IMRT), requiring thorough testing of planning and treatment delivery systems. Ideally, the phantoms used should be anatomically realistic, have radiologic properties identical to those of the tissues concerned, and allow for the use of a variety of devices to verify dose and dose distribution in any target or normaltissue structure. A phantom that approaches the foregoing characteristics has been designed and built; its specific purpose is verification for IMRT treatments in the head-andneck region. This semi-anatomic phantom, HANK, is constructed of Perspex (Imperial Chemical Industries, London, U.K.) and provides for the insertion of heterogeneities simulating air cavities in a range of fixed positions. Chamber inserts are manufactured to incorporate either a standard thimble ionization chamber (0.125 cm3: PTW, Freiburg, Germany) or a smaller PinPoint chamber (0.015 cm3: PTW), and measurements can be made with either chamber in a range of positions throughout the phantom. Coronal films can also be acquired within the phantom, and additional solid blocks of Perspex allow for transverse films to be acquired within the head region. Initial studies using simple conventional head-and-neck plans established the reproducibility of the phantom and the measurement devices to within the setup uncertainty of +/- 0.5 mm. Subsequent verification of 9 clinical head-and-neck IMRT plans demonstrated the efficacy of the phantom in making a range of patient-specific dose measurements in regions of dosimetric and clinical interest. Agreement between measured values and those predicted by the Pinnacle3 treatment planning system (Philips Medical Systems, Andover, MA) was found to be generally good, with a mean error on the calculated dose to each point of +0.2% (range: -4.3% to +2.2%; n = 9) for the primary planning target volume (PTV), -0.1% (range: -1.5% to +2.0%; n = 8) for the nodal PTV, and +0.0% (range: -1.8% to +4.3%, n = 9) for the spinal cord. The suitability of the phantom for measuring combined dose distributions using radiographic film was also evaluated. The phantom has proved to be a valuable tool in the development and implementation of clinical head-and-neck IMRT, allowing for accurate verification of absolute dose and dose distributions in regions of clinical and dosimetric interest.

Travelling and splitting of a wave of hedgehog expression involved in spider-head segmentation.

PubMed

Kanayama, Masaki; Akiyama-Oda, Yasuko; Nishimura, Osamu; Tarui, Hiroshi; Agata, Kiyokazu; Oda, Hiroki

2011-10-11

During development segmentation is a process that generates a spatial periodic pattern. Peak splitting of waves of gene expression is a mathematically predicted, simple strategy accounting for this type of process, but it has not been well characterized biologically. Here we show temporally repeated splitting of gene expression into stripes that is associated with head axis growth in the spider Achaearanea embryo. Preceding segmentation, a wave of hedgehog homologue gene expression is observed to travel posteriorly during development stage 6. This stripe, co-expressing an orthodenticle homologue, undergoes two cycles of splitting and shifting accompanied by convergent extension, serving as a generative zone for the head segments. The two orthodenticle and odd-paired homologues are identified as targets of Hedgehog signalling, and evidence suggests that their activities mediate feedback to maintain the head generative zone and to promote stripe splitting in this zone. We propose that the 'stripe-splitting' strategy employs genetic components shared with Drosophila blastoderm subdivision, which are required for participation in an autoregulatory signalling network.

Neighborhood Economic Disadvantage and Children's Cognitive and Social-Emotional Development: Exploring Head Start Classroom Quality as a Mediating Mechanism.

PubMed

McCoy, Dana Charles; Connors, Maia C; Morris, Pamela A; Yoshikawa, Hirokazu; Friedman-Krauss, Allison H

Past research has shown robust relationships between neighborhood socioeconomic disadvantage and children's school achievement and social-emotional outcomes, yet the mechanisms for explaining these relationships are poorly understood. The present study uses data from 1,904 Head Start participants enrolled in the Head Start Impact Study to examine the role that classroom structural and relational quality play in explaining the association between neighborhood poverty and children's developmental gains over the preschool year. Results suggest that neighborhood poverty is directly related to lower levels of classroom quality, and lower gains in early literacy and math scores. Indirect relationships were also found between neighborhood poverty and children's social-emotional outcomes (i.e., approaches to learning and behavior problems) via differences in the physical resources and negative student-teacher relationships within classrooms. These findings highlight the need for policy initiatives to consider community characteristics as potential predictors of disparities in classroom quality and children's cognitive and social-emotional development in Head Start.

Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

PubMed

Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

2009-11-10

Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon LPS induced suppression of defensive rage. The results demonstrate that LPS suppresses defensive rage by acting through peripheral TNF-alpha in periphery and that central effects of LPS suppression of defensive rage are mediated through PGE(2) and 5-HT(1A) receptors in the medial hypothalamus.

A Multi-channel Semicircular Canal Neural Prosthesis Using Electrical Stimulation to Restore 3D Vestibular Sensation

PubMed Central

Della Santina, Charles C.; Migliaccio, Americo A.; Patel, Amit H.

2009-01-01

Bilateral loss of vestibular sensation can be disabling. Those afflicted suffer illusory visual field movement during head movements, chronic disequilibrium and postural instability due to failure of vestibulo-ocular and vestibulo-spinal reflexes. A neural prosthesis that emulates the normal transduction of head rotation by semicircular canals could significantly improve quality of life for these patients. Like the 3 semicircular canals in a normal ear, such a device should at least transduce 3 orthogonal (or linearly separable) components of head rotation into activity on corresponding ampullary branches of the vestibular nerve. We describe the design, circuit performance and in vivo application of a head-mounted, semi-implantable multi-channel vestibular prosthesis that encodes head movement in 3 dimensions as pulse-frequency-modulated electrical stimulation of 3 or more ampullary nerves. In chinchillas treated with intratympanic gentamicin to ablate vestibular sensation bilaterally, prosthetic stimuli elicited a partly compensatory angular vestibulo-ocular reflex in multiple planes. Minimizing misalignment between the axis of eye and head rotation, apparently caused by current spread beyond each electrode’s targeted nerve branch, emerged as a key challenge. Increasing stimulation selectivity via improvements in electrode design, surgical technique and stimulus protocol will likely be required to restore AVOR function over the full range of normal behavior. PMID:17554821

Addition of lysophospholipids with large head groups to cells inhibits Shiga toxin binding.

PubMed

Ailte, Ieva; Lingelem, Anne Berit Dyve; Kavaliauskiene, Simona; Bergan, Jonas; Kvalvaag, Audun Sverre; Myrann, Anne-Grethe; Skotland, Tore; Sandvig, Kirsten

2016-07-26

Shiga toxin (Stx), an AB5 toxin, binds specifically to the neutral glycosphingolipid Gb3 at the cell surface before being transported into cells. We here demonstrate that addition of conical lysophospholipids (LPLs) with large head groups inhibit Stx binding to cells whereas LPLs with small head groups do not. Lysophosphatidylinositol (LPI 18:0), the most efficient LPL with the largest head group, was selected for in-depth investigations to study how the binding of Stx is regulated. We show that the inhibition of Stx binding by LPI is reversible and possibly regulated by cholesterol since addition of methyl-β-cyclodextrin (mβCD) reversed the ability of LPI to inhibit binding. LPI-induced inhibition of Stx binding is independent of signalling and membrane turnover as it occurs in fixed cells as well as after depletion of cellular ATP. Furthermore, data obtained with fluorescent membrane dyes suggest that LPI treatment has a direct effect on plasma membrane lipid packing with shift towards a liquid disordered phase in the outer leaflet, while lysophosphoethanolamine (LPE), which has a small head group, does not. In conclusion, our data show that cellular treatment with conical LPLs with large head groups changes intrinsic properties of the plasma membrane and modulates Stx binding to Gb3.

Effect of neck flexor muscle activation on impact velocity of the head during backward falls in young adults.

PubMed

Choi, W J; Robinovitch, S N; Ross, S A; Phan, J; Cipriani, D

2017-11-01

Falls are a common cause of traumatic brain injuries (TBI) across the lifespan. A proposed but untested hypothesis is that neck muscle activation influences impact severity and risk for TBI during a fall. We conducted backward falling experiments to test whether activation of the neck flexor muscles facilitates the avoidance of head impact, and reduces impact velocity if the head contacts the ground. Young adults (n=8) fell from standing onto a 30cm thick gymnastics mat while wearing a helmet. Participants were instructed to fall backward and (a) prevent their head from impacting the mat ("no head impact" trials); (b) allow their head to impact the mat, but with minimal impact severity ("soft impact" trials); and (c) allow their head to impact the mat, while inhibiting efforts to reduce impact severity ("hard impact" trials). Trial type associated with peak magnitude of electromyographic activity of the sternocleidomastoid (SCM) muscles (p<0.017), and with the vertical and horizontal velocity of the head at impact (p<0.001). Peak SCM activations, expressed as percent maximal voluntary isometric contraction (%MVIC), averaged 75.3, 67.5, and 44.5%MVIC in "no head impact", "soft impact", and "hard impact" trials, respectively. When compared to "soft impact" trials, vertical impact velocities in "hard impact" trials averaged 87% greater (3.23 versus 1.73m/s) and horizontal velocities averaged 83% greater (2.74 versus 1.50m/s). For every 10% increase in SCM %MVIC, vertical impact velocity decreased 0.24m/s and horizontal velocity decreased 0.22m/s. We conclude that SCM activation contributes to the prevention and modulation of head impact severity during backward falls. Copyright © 2017 Elsevier Ltd. All rights reserved.

Community Violence, Family Conflict, and Preschoolers' Socioemotional Functioning

ERIC Educational Resources Information Center

Farver, Jo Ann M.; Xu, Yiyuan; Eppe, Stefanie; Fernandez, Alicia; Schwartz, David

2005-01-01

This study examined the relations among family conflict, community violence, and young children's socioemotional functioning and explored how children's social cognition and mothers' psychological functioning may mediate the outcomes associated with this exposure. Mothers of 431 Head Start preschoolers completed questionnaires about their family…

MATERNAL DEPRESSION AND THE DEVELOPMENT OF EXECUTIVE FUNCTION AND BEHAVIOR PROBLEMS IN HEAD START: INDIRECT EFFECTS THROUGH PARENTING.

PubMed

Baker, Claire E

2018-03-01

The present study used a large, nationally representative sample of Head Start children (N=3,349) from the Family and Child Experiences Survey of 2009 (FACES) to examine associations among maternal depression (measured when children were ˜36 months old) and children's executive function (EF) and behavior problems (measured when children were ˜48 months old). Preliminary analyses revealed that 36% of mothers in the sample had clinically significant levels of depressive symptoms. Furthermore, a path analysis with demographic controls showed a mediation effect that was significant and quite specific; mother-reported warmth (and not mother-child reading) mediated the path between maternal depression, children's EF, and behavior problems. Findings provide empirical support for a family process model in which warm, sensitive parenting supports children's emerging self-regulation and reduces the likelihood of early onset behavior problems in families in which children are exposed to maternal depression. © 2018 Michigan Association for Infant Mental Health.

Head and neck cancers associated with exposure to the September 11, 2001 World Trade Center terrorist attacks.

PubMed

Leeman, Jonathan E; McBride, Sean M; Spielsinger, Daniel; Sherman, Eric J; Wong, Richard; Riaz, Nadeem; Lee, Nancy Y; Tsai, Chiaojung Jillian

2018-06-15

Exposure at the World Trade Center (WTC) terrorist collapse site on September 11, 2001 has been associated with increased cancer risk, though observational studies have identified very few cases of head and neck cancer (HNC) in exposed individuals. Eighty seven patients were identified who presented to our institution with HNC diagnosed from 2002 to 2017 who reported WTC exposure. The annual number and proportion of WTC-exposed HNC patients has been steadily increasing since 2002, with most cancers developing >10 years following the event. Furthermore, WTC-exposed patients with human papillomavirus (HPV)-positive OPC experienced significantly inferior outcomes compared with non-WTC exposed patients with HPV+ OPC (disease free survival 80.1% vs. 65.6% at 4 years, p = 0.04). This single institution study cannot establish evidence of exposure-mediated causation but higher recurrence rates in the WTC-exposed HPV+ OPC population suggest a treatment refractory tumor biology and possible exposure synergism with HPV-mediated oncogenesis. © 2018 UICC.

LCoS-SLM technology based on Digital Electro-optics Platform and using in dynamic optics for application development

NASA Astrophysics Data System (ADS)

Tsai, Chun-Wei; Wang, Chen; Lyu, Bo-Han; Chu, Chen-Hsien

2017-08-01

Digital Electro-optics Platform is the main concept of Jasper Display Corp. (JDC) to develop various applications. These applications are based on our X-on-Silicon technologies, for example, X-on-Silicon technologies could be used on Liquid Crystal on Silicon (LCoS), Micro Light-Emitting Diode on Silicon (μLEDoS), Organic Light-Emitting Diode on Silicon (OLEDoS), and Cell on Silicon (CELLoS), etc. LCoS technology is applied to Spatial Light Modulator (SLM), Dynamic Optics, Wavelength Selective Switch (WSS), Holographic Display, Microscopy, Bio-tech, 3D Printing and Adaptive Optics, etc. In addition, μLEDoS technology is applied to Augmented Reality (AR), Head Up Display (HUD), Head-mounted Display (HMD), and Wearable Devices. Liquid Crystal on Silicon - Spatial Light Modulator (LCoSSLM) based on JDC's On-Silicon technology for both amplitude and phase modulation, have an expanding role in several optical areas where light control on a pixel-by-pixel basis is critical for optimum system performance. Combination of the advantage of hardware and software, we can establish a "dynamic optics" for the above applications or more. Moreover, through the software operation, we can control the light more flexible and easily as programmable light processor.

Examination of the properties of IMRT and VMAT beams and evaluation against pre-treatment quality assurance results

NASA Astrophysics Data System (ADS)

Crowe, S. B.; Kairn, T.; Middlebrook, N.; Sutherland, B.; Hill, B.; Kenny, J.; Langton, C. M.; Trapp, J. V.

2015-03-01

This study aimed to provide a detailed evaluation and comparison of a range of modulated beam evaluation metrics, in terms of their correlation with QA testing results and their variation between treatment sites, for a large number of treatments. Ten metrics including the modulation index (MI), fluence map complexity, modulation complexity score (MCS), mean aperture displacement (MAD) and small aperture score (SAS) were evaluated for 546 beams from 122 intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment plans targeting the anus, rectum, endometrium, brain, head and neck and prostate. The calculated sets of metrics were evaluated in terms of their relationships to each other and their correlation with the results of electronic portal imaging based quality assurance (QA) evaluations of the treatment beams. Evaluation of the MI, MAD and SAS suggested that beams used in treatments of the anus, rectum, head and neck were more complex than the prostate and brain treatment beams. Seven of the ten beam complexity metrics were found to be strongly correlated with the results from QA testing of the IMRT beams (p < 0.00008). For example, values of SAS (with multileaf collimator apertures narrower than 10 mm defined as ‘small’) less than 0.2 also identified QA passing IMRT beams with 100% specificity. However, few of the metrics are correlated with the results from QA testing of the VMAT beams, whether they were evaluated as whole 360° arcs or as 60° sub-arcs. Select evaluation of beam complexity metrics (at least MI, MCS and SAS) is therefore recommended, as an intermediate step in the IMRT QA chain. Such evaluation may also be useful as a means of periodically reviewing VMAT planning or optimiser performance.

Validation of the relative insensitivity of volumetric-modulated arc therapy (VMAT) plan quality to gantry space resolution

PubMed Central

Cora, Stefania; Khan, Ehsan Ullah

2017-01-01

Abstract Volumetric-modulated arc therapy (VMAT) is an efficient form of radiotherapy used to deliver intensity-modulated radiotherapy beams. The aim of this study was to investigate the relative insensitivity of VMAT plan quality to gantry angle spacing (GS). Most previous VMAT planning and dosimetric work for GS resolution has been conducted for single arc VMAT. In this work, a quantitative comparison of dose–volume indices (DIs) was made for partial-, single- and double-arc VMAT plans optimized at 2°, 3° and 4° GS, representing a large variation in deliverable multileaf collimator segments. VMAT plans of six prostate cancer and six head-and-neck cancer patients were simulated for an Elekta SynergyS® Linac (Elekta Ltd, Crawley, UK), using the SmartArc™ module of Pinnacle³ TPS, (version 9.2, Philips Healthcare). All optimization techniques generated clinically acceptable VMAT plans, except for the single-arc for the head-and-neck cancer patients. Plan quality was assessed by comparing the DIs for the planning target volume, organs at risk and normal tissue. A GS of 2°, with finest resolution and consequently highest intensity modulation, was considered to be the reference, and this was compared with GS 3° and 4°. The differences between the majority of reference DIs and compared DIs were <2%. The metrics, such as treatment plan optimization time and pretreatment (phantom) dosimetric calculation time, supported the use of a GS of 4°. The ArcCHECK™ phantom–measured dosimetric agreement verifications resulted in a >95.0% passing rate, using the criteria for γ (3%, 3 mm). In conclusion, a GS of 4° is an optimal choice for minimal usage of planning resources without compromise of plan quality. PMID:27974507

Context-Dependent Modulation of GABAAR-Mediated Tonic Currents.

PubMed

Patel, Bijal; Bright, Damian P; Mortensen, Martin; Frølund, Bente; Smart, Trevor G

2016-01-13

Tonic GABA currents mediated by high-affinity extrasynaptic GABAA receptors, are increasingly recognized as important regulators of cell and neuronal network excitability. Dysfunctional GABAA receptor signaling that results in modified tonic GABA currents is associated with a number of neurological disorders. Consequently, developing compounds to selectively modulate the activity of extrasynaptic GABAA receptors underlying tonic inhibition is likely to prove therapeutically useful. Here, we examine the GABAA receptor subtype selectivity of the weak partial agonist, 5-(4-piperidyl)isoxazol-3-ol (4-PIOL), as a potential mechanism for modulating extrasynaptic GABAA receptor-mediated tonic currents. By using recombinant GABAA receptors expressed in HEK293 cells, and native GABAA receptors of cerebellar granule cells, hippocampal neurons, and thalamic relay neurons, 4-PIOL evidently displayed differential agonist and antagonist-type profiles, depending on the extrasynaptic GABAA receptor isoforms targeted. For neurons, this resulted in differential modulation of GABA tonic currents, depending on the cell type studied, their respective GABAA receptor subunit compositions, and critically, on the ambient GABA levels. Unexpectedly, 4-PIOL revealed a significant population of relatively low-affinity γ2 subunit-containing GABAA receptors in the thalamus, which can contribute to tonic inhibition under specific conditions when GABA levels are raised. Together, these data indicate that partial agonists, such as 4-PIOL, may be useful for modulating GABAA receptor-mediated tonic currents, but the direction and extent of this modulation is strongly dependent on relative expression levels of different extrasynaptic GABAA receptor subtypes, and on the ambient GABA levels. A background level of inhibition (tonic) is important in the brain for controlling neuronal excitability. Increased levels of tonic inhibition are associated with some neurological disorders but there are no specific ligands capable of selectively reducing tonic inhibition. Here we explore the use of a GABA partial agonist as a selective chemical tool in three different brain regions. We discover that the activity of a partial agonist is heavily dependent upon the GABAA receptor subunit composition underpinning tonic inhibition, and on the ambient levels of GABA in the brain. Copyright © 2016 Patel et al.

Context-Dependent Modulation of GABAAR-Mediated Tonic Currents

PubMed Central

Patel, Bijal; Bright, Damian P.; Mortensen, Martin; Frølund, Bente

2016-01-01

Tonic GABA currents mediated by high-affinity extrasynaptic GABAA receptors, are increasingly recognized as important regulators of cell and neuronal network excitability. Dysfunctional GABAA receptor signaling that results in modified tonic GABA currents is associated with a number of neurological disorders. Consequently, developing compounds to selectively modulate the activity of extrasynaptic GABAA receptors underlying tonic inhibition is likely to prove therapeutically useful. Here, we examine the GABAA receptor subtype selectivity of the weak partial agonist, 5-(4-piperidyl)isoxazol-3-ol (4-PIOL), as a potential mechanism for modulating extrasynaptic GABAA receptor-mediated tonic currents. By using recombinant GABAA receptors expressed in HEK293 cells, and native GABAA receptors of cerebellar granule cells, hippocampal neurons, and thalamic relay neurons, 4-PIOL evidently displayed differential agonist and antagonist-type profiles, depending on the extrasynaptic GABAA receptor isoforms targeted. For neurons, this resulted in differential modulation of GABA tonic currents, depending on the cell type studied, their respective GABAA receptor subunit compositions, and critically, on the ambient GABA levels. Unexpectedly, 4-PIOL revealed a significant population of relatively low-affinity γ2 subunit-containing GABAA receptors in the thalamus, which can contribute to tonic inhibition under specific conditions when GABA levels are raised. Together, these data indicate that partial agonists, such as 4-PIOL, may be useful for modulating GABAA receptor-mediated tonic currents, but the direction and extent of this modulation is strongly dependent on relative expression levels of different extrasynaptic GABAA receptor subtypes, and on the ambient GABA levels. SIGNIFICANCE STATEMENT A background level of inhibition (tonic) is important in the brain for controlling neuronal excitability. Increased levels of tonic inhibition are associated with some neurological disorders but there are no specific ligands capable of selectively reducing tonic inhibition. Here we explore the use of a GABA partial agonist as a selective chemical tool in three different brain regions. We discover that the activity of a partial agonist is heavily dependent upon the GABAA receptor subunit composition underpinning tonic inhibition, and on the ambient levels of GABA in the brain. PMID:26758848

Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

PubMed Central

Pankratov, Yuriy

2017-01-01

Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. PMID:28845311

Dopamine modulates an intrinsic mGluR5-mediated depolarization underlying prefrontal persistent activity

PubMed Central

Sidiropoulou, Kyriaki; Lu, Fang-Min; Fowler, Melissa A.; Xiao, Rui; Phillips, Christopher; Ozkan, Emin D.; Zhu, Michael X.; White, Francis J.; Cooper, Donald C.

2009-01-01

Intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons are capable of maintaining persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory possibly by modulating intrinsic neuronal properties. Here we use patch-clamp recording of layer 5 PFC pyramidal neurons to identify an action potential burst-evoked intrinsic mGluR5-mediated postsynaptic depolarization that initiates an activated state. Depolarization occurs in the absence of recurrent synaptic activity and is reduced by a postsynaptic dopamine D1/5 receptor pathway. The depolarization is substantially diminished following behavioral sensitization to cocaine; moreover the D1/5 receptor modulation is lost. We propose the burst-evoked intrinsic depolarization to be a novel form of short-term cellular memory that is modulated by dopamine and cocaine experience. PMID:19169252

Nitrogen modulation of legume root architecture signaling pathways involves phytohormones and small regulatory molecules.

PubMed

Mohd-Radzman, Nadiatul A; Djordjevic, Michael A; Imin, Nijat

2013-10-01

Nitrogen, particularly nitrate is an important yield determinant for crops. However, current agricultural practice with excessive fertilizer usage has detrimental effects on the environment. Therefore, legumes have been suggested as a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely form nitrogen-fixing nodules through symbiotic interaction with specialized soil bacteria. Legumes possess a highly plastic root system which modulates its architecture according to the nitrogen availability in the soil. Understanding how legumes regulate root development in response to nitrogen availability is an important step to improving root architecture. The nitrogen-mediated root development pathway starts with sensing soil nitrogen level followed by subsequent signal transduction pathways involving phytohormones, microRNAs and regulatory peptides that collectively modulate the growth and shape of the root system. This review focuses on the current understanding of nitrogen-mediated legume root architecture including local and systemic regulations by different N-sources and the modulations by phytohormones and small regulatory molecules.

Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase

PubMed Central

Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang

2014-01-01

γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes. PMID:24799560

CTLA-4+ Regulatory T Cells Increased in Cetuximab Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor Prognosis

PubMed Central

Jie, Hyun-Bae; Schuler, Patrick J.; Lee, Steve C.; Srivastava, Raghvendra M.; Argiris, Athanassios; Ferrone, Soldano; Whiteside, Theresa L.; Ferris, Robert L.

2015-01-01

The EGFR-targeted antibody cetuximab is effective against head and neck cancer (HNC), but in only 15 – 20% of patients, and the variability and extent of cetuximab-mediated cellular immunity is not fully understood. We hypothesized that regulatory T cells (Treg) may exert a functional and clinical impact on antitumor immunity in cetuximab-treated individuals. The frequency, immunosuppressive phenotype and activation status of Treg and NK cells were analyzed in the circulation and tumor microenvironment of cetuximab-treated HNC patients enrolled in a novel neoadjuvant, single-agent cetuximab clinical trial. Notably, cetuximab treatment increased the frequency of CD4+FOXP3+ intratumoral Treg expressing CTLA-4, CD39 and TGF-β. These Treg suppressed cetuximab-mediated ADCC and their presence correlated with poor clinical outcome in two prospective clinical trial cohorts. Cetuximab expanded CTLA-4+FOXP3+ Treg in vitro, in part by inducing DC maturation, in combination with TGF-β and TCR triggering. Importantly, cetuximab-activated NK cells selectively eliminated intratumoral Treg but preserved effector T cells. In ex vivo assays, ipilimumab targeted CTLA-4+ Treg and restored cytolytic functions of NK cells mediating ADCC. Taken together, our results argue that differences in Treg-mediated suppression contribute to the clinical response to cetuximab treatment, suggesting its improvement by adding ipilimumab or other strategies of Treg ablation to promote anti-tumor immunity. PMID:25832655

Innate immune signaling through differential RIPK1 expression promote tumor progression in head and neck squamous cell carcinoma.

PubMed

McCormick, Kevin D; Ghosh, Arundhati; Trivedi, Sumita; Wang, Lin; Coyne, Carolyn B; Ferris, Robert L; Sarkar, Saumendra N

2016-05-01

Head and neck squamous cell carcinoma (HNSCC) is a devastating disease for which new treatments, such as immunotherapy are needed. Synthetic double-stranded RNAs, which activate toll-like receptor 3 (TLR3), have been used as potent adjuvants in cancer immunotherapy by triggering a proapoptotic response in cancer cells. A better understanding of the mechanism of TLR3-mediated apoptosis and its potential involvement in controlling tumor metastasis could lead to improvements in current treatment. Using paired, autologous primary and metastatic HNSCC cells we previously showed that metastatic, but not primary tumor-derived cells, were unable to activate prosurvival NF-κB in response to p(I):p(C) resulting in an enhanced apoptotic response. Here, we show that transcriptional downregulation of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in metastatic HNSCC cells causes a loss of TLR3-mediated NF-κB signaling, resulting in enhanced apoptosis. Loss of RIPK1 strongly correlates with metastatic disease in a cohort of HNSCC patients. This downregulation of RIPK1 is possibly mediated by enhanced methylation of the RIPK1 promoter in tumor cells and enhances protumorigenic properties such as cell migration. The results described here establish a novel mechanism of TLR3-mediated apoptosis in metastatic cells and may create new opportunities for using double stranded RNA to target metastatic tumor cells. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and CD56dim NK cells.

PubMed

Morandi, Fabio; Ferretti, Elisa; Castriconi, Roberta; Dondero, Alessandra; Petretto, Andrea; Bottino, Cristina; Pistoia, Vito

2011-11-24

Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we investigated sHLA-G-mediated modulation of (1) chemokine receptor and NK receptor expression and function and (2) cytokine and chemokine secretion in CD56bright and CD56dim NK cells. sHLA-G-treated or untreated peripheral blood (PB) and tonsil NK cells were analyzed for chemokine receptor and NK receptor expression by flow cytometry. sHLA-G down-modulated (1) CXCR3 on PB and tonsil CD56bright and CD56dim, (2) CCR2 on PB and tonsil CD56bright, (3) CX3CR1 on PB CD56dim, (4) CXCR5 on tonsil CD56dim, and (5) CD94/NKG2A on PB and tonsil CD56brigh) and CD56dim NK cells. Such sHLA-G-mediated down-modulations were reverted by adding anti-HLA-G or anti-ILT2 mAbs. sHLA-G inhibited chemotaxis of (1) PB NK cells toward CXCL10, CXCL11, and CX3CL1 and (2) PB CD56bright NK cells toward CCL2 and CXCL10. IFN-γ secretion induced by NKp46 engagement was inhibited by NKG2A engagement in untreated but not in sHLA-G-treated NK cells. sHLA-G up-regulated secretion of (1) CCL22 in CD56bright and CD56dim and (2) CCL2, CCL8, and CXCL2-CXCL3 in CD56dim PB NK cells. Signal transduction experiments showed sHLA-G-mediated down-modulation of Stat5 phosphorylation in PB NK cells. In conclusion, our data delineated novel mechanisms of sHLA-G-mediated inhibition of NK-cell functions.

Ultrasound-Mediated Biophotonic Imaging: A Review of Acousto-Optical Tomography and Photo-Acoustic Tomography

PubMed Central

Wang, Lihong V.

2004-01-01

This article reviews two types of ultrasound-mediated biophotonic imaging–acousto-optical tomography (AOT, also called ultrasound-modulated optical tomography) and photo-acoustic tomography (PAT, also called opto-acoustic or thermo-acoustic tomography)–both of which are based on non-ionizing optical and ultrasonic waves. The goal of these technologies is to combine the contrast advantage of the optical properties and the resolution advantage of ultrasound. In these two technologies, the imaging contrast is based primarily on the optical properties of biological tissues, and the imaging resolution is based primarily on the ultrasonic waves that either are provided externally or produced internally, within the biological tissues. In fact, ultrasonic mediation overcomes both the resolution disadvantage of pure optical imaging in thick tissues and the contrast and speckle disadvantages of pure ultrasonic imaging. In our discussion of AOT, the relationship between modulation depth and acoustic amplitude is clarified. Potential clinical applications of ultrasound-mediated biophotonic imaging include early cancer detection, functional imaging, and molecular imaging. PMID:15096709

LPS-treated bone marrow-derived dendritic cells induce immune tolerance through modulating differentiation of CD4+ regulatory T cell subpopulations mediated by 3G11 and CD127.

PubMed

Zhou, Fang; Zhang, Guang-Xian; Rostami, Abdolmohamad

2017-06-01

Intravenous transfer of LPS-treated bone marrow-derived dendritic cells blocks development of autoimmunity induced by CD4 + T cells in vivo. However, cellular mechanisms of dendritic cell-mediated immune tolerance have not yet been fully elucidated. Here, we report that there are two new subpopulations of CD4 + CD25 + FoxP3 + GITR + regulatory T cells (CD127 + 3G11 + and CD127 + 3G11 - cells). LPS-treated dendritic cells facilitate development of CD4 + CD127 + 3G11 - regulatory T cells but inhibit that of CD4 + CD127 + 3G11 + regulatory T cells. LPS-induced tolerogenic dendritic cells may cause immune tolerance through modulating balance of different subsets of CD4 + regulatory T cells mediated by CD127 and 3G11. Our results imply a new potential cellular mechanism of dendritic cell-mediated immune tolerance.

Inducible MicroRNA-3570 Feedback Inhibits the RIG-I-Dependent Innate Immune Response to Rhabdovirus in Teleost Fish by Targeting MAVS/IPS-1.

PubMed

Xu, Tianjun; Chu, Qing; Cui, Junxia; Bi, Dekun

2018-01-15

Effectively recognizing invading viruses and subsequently inducing innate antiviral immunity are essential for host antiviral defense. Although these processes are closely regulated by the host to maintain immune balance, viruses have evolved the ability to downregulate or upregulate these processes for their survival. MicroRNAs (miRNAs) are a family of small noncoding RNAs that play vital roles in modulating host immune response. Accumulating evidence demonstrates that host miRNAs as mediators are involved in regulating viral replication and host antiviral immunity in mammals. However, the underlying regulatory mechanisms in fish species are still poorly understood. Here, we found that rhabdovirus infection significantly upregulated host miR-3570 expression in miiuy croaker macrophages. Induced miR-3570 negatively modulated RNA virus-triggered type I interferon (IFN) and antiviral gene production, thus facilitating viral replication. Furthermore, miR-3570 was found to target and posttranscriptionally downregulate mitochondrial antiviral signaling protein (MAVS), which functions as a platform for innate antiviral signal transduction. Moreover, we demonstrated that miR-3570 suppressed the expression of MAVS, thereby inhibiting MAVS-mediated NF-κB and IRF3 signaling. The collective results demonstrated a novel regulation mechanism of MAVS-mediated immunity during RNA viral infection by miRNA. IMPORTANCE RNA viral infection could upregulate host miR-3570 expression in miiuy croaker macrophages. Induced miR-3570 negatively modulates RNA virus-triggered type I IFN and antiviral gene production, thus facilitating viral replication. Remarkably, miR-3570 could target and inhibit MAVS expression, which thus modulates MAVS-mediated NF-κB and IRF3 signaling. The collective results of this study suggest a novel regulation mechanism of MAVS-mediated immunity during RNA viral infection by miR-3570. Thus, a novel mechanism for virus evasion in fish is proposed. Copyright © 2018 American Society for Microbiology.

Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat.

PubMed

Khasar, S G; Reichling, D B; Green, P G; Isenberg, W M; Levine, J D

2003-01-01

The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception. These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control an ongoing vagus-mediated adjustment in the organism's nociceptive sensitivity.

Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity

PubMed Central

Harsono, Mimily; Pourcyrous, Massroor; Jolly, Elliott J.; de Jongh Curry, Amy; Fedinec, Alexander L.; Liu, Jianxiong; Basuroy, Shyamali; Zhuang, Daming; Leffler, Charles W.

2016-01-01

Epileptic seizures in neonates cause cerebrovascular injury and impairment of cerebral blood flow (CBF) regulation. In the bicuculline model of seizures in newborn pigs, we tested the hypothesis that selective head cooling prevents deleterious effects of seizures on cerebral vascular functions. Preventive or therapeutic ictal head cooling was achieved by placing two head ice packs during the preictal and/or ictal states, respectively, for the ∼2-h period of seizures. Head cooling lowered the brain and core temperatures to 25.6 ± 0.3 and 33.5 ± 0.1°C, respectively. Head cooling had no anticonvulsant effects, as it did not affect the bicuculline-evoked electroencephalogram parameters, including amplitude, duration, spectral power, and spike frequency distribution. Acute and long-term cerebral vascular effects of seizures in the normothermic and head-cooled groups were tested during the immediate (2–4 h) and delayed (48 h) postictal periods. Seizure-induced cerebral vascular injury during the immediate postictal period was detected as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive staining of cerebral arterioles and a surge of brain-derived circulating endothelial cells in peripheral blood in the normothermic group, but not in the head-cooled groups. During the delayed postictal period, endothelium-dependent cerebral vasodilator responses were greatly reduced in the normothermic group, indicating impaired CBF regulation. Preventive or therapeutic ictal head cooling mitigated the endothelial injury and greatly reduced loss of postictal cerebral vasodilator functions. Overall, head cooling during seizures is a clinically relevant approach to protecting the neonatal brain by preventing cerebrovascular injury and the loss of the endothelium-dependent control of CBF without reducing epileptiform activity. PMID:27591217

Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters

PubMed Central

2017-01-01

The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based pathway analysis were used to predict EGFR-mediated transporter regulation. Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS-MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1 and BCRP as well as their membrane expressions and transport activities, while MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were increased. AKT inhibition reduced all transporters. Exposure to methotrexate for 24 h led to a decreased viability, an effect that was reversed by cetuximab. In conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways. Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens possibilities for further research into nephroprotective comedication therapies. PMID:28493713

Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters.

PubMed

Caetano-Pinto, Pedro; Jamalpoor, Amer; Ham, Janneke; Goumenou, Anastasia; Mommersteeg, Monique; Pijnenburg, Dirk; Ruijtenbeek, Rob; Sanchez-Romero, Natalia; van Zelst, Bertrand; Heil, Sandra G; Jansen, Jitske; Wilmer, Martijn J; van Herpen, Carla M L; Masereeuw, Rosalinde

2017-06-05

The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based pathway analysis were used to predict EGFR-mediated transporter regulation. Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS-MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1 and BCRP as well as their membrane expressions and transport activities, while MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were increased. AKT inhibition reduced all transporters. Exposure to methotrexate for 24 h led to a decreased viability, an effect that was reversed by cetuximab. In conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways. Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens possibilities for further research into nephroprotective comedication therapies.

Optoelectronic Mounting Structure

DOEpatents

Anderson, Gene R.; Armendariz, Marcelino G.; Baca, Johnny R. F.; Bryan, Robert P.; Carson, Richard F.; Chu, Dahwey; Duckett, III, Edwin B.; McCormick, Frederick B.; Peterson, David W.; Peterson, Gary D.; Reber, Cathleen A.; Reysen, Bill H.

2004-10-05

An optoelectronic mounting structure is provided that may be used in conjunction with an optical transmitter, receiver or transceiver module. The mounting structure may be a flexible printed circuit board. Thermal vias or heat pipes in the head region may transmit heat from the mounting structure to the heat spreader. The heat spreader may provide mechanical rigidity or stiffness to the heat region. In another embodiment, an electrical contact and ground plane may pass along a surface of the head region so as to provide an electrical contact path to the optoelectronic devices and limit electromagnetic interference. In yet another embodiment, a window may be formed in the head region of the mounting structure so as to provide access to the heat spreader. Optoelectronic devices may be adapted to the heat spreader in such a manner that the devices are accessible through the window in the mounting structure.

High-resolution, continuous field-of-view (FOV), non-rotating imaging system

NASA Technical Reports Server (NTRS)

Huntsberger, Terrance L. (Inventor); Stirbl, Robert C. (Inventor); Aghazarian, Hrand (Inventor); Padgett, Curtis W. (Inventor)

2010-01-01

A high resolution CMOS imaging system especially suitable for use in a periscope head. The imaging system includes a sensor head for scene acquisition, and a control apparatus inclusive of distributed processors and software for device-control, data handling, and display. The sensor head encloses a combination of wide field-of-view CMOS imagers and narrow field-of-view CMOS imagers. Each bank of imagers is controlled by a dedicated processing module in order to handle information flow and image analysis of the outputs of the camera system. The imaging system also includes automated or manually controlled display system and software for providing an interactive graphical user interface (GUI) that displays a full 360-degree field of view and allows the user or automated ATR system to select regions for higher resolution inspection.

Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats.

PubMed

Ghosh, Arijit; Dhumal, V R; Tilak, A V; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A

2011-01-01

To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions.

Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

PubMed Central

Ghosh, Arijit; Dhumal, V. R.; Tilak, A. V.; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A.

2011-01-01

Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions. PMID:21701638

SHIPPING CONTAINER FOR RADIOACTIVE MATERIAL

DOEpatents

Nachbar, H.D.; Biggs, B.B.; Tariello, P.J.; George, K.O.

1963-01-15

A shipping container is described for transponting a large number of radioactive nuclear fuel element modules which produce a substantial amount of heat. The container comprises a primary pressure vessel and shield, and a rotatable head having an access port that can be indexed with module holders in the container. In order to remove heat generated in the fuel eleme nts, a heat exchanger is arranged within the container and in contact with a heat exchange fluid therein. The heat exchanger communicates with additional external heat exchangers, which dissipate heat to the atmosphere. (AEC)

KSC-08pd1266

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- The crew for the STS-124 mission departs NASA's Kennedy Space Center after a successful launch dress rehearsal called the terminal countdown demonstration test. Seen here are Commander Mark Kelly and Mission Specialist Greg Chamitoff heading for the T-38 training jets for their flight back to Houston. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

KSC-08pd1265

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- The crew for the STS-124 mission departs NASA's Kennedy Space Center after a successful launch dress rehearsal called the terminal countdown demonstration test. Seen here are Mission Specialists Ron Garan and Karen Nyberg heading for the T-38 training jets for their flight back to Houston. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

Boeing CST-100 Starliner Base Heat Shield Installation

NASA Image and Video Library

2018-03-15

On March 15, the base heat shield for Boeing’s CST-100 Starliner was freshly installed on the bottom of Spacecraft 1 in the High Bay of the Commercial Crew and Cargo Processing Facility at Kennedy Space Center. This is the spacecraft that will fly during the Pad Abort Test. The next step involves installation of the back shells and forward heat shield, and then the crew module will be mated to the service module for a fit check. Finally, the vehicle will head out to White Sands Missile Range in New Mexico for testing.

pH-Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid-Based Delivery Systems.

PubMed

Oumzil, Khalid; Benizri, Sébastien; Tonelli, Giovanni; Staedel, Cathy; Appavoo, Ananda; Chaffanet, Max; Navailles, Laurence; Barthélémy, Philippe

2015-11-01

Lipid-based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3'-orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH-sensitive liposomes. ONL-based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH-cleavable nucleolipids to control the stability of lipid-based delivery systems represents a promising approach for the intracellular delivery of drug cargos. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radical chemo-irradiation using intensity-modulated radiotherapy for locally advanced head and neck cancer in elderly patients: Experience from a tertiary care center in South India.

PubMed

Chalissery, J R; Sudheeran, P C; Varghese, K M; Venkatesan, K

2016-01-01

To assess the feasibility, tolerance and response of radical chemo irradiation using Intensity modulated Radiotherapy [IMRT] in elderly patients [age >65] with locally advanced head and neck cancer. Patients aged 65 and above [range 65 to 84years] registered in oncology outpatient unit in our institution between December 2011 to 2014, with stage III and IV head and neck cancer were treated with radical dose of radiotherapy using IMRT and concurrent chemotherapy with cisplatin 40mg/sq.m weekly. Response evaluation and toxicity profile assessment was done 6 to 8 weeks after completion of treatment and 3 monthly thereafter with median follow up of 3 years. Total number of patients analysed were 47. 43(91.5%) patients tolerated 66-.70Gy of radiotherapy and 4 or more cycles of weekly chemotherapy with cisplatin. First follow up evaluation at 6 to 8 weeks showed 81% patients having complete loco regional response. Grade III skin reaction and mucositis was noticed in 24% and 47% respectively. No grade III neutropenia observed. Median follow up of 3 years showed a complete local control in 53% and overall survival of 60%. Radical chemo irradiation with IMRT in elderly patients is a feasible option. Long term local control and overall survival benefits needs to be followed up.

Statistical process control analysis for patient quality assurance of intensity modulated radiation therapy

NASA Astrophysics Data System (ADS)

Lee, Rena; Kim, Kyubo; Cho, Samju; Lim, Sangwook; Lee, Suk; Shim, Jang Bo; Huh, Hyun Do; Lee, Sang Hoon; Ahn, Sohyun

2017-11-01

This study applied statistical process control to set and verify the quality assurances (QA) tolerance standard for our hospital's characteristics with the criteria standards that are applied to all the treatment sites with this analysis. Gamma test factor of delivery quality assurances (DQA) was based on 3%/3 mm. Head and neck, breast, prostate cases of intensity modulated radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT) were selected for the analysis of the QA treatment sites. The numbers of data used in the analysis were 73 and 68 for head and neck patients. Prostate and breast were 49 and 152 by MapCHECK and ArcCHECK respectively. C p value of head and neck and prostate QA were above 1.0, C pml is 1.53 and 1.71 respectively, which is close to the target value of 100%. C pml value of breast (IMRT) was 1.67, data values are close to the target value of 95%. But value of was 0.90, which means that the data values are widely distributed. C p and C pml of breast VMAT QA were respectively 1.07 and 2.10. This suggests that the VMAT QA has better process capability than the IMRT QA. Consequently, we should pay more attention to planning and QA before treatment for breast Radiotherapy.

FlySPEX: a flexible multi-angle spectropolarimetric sensing system

NASA Astrophysics Data System (ADS)

Snik, Frans; Keller, Christoph U.; Wijnen, Merijn; Peters, Hubert; Derks, Roy; Smulders, Edwin

2016-05-01

Accurate multi-angle spectropolarimetry permits the detailed and unambiguous characterization of a wide range of objects. Science cases and commercial applications include atmospheric aerosol studies, biomedical sensing, and food quality control. We introduce the FlySPEX spectropolarimetric fiber-head that constitutes the essential building block of a novel multi-angle sensing system. A combination of miniaturized standard polarization optics inside every fiber-head encodes the full linear polarization information as a spectral modulation of the light that enters two regular optical fibers. By orienting many FlySPEX fiber-heads in any desired set of directions, a fiber bundle contains the complete instantaneous information on polarization as a function of wavelength and as a function of the set of viewing directions. This information is to be recorded by one or several multi-fiber spectrometers. Not only is this system flexible in the amount of viewing directions and their configuration, it also permits multiplexing different wavelength ranges and spectral resolutions by implementing different spectrometers. We present the design and prototyping for a FlySPEX fiber-head that is optimized for both polarimetric accuracy and commercial series production. We integrate the polarimetric calibration of each FlySPEX fiber-head in the manufacturing process.

Reirradiation of head and neck cancer: Long-term disease control and toxicity.

PubMed

Bots, Wouter T C; van den Bosch, Sven; Zwijnenburg, Ellen M; Dijkema, Tim; van den Broek, Guido B; Weijs, Willem L J; Verhoef, Lia C G; Kaanders, Johannes H A M

2017-06-01

The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122-1130, 2017. © 2017 The Authors Head & Neck Published by Wiley Periodicals, Inc.

Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland

USDA-ARS?s Scientific Manuscript database

The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a comp...

Perceived Discrimination, Psychological Distress, and Current Smoking Status: Results From the Behavioral Risk Factor Surveillance System Reactions to Race Module, 2004–2008

PubMed Central

Peppone, Luke J.; Alcaraz, Kassandra; McQueen, Amy; Guido, Joseph J.; Carroll, Jennifer K.; Shacham, Enbal; Morrow, Gary R.

2012-01-01

Objectives. We examined the association between perceived discrimination and smoking status and whether psychological distress mediated this relationship in a large, multiethnic sample. Methods. We used 2004 through 2008 data from the Behavioral Risk Factor Surveillance System Reactions to Race module to conduct multivariate logistic regression analyses and tests of mediation examining associations between perceived discrimination in health care and workplace settings, psychological distress, and current smoking status. Results. Regardless of race/ethnicity, perceived discrimination was associated with increased odds of current smoking. Psychological distress was also a significant mediator of the discrimination–smoking association. Conclusions. Our results indicate that individuals who report discriminatory treatment in multiple domains may be more likely to smoke, in part, because of the psychological distress associated with such treatment. PMID:22420821

A dendritic cell-stromal axis maintains immune responses in lymph nodes

PubMed Central

Kumar, Varsha; Dasoveanu, Dragos C.; Chyou, Susan; Tzeng, Te-Chen; Rozo, Cristina; Liang, Yong; Stohl, William; Fu, Yang-Xin; Ruddle, Nancy; Lu, Theresa T.

2015-01-01

Summary Within secondary lymphoid tissues, stromal reticular cells support lymphocyte function, and targeting reticular cells is a potential strategy for controlling pathogenic lymphocytes in disease. However, the mechanisms that regulate reticular cell function are not well understood. Here we found that during an immune response in lymph nodes, dendritic cells (DCs) maintain reticular cell survival in multiple compartments. DC-derived lymphotoxin beta receptor (LTβR) ligands were critical mediators, and LTβR signaling on reticular cells mediated cell survival by modulating podoplanin (PDPN). PDPN modulated integrin-mediated cell adhesion, which maintained cell survival. This DC-stromal axis maintained lymphocyte survival and the ongoing immune response. Our findings provide insight into the functions of DCs, LTβR, and PDPN and delineate a DC-stromal axis that can potentially be targeted in autoimmune or lymphoproliferative diseases. PMID:25902483

Improved Dosimetric and Clinical Outcomes With Intensity-Modulated Radiotherapy for Head-and-Neck Cancer of Unknown Primary Origin

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

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.ed; Li Baoqing; Farwell, D. Gregory

2011-03-01

Purpose: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. Results: The 2-year estimates of overall survival, local-regional control,more » and disease-specific survival for the entire patient population were 86%, 89%, and84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p > 0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p < 0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p < 0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p < 0.001). Conclusions: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.« less

Modeling of signaling crosstalk-mediated drug resistance and its implications on drug combination.

PubMed

Sun, Xiaoqiang; Bao, Jiguang; You, Zhuhong; Chen, Xing; Cui, Jun

2016-09-27

The efficacy of pharmacological perturbation to the signaling transduction network depends on the network topology. However, whether and how signaling dynamics mediated by crosstalk contributes to the drug resistance are not fully understood and remain to be systematically explored. In this study, motivated by a realistic signaling network linked by crosstalk between EGF/EGFR/Ras/MEK/ERK pathway and HGF/HGFR/PI3K/AKT pathway, we develop kinetic models for several small networks with typical crosstalk modules to investigate the role of the architecture of crosstalk in inducing drug resistance. Our results demonstrate that crosstalk inhibition diminishes the response of signaling output to the external stimuli. Moreover, we show that signaling crosstalk affects the relative sensitivity of drugs, and some types of crosstalk modules that could yield resistance to the targeted drugs were identified. Furthermore, we quantitatively evaluate the relative efficacy and synergism of drug combinations. For the modules that are resistant to the targeted drug, we identify drug targets that can not only increase the relative drug efficacy but also act synergistically. In addition, we analyze the role of the strength of crosstalk in switching a module between drug-sensitive and drug-resistant. Our study provides mechanistic insights into the signaling crosstalk-mediated mechanisms of drug resistance and provides implications for the design of synergistic drug combinations to reduce drug resistance.

Polysaccharide of Black cumin (Nigella sativa) modulates molecular signaling cascade of gastric ulcer pathogenesis.

PubMed

Manjegowda, Srikanta Belagihalli; Rajagopal, Harsha Mysore; Dharmesh, Shylaja Mallaiah

2017-08-01

Gastric ulcer is a multi-step disease and healing requires a complex process including repair and re-architecture of gastric mucosa with the involvement of molecular events. Current study was designed to understand the gastric ulcer healing mechanism of rhamnogalacturonan-I type pectic polysaccharide of black cumin (BCPP) utilizing acetic acid induced gastric ulcers in rats. BCPP fed groups at 200mg/kg b.w. for 10days showed up to 85% healing of gastric ulcers with modulation of key molecular events involved in ulcer healing process such as increase in gastric mucin content, cyclooxygenase-2 (Cox-2) and prostaglandin E 2 (PGE 2 ). The increase in extracellular signal-regulated kinase-2 (ERK-2) indicated that, BCPP could induce PGE-2 synthesis by increasing ERK-2 mediated COX-2 activity. Increase in matrix metalloproteinase-2 (MMP-2) and decrease in MMP-9 levels in BCPP treated groups indicated differential regulation of MMP-2 and 9, an essential event required for gastric mucosal re-modulation. BCPP containing bound phenolics (26mg/g) might have also played a role in increasing speed and quality of ulcer healing by inhibiting H + , K + -ATPase and decreasing free radical mediated oxidation and cellular damages. Overall, studies showed that the polysaccharide can mediate ulcer healing by modulating signaling pathways involved in either ulcer aggravation or healing process. Copyright © 2017. Published by Elsevier B.V.

Immunology and Immunotherapy of Head and Neck Cancer

PubMed Central

Ferris, Robert L.

2015-01-01

The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented. PMID:26351330

The C-module-binding factor supports amplification of TRE5-A retrotransposons in the Dictyostelium discoideum genome.

PubMed

Bilzer, Annika; Dölz, Heike; Reinhardt, Alexander; Schmith, Anika; Siol, Oliver; Winckler, Thomas

2011-01-01

Retrotransposable elements are molecular parasites that have invaded the genomes of virtually all organisms. Although retrotransposons encode essential proteins to mediate their amplification, they also require assistance by host cell-encoded machineries that perform functions such as DNA transcription and repair. The retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a notable amount of both sense and antisense RNAs, which are generated from element-internal promoters, located in the A module and the C module, respectively. We observed that TRE5-A retrotransposons depend on the C-module-binding factor (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal domain of CbfA was found to be required and sufficient to mediate the accumulation of TRE5-A transcripts, but it did not support productive retrotransposition of TRE5-A. This result suggests different roles for CbfA protein domains in the regulation of TRE5-A retrotransposition frequency in D. discoideum cells. Although CbfA binds to the C module in vitro, the factor regulates neither C-module nor A-module promoter activity in vivo. We speculate that CbfA supports the amplification of TRE5-A retrotransposons by suppressing the expression of an as yet unidentified component of the cellular posttranscriptional gene silencing machinery.

Flavonoid Naringenin: A Potential Immunomodulator for Chlamydia trachomatis Inflammation

PubMed Central

Yilma, Abebayehu N.; Singh, Shree R.; Morici, Lisa; Dennis, Vida A.

2013-01-01

Chlamydia trachomatis, the agent of bacterial sexually transmitted infections, can manifest itself as either acute cervicitis, pelvic inflammatory disease, or a chronic asymptomatic infection. Inflammation induced by C. trachomatis contributes greatly to the pathogenesis of disease. Here we evaluated the anti-inflammatory capacity of naringenin, a polyphenolic compound, to modulate inflammatory mediators produced by mouse J774 macrophages infected with live C. trachomatis. Infected macrophages produced a broad spectrum of inflammatory cytokines (GM-CSF, TNF, IL-1β, IL-1α, IL-6, IL-12p70, and IL-10) and chemokines (CCL4, CCL5, CXCL1, CXCL5, and CXCL10) which were downregulated by naringenin in a dose-dependent manner. Enhanced protein and mRNA gene transcript expressions of TLR2 and TLR4 in addition to the CD86 costimulatory molecule on infected macrophages were modulated by naringenin. Pathway-specific inhibition studies disclosed that p38 mitogen-activated-protein kinase (MAPK) is involved in the production of inflammatory mediators by infected macrophages. Notably, naringenin inhibited the ability of C. trachomatis to phosphorylate p38 in macrophages, suggesting a potential mechanism of its attenuation of concomitantly produced inflammatory mediators. Our data demonstrates that naringenin is an immunomodulator of inflammation triggered by C. trachomatis, which possibly may be mediated upstream by modulation of TLR2, TLR4, and CD86 receptors on infected macrophages and downstream via the p38 MAPK pathway. PMID:23766556

Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway.

PubMed

Feng, Xiuyan; Zhang, Yiqian; Shao, Ningjun; Wang, Yanhui; Zhuang, Zhizhi; Wu, Ping; Lee, Matthew J; Liu, Yingli; Wang, Xiaonan; Zhuang, Jieqiu; Delpire, Eric; Gu, Dingying; Cai, Hui

2015-05-15

Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in maintaining blood pressure. Aldosterone is known to modulate NCC abundance. Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To exclude the influence of SPAK signaling pathway on the role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we investigated the effects of dietary salt changes and aldosterone on NCC abundance in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet significantly increased total NCC abundance while reducing ERK1/2 phosphorylation, whereas high-salt diet decreased total NCC while increasing ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression, an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and reversed the aldosterone-mediated increments of NCC partly by increasing NCC ubiquitination. Therefore, these data suggest that aldosterone modulates NCC abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal pathway in SPAK KO mice and part of the effects of dietary salt changes may be mediated by aldosterone in the DCTs.

Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway

PubMed Central

Feng, Xiuyan; Zhang, Yiqian; Shao, Ningjun; Wang, Yanhui; Zhuang, Zhizhi; Wu, Ping; Lee, Matthew J.; Liu, Yingli; Wang, Xiaonan; Zhuang, Jieqiu; Delpire, Eric; Gu, Dingying

2015-01-01

Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in maintaining blood pressure. Aldosterone is known to modulate NCC abundance. Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To exclude the influence of SPAK signaling pathway on the role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we investigated the effects of dietary salt changes and aldosterone on NCC abundance in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet significantly increased total NCC abundance while reducing ERK1/2 phosphorylation, whereas high-salt diet decreased total NCC while increasing ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression, an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and reversed the aldosterone-mediated increments of NCC partly by increasing NCC ubiquitination. Therefore, these data suggest that aldosterone modulates NCC abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal pathway in SPAK KO mice and part of the effects of dietary salt changes may be mediated by aldosterone in the DCTs. PMID:25761881

Backpacking. Outdoor Living Skills Series. Instructor Manual.

ERIC Educational Resources Information Center

Mentis, Jim

Intended for use by those who teach or work with youth in classroom or organizational settings, this self-contained module is designed to teach novices how to prepare for and conduct a safe backpack trip. Initial chapters present background information under nine headings: introduction (objectives, backpack history, information about Missouri…

Efficient Operation of Conductively Cooled Ho:Tm:LuLiF Laser Oscillator/Amplifier

NASA Technical Reports Server (NTRS)

Yu, Jirong; Bai, Yingxin; Trieu, Bo; Petros, M.; Petzar, Paul; Lee, Hyung; Singh, U.

2008-01-01

A conductively-cooled Ho:Tm:LuLiF laser oscillator generates 1.6J normal mode pulses at 10Hz with optical to optical efficiency of 20%. When the laser head module is used as the amplifier, the double-pass small-signal amplification excesses 25.

76 FR 68460 - Findings of Research Misconduct

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-04

... Plasticity after Head Injury,'' D.A. Hovda, P.I. R01 NS052406, ``Age-dependent Ketone Metabolism after Brain Injury,'' M.L. Prims, P.I. K08 NS002197, ``NMDA Receptor Dysfunction after Traumatic Brain Injury,'' C.C... of calcium influx and modulation of local neurotransmitters as hallmarks of pediatric traumatic brain...

Relating Neuronal to Behavioral Performance: Variability of Optomotor Responses in the Blowfly

PubMed Central

Rosner, Ronny; Warzecha, Anne-Kathrin

2011-01-01

Behavioral responses of an animal vary even when they are elicited by the same stimulus. This variability is due to stochastic processes within the nervous system and to the changing internal states of the animal. To what extent does the variability of neuronal responses account for the overall variability at the behavioral level? To address this question we evaluate the neuronal variability at the output stage of the blowfly's (Calliphora vicina) visual system by recording from motion-sensitive interneurons mediating head optomotor responses. By means of a simple modelling approach representing the sensory-motor transformation, we predict head movements on the basis of the recorded responses of motion-sensitive neurons and compare the variability of the predicted head movements with that of the observed ones. Large gain changes of optomotor head movements have previously been shown to go along with changes in the animals' activity state. Our modelling approach substantiates that these gain changes are imposed downstream of the motion-sensitive neurons of the visual system. Moreover, since predicted head movements are clearly more reliable than those actually observed, we conclude that substantial variability is introduced downstream of the visual system. PMID:22066014

Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

PubMed

Erental, Ariel; Sharon, Idith; Engelberg-Kulka, Hanna

2012-01-01

In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

Ebola Virus Modulates Transforming Growth Factor β Signaling and Cellular Markers of Mesenchyme-Like Transition in Hepatocytes

PubMed Central

Wahl-Jensen, Victoria; Safronetz, David; Trost, Brett; Hoenen, Thomas; Arsenault, Ryan; Feldmann, Friederike; Traynor, Dawn; Postnikova, Elena; Kusalik, Anthony; Napper, Scott; Blaney, Joseph E.; Feldmann, Heinz; Jahrling, Peter B.

2014-01-01

ABSTRACT Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. Although EBOV is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. We employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes. Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-β)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-β signaling in the kinome data sets correlated with the upregulation of TGF-β secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-β signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection. To gain perspective on the cellular consequence of TGF-β signaling modulation during EBOV infection, we assessed cellular markers associated with upregulation of TGF-β signaling. We observed upregulation of matrix metalloproteinase 9, N-cadherin, and fibronectin expression with concomitant reductions in the expression of E-cadherin and claudin-1, responses that are standard characteristics of an epithelium-to-mesenchyme-like transition. Additionally, we identified phosphorylation events downstream of TGF-β that may contribute to this process. From these observations, we propose a model for a broader role of TGF-β-mediated signaling responses in the pathogenesis of Ebola virus disease. IMPORTANCE Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most lethal Ebola virus species, with case fatality rates of up to 90%. Although EBOV is considered a worldwide concern, many questions remain regarding EBOV molecular pathogenesis. As it is appreciated that many cellular processes are regulated through kinase-mediated phosphorylation events, we employed temporal kinome analysis to investigate the functional responses of human hepatocytes to EBOV infection. Administration of kinase inhibitors targeting signaling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also demonstrated that EBOV infection modulated TGF-β-mediated signaling responses and promoted “mesenchyme-like” phenotypic changes. Taken together, these results demonstrated that EBOV infection specifically modulates TGF-β-mediated signaling responses in epithelial cells and may have broader implications in EBOV pathogenesis. PMID:24942569