DOE Office of Scientific and Technical Information (OSTI.GOV)
Lund, Leif R; Romer, John; Thomasset, Nicole
Postlactational involution of the mammary gland is characterized by two distinct physiological events: apoptosis of the secretory, epithelial cells undergoing programmed cell death, and proteolytic degradation of the mammary gland basement membrane. We examined the spatial and temporal patterns of apoptotic cells in relation to those of proteinases during involution of the BALB/c mouse mammary gland. Apoptosis was almost absent during lactation but became evident at day 2 of involution, when {beta}-casein gene expression was still high. Apoptotic cells were then seen at least up to day 8 of involution, when {beta}-casein gene expression was being extinguished. Expression of sulfatedmore » glycoprotein-2 (SGP-2), interleukin-1{beta} converting enzyme (ICE) and tissue inhibitor of metalloproteinases-1 was upregulated at day 2, when apoptotic cells were seen initially. Expression of the matrix metalloproteinases gelatinase A and stromelysin-1 and the serine proteinase urokinase-type plasminogen activator, which was low during lactation, was strongly upregulated in parallel starting at day 4 after weaning, coinciding with start of the collapse of the lobulo-alveolar structures and the intensive tissue remodeling in involution. The major sites of mRNA synthesis for these proteinases were fibroblast-like cells in the periductal stroma and stromal cells surrounding the collapsed alveoli, suggesting that the degradative phase of involution is due to a specialized mesenchymal-epithelial interaction. To elucidate the functional role of these proteinases during involution, at the onset of weaning we treated mice systemically with the glucocorticoid hydrocortisone, which is known to inhibit mammary gland involution. Although the initial wave of apoptotic cells appeared in the lumina of the gland, the dramatic regression and tissue remodeling usually evident by day 5 was substantially inhibited by systemic treatment with hydrocortisone. mRNA and protein for gelatinase A, stromelysin-1 and uPA were weakly induced, if at all, in hydrocortisonetreated mice. Furthermore, mRNA for membrane-type matrix metalloproteinase decreased after hydrocortisone treatment and paralleled the almost complete inhibition of activation of latent gelatinase A. Concomitantly, the gland filled with an overabundance of milk. Our data support the hypothesis that there are at least two distinct phases of involution: an initial phase, characterized by induction of the apoptosis-associated genes SGP-2 and ICE and apoptosis of fully differentiated mammary epithelial cells without visible degradation of the extracellular matrix, and a second phase, characterized by extracellular matrix remodeling and altered mesenchymal-epithelial interactions, followed by apoptosis of cells that are losing differentiated functions.« less
The Weyl-Lanczos equations and the Lanczos wave equation in four dimensions as systems in involution
NASA Astrophysics Data System (ADS)
Dolan, P.; Gerber, A.
2003-07-01
The Weyl-Lanczos equations in four dimensions form a system in involution. We compute its Cartan characters explicitly and use Janet-Riquier theory to confirm the results in the case of all space-times with a diagonal metric tensor and for the plane wave limit of space-times. We write the Lanczos wave equation as an exterior differential system and, with assistance from Janet-Riquier theory, we compute its Cartan characters and find that it forms a system in involution. We compare these Cartan characters with those of the Weyl-Lanczos equations. All results hold for the real analytic case.
Lilla, Jennifer N.; Joshi, Ravi V.; Craik, Charles S.; Werb, Zena
2009-01-01
The plasminogen cascade of serine proteases directs both development and tumorigenesis in the mammary gland. Plasminogen can be activated to plasmin by urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasma kallikrein (PKal). The dominant plasminogen activator for mammary involution is PKal, a serine protease that participates in the contact activation system of blood coagulation. We observed that the prekallikrein gene (Klkb1) is expressed highly in the mammary gland during stromal remodeling periods including puberty and postlactational involution. We used a variant of ecotin (ecotin-PKal), a macromolecular inhibitor of serine proteases engineered to be highly specific for active PKal, to demonstrate that inhibition of PKal with ecotin-PKal delays alveolar apoptosis, adipocyte replenishment, and stromal remodeling in the involuting mammary gland, producing a phenotype resembling that resulting from plasminogen deficiency. Using biotinylated ecotin-PKal, we localized active PKal to connective tissue-type mast cells in the mammary gland. Taken together, these results implicate PKal as an effector of the plasminogen cascade during mammary development. PMID:19297327
NOTCH3 regulates stem-to-mural cell differentiation in infantile hemangioma.
Edwards, Andrew K; Glithero, Kyle; Grzesik, Peter; Kitajewski, Alison A; Munabi, Naikhoba Co; Hardy, Krista; Tan, Qian Kun; Schonning, Michael; Kangsamaksin, Thaned; Kitajewski, Jan K; Shawber, Carrie J; Wu, June K
2017-11-02
Infantile hemangioma (IH) is a vascular tumor that begins with rapid vascular proliferation shortly after birth, followed by vascular involution in early childhood. We have found that NOTCH3, a critical regulator of mural cell differentiation and maturation, is expressed in hemangioma stem cells (HemSCs), suggesting that NOTCH3 may function in HemSC-to-mural cell differentiation and pathological vessel stabilization. Here, we demonstrate that NOTCH3 is expressed in NG2+PDGFRβ+ perivascular HemSCs and CD31+GLUT1+ hemangioma endothelial cells (HemECs) in proliferating IHs and becomes mostly restricted to the αSMA+NG2loPDGFRβlo mural cells in involuting IHs. NOTCH3 knockdown in HemSCs inhibited in vitro mural cell differentiation and perturbed αSMA expression. In a mouse model of IH, NOTCH3 knockdown or systemic expression of the NOTCH3 inhibitor, NOTCH3 Decoy, significantly decreased IH blood flow, vessel caliber, and αSMA+ perivascular cell coverage. Thus, NOTCH3 is necessary for HemSC-to-mural cell differentiation, and adequate perivascular cell coverage of IH vessels is required for IH vessel stability.
On the construction of unitary quantum group differential calculus
NASA Astrophysics Data System (ADS)
Pyatov, Pavel
2016-10-01
We develop a construction of the unitary type anti-involution for the quantized differential calculus over {{GL}}q(n) in the case | q| =1. To this end, we consider a joint associative algebra of quantized functions, differential forms and Lie derivatives over {{GL}}q(n)/{{SL}}q(n), which is bicovariant with respect to {{GL}}q(n)/{{SL}}q(n) coactions. We define a specific non-central spectral extension of this algebra by the spectral variables of three matrices of the algebra generators. In the spectrally expended algebra, we construct a three-parametric family of its inner automorphisms. These automorphisms are used for the construction of the unitary anti-involution for the (spectrally extended) calculus over {{GL}}q(n). This work has been funded by the Russian Academic Excellence Project ‘5-100’. The results of section 5 (propositions 5.2, 5.3 and theorem 5.5) have been obtained under support of the RSF grant No.16-11-10160.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Kyung-Jin; Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799; Yun, Jang-Hyuk
Highlights: • PEDF was expressed and induced during the involuting phase of IH. • PEDF inhibited the cell growth of the involuting HemECs in an autocrine manner. • PEDF suppression restored the impaired cell growth of the involuting HemECs. - Abstract: Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused onmore » the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.« less
STAT signaling in mammary gland differentiation, cell survival and tumorigenesis
Haricharan, S; Li, Y
2013-01-01
The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. PMID:23541951
Sánchez-Castellanos, M E; Sandoval-Tress, C; Hernández-Torres, M
2006-01-01
The omphalomesenteric duct is an embryonic structure which communicates the vitelline duct with the midgut. It normally disappears between the fifth and ninth weeks of intrauterine life. Anomalies related with the total or partial absence of this involution are show in 2 % of the population. We report a case of persistence of the omphalomesenteric duct and review the bibliography to establish the differences between this anomaly and umbilical granuloma, which is the main differential diagnosis.
Gene regulatory networks in lactation: identification of global principles using bioinformatics.
Lemay, Danielle G; Neville, Margaret C; Rudolph, Michael C; Pollard, Katherine S; German, J Bruce
2007-11-27
The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood. Mammary gland microarray data, cellular localization data, protein-protein interactions, and literature-mined genes were integrated and analyzed using statistics, principal component analysis, gene ontology analysis, pathway analysis, and network analysis to identify global biological principles that govern molecular events during pregnancy, lactation, and involution. Several key principles were derived: (1) nearly a third of the transcriptome fluctuates to build, run, and disassemble the lactation apparatus; (2) genes encoding the secretory machinery are transcribed prior to lactation; (3) the diversity of the endogenous portion of the milk proteome is derived from fewer than 100 transcripts; (4) while some genes are differentially transcribed near the onset of lactation, the lactation switch is primarily post-transcriptionally mediated; (5) the secretion of materials during lactation occurs not by up-regulation of novel genomic functions, but by widespread transcriptional suppression of functions such as protein degradation and cell-environment communication; (6) the involution switch is primarily transcriptionally mediated; and (7) during early involution, the transcriptional state is partially reverted to the pre-lactation state. A new hypothesis for secretory diminution is suggested - milk production gradually declines because the secretory machinery is not transcriptionally replenished. A comprehensive network of protein interactions during lactation is assembled and new regulatory gene targets are identified. Less than one fifth of the transcriptionally regulated nodes in this lactation network have been previously explored in the context of lactation. Implications for future research in mammary and cancer biology are discussed.
STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.
Haricharan, S; Li, Y
2014-01-25
The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Singh-Mallah, Gagandeep; McMahon, Christopher D; Guan, Jian; Singh, Kuljeet
2017-12-01
In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function. © 2017 Wiley Periodicals, Inc.
Llewellyn, S; Fitzpatrick, R; Kenny, D A; Patton, J; Wathes, D C
2008-05-01
Rapid uterine involution in the postpartum period of dairy cows is important to achieve a short interval to conception. Expression patterns for members of the insulin-like growth factor (IGF) family were determined by in situ hybridisation at day 14+/-0.4 postpartum (n=12 cows) to investigate a potential role for IGFs in modulating uterine involution. Expression in each uterine tissue region was measured as optical density units and data were analysed according to region and horn. IGF-I mRNA was localized to the sub-epithelial stroma (SES) of inter-caruncular and caruncular endometrium. Both IGF-II and IGF-1R expression was detected in the deep endometrial stroma (DES), the caruncular stroma and myometrium. IGFBP-2, IGFBP-4 and IGFBP-6 mRNAs were all localised to the SES of inter-caruncular and caruncular uterine tissue, and in the DES and caruncular stroma, with IGFBP-4 mRNA additionally expressed in myometrium. IGFBP-3 mRNA was only detectable in luminal epithelium. IGFBP-5 mRNA was found in myometrium, inter-caruncular and caruncular SES and caruncular stroma. These data support a role for IGF-I and IGF-II in the extensive tissue remodelling and repair which the postpartum uterus undergoes to return to its non-pregnant state. The differential expression of binding proteins between tissues (IGFBP-3 in epithelium, IGFBP-2, -4, -5 and -6 in stroma and IGFBP-4 and -5 in myometrium) suggest tight control of IGF activity within each compartment. Differential expression of many members of the IGF family between the significantly larger previously gravid horn and the previously non-gravid horn may relate to differences in their rate of tissue remodelling.
Llewellyn, S.; Fitzpatrick, R.; Kenny, D.A.; Patton, J.; Wathes, D.C.
2008-01-01
Rapid uterine involution in the postpartum period of dairy cows is important to achieve a short interval to conception. Expression patterns for members of the insulin-like growth factor (IGF) family were determined by in situ hybridisation at day 14 ± 0.4 postpartum (n = 12 cows) to investigate a potential role for IGFs in modulating uterine involution. Expression in each uterine tissue region was measured as optical density units and data were analysed according to region and horn. IGF-I mRNA was localized to the sub-epithelial stroma (SES) of inter-caruncular and caruncular endometrium. Both IGF-II and IGF-1R expression was detected in the deep endometrial stroma (DES), the caruncular stroma and myometrium. IGFBP-2, IGFBP-4 and IGFBP-6 mRNAs were all localised to the SES of inter-caruncular and caruncular uterine tissue, and in the DES and caruncular stroma, with IGFBP-4 mRNA additionally expressed in myometrium. IGFBP-3 mRNA was only detectable in luminal epithelium. IGFBP-5 mRNA was found in myometrium, inter-caruncular and caruncular SES and caruncular stroma. These data support a role for IGF-I and IGF-II in the extensive tissue remodelling and repair which the postpartum uterus undergoes to return to its non-pregnant state. The differential expression of binding proteins between tissues (IGFBP-3 in epithelium, IGFBP-2, -4, -5 and -6 in stroma and IGFBP-4 and -5 in myometrium) suggest tight control of IGF activity within each compartment. Differential expression of many members of the IGF family between the significantly larger previously gravid horn and the previously non-gravid horn may relate to differences in their rate of tissue remodelling. PMID:18258405
Generalized Moore Penrose Inverse of Normal Elements in a Ring with Involution
NASA Astrophysics Data System (ADS)
Titi Udjiani, SRRM; Harjito; Suryoto; Prima P, Nikken
2018-01-01
Based on the definition of a normal element in a ring with involution, it is found that each normal element is commutatively with the product of itself and the involution of itself. On the other hand, if the element of a ring with involution has generalized Moore Penrose inverse, then the element is also commutative with the product of itself and the involution of itself. In this paper, the phenomenon of the similarity properties from normal elements and generalized Moore Penrose inverse is used to establish the relationship between of them with them. .
Congenital telangiectatic atrophic patch on a healthy child.
Teresa Garcia-Romero, Maria; Ching, Joyce C Y; Ho, Nhung
2014-01-01
Rapidly involuting congenital hemangiomas (RICHs) are rare vascular tumors that have a proliferative phase in utero, present fully grown at birth, and have a fast involution phase after birth. Even rarer cases have completed involution in utero and present at birth as an atrophic plaque with redundant skin. We present one case of a RICH that underwent involution in utero and revise the diagnostic and management implications.
Modified Involute Helical Gears: Computerized Design, Simulation of Meshing, and Stress Analysis
NASA Technical Reports Server (NTRS)
Handschuh, Robert (Technical Monitor); Litvin, Faydor L.; Gonzalez-Perez, Ignacio; Carnevali, Luca; Kawasaki, Kazumasa; Fuentes-Aznar, Alfonso
2003-01-01
The computerized design, methods for generation, simulation of meshing, and enhanced stress analysis of modified involute helical gears is presented. The approaches proposed for modification of conventional involute helical gears are based on conjugation of double-crowned pinion with a conventional helical involute gear. Double-crowning of the pinion means deviation of cross-profile from an involute one and deviation in longitudinal direction from a helicoid surface. Using the method developed, the pinion-gear tooth surfaces are in point-contact, the bearing contact is localized and oriented longitudinally, and edge contact is avoided. Also, the influence of errors of aligment on the shift of bearing contact, vibration, and noise are reduced substantially. The theory developed is illustrated with numerical examples that confirm the advantages of the gear drives of the modified geometry in comparison with conventional helical involute gears.
Modified Involute Helical Gears: Computerized Design, Simulation of Meshing and Stress Analysis
NASA Technical Reports Server (NTRS)
2003-01-01
The computerized design, methods for generation, simulation of meshing, and enhanced stress analysis of modified involute helical gears is presented. The approaches proposed for modification of conventional involute helical gears are based on conjugation of double-crowned pinion with a conventional helical involute gear. Double-crowning of the pinion means deviation of cross-profile from an involute one and deviation in longitudinal direction from a helicoid surface. Using the method developed, the pinion-gear tooth surfaces are in point-contact, the bearing contact is localized and oriented longitudinally, and edge contact is avoided. Also, the influence of errors of alignment on the shift of bearing contact, vibration, and noise are reduced substantially. The theory developed is illustrated with numerical examples that confirm the advantages of the gear drives of the modified geometry in comparison with conventional helical involute gears.
Meng, Qingyong; Zhao, Yiqiang; Chen, Lei; Zhang, Hongquan; Xue, Lixiang; Zhang, Xiuqing; Lengner, Christopher; Yu, Zhengquan
2015-01-01
Hair follicles (HF) undergo precisely regulated recurrent cycles of growth, cessation, and rest. The transitions from anagen (growth), to catagen (regression), to telogen (rest) involve a physiological involution of the HF. This process is likely coordinated by a variety of mechanisms including apoptosis and loss of growth factor signaling. However, the precise molecular mechanisms underlying follicle involution after hair keratinocyte differentiation and hair shaft assembly remain poorly understood. Here we demonstrate that a highly conserved microRNA, miR-22 is markedly upregulated during catagen and peaks in telogen. Using gain- and loss-of-function approaches in vivo, we find that miR-22 overexpression leads to hair loss by promoting anagen-to-catagen transition of the HF, and that deletion of miR-22 delays entry to catagen and accelerates the transition from telogen to anagen. Ectopic activation of miR-22 results in hair loss due to the repression a hair keratinocyte differentiation program and keratinocyte progenitor expansion, as well as promotion of apoptosis. At the molecular level, we demonstrate that miR-22 directly represses numerous transcription factors upstream of phenotypic keratin genes, including Dlx3, Foxn1, and Hoxc13. We conclude that miR-22 is a critical post-transcriptional regulator of the hair cycle and may represent a novel target for therapeutic modulation of hair growth. PMID:26020521
Microfabricated Segmented-Involute-Foil Regenerator for Stirling Engines
NASA Technical Reports Server (NTRS)
Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gedeon, David; Qiu, Songgang; Wood, Gary; Kelly, Kevin; McLean, Jeffrey
2010-01-01
An involute-foil regenerator was designed, microfabricated, and tested in an oscillating-flow test rig. The concept consists of stacked involute-foil nickel disks (see figure) microfabricated via a lithographic process. Test results yielded a performance of about twice that of the 90-percent random-fiber currently used in small Stirling converters. The segmented nature of the involute- foil in both the axial and radial directions increases the strength of the structure relative to wrapped foils. In addition, relative to random-fiber regenerators, the involute-foil has a reduced pressure drop, and is expected to be less susceptible to the release of metal fragments into the working space, thus increasing reliability. The prototype nickel involute-foil regenerator was adequate for testing in an engine with a 650 C hot-end temperature. This is lower than that required by larger engines, and high-temperature alloys are not suited for the lithographic microfabrication approach.
Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland
2015-09-01
knock down. 15. SUBJECT TERMS Cell Adhesion, Involution, Metastasis, Latent TGFbeta Binding Protein, Pregnancy -associated Breast Cancer 16...Cell-matrix Adhesion, Involution, Metastasis, Latent TGF-beta Binding Protein, Pregnancy -associated Breast Cancer 3. ACCOMPLISHMENTS: Ø What were
Thermal and Structural Analysis of Micro-Fabricated Involute Regenerators
NASA Astrophysics Data System (ADS)
Qiu, Songgang; Augenblick, Jack E.
2005-02-01
Long-life, high-efficiency power generators based on free-piston Stirling engines are an energy conversion solution for future space power generation and commercial applications. As part of the efforts to further improve Stirling engine efficiency and reliability, a micro-fabricated, involute regenerator structure is proposed by a Cleveland State University-led regenerator research team. This paper reports on thermal and structural analyses of the involute regenerator to demonstrate the feasibility of the proposed regenerator. The results indicate that the involute regenerator has extremely high axial stiffness to sustain reasonable axial compression forces with negligible lateral deformation. The relatively low radial stiffness may impose some challenges to the appropriate installation of the in-volute regenerators.
The RNA binding protein Ars2 supports hematopoiesis at multiple levels.
Elahi, Seerat; Egan, Shawn M; Holling, G Aaron; Kandefer, Rachel L; Nemeth, Michael J; Olejniczak, Scott H
2018-05-15
Recent biochemical characterization of Arsenic resistance protein 2 (Ars2) has established it as central to determining the fate of nascent RNA polymerase II (RNAPII) transcripts. Through interactions with the nuclear 5'-7-methylguanosine (7mG) cap binding complex (CBC), Ars2 promotes co-transcriptional processing coupled with nuclear export or degradation of several classes of RNAPII transcripts, allowing for gene expression programs that facilitate rapid and sustained proliferation of immortalized cells in culture. However, rapidly dividing cells in culture do not represent the physiological condition of the vast majority of cells in an adult mammal. To examine functions of Ars2 in a physiological setting we generated inducible Ars2 knockout mice and found that deletion of Ars2 from adult mice resulted in defective hematopoiesis in bone marrow and thymus. Importantly, only some of this defect could be explained by the requirement of Ars2 for rapid proliferation, which we found to be cell-type specific in vivo. Rather Ars2 was required for survival of developing thymocytes and for limiting differentiation of bone marrow resident long-term hematopoietic stem cells (LT-HSCs). As a result, Ars2 knockout led to rapid thymic involution and loss of the ability of mice to regenerate peripheral blood following myeloablation. These in vivo data demonstrate that Ars2 expression is important at several steps of hematopoiesis, likely because Ars2 acts on gene expression programs underlying essential cell fate decisions such as the decision to die, to proliferate, or to differentiate. Copyright © 2018. Published by Elsevier Inc.
Physiologically activated mammary fibroblasts promote postpartum mammary cancer
Guo, Qiuchen; Burchard, Julja; Spellman, Paul
2017-01-01
Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced breast involution is implicated, as the collagen-rich, immunosuppressive microenvironment of the involuting mammary gland is tumor promotional in mice. To investigate the role of mammary fibroblasts, isolated mammary PDGFRα+ cells from nulliparous and postweaning mice were assessed for activation phenotype and protumorigenic function. Fibroblast activation during involution was evident by increased expression of fibrillar collagens, lysyl oxidase, Tgfb1, and Cxcl12 genes. The ability of mammary tumors to grow in an isogenic, orthotopic transplant model was increased when tumor cells were coinjected with involution-derived compared with nulliparous-derived mammary fibroblasts. Mammary tumors in the involution-fibroblast group had increased Ly6C+ monocytes at the tumor border, and decreased CD8+ T cell infiltration and tumor cell death. Ibuprofen treatment suppressed involution-fibroblast activation and tumor promotional capacity, concurrent with decreases in tumor Ly6C+ monocytes, and increases in intratumoral CD8+ T cell infiltration, granzyme levels, and tumor cell death. In total, our data identify a COX/prostaglandin E2 (PGE2)–dependent activated mammary fibroblast within the involuting mammary gland that displays protumorigenic, immunosuppressive activity, identifying fibroblasts as potential targets for the prevention and treatment of postpartum breast cancer. PMID:28352652
Ye, Xi; Abou‐Rayyah, Yassir; Bischoff, Joyce; Ritchie, Alison; Sebire, Neil J; Watts, Patrick
2016-01-01
Abstract Infantile haemangioma (IH), the most common neoplasm in infants, is a slowly resolving vascular tumour. Vascular endothelial growth factor A (VEGF‐A), which consists of both the pro‐ and anti‐angiogenic variants, contributes to the pathogenesis of IH. However, the roles of different VEGF‐A variants in IH progression and its spontaneous involution is unknown. Using patient‐derived cells and surgical specimens, we showed that the relative level of VEGF‐A165b was increased in the involuting phase of IH and the relative change in VEGF‐A isoforms may be dependent on endothelial differentiation of IH stem cells. VEGFR signalling regulated IH cell functions and VEGF‐A165b inhibited cell proliferation and the angiogenic potential of IH endothelial cells in vitro and in vivo. The inhibition of angiogenesis by VEGF‐A165b was associated with the extent of VEGF receptor 2 (VEGFR2) activation and degradation and Delta‐like ligand 4 (DLL4) expression. These results indicate that VEGF‐A variants can be regulated by cell differentiation and are involved in IH progression. We also demonstrated that DLL4 expression was not exclusive to the endothelium in IH but was also present in pericytes, where the expression of VEGFR2 is absent, suggesting that pericyte‐derived DLL4 may prevent sprouting during involution, independently of VEGFR2. Angiogenesis in IH therefore appears to be controlled by DLL4 within the endothelium in a VEGF‐A isoform‐dependent manner, and in perivascular cells in a VEGF‐independent manner. The contribution of VEGF‐A isoforms to disease progression also indicates that IH may be associated with altered splicing. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:26957058
E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.
Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M
2015-10-01
Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53(-/-) mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy.
E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution
Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M
2015-01-01
Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53−/− mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy. PMID:25656653
Hanna, Mirette; Dumas, Isabelle; Orain, Michèle; Jacob, Simon; Têtu, Bernard; Sanschagrin, François; Bureau, Alexandre; Poirier, Brigitte; Diorio, Caroline
2017-01-01
Increased levels of pro-inflammatory markers and decreased levels of anti-inflammatory markers in the breast tissue can result in local inflammation. We aimed to investigate whether local inflammation in the breast tissue is associated with age-related lobular involution, a process inversely related to breast cancer risk. Levels of eleven pro- and anti-inflammatory markers were assessed by immunohistochemistry in normal breast tissue obtained from 164 pre- and postmenopausal breast cancer patients. Involution status of the breast (degree of lobular involution and the predominant lobule type) was microscopically assessed in normal breast tissue on hematoxylin-eosin stained mastectomy slides. Multivariate generalized linear models were used to assess the associations. In age-adjusted analyses, higher levels of pro-inflammatory markers IL-6, TNF-α, CRP, COX-2, leptin, SAA1 and IL-8; and anti-inflammatory marker IL-10, were inversely associated with the prevalence of complete lobular involution (all P≤0.04). Higher levels of the pro-inflammatory marker COX-2 were also associated with lower prevalence of predominant type 1/no type 3 lobules in the breast, an indicator of complete involution, in age-adjusted analysis (P = 0.017). Higher tissue levels of inflammatory markers, mainly the pro-inflammatory ones, are associated with less involuted breasts and may consequently be associated with an increased risk of developing breast cancer. PMID:28846716
Gierach, Gretchen L.; Patel, Deesha A.; Pfeiffer, Ruth M.; Figueroa, Jonine D.; Linville, Laura; Papathomas, Daphne; Johnson, Jason M.; Chicoine, Rachael E.; Herschorn, Sally D.; Shepherd, John A.; Wang, Jeff; Malkov, Serghei; Vacek, Pamela M.; Weaver, Donald L.; Fan, Bo; Mahmoudzadeh, Amir Pasha; Palakal, Maya; Xiang, Jackie; Oh, Hannah; Horne, Hisani N.; Sprague, Brian L.; Hewitt, Stephen M.; Brinton, Louise A.; Sherman, Mark E.
2016-01-01
Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLUs), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (peri-lesional). Three measures inversely related to TDLU involution (TDLU count/mm2, median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40–65, were related to MD area (quantified with thresholding software) and volume (assessed with a density phantom) by analysis of covariance, stratified by menopausal status and adjusted for confounders. Among premenopausal women, TDLU count was directly associated with percent peri-lesional MD (P-trend=0.03), but not with absolute dense area/volume. Greater TDLU span was associated with elevated percent dense area/volume (P-trend<0.05) and absolute peri-lesional MD (P=0.003). Acini count was directly associated with absolute peri-lesional MD (P=0.02). Greater TDLU involution (all metrics) was associated with increased nondense area/volume (P-trend≤0.04). Among postmenopausal women, TDLU measures were not significantly associated with MD. Among premenopausal women, reduced TDLU involution was associated with higher area and volumetric MD, particularly in peri-lesional parenchyma. Data indicating that TDLU involution and MD are correlated markers of breast cancer risk suggest that associations of MD with breast cancer may partly reflect amounts of at-risk epithelium. If confirmed, these results could suggest a prevention paradigm based on enhancing TDLU involution and monitoring efficacy by assessing MD reduction. PMID:26645278
Diode laser for the treatment of telangiectasias following hemangioma involution.
Cerrati, Eric W; O, Teresa M; Chung, Hoyun; Waner, Milton
2015-02-01
Infantile hemangiomas are well known for their rapid growth during the first 6 to 9 months of life, followed by a spontaneous but slow involution. The standard of care is to treat these lesions at an early age with propranolol to expedite the involution process; however, surgery still remains an active component in the management. Medical treatment with propranolol or natural involution will often result in residual telangiectasias. We evaluated the efficacy of using a diode laser as a treatment for telangiectasias following cervicofacial infantile hemangioma involution. Case series with chart review. Tertiary care hospital and practice specializing in the care of vascular anomalies. Twenty patients, aged 4 months to 11 years (average 2.69 years), underwent treatment with a 532-nm diode laser to treat the residual telangiectasias following hemangioma involution. All procedures were performed in the operating room. To assess the efficacy, we independently evaluated pre- and posttreatment digital photographs and ranked them on a 0- to 4-point scale (0 = no change and 4 = complete response). Adverse reactions were also recorded. The telangiectasias showed considerable improvement following treatment. In more than half of the patients treated, the affected area demonstrated a complete response. No adverse reactions were noted. A 532-nm diode laser effectively treats the remaining telangiectasias following hemangioma involution. Whether used independently or in conjunction with other treatment modalities, the diode laser should be part of the surgical armamentarium when treating infantile hemangiomas. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.
A Microfabricated Involute-Foil Regenerator for Stirling Engines
NASA Technical Reports Server (NTRS)
Tew, Roy; Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gedeon, David; Kelly, Kevin; McLean, Jeffrey; Qiu, Songgang
2007-01-01
A segmented involute-foil regenerator has been designed, microfabricated and tested in an oscillating-flow rig with excellent results. During the Phase I effort, several approximations of parallel-plate regenerator geometry were chosen as potential candidates for a new microfabrication concept. Potential manufacturers and processes were surveyed. The selected concept consisted of stacked segmented-involute-foil disks (or annular portions of disks), originally to be microfabricated from stainless-steel via the LiGA (lithography, electroplating, and molding) process and EDM. During Phase II, re-planning of the effort led to test plans based on nickel disks, microfabricated via the LiGA process, only. A stack of nickel segmented-involute-foil disks was tested in an oscillating-flow test rig. These test results yielded a performance figure of merit (roughly the ratio of heat transfer to pressure drop) of about twice that of the 90 percent random fiber currently used in small approx.100 W Stirling space-power convertors-in the Reynolds Number range of interest (50 to 100). A Phase III effort is now underway to fabricate and test a segmented-involute-foil regenerator in a Stirling convertor. Though funding limitations prevent optimization of the Stirling engine geometry for use with this regenerator, the Sage computer code will be used to help evaluate the engine test results. Previous Sage Stirling model projections have indicated that a segmented-involute-foil regenerator is capable of improving the performance of an optimized involute-foil engine by 6 to 9 percent; it is also anticipated that such involute-foil geometries will be more reliable and easier to manufacture with tight-tolerance characteristics, than random-fiber or wire-screen regenerators. Beyond the near-term Phase III regenerator fabrication and engine testing, other goals are (1) fabrication from a material suitable for high temperature Stirling operation (up to 850 C for current engines; up to 1200 C for a potential engine-cooler for a Venus mission), and (2) reduction of the cost of the fabrication process to make it more suitable for terrestrial applications of segmented involute foils. Past attempts have been made to use wrapped foils to approximate the large theoretical figures of merit projected for parallel plates. Such metal wrapped foils have never proved very successful, apparently due to the difficulties of fabricating wrapped-foils with uniform gaps and maintaining the gaps under the stress of time-varying temperature gradients during start-up and shut-down, and relatively-steady temperature gradients during normal operation. In contrast, stacks of involute-foil disks, with each disk consisting of multiple involute-foil segments held between concentric circular ribs, have relatively robust structures. The oscillating-flow rig tests of the segmented-involute-foil regenerator have demonstrated a shift in regenerator performance strongly in the direction of the theoretical performance of ideal parallel-plate regenerators.
A Microfabricated Involute-Foil Regenerator for Stirling Engines
NASA Technical Reports Server (NTRS)
Tew, Roy; Ibrahim, Mounir; Danila, Daniel; Simon, Terry; Mantell, Susan; Sun, Liyong; Gedeon, David; Kelly, Kevin; McLean, Jeffrey; Wood, Gary;
2007-01-01
A segmented involute-foil regenerator has been designed, microfabricated and tested in an oscillating-flow rig with excellent results. During the Phase I effort, several approximations of parallel-plate regenerator geometry were chosen as potential candidates for a new microfabrication concept. Potential manufacturers and processes were surveyed. The selected concept consisted of stacked segmented-involute-foil disks (or annular portions of disks), originally to be microfabricated from stainless-steel via the LiGA (lithography, electroplating, and molding) process and EDM (electric discharge machining). During Phase II, re-planning of the effort led to test plans based on nickel disks, microfabricated via the LiGA process, only. A stack of nickel segmented-involute-foil disks was tested in an oscillating-flow test rig. These test results yielded a performance figure of merit (roughly the ratio of heat transfer to pressure drop) of about twice that of the 90% random fiber currently used in small 100 W Stirling space-power convertors in the Reynolds Number range of interest (50-100). A Phase III effort is now underway to fabricate and test a segmented-involute-foil regenerator in a Stirling convertor. Though funding limitations prevent optimization of the Stirling engine geometry for use with this regenerator, the Sage computer code will be used to help evaluate the engine test results. Previous Sage Stirling model projections have indicated that a segmented-involute-foil regenerator is capable of improving the performance of an optimized involute-foil engine by 6-9%; it is also anticipated that such involute-foil geometries will be more reliable and easier to manufacture with tight-tolerance characteristics, than random-fiber or wire-screen regenerators. Beyond the near-term Phase III regenerator fabrication and engine testing, other goals are (1) fabrication from a material suitable for high temperature Stirling operation (up to 850 C for current engines; up to 1200 C for a potential engine-cooler for a Venus mission), and (2) reduction of the cost of the fabrication process to make it more suitable for terrestrial applications of segmented involute foils. Past attempts have been made to use wrapped foils to approximate the large theoretical figures of merit projected for parallel plates. Such metal wrapped foils have never proved very successful, apparently due to the difficulties of fabricating wrapped-foils with uniform gaps and maintaining the gaps under the stress of time-varying temperature gradients during start-up and shut-down, and relatively-steady temperature gradients during normal operation. In contrast, stacks of involute-foil disks, with each disk consisting of multiple involute-foil segments held between concentric circular ribs, have relatively robust structures. The oscillating-flow rig tests of the segmented-involute-foil regenerator have demonstrated a shift in regenerator performance strongly in the direction of the theoretical performance of ideal parallel-plate regenerators.
General relativity in two dimensions: A Hamilton-Jacobi analysis
NASA Astrophysics Data System (ADS)
Bertin, M. C.; Pimentel, B. M.; Pompeia, P. J.
2010-11-01
We analyzed the constraint structure of the Einstein-Hilbert first-order action in two dimensions using the Hamilton-Jacobi approach. We were able to find a set of involutive, as well as a set of non-involutive constraints. Using generalized brackets we showed how to assure integrability of the theory, to eliminate the set of non-involutive constraints and how to build the field equations.
Symmetric products of a real curve and the moduli space of Higgs bundles
NASA Astrophysics Data System (ADS)
Baird, Thomas John
2018-03-01
Consider a Riemann surface X of genus g ≥ 2 equipped with an antiholomorphic involution τ. This induces a natural involution on the moduli space M(r , d) of semistable Higgs bundles of rank r and degree d. If D is a divisor such that τ(D) = D, this restricts to an involution on the moduli space M(r , D) of those Higgs bundles with fixed determinant O(D) and trace-free Higgs field. The fixed point sets of these involutions M(r , d) τ and M(r , D) τ are (A , A , B) -branes introduced by Baraglia and Schaposnik (2016). In this paper, we derive formulas for the mod 2 Betti numbers of M(r , d) τ and M(r , D) τ when r = 2 and d is odd. In the course of this calculation, we also compute the mod 2 cohomology ring of Symm(X) τ, the fixed point set of the involution induced by τ on symmetric products of the Riemann surface.
NASA Technical Reports Server (NTRS)
Steffen, J. M.; Musacchia, X. J.
1984-01-01
Hindlimb muscle atrophy, thymic involution and adrenal hypertrophy in rats during spaceflight can be simulated using suspension models. Skeletal muscle and thymus are sensitive to gluco-corticoids (GC), and previous studies have demonstrated that muscle atrophy in suspended rats is associated with increased GC receptor concentration. The objectives were to confirm thymic involution during suspension, and determine if involution correlated with increased GC receptor concentration. Seven days of antiorthostatic (AO) suspension of rats produced a significant (P less than 0.001) reduction in thymic wet weight not associated with an alteration of percent water content. GC receptor concentration (pmol/mg protein) decreased 20 percent (P less than 0.025) in thymus glands from 7 day AO suspended rats. Suspension, therefore, is associated with involution of the thymus, but this is not dependent upon AO positioning. Thymus GC receptor concentrations were depressed in 7-day suspended rats, in contrast with previous observations on skeletal muscle, suggesting that different mechanisms may underlie these responses.
Thymic involution in the suspended rat - Adrenal hypertrophy and glucocorticoid receptor content
NASA Technical Reports Server (NTRS)
Steffen, J. M.; Musacchia, X. J.
1986-01-01
The relationship between thymic involution and adrenal hypertrophy is studied. The thymus, adrenal glands, and tissue water content are evaluated in male Sprague rats suspended in antiorthostatic (AO) or orthostatic (O) positions. A 50 percent decrease in the wet weight of the thymus and hypertrophy of the adrenal glands are observed during the seven days of AO suspension. After seven days of recovery the thymus weight is increased to control level; however, the hypertrophy of the adrenal glands remains unchanged. Thymic and renal responses in O postioned rats are similar to AO reactions. Thymic glucocorticoid (GC) receptor concentrations in the rats are analyzed; a 20 percent decrease in GC receptor site concentration, which is related to thymic involution, is detected in both AO and O rats. It is concluded that there is a temporal correlation between thymic involution and adrenal hypertrophy, which is not affected by AO positioning, and thymic involution is not associated with an increased sensitivity to GC.
Szymanowska, Malgorzata; Hendry, Kay A K; Robinson, Claire; Kolb, Andreas F
2009-01-01
Extracellular matrix metalloproteinase inducer (EMMPRIN/basigin/CD147) is a cell surface protein, which has been associated with the induction of matrix metalloproteinase (MMP) genes during cancer metastasis. EMMPRIN plays a role in a variety of physiological processes as is evident by the diverse deficiencies detectable in EMMPRIN knockout mice. We have analysed the role of EMMPRIN in the induction of MMP genes during mammary gland differentiation and involution. Co-transfection studies showed that EMMPRIN has diverse effects on MMP promoter activity in different mammary and non-mammary cell lines. Expression of EMMPRIN mRNA is enhanced markedly by insulin in a mammary gland cell line but appears to have no direct effect on MMP gene expression in these cells. Microarray analysis and quantitative PCR show that EMMPRIN is expressed throughout mammary gland differentiation in the mouse. Its expression decreases during early pregnancy and briefly after induction of mammary gland involution by litter removal. Immunohistochemical analysis shows that EMMPRIN expression is limited to the stromal compartment during pregnancy, whereas it is strongly expressed in the epithelium during lactation. In summary the data argue against a causal role for EMMPRIN for the induction of MMP gene expression during adult mammary gland development. These data therefore support a physiological role for EMMPRIN other than MMP induction in mammary gland biology. 2008 Wiley-Liss, Inc.
Michalkova, Veronika; Didion, Elise M.; Xiao, Yanyu; Attardo, Geoffrey M.; Aksoy, Serap
2018-01-01
Tsetse flies are important vectors of human and animal trypanosomiasis. Ability to reduce tsetse populations is an effective means of disease control. Lactation is an essential component of tsetse’s viviparous reproductive physiology and requires a dramatic increase in the expression and synthesis of milk proteins by the milk gland organ in order to nurture larval growth. In between each gonotrophic cycle, tsetse ceases milk production and milk gland tubules undergo a nearly two-fold reduction in width (involution). In this study, we examined the role autophagy plays during tsetse fly milk gland involution and reproductive output. Autophagy genes show elevated expression in tissues associated with lactation, immediately before or within two hours post-parturition, and decline at 24-48h post-parturition. This expression pattern is inversely correlated with that of the milk gland proteins (lactation-specific protein coding genes) and the autophagy inhibitor fk506-bp1. Increased expression of Drosophila inhibitor of apoptosis 1, diap1, was also observed in the milk gland during involution, when it likely prevents apoptosis of milk gland cells. RNAi-mediated knockdown of autophagy related gene 8a (atg8a) prevented rapid milk gland autophagy during involution, prolonging gestation, and reducing fecundity in the subsequent gonotrophic cycle. The resultant inhibition of autophagy reduced the recovery of stored lipids during the dry (non-lactating) periods by 15–20%. Ecdysone application, similar to levels that occur immediately before birth, induced autophagy, and increased milk gland involution even before abortion. This suggests that the ecdysteroid peak immediately preceding parturition likely triggers milk gland autophagy. Population modeling reveals that a delay in involution would yield a negative population growth rate. This study indicates that milk gland autophagy during involution is critical to restore nutrient reserves and allow efficient transition between pregnancy cycles. Targeting post-birth phases of reproduction could be utilized as a novel mechanism to suppress tsetse populations and reduce trypanosomiasis. PMID:29385123
Nguyen, Tina Tu-Thu Ngoc; Shynlova, Oksana; Lye, Stephen J.
2016-01-01
Pregnancy, spontaneous term labor (TL), and postpartum (PP) involution are associated with changes in the cellular and extracellular matrix composition of the uterus. Both the uterine smooth muscle (myometrium) and the infiltrating peripheral blood leukocytes involved in the activation of labor secrete extracellular matrix-degrading enzymes (matrix metalloproteinases, MMPs) that can modulate cellular behavior and barrier function. MMP expression is induced by mechanical stretch in several tissues. We hypothesized that the expression and activity of myometrial MMPs and their tissue inhibitors (TIMPs) are modulated in preparation for TL and PP involution and are regulated by mechanical stretch of uterine walls imposed by the growing fetus. Myometrial tissues were collected from bilaterally and unilaterally pregnant rats across gestation, TL, and PP. Total RNA and proteins were subjected to real-time PCR and immunoblotting, respectively, and tissue localization and activity was examined by immunohistochemistry and in situ zymography. We found that Mmp7, Mmp11, and Mmp12 mRNA levels were upregulated during TL and PP, while Mmp2, Mmp3, Mmp8, Mmp9, Mmp10, and Mmp13 mRNAs were only upregulated during PP. Timp1–Timp4 were stably expressed throughout gestation with some fluctuations PP. Active MMP2 was induced in the empty uterine horn during gestation and in the gravid PP uterus, suggesting negative regulation by biological mechanical stretch. We conclude that specific subsets of uterine MMPs are differentially regulated in the rat myometrium in preparation for two major events: TL and PP uterine involution. PMID:27251092
Circulating Sex Hormones and Terminal Duct Lobular Unit Involution of the Normal Breast
Khodr, Zeina G.; Sherman, Mark E.; Pfeiffer, Ruth M.; Gierach, Gretchen L.; Brinton, Louise A.; Falk, Roni T.; Patel, Deesha A.; Linville, Laura M.; Papathomas, Daphne; Clare, Susan E.; Visscher, Daniel W.; Mies, Carolyn; Hewitt, Stephen M.; Storniolo, Anna Maria V.; Rosebrock, Adrian; Caban, Jesus J.; Figueroa, Jonine D.
2014-01-01
Background Terminal duct lobular units (TDLUs) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011). Methods We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n=390): TDLU counts, median TDLU span, and median acini counts per TDLU. Relative risks (RRs, for continuous measures), odds ratios (ORs, for categorical measures), 95% confidence intervals (CIs), and p-trends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders. Results Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18, 95% CI: 1.07-1.31; p-trend=0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80, 95% CI: 0.72-0.89; p-trend<0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61, 95% CI: 1.32-1.97; p-trend<0.0001) and testosterone (RRT3vsT1: 1.32, 95% CI: 1.09-1.59; p-trend=0.0043) were associated with higher TDLU counts. Conclusions These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution. Impact Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis. PMID:25472681
Lacher, M D; Siegenthaler, A; Jäger, R; Yan, Xi; Hett, S; Xuan, L; Saurer, S; Lareu, R R; Dharmarajan, A M; Friis, R
2003-05-01
Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3beta (GSK-3beta), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.
Treatment of liver hydatidosis: How to treat an asymptomatic carrier?
Frider, Bernardo; Larrieu, Edmundo
2010-01-01
Liver hydatidosis is the most common clinical presentation of cystic echinococcosis (CE). Ultrasonographic mass surveys have demonstrated the true prevalence, including the asymptomatic characteristic of the majority of cases, providing new insight into the natural history of the disease. This raises the question of whether to treat or not to treat these patients, due to the high and unsuspected prevalence of CE. The high rate of liver/lung frequencies of cyst localization, the autopsy findings, and the involution of cysts demonstrated in long time follow-up of asymptomatic carriers contribute to this discussion. The decision to treat an asymptomatic patient by surgery, albendazole, or puncture aspiration injection and reaspiration or to wait and watch, is based on conflicting reports in the literature, the lack of complications in untreated patients over time, and the spontaneous disappearance and involution of cysts. All these points contribute to difficulties of individual clinical decisions. The patients should be informed of the reasons and the risks of watchful/waiting without treatment, the possibility of complications, and the risks of the other options. As more information on the natural history of liver hydatidosis is acquired, selection of the best treatment will be come easier. Without this knowledge it would be very difficult to establish definitive rules of treatment. At present, it is possible to manage these patients over time and to wait for the best moment for treatment. Follow-up studies must be conducted to achieve this objective. PMID:20806427
Uterine involution: its role in regulating postpartum intervals.
Kiracofe, G H
1980-01-01
An involuting uterus is a temporary barrier to fertility in cows, ewes and sows. Parturition is followed by a period when conception is not possible: about 1 week in sows and about 3 weeks in cows and ewes. Estrus and ovulation seldom occur together during this period and, if fertilization occurred and the embryo reached the uterus, placentation would be virtually impossible. The period of no fertility is followed by 2 to 3 weeks when fertility is possible, but not optimal. The extent to which the involuting uterus contributes to infertility during the second period is difficult to determine. Embryonic mortality in sows bred during this latter period appears to be a major cause of reduced litter size, so changes in uterine environment associated with involution may be essential for optimum fertility. Conception rate is lower up to 40 days after parturition than later in cows and ewes. Uterine involution appears not to be a barrier to fertility after 3 to 4 weeks postpartum in sows or 5 to 6 weeks postpartum in cows and ewes unless delayed by inflammation or infection.
Mechanisms for pituitary tumorigenesis: the plastic pituitary
Melmed, Shlomo
2003-01-01
The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease. PMID:14660734
[Characteristics of the pineal gland and thymus relationship in aging].
Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M; Trofimov, A V; Sevost'ianova, N N
2011-01-01
The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.
2015-07-01
invasion and metastasis in animal models, data consistent with involution driving tumor progression. We have also shown that the promotional effects...next scheduled continuing review on July 21, 2016. Submission for HRPO approval has been obtained and in place until summer 2016 as well. b. Animal ...Approval Issues – The samples from our murine models of involution with and without tumor xenografts in the animals are all collected and in use. Year
Apoptosis in the areas of squamous differentiation of irritated seborrheic keratosis.
Pesce, C; Scalora, S
2000-03-01
Seborrheic keratosis (SK) consists of a localized proliferation of basaloid keratinocytes, often accompanied by hyperkeratosis and hyperpigmentation. In irritated SK, these features are associated with areas of squamous differentiation with larger keratinocytes and squamous cell eddies. This work is concerned with the evaluation of apoptosis, as demonstrated by the TUNEL method, in the different varieties of SK. Apoptosis was highly expressed in the areas of squamous differentiation of irritated SK, but only mildly increased in the other varieties of SK. These data support the hypothesis that apoptosis has a role in the squamous differentiation of irritated SK. In consideration also of previous data showing that irritated SK is associated with downregulation of EGF-R expression and 125I-EGF binding, we postulate that the morphologic features of irritated SK could correspond to an involution phase of the disease, characterized by altered cell balance with inadequate cell renewal and increased cell loss.
Garfin, Phillip M.; Min, Dullei; Bryson, Jerrod L.; Serwold, Thomas; Edris, Badreddin; Blackburn, Clare C.; Richie, Ellen R.; Weinberg, Kenneth I.; Manley, Nancy R.; Viatour, Patrick
2013-01-01
Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow–independent mechanism, identifying a novel pathway to target to increase thymic function in patients. PMID:23669396
Adipocyte and leptin accumulation in tumor-induced thymic involution.
Lamas, Alejandro; Lopez, Elena; Carrio, Roberto; Lopez, Diana M
2016-01-01
Cell-mediated immunity is an important defense mechanism against pathogens and developing tumor cells. The thymus is the main lymphoid organ involved in the formation of the cell-mediated immune response by the maturation and differentiation of lymphocytes that travel from the bone marrow, through the lymphatic ducts, to become T lymphocytes. Thymic involution has been associated with aging; however, other factors such as obesity, viral infection and tumor development have been shown to increase the rate of shrinkage of this organ. The heavy infiltration of adipocyte fat cells has been reported in the involuted thymuses of aged mice. In the present study, the possible accumulation of such cells in the thymus during tumorigenesis was examined by immunohistochemistry. A significant number of adipocytes around and infiltrating the thymuses of tumor-bearing mice was observed. Leptin is a pro-inflammatory adipocytokine that enhances thymopoiesis and modulates T cell immune responses. The levels of leptin and adiponectin, another adipocytokine that has anti-inflammatory properties, were examined by western blot analysis. While no changes were observed in the amounts of adiponectin present in the thymuses of the normal and tumor-bearing mice, significantly higher levels of leptin were detected in the thymocytes of the tumor-bearing mice. This correlated with an increase in the expression of certain cytokines, such as interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). The co-culture of thymocytes isolated from normal mice with ex vivo isolated adipocytes from tumor-bearing mice yielded similar results. Our findings suggest that the infiltration and accumulation of adipocytes in the thymuses of tumor-bearing mice play an important role in their altered morphology and functions.
Tan, Jianxin; Wang, Yajun; Zhang, Nannan; Zhu, Xike
2016-08-01
Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been reported to be up-regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-β1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-β1 functions a dual role in age-related thymic involution. On one hand, up-regulation of TGF-β1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-β1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-β1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-β1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly. © 2016 International Federation for Cell Biology.
Terminal Duct Lobular Unit Involution of the Normal Breast: Implications for Breast Cancer Etiology
Pfeiffer, Ruth M.; Patel, Deesha A.; Linville, Laura; Brinton, Louise A.; Gierach, Gretchen L.; Yang, Xiaohong R.; Papathomas, Daphne; Visscher, Daniel; Mies, Carolyn; Degnim, Amy C.; Anderson, William F.; Hewitt, Stephen; Khodr, Zeina G.; Clare, Susan E.; Storniolo, Anna Maria; Sherman, Mark E.
2014-01-01
Background Greater degrees of terminal duct lobular unit (TDLU) involution have been linked to lower breast cancer risk; however, factors that influence this process are poorly characterized. Methods To study this question, we developed three reproducible measures that are inversely associated with TDLU involution: TDLU counts, median TDLU span, and median acini counts/TDLU. We determined factors associated with TDLU involution using normal breast tissues from 1938 participants (1369 premenopausal and 569 postmenopausal) ages 18 to 75 years in the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Multivariable zero-inflated Poisson models were used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) for factors associated with TDLU counts, and multivariable ordinal logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for factors associated with categories of median TDLU span and acini counts/TDLU. Results All TDLU measures started declining in the third age decade (all measures, two-sided P trend ≤ .001); and all metrics were statistically significantly lower among postmenopausal women. Nulliparous women demonstrated lower TDLU counts compared with uniparous women (among premenopausal women, RR = 0.79, 95% CI = 0.73 to 0.85; among postmenopausal, RR = 0.67, 95% CI = 0.56 to 0.79); however, rates of age-related TDLU decline were faster among parous women. Other factors were related to specific measures of TDLU involution. Conclusion Morphometric analysis of TDLU involution warrants further evaluation to understand the pathogenesis of breast cancer and assessing its role as a progression marker for women with benign biopsies or as an intermediate endpoint in prevention studies. PMID:25274491
Bodelon, Clara; Oh, Hannah; Chatterjee, Nilanjan; Garcia-Closas, Montserrat; Palakal, Maya; Sherman, Mark E.; Pfeiffer, Ruth M.; Geller, Berta; Vacek, Pamela; Weaver, Donald L.; Chicoine, Rachael; Papathomas, Daphne; Xiang, Jackie; Patel, Deesha A.; Khodr, Zeina G.; Linville, Laura; Clare, Susan E.; Visscher, Daniel W.; Mies, Carolyn; Hewitt, Stephen M.; Brinton, Louise A.; Storniolo, Anna Maria V.; He, Chunyan; Chanock, Stephen J.
2016-01-01
Terminal duct lobular units (TDLUs) are the predominant source of future breast cancers, and lack of TDLU involution (higher TDLU counts, higher acini count per TDLU and the product of the two) is a breast cancer risk factor. Numerous breast cancer susceptibility single nucleotide polymorphisms (SNPs) have been identified, but whether they are associated with TDLU involution is unknown. In a pooled analysis of 872 women from two studies, we investigated 62 established breast cancer SNPs and relationships with TDLU involution. Poisson regression models with robust variance were used to calculate adjusted per-allele relative risks (with the non-breast cancer risk allele as the referent) and 95% confidence intervals between TDLU measures and each SNP. All statistical tests were two-sided; P<0.05 was considered statistically significant. Overall, 36 SNPs (58.1%) were related to higher TDLU counts although this was not statistically significant (P=0.25). Six of the 62 SNPs (9.7%) were nominally associated with at least one TDLU measure: rs616488 (PEX14), rs11242675 (FOXQ1) and rs6001930 (MKL1) were associated with higher TDLU count (P=0.047, 0.045 and 0.031, respectively); rs1353747 (PDE4D) and rs6472903 (8q21.11) were associated with higher acini count per TDLU (P=0.007 and 0.027, respectively); and rs1353747 (PDE4D) and rs204247 (RANBP9) were associated with the product of TDLU and acini counts (P=0.024 and 0.017, respectively). Our findings suggest breast cancer SNPs may not strongly influence TDLU involution. Agnostic genome-wide association studies of TDLU involution may provide new insights on its biologic underpinnings and breast cancer susceptibility. PMID:27859137
Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrián; Sáez-Freire, María del Mar; García-Cenador, Begoña; García-Criado, Javier; Pérez-Andrés, Martín; de Matos, Alberto Orfao; Cañamero, Marta; Mao, Jian-Hua; Gridley, Thomas; Castellanos-Martín, Andrés; Pérez-Losada, Jesús
2015-01-01
Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pre-tumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load- were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper post-lactational involution of the breast. At three days post-lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels pAKT1, resulting in decreased apoptosis. The presence of abundant non-involuted ducts was still present at 30 days post-lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres, and to an increase in the number of tumors. Our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of post-lactational involution and breast tumorigenesis in Snai2-null mutant mice. PMID:26096931
On classifying the divisor involutions in Calabi-Yau threefolds
NASA Astrophysics Data System (ADS)
Gao, Xin; Shukla, Pramod
2013-11-01
In order to support the odd moduli in models of (type IIB) string compactification, we classify the Calabi-Yau threefolds with h 1,1 ≤ 4 which exhibit pairs of identical divisors, with different line-bundle charges, mapping to each other under possible divisor exchange involutions. For this purpose, the divisors of interest are identified as completely rigid surface, Wilson surface, K3 surface and some other deformation surfaces. Subsequently, various possible exchange involutions are examined under the symmetry of Stanley-Reisner Ideal. In addition, we search for the Calabi-Yau theefolds which contain a divisor with several disjoint components. Under certain reflection involution, such spaces also have nontrivial odd components in (1,1)-cohomology class. String compactifications on such Calabi-Yau orientifolds with non-zero could be promising for concrete model building in both particle physics and cosmology. In the spirit of using such Calabi-Yau orientifolds in the context of LARGE volume scenario, we also present some concrete examples of (strong/weak) swiss-cheese type volume form.
Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox
Guo, Qiuchen; Betts, Courtney; Pennock, Nathan; Mitchell, Elizabeth; Schedin, Pepper
2017-01-01
Transforming Growth Factor-β (TGF-β) signaling in cancer has been termed the “TGF-β paradox”, acting as both a tumor suppresser and promoter. The complexity of TGF-β signaling within the tumor is context dependent, and greatly impacted by cellular crosstalk between TGF-β responsive cells in the microenvironment including adjacent epithelial, endothelial, mesenchymal, and hematopoietic cells. Here we utilize normal, weaning-induced mammary gland involution as a tissue microenvironment model to study the complexity of TGF-β function. This article reviews facets of mammary gland involution that are TGF-β regulated, namely mammary epithelial cell death, immune activation, and extracellular matrix remodeling. We outline how distinct cellular responses and crosstalk between cell types during physiologically normal mammary gland involution contribute to simultaneous tumor suppressive and promotional microenvironments. We also highlight alternatives to direct TGF-β blocking anti-cancer therapies with an emphasis on eliciting concerted microenvironmental-mediated tumor suppression. PMID:28098775
Liquid nitrogen cryotherapy for lip mucous membrane venous malformation in infants.
Zhang, Da-Ming; Wang, You-Yuan; Lin, Zhao-Yu; Yang, Zhao-Hui; Chen, Wei-Liang
2015-03-01
Lip mucous membrane venous malformations are common benign lesions in infants. This clinical study evaluates the efficacy and safety of liquid nitrogen cryotherapy used to treat this condition. A total of 84 pediatric patients undergoing liquid nitrogen cryotherapy for venous malformations involving the lips were reviewed, with 45 males and 39 females treated. The overall median age at mucous membrane venous malformation diagnosis was 5.6 months (range 2-18 months). The venous malformations involved the vermilion of the lower lip in 44 cases, the vermilion of the upper lip in 31 cases, and both vermilions in 9 cases. No complications due to anesthesia occurred. After a follow-up period of 2-38 months (mean 25 months), 65 lesions (77.4 %) were completely involuted, 14 lesions (16.7 %) were mostly involuted, and 5 lesions (5.9 %) were partially involuted; no lesions showed a minor amount of involution. Liquid nitrogen cryotherapy is an effective, simple, and safe management tool for mucous membrane venous malformations of the lip in infants.
2016-09-01
differences with an alpha level of 0.05 using a two-sided paired t- test . 2x2 factorial design with 10 samples for each cohort provides 86% power to detect...of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other...prognosis and prevention of post -partum breast cancer?” 5b. GRANT NUMBER W81XWH-13-1-0078 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Virginia F. Borges
Open groups of constraints. Integrating arbitrary involutions
NASA Astrophysics Data System (ADS)
Batalin, Igor; Marnelius, Robert
1998-11-01
A new type of quantum master equation is presented which is expressed in terms of a recently introduced quantum antibracket. The equation involves only two operators: an extended nilpotent BFV-BRST charge and an extended ghost charge. It is proposed to determine the generalized quantum Maurer-Cartan equations for arbitrary open groups. These groups are the integration of constraints in arbitrary involutions. The only condition for this is that the constraint operators may be embedded in an odd nilpotent operator, the BFV-BRST charge. The proposal is verified at the quasigroup level. The integration formulas are also used to construct a generating operator for quantum antibrackets of operators in arbitrary involutions.
Kulikov, A V; Arkhipova, L V; Kulikov, D A; Smirnova, G N; Kulikova, P A
2013-01-01
A novel method for recording the aggressive behavior in newly formed hierarchic communities has been developed. A temporal and age-related dynamics of the accidental thymus involution in mammals has been studied.
SOCS3 promotes apoptosis of mammary differentiated cells.
Le Provost, Fabienne; Miyoshi, Keiko; Vilotte, Jean-Luc; Bierie, Brian; Robinson, Gertraud W; Hennighausen, Lothar
2005-12-30
Growth and function of the mammary gland is regulated by cytokines and modulated by suppressor of cytokine signalling (SOCS) proteins. In vitro experiments demonstrated that SOCS3 can inhibit PRL induction of milk protein gene expression and STAT5 activation. We explored the SOCS3 expression pattern during mouse mammary development and its regulation by PRL and GH in wild-type and STAT5a-null mammary tissue. Our results suggest that, in vivo, PRL stimulates SOCS3 expression in stromal adipocytes, independently of STAT5a stimulation. In mammary epithelial cells, SOCS3 expression appears to be related to STAT3 activation. Together, our results are consistent with a role of SOCS3 in the mammary gland by promoting apoptosis of differentiated cells (adipocytes during gestation and epithelial cells during involution).
An Alternate Approach to Alternating Sums: A Method to DIE for
ERIC Educational Resources Information Center
Benjamin, Arthur T.; Quinn, Jennifer J.
2008-01-01
Positive sums count. Alternating sums match. Alternating sums of binomial coefficients, Fibonacci numbers, and other combinatorial quantities are analyzed using sign-reversing involutions. In particular, we describe the quantity being considered, match positive and negative terms through an Involution, and count the Exceptions to the matching rule…
Prochukhanov, R A; Rostovtseva, T I
1977-11-01
A method of quantitative histenzymatic analysis was applied for determination of the involution changes of the neuroendocrine system. The activity of NAD- and NADP-reductases, acid and alkaline phosphatases, glucose-6-phosphoric dehydrogenase, 3-OH-steroid-dehydrogenase, 11-hydroxysteroid dehydrogenases was investigated in the adenohypophysis and in the adrenal cortex of rats aged 4 and 12 months. There were revealed peculiarities attending the structural-metabolic provision of physiological reconstructions of the neuro-endocrine system under conditions of the estral cycle at the early involution stages. An initial reduction of the cell ular-vascular transport with the retention of the functional activity of the intracellular organoids was demonstrated in ageing animals.
Involution symmetries and the PMNS matrix
NASA Astrophysics Data System (ADS)
Pal, Palash B.; Byakti, Pritibhajan
2017-10-01
C S Lam has suggested that the PMNS matrix (or at least some of its elements) can be predicted by embedding the residual symmetry of the leptonic mass terms into a bigger symmetry. We analyse the possibility that the residual symmetries consist of involution generators only and explore how Lam's idea can be implemented.
Surface family with a common involute asymptotic curve
NASA Astrophysics Data System (ADS)
Bayram, Ergi˙n; Bi˙li˙ci˙, Mustafa
2016-03-01
We construct a surface family possessing an involute of a given curve as an asymptotic curve. We express necessary and sufficient conditions for that curve with the above property. We also present natural results for such ruled surfaces. Finally, we illustrate the method with some examples, e.g. circles and helices as given curves.
NASA Astrophysics Data System (ADS)
Zbiciak, M.; Grabowik, C.; Janik, W.
2015-11-01
Nowadays the design constructional process is almost exclusively aided with CAD/CAE/CAM systems. It is evaluated that nearly 80% of design activities have a routine nature. These design routine tasks are highly susceptible to automation. Design automation is usually made with API tools which allow building original software responsible for adding different engineering activities. In this paper the original software worked out in order to automate engineering tasks at the stage of a product geometrical shape design is presented. The elaborated software works exclusively in NX Siemens CAD/CAM/CAE environment and was prepared in Microsoft Visual Studio with application of the .NET technology and NX SNAP library. The software functionality allows designing and modelling of spur and helicoidal involute gears. Moreover, it is possible to estimate relative manufacturing costs. With the Generator module it is possible to design and model both standard and non-standard gear wheels. The main advantage of the model generated in such a way is its better representation of an involute curve in comparison to those which are drawn in specialized standard CAD systems tools. It comes from fact that usually in CAD systems an involute curve is drawn by 3 points that respond to points located on the addendum circle, the reference diameter of a gear and the base circle respectively. In the Generator module the involute curve is drawn by 11 involute points which are located on and upper the base and the addendum circles therefore 3D gear wheels models are highly accurate. Application of the Generator module makes the modelling process very rapid so that the gear wheel modelling time is reduced to several seconds. During the conducted research the analysis of differences between standard 3 points and 11 points involutes was made. The results and conclusions drawn upon analysis are shown in details.
Schmidt, R; Steinberg, H
2016-06-01
Against the background of current discussions on the classification of psychiatric disorders, this study analyses and discusses the East-German psychiatrist Dietfried Müller-Hegemann's concept of a clinical classification of depressions of 1964.In his paper, Müller-Hegemann differentiated between two main forms of depression, namely the "vitally tinged depression" (= melancholy), found mainly in the depressive phases of the manic-depressive disorder, and the "depressive disgruntlement" (= dysthymia) seen in "reactive and neurotic depression", "involutional depression", and in the depressive states in psychopathic personalities. Due to a lack of sufficient biological evidence, Müller-Hegemann refrained from a purely etiological differentiation.His proposal is significant in so far as it provided a classification that could easily be used in clinical practice, and at the same time, by pointing to the traditional concept of melancholy and by calling for a differentiated psychopathology, anticipated aspects of topical interest. © Georg Thieme Verlag KG Stuttgart · New York.
Lanctôt, S; Fustier, P; Taherian, A R; Bisakowski, B; Zhao, X; Lacasse, P
2017-03-01
The transition from lactation to the dry period in dairy cows is a period of high risk for acquiring new intramammary infections. This risk is reduced when the involution of the mammary gland is completed. Accordingly, approaches that speed up the involution process after drying-off could reduce the incidence of mastitis. The current study aimed to develop a biological response modifier that could be injected into cow teats to promote immune cell migration and speed up involution. Chitosan, a natural polysaccharide derived from chitin, is able to trigger host innate immunity. We developed 2 formulations made from either high- or low-viscosity chitosan. Both are liquid at room temperature but form a hydrogel at body temperature. In the first experiment, each udder quarter of 7 Holstein cows in late lactation was randomly assigned at drying-off to receive one of the following intramammary infusions: 2.5 or 5 mL of 5% (wt/vol) low-viscosity chitosan hydrogel, 5 mL of 5% high-viscosity chitosan hydrogel, or 5 mL of water. Milk (mammary secretion) samples were collected from each quarter on d -4, -1 (drying-off), 1, 3, 5, 7, and 10. Milk somatic cell counts and the concentrations of involution markers such as BSA, lactate dehydrogenase, and lactoferrin were measured in each sample. In comparison with the control, the chitosan hydrogel infusions significantly hastened the increases in somatic cell counts, BSA and lactoferrin concentrations, and lactate dehydrogenase activity in mammary secretions. No major differences between sources or volumes of chitosan were observed for the measured parameters. The compatibility of this approach with an internal teat sealant was verified in the second experiment. Each udder quarter of 8 Holstein cows was randomly assigned at drying-off to receive one of the following intramammary infusions: 5 mL of 2% low-viscosity chitosan hydrogel, 4 g of an internal teat sealant, a combination of sealant and chitosan, or 5 mL of water. Milk (mammary secretion) samples were collected from each quarter on d -4, -1 (drying-off), 5, and 10 to measure involution markers. These results suggest that chitosan hydrogel infusion hastened mammary gland involution and activate immune response, which may reduce the risk of acquiring new intramammary infections during the drying-off period. Those results were not affected by the presence of the teat sealant, showing that both approaches are fully compatible and could be used in combination. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Tsuneki, Masayuki; Hardee, Steven; Michaud, Michael; Morotti, Raffaella; Lavik, Erin; Madri, Joseph A.
2015-01-01
Microvascular endothelial cells cultured in three-dimensional hydrogel scaffolds form a network of microvessel structures when implanted subcutaneously in mice, inosculate with host vessels and over time remodel into large ectatic vascular structures resembling hemangiomas. When compared to infantile hemaniomas similarities were noted including a temporal progression from a morphological appearance of a proliferative phase to the appearance of an involuted phase mimicking the proliferative and involutional phases of infantile hemangioma. Consistent with the progression of a proliferative phase to an involuted phase, both the murine implants and human biopsy tissue exhibit reduced expression of Ajuba, YAP and Survivin labeling as they progressed over time. Significant numbers of CD45+, CD11b+, Mac3+ mononuclear cells were found at the 2 week time point in our implant model which correlated with the presence of CD45+, CD68+ mononuclear cells observed in biopsies of human proliferative phase hemangiomas. At the 4 week time point in our implant model only small numbers of CD45+ cells were detected, which again correlated with our findings of significantly diminished CD45+, CD68+ mononuclear cells in human involutional phase hemangiomas. The demonstration of mononuclear cell infiltration transiently in the proliferative phase of these lesions suggests that the vascular proliferation and/or regression may be driven in part by an immune response. Gross and microscopic morphological appearances of human proliferative and involutional hemangiomas and our implant model correlate well with each other as do the expression levels of Hippo pathway components (Ajuba and YAP) and Survivin and correlate with proliferation in these entities. Inhibitors of Survivin and Ajuba (which we have demonstrated to inhibit proliferation and increase apoptosis in murine hemangioma cell tissue culture) may have potential as other beneficial treatments for proliferating infantile hemangiomas. This implant model may have potential as a modest through-put screen for testing and development of therapeutics targeted at the proliferative phase of infantile hemangiomas, reducing the subsequent post-involutional scarring sometimes associated with these lesions. PMID:25961170
DOE Office of Scientific and Technical Information (OSTI.GOV)
Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian
Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2more » oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.« less
Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian; ...
2015-06-22
Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2more » oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.« less
NASA Technical Reports Server (NTRS)
Ingber, D. E.
1992-01-01
Angiogenesis, the growth of blood capillaries, is regulated by soluble growth factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic mitogens act over large distances to initiate capillary growth whereas changes in ECM govern whether individual cells will grow, differentiate, or involute in response to these stimuli in the local tissue microenvironment. Analysis of this local control mechanism has revealed that ECM molecules switch capillary endothelial cells between differentiation and growth by both binding specific transmembrane integrin receptors and physically resisting cell-generated mechanical loads that are applied to these receptors. Control of capillary endothelial cell form and function therefore may be exerted by altering the mechanical properties of the ECM as well as its chemical composition. Understanding of this mechanochemical control mechanism has led to the development of new angiogenesis inhibitors that may be useful for the treatment of cancer.
[Functional morphology of the submandibular salivary glands of white rats during aging involution].
Rybakova, M G
1979-12-01
Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.
1992-05-21
phenolic resin. The warp/fill primary structure laminate plies are laid up next followed by the exit cone bias involute. The subassembly was vacuum bagged...CARBON FIBER/EPOXT 7075-T73 ALUMINUM 7kCo4x>€ axmjtuma* ROUNDING RING CARBON PHENOLIC INVOLUTE CARBON PHENOLIC LAMINATED INSULATION. MXSI-55...DESIGNS AND CURRENT STATUS *n ,.Wn„nd Composite Case. The older Sentry motor design employed a hybrid ( Kevlar -graphlte) fUament-wound ewe. *« S
Computing Gröbner and Involutive Bases for Linear Systems of Difference Equations
NASA Astrophysics Data System (ADS)
Yanovich, Denis
2018-02-01
The computation of involutive bases and Gröbner bases for linear systems of difference equations is solved and its importance for physical and mathematical problems is discussed. The algorithm and issues concerning its implementation in C are presented and calculation times are compared with the competing programs. The paper ends with consideration on the parallel version of this implementation and its scalability.
The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I.
Burgess, W; Liu, Q; Zhou, J; Tang, Q; Ozawa, A; VanHoy, R; Arkins, S; Dantzer, R; Kelley, K W
1999-01-01
Why a primary lymphoid organ such as the thymus involutes during aging remains a fundamental question in immunology. Aging is associated with a decrease in plasma growth hormone (somatotropin) and IGF-I, and this somatopause of aging suggests a connection between the neuroendocrine and immune systems. Several investigators have demonstrated that treatment with either growth hormone or IGF-I restores architecture of the involuted thymus gland by reversing the loss of immature cortical thymocytes and preventing the decline in thymulin synthesis that occurs in old or GH-deficient animals and humans. The proliferation, differentiation and functions of other components of the immune system, including T and B cells, macrophages and neutrophils, also demonstrate age-associated decrements that can be restored by IGF-I. Knowledge of the mechanism by which cytokines and hormones influence hematopoietic cells is critical to improving the health of aged individuals. Our laboratory has recently demonstrated that IGF-I prevents apoptosis in promyeloid cells, which subsequently permits these cells to differentiate into neutrophils. We also demonstrated that IL-4 acts much like IGF-I to promote survival of promyeloid cells and to activate the enzyme phosphatidylinositol 3'-kinase (PI 3-kinase). However, the receptors for IGF-I and IL-4 are completely different, with the intracellular beta chains of the IGF receptor possessing intrinsic tyrosine kinase activity and the alpha and gammac subunit of the heterodimeric IL-4 receptor utilizing the Janus kinase family of nonreceptor protein kinases to tyrosine phosphorylate downstream targets. Both receptors share many of the components of the PI 3-kinase signal transduction pathway, converging at the level of insulin receptor substrate-1 or insulin receptor subtrate-2 (formally known as 4PS, or IL-4 Phosphorylated Substrate). Our investigations with IGF-I and IL-4 suggest that PI 3-kinase inhibits apoptosis by maintaining high levels of the anti-apoptotic protein Bcl-2. The sharing of common activation molecules, despite vastly different protein structures of their receptors, forms a molecular explanation for the possibility of cross talk between IL-4 and IGF-I in regulating many of the events associated with hematopoietic differentiation, proliferation and survival.
Targeting the Prometastatic Microenvironment of the Involuting mammary gland
2016-09-01
metastatic variants and by lentiviral knock down. 15. SUBJECT TERMS Cell Adhesion, Involution, Metastasis, Latent TGFbeta Binding Protein, Pregnancy...metastatic parental cell line (Report year 2 Fig. 4). We generated a lentiviral knock down system that effectively reduced LTBP1 expression within this cell...this pilot set of animals and will be infecting and following a larger cohort by IVIS to track the effect of knocking down Ltbp1 on metastasis in
Chen, Wei-liang; Huang, Zhi-quan; Zhang, Da-ming; Chai, Qiang
2010-04-01
Surgical excision is useful only for localized and limited lesions. The purpose of this study was to evaluate the clinical curative effect of percutaneous sclerotherapy of massive venous malformations of the face and neck using fibrin glue combined with OK-432 and pingyangmycin. Eighteen patients with massive venous malformations were treated with an injection of fibrin glue combined with OK-432 and pingyangmycin. All the patients had extreme swelling postoperatively with no major complications. The follow-up period ranged from 6 to 12 months. Twelve lesions were completely involuted, 4 lesions were mostly involuted, and 2 lesions were partially involuted. All of the patients had normal liver and kidney functions. None of the patients presented with hematologic toxic effects or signs of pulmonary involvement. Percutaneous sclerotherapy using fibrin glue combined with OK-432 and pingyangmycin provided a simple, safe, and reliable alternative treatment for massive venous malformations.
Face Gear Drive with Spur Involute Pinion: Geometry, Generation by a Worm, Stress Analysis
NASA Technical Reports Server (NTRS)
Litvin, Faydor L.; Fuentes, Alfonso; Zanzi, Claudio; Pontiggia, Matteo; Handschuh, Robert F. (Technical Monitor)
2002-01-01
A face gear drive with a spur involute pinion is considered. The generation of the face gear is based on application of a grinding or cutting worm whereas the conventional method of generation is based on application of an involute shaper. An analytical approach is proposed for the determination of: (1) the worm thread surface; (2) avoidance of singularities of the worm thread surface, (air) dressing of the worm; and (3) determination of stresses of the face-gear drive. A computer program for simulation of meshing and contact of the pinion and face-gear has been developed. Correction of machine-tool settings is proposed for reduction of the shift of the bearing contact caused by misalignment. An automatic development of the model of five contacting teeth has been proposed for stress analysis. Numerical examples for illustration of the developed theory are provided.
Horne, Hisani N; Sherman, Mark E; Pfeiffer, Ruth M; Figueroa, Jonine D; Khodr, Zeina G; Falk, Roni T; Pollak, Michael; Patel, Deesha A; Palakal, Maya M; Linville, Laura; Papathomas, Daphne; Geller, Berta; Vacek, Pamela M; Weaver, Donald L; Chicoine, Rachael; Shepherd, John; Mahmoudzadeh, Amir Pasha; Wang, Jeff; Fan, Bo; Malkov, Serghei; Herschorn, Sally; Hewitt, Stephen M; Brinton, Louise A; Gierach, Gretchen L
2016-02-18
Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease. Serum IGF-I, IGFBP-3 and IGF-I:IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area ("TDLU count"), median TDLU diameter ("TDLU span"), and number of acini per TDLU ("acini count"). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density. Higher IGF-I levels among postmenopausal women and an elevated IGF-I:IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU. These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system.
Intermittent midline suprasternal neck mass caused by superior herniation of the thymus.
Su, Siew Choo; Hess, Thomas; Whybourne, Annie; Chang, Anne B
2015-03-01
Neck masses in infants and children have a wide differential diagnosis. However, neck masses apparent only during raised intrathoracic pressure are rare with a limited number of causes, including superior herniation of the normal thymus, apical lung herniation, jugular phlebectasia and laryngocoele. These conditions can easily be differentiated from one another by imaging. We present an infant with intermittent suprasternal neck mass visible only during increased intrathoracic pressure, produced either by crying or straining. Diagnosis of superior herniation of the thymus into the neck was confirmed by ultrasonography with the characteristic sonographic appearances of the normal thymus as well as its shape, size and location. Ultrasonography should be the first imaging modality of choice. Management of superior herniation of the thymus into the neck should be conservative as the thymus naturally involutes with increasing age. Awareness of the differential diagnosis of neck swelling present only on Vasalva manoeuvre or increased intrathoracic pressure is important to prevent unnecessary tests, avoid radiation, biopsy and surgery. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
2013-10-01
experiments, a statistically significant data is not yet available. Additional experiments are needed for us to be able to draw conclu comb Figure...well-defined stress pathways, UPR and autophagy, are involved breast involution regulation. Using published gene expression array datasets from...performed involution time-course experiments using both low-dose drug interventions and an autophagy-related gene 7 (ATG7) deletion mouse model
Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A
2016-02-01
Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. Copyright © 2015 Elsevier Inc. All rights reserved.
Mee, J F; Buckley, F; Ryan, D; Dillon, P
2009-04-01
The objectives of the study were to characterize an ultrasound reproductive tract scoring (URTS) system to assess suitability for breeding in dairy cows, to describe the prevalence of these scores in commercial dairy herds and to examine their relationship with subsequent fertility. Ultrasound examinations (7797) were performed on 5751 Holstein-Friesian cows prior to breeding in 62 seasonally calving herds over 2 years. Data recorded from images of both ovaries and the uterus were combined into a six point scoring system and the prevalence of cows with cystic ovarian follicles and uterine abscesses and adhesions was recorded separately. The prevalence of ovulatory cows which had completed uterine involution (score 1), or had mild (2) or moderate endometritis (3) was 62.5%, 21.7% and 2.2%, respectively. The prevalence of anovulatory cows with moderate endometritis (4), ovulatory cows with pyometra (5) and anovulatory cows which had completed uterine involution (6) was 3.3%, 2.2% and 8.1%, respectively. The interval between calving and examination differed between cows with each of the scores 1, 2, 5 and 6 (61, 46, 53 and 50 days, respectively, p < 0.05) but not between cows with scores 3 and 4 (37 and 35 days, respectively). Ovulatory cows which had completed uterine involution (score 1) had a higher likelihood of pregnancy to first service than ovulatory or anovulatory cows which had not completed uterine involution (p = 0.10). The prevalence of cows with cystic ovarian follicles or abscesses or adhesions of the reproductive tract was 3.9% and 1.2%, respectively. In conclusion, 29% and 11% of cows in seasonally calving and breeding dairy herds had not completed uterine involution or were anovulatory prior to the mating start date, respectively. Both conditions, detected using a URTS system, significantly reduced first service pregnancy rate in these pasture-based dairy herds.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1980-01-01
The mathematical modeling of 11 different concentrating collectors is documented and instructions are given for use of the computer code. The 11 concentrators modeled are: faceted mirror concentration; fixed mirror, two-axis tracking receiver; parabolic trough collector; linear Fresnel; incremental reflector; inflated cylindrical concentrator; CPC-involute reflector with evacuated receiver; CPC-parabolic/involute reflector; V trough collectors, imaging collapsing concentrator; and parabolic dish collector. (MHR)
Modeling of thermal processes arising during shaping gears with internal non-involute teeth
NASA Astrophysics Data System (ADS)
Kanatnikov, N. V.; Kanatnikova, P. A.; Vlasov, V. V.; Pashmentova, A. S.
2018-03-01
The paper presents a model for predicting the thermal processes arising during shaping gears with internal non-involute teeth. The kinematics of cutting is modeled due to the analytical model. Chipping is modeled using the finite element method. The experiment is based on the method of infrared photography of the cutting process. The simulation results showed that the maximum temperatures and heat flows in the tool vary by more than 10% when the rake and clearance angels of the cutting are changed.
Hydraulic involute cam actuator
Love, Lonnie J [Knoxville, TN; Lind, Randall F [Loudon, TX
2011-11-01
Mechanical joints are provided in which the angle between a first coupled member and a second coupled member may be varied by mechanical actuators. In some embodiments the angle may be varied around a pivot axis in one plane and in some embodiments the angle may be varied around two pivot axes in two orthogonal planes. The joints typically utilize a cam assembly having two lobes with an involute surface. Actuators are configured to push against the lobes to vary the rotation angle between the first and second coupled member.
Helicopter Transmission Vibration and Noise Reduction Program. Volume II. User’s Manual
1978-03-01
Howells, Joseph W. Lenski, Jr., Raymond J. Drago Boeing Vertol Company P.O. Box 16858 Philadelphia, Pa. 19142 -7 March 1978 Final Report for Period...involute spur gears, where RM is the root circle radius and RT defines the manufactured starting point of the involute profile. According to Equations (1...radius. No check for this is prcvided. Use columns 53 through 65. Card 4 Gear design data, continued. Format (6E 13.5) 88 11 I1 SA - ~ --~-.i a. RT ]. R
Enei Gahona, Maria Leonor; Machado Filho, Carlos d' Aparecida Santos
2012-01-01
Through iconography, we show a case of keratoacanthoma (KA) on the nasal dorsum at two different stages of evolution (maturation and regression) and its similarity with images of the Mount St. Helens volcano and the Orcus Patera crater. Using these illustrations, we highlight why the crateriform aspect of this tumor is included in its classic clinical description. Moreover, we photographically documented the self-involuting tendency of KA, an aspect that is seldom documented in the literature.
Maugans, Todd; Sheridan, Rachel M; Adams, Denise; Gupta, Anita
2011-07-01
Lumbosacral cutaneous vascular anomalies associated with neural tube defects are frequently described in the literature as "hemangiomas." The classification system for pediatric vascular anomalies developed by the International Society for the Study of Vascular Anomalies provides a framework to accurately diagnose these lesions. To apply this classification to vascular cutaneous anomalies overlying myelodysplasias. A retrospective analysis of patients with neural tube defects and lumbosacral cutaneous vascular lesions was performed. All eligible patients had detailed histopathologic analysis of skin and spinal cord/placode lesions. Clinical and radiologic features were analyzed. Conventional histology and GLUT-1 immunostaining were performed to differentiate infantile capillary hemangiomas from capillary vascular malformations. Ten cases with cutaneous lesions associated with neural tube defects were reviewed. Five lesions were diagnosed as infantile capillary hemangiomas based upon histology and positive GLUT-1 endothelial reactivity. These lesions had a strong association with dermal sinus tracts. No reoperations were required for residual intraspinal vascular lesions, and overlying cutaneous vascular anomalies involuted with time. The remaining 5 lesions were diagnosed as capillary malformations. These occurred with both open and closed neural tube defects, did not involute, and demonstrated enlargement and darkening due to vascular congestion. The International Society for the Study of Vascular Anomalies scheme should be used to describe the cutaneous vascular lesions associated with neural tube defects: infantile capillary hemangiomas and capillary malformations. We advocate that these lesions be described as "vascular anomalies" or "stains" pending accurate diagnosis by clinical, histological, and immunohistochemical evaluations.
The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis
Goddard, Erica T.; Hill, Ryan C.; Nemkov, Travis; D’Alessandro, Angelo; Hansen, Kirk C.; Maller, Ori; Mongoue-Tchokote, Solange; Mori, Motomi; Partridge, Ann H.; Borges, Virginia F.; Schedin, Pepper
2017-01-01
Postpartum breast cancer patients are at increased risk for metastasis compared to age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the post-lactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, ECM remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent with weaning-induced liver involution and establishment of a pro-metastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning Balb/c mice compared to nulliparous controls. Human relevance is suggested by a ~3-fold increase in liver metastasis in postpartum breast cancer patients (n=564) and by liver-specific tropism (n=117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer. PMID:27974414
Kyathanahalli, Chandrashekara; Marks, Jason; Nye, Kennedy; Lao, Belinda; Albrecht, Eugene D.; Aberdeen, Graham W.; Nathanielsz, Peter W.; Jeyasuria, Pancharatnam
2013-01-01
A successful postpartum involution permits the postnatal uterus to rapidly regain its prepregnancy function and size to ultimately facilitate an ensuing blastocyst implantation. This study investigates the molecular mechanisms that govern the initiation of the involution process by examining the signaling events that occur as the uterus transitions from the pregnant to postnatal state. Using mouse and baboon uteri, we found a remarkable cross-species conservation at the signal transduction level as the pregnant uterus initiates and progresses through the involution process. This study originated with the observation of elevated levels of caspase-3 activation in both the laboring mouse and baboon uterus, which we found to be apoptotic in nature as evidenced by the concurrent appearance of cleaved poly(ADP-ribose) polymerase. We previously defined a nonapoptotic and potential tocolytic role for uterine caspase-3 during pregnancy regulated by increased antiapoptotic signaling mediated by myeloid cell leukemia sequence 1 and X-linked inhibitor of apoptosis. In contrast, this study determined that diminished antiapoptotic signaling in the postpartum uterus allowed for both endometrial apoptotic and myometrial autophagic episodes, which we speculate are responsible for the rapid reduction in size of the postpartum uterus. Using our human telomerase immortalized myometrial cell line and the Simian virus-40 immortalized endometrial cell line (12Z), we demonstrated that the withdrawal of antiapoptotic signaling was also an upstream event for both the autophagic and apoptotic processes in the human uterine myocyte and endometrial epithelial cell. PMID:24140717
NASA Astrophysics Data System (ADS)
Fackerell, E. D.; Hartley, D.; Tucker, R. W.
We examine in detail the Cauchy problem for a class of non-linear hyperbolic equations in two independent variables. This class is motivated by the analysis of the dynamics of a line of non-linearly coupled particles by Fermi, Pasta, and Ulam and extends the recent investigation of this problem by Gardner and Kamran. We find conditions for the existence of a 1-stable Cartan characteristic of a Pfaffian exterior differential system whose integral curves provide a solution to the Cauchy problem. The same obstruction to involution is exposed in Darboux's method of integration and the two approaches are compared. A class of particular solutions to the obstruction is constructed.
Lu, Theresa T.; Browning, Jeffrey L.
2014-01-01
Lymphoid organs are meeting zones where lymphocytes come together and encounter antigens present in the blood and lymph or as delivered by cells migrating from the draining tissue bed. The exquisite efficiency of this process relies heavily on highly specialized anatomy to direct and position the various players. Gated entry and exit control access to these theaters and reticular networks and associated chemokines guide cells into the proper sections. Lymphoid tissues are remarkably plastic, being able to expand dramatically and then involute upon resolution of the danger. All of the reticular scaffolds and vascular and lymphatic components adapt accordingly. As such, the lymph node (LN) is a wonderful example of a physiologic remodeling process and is potentially a guide to study such elements in pathological settings such as fibrosis, chronic infection, and tumor metastasis. The lymphotoxin/LIGHT axis delivers critical differentiation signals that direct and hone differentiation of both reticular networks and the vasculature. Considerable progress has been made recently in understanding the mesenchymal differentiation pathways leading to these specialized networks and in the remodeling that occurs in reactive LNs. In this article, we will review some new advances in the area in terms of developmental, differentiation, and maintenance events mediated by this axis. PMID:24575096
Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress
Wollny, Damian; Clark, Rod J.; Roopra, Avtar; Colman, Ricki J.; MacDougald, Ormond A.; Shedd, Timothy A.; Nelson, David W.; Yen, Mei-I; Yen, Chi-Liang Eric; Alexander, Caroline M.
2014-01-01
Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology. PMID:25101993
Chen, Wei-Liang; Yang, Zhao-Hui; Bai, Zhi-Bao; Wang, Yong-Yuan; Huang, Zhi-Quan; Wang, Yong-Jie
2008-12-01
Venous malformations of the face and neck involve multiple anatomical spaces and encase critical neuromuscular structures, making surgical treatment difficult; high recurrence rates and high morbidity are well documented. The purpose of this study was to evaluate the clinical curative effect of combination compartmentalisation and sclerotherapy for the treatment of massive venous malformations of the face and neck. Sixteen patients with massive venous malformations of the face and neck region (12 males and four females; mean age: 14.9 years, range: 6-22 years) were treated with compartmentalisation using silk sutures followed by injections of 0.1 mg OK-432 and 8 mg pingyangmycin into each small compartment. The injections were performed every two weeks. All lesions received three to six treatments. All the patients had significant swelling and mild pain postoperatively for a period of one to two weeks with no major complications. One patient had transient facial paresis, which resolved spontaneously within two weeks. The follow-up period ranged from three to 14 months (median: 7.1 months). The treatments resulted in the following: four of the lesions were completely involuted, six were mostly involuted, five were partially involuted, and one experienced a small involution. All of the patients had normal liver and kidney functions and normal lung fields on chest X-ray. Compartmentalisation followed by injection of OK-432 and pingyangmycin into each compartment provided a simple, safe, and reliable alternative treatment for massive venous malformations of the face and neck.
Mechanism of age-dependent involution in embryonic chick notochords.
Ghanem, E; Cornelissen, M; Thierens, H; De Ridder, L
1996-07-15
To study the possible mechanism of the age-dependent involution of the notochord, isolated mesenchyme-free notochords of chick embryos were cultured in vitro and compared with their counterparts in vivo. Two different aspects were evaluated: (1) DNA synthesis measured by [3H]thymidine incorporation and visualized by autoradiography and (2) cell death quantified by counting the number of pyknotic nuclei. The results demonstrate that [3H]thymidine uptake by notochords shows an age-dependent decrease in vitro as well as in vivo. The number of [3H]thymidine-labelled notochord cells, however, is higher in vitro than in vivo. At the same time, there is an age-dependent increase in pyknosis in the notochord in vivo and in vitro. So, during the aging process, the number of both pyknotic nuclei and of [3H]thymidine-labelled nuclei suggest a high turnover of notochord cells in vitro. From these results, we can conclude that the process of involution in aging notochord seems to be controlled by a programmed intrinsic process, which might be influenced partially by the microenvironment in vivo.
c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3
Sutherland, Kate D; Vaillant, François; Alexander, Warren S; Wintermantel, Tim M; Forrest, Natasha C; Holroyd, Sheridan L; McManus, Edward J; Schutz, Gunther; Watson, Christine J; Chodosh, Lewis A; Lindeman, Geoffrey J; Visvader, Jane E
2006-01-01
Suppressor of cytokine signalling (SOCS) proteins are critical attenuators of cytokine-mediated signalling in diverse tissues. To determine the importance of Socs3 in mammary development, we generated mice in which Socs3 was deleted in mammary epithelial cells. No overt phenotype was evident during pregnancy and lactation, indicating that Socs3 is not a key physiological regulator of prolactin signalling. However, Socs3-deficient mammary glands exhibited a profound increase in epithelial apoptosis and tissue remodelling, resulting in precocious involution. This phenotype was accompanied by augmented Stat3 activation and a marked increase in the level of c-myc. Moreover, induction of c-myc before weaning using an inducible transgenic model recapitulated the Socs3 phenotype, and elevated expression of likely c-myc target genes, E2F-1, Bax and p53, was observed. Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution. PMID:17139252
Involution and Difference Schemes for the Navier-Stokes Equations
NASA Astrophysics Data System (ADS)
Gerdt, Vladimir P.; Blinkov, Yuri A.
In the present paper we consider the Navier-Stokes equations for the two-dimensional viscous incompressible fluid flows and apply to these equations our earlier designed general algorithmic approach to generation of finite-difference schemes. In doing so, we complete first the Navier-Stokes equations to involution by computing their Janet basis and discretize this basis by its conversion into the integral conservation law form. Then we again complete the obtained difference system to involution with eliminating the partial derivatives and extracting the minimal Gröbner basis from the Janet basis. The elements in the obtained difference Gröbner basis that do not contain partial derivatives of the dependent variables compose a conservative difference scheme. By exploiting arbitrariness in the numerical integration approximation we derive two finite-difference schemes that are similar to the classical scheme by Harlow and Welch. Each of the two schemes is characterized by a 5×5 stencil on an orthogonal and uniform grid. We also demonstrate how an inconsistent difference scheme with a 3×3 stencil is generated by an inappropriate numerical approximation of the underlying integrals.
Efficiency of nonstandard and high contact ratio involute spur gears
NASA Technical Reports Server (NTRS)
Anderson, N. E.; Loewenthal, S. H.
1984-01-01
A power loss prediction was extended to include involute spur gears of nonstandard proportions. The method is used to analyze the effects of modified addendum, tooth thickness, and gear center distance in addition to the parameters previously considered which included gear diameter, pitch, pressure angle, face width, oil viscosity, speed, and torque. Particular emphasis was placed on high contact ratio gearing (contact ratios greater than two). Despite their higher sliding velocities, high contact ratio gears are designed to levels of efficiency comparable to those of conventional gears while retaining their advantages through proper selection of gear geometry.
Efficiency of nonstandard and high contact ratio involute spur gears
NASA Technical Reports Server (NTRS)
Anderson, N. E.; Loewenthal, S. H.
1986-01-01
A power loss prediction was extended to include involute spur gears of nonstandard proportions. The method is used to analyze the effects of modified addendum, tooth thickness, and gear center distance in addition to the parameters previously considered which included gear diameter, pitch, pressure angle, face width, oil viscosity, speed, and torque. Particular emphasis was placed on high contact ratio gearing (contact ratios greater than two). Despite their higher sliding velocities, high contact ratio gears are designed to levels of efficiency comparable to those of conventional gears while retaining their advantages through proper selection of gear geometry.
Non-Standard Gearing as the Possibility of Increasing Resistance to Pitting
NASA Astrophysics Data System (ADS)
Kopiláková, Beáta; Bošanský, Miroslav
2014-12-01
In this article are shown the influence of the type non-standard gearing to reduce damage to the pitting. The introduction of the article describes a fundamental difference between the involute and non-involute gearing and the influence of some parameters, especially of the slip ratio to damage of gearing. The paper describes the principle of evaluation pitting by makrofoto graphical method, too and also shows the basic results of the experiment, which was executed on two types of gearing (HCR gearing and C-C gearing) on the Niemanńs stend in term of the damage to pitting.
Kolotilin, G F; Vasil'ev, V D
1988-01-01
Using clinico-psychopathological methods of examination the authors studied 93 schizophrenics with a delirious variant of the Kandinsky-Clérambaut syndrome who had committed violent antisocial actions (VAA). It has been ascertained that peculiarities of the clinical course at the time when the VAA was committed reflect the stages of the development of the syndrome: the initial stage, the stage of delirious personification of psychic automatisms and the stage of involution of the delirious variant of the Kandinsky-Clérambaut syndrome. It has been established that the more acute the psychosis the higher the significance in the psychopathological mechanisms of VAA of clinical manifestations of the syndrome and lower the role of social and personality factors.
bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship.
Strasser, A; Harris, A W; Cory, S
1991-11-29
Early death is the fate of most developing T lymphocytes. Because bcl-2 can promote cell survival, we tested its impact in mice expressing an E mu-bcl-2 transgene within the T lymphoid compartment. The T cells showed remarkably sustained viability and some spontaneous differentiation in vitro. They also resisted killing by lymphotoxic agents. Although total T cell numbers and the rate of thymic involution were unaltered, the response to immunization was enhanced, consistent with reduced death of activated T cells. No T cells reactive with self-superantigens appeared in the lymph nodes, but an excess was found in the thymus. These observations, together with previous findings on B cells, suggest that modulated bcl-2 expression is a determinant of life and death in normal lymphocytes.
Emerging strategies to boost thymic function
Holländer, Georg A.; Krenger, Werner; Blazar, Bruce R.
2011-01-01
The thymus constitutes the primary lymphoid organ for the generation of T cells. Its function is particularly susceptible to various negative influences ranging from age-related involution to atrophy as a consequence of malnutrition, infection or harmful iatrogenic influences such as chemotherapy and radiation. The loss of regular thymus function significantly increases the risk for infections and cancer because of a restricted capacity for immune surveillance. In recent years, thymus-stimulatory, -regenerative and -protective strategies have been developed to enhance and repair thymus function in the elderly and in individuals undergoing hematopoietic stem cell transplantation. These strategies include the use of sex steroid ablation, the administration of growth and differentiation factors, the inhibition of p53, and the transfer of T cell progenitors to alleviate the effects of thymus dysfunction and consequent T cell deficiency. PMID:20447867
Youm, Yun-Hee; Yang, Hyunwon; Amin, Raj; Smith, Steven R.; Leff, Todd; Dixit, Vishwa Deep
2010-01-01
Age-related thymic involution is characterized by reduction in T cell production together with ectopic adipocyte development within the hematopoietic and thymic niches. PPARγ is required for adipocyte development, glucose homeostasis and is a target for several insulin-sensitizing drugs. Our prior studies showed that age-related elevation of PPARγ expression in thymic stromal cells is associated with thymic involution. Here, using clinically relevant pharmacological and genetic manipulations in mouse models, we provide evidence that activation of PPARγ leads to reduction in thymopoiesis. Treatment of aged mice with anti-hyperglycemic PPARγ-ligand class of Thiazolidinedione drug, Rosiglitazone caused robust thymic expression of classical pro-adipogenic transcripts. Rosiglitazone reduced thymic cellularity, lowered the naïve T cell number and T cell receptor excision circles (TRECs) indicative of compromised thymopoiesis. To directly investigate whether PPARγ activation induces thymic involution, we created transgenic mice with constitutive-active PPARγ (CA-PPARg) fusion protein in cells of adipogenic lineage. Importantly, CA-PPARγ transgene was expressed in thymus and in Fibroblast Specific Protein-1/S100A4 (FSP1+) cells, a marker of secondary mesenchymal cells. The CAPPARγ fusion protein mimicked the liganded PPARγ receptor and the transgenic mice displayed increased ectopic thymic adipogenesis and reduced thymopoiesis. Furthermore, the reduction in thymopoiesis in CA-PPARγ mice was associated with higher bone marrow adiposity and lower hematopoietic stem cell progenitor pool. Consistent with lower thymic output, CAPPARγ transgenic mice had restricted T cell receptor (TCR) repertoire diversity. Collectively, our data suggest that activation of PPARγ accelerates thymic aging and thymus-specific PPARγ antagonist may forestall age-related decline in T cell diversity. PMID:20374200
Ron, Micha; Israeli, Galit; Seroussi, Eyal; Weller, Joel I; Gregg, Jeffrey P; Shani, Moshe; Medrano, Juan F
2007-01-01
Background Many studies have found segregating quantitative trait loci (QTL) for milk production traits in different dairy cattle populations. However, even for relatively large effects with a saturated marker map the confidence interval for QTL location by linkage analysis spans tens of map units, or hundreds of genes. Combining mapping and arraying has been suggested as an approach to identify candidate genes. Thus, gene expression analysis in the mammary gland of genes positioned in the confidence interval of the QTL can bridge the gap between fine mapping and quantitative trait nucleotide (QTN) determination. Results We hybridized Affymetrix microarray (MG-U74v2), containing 12,488 murine probes, with RNA derived from mammary gland of virgin, pregnant, lactating and involuting C57BL/6J mice in a total of nine biological replicates. We combined microarray data from two additional studies that used the same design in mice with a total of 75 biological replicates. The same filtering and normalization was applied to each microarray data using GeneSpring software. Analysis of variance identified 249 differentially expressed probe sets common to the three experiments along the four developmental stages of puberty, pregnancy, lactation and involution. 212 genes were assigned to their bovine map positions through comparative mapping, and thus form a list of candidate genes for previously identified QTLs for milk production traits. A total of 82 of the genes showed mammary gland-specific expression with at least 3-fold expression over the median representing all tissues tested in GeneAtlas. Conclusion This work presents a web tool for candidate genes for QTL (cgQTL) that allows navigation between the map of bovine milk production QTL, potential candidate genes and their level of expression in mammary gland arrays and in GeneAtlas. Three out of four confirmed genes that affect QTL in livestock (ABCG2, DGAT1, GDF8, IGF2) were over expressed in the target organ. Thus, cgQTL can be used to determine priority of candidate genes for QTN analysis based on differential expression in the target organ. PMID:17584498
Advanced Face Gear Surface Durability Evaluations
NASA Technical Reports Server (NTRS)
Lewicki, David G.; Heath, Gregory F.
2016-01-01
The surface durability life of helical face gears and isotropic super-finished (ISF) face gears was investigated. Experimental fatigue tests were performed at the NASA Glenn Research Center. Endurance tests were performed on 10 sets of helical face gears in mesh with tapered involute helical pinions, and 10 sets of ISF-enhanced straight face gears in mesh with tapered involute spur pinions. The results were compared to previous tests on straight face gears. The life of the ISF configuration was slightly less than that of previous tests on straight face gears. The life of the ISF configuration was slightly greater than that of the helical configuration.
Practices related to postpartum uterine involution in the Western Highlands of Guatemala.
Radoff, K A; Thompson, Lisa M; Bly, K C; Romero, Carolina
2013-03-01
Guatemala has the third highest level of maternal mortality in Latin America. Postpartum haemorrhage is the main cause of maternal mortality. In rural Guatemala, most women rely on Traditional Birth Attendants (TBAs) during labour, delivery, and the postpartum period. Little is known about current postpartum practices that may contribute to uterine involution provided by Mam- and Spanish-speaking TBAs in the Western Highlands of Guatemala. a qualitative study was conducted with 39 women who participated in five focus groups in the San Marcos Department of Guatemala. Questions regarding postpartum practices were discussed during four focus groups of TBAs and one group of auxiliary nurses. three postpartum practices believed to aid postpartum uterine involution were identified: use of the chuj (Mam) (Spanish, temazcal), a traditional wood-fired sauna-bath used by Mam-speaking women; herbal baths and teas; and administration of biomedicines. TBAs provide the majority of care to women during childbirth and the postpartum period and have developed a set of practices to prevent and treat postpartum haemorrhage. Integration of these practices may prove an effective method to reduce maternal morbidity and mortality in the Western Highlands of Guatemala. Copyright © 2011 Elsevier Ltd. All rights reserved.
Practices related to postpartum uterine involution in the Western Highlands of Guatemala
Radoff, K.A.; Thompson, Lisa M.; Bly, KC; Romero, Carolina
2013-01-01
Background Guatemala has the third highest level of maternal mortality in Latin America. Postpartum haemorrhage is the main cause of maternal mortality. In rural Guatemala, most women rely on Traditional Birth Attendants (TBAs) during labour, delivery, and the postpartum period. Little is known about current postpartum practices that may contribute to uterine involution provided by Mam- and Spanish-speaking TBAs in the Western Highlands of Guatemala. Methods a qualitative study was conducted with 39 women who participated in five focus groups in the San Marcos Department of Guatemala. Questions regarding postpartum practices were discussed during four focus groups of TBAs and one group of auxiliary nurses. Results three postpartum practices believed to aid postpartum uterine involution were identified: use of the chuj (Mam) (Spanish, temazcal), a traditional wood-fired sauna-bath used by Mam-speaking women; herbal baths and teas; and administration of biomedicines. Conclusions TBAs provide the majority of care to women during childbirth and the postpartum period and have developed a set of practices to prevent and treat postpartum haemorrhage. Integration of these practices may prove an effective method to reduce maternal morbidity and mortality in the Western Highlands of Guatemala. PMID:22762787
RDS-21 Face-Gear Surface Durability Tests
NASA Technical Reports Server (NTRS)
Lewicki, David G.; Heath, Gregory F.; Filler, Robert R.; Slaughter, Stephen C.; Fetty, Jason
2007-01-01
Experimental fatigue tests were performed to determine the surface durability life of a face gear in mesh with a tapered spur involute pinion. Twenty-four sets of gears were tested at three load levels: 7200, 8185, and 9075 lb-in face gear torque, and 2190 to 3280 rpm face gear speed. The gears were carburized and ground, shot-peened and vibro-honed, and made from VIM-VAR Pyrowear 53 steel per AMS 6308. The tests produced 17 gear tooth spalling failures and 7 suspensions. For all the failed sets, spalling occurred on at least one tooth of all the pinions. In some cases, the spalling initiated a crack in the pinion teeth which progressed to tooth fracture. Also, spalling occurred on some face gear teeth. The AGMA endurance allowable stress for a tapered spur involute pinion in mesh with a face gear was determined to be 275 ksi for the material tested. For the application of a tapered spur involute pinion in mesh with a face gear, proper face gear shim controlled the desired gear tooth contact pattern while proper pinion shim was an effective way of adjusting backlash without severely affecting the contact pattern.
NASA Astrophysics Data System (ADS)
Mankoč Borštnik, N. S.; Nielsen, H. B.
2006-12-01
The genuine Kaluza-Klein-like theories--with no fields in addition to gravity--have difficulties with the existence of massless spinors after the compactification of some space dimensions \\cite{witten}. We proposed (Phys. Lett. B 633 (2006)771) such a boundary condition for spinors in 1+5 compactified on a flat disk that ensures masslessness of spinors in d=1+3 as well as their chiral coupling to the corresponding background gauge field (which solves equations of motion for a free field linear in the Riemann curvature). In this paper we study the same toy model: M^{(1+3)} x M^{(2)}, looking this time for an involution which transforms a space of solutions of Weyl equations in d=1+5 from the outside of the flat disk in x^5 and x^6 into its inside, allowing massless spinor of only one handedness--and accordingly assures mass protection--and of one charge--1/2--and infinitely many massive spinors of the same charge, chirally coupled to the corresponding background gauge field. We reformulate the operator of momentum so that it is Hermitean on the vector space of spinor states obeying the involution boundary condition.
Oh, Hannah; Pfeiffer, Ruth M; Falk, Roni T; Horne, Hisani N; Xiang, Jackie; Pollak, Michael; Brinton, Louise A; Storniolo, Anna Maria V; Sherman, Mark E; Gierach, Gretchen L; Figueroa, Jonine D
2018-08-01
Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin-like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 and 2012 (75% premenopausal), serum concentrations of IGF-I and binding protein (IGFBP)-3 were quantified using enzyme-linked immunosorbent assay. Hematoxilyn and eosin-stained tissue sections were assessed for numbers of TDLUs ("TDLU count"). Zero-inflated Poisson regression models with a robust variance estimator were used to estimate relative risks (RRs) for association of IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p = 0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p < 0.0001). Postmenopausal IGFBP-3 was inversely associated with TDLU count among AA (RR T3vs.T1 = 0.49, 95% CI = 0.28-0.84, p-trend = 0.04) and Caucasian (RR T3vs.T1 =0.64, 95% CI = 0.42-0.98, p-trend = 0.04) women. In premenopausal women, higher IGF-I:IGFBP-3 ratios were associated with higher TDLU count in Caucasian (RR T3vs.T1 =1.33, 95% CI = 1.02-1.75, p-trend = 0.04), but not in AA (RR T3vs.T1 =0.65, 95% CI = 0.42-1.00, p-trend = 0.05), women. Our data suggest a role of the IGF system, particularly IGFBP-3, in TDLU involution of the normal breast, a breast cancer risk factor, among Caucasian and AA women. © 2018 UICC.
The Riemann-Lanczos equations in general relativity and their integrability
NASA Astrophysics Data System (ADS)
Dolan, P.; Gerber, A.
2008-06-01
The aim of this paper is to examine the Riemann-Lanczos equations and how they can be made integrable. They consist of a system of linear first-order partial differential equations that arise in general relativity, whereby the Riemann curvature tensor is generated by an unknown third-order tensor potential field called the Lanczos tensor. Our approach is based on the theory of jet bundles, where all field variables and all their partial derivatives of all relevant orders are treated as independent variables alongside the local manifold coordinates (xa) on the given space-time manifold M. This approach is adopted in (a) Cartan's method of exterior differential systems, (b) Vessiot's dual method using vector field systems, and (c) the Janet-Riquier theory of systems of partial differential equations. All three methods allow for the most general situations under which integrability conditions can be found. They give equivalent results, namely, that involutivity is always achieved at all generic points of the jet manifold M after a finite number of prolongations. Two alternative methods that appear in the general relativity literature to find integrability conditions for the Riemann-Lanczos equations generate new partial differential equations for the Lanczos potential that introduce a source term, which is nonlinear in the components of the Riemann tensor. We show that such sources do not occur when either of method (a), (b), or (c) are used.
The spectrum of STAT functions in mammary gland development
Hughes, Katherine; Watson, Christine J.
2012-01-01
The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764
Drepper, H
1985-07-01
The superficial angiomas and nevi arise from the endothelial cells, the pigment-cell-system or the epidermal cells. Hemangiomas are benign tumours of the endothelial cells appearing predominantly in female newborn infants. Depending on localisation, growth and proliferation there is a tendency for spontaneous involution. For irreversible dysfunction or anatomical deformities surgical resection during the growth phase of the hemangioma is indicated. Surgery may be necessary to improve the functional and esthetic appearance after spontaneous involution causing loose residual skin. Radiotherapy of the lesion is rarely indicated. Systemic steroid therapy in cooperation with the pediatrician should be reserved only for desperate cases such as Kasabach-Merrit-Syndrome. Port wine nevi without scars can be covered with skin tanning cosmetics. Argon-Laser-Therapy is not yet so selective that healing can be achieved with certainty and without scars. Clinical progression requires surgery, especially for racemose angiectasia. Arterial embolization should only be used under special conditions, and then only as pretreatment. Lymphangiomas are mostly angiectatic processes, especially of lymphatic vascular tissue and vessels. Even large cystic lymphangiomas can be treated quite well by surgery, but operations on large diffuse invasive lymphangiomas often cause lymphedema and infection similar to erysipelas leading to pseudorecurrence. The benign malformations of the pigment cell system require clear differentiation from malignant melanoma and its precursors. Malignant melanoma develops more frequently from congenital nevi of the deep type than from other pigmented lesions. Malignant melanomas arising from giant nevi are usually diagnosed too late so that almost all patients die. Removal of giant nevi as early as possible is recommended. The epidermal malformations, too, need accurate diagnosis. Multisymptomatic syndromes such as the Basal-Cell-Nevus-Syndrome, and vascular and pigment cell abnormalities require special care.
Genetic selection for coping style predicts stressor susceptibility.
Veenema, A H; Meijer, O C; de Kloet, E R; Koolhaas, J M
2003-03-01
Genetically selected aggressive (SAL) and nonaggressive (LAL) male wild house-mice which show distinctly different coping styles, also display a differential regulation of the hypothalamic-pituitary-adrenal axis after exposure to an acute stressor. To test the hypothesis that coping style predicts stressor susceptibility, the present study examined line differences in response to a chronic stressor. Chronic psychosocial stress was evoked using two paradigms. In the first paradigm, a SAL or LAL male was living in sensory contact (except tactile contact) with a dominant SAL male for 25 days (sensory contact stress). In the second paradigm, a SAL or LAL male was, in addition to the first paradigm, defeated by a SAL male for 21 consecutive days (defeat stress). The sensory contact stressor induced in LAL mice chronic body weight loss and increased plasma adrenocorticotropic hormone levels compared to SAL mice and increased corticosterone levels, thymus involution and lower hippocampal mineralocorticoid receptor (MR) : glucocorticoid receptor (GR) ratio compared to LAL controls. The defeat stressor increased corticosterone secretion and caused adrenal hypertrophy and thymus involution in both mouse lines. Defeated LAL mice showed long-lasting body weight loss and higher corticosterone concentrations than SAL mice and lower hippocampal MR : GR ratio and decreased immobility behaviour in the forced swimming test than LAL controls. Hypothalamic corticotropin-releasing hormone mRNA expression was higher in defeated SAL than in controls. The present data show that both stress paradigms induced line-dependent physiological and neuroendocrine changes, but that the sensory contact stressor produced chronic stress symptoms in LAL mice only. This latter stress paradigm therefore seems promising to analyse the role of genetic factors in the individual differences in stress-related psychopathology.
Supplemental vitamin A prevents the acute radiation-induced defect in wound healing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Levenson, S.M.; Gruber, C.A.; Rettura, G.
Acute radiation injury leads to thymic involution, adrenal enlargement, leukopenia, thrombocytopenia, gastrointestinal ulceration, and impaired wound healing. The authors hypothesized that supplemental vitamin A would mitigate these adverse effects in rats exposed to acute whole-body radiation. To test their hypothesis, dorsal skin incisions and subcutaneous implantation of polyvinyl alcohol sponges were performed in anesthetized Sprague-Dawley rats at varying times following sham radiation or varying doses of whole-body radiation (175-850 rad). In each experiment, the control diet (which contains about 18,000 IU vit. A/kg chow (3 X the NRC RDA for normal rats)) was supplemented with 150,000 IU vit. A/kg dietmore » beginning at, before, or after sham radiation and wounding or radiation and wounding. The supplemental vitamin A prevented the impaired wound healing and lessened the weight loss, leukopenia, thrombocytopenia, thymic involution, adrenal enlargement, decrease in splenic weight, and gastric ulceration of the radiated (750-850 rad) wounded rats. This was true whether the supplemental vitamin A was begun before (2 or 4 days) or after (1-2 hours to 4 days) radiation and wounding; the supplemental vitamin A was more effective when started before or up to 2 days after radiation and wounding. The authors believe that prevention of the impaired wound healing following radiation by supplemental vitamin A is due to its enhancing the early inflammatory reaction to wounding, including increasing the number of monocytes and macrophages at the wound site; possible effect on modulating collagenase activity; effect on epithelial cell (and possible mesenchymal cell) differentiation; stimulation of immune responsiveness; and lessening of the adverse effects of radiation.« less
Differential invariants in nonclassical models of hydrodynamics
NASA Astrophysics Data System (ADS)
Bublik, Vasily V.
2017-10-01
In this paper, differential invariants are used to construct solutions for equations of the dynamics of a viscous heat-conducting gas and the dynamics of a viscous incompressible fluid modified by nanopowder inoculators. To describe the dynamics of a viscous heat-conducting gas, we use the complete system of Navier—Stokes equations with allowance for heat fluxes. Mathematical description of the dynamics of liquid metals under high-energy external influences (laser radiation or plasma flow) includes, in addition to the Navier—Stokes system of an incompressible viscous fluid, also heat fluxes and processes of nonequilibrium crystallization of a deformable fluid. Differentially invariant solutions are a generalization of partially invariant solutions, and their active study for various models of continuous medium mechanics is just beginning. Differentially invariant solutions can also be considered as solutions with differential constraints; therefore, when developing them, the approaches and methods developed by the science schools of academicians N. N. Yanenko and A. F. Sidorov will be actively used. In the construction of partially invariant and differentially invariant solutions, there are overdetermined systems of differential equations that require a compatibility analysis. The algorithms for reducing such systems to involution in a finite number of steps are described by Cartan, Finikov, Kuranishi, and other authors. However, the difficultly foreseeable volume of intermediate calculations complicates their practical application. Therefore, the methods of computer algebra are actively used here, which largely helps in solving this difficult problem. It is proposed to use the constructed exact solutions as tests for formulas, algorithms and their software implementations when developing and creating numerical methods and computational program complexes. This combination of effective numerical methods, capable of solving a wide class of problems, with analytical methods makes it possible to make the results of mathematical modeling more accurate and reliable.
NASA Technical Reports Server (NTRS)
Barth, Timothy
2005-01-01
The role of involutions in energy stability of the discontinuous Galerkin (DG) discretization of Maxwell and magnetohydrodynamic (MHD) systems is examined. Important differences are identified in the symmetrization of the Maxwell and MHD systems that impact the construction of energy stable discretizations using the DG method. Specifically, general sufficient conditions to be imposed on the DG numerical flux and approximation space are given so that energy stability is retained These sufficient conditions reveal the favorable energy consequence of imposing continuity in the normal component of the magnetic induction field at interelement boundaries for MHD discretizations. Counterintuitively, this condition is not required for stability of Maxwell discretizations using the discontinuous Galerkin method.
Natural history of age-related lobular involution and impact on breast cancer risk.
Radisky, Derek C; Visscher, Daniel W; Frank, Ryan D; Vierkant, Robert A; Winham, Stacey; Stallings-Mann, Melody; Hoskin, Tanya L; Nassar, Aziza; Vachon, Celine M; Denison, Lori A; Hartmann, Lynn C; Frost, Marlene H; Degnim, Amy C
2016-02-01
Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk.
TNFα Post-Translationally Targets ZnT2 to Accumulate Zinc in Lysosomes.
Hennigar, Stephen R; Kelleher, Shannon L
2015-10-01
Mammary epithelial cells undergo widespread lysosomal-mediated cell death (LCD) during early mammary gland involution. Recently, we demonstrated that tumor necrosis factor-α (TNFα), a cytokine released during early involution, redistributes the zinc (Zn) transporter ZnT2 to accumulate Zn in lysosomes and activate LCD and involution. The objective of this study is to determine how TNFα retargets ZnT2 to lysosomes. We tested the hypothesis that TNFα signaling dephosphorylates ZnT2 to uncover a highly conserved dileucine motif (L294L) in the C-terminus of ZnT2, allowing adaptor protein complex-3 (AP-3) to bind and traffic ZnT2 to lysosomes. Confocal micrographs showed that TNFα redistributed wild-type (WT) ZnT2 from late endosomes (Pearson's coefficient = 0.202 ± 0.05 and 0.097 ± 0.03; P<0.05) to lysosomes (0.292 ± 0.03 and 0.649 ± 0.03; P<0.0001), which increased lysosomal Zn (P<0.0001) and activated LCD (P<0.0001) compared to untreated cells. Mutation of the dileucine motif (L294V) eliminated the ability of TNFα to redistribute ZnT2 from late endosomes to lysosomes, increase lysosomal Zn, or activate LCD. Moreover, TNFα increased (P<0.05) AP-3 binding to wt ZnT2 but not to L294V immunoprecipitates. Finally, using phospho- and dephospho-mimetics of predicted phosphorylation sites (T281, T288, and S296), we found that dephosphorylated S296 was required to target ZnT2 to accumulate Zn in lysosomes and activate LCD. Our findings suggest that women with variation in the C-terminus of ZnT2 may be at risk for inadequate involution and breast disease due the inability to traffic ZnT2 to lysosomes. © 2015 Wiley Periodicals, Inc.
Mechanical strain induces involution-associated events in mammary epithelial cells
Quaglino, Ana; Salierno, Marcelo; Pellegrotti, Jesica; Rubinstein, Natalia; Kordon, Edith C
2009-01-01
Background Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary gland involution. Then, it has been suggested that cell stretching caused by milk accumulation after weaning might be the first stimulus that initiates the complete remodeling of the mammary gland. However, no previous report has demonstrated the impact of mechanical stress on mammary cell physiology. To address this issue, we have designed a new practical device that allowed us to evaluate the effects of radial stretching on mammary epithelial cells in culture. Results We have designed and built a new device to analyze the biological consequences of applying mechanical stress to cells cultured on flexible silicone membranes. Subsequently, a geometrical model that predicted the percentage of radial strain applied to the elastic substrate was developed. By microscopic image analysis, the adjustment of these calculations to the actual strain exerted on the attached cells was verified. The studies described herein were all performed in the HC11 non-tumorigenic mammary epithelial cell line, which was originated from a pregnant BALB/c mouse. In these cells, as previously observed in other tissue types, mechanical stress induced ERK1/2 phosphorylation and c-Fos mRNA and protein expression. In addition, we found that mammary cell stretching triggered involution associated cellular events as Leukemia Inhibitory Factor (LIF) expression induction, STAT3 activation and AKT phosphorylation inhibition. Conclusion Here, we show for the first time, that mechanical strain is able to induce weaning-associated events in cultured mammary epithelial cells. These results were obtained using a new practical and affordable device specifically designed for such a purpose. We believe that our results indicate the relevance of mechanical stress among the early post-lactation events that lead to mammary gland involution. PMID:19615079
Figueroa, Jonine D; Pfeiffer, Ruth M; Brinton, Louise A; Palakal, Maya M; Degnim, Amy C; Radisky, Derek; Hartmann, Lynn C; Frost, Marlene H; Stallings Mann, Melody L; Papathomas, Daphne; Gierach, Gretchen L; Hewitt, Stephen M; Duggan, Maire A; Visscher, Daniel; Sherman, Mark E
2016-08-01
Lesser degrees of terminal duct-lobular unit (TDLU) involution predict higher breast cancer risk; however, standardized measures to quantitate levels of TDLU involution have only recently been developed. We assessed whether three standardized measures of TDLU involution, with high intra/inter pathologist reproducibility in normal breast tissue, predict subsequent breast cancer risk among women in the Mayo benign breast disease (BBD) cohort. We performed a masked evaluation of biopsies from 99 women with BBD who subsequently developed breast cancer (cases) after a median of 16.9 years and 145 age-matched controls. We assessed three metrics inversely related to TDLU involution: TDLU count/mm(2), median TDLU span (microns, which approximates acini content), and median category of acini counts/TDLU (0-10; 11-20; 21-30; 31-50; >50). Associations with subsequent breast cancer risk for quartiles (or categories of acini counts) of each of these measures were assessed with multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI). In multivariable models, women in the highest quartile compared to the lowest quartiles of TDLU counts and TDLU span measures were significantly associated with subsequent breast cancer diagnoses; TDLU counts quartile4 versus quartile1, OR = 2.44, 95 %CI 0.96-6.19, p-trend = 0.02; and TDLU spans, quartile4 versus quartile1, OR = 2.83, 95 %CI = 1.13-7.06, p-trend = 0.03. Significant associations with categorical measures of acini counts/TDLU were also observed: compared to women with median category of <10 acini/TDLU, women with >25 acini counts/TDLU were at significantly higher risk, OR = 3.40, 95 %CI 1.03-11.17, p-trend = 0.032. Women with TDLU spans and TDLU count measures above the median were at further increased risk, OR = 3.75 (95 %CI 1.40-10.00, p-trend = 0.008), compared with women below the median for both of these metrics. Similar results were observed for combinatorial metrics of TDLU acini counts/TDLU, and TDLU count. Standardized quantitative measures of TDLU counts and acini counts approximated by TDLU span measures or visually assessed in categories are independently associated with breast cancer risk. Visual assessment of TDLU numbers and acini content, which are highly reproducible between pathologists, could help identify women at high risk for subsequent breast cancer among the million women diagnosed annually with BBD in the US.
Figueroa, Jonine D.; Pfeiffer, Ruth M.; Brinton, Louise A.; Palakal, Maya M.; Degnim, Amy C.; Radisky, Derek; Hartmann, Lynn C.; Frost, Marlene H.; Mann, Melody L. Stallings; Papathomas, Daphne; Gierach, Gretchen L.; Hewitt, Stephen M.; Duggan, Maire A.; Visscher, Daniel; Sherman, Mark E.
2016-01-01
Lesser degrees of terminal duct-lobular unit (TDLU) involution predict higher breast cancer risk; however, standardized measures to quantitate levels of TDLU involution have only recently been developed. We assessed whether three standardized measures of TDLU involution, with high intra/inter pathologist reproducibility in normal breast tissue, predict subsequent breast cancer risk among women in the Mayo benign breast disease (BBD) cohort. We performed a masked evaluation of biopsies from 99 women with BBD who subsequently developed breast cancer (cases) after a median of 16.9 years and 145 age-matched controls. We assessed three metrics inversely related to TDLU involution: TDLU count/mm2, median TDLU span (microns, which approximates acini content), and median category of acini counts/TDLU (0–10; 11–20; 21–30; 31–50; >50). Associations with subsequent breast cancer risk for quartiles (or categories of acini counts) of each of these measures were assessed with multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI). In multivariable models, women in the highest quartile compared to the lowest quartiles of TDLU counts and TDLU span measures were significantly associated with subsequent breast cancer diagnoses; TDLU counts quartile4 versus quartile1, OR = 2.44, 95 %CI 0.96–6.19, p-trend = 0.02; and TDLU spans, quartile4 versus quartile1, OR = 2.83, 95 %CI = 1.13–7.06, p-trend = 0.03. Significant associations with categorical measures of acini counts/TDLU were also observed: compared to women with median category of <10 acini/TDLU, women with >25 acini counts/TDLU were at significantly higher risk, OR = 3.40, 95 %CI 1.03–11.17, p-trend = 0.032. Women with TDLU spans and TDLU count measures above the median were at further increased risk, OR = 3.75 (95 %CI 1.40–10.00, p-trend = 0.008), compared with women below the median for both of these metrics. Similar results were observed for combinatorial metrics of TDLU acini counts/TDLU, and TDLU count. Standardized quantitative measures of TDLU counts and acini counts approximated by TDLU span measures or visually assessed in categories are independently associated with breast cancer risk. Visual assessment of TDLU numbers and acini content, which are highly reproducible between pathologists, could help identify women at high risk for subsequent breast cancer among the million women diagnosed annually with BBD in the US. PMID:27488681
Fu, Y; Yang, Z-G; Zhao, L-Y
2017-03-01
To study pathogenic features of pediatric hemangiomas, we successfully established a model in mice, by transplanting human hemangioma tissues. The hemangioma from the leg of a two-month-old infant was dissected and sliced into several pieces. During a careful surgical procedure, the hemangioma tissues were individually transplanted into skin incisions in anesthetized mice. The volume of the transplanted tumors was measured and the changes in shape recorded at 1 day, and at 1, 2, 3, 4, 5 and 6 months after the transplantation. HE dyeing, CD31 and Glut1 IHC were applied to tumors in the proliferation and involuting phases. Also, 10 survival tumors and 10 normal tissues from infants undergoing circumcisions (control tissues) were used to determine their Angiotensin 1 (Ang1), Angiotensin 2 (Ang2), Tie2, and endothelium growth factor (VEGF) expression levels by IHC method. We observed all the tumors going through the same stages, where after two months their volumes increased sharply and then after 4 months they all began to recede. During the proliferative phase, newly born capillaries could be seen and the tumor elasticity increased (bright red color). During the involuting phase, the color faded away and the tumors became harder and were almost gone by 6 months. During the first two months after transplantation, HE dyeing showed hypertrophied and proliferating endothelial cells accumulating inside the tumors with irregular cavities inside blood vessels being filled by them. During the involuting phase (at 4 months), the lumen in blood vessels was distinctly enlarged while fiber and adipose tissue had significantly deposited. The transplanted and original tumors tested positive for CD31 and Glut1 dyeing, without significant differences. Compared with control samples, the Ang1 expression of the transplanted tumor in both the hyperplasia and proliferative phases was stably low (p<0.05), while expressions of Ang2 and Tie2 were both stably high (p<0.05). The VEGF expression in the tumors, however, was high during the proliferative phase (p<0.05), while the VEGF of the involuting phase showed no significant differences from that of the normal samples (p>0.05). We showed the reliability of the mouse model in reflecting the pathologic evolution of the proliferation and involuting phases of infantile hemangiomas. Angiogenic mediators Ang1, Ang2 and Tie2 may be abnormally expressed and play important roles in the development of this angiogenic disease.
Fine needle aspiration cytology versus frozen section in branchial cleft cysts.
Begbie, F; Visvanathan, V; Clark, L J
2015-02-01
Branchial cleft cysts occur because of a failure of involution of the second branchial cleft. However, as well-differentiated squamous cell carcinoma can mimic branchial cleft cysts, there is a lack of consensus on the appropriate management of cystic neck lumps. To report our experience of fine needle aspiration cytology and frozen section examination in the management of cystic neck lumps. Retrospective case note review of patients managed in the Southern General Hospital, Scotland, UK. The sensitivity of fine needle aspiration cytology and frozen section for detecting branchial cleft cysts was 75 per cent and 100 per cent respectively. Two patients who did not undergo intra-operative frozen section examination were either over- or under-treated, which is discussed. Adult patients subjected to surgical excision of a suspected branchial cyst should undergo intra-operative frozen section analysis regardless of clinical suspicion for malignancy. This part of management is critical to ensure patients are offered appropriate treatment.
Senescent changes in the ribosomes of animal cells in vivo and in vitro
NASA Technical Reports Server (NTRS)
Miquel, J.; Johnson, J. E., Jr.
1979-01-01
The paper examines RNA-ribosomal changes observed in protozoa and fixed postmitotic cells, as well as the characteristics of intermitotic cells. Attention is given to a discussion of the implications of the reported ribosomal changes as to the senescent deterioration of protein synthesis and physiological functions. A survey of the literature suggests that, while the data on ribosomal change in dividing cells both in vivo and in vitro are inconclusive, there is strong histological and biochemical evidence in favor of some degree of quantitative ribosomal loss in fixed postmitotic cells. Since these decreases in ribosomes are demonstrated in differential cells from nematodes, insects and mammals, they may represent a universal manifestation of cytoplasmic senescence in certain types of fixed postmitotic animal cells. The observed variability in ribosomal loss for cells belonging to the same type suggests that this involution phenomenon is rather related to the wear and tear suffered by a particular cell.
NASA Technical Reports Server (NTRS)
Mark, W. D.
1979-01-01
Application of the transfer function approach to predict the resulting interior noise contribution requires gearbox vibration sources and paths to be characterized in the frequency domain. Tooth-face deviations from perfect involute surfaces were represented in terms of Legendre polynomials which may be directly interpreted in terms of tooth-spacing errors, mean and random deviations associated with involute slope and fullness, lead mismatch and crowning, and analogous higher-order components. The contributions of these components to the spectrum of the static transmission error is discussed and illustrated using a set of measurements made on a pair of helicopter spur gears. The general methodology presented is applicable to both spur and helical gears.
Haricharan, S; Hein, S M; Dong, J; Toneff, M J; Aina, O H; Rao, P H; Cardiff, R D; Li, Y
2014-12-11
Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP(+) mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC.
Characterization of focal breast lesions by means of elastography.
Fischer, T; Sack, I; Thomas, A
2013-09-01
The modern method of sonoelastography of the breast is used for differentiating focal lesions. This review gives an overview of the different techniques available and discusses their roles in the routine clinical setting. The presented techniques include compression or vibration elastography as well as shear wave elastography. Descriptions of the methods are supplemented by a discussion of the clinical role of each technique based on the most recent literature. We discuss by outlining two recent experimental approaches - MRI and tomosynthesis elastography. Currently available data suggest that elastography is an important supplementary tool for the differentiation of breast tumors under routine clinical conditions. The specificity improves with the immediate availability of additional diagnostic information using real-time techniques and/or the calculation of strain ratios (SR). Elastography is especially helpful in women with involuted breasts for differentiating BI-RADS-US 3 and 4 lesions and for evaluating very small cancers without the typical imaging features of malignancy. Here, elastography techniques are highly specific, while the sensitivity decreases compared to B-mode ultrasound. SR calculation is especially helpful in women who have a high risk of breast cancer and high pretest likelihood. B-mode ultrasound is still the first-line method for the initial evaluation of the breast. If suspicious findings are detected, elastography with or without SR calculation is the most crucial supplementary tool. © Georg Thieme Verlag KG Stuttgart · New York.
Matsuoka, Kazuhiko; Tsuji, Daisuke; Taki, Takao; Itoh, Kohji
2011-10-01
Sandhoff disease (SD) is a lysosomal disease caused by a mutation of the HEXB gene associated with excessive accumulation of GM2 ganglioside (GM2) in lysosomes and neurological manifestations. Production of autoantibodies against the accumulated gangliosides has been reported to be involved in the progressive pathogenesis of GM2 gangliosidosis, although the underlying mechanism has not been fully elucidated. The thymus is the key organ in the acquired immune system including the development of autoantibodies. We showed here that thymic involution and an increase in cell death in the organ occur in SD model mice at a late stage of the pathogenesis. Dramatic increases in the populations of Annexin-V(+) cells and terminal deoxynucletidyl transferase dUTP nick end labeling (TUNEL) (+) cells were observed throughout the thymuses of 15-week old SD mice. Enhanced caspase-3/7 activation, but not that of caspase-1/4, -6 ,-8, or -9, was also demonstrated. Furthermore, the serum level of corticosterone, a potent inducer of apoptosis of thymocytes, was elevated during the same period of apoptosis. Our studies suggested that an increase in endocrine corticosterone may be one of the causes that accelerate the apoptosis of thymocytes leading to thymic involution in GM2 gangliosidosis, and thus can be used as a disease marker for evaluation of the thymic condition and disease progression.
Chaudhary, Anshul; Kumar, Vinod; Singh, Prashant K; Sharma, Pradeep; Bairagya, Hridoy R; Kaur, Punit; Sharma, Sujata; Chauhan, Shyam S; Singh, Tej P
2018-04-15
Secretory signalling glycoprotein (SPX-40) from mammary gland is highly expressed during involution. This protein is involved in a programmed cell death during tissue remodelling which occurs at the end of lactation. SPX-40 was isolated and purified from buffalo (SPB-40) from the samples obtained during involution. One solution of SPB-40 was made by dissolving it in buffer containing 25 mM Tris-HCl and 50 mM NaCl at pH 8.0. Another solution was made by adding 25% ethanol to the above solution. The biological effects of SPB-40 dissolved in above two solutions were evaluated on MCF-7 breast cancer cell lines. Free SPB-40 indicated significant pro-apoptotic effects while ethanol exposed SPB-40 showed considerably reduced effects on the apoptosis. SPB-40 was crystallized in the native state. The crystals of SPB-40 were soaked in four separate solutions containing 25% acetone, 25% ethanol, 25% butanol and 25% MPD. Four separate data sets were collected and their structures were determined at high resolutions. In all the four structures, the molecules of acetone, ethanol, butanol and MPD respectively were observed in the hydrophobic binding pocket of SPB-40. As a result of which, the conformation of Trp78 was altered thus blocking the binding site in SPB-40 leading to the loss of activity. Copyright © 2018. Published by Elsevier Inc.
Oltenacu, P A; Britt, J H; Braun, R K; Mellenberger, R W
1983-03-01
Data were from 492 Holstein cows calved between October, 1976, and May, 1977, in eight herds in Michigan. Diameter of the cervix of each cow was estimated by palpation at 8 to 21 days postpartum and again 2 wk later. Parturition and postpartum discharge from the genital tract were classified as normal or abnormal. Size of the cervix between 12 and 26 days postpartum was classified as small, medium, or large within two parity groups. Incidence of abnormal parturition and incidence of abnormal postpartum discharge were 14.1 and 38.0%. Involution of the cervix was affected by parity and type of postpartum discharge. Involution of the cervix occurred sooner postpartum in primiparous than in multiparous cows and sooner postpartum in cows with normal discharge than in cows with abnormal discharge. The greatest difference in cervix diameter between cows with normal or abnormal discharges was 10 mm at 3 wk postpartum. Days from parturition to first detected estrus and first service were extended by abnormal postpartum discharge but not by abnormal parturition. First-service conception rate was lower and days from parturition to conception were higher in cows with medium or large cervices compared to cows with small cervices. Type of postpartum discharge and size of cervix early postpartum may be useful for predicting subsequent reproductive performance in dairy cows.
Chen, W-l; Huang, Z-q; Chai, Q; Zhang, D-m; Wang, Y-y; Wang, H-j; Wang, L; Fan, S
2011-06-01
Picibanil (OK-432) and bleomycin have been used as alternative sclerosing agents for lymphatic malformations. This study evaluated the clinical curative effect of sclerotherapy using fibrin glue combined with OK-432 and bleomycin for the treatment of macrocystic lymphatic malformations of the face and neck. Fifteen paediatric patients (6 males; 9 females, aged 13 months to 14 years) who had received percutaneous sclerotherapy for massive macrocystic lymphatic malformations of the face and neck were retrospectively reviewed. Affected regions included the neck, parotid region and parapharynx, mouth floor, face and cheek, and orbital regions. All patients showed preoperative symptoms of space-occupying lesions between 4 cm × 5 cm and 12 cm × 16 cm in size. Fibrin glue with OK-432 and bleomycin was injected under general anaesthesia. All patients received preoperative and follow-up CT scans. Outcomes were assessed by three surgeons. All patients exhibited mid-facial swelling for 3-4 weeks after surgery, but no major complications. Follow-up periods ranged from 8 to 16 months. Eight lesions were completely involuted, five were mostly involuted, and two were partially involuted. Percutaneous sclerotherapy using fibrin glue with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for massive macrocystic lymphatic malformations of the face and neck. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
NASA Technical Reports Server (NTRS)
Ibrahim, Mounir B.; Gedeon, David; Wood, Gary; McLean, Jeffrey
2009-01-01
Under Phase III of NASA Research Announcement contract NAS3-03124, a prototype nickel segmented-involute-foil regenerator was microfabricated and tested in a Sunpower Frequency-Test-Bed (FTB) Stirling convertor. The team for this effort consisted of Cleveland State University, Gedeon Associates, Sunpower Inc. and International Mezzo Technologies. Testing in the FTB convertor produced about the same efficiency as testing with the original random-fiber regenerator. But the high thermal conductivity of the prototype nickel regenerator was responsible for a significant performance degradation. An efficiency improvement (by a 1.04 factor, according to computer predictions) could have been achieved if the regenerator was made from a low-conductivity material. Also, the FTB convertor was not reoptimized to take full advantage of the microfabricated regenerator s low flow resistance; thus, the efficiency would likely have been even higher had the FTB been completely reoptimized. This report discusses the regenerator microfabrication process, testing of the regenerator in the Stirling FTB convertor, and the supporting analysis. Results of the pre-test computational fluid dynamics (CFD) modeling of the effects of the regenerator-test-configuration diffusers (located at each end of the regenerator) are included. The report also includes recommendations for further development of involute-foil regenerators from a higher-temperature material than nickel.
STRAWBERRY HEMANGIOMAS—The Natural History of the Untreated Lesion
Jacobs, Alvin H.
1957-01-01
A review of the literature on the natural history of strawberry hemangiomas revealed over-whelming evidence of the satisfactory spontaneous involution of over 95 per cent of these lesions without the scarring and danger of other sequelae inherent in the various forms of treatment. In a study of 105 strawberry nevi observed for more than one year, 97 per cent of the lesions had either completely disappeared or were regressing satisfactorily. A cross-section study of 1,735 consecutively examined children in routine pediatric practice showed hemangiomas to be present in 10.1 per cent of all infants from birth to one year of age but that this incidence drops to 1.5 per cent in children over five years of age, confirming the fact of spontaneous involution. PMID:13383382
Generation and Computerized Simulation of Meshing and Contact of Modified Involute Helical Gears
NASA Technical Reports Server (NTRS)
Litvin, Faydor L.; Chen, Ningxin; Lu, Jian
1995-01-01
The design and generation of modified involute helical gears that have a localized and stable bearing contact, and reduced noise and vibration characteristics are described. The localization of the bearing contact is achieved by the mismatch of the two generating surfaces that are used for generation of the pinion and the gear. The reduction of noise and vibration will be achieved by application of a parabolic function of transmission errors that is able to absorb the almost linear function of transmission errors caused by gear misalignment. The meshing and contact of misaligned gear drives can be analyzed by application of computer programs that have been developed. The computations confirmed the effectiveness of the proposed modification of the gear geometry. A numerical example that illustrates the developed theory is provided.
Chew, G L; Huang, D; Huo, C W; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M D; Hopper, J L; Henderson, M A; Haviv, I; Thompson, E W
2013-07-01
Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk.
Cellular mechanism of estrogen-induced thymic involution in wall lizard: caspase-dependent action.
Hareramadas, Batchu; Rai, Umesh
2006-05-01
The present study, for the first time in an ectothermic vertebrate, demonstrates the cellular mechanism of estrogen-induced thymic involution. Ovariectomy in lizards during the preparatory phase of the reproductive cycle resulted in distinct differentiation of cortico-medullary regions and increase in cellularity, especially in the cortical region. The ovariectomy-induced changes were reversed following administration of 17-estradiol (E2), suggesting a primary role of E2 in causing thymic atrophy. To understand the cellular mechanism of E2-induced thymic atrophy, in vitro effect of E2 was investigated on thymocyte proliferation and apoptosis. E2 decreased the uptake of tritiated thymidine (3H-TdR) by thymocytes in a dose-dependent manner, suggesting that estrogen directly inhibits the thymocyte proliferation. Unlike proliferation, E2 did not have any direct effect on thymocyte apoptosis, as evident by DNA gel electrophoretic, flow cytometric or fluorescence microscopic studies. However, in the presence of thymic epithelial cell-rich stromal components (TEC), E2 treatment at low or high concentrations resulted in depolarization of plasma membrane, DNA fragmentation and decrease in DNA content. This suggests that E2 indirectly, through TEC-secreted factors, controls thymocyte apoptosis. Similar result was observed following fluorescence microscopy. The indirect effect of E2 was further ascertained with the findings that E2-pretreated TEC-conditioned medium accelerated the thymocyte apoptosis. Nevertheless, exposure of thymocytes to E2 was seen to be inevitable for the apoptotic action of TEC-secreted paracrine factors. In the presence of TEC, a positive reaction for caspase-3, -7 and -9 and enzyme substrate, poly(ADP-ribose) polymerase (PARP) in response to E2 suggests the caspase-dependent thymocyte apoptosis in the wall lizard Hemidactylus flaviviridis. Further, E2 was shown to act through genomic pathway, since the receptor antagonist tamoxifen and transcription/translation inhibitors blocked its apoptotic action. Interestingly, the apoptotic effect of E2 was effectively decreased by progesterone.
Osada, Masako; Jardine, Logan; Misir, Ruth; Andl, Thomas; Millar, Sarah E; Pezzano, Mark
2010-02-08
Thymic epithelial cell (TEC) microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus. Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+) Foxn1(+) and Aire(+) TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments. Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic degeneration associated with cancer therapy and bone marrow transplants.
Multicystic dysplastic kidney: a retrospective study.
Sharada, Sathish; Vijayakumar, Mahalingam; Nageswaran, Prahlad; Ekambaram, Sudha; Udani, Amish
2014-08-01
To report the renal structural and functional anomalies in children with multicystic dysplastic kidneys. Retrospective descriptive analysis of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology unit over a period of 6 years. Antenatal diagnosis of multicystic dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and 4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest renal abnormality. The serum creatinine values were higher (P=0.006) in children with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was significantly associated with complete involution (P=<0.023). None of the patients developed hypertension and 2 (6.4%) had renal failure. Close nephrological follow-up is needed in children with multicystic dysplasia of kidneys.
NASA Technical Reports Server (NTRS)
Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gadeon, David; Qiu, Songgang; Wood, Gary; Kelly, Kevin; McLean, Jeffrey
2007-01-01
An actual-size microfabricated regenerator comprised of a stack of 42 disks, 19 mm diameter and 0.25 mm thick, with layers of microscopic, segmented, involute-shaped flow channels was fabricated and tested. The geometry resembles layers of uniformly-spaced segmented-parallel-plates, except the plates are curved. Each disk was made from electro-plated nickel using the LiGA process. This regenerator had feature sizes close to those required for an actual Stirling engine but the overall regenerator dimensions were sized for the NASA/Sunpower oscillating-flow regenerator test rig. Testing in the oscillating-flow test rig showed the regenerator performed extremely well, significantly better than currently used random-fiber material, producing the highest figures of merit ever recorded for any regenerator tested in that rig over its approximately 20 years of use.
2013-01-01
Introduction Latent TGFβ binding proteins (LTBPs) govern TGFβ presentation and activation and are important for elastogenesis. Although TGFβ is well-known as a tumor suppressor and metastasis promoter, and LTBP1 is elevated in two distinct breast cancer metastasis signatures, LTBPs have not been studied in the normal mammary gland. Methods To address this we have examined Ltbp1 promoter activity throughout mammary development using an Ltbp1L-LacZ reporter as well as expression of both Ltbp1L and 1S mRNA and protein by qRT-PCR, immunofluorescence and flow cytometry. Results Our data show that Ltbp1L is transcribed coincident with lumen formation, providing a rare marker distinguishing ductal from alveolar luminal lineages. Ltbp1L and Ltbp1S are silent during lactation but robustly induced during involution, peaking at the stage when the remodeling process becomes irreversible. Ltbp1L is also induced within the embryonic mammary mesenchyme and maintained within nipple smooth muscle cells and myofibroblasts. Ltbp1 protein exclusively ensheaths ducts and side branches. Conclusions These data show Ltbp1 is transcriptionally regulated in a dynamic manner that is likely to impose significant spatial restriction on TGFβ bioavailability during mammary development. We hypothesize that Ltbp1 functions in a mechanosensory capacity to establish and maintain ductal luminal cell fate, support and detect ductal distension, trigger irreversible involution, and facilitate nipple sphincter function. PMID:24262428
Friedmann, Y; Daniel, C W
1996-07-10
The murine homeobox genes Msx-1 and Msx-2 are related to the Drosophila msh gene and are expressed in a variety of tissues during mouse embryogenesis. We now report the developmentally regulated expression of Msx-1 and Msx-2 in the mouse mammary gland and show that their expression patterns point toward significant functional roles. Msx-1 and Msx-2 transcripts were present in glands of virgin mice and in glands of mice in early pregnancy, but transcripts decreased dramatically during late pregnancy. Low levels of Msx-1 transcripts were detected in glands from lactating animals and during the first days of involution, whereas Msx-2 expression was not detected during lactation or early involution. Expression of both genes increased gradually as involution progressed. Msx-2 but not Msx-1 expression was decreased following ovariectomy or following exposure to anti-estrogen implanted directly into the gland. Hormonal regulation of Msx-2 expression was confirmed when transcripts returned to normal levels after estrogen was administered to ovariectomized animals. In situ molecular hybridization for Msx-1 showed transcripts localized to the mammary epithelium, whereas Msx-2 expression was confined to the periductal stroma. Mammary stroma from which mammary epithelium had been removed did not transcribe detectable amounts of Msx-2, showing that expression is regulated by contiguous mammary epithelium, and indicating a role for these homeobox genes in mesenchymal-epithelial interactions during mammary development.
Pseudomamma of the inguinal region in a female patient: A case report
Marinopoulos, Spyridon; Arampatzis, Ioannis; Zagouri, Flora; Dimitrakakis, Constantine
2015-01-01
Introduction Supernumerary breasts are relative common benign congenital anomalies. General population occurrence rates vary up to 6% according to ethnicity and gender. Higher incidence is recorded in Asian individuals, especially Japanese. Embryonic breast development of the mammary ridge (milk line) is explained and supernumerary breast tissue resulting from involution failure of any portion of the embryonic mammary folds is described. Presentation of case We report a case of supernumerary breast (pseudomamma) in a female occupying her right inguinal region that was treated in the breast unit of our hospital. Differential diagnosis, imaging methods, operative approach, surgical treatment and histological verification are specified. Discussion Classification system for supernumerary breast tissue is presented, high risk population is identified and congenital malformations linked to it are outlined. Evaluation of diagnostic workup and limitations are stated. Cancerous degeneration and justification for surgical removal of the accessory gland is discussed. Conclusion Differential diagnosis of lesions along the milk line should always be inclusive of developmental abnormalities such as any type of supernumerary breast, often overlooked due to small size, although carrying a malignant potential equal to normally positioned breasts. Surgical correction is a sensible approach, often encouraged by the patients. Additional evaluation is recommended due to the frequent accompanying urinary tract and cardiac anomalies. PMID:26011805
Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention
Martinson, Holly A.; Lyons, Traci R.; Giles, Erin D.; Borges, Virginia F.; Schedin, Pepper
2014-01-01
The magnitude of the breast cancer problem implores researchers to aggressively investigate prevention strategies. However, several barriers currently reduce the feasibility of breast cancer prevention. These barriers include the inability to accurately predict future breast cancer diagnosis at the individual level, the need for improved understanding of when to implement interventions, uncertainty with respect to optimal duration of treatment, and negative side effects associated with currently approved chemoprevention therapies. None-the-less, the unique biology of the mammary gland, with its postnatal development and conditional terminal differentiation, may permit the resolution of many of these barriers. Specifically, lifecycle-specific windows of breast cancer risk have been identified that may be amenable to risk-reducing strategies. Here, we argue for prevention research focused on two of these lifecycle windows of risk: postpartum mammary gland involution and peri-menopause. We provide evidence that these windows are highly amenable to targeted, limited duration treatments. Such approaches could result in the prevention of postpartum and postmenopausal breast cancers, correspondingly. PMID:23664839
Anticommutative extension of the Adler map
NASA Astrophysics Data System (ADS)
Konstantinou-Rizos, S.; Mikhailov, A. V.
2016-07-01
We construct a noncommutative (Grassmann) extension of the well-known Adler Yang-Baxter map. It satisfies the Yang-Baxter equation, it is reversible and birational. Our extension preserves all the properties of the original map except the involutivity.
Handbook on Face Gear Drives with a Spur Involute Pinion
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Egelja, A.; Tan, J.; Chen, D. Y.-D.; Heath, G.
2000-01-01
The use of face gears in power transmission and drive systems has a significant number of benefits. Face gears allow a variety of new transmission arrangements as well as high reduction ratio capability. This leads to drive system weight reduction and improvements in performance. In this work, basic information about the design and analysis of face gear drives is presented. The work considers face gears in mesh with spur involute pinions for both intersecting axes and offset drives. Tooth geometry, kinematics, generation of face gears with localized bearing contact by cutting and grinding, avoidance of tooth undercutting, avoidance of tooth pointing, tooth contact analysis, and algorithms for the simulation of meshing and contact arc all topics which are discussed. In addition, applications of face gear drives are presented. Included are design uses in aerospace applications such as helicopter transmissions, split-torque face gear arrangements, comparisons of face gears with bevel gears, and general design considerations.
Analysis of the vibratory excitation arising from spiral bevel gears
NASA Technical Reports Server (NTRS)
Mark, William D.
1987-01-01
Tools required to understand and predict in terms of its underlying causes the vibratory excitation arising from meshing spiral bevel gears are developed. A generalized three component transmission error of meshing spiral bevel gears is defined. Equations are derived that yield the three components of the generalized transmission error in terms of deviations of tooth running surfaces from equispaced perfect spherical involute surfaces and tooth/gearbody elastic deformations arising from the three components of the generalized force transmitted by the meshing gears. A method for incorporating these equations into the equations of motion of a gear system is described. Equations are derived for the three components of the generalized force transmitted by the gears which are valid whenever inertial effects of the meshing gears and their supports are negligible. Bearing offsets from the positions occupied by the shaft centerlines of perfect spherical involute bevel gears and bearing/bearing support flexibilities enter into the computation of these forces.
Integrable generalizations of non-linear multiple three-wave interaction models
NASA Astrophysics Data System (ADS)
Jurčo, Branislav
1989-07-01
Integrable generalizations of multiple three-wave interaction models in terms of r-matrix formulation are investigated. The Lax representations, complete sets of first integrals in involution are constructed, the quantization leading to Gaudin's models is discussed.
Angiolymphoid Hyperplasia with Eosinophilia: A Case Report
Esteves, Paola; Barbalho, Marcella; Lima, Tiago; Quintella, Leonardo; Niemeyer-Corbellini, João Paulo; Ramos-e-Silva, Marcia
2015-01-01
Angiolymphoid hyperplasia with eosinophilia is a rare disease considered as being a vascular malformation resulting from a subjacent arteriovenous shunt. It affects mostly the head of women between 20 and 40 years old and may present spontaneous involution. PMID:26120306
Academic Reform: The More We Change, the Worse We Get
ERIC Educational Resources Information Center
Pearl, Arthur
1970-01-01
University-developed technologies contribute pollutants; academic credentialism legitimizes racism; scholastic involution produces a mandarin class; the university's "innovations reinforce the existing system. The university is aimless, and because it is, its attempted reforms amount to trivia. (Author)
Ability Grouping and Differentiated Instruction in an Era of Data-Driven Decision Making
ERIC Educational Resources Information Center
Park, Vicki; Datnow, Amanda
2017-01-01
Despite data-driven decision making being a ubiquitous part of policy and school reform efforts, little is known about how teachers use data for instructional decision making. Drawing on data from a qualitative case study of four elementary schools, we examine the logic and patterns of teacher decision making about differentiation and ability…
Temporal competition between differentiation programs determines cell fate choice
NASA Astrophysics Data System (ADS)
Kuchina, Anna; Espinar, Lorena; Cagatay, Tolga; Balbin, Alejandro; Alvarado, Alma; Garcia-Ojalvo, Jordi; Suel, Gurol
2011-03-01
During pluripotent differentiation, cells adopt one of several distinct fates. The dynamics of this decision-making process are poorly understood, since cell fate choice may be governed by interactions between differentiation programs that are active at the same time. We studied the dynamics of decision-making in the model organism Bacillus subtilis by simultaneously measuring the activities of competing differentiation programs (sporulation and competence) in single cells. We discovered a precise switch-like point of cell fate choice previously hidden by cell-cell variability. Engineered artificial crosslinks between competence and sporulation circuits revealed that the precision of this choice is generated by temporal competition between the key players of two differentiation programs. Modeling suggests that variable progression towards a switch-like decision might represent a general strategy to maximize adaptability and robustness of cellular decision-making.
Bidimensional and Doppler ultrasonographic evaluation of postpartum uterine involution in the queen.
Blanco, P G; Rodríguez, R; Batista, P R; Barrena, J P; Arias, D O; Gobello, C
2015-07-01
The aim of this study was to describe bidimensional and Doppler ultrasonographic changes of uterine involution during normal feline puerperium. Secondary, the postpartum vaginal discharge was described. Twelve pregnant female cats were included in this study. After queening, vulvar discharge was grossly and microscopically examined daily. Bidimensional and Doppler ultrasonographic examinations of the uterus were performed on Days -4 to -2, 4, 11, 18, and 25 from parturition. Total uterine diameter, uterine wall thickness, uterine lumen contents, peak systolic velocity, end diastolic velocity, and resistance index of uterine arteries were measured. The cats presented serosanguineous vulvar discharge for a mean of 3 ± 1 days after parturition, and the cytology revealed 70% to 80% of erythrocytes, which progressively decreased up to Day 13. Immediately after parturition, there were less than 20% neutrophils, and this percentage gradually diminished to 0% to 1% at the end of the study. Uterine total diameter diminished up to Day 25 (P < 0.01), when ultrasonographic uterine dimensions were similar to that of anestrus. A progressive decrease of uterine wall thickness (P < 0.05), uterine lumen contents (P < 0.01), peak systolic velocity (P < 0.01), and end diastolic velocity (P < 0.01) was found throughout the study period. Conversely, resistance index increased during the first week after parturition (P < 0.01). It is concluded that the uterine artery blood flow progressively decreased during the first 25 days after parturition, which was associated with the bidimensional ultrasonographic regression of the organ. Although lochial discharge disappeared far before ultrasonographic involution, cytologic findings further corroborated the duration of this regression process. Copyright © 2015 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yu, Simon Chun Ho, E-mail: simonyu@cuhk.edu.hk; Lau, Tiffany Wing Wa; Tang, Peggy
PurposeTo evaluate the microvascular distribution of lipiodol–ethanol, the histological change of the tumor lesion, and the status of tumor involution over time in hepatocellular carcinoma (HCC) following transarterial ethanol ablation (TEA), in lesions that showed CT evidence of complete tumor response.Materials and methodsPatients with unresectable HCC were treated (183 patients, 242 lesions) with TEA using lipiodol–ethanol mixture (LEM) mixed in 2:1 ratio by volume and followed with CT at 3-month intervals for a median of 14.1 months. Liver tumors (n = 131) that showed CT evidence of complete tumor response, defined as the absence of any enhancing tumor throughout the follow-up period, weremore » included. The surgical specimens of five patients who subsequently received partial hepatectomy were available for histological assessment. The microvascular distribution of LEM and the degree of tumor necrosis were analyzed. Tumor involution over time was assessed with CT in lesions that showed complete response.ResultsLipid stain revealed lipiodol infiltration throughout arterioles, intratumoral sinusoidal spaces, tumor capsule, and peritumoral portal venules. Complete tumor necrosis (100 %) occurred in all 5 surgical specimens. The median (IQR) percentage tumor volume compared to baseline volumes at 12, 36, and 60 months was 32 % (23.5–52.5 %), 22 % (8–31 %), and 13.5 % (6–21.5 %), respectively.ConclusionIntrahepatic HCC lesion that showed CT evidence of complete tumor response following TEA is associated with histological evidence of LEM infiltration throughout the intratumoral and peritumoral vasculature and complete tumor necrosis, as well as sustained reduction in tumor volume over time.« less
Fonseca, F A; Britt, J H; McDaniel, B T; Wilk, J C; Rakes, A H
1983-05-01
Two hundred and twelve Holstein and Jersey cows were in a study to determine factors that affected reproductive traits. First ovulation occurred about 3 wk postpartum, and interval to first ovulation was greater in cows that had clinical abnormalities postpartum than in normal cows. Jerseys producing more milk ovulated sooner postpartum than lower producing herdmates. Involution of cervix and uterus occurred later postpartum in cows that had clinical problems postpartum. Involution of genital tract occurred later postpartum in older cows and sooner postpartum in cows that had higher milk yields. Duration of first postpartum estrous cycle was 4 days less than for second postpartum cycle. Percentages of estrous cycles detected by standing estrus were 43 and 73% for Holsteins and Jerseys. Estrous detection rates were highest for cows that produced slightly above the mean milk yield and did not differ between cows in highest and lowest milk production quartiles. First detected estrus and days to first insemination occurred later postpartum in Holsteins as milk yield deviation from herdmates increased, regardless of sign. In Jerseys, days to first insemination and days open increased linearly as milk yield increased. Days to first insemination and conception were greater in cows with postpartum clinical problems. Conception rate at first insemination postpartum increased in proportion to concentration of progesterone in blood samples collected during 12 days before first insemination. Overall, clinical problems at parturition and postpartum lowered reproductive performance in both breeds. There was a slight antagonism between milk yield and reproductive performance (days open) in Jerseys but not in Holsteins.
Feedback-Equivalence of Nonlinear Systems with Applications to Power System Equations.
NASA Astrophysics Data System (ADS)
Marino, Riccardo
The key concept of the dissertation is feedback equivalence among systems affine in control. Feedback equivalence to linear systems in Brunovsky canonical form and the construction of the corresponding feedback transformation are used to: (i) design a nonlinear regulator for a detailed nonlinear model of a synchronous generator connected to an infinite bus; (ii) establish which power system network structures enjoy the feedback linearizability property and design a stabilizing control law for these networks with a constraint on the control space which comes from the use of d.c. lines. It is also shown that the feedback linearizability property allows the use of state feedback to contruct a linear controllable system with a positive definite linear Hamiltonian structure for the uncontrolled part if the state space is even; a stabilizing control law is derived for such systems. Feedback linearizability property is characterized by the involutivity of certain nested distributions for strongly accessible analytic systems; if the system is defined on a manifold M diffeomorphic to the Euclidean space, it is established that the set where the property holds is a submanifold open and dense in M. If an analytic output map is defined, a set of nested involutive distributions can be always defined and that allows the introduction of an observability property which is the dual concept, in some sense, to feedback linearizability: the goal is to investigate when a nonlinear system affine in control with an analytic output map is feedback equivalent to a linear controllable and observable system. Finally a nested involutive structure of distributions is shown to guarantee the existence of a state feedback that takes a nonlinear system affine in control to a single input one, both feedback equivalent to linear controllable systems, preserving one controlled vector field.
Real topological entropy versus metric entropy for birational measure-preserving transformations
NASA Astrophysics Data System (ADS)
Abarenkova, N.; Anglès d'Auriac, J.-Ch.; Boukraa, S.; Maillard, J.-M.
2000-10-01
We consider a family of birational measure-preserving transformations of two complex variables, depending on one parameter for which simple rational expressions for the dynamical zeta function have been conjectured, together with an equality between the topological entropy and the logarithm of the Arnold complexity (divided by the number of iterations). Similar results have been obtained for the adaptation of these two concepts to dynamical systems of real variables, yielding to introduce a “real topological entropy” and a “real Arnold complexity”. We try to compare, here, the Kolmogorov-Sinai metric entropy and this real Arnold complexity, or real topological entropy, on this particular example of a one-parameter dependent birational transformation of two variables. More precisely, we analyze, using an infinite precision calculation, the Lyapunov characteristic exponents for various values of the parameter of the birational transformation, in order to compare these results with the ones for the real Arnold complexity. We find a quite surprising result: for this very birational example, and, in fact, for a large set of birational measure-preserving mappings generated by involutions, the Lyapunov characteristic exponents seem to be equal to zero or, at least, extremely small, for all the orbits we have considered, and for all values of the parameter. Birational measure-preserving transformations, generated by involutions, could thus allow to better understand the difference between the topological description and the probabilistic description of discrete dynamical systems. Many birational measure-preserving transformations, generated by involutions, seem to provide examples of discrete dynamical systems which can be topologically chaotic while they are metrically almost quasi-periodic. Heuristically, this can be understood as a consequence of the fact that their orbits seem to form some kind of “transcendental foliation” of the two-dimensional space of variables.
Goel, Ruchi; Sanoria, Abhilasha; Kumar, Sushil; Arya, Deepanjali; Nagpal, Smriti; Rathie, Neha
2017-01-01
The study aims to compare the effectiveness and complications of transconjunctival retractor plication (TRP) with lateral tarsal strip (LTS) and the polypropylene sling (PS) surgery for treatment of involutional lower lid ectropion. A prospective randomised pilot study was conducted on 30 eyes of 30 patients suffering from epiphora having horizontal eyelid laxity >6mm and age >50 years at a tertiary care centre from December 2014 to March 2015. They were randomly divided into two equal groups for TRP with LTS (group A) and PS (group B). Success was defined as relief in epiphora and lid laxity ≤4mm at 12 months post operatively. There were 19 male and 11 female patients with age ranging from 55-80 years. The mean grade of ectropion was 2.80±1.32 in group A and 2.87±1.60 in group B. The preoperative horizontal laxity increased with the grade of ectropion (p <0.001) while medial canthal laxity was variable. The average surgical time per procedure in group A was 66 minutes and in group B was 24 minutes. Group A had a success rate of 93.33%, while group B had a success rate of 87%. Post-operative complications occurred in 2 eyes in group B only. Both LTS with TRP and PS are effective in the management of involutional ectropion. LTS with TRP though more invasive has higher success rates and a lower incidence of complications as compared to PS. However, PS is an easy to perform out- patient procedure that is faster and better tolerated in old patients.
Simon, Ute; Brüggemann, Rainer; Pudenz, Stefan
2004-04-01
Decisions about sustainable development demand spatially differentiated evaluations. As an example, we demonstrate the evaluation of water management strategies in the cities of Berlin and Potsdam (Germany) with respect to their ecological effects in 14 sections of the surface water system. Two decision support systems were compared, namely PROMETHEE, which is designed to obtain a clear decision (linear ranking), and Hasse Diagram Technique (HDT), normally providing more than one favourable solution (partial order). By PROMETHEE, the spatial differentiation had unwanted effects on the result, negating the stakeholders determined weighting of indicators. Therefore, the stakeholder can barely benefit from the convenience of obtaining a clear decision (linear ranking). In contrast, the result obtained by HDT was not influenced by spatial differentiation. Furthermore, HDT provided helpful tools to analyse the evaluation result, such as the concept of antagonistic indicators to discover conflicts in the evaluation process.
On the Construction of Involutory Rhotrices
ERIC Educational Resources Information Center
Usaini, S.
2012-01-01
An involutory matrix is a matrix that is its own inverse. Such matrices are of great importance in matrix theory and algebraic cryptography. In this note, we extend this involution to rhotrices and present their properties. We have also provided a method of constructing involutory rhotrices.
Deployment of Large-Size Shell Constructions by Internal Pressure
NASA Astrophysics Data System (ADS)
Pestrenin, V. M.; Pestrenina, I. V.; Rusakov, S. V.; Kondyurin, A. V.
2015-11-01
A numerical study on the deployment pressure (the minimum internal pressure bringing a construction from the packed state to the operational one) of large laminated CFRP shell structures is performed using the ANSYS engineering package. The shell resists both membrane and bending deformations. Structures composed of shell elements whose median surface has an involute are considered. In the packed (natural) states of constituent elements, the median surfaces coincide with their involutes. Criteria for the termination of stepwise solution of the geometrically nonlinear problem on determination of the deployment pressure are formulated, and the deployment of cylindrical, conical (full and truncated cones), and large-size composite shells is studied. The results obtained are shown by graphs illustrating the deployment pressure in relation to the geometric and material parameters of the structure. These studies show that large pneumatic composite shells can be used as space and building structures, because the deployment pressure in them only slightly differs from the excess pressure in pneumatic articles made from films and soft materials.
Supplementary comparison EURAMET.L-S24 on involute gear standards
NASA Astrophysics Data System (ADS)
Kniel, K.; Chanthawong, N.; Eastman, N.; Frazer, R.; Kupko, V.; Osawa, S.; Xue, Z.
2014-01-01
At its meeting in 2007, the EURAMET TC-Length decided to run an intercomparison of involute gear standards as a regional comparison with non-European involvement. The Physikalisch-Technische Bundesanstalt, Braunschweig und Berlin, Germany (PTB) was identified as the pilot laboratory, responsible for planning, organizing and analyzing the comparison. In all, seven participants from China, Germany, Japan, Thailand, Ukraine, United Kingdom and USA were asked to measure three different gear standards specialized for profile, helix and pitch measurements. The measurements started mid 2008 and were finished at the end of 2010. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The comparison was registered as the supplementary comparison EURAMET.L-S24. The final report has been peer-reviewed and approved for publication by the CCL WG-MRA, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.
Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi
2013-12-31
While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Genest, Vincent X.; Vinet, Luc; Zhedanov, Alexei
The algebra H of the dual -1 Hahn polynomials is derived and shown to arise in the Clebsch-Gordan problem of sl{sub -1}(2). The dual -1 Hahn polynomials are the bispectral polynomials of a discrete argument obtained from the q{yields}-1 limit of the dual q-Hahn polynomials. The Hopf algebra sl{sub -1}(2) has four generators including an involution, it is also a q{yields}-1 limit of the quantum algebra sl{sub q}(2) and furthermore, the dynamical algebra of the parabose oscillator. The algebra H, a two-parameter generalization of u(2) with an involution as additional generator, is first derived from the recurrence relation of themore » -1 Hahn polynomials. It is then shown that H can be realized in terms of the generators of two added sl{sub -1}(2) algebras, so that the Clebsch-Gordan coefficients of sl{sub -1}(2) are dual -1 Hahn polynomials. An irreducible representation of H involving five-diagonal matrices and connected to the difference equation of the dual -1 Hahn polynomials is constructed.« less
Investigation for Molecular Attraction Impact Between Contacting Surfaces in Micro-Gears
NASA Astrophysics Data System (ADS)
Yang, Ping; Li, Xialong; Zhao, Yanfang; Yang, Haiying; Wang, Shuting; Yang, Jianming
2013-10-01
The aim of this research work is to provide a systematic method to perform molecular attraction impact between contacting surfaces in micro-gear train. This method is established by integrating involute profile analysis and molecular dynamics simulation. A mathematical computation of micro-gear involute is presented based on geometrical properties, Taylor expression and Hamaker assumption. In the meantime, Morse potential function and the cut-off radius are introduced with a molecular dynamics simulation. So a hybrid computational method for the Van Der Waals force between the contacting faces in micro-gear train is developed. An example is illustrated to show the performance of this method. The results show that the change of Van Der Waals force in micro-gear train has a nonlinear characteristic with parameters change such as the modulus of the gear and the tooth number of gear etc. The procedure implies a potential feasibility that we can control the Van Der Waals force by adjusting the manufacturing parameters for gear train design.
NASA Technical Reports Server (NTRS)
Litvin, Faydor L.; Fuentes, Alfonso; Gonzalez-Perez, Ignacio; Piscopo, Alessandro; Ruzziconi, Paolo
2005-01-01
A new type of face-gear drive with intersected axes of rotation formed by a helical involute pinion and conjugated face-gear has been investigated. Generation of face-gears by a shaper free of undercutting and pointing has been investigated. A new method of grinding or cutting of face-gears by a worm of special shape has been developed. A computerized design procedure has been developed to avoid undercutting and pointing by a shaper or by a generating worm. Also, a method to determine the limitations of the helix angle magnitude has been developed. The method provides a localization of the bearing contact to reduce the shift of bearing contact caused by misalignment. The analytical method provides a simulation of the meshing and contact of misaligned gear drives. An automatic mesh generation method has been developed and used to conduct a 3D contact stress analysis of several teeth. The theory developed is illustrated with several examples.
Furken, C; Hoedemaker, M
2014-01-01
To determine the effects of rumen-protected choline (RPC) on health and reproduction in dairy cows. A total of 298 primi- and multiparous German Holstein cows of a high-production dairy herd (average daily milk yield: 32 l) were assigned randomly to a control or treatment group and were hand fed with 0 or 60 g/d of RPC as ReaShure®, respectively, from 21 days before expected calving to 21 days post partum (p. p.) as a top dressing. Health data was analyzed for the incidence of fever within the first 10 days in milk (DIM) as well as the incidence of diseases and the culling rate within the first 200 DIM. Reproduction data were evaluated in terms of the calving data, uterine involution on days 10, 21 and 42 p. p., uterine cytology at day 42 p. p., progesterone concentrations during weeks 3 and 5 p. p. and certain fertility measures. In the statistical analysis, it was differentiated between the control and treatment groups and between primi- and multiparous animals, and their interactions were analyzed. The treatment group had less cows with subclinical endometritis, higher sickness rates after day 100 p. p., lower numbers of stillbirths and more cyclic cows in week 5 p. p. compared to the control group (p < 0.05). Primipara in contrast to multipara had fever more frequently, higher rates of subclinical ketosis p. p., metritis and lameness, higher numbers of sick cows in the first 30 DIM, higher rates of stillbirths and dystocia, showed impaired involution of the uterus on day 10 p. p., fewer animals were cyclic during week 5 p. p. and less animals were culled (p < 0.05). Statistically significant interactions indicated that more heifers of the treatment group were lame, more heifers of the control group developed fever and subclinical endometritis, cows of the treatment group suffered more metritis and were sick more often in the first 30 DIM, and cows of the control group had more dystocia (p < 0.05). Overall, supplementing RPC had only minor effects on the health status and reproduction. Further research in other dairy herds should focus on this topic.
Rice, Megan S; Tamimi, Rulla M; Connolly, James L; Collins, Laura C; Shen, Dejun; Pollak, Michael N; Rosner, Bernard; Hankinson, Susan E; Tworoger, Shelley S
2012-03-13
Previous research in the Nurses' Health Study (NHS) and the NHSII observed that, among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules (a marker of complete involution) versus other lobule types were at lower risk of subsequent breast cancer. Studies in animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit involution of lobules in the breast; however, this has not been studied in humans. We conducted a cross-sectional study among 472 women in the NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and 2002 and provided blood samples between 1996 and 1999. A pathologist, blinded to exposure status, classified lobule type in normal adjacent tissue on available biopsy slides according to the number of acini per lobule. For each participant, the pathologist determined the predominant lobule type (that is, type 1, type 2, or type 3) and whether any type 1 or any type 3 lobules were present. Lobule type was then classified as: predominant type 1/no type 3 lobules, which is suggestive of complete involution; or other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and the ratio of IGF-1:IGFBP-3 levels with lobule type. In univariate analyses, greater age, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type 1/no type 3 lobules (P < 0.05). In multivariate models adjusting for age and assay batch, higher IGF-1 levels were associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.37, 95% confidence interval = 0.15 to 0.89). Greater ratios of IGF-1:IGFBP-3 levels were also associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.26, 95% confidence interval = 0.11 to 0.64). These results were slightly attenuated after adjustment for other potential predictors of lobule type. Higher IGF-1 levels and a greater IGF-1:IGFBP-3 ratio were associated with decreased odds of having predominant type 1 lobules/no type 3 lobules among women with proliferative BBD in the NHSII. This study provides further evidence for the role of insulin-like growth factors in the structure of breast lobules and lobular involution.
The Mammary Stem Cell Hierarchy: A Looking Glass into Heterogeneous Breast Cancer Landscapes
Sreekumar, Amulya; Roarty, Kevin; Rosen, Jeffrey M.
2015-01-01
The mammary gland is a dynamic organ that undergoes extensive morphogenesis during the different stages of embryonic development, puberty, estrus, pregnancy, lactation and involution. Systemic and local cues underlie this constant tissue remodeling and act by eliciting an intricate pattern of responses in the mammary epithelial and stromal cells. Decades of studies utilizing methods such as transplantation and lineage tracing have identified a complex hierarchy of mammary stem cells, progenitors and differentiated epithelial cells that fuel mammary epithelial development. Importantly, these studies have extended our understanding of the molecular crosstalk between cell types, and signaling pathways maintaining normal homeostasis that often are deregulated during tumorigenesis. While several questions remain, this research has many implications for breast cancer. Fundamental among these are the identification of the cells of origin for the multiple subtypes of breast cancer and the understanding of tumor heterogeneity. A deeper understanding of these critical questions will unveil novel breast cancer drug targets and treatment paradigms. In this review, we provide a current overview of normal mammary development and tumorigenesis from a stem cell perspective. PMID:26206777
Ortega-Molina, Ana; Boss, Isaac W; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A; Gascoyne, Randy D; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M; Wendel, Hans-Guido
2015-10-01
The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways.
Ortega-Molina, Ana; Boss, Isaac W.; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W.; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A.; Gascoyne, Randy D.; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M.; Wendel, Hans-Guido
2015-01-01
The lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). However, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center (GC) involution, impedes B cell differentiation and class switch recombination (CSR). Integrative genomic analyses indicate that KMT2D affects H3K4 methylation and expression of a specific set of genes including those in the CD40, JAK-STAT, Toll-like receptor, and B cell receptor pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3, and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell activating pathways. PMID:26366710
Watt, Ashalyn P; Sharp, Julie A; Lefevre, Christophe; Nicholas, Kevin R
2012-03-01
WAP four disulfide core domain 2 (WFDC2) is a four disulfide core (4-DSC) protein secreted in the milk of the tammar wallaby. It is comprised of two 4-DSC domains assigned domain III at the NH2-terminal end and domain II at the COOH-terminal end. The WFDC2 gene was expressed only during pregnancy, early lactation, towards the end of lactation and involution. The WFDC2 protein showed antibacterial activity against Staphylococcus aureus, Salmonella enterica and Pseudomonas aeruginosa and this activity resided with domain II. There was no antibacterial activity detected against Enterococcus faecalis. The observed expression pattern of tammar WFDC2 and its antibacterial activity suggests a role to either reduce mastitis in the mammary gland caused by S. aureus or to protect the gut of the young at a time when it is not immune-competent. The latter effect could be achieved without disturbing the balance of commensal gut flora such as E. faecalis. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
Differentiated Instruction in a Data-Based Decision-Making Context
ERIC Educational Resources Information Center
Faber, Janke M.; Glas, Cees A. W.; Visscher, Adrie J.
2018-01-01
In this study, the relationship between differentiated instruction, as an element of data-based decision making, and student achievement was examined. Classroom observations (n = 144) were used to measure teachers' differentiated instruction practices and to predict the mathematical achievement of 2nd- and 5th-grade students (n = 953). The…
NASA Technical Reports Server (NTRS)
Acharya, Arun (Inventor); Gottzmann, Christian F. (Inventor); Lockett, Michael J. (Inventor); Schneider, James S. (Inventor); Victor, Richard A. (Inventor); Zawierucha, Robert (Inventor)
1994-01-01
An apparatus comprising a rotatable mass of structured packing for mass or heat transfer between two contacting fluids of different densities wherein the packing mass is made up of corrugated sheets of involute shape relative to the axis of the packing mass and form a logarithmic spiral curved counter to the direction of rotation.
Lattices, vertex algebras, and modular categories
NASA Astrophysics Data System (ADS)
van Ekeren, Jethro
2018-03-01
In this note we give an account of recent progress on the construction of holomorphic vertex algebras as cyclic orbifolds as well as related topics in lattices and modular categories. We present a novel computation of the Schur indicator of a lattice involution orbifold using finite Heisenberg groups and discriminant forms.
Šavc, Miha; Kenny, David A; Beltman, Marijke E
2016-05-01
The aim of this study was to compare the effects of two parturition induction protocols with a nontreated control group, on interval to calving, calving ease, postpartum uterine health, and ovarian cyclicity in beef heifers. At Day 285 of gestation, 81 crossbred recipient beef heifers carrying purebred Simmental fetuses, were blocked by live-weight, body condition score, expected calving date and fetal sex, and assigned to one of three groups: (1) control (CON; no induction treatment, n = 29); (2) induction with corticosteroids (CORT; n = 27); or (3) induction with corticosteroids plus prostaglandin (CORT + PG; n = 25). Interval from induction to calving in hours and calving ease on a scale of 1 to 5 were recorded. Vaginal mucus samples were collected on Day 21 and Day 42 after calving (Day 0) by means of a Metricheck and scored on a scale of 0 to 3. Reproductive tract examinations were conducted on Day 21 and Day 42 after calving, and uterine cytology samples were obtained on Day 21. A positive cytologic sample was defined as greater than 18% neutrophils in the sample obtained via a cytobrush technique. Cows were considered to have resumed ovarian cyclicity if the presence of the CL was confirmed. Data were analyzed using the Mixed (normally distributed data) and Genmod (nonparametric data) procedures of SAS (v. 9.3). The interval from treatment to calving was longer (P < 0.0001) for CON (161.9 ± 15.12 hours) animals compared with CORT (39.7 ± 11.64 hours) or CORT + PG (32.6 ± 12.10 hours), which did not differ. Treatment did not affect calving difficulty score. There was also no difference in incidence of retained placenta between the three groups. At Day 21 postpartum, cytology score tended to be higher for both induced groups (48%) compared with the control animals (24%), but this was not the case for vaginal mucus score (CON 52%, CORT 70%, and CORT + PG 52%). A higher proportion of CON had an involuted uterus by Day 21 postpartum (69%) compared with both induced groups (CORT 48%, CORT + PG 32%). Day 21 ovarian cyclicity was higher in both CON (52%) and CORT (59%) compared with CORT + PG (29%). By Day 42, there was no difference in ovarian cyclicity or uterine involution between CON and CORT; however, a positive relationship was observed between uterine involution score on Day 21 and return to cyclicity on Day 42 in these two groups. There was a negative relationship between uterine involution score and return to cyclicity in the CORT + PG group, and these animals were slower (P < 0.05) to resume cyclicity by Day 42 with a larger proportion animals having evidence of having resumed postpartum ovarian cyclicity in both CON (P = 0.03) and CORT compared with CORT + PG on Day 42. In conclusion, the use of corticosteroid-based treatments is an effective strategy to advance parturition in full term dams and does not have a negative effect on calving progress or dam health. However, when prostaglandin is also included in the protocol, these treatments may lead to greater delay in uterine involution with increased chance of uterine infection and slower resumption of ovarian cyclicity. Copyright © 2016 Elsevier Inc. All rights reserved.
Sugimoto, Katsutoshi; Shiraishi, Junji; Moriyasu, Fuminori; Doi, Kunio
2009-04-01
To develop a computer-aided diagnostic (CAD) scheme for classifying focal liver lesions (FLLs) by use of physicians' subjective classification of echogenic patterns of FLLs on baseline and contrast-enhanced ultrasonography (US). A total of 137 hepatic lesions in 137 patients were evaluated with B-mode and NC100100 (Sonazoid)-enhanced pulse-inversion US; lesions included 74 hepatocellular carcinomas (HCCs) (23: well-differentiated, 36: moderately differentiated, 15: poorly differentiated HCCs), 33 liver metastases, and 30 liver hemangiomas. Three physicians evaluated single images at B-mode and arterial phases with a cine mode. Physicians were asked to classify each lesion into one of eight B-mode and one of eight enhancement patterns, but did not make a diagnosis. To classify five types of FLLs, we employed a decision tree model with four decision nodes and four artificial neural networks (ANNs). The results of the physicians' pattern classifications were used successively for four different ANNs in making decisions at each of the decision nodes in the decision tree model. The classification accuracies for the 137 FLLs were 84.8% for metastasis, 93.3% for hemangioma, and 98.6% for all HCCs. In addition, the classification accuracies for histological differentiation types of HCCs were 65.2% for well-differentiated HCC, 41.7% for moderately differentiated HCC, and 80.0% for poorly differentiated HCC. This CAD scheme has the potential to improve the diagnostic accuracy of liver lesions. However, the accuracy in the histologic differential diagnosis of HCC based on baseline and contrast-enhanced US is still limited.
Yan, Fenggen; Mo, Xiumei; Liu, Junfeng; Ye, Siqi; Zeng, Xing; Chen, Dacan
2017-11-01
The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress‑mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.
Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy
Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi
2013-01-01
While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast—it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray—these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001 PMID:24381245
Nair, Shalini Rajandran; Tan, Li Kuo; Mohd Ramli, Norlisah; Lim, Shen Yang; Rahmat, Kartini; Mohd Nor, Hazman
2013-06-01
To develop a decision tree based on standard magnetic resonance imaging (MRI) and diffusion tensor imaging to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). 3-T brain MRI and DTI (diffusion tensor imaging) were performed on 26 PD and 13 MSA patients. Regions of interest (ROIs) were the putamen, substantia nigra, pons, middle cerebellar peduncles (MCP) and cerebellum. Linear, volumetry and DTI (fractional anisotropy and mean diffusivity) were measured. A three-node decision tree was formulated, with design goals being 100 % specificity at node 1, 100 % sensitivity at node 2 and highest combined sensitivity and specificity at node 3. Nine parameters (mean width, fractional anisotropy (FA) and mean diffusivity (MD) of MCP; anteroposterior diameter of pons; cerebellar FA and volume; pons and mean putamen volume; mean FA substantia nigra compacta-rostral) showed statistically significant (P < 0.05) differences between MSA and PD with mean MCP width, anteroposterior diameter of pons and mean FA MCP chosen for the decision tree. Threshold values were 14.6 mm, 21.8 mm and 0.55, respectively. Overall performance of the decision tree was 92 % sensitivity, 96 % specificity, 92 % PPV and 96 % NPV. Twelve out of 13 MSA patients were accurately classified. Formation of the decision tree using these parameters was both descriptive and predictive in differentiating between MSA and PD. • Parkinson's disease and multiple system atrophy can be distinguished on MR imaging. • Combined conventional MRI and diffusion tensor imaging improves the accuracy of diagnosis. • A decision tree is descriptive and predictive in differentiating between clinical entities. • A decision tree can reliably differentiate Parkinson's disease from multiple system atrophy.
Effect of postpartum suppression of ovulation on uterine involution in dairy cows.
Heppelmann, M; Brömmling, A; Weinert, M; Piechotta, M; Wrenzycki, C; Bollwein, H
2013-09-15
The objective of this study was to investigate the effect of time of first postpartum ovulation after calving on uterine involution in dairy cows with and without uterine puerperal disease. Transvaginal follicular puncture (FP) of follicles >6 mm suppressed ovulation and development of a CL until Day 42 after calving. Fifty-three lactating Holstein Friesian cows (3.4 ± 1.2 years old, parity 2.5 ± 1.0 [median ± mean absolute deviation]) were divided into groups on the basis of the presence (UD+) or absence (UD-) of uterine disease and whether FP was carried out (FP+) or not (FP-). Uterine disease was defined as the occurrence of retained fetal membranes and/or metritis. This resulted in the following groups: UD-FP- (n = 15), UD-FP+ (n = 13), UD+FP- (n = 13), and UD+FP+ (n = 12). A general examination, vaginoscopy, transrectal palpation, and transrectal B-mode sonography of the reproductive organs were conducted on Days 8, 11, 18, and 25 and then every 10 days until Day 65 after calving. After hormonal synchronization of ovulation (cloprostenol between Days 55 and 60 postpartum and GnRH 2 days later), cows were inseminated in the next spontaneous estrus. On average, the cows ovulated on Day 21.0 ± 6.0 (UD-FP-), 50.0 ± 4.0 (UD-FP+), 16.0 ± 3.0 (UD+FP-), and 48.0 ± 2.0 (UD+FP+) postpartum. Calving-to-conception interval and first-service conception rates were not affected by FP (P > 0.05). Healthy cows with FP had smaller (P < 0.05) uterine horn and cervical diameters assessed sonographically than cows without FP. FP reduced the prevalence of purulent vaginal discharge and uterine size assessed transrectally in UD+ cows (P < 0.05). The results showed that suppression of an early ovulation by transvaginal FP improved uterine involution in cows with and without uterine disease. Copyright © 2013 Elsevier Inc. All rights reserved.
NASA Technical Reports Server (NTRS)
Ibrahim, Mounir B.; Tew, Roy C.; Gedeon, David; Wood, Gary; McLean, Jeff
2008-01-01
Under Phase II of a NASA Research Award contract, a prototype nickel segmented-involute-foil regenerator was microfabricated via LiGA and tested in the NASA/Sunpower oscillating-flow test rig. The resulting figure-of-merit was about twice that of the approx.90% porosity random-fiber material currently used in the small 50-100 W Stirling engines recently manufactured for NASA. That work was reported at the 2007 International Energy Conversion Engineering Conference in St. Louis, was also published as a NASA report, NASA/TM-2007-2149731, and has been more completely described in a recent NASA Contractor Report, NASA/CR-2007-2150062. Under a scaled-back version of the original Phase III plan, a new nickel segmentedinvolute- foil regenerator was microfabricated and has been tested in a Sunpower Frequency-Test-Bed (FTB) Stirling convertor. Testing in the FTB convertor produced about the same efficiency as testing with the original random-fiber regenerator. But the high thermal conductivity of the prototype nickel regenerator was responsible for a significant performance degradation. An efficiency improvement (by a 1.04 factor, according to computer predictions) could have been achieved if the regenerator been made from a low-conductivity material. Also the FTB convertor was not reoptimized to take full advantage of the microfabricated regenerator's low flow resistance; thus the efficiency would likely have been even higher had the FTB been completely reoptimized. This report discusses the regenerator microfabrication process, testing of the regenerator in the Stirling FTB convertor, and the supporting analysis. Results of the pre-test computational fluid dynamics (CFD) modeling of the effects of the regenerator-test-configuration diffusers (located at each end of the regenerator) is included. The report also includes recommendations for accomplishing further development of involute-foil regenerators from a higher-temperature material than nickel.
NASA Astrophysics Data System (ADS)
Lehmkuhl, Frank
2017-04-01
In the cold and continental areas of Central and High Asia periglacial landform assembles, sediment structures and processes are mainly influenced and determinated by the existence of soil humidity during the freeze-thaw cycles. This results in cryogenic processes and periglacial landforms such as earth hummocks, patterned ground or solifluction. The distribution of rock glaciers as clear indicators of permafrost is also determined by rock fall or moraine debris composed of large boulders (e.g. granite). Periglacial features and landforms have been used to reconstruct past climatic conditions, e.g. relict involutions and ice-wedge casts provide evidence for the distribution of former permafrost, e.g. for the Last Glacial Maximum. Past temperatures, e.g. mean annual air temperatures, can be estimated from these periglacial features. Examples from late Holocene solifluction activity in the Altai, Khangai, and north-eastern Tibetan Plateau show different intensity of solifluction processes during the Late Holocene and Little Ice Age by decrease of temperature and more soil humidity. The distribution of past permafrost in some regions is still a matter of debate due to different interpretations of sediment structures: Sometimes features described as ice-wedge casts may be caused by roots or desiccation cracks due to drying of clay rich sediments. Seismically deformed unconsolidated deposits (seismites) can also be misinterpreted as periglacial involutions. The lack of certain landform assemblages and sediment structures does not necessarily mean that the area had no permafrost as moisture conditions also to a large degree govern periglacial landform generation and not only temperature. They can be ordered in Central Asia as follows (from highest moisture availability to lowest): solifluction - rock glacier - permafrost involutions - ice-wedge casts - sand wedge casts. Reference: LEHMKUHL, F. (2016): Modern and past periglacial features in Central Asia and their implication for paleoclimate reconstructions. - Progress in Physical Geography 40: 369-391. DOI: 10.1177/0309133315615778
Do Processing Patterns of Strengths and Weaknesses Predict Differential Treatment Response?
ERIC Educational Resources Information Center
Miciak, Jeremy; Williams, Jacob L.; Taylor, W. Pat; Cirino, Paul T.; Fletcher, Jack M.; Vaughn, Sharon
2016-01-01
No previous empirical study has investigated whether the learning disabilities (LD) identification decisions of proposed methods to operationalize processing strengths and weaknesses approaches for LD identification are associated with differential treatment response. We investigated whether the identification decisions of the…
Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases
USDA-ARS?s Scientific Manuscript database
Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk prod...
Fat-containing soft-tissue masses in children.
Sheybani, Elizabeth F; Eutsler, Eric P; Navarro, Oscar M
2016-12-01
The diagnosis of soft-tissue masses in children can be difficult because of the frequently nonspecific clinical and imaging characteristics of these lesions. However key findings on imaging can aid in diagnosis. The identification of macroscopic fat within a soft-tissue mass narrows the differential diagnosis considerably and suggests a high likelihood of a benign etiology in children. Fat can be difficult to detect with sonography because of the variable appearance of fat using this modality. Fat is easier to recognize using MRI, particularly with the aid of fat-suppression techniques. Although a large portion of fat-containing masses in children are adipocytic tumors, a variety of other tumors and mass-like conditions that contain fat should be considered by the radiologist confronted with a fat-containing mass in a child. In this article we review the sonographic and MRI findings in the most relevant fat-containing soft-tissue masses in the pediatric age group, including adipocytic tumors (lipoma, angiolipoma, lipomatosis, lipoblastoma, lipomatosis of nerve, and liposarcoma); fibroblastic/myofibroblastic tumors (fibrous hamartoma of infancy and lipofibromatosis); vascular anomalies (involuting hemangioma, intramuscular capillary hemangioma, phosphate and tensin homologue (PTEN) hamartoma of soft tissue, fibro-adipose vascular anomaly), and other miscellaneous entities, such as fat necrosis and epigastric hernia.
Liarte, Sergio; Chaves-Pozo, Elena; García-Alcazar, Alicia; Mulero, Victoriano; Meseguer, José; García-Ayala, Alfonsa
2007-01-01
Background Leukocytes are found within the testis of most, if not all, mammals and are involved in immunological surveillance, physiological regulation and tissue remodelling. The testis of seasonal breeding fish undergoes a regression process. In the present study, the second reproductive cycle (RC) of the protandrous seasonal teleost fish, gilthead seabream, was investigated and the presence of leukocytes analysed. Special attention has been paid to the testicular degenerative process which is particularly active in the last stage of the second RC probably due to the immediacy of the sex change process. Methods Sexually mature specimens (n = 10–18 fish/month) were sampled during the second RC. Some specimens were intraperitoneally injected with bromodeoxyuridin (BrdU) before sampling. Light and electron microscopy was used to determine the different stages of gonadal development and the presence of leukocytes and PCR was used to analyse the gene expression of a testis-differentiating gene and of specific markers for macrophages and B and T lymphocytes. Immunocytochemistry and flow cytometry were performed using a specific antibody against acidophilic granulocytes from the gilthead seabream. Cell proliferation was detected by immunocytochemistry using an anti-BrdU antibody and apoptotic cells by in situ detection of DNA fragmentation. Results The fish in the western Mediterranean area developed as males during the first two RCs. The testis of all the specimens during the second RC underwent a degenerative process, which started at post-spawning and was enhanced during the testicular involution stage, when vitellogenic oocytes appeared in the ovary accompanied by a progressive increase in the ovarian index. However, only 40% of specimens were females in the third RC. Leukocytes (acidophilic granulocytes, macrophages and lymphocytes) were present in the gonad and acidophilic granulocyte infiltration occurred during the last two stages. At the same time DMRT1 gene expression decreased. Conclusions The results demonstrate that innate and adaptive immune cells are present in the gonads of gilthead seabream. Moreover, the whole fish population underwent a testicular degenerative process prior to sex change, characterized by high rates of apoptosis and necrosis and accompanied by an infiltration of acidophilic granulocytes and a decrease in DMRT1 levels. PMID:17547755
Macias, Hector
2012-01-01
The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial/mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development – pubertal growth, pregnancy, lactation and involution – occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone and estrogen, as well as IGF1, to create a ductal tree that fills the fat pad. Upon pregnancy the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its pre-pregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease. PMID:22844349
STEAM GENERATOR FOR GAS COOLED NUCLEAR REACTORS
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
1960-03-14
A steam generator for a gas-cooled nuclear reactor is disposed inside the same pressure vessel as the reactor and has a tube system heated by the gas circulating through the reactor; the pressure vessel is double-walled, and the interspace between these two walls is filled with concrete serving as radiation shielding. The steam generator has a cylindricaIly shaped vertical casing, through which the heating gas circulates, while the tubes are arranged in a plurality of parallel horizontal planes and each of them have the shape of an involute of a circle. The tubes are uniformly distributed over the available surfacemore » in the plane, all the tubes of the same plane being connected in parallel. The exterior extremities of these involute-shaped tubes are each connected with similar tubes disposed in the adjacent lower situated plane, while the interior extremities are connected with tubes in the adjacent higher situated plane. The alimentation of the tubes is performed over annular headers. The tube system is self-supporting, the tubes being joined together by welded spacers. The fluid flow in the tubes is performed by forced circulation. (NPO)« less
NASA Astrophysics Data System (ADS)
Abadjiev, Valentin; Abadjieva, Emilia
2016-06-01
Hyperboloid gear drives with face mating gears are used to transform rotations between shafts with non-parallel and non-intersecting axes. A special case of these transmissions are Spiroid and Helicon gear drives. The classical gear drives of this type are the Archimedean ones. The objective of this study are hyperboloid gear drives with face meshing, when the pinion possesses threads of conic convolute, Archimedean and involute types, or the pinion has threads of cylindrical convolute, Archimedean and involute types. For simplicity, all three types transmis- sions with face mating gears and a conic pinion are titled Spiroid and all three types transmissions with face mating gears and a cylindrical pinion are titled Helicon. Principles of the mathematical modelling of tooth contact synthesis are discussed in this study. The presented research shows that the synthesis is realized by application of two mathematical models: pitch contact point and mesh region models. Two approaches for synthesis of the gear drives in accordance with Olivier's principles are illustrated. The algorithms and computer programs for optimization synthesis and design of the studied hyperboloid gear drives are presented.
Ghrelin promotes thymopoiesis during aging
Dixit, Vishwa Deep; Yang, Hyunwon; Sun, Yuxiang; Weeraratna, Ashani T.; Youm, Yun-Hee; Smith, Roy G.; Taub, Dennis D.
2007-01-01
The decline in adaptive immunity, T lymphocyte output, and the contraction of the TCR repertoire with age is largely attributable to thymic involution. The loss of thymic function with age may be due to diminished numbers of progenitors and the loss of critical cytokines and hormones from the thymic microenvironment. We have previously demonstrated that the orexigenic hormone ghrelin is expressed by immune cells and regulates T cell activation and inflammation. Here we report that ghrelin and ghrelin receptor expression within the thymus diminished with progressive aging. Infusion of ghrelin into 14-month-old mice significantly improved the age-associated changes in thymic architecture and thymocyte numbers, increasing recent thymic emigrants and improving TCR diversity of peripheral T cell subsets. Ghrelin-induced thymopoiesis during aging was associated with enhanced early thymocyte progenitors and bone marrow–derived Lin–Sca1+cKit+ cells, while ghrelin- and growth hormone secretagogue receptor–deficient (GHS-R–deficient) mice displayed enhanced age-associated thymic involution. Leptin also enhanced thymopoiesis in aged but not young mice. Our findings demonstrate what we believe to be a novel role for ghrelin and its receptor in thymic biology and suggest a possible therapeutic benefit of harnessing this pathway in the reconstitution of thymic function in immunocompromised subjects. PMID:17823656
Extracellular matrix components in breast cancer progression and metastasis.
Oskarsson, Thordur
2013-08-01
The extracellular matrix (ECM) is composed of highly variable and dynamic components that regulate cell behavior. The protein composition and physical properties of the ECM govern cell fate through biochemical and biomechanical mechanisms. This requires a carefully orchestrated and thorough regulation considering that a disturbed ECM can have serious consequences and lead to pathological conditions like cancer. In breast cancer, many ECM proteins are significantly deregulated and specific matrix components promote tumor progression and metastatic spread. Intriguingly, several ECM proteins that are associated with breast cancer development, overlap substantially with a group of ECM proteins induced during the state of tissue remodeling such as mammary gland involution. Fibrillar collagens, fibronectin, hyaluronan and matricellular proteins are matrix components that are common to both involution and cancer. Moreover, some of these proteins have in recent years been identified as important constituents of metastatic niches in breast cancer. In addition, specific ECM molecules, their receptors or enzymatic modifiers are significantly involved in resistance to therapeutic intervention. Further analysis of these ECM proteins and the downstream ECM mediated signaling pathways may provide a range of possibilities to identify druggable targets against advanced breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.
Prevot, S; Audouin, J; Andre-Bougaran, J; Griffais, R; Le Tourneau, A; Fournier, J G; Diebold, J
1992-03-01
An enlargement of the thymus suggesting a tumor was discovered in a 28-year-old man who had early-stage acquired immune deficiency syndrome. A biopsy was performed. The adipose involuted thymus, with persistence of many Hassall's corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that previously described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p24 human immunodeficiency virus protein were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells), and also in many cells that may have been either lymphocytes and/or epithelial cells in the interfollicular areas. The tissue was negative for Epstein-Barr virus DNA sequences, as determined by the polymerase chain reaction. These observations identify the first state of infection of the thymus in a human immune deficiency virus-infected adult, preceding the severe involution with lymphoid depletion observed in all fatal cases of acquired immunodeficiency syndrome in which the thymus has been analyzed.
Decisions that Make a Difference in Detecting Differential Item Functioning
ERIC Educational Resources Information Center
Sireci, Stephen G.; Rios, Joseph A.
2013-01-01
There are numerous statistical procedures for detecting items that function differently across subgroups of examinees that take a test or survey. However, in endeavouring to detect items that may function differentially, selection of the statistical method is only one of many important decisions. In this article, we discuss the important decisions…
Music and Video Gaming during Breaks: Influence on Habitual versus Goal-Directed Decision Making.
Liu, Shuyan; Schad, Daniel J; Kuschpel, Maxim S; Rapp, Michael A; Heinz, Andreas
2016-01-01
Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes.
Music and Video Gaming during Breaks: Influence on Habitual versus Goal-Directed Decision Making
Kuschpel, Maxim S.; Rapp, Michael A.; Heinz, Andreas
2016-01-01
Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes. PMID:26982326
Kumar, Gautam; Kothare, Mayuresh V
2013-12-01
We derive conditions for continuous differentiability of inter-spike intervals (ISIs) of spiking neurons with respect to parameters (decision variables) of an external stimulating input current that drives a recurrent network of synaptically connected neurons. The dynamical behavior of individual neurons is represented by a class of discontinuous single-neuron models. We report here that ISIs of neurons in the network are continuously differentiable with respect to decision variables if (1) a continuously differentiable trajectory of the membrane potential exists between consecutive action potentials with respect to time and decision variables and (2) the partial derivative of the membrane potential of spiking neurons with respect to time is not equal to the partial derivative of their firing threshold with respect to time at the time of action potentials. Our theoretical results are supported by showing fulfillment of these conditions for a class of known bidimensional spiking neuron models.
Structure and Style in Career Decision Making.
ERIC Educational Resources Information Center
Kortas, Linda; And Others
1992-01-01
The Career Decision Scale, Assessment of Career Decision Making, and Cognitive Differentiation Grid were administered to 598 community college students. Results indicated a relationship between decision-making styles and vocational construct structure. Poorly developed vocational schemas predispose individuals toward dependent and intuitive…
2012-01-01
Abstract Recent progress in stem cell biology, notably cell fate conversion, calls for novel theoretical understanding for cell differentiation. The existing qualitative concept of Waddington’s “epigenetic landscape” has attracted particular attention because it captures subsequent fate decision points, thus manifesting the hierarchical (“tree-like”) nature of cell fate diversification. Here, we generalized a recent work and explored such a developmental landscape for a two-gene fate decision circuit by integrating the underlying probability landscapes with different parameters (corresponding to distinct developmental stages). The change of entropy production rate along the parameter changes indicates which parameter changes can represent a normal developmental process while other parameters’ change can not. The transdifferentiation paths over the landscape under certain conditions reveal the possibility of a direct and reversible phenotypic conversion. As the intensity of noise increases, we found that the landscape becomes flatter and the dominant paths more straight, implying the importance of biological noise processing mechanism in development and reprogramming. We further extended the landscape of the one-step fate decision to that for two-step decisions in central nervous system (CNS) differentiation. A minimal network and dynamic model for CNS differentiation was firstly constructed where two three-gene motifs are coupled. We then implemented the SDEs (Stochastic Differentiation Equations) simulation for the validity of the network and model. By integrating the two landscapes for the two switch gene pairs, we constructed the two-step development landscape for CNS differentiation. Our work provides new insights into cellular differentiation and important clues for better reprogramming strategies. PMID:23300518
Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland
2017-11-01
Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland. 21702-5012 DISTRIBUTION STATEMENT: Approved for... Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT Approved...5 days. Knockdown was assessed by PCR. Efficient knockdown of LTBP1 was observed within 24 hours and maintained throughout the time course
Drinfeld-Sokolov reduction in quantum algebras: canonical form of generating matrices
NASA Astrophysics Data System (ADS)
Gurevich, Dimitri; Saponov, Pavel; Talalaev, Dmitry
2018-04-01
We define the second canonical forms for the generating matrices of the Reflection Equation algebras and the braided Yangians, associated with all even skew-invertible involutive and Hecke symmetries. By using the Cayley-Hamilton identities for these matrices, we show that they are similar to their canonical forms in the sense of Chervov and Talalaev (J Math Sci (NY) 158:904-911, 2008).
[Anatomo-functional changes in the prostate and seminal vesicles with aging].
Mantovani, F; Mastromarino, G; Colombo, F; Canclini, L; Fenice, O
1993-10-01
The anatomo-functional modifications of the prostate and the seminal pathways during the genital apparatus aging, (prostatic hyperplasia and hypotrophy of the seminal pathways and testis), are caused by hormonal modifications (inconstant increase of the gonadotropins LH-FSH, decrease of the peripheric utilization of testosterone, alterations of the adrenal secretion), by anatomical involutions (degenerations of the glandular, stromal and vascular components).
A coaxial-output capacitor-loaded annular pulse forming line.
Li, Rui; Li, Yongdong; Su, Jiancang; Yu, Binxiong; Xu, Xiudong; Zhao, Liang; Cheng, Jie; Zeng, Bo
2018-04-01
A coaxial-output capacitor-loaded annular pulse forming line (PFL) is developed in order to reduce the flat top fluctuation amplitude of the forming quasi-square pulse and improve the quality of the pulse waveform produced by a Tesla-pulse forming network (PFN) type pulse generator. A single module composed of three involute dual-plate PFNs is designed, with a characteristic impedance of 2.44 Ω, an electrical length of 15 ns, and a sustaining voltage of 60 kV. The three involute dual-plate PFNs connected in parallel have the same impedance and electrical length. Due to the existed small inductance and capacitance per unit length in each involute dual-plate PFN, the upper cut-off frequency of the PFN is increased. As a result, the entire annular PFL has better high-frequency response capability. Meanwhile, the three dual-plate PFNs discharge in parallel, which is much closer to the coaxial output. The series connecting inductance between adjacent two modules is significantly reduced when the annular PFL modules are connected in series. The pulse waveform distortion is reduced when the pulse transfers along the modules. Finally, the shielding electrode structure is applied on both sides of the module. The electromagnetic field is restricted in the module when a single module discharges, and the electromagnetic coupling between the multi-stage annular PFLs is eliminated. Based on the principle of impedance matching between the multi-stage annular PFL and the coaxial PFL, the structural optimization design of a mixed PFL in a Tesla type pulse generator is completed with the transient field-circuit co-simulation method. The multi-stage annular PFL consists of 18 stage annular PFL modules in series, with the characteristic impedance of 44 Ω, the electrical length of 15 ns, and the sustaining voltage of 1 MV. The mixed PFL can generate quasi-square electrical pulses with a pulse width of 43 ns, and the fluctuation ratio of the pulse flat top is less than 8% when the pulse rise time is about 5 ns.
A coaxial-output capacitor-loaded annular pulse forming line
NASA Astrophysics Data System (ADS)
Li, Rui; Li, Yongdong; Su, Jiancang; Yu, Binxiong; Xu, Xiudong; Zhao, Liang; Cheng, Jie; Zeng, Bo
2018-04-01
A coaxial-output capacitor-loaded annular pulse forming line (PFL) is developed in order to reduce the flat top fluctuation amplitude of the forming quasi-square pulse and improve the quality of the pulse waveform produced by a Tesla-pulse forming network (PFN) type pulse generator. A single module composed of three involute dual-plate PFNs is designed, with a characteristic impedance of 2.44 Ω, an electrical length of 15 ns, and a sustaining voltage of 60 kV. The three involute dual-plate PFNs connected in parallel have the same impedance and electrical length. Due to the existed small inductance and capacitance per unit length in each involute dual-plate PFN, the upper cut-off frequency of the PFN is increased. As a result, the entire annular PFL has better high-frequency response capability. Meanwhile, the three dual-plate PFNs discharge in parallel, which is much closer to the coaxial output. The series connecting inductance between adjacent two modules is significantly reduced when the annular PFL modules are connected in series. The pulse waveform distortion is reduced when the pulse transfers along the modules. Finally, the shielding electrode structure is applied on both sides of the module. The electromagnetic field is restricted in the module when a single module discharges, and the electromagnetic coupling between the multi-stage annular PFLs is eliminated. Based on the principle of impedance matching between the multi-stage annular PFL and the coaxial PFL, the structural optimization design of a mixed PFL in a Tesla type pulse generator is completed with the transient field-circuit co-simulation method. The multi-stage annular PFL consists of 18 stage annular PFL modules in series, with the characteristic impedance of 44 Ω, the electrical length of 15 ns, and the sustaining voltage of 1 MV. The mixed PFL can generate quasi-square electrical pulses with a pulse width of 43 ns, and the fluctuation ratio of the pulse flat top is less than 8% when the pulse rise time is about 5 ns.
Kolozsvari, Rudolf; Galajda, Zoltan; Ungvari, Tamas; Szabo, Gabor; Racz, Ildikó; Szerafin, Tamás; Herzfeld, István; Edes, István; Peterffy, Arpad; Koszegi, Zsolt
2012-01-30
The left internal mammary artery (LIMA) is the choice for grafting of the left anterior descending coronary artery (LAD). One possible mechanism of the rare graft failure involve the presence of competitive flow. 105 patients who had undergone coronary bypass grafting between 1998 and 2000 were included in this observational study. The recatheterizations were performed 28 months after the operations. The rate of patency the LIMA grafts was determined, and the cases with graft failure were analyzed. The LIMA graft was patent in 99 patients (94%). Six patients (6%) exhibited diffuse involution of the graft (string sign). The string sign was always associated with competitive flow as the basis of the LIMA graft involution. In one case quantitative re-evaluation of the preoperative coronary angiography revealed merely less than 50% diameter stenosis on the LAD with a nonligated side-branch of the LIMA. At recatheterization in two patients the pressure wire measurements demonstrated only a non-significant decrease of the fractional flow reserve (0.83 and 0.89), despite the 53% and 57% diameter stenosis in the angiogram. Another patient displayeda significant regression of the LAD lesion between the pre- and postoperative coronary angiography (from 76% to 44%) as the cause of the development of the competitive flow. In one instance, a radial artery graft on the LAD during a redo bypass operation resulted in competitive flow in the radial graft due to the greater diameter than that of the LIMA. In a further patient, competitive flow developed from a short sequential part of the LIMA graft between the nonsignificantly stenosed diagonal branch and the LAD, with involution of the main part of the graft to the diagonal branch. The most common cause of the development of the string sign of a LIMA graft due to competitive flow is overassessment of the lesion of the LAD. Regression of a previous lesion or some other neighboring graft can also cause the phenomenon.
Differential neural circuitry and self-interest in real vs hypothetical moral decisions
Dalgleish, Tim; Thompson, Russell; Evans, Davy; Schweizer, Susanne; Mobbs, Dean
2012-01-01
Classic social psychology studies demonstrate that people can behave in ways that contradict their intentions—especially within the moral domain. We measured brain activity while subjects decided between financial self-benefit (earning money) and preventing physical harm (applying an electric shock) to a confederate under both real and hypothetical conditions. We found a shared neural network associated with empathic concern for both types of decisions. However, hypothetical and real moral decisions also recruited distinct neural circuitry: hypothetical moral decisions mapped closely onto the imagination network, while real moral decisions elicited activity in the bilateral amygdala and anterior cingulate—areas essential for social and affective processes. Moreover, during real moral decision-making, distinct regions of the prefrontal cortex (PFC) determined whether subjects make selfish or pro-social moral choices. Together, these results reveal not only differential neural mechanisms for real and hypothetical moral decisions but also that the nature of real moral decisions can be predicted by dissociable networks within the PFC. PMID:22711879
Differentiation, Resistance and Courage: At Work in the Infant School
ERIC Educational Resources Information Center
Dixon, Annabelle
2013-01-01
It is self-evident that, given a group of very active young children and four walls within which to contain them, certain decisions have to be made fairly rapidly: what happens, where it happens, and when seem to be the most obviously pressing. When and how does differentiation come into play? Is it only when making decisions about grouping the…
1989-01-01
The angiogenic factor, basic fibroblast growth factor (FGF), either stimulates endothelial cell growth or promotes capillary differentiation depending upon the microenvironment in which it acts. Analysis of various in vitro models of spontaneous angiogenesis, in combination with time-lapse cinematography, demonstrated that capillary tube formation was greatly facilitated by promoting multicellular retraction and cell elevation above the surface of the rigid culture dish or by culturing endothelial cells on malleable extracellular matrix (ECM) substrata. These observations suggested to us that mechanical (i.e., tension-dependent) interactions between endothelial cells and ECM may serve to regulate capillary development. To test this hypothesis, FGF-stimulated endothelial cells were grown in chemically defined medium on bacteriological (nonadhesive) dishes that were precoated with different densities of fibronectin. Extensive cell spreading and growth were promoted by fibronectin coating densities that were highly adhesive (greater than 500 ng/cm2), whereas cell rounding, detachment, and loss of viability were observed on dishes coated with low fibronectin concentrations (less than 100 ng/cm2). Intermediate fibronectin coating densities (100-500 ng/cm2) promoted cell extension, but they could not completely resist cell tractional forces. Partial retraction of multicellular aggregates resulted in cell shortening, cessation of growth, and formation of branching tubular networks within 24-48 h. Multicellular retraction and subsequent tube formation also could be elicited on highly adhesive dishes by overcoming the mechanical resistance of the substratum using higher cell plating numbers. Dishes coated with varying concentrations of type IV collagen or gelatin produced similar results. These results suggest that ECM components may act locally to regulate the growth and pattern- regulating actions of soluble FGF based upon their ability to resist cell-generated mechanical loads. Thus, we propose that FGF-stimulated endothelial cells may be "switched" between growth, differentiation, and involution modes during angiogenesis by altering the adhesivity or mechanical integrity of their ECM. PMID:2473081
On the Inverse Mapping of the Formal Symplectic Groupoid of a Deformation Quantization
NASA Astrophysics Data System (ADS)
Karabegov, Alexander V.
2004-10-01
To each natural star product on a Poisson manifold $M$ we associate an antisymplectic involutive automorphism of the formal neighborhood of the zero section of the cotangent bundle of $M$. If $M$ is symplectic, this mapping is shown to be the inverse mapping of the formal symplectic groupoid of the star product. The construction of the inverse mapping involves modular automorphisms of the star product.
[Cervical congenital hemangioma: diagnosis and management difficulties].
Clay, J-C; Bourgain, A; Chaffiotte, C; Brevière, G; Pellerin, P; Deruelle, P
2009-01-01
Rapidly involuting congenital haemangioma (RICH) is a rare vascular tumour whose antenatal diagnosis is difficult. During ultrasound examination at 32nd weeks' gestation, a voluminous heterogeneous cephalic lesion was discovered that could be a haemangioma or a teratoma. A caesarean delivery was performed. The tumour was removed directly after birth. The pathology examination concluded on a RICH. Antenatal, prepartum and postnatal management are not consensual and must consider the lesion size.
Knorre, P
1976-01-01
In the third stage of labour we must expect an increase of blood lost and placental retentions after preceded interruption. An accumulation of manual detaching of placenta we ascertained for preceded abortion only. In the childbed we found an certained increase of disturbances in uterine involution. We think, that some consequences for medical care in pregnancies, following abortion and interruption, are very important.
FOXOs attenuate bone formation by suppressing Wnt signaling
Iyer, Srividhya; Ambrogini, Elena; Bartell, Shoshana M.; Han, Li; Roberson, Paula K.; de Cabo, Rafael; Jilka, Robert L.; Weinstein, Robert S.; O’Brien, Charles A.; Manolagas, Stavros C.; Almeida, Maria
2013-01-01
Wnt/β-catenin/TCF signaling stimulates bone formation and suppresses adipogenesis. The hallmarks of skeletal involution with age, on the other hand, are decreased bone formation and increased bone marrow adiposity. These changes are associated with increased oxidative stress and decreased growth factor production, which activate members of the FOXO family of transcription factors. FOXOs in turn attenuate Wnt/β-catenin signaling by diverting β-catenin from TCF- to FOXO-mediated transcription. We show herein that mice lacking Foxo1, -3, and -4 in bipotential progenitors of osteoblast and adipocytes (expressing Osterix1) exhibited increased osteoblast number and high bone mass that was maintained in old age as well as decreased adiposity in the aged bone marrow. The increased bone mass in the Foxo-deficient mice was accounted for by increased proliferation of osteoprogenitor cells and bone formation resulting from upregulation of Wnt/β-catenin signaling and cyclin D1 expression, but not changes in redox balance. Consistent with this mechanism, β-catenin deletion in Foxo null cells abrogated both the increased cyclin D1 expression and proliferation. The elucidation of a restraining effect of FOXOs on Wnt signaling in bipotential progenitors suggests that FOXO activation by accumulation of age-associated cellular stressors may be a seminal pathogenetic mechanism in the development of involutional osteoporosis. PMID:23867625
Extraction of collagenase from the involuting rat uterus.
Weeks, J G; Halme, J; Woessner, J F
1976-08-12
Collagenase (EC 3.4.24.3) activity can be measured directly in homogenates of the involuting rat uterus. Latent forms of collagenase are activated by a brief exposure to trypsin; trypsin activity is then blocked with soybean trypsin inhibitor. Homogenizing conditions have been developed that permit 90-95% recovery of the total active and latent collagenase activity in a 6000 X g pellet, where it is presumably bound to its collagen substrate. This insoluble activity can then be extracted by heating to 60 degrees C for 4 min in 0.04 M Tris - HCl buffer, pH 7.5, containing 0.1 M CaCl2. Methods are presented for the estimation of the recovery of collagenase in the extracts; this approximates 65-70% of the total. Small amounts of activity can also be extracted from rat liver and kidney. This extraction procedure should be of use in purifying collagenase without culturing the enzyme-producing tissue and in the direct assay of tissue collagenase activity. The activity extracted from rat uterus has been proven to be collagenase by its characteristic pattern of collagen breakdown products on disc electrophoresis and by the split of tropocollagen at interband 41 as shown by electron microscopy of reconstituted fragments. The activity is inhibited by EDTA, and this inhibition is not reversed by calcium or zinc ions.
[Hemangiomas and vascular malformations of the head and neck].
Hassmann-Poznańska, Elibieta; Kurzyna, Agnieszka
2006-01-01
This paper presents the review of current knowledge regarding vascular lesions of the head and neck. For many years the term hemangioma was used to describe all vascular lesions. Mulliken and Glowacki classified congenital vascular lesions and recognized two distinct entities, hemangiomas-vascular tumors and vascular malformations. Hemangiomas are usually not present at birth, proliferate during first year of life and then involute. They are composed of proliferating endothelial cells. Vascular malformations are always present at birth although not always apparent, increase slowly in size throughout whole life and never involute. They enlarge by hypertrophy of malformed vessels. Vascular malformations can be further subdivided according to the type of involved vessels as arterial, arteriovenous, venous, capillary or lymphatic. Accurate diagnosis of hemangiomas and vascular malformations remains a challenge for physicians. Although majority of hemangiomas are self limiting lesions some of them may develop complications such as; ulceration, airway obstruction, ophthalmic complications, psychosocial consequences. Segmental hemangiomas are associated with the risk of structural anomalies such as those that occur in PHACE syndrome. Clinical presentation and forms of treatment of various forms of vascular malformations are presented. Vascular malformations have to be treated according to their histopathology and location, as well as their hemodynamic features shown by radiological examinations.
Jamroz, Ewa; Głuszkiewicz, Ewa; Madziara, Wojciech; Kiełtyka, Aleksandra
2011-01-01
Opsoclonus-myoclonus syndrome, also named Myoclonic Encephalopathy of Infants, Opsoclonus- Myoclonus Ataxia, Dancing Eyes - Dancing Feet Syndrome, Dancing Eyes Syndrome, Kinsbourne syndrome, is a rare, paraneoplastic or possibly post-viral chronic neurological disorder. The age of presentation ranges from 6 months to 3 years. In 50% of affected children the syndrome is associated with an underlying occult or clinically apparent neuroblastoma. In most patients the tumour is localized, small and well differentiated, with no NMYC gene copy number amplification. The syndrome may also occur after tumour resection or at relapse. The opsoclonus-myoclonus syndrome can occur in children without neuroblastoma, in such idiopathiccases, the onset of neurological symptoms is related to infection. It is assumed, that in idiopathic cases the syndrome could have developed in the course of neuroblastoma which had undergone a complete spontaneous regression. The most characteristic clinical features of opsoclonus-myoclonus syndrome are: opsoclonus, myoclonus, ataxia, irritability, mutism and sleep disturbances. The disease course is usually long-term with episodes of remission and relapses. Approximately 80% of children with opsoclonus-myoclonus syndrome suffer from mild to severe neurological handicaps, mainly cognitive impairment. The authors present a 2-year old boy with opsoclonus-myoclonus syndrome preceded by involution of prenatally documented retroperitoneal area tumour.
Pluripotency factors in embryonic stem cells regulate differentiation into germ layers.
Thomson, Matt; Liu, Siyuan John; Zou, Ling-Nan; Smith, Zack; Meissner, Alexander; Ramanathan, Sharad
2011-06-10
Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to a differentiated cell state. Here, we asked how mouse embryonic stem cells (ESCs) leave the pluripotent state and choose between germ layer fates. By analyzing the dynamics of the transcriptional circuit that maintains pluripotency, we found that Oct4 and Sox2, proteins that maintain ESC identity, also orchestrate germ layer fate selection. Oct4 suppresses neural ectodermal differentiation and promotes mesendodermal differentiation; Sox2 inhibits mesendodermal differentiation and promotes neural ectodermal differentiation. Differentiation signals continuously and asymmetrically modulate Oct4 and Sox2 protein levels, altering their binding pattern in the genome, and leading to cell fate choice. The same factors that maintain pluripotency thus also integrate external signals and control lineage selection. Our study provides a framework for understanding how complex transcription factor networks control cell fate decisions in progenitor cells. Copyright © 2011 Elsevier Inc. All rights reserved.
Effects of trial complexity on decision making.
Horowitz, I A; ForsterLee, L; Brolly, I
1996-12-01
The ability of a civil jury to render fair and rational decisions in complex trials has been questioned. However, the nature, dimensions, and effects of trial complexity on decision making have rarely been addressed. In this research, jury-eligible adults saw a videotape of a complex civil trial that varied in information load and complexity of the language of the witnesses. Information load and complexity differentially affected liability and compensatory decisions. An increase in the number of plaintiffs decreased blameworthiness assigned to the defendant despite contrary evidence and amount of probative evidence processed. Complex language did not affect memory but did affect jurors' ability to appropriately compensate differentially worthy plaintiffs. Jurors assigned compensatory awards commensurate with the plaintiffs' injuries only under low-load and less complex language conditions.
T Cell LEGO: Identifying the Master Builders and What They Do.
Li, Jasmine; Turner, Stephen J
2018-02-20
Understanding how cell fate decisions are made during cellular differentiation and the mechanisms that drive them is a holy grail of cell biology. In this issue of Immunity, Hu et al. (2018) and Johnson et al. (2018) demonstrate that key transcriptional regulators and global changes in nuclear architecture underlie differentiation decisions during T cell development. Copyright © 2018 Elsevier Inc. All rights reserved.
Shynlova, Oksana; Tsui, Prudence; Dorogin, Anna; Langille, B Lowell; Lye, Stephen J
2007-04-01
While the insulin-like growth factor (IGF) system is known to regulate uterine function during the estrous cycle, there are limited data on its role in myometrial growth and development during pregnancy. To address this issue, we defined the expression of the Igf hormones (1 and 2), their binding proteins (Igfbp 1-6), and Igf1r receptor genes in pregnant, laboring, and postpartum rat myometrium by real-time PCR. IGF family genes were differentially expressed throughout gestation. Igf1 and Igfbp1 mRNA levels were upregulated during proliferative phase (Days 6-12) of rat gestation. Igfbp3 gene expression also was elevated in proliferating smooth muscle cells (SMCs) and was highest at the time of transition between proliferative and synthetic phases (Days 12-15). Igfbp6 gene expression profile paralleled plasma progesterone (P4) concentrations, peaking during the synthetic phase (Days 17-19) and decreasing thereafter. Administration of P4 at late pregnancy (starting from Day 20) to maintain elevated plasma P4 concentrations blocked the onset of labor and prevented the fall in Igfbp6 mRNA levels. In contrast, the treatment of pregnant rats with the P4 receptor antagonist RU486 on Day 19 induced preterm labor and the premature decrease of Igfbp6 gene expression. Igfbp2 gene expression was transiently upregulated during the contractile phase of gestation (Days 21-23) solely in the gravid horn of unilaterally pregnant rats, but it was not affected in P4- or RU486-treated animals, supporting a role for mechanical stretch imposed by the growing fetuses. Igfbp5 gene was induced during postpartum involution. Our results suggest the importance of the IGF system in phenotypic and functional changes of myometrial SMCs throughout gestation in preparation for labor.
Anguiano, B; Rojas-Huidobro, R; Delgado, G; Aceves, C
2004-11-01
Peripartum is a crucial period for mammary gland final differentiation and the onset of lactation. Although the 'trigger' for lactogenesis depends on several hormones, a key factor is the peripartum prolactin (PRL) pulse whose deletion results in a failure to initiate milk production. Other hormones having a critical role during this period but exerting a contrary effect are the thyronines. A transitory hypothyroidism occurs at peripartum in serum and several other extrathyroidal tissues, whereas the induction of hyperthyroidism during late pregnancy is associated with the absence of lactation after delivery. We analyzed the mammary gland during pregnancy and lactation for: (a) the type and amount of thyroid receptors (TRs), (b) the local triiodothyronine (T3) generation catalyzed by type I deiodinase (Dio1), (c) the Dio1 response to norepinephrine (NE) and (d) the effect on Dio1 and TRs of blocking the PRL pulse at peripartum. Our data showed that during pregnancy the mammary gland contains Dio1 in low amounts associated with the highest expression of TRalpha1; whereas during lactation the gland shows high levels of both Dio1 and TRalpha1. However, at peripartum, both TRs and Dio1 decrease, and Dio1 becomes refractory to NE. This refractoriness disappears when the PRL pulse is blocked by the dopamine agonist bromocriptine. This blockade is also accompanied by a significant decrease in cyclin D1 expression. Our data suggested that the peripartum PRL pulse is part of a protective mechanism against precocious differentiation and/or premature involution of the alveolar epithelium due to T3 overexposure.
Antibiotics for coughing in general practice: a qualitative decision analysis.
Coenen, S; Van Royen, P; Vermeire, E; Hermann, I; Denekens, J
2000-10-01
In family practice, medical decisions are prompted most often by complaints about coughing. There is no single yardstick for the differential diagnosis of respiratory tract infections (RTIs). In 80% of cases, the excessive use of antibiotics in the treatment of RTIs is caused by the prescription behaviour of GPs. Our aim was to explicate GPs' diagnostic (and therapeutic) decisions regarding adult patients who consult them with complaints about coughing, and to investigate what determines decision making. Exploratory, descriptive focus groups were held with GPs. Hypotheses were generated on the basis of 'qualitative content analysis'. Results. Twenty-four GPs participated in four semi-structured group discussions. In order to differentiate RTIs from other possible diagnoses, less likely diagnoses were not ruled out explicitly. In the case of suspected RTI, there was a low degree of certainty in the differentiation between RTIs (e.g. between bronchitis and pneumonia). Clinical signs and symptoms, which determine the probability of disease, often left GPs with reasonable diagnostic doubt. In the end, the decision whether or not to prescribe antibiotics was taken. GPs' prescription behaviour was also determined by doctor- and patient-related factors (e.g. having missed pneumonia once, patient expectations). The 'chagrin factor' explains why these factors lead to a shift in the action threshold, in favour of antibiotics. This inductive research method enabled the generation of meaningful hypotheses regarding the complex decision processes pursued by GPs. The authors are developing an educational intervention that builds on these findings, focusing on the prescribing decision.
Discovery of a New Cellular Motion and Its Relevance to Breast Cancer and Involution
2014-02-01
motion (CAMo), live cell imaging , confocal microscopy Overall Project Summary: During this first year of funding we have concentrated our work to...cell types in 3D cultures and in vivo. Subtask 1.1a: Real time live cell imaging using confocal microscopy will be used to image cellular movement...exciting as they are important steps in understanding behavior of normal myoepithelial cells using live cell imaging in physiologically
USDA-ARS?s Scientific Manuscript database
Plasma membrane Ca2+-ATPase 2 (PMCA2) knockout mice showed that ~ 60 % of calcium in milk is transported across the mammary cells apical membrane by PMCA2. The remaining milk calcium is thought to arrive via the secretory pathway through the actions of secretory pathway Ca2+-ATPase’s 1 and/or 2 (SP...
Identification of Sonic Hedgehog-Induced Stromal Factors That Stimulate Prostate Tumor Growth
2006-11-01
LN -Shh xenograft tumors is unabated after castration of the host mouse. However, castration of mice bearing LNCaP + Gli3-/- UGSM bi-clonal...canonical xenograft undergoes involution and growth arrest, growth of LN -Shh xenograft tumors is unabated after castration. As we have shown...signalingindependent of Shh ligand in tumor stroma accelerates tumor growth. We have identified potential stromal Shh target genes in xenograft tumors and have begun
2011-06-01
provokes lung metastasis. (5) Both STAT3 and SLC5A8 knockout showed the similar phenotype, like mammary gland involution delay, mastitis and...100 ng/ml cholera toxin, 0.01mg/ml bovine insulin and 500 ng/ml hydrocortisone. HBL100 cells was grown in McCoy 5A with 10% FBS. MCF7 and BT20
Combining universal and odd RR axions for aligned natural inflation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, Xin; Li, Tianjun; Shukla, Pramod, E-mail: xingao@vt.edu, E-mail: tli@itp.ac.cn, E-mail: pkshukla@to.infn.it
2014-10-01
We successfully embed the Kim-Nilles-Peloso (KNP) alignment mechanism for enhancing the axion decay constant in the context of large volume type IIB orientifolds. The flat direction is generated in the plane of (C{sub 0}-C{sub 2}) axions corresponding to the involutively even universal axion C{sub 0} and odd axion C{sub 2}, respectively. The moduli stabilization with large volume scheme has been established as well.
Role of Autophagy in Keratin Homeostasis in Breast Cancer
2014-03-01
weaning of pups, involution commences where the mammary gland reverts to its pre- pregnant state (Brisken and O’Malley, 2010). Pubertal mouse mammary...estrogen, progesterone and prolactin and local growth factors such as Insulin growth factor-1 (IGF-1), Hepatocyte growth factor (HGF), and Fibroblast growth...lentiviral infection. Following infection, resistant colonies were allowed to emerge and independent colonies
Mammary Cancer and Activation of Transposable Elements
2015-03-01
EGFP). No other cell type in the mammary fat pad was observed to express EGFP. Wholemount and FACS analyses of mammary fat pads after involution from...were sacrificed for PI-MEC isolation in groups of up to 4 control or cancer-prone uniparous or triparous females. Both 4 th mammary fat pads were...to unknown reason (n=46), and smaller numbers of animals with various conditions (malocclusion, head tilt , dystocia, respiratory complaints, identity
Constraint reasoning in deep biomedical models.
Cruz, Jorge; Barahona, Pedro
2005-05-01
Deep biomedical models are often expressed by means of differential equations. Despite their expressive power, they are difficult to reason about and make decisions, given their non-linearity and the important effects that the uncertainty on data may cause. The objective of this work is to propose a constraint reasoning framework to support safe decisions based on deep biomedical models. The methods used in our approach include the generic constraint propagation techniques for reducing the bounds of uncertainty of the numerical variables complemented with new constraint reasoning techniques that we developed to handle differential equations. The results of our approach are illustrated in biomedical models for the diagnosis of diabetes, tuning of drug design and epidemiology where it was a valuable decision-supporting tool notwithstanding the uncertainty on data. The main conclusion that follows from the results is that, in biomedical decision support, constraint reasoning may be a worthwhile alternative to traditional simulation methods, especially when safe decisions are required.
Do neurocognitive deficits in decision making differentiate conduct disorder subtypes?
Fanti, Kostas A; Kimonis, Eva R; Hadjicharalambous, Maria-Zoe; Steinberg, Laurence
2016-09-01
The present study aimed to test whether neurocognitive deficits involved in decision making underlie subtypes of conduct-disorder (CD) differentiated on the basis of callous-unemotional (CU) traits. Eighty-five participants (M age = 10.94 years) were selected from a sample of 1200 children based on repeated assessment of CD and CU traits. Participants completed a multi-method battery of well-validated measures of risky decision making and associated constructs of selective attention and future orientation (Stroop, Stoplight, and Delay-Discounting Tasks). Findings indicated that impaired decision making, selective attention, and future orientation contribute to the antisocial presentations displayed by children with CD, irrespective of level of CU traits. Youth high on CU traits without CD showed less risky decision making, as indicated by their performance on the Stoplight laboratory task, than those high on both CD and CU traits, suggesting a potential protective factor against the development of antisocial behavior.
NASA Astrophysics Data System (ADS)
Li, Hong; Zhang, Li; Jiao, Yong-Chang
2016-07-01
This paper presents an interactive approach based on a discrete differential evolution algorithm to solve a class of integer bilevel programming problems, in which integer decision variables are controlled by an upper-level decision maker and real-value or continuous decision variables are controlled by a lower-level decision maker. Using the Karush--Kuhn-Tucker optimality conditions in the lower-level programming, the original discrete bilevel formulation can be converted into a discrete single-level nonlinear programming problem with the complementarity constraints, and then the smoothing technique is applied to deal with the complementarity constraints. Finally, a discrete single-level nonlinear programming problem is obtained, and solved by an interactive approach. In each iteration, for each given upper-level discrete variable, a system of nonlinear equations including the lower-level variables and Lagrange multipliers is solved first, and then a discrete nonlinear programming problem only with inequality constraints is handled by using a discrete differential evolution algorithm. Simulation results show the effectiveness of the proposed approach.
Odic, Darko
2017-01-01
Leibovich et al. suggest that congruency effects in number perception (biases towards smaller, denser, etc., dots) are evidence for the number's dependence on these dimensions. I argue that they fail to differentiate between effects at three distinct levels of number perception - encoding, representations, and decision making - and that differentiating between these allows the number to be independent from, but correlated with, non-numeric dimensions.
Van Petegem, Stijn; Beyers, Wim; Brenning, Katrijn; Vansteenkiste, Maarten
2013-12-01
The present investigation focuses on the associations between adolescents' insecure attachment styles (i.e., anxiety and avoidance) and their autonomous functioning in family decision making. In line with recent insights in the construct of adolescent autonomy, we combined two perspectives on autonomy, differentiating between the degree of independent versus dependent functioning and the self-endorsed and pressuring motives underlying (in)dependent functioning. A longitudinal sample of 327 adolescents (age range = 13-20 years; 64 % girls) completed questionnaires on attachment to the mother and father and on both autonomy operationalisations on two measurement moments spanning a 1-year interval. Structural equation modeling showed that attachment avoidance generally was unrelated to the degree of independent decision making and the motives underlying independent decision making, but related to more pressuring motives for dependent decision making. Anxiety, on the other hand, was associated with a lower degree of independent decision making as well as with more pressuring motives for both independent and dependent decision making. Cross-lagged paths were generally in line with these findings. Theoretical implications are outlined in the discussion.
Grinenko, Tatyana; Eugster, Anne; Thielecke, Lars; Ramasz, Beáta; Krüger, Anja; Dietz, Sevina; Glauche, Ingmar; Gerbaulet, Alexander; von Bonin, Malte; Basak, Onur; Clevers, Hans; Chavakis, Triantafyllos; Wielockx, Ben
2018-05-15
Hematopoietic stem cells (HSCs) continuously replenish all blood cell types through a series of differentiation steps and repeated cell divisions that involve the generation of lineage-committed progenitors. However, whether cell division in HSCs precedes differentiation is unclear. To this end, we used an HSC cell-tracing approach and Ki67 RFP knock-in mice, in a non-conditioned transplantation model, to assess divisional history, cell cycle progression, and differentiation of adult HSCs. Our results reveal that HSCs are able to differentiate into restricted progenitors, especially common myeloid, megakaryocyte-erythroid and pre-megakaryocyte progenitors, without undergoing cell division and even before entering the S phase of the cell cycle. Additionally, the phenotype of the undivided but differentiated progenitors correlated with the expression of lineage-specific genes and loss of multipotency. Thus HSC fate decisions can be uncoupled from physical cell division. These results facilitate a better understanding of the mechanisms that control fate decisions in hematopoietic cells.
1984-07-01
r N 2 sin y (D-345) A7 0 -r- 1 rc1 N3 1 cos y (D-346) A71 cosr - 86) + a s, sin (B -01 (D- 347 ) 118 ’ .+ + ’ • ., , , ’ , ,• i...Note that this is also now independent of entrance or exit condition. Nowo F23 (eq Dl-520) is substituted into the above expression. This leads to: 02
Quantum mechanics from an equivalence principle
DOE Office of Scientific and Technical Information (OSTI.GOV)
Faraggi, A.E.; Matone, M.
1997-05-15
The authors show that requiring diffeomorphic equivalence for one-dimensional stationary states implies that the reduced action S{sub 0} satisfies the quantum Hamilton-Jacobi equation with the Planck constant playing the role of a covariantizing parameter. The construction shows the existence of a fundamental initial condition which is strictly related to the Moebius symmetry of the Legendre transform and to its involutive character. The universal nature of the initial condition implies the Schroedinger equation in any dimension.
Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland
2014-09-01
analyses. To assess expression of Ltbp1 in breast cancer we began by mining in silico data using database available online specifically Kaplan-Meier... Dermatology , New York University School of Medicine, 550 First Ave, New York, NY 10016, USA Full list of author information is available at the end of the...1Department of Cell Biology, New York University School of Medicine, New York, NY, USA. 2The Ronald O Perelman Department of Dermatology , New York
Beltrán-Frutos, E; Seco-Rovira, V; Ferrer, C; Madrid, J F; Sáez, F J; Canteras, M; Pastor, L M
2016-04-01
The aim of this study was to evaluate the cellular changes that occur in the hamster testicular interstitium in two very different physiological situations involving testicular involution: ageing and exposure to a short photoperiod. The animals were divided into an 'age group' with three subgroups - young, adult and old animals - and a 'regressed group' with animals subjected to a short photoperiod. The testicular interstitium was characterised by light and electron microscopy. Interstitial cells were studied histochemically with regard to their proliferation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling (TUNEL+) and testosterone synthetic activity. We identified two types of Leydig cell: Type A cells showed a normal morphology, while Type B cells appeared necrotic. With ageing, pericyte proliferation decreased but there was no variation in the index of TUNEL-positive Leydig cells. In the regressed group, pericyte proliferation was greater and TUNEL-positive cells were not observed in the interstitium. The testicular interstitium suffered few ultrastructural changes during ageing and necrotic Leydig cells were observed. In contrast, an ultrastructural involution of Leydig cells with no necrosis was observed in the regressed group. In conclusion, the testicular interstitium of Mesocricetus auratus showed different cellular changes in the two groups (age and regressed), probably due to the irreversible nature of ageing and the reversible character of changes induced by short photoperiod.
Pai, Vaibhav P.; Hernandez, Laura L.; Stull, Malinda A.; Horseman, Nelson D.
2015-01-01
Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7 receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7 receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7 is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer. PMID:25664318
NASA Astrophysics Data System (ADS)
Abadjiev, Valentin; Abadjieva, Emilia
2016-09-01
Hyperboloid gear drives with face mating gears are used to transform rotations between shafts with non-parallel and non-intersecting axes. A special case of these transmissions are Spiroid1 and Helicon gear drives. The classical gear drives of this type are Archimedean ones. The objective of this study are hyperboloid gear drives with face meshing, when the pinion has threads of conic convolute, Archimedean and involute types, or the pinion has threads of cylindrical convolute, Archimedean and involute types. For simplicity, all three type transmissions with face mating gears and a conic pinion are titled Spiroid and all three type trans- missions with face mating gears and a cylindrical pinion are titled Helicon. Principles of the mathematical modelling of tooth contact synthesis are discussed in Part 1: Basic theoretical and CAD experience of this study. The second part of this article is a brief overview of the innovations and inventions created in this field at the Institute of Mechanics - Bulgarian Academy of Sciences in the last three decades. This study is also dedicated on elaboration of the specialized face gear sets for implementation into bio-robot hand. It is based on the application of 3D software technology, using 3D print for the realization of the physical models of the gear drives.
Efficacy of Oral Etidronate for Skeletal Diseases in Japan
Takeda, Tsuyoshi; Sato, Yoshihiro
2005-01-01
Etidronate is an oral bisphosphonate compound that is known to reduce bone resorption through the inhibition of osteoclastic activity. The efficacy of etidronate for involutional (postmenopausal and senile) and glucocorticoid-induced osteoporosis, as well as that for other skeletal diseases, was reviewed in Japanese patients. Cyclical etidronate treatment (200 mg or 400 mg/day for 2 weeks about every 3 months) increases the lumbar bone mineral density (BMD) in patients with involutional osteoporosis and prevents incident vertebral fractures in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic patients after stroke are prevented, and the lumbar BMD is possibly increased, preventing fragile fractures in adult patients with osteogenesis imperfecta type I. Furthermore, proximal bone resorption around the femoral stem is reduced and some complications may be prevented in patients who undergo cementless total hip arthroplasty. Oral etidronate treatment may also help to transiently relieve metastatic cancer bone pain followed by a decrease in abnormally raised bone resorption in patients with painful bone metastases from primary cancer sites, such as the lung, breast and prostate. Thus, oral etidronate treatment is suggested to be efficacious for osteoporosis, as well as other skeletal diseases associated with increased bone resorption, in Japanese patients. Randomized controlled trials needed to be conducted on a large number of patients to confirm these effects. PMID:15988801
Differentiating Writing Instruction: Meeting the Diverse Needs of Authors in a Classroom
ERIC Educational Resources Information Center
Shea, Mary
2015-01-01
This article outlines a rational for responsive, differentiated writing instruction that targets students' identified needs with respect to various dimensions of the writing process. Discussed is a cycle that requires ongoing assessment, instructional decision-making, responsive, differentiated instruction, guided practice, and assessment.…
Sharifi, Reza; Hoedemaker, Martina
2009-01-01
The objective of this retrospective field study was to associate the type and smell of discharge, the size of the uterus, the ovarian and treatment status, and the time to diagnosis of animals with chronic clinical endometritis (CCE) with the incidence of ovarian cysts and with a marked loss in body condition in German Holstein Friesian cows. Two hundred and sixty-four cows diagnosed with CCE from day 14 to day 42 postpartum participated in this study. In addition, 100 days milk production and the parity of the animals were included in the analysis. With the use of logistic regression, a purulent vaginal discharge (≥ 50% pus), the decision not to treat the animals for CCE and a high 100 days milk production proved to be significant factors for the incidence of ovarian cysts. Additionally, the type of discharge showed interactions with the parity and the smell of the discharge, as more animals with fetid and purulent discharge and more animals in the first lactation with a purulent discharge developed ovarian cysts. A high milk production and the parity showed associations with an excessive body condition score loss. Additionally, more animals with a diagnosis of an oversized uterus in comparison to cows with an early involution experienced a considerable reduction in their nutritional condition. PMID:19934600
ERIC Educational Resources Information Center
Smets, Wouter
2017-01-01
This paper presents a checklist that scaffolds teachers' professional decision-making with regard to differentiated instruction. It discusses the way the concept of differentiated instruction may be applied in an evidence-informed way by presenting a checklist for high-quality differentiated instruction (DI). We tried to tackle the question of how…
Parker, G; McCraw, S; Hadzi-Pavlovic, D
2015-07-15
Studies suggest that differentiating melancholic from non-melancholic depressive disorders is advanced by use of illness course as well as symptom variables but, in practice, potentially differentiating variables are generally positioned as having equal value. Judging that differentiating features are more likely to vary in their signal intensity, we sought to determine the number of features required to effect differentiation and their hierarchical order. The 24-item clinician-rated Sydney Melancholia Prototype Index (SMPI-CR) was completed for 364 unipolar depressed patients. The sample was divided into two cohorts according to the recruitment period. An RPART classification tree analysis identified the most discriminating SMPI items in the development sample of 197 patients, and examined the sensitivity and specificity of the diagnostic decisions, then sought to replicate findings in a validation sample of 169 patients. Independent analyses of putative SMPI items identified only seven items as required to discriminate those with clinically-diagnosed melancholic or non-melancholic depression when the conditions were examined separately. An RPART analysis considering differentiation of melancholic and non-melancholic depression in the total samples retained five of those items in the classification tree, three of which were non-symptom items, and with 92% sensitivity and 80% specificity in the development sample. This reduced item set showed 93% sensitivity and 82% specificity in the validation sample. Our clinical judgment of melancholic or non-melancholic depression may not correspond with the clinical logic employed by other clinicians. Only five SMPI items were required to derive a succinct and efficient decision tree, comprising high sensitivity and specificity in differentiating melancholic and non-melancholic depression. Current study findings provide an empirical model that could enrich clinicians׳ approach to differentiating melancholic and non-melancholic depression. Copyright © 2015 Elsevier B.V. All rights reserved.
ERIC Educational Resources Information Center
Mims, Wyn, M.; Lockley, Jeannie
2017-01-01
A fourth-grade teacher utilized action research in order to make data-driven decisions about reading interventions with her students. The teacher decided on a broad intervention, which was differentiating reading instruction, implemented differentiated instruction, collected data and continuously adjusted interventions based on monitoring data.…
The Role of Personal Ethical Checking in Courageous School Leadership
ERIC Educational Resources Information Center
Buskey, Frederick C.; Pitts, Eric M.
2013-01-01
When school leaders make calculated decisions to deviate from hierarchical or cultural directives and norms, they may be viewed as mavericks or brigands. This paper details a process of ethical checking to help differentiate ethical decisions from more arbitrary or self-serving decisions. The paper examines conflicts inherent in many professional…
The Relationship of Sex Role and Career Factors in Career Decision Making.
ERIC Educational Resources Information Center
Piggott, Tonya; And Others
Although the effects of sex-role socialization factors on career decision-making have received increased attention, little research has assessed the relationship between sex role variables and the factors affecting career decision-making. Differential effects and interactions of sex, sex role orientation, and sex role attitudes on six factors…
Differential Effects of Insular and Ventromedial Prefrontal Cortex Lesions on Risky Decision-Making
ERIC Educational Resources Information Center
Clark, L.; Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.
2008-01-01
The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear…
Decision Accuracy in Computer-Mediated versus Face-to-Face Decision-Making Teams.
Hedlund; Ilgen; Hollenbeck
1998-10-01
Changes in the way organizations are structured and advances in communication technologies are two factors that have altered the conditions under which group decisions are made. Decisions are increasingly made by teams that have a hierarchical structure and whose members have different areas of expertise. In addition, many decisions are no longer made via strictly face-to-face interaction. The present study examines the effects of two modes of communication (face-to-face or computer-mediated) on the accuracy of teams' decisions. The teams are characterized by a hierarchical structure and their members differ in expertise consistent with the framework outlined in the Multilevel Theory of team decision making presented by Hollenbeck, Ilgen, Sego, Hedlund, Major, and Phillips (1995). Sixty-four four-person teams worked for 3 h on a computer simulation interacting either face-to-face (FtF) or over a computer network. The communication mode had mixed effects on team processes in that members of FtF teams were better informed and made recommendations that were more predictive of the correct team decision, but leaders of CM teams were better able to differentiate staff members on the quality of their decisions. Controlling for the negative impact of FtF communication on staff member differentiation increased the beneficial effect of the FtF mode on overall decision making accuracy. Copyright 1998 Academic Press.
Differential short-term memorisation for vocal and instrumental rhythms.
Klyn, Niall A M; Will, Udo; Cheong, Yong-Jeon; Allen, Erin T
2016-07-01
This study explores differential processing of vocal and instrumental rhythms in short-term memory with three decision (same/different judgments) and one reproduction experiment. In the first experiment, memory performance declined for delayed versus immediate recall, with accuracy for the two rhythms being affected differently: Musicians performed better than non-musicians on clapstick but not on vocal rhythms, and musicians were better on vocal rhythms in the same than in the different condition. Results for the second experiment showed that concurrent sub-vocal articulation and finger-tapping differentially affected the two rhythms and same/different decisions, but produced no evidence for articulatory loop involvement in delayed decision tasks. In a third experiment, which tested rhythm reproduction, concurrent sub-vocal articulation decreased memory performance, with a stronger deleterious effect on the reproduction of vocal than of clapstick rhythms. This suggests that the articulatory loop may only be involved in delayed reproduction not in decision tasks. The fourth experiment tested whether differences between filled and empty rhythms (continuous vs. discontinuous sounds) can explain the different memorisation of vocal and clapstick rhythms. Though significant differences were found for empty and filled instrumental rhythms, the differences between vocal and clapstick can only be explained by considering additional voice specific features.
The influence of discrete emotions on judgement and decision-making: a meta-analytic review.
Angie, Amanda D; Connelly, Shane; Waples, Ethan P; Kligyte, Vykinta
2011-12-01
During the past three decades, researchers interested in emotions and cognition have attempted to understand the relationship that affect and emotions have with cognitive outcomes such as judgement and decision-making. Recent research has revealed the importance of examining more discrete emotions, showing that same-valence emotions (e.g., anger and fear) differentially impact judgement and decision-making outcomes. Narrative reviews of the literature (Lerner & Tiedens, 2006 ; Pham, 2007 ) have identified some under-researched topics, but provide a limited synthesis of findings. The purpose of this study was to review the research examining the influence of discrete emotions on judgement and decision-making outcomes and provide an assessment of the observed effects using a meta-analytic approach. Results, overall, show that discrete emotions have moderate to large effects on judgement and decision-making outcomes. However, moderator analyses revealed differential effects for study-design characteristics and emotion-manipulation characteristics by emotion type. Implications are discussed.
STAT5A Regulates the Survival of Mammary Epithelial Cells and the Development of Mammary Cancer
2002-07-01
2000. This manuscript reviewed the known mouse models of human disease generated with the TGFux gene including the work with the TGFct/Stat5aKO. This...AND LOTHAR HENNIGHAUSEN Laboratory of Genetics and Physiology (R.C.H., B.B., L.Z., L.H.), National Institute of Diabetes, Digestive and Kidney Diseases ...pregnancy dams lactogenic stimuli, and that lactation could resume after 6 d often displayed symptoms of mastitis and invasion of the of involution
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stefanczyk, Ludomir, E-mail: stefanczyk_l@wp.pl; Czeczotka, Jaroslaw; Elgalal, Marcin
2011-02-15
The treatment of posttraumatic aneurysms of peripheral arteries using covered stents is increasingly commonplace. We present the case of a 10-year-old girl with a pseudoaneurysm of the subclavian artery complicated by an arteriobronchial fistula with hemorrhaging into the bronchial tree and distal subclavian artery occlusion. Despite the lack of artery patency, endovascular stent graft implantation was successful. Pseudoaneurysm exclusion and involution was achieved, together with a patent implant and maintained collateral circulation patency.
Ultrasonographic monitoring of a spontaneous abortion in an owl monkey (Aotus nancymaae).
Schuler, A Michele; Parks, Virginia L; Abee, Christian R; Scammell, Jonathan G
2007-07-01
This case report describes the ultrasonographic findings during an idiopathic spontaneous abortion in an owl monkey. The female owl monkey presented for a transabdominal ultrasonogram to evaluate her pregnancy. This evaluation is a routine monitoring procedure in our owl monkey breeding colony. Although the fetus and placenta appeared normal at the initial scan, no fetal heartbeat could be detected. We followed the abortion with serial ultrasonographic scans and documented complete involution of the uterus post-abortion.
Biological Function of Plasma Kallikrein in Mammary Gland Stromal Development and Tumor Metastasis
2008-03-01
mammary gland as well as to identify targets of PKal activity during involution. Furthermore, mast cells are required for normal mammary duct branching...litters were generated, and no live homozygous mutant animals were identified . Wild-type and heterozygous mice appeared in nearly all litters, and of...to identify homozygous mutants in utero. F2 litters from heterozygous crosses were analyzed at embryonic day (E) 12, 10.5, 9.5, 8, and 7.5. At E12
1982-11-01
Report) IS. SUPPLEMENTARY NOTES It. KEY WORDS (Contin~ue an reverse aide It neoocemry and Identity by block number) Gear train S&A mechanism M739 fuze...as in the escapement. A simulation run with the dimensions of the M739 safing and arming mechanism showed excellent agreament with experimental...well as all non-impact contact forces. This program was extensively tested for the configuration no. 2 data (fig. 2) of the M739 fuze S&A mechanism
Understanding the Link Between Pregnancy and Breast Cancer
2014-06-01
injected in the mammary glands of nude mice females and 2 groups were generated virgin group and the pregnant group, in which a male was added for mating...to modulate the effect of collagen. A key mediator of involution is the insulin -like growth factor binding protein 5 (IGFBP-5) 6-9. IGFBP-5 is...expressing PAPP-A were used. We found that rIGFBP-5 is resistant to cleavage by PAPP-A in the absence of collagen (Fig. 2f). Upon addition of
Histological variants of cutaneous Kaposi sarcoma
Grayson, Wayne; Pantanowitz, Liron
2008-01-01
This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS) lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage); morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented. PMID:18655700
Lymphoidal involution and delayed homograft rejection in hypoxia-exposed mice.
NASA Technical Reports Server (NTRS)
Kmetz, J. M.; Anthony, A.
1972-01-01
Investigation of the relationship between histologic and cytochemical response patterns of the thymus, spleen, and lymph nodes of mice exposed to moderate hypoxia (380 mm Hg), and study, by histologic analysis, of the effect of hypoxia exposure on the skin homograft reaction used as an index of immunologic potential. The results obtained include the finding that functional changes in lymphatic organs occur during early weeks of hypoxia acclimation and that these changes probably reduce the ability of an animal to react to an immunological challenge.
Chatmethakul, Trassanee; Bhat, Ramachandra; Alkaabi, Maryam; Siddiqui, Abdul; Peevy, Keith; Zayek, Michael
2016-07-01
Multifocal and diffuse infantile hepatic hemangioendotheliomas commonly present with signs of high-output congestive heart failure. In addition, prolonged persistent pulmonary overcirculation eventually leads to the development of pulmonary hypertension at a later age. We report a 2-day old, full-term infant with multifocal, large infantile hepatic hemangioendothelioma, who presented with an early onset of pulmonary hypertension, managed successfully with supportive care and systemic therapy directed toward the involution of infantile hepatic hemangioendothelioma.
Effects of imperfect automation on decision making in a simulated command and control task.
Rovira, Ericka; McGarry, Kathleen; Parasuraman, Raja
2007-02-01
Effects of four types of automation support and two levels of automation reliability were examined. The objective was to examine the differential impact of information and decision automation and to investigate the costs of automation unreliability. Research has shown that imperfect automation can lead to differential effects of stages and levels of automation on human performance. Eighteen participants performed a "sensor to shooter" targeting simulation of command and control. Dependent variables included accuracy and response time of target engagement decisions, secondary task performance, and subjective ratings of mental work-load, trust, and self-confidence. Compared with manual performance, reliable automation significantly reduced decision times. Unreliable automation led to greater cost in decision-making accuracy under the higher automation reliability condition for three different forms of decision automation relative to information automation. At low automation reliability, however, there was a cost in performance for both information and decision automation. The results are consistent with a model of human-automation interaction that requires evaluation of the different stages of information processing to which automation support can be applied. If fully reliable decision automation cannot be guaranteed, designers should provide users with information automation support or other tools that allow for inspection and analysis of raw data.
Neural basis of decision making guided by emotional outcomes
Matsuda, Yoshi-Taka; Fujimura, Tomomi; Ueno, Kenichi; Asamizuya, Takeshi; Suzuki, Chisato; Cheng, Kang; Okanoya, Kazuo; Okada, Masato
2015-01-01
Emotional events resulting from a choice influence an individual's subsequent decision making. Although the relationship between emotion and decision making has been widely discussed, previous studies have mainly investigated decision outcomes that can easily be mapped to reward and punishment, including monetary gain/loss, gustatory stimuli, and pain. These studies regard emotion as a modulator of decision making that can be made rationally in the absence of emotions. In our daily lives, however, we often encounter various emotional events that affect decisions by themselves, and mapping the events to a reward or punishment is often not straightforward. In this study, we investigated the neural substrates of how such emotional decision outcomes affect subsequent decision making. By using functional magnetic resonance imaging (fMRI), we measured brain activities of humans during a stochastic decision-making task in which various emotional pictures were presented as decision outcomes. We found that pleasant pictures differentially activated the midbrain, fusiform gyrus, and parahippocampal gyrus, whereas unpleasant pictures differentially activated the ventral striatum, compared with neutral pictures. We assumed that the emotional decision outcomes affect the subsequent decision by updating the value of the options, a process modeled by reinforcement learning models, and that the brain regions representing the prediction error that drives the reinforcement learning are involved in guiding subsequent decisions. We found that some regions of the striatum and the insula were separately correlated with the prediction error for either pleasant pictures or unpleasant pictures, whereas the precuneus was correlated with prediction errors for both pleasant and unpleasant pictures. PMID:25695644
Neural basis of decision making guided by emotional outcomes.
Katahira, Kentaro; Matsuda, Yoshi-Taka; Fujimura, Tomomi; Ueno, Kenichi; Asamizuya, Takeshi; Suzuki, Chisato; Cheng, Kang; Okanoya, Kazuo; Okada, Masato
2015-05-01
Emotional events resulting from a choice influence an individual's subsequent decision making. Although the relationship between emotion and decision making has been widely discussed, previous studies have mainly investigated decision outcomes that can easily be mapped to reward and punishment, including monetary gain/loss, gustatory stimuli, and pain. These studies regard emotion as a modulator of decision making that can be made rationally in the absence of emotions. In our daily lives, however, we often encounter various emotional events that affect decisions by themselves, and mapping the events to a reward or punishment is often not straightforward. In this study, we investigated the neural substrates of how such emotional decision outcomes affect subsequent decision making. By using functional magnetic resonance imaging (fMRI), we measured brain activities of humans during a stochastic decision-making task in which various emotional pictures were presented as decision outcomes. We found that pleasant pictures differentially activated the midbrain, fusiform gyrus, and parahippocampal gyrus, whereas unpleasant pictures differentially activated the ventral striatum, compared with neutral pictures. We assumed that the emotional decision outcomes affect the subsequent decision by updating the value of the options, a process modeled by reinforcement learning models, and that the brain regions representing the prediction error that drives the reinforcement learning are involved in guiding subsequent decisions. We found that some regions of the striatum and the insula were separately correlated with the prediction error for either pleasant pictures or unpleasant pictures, whereas the precuneus was correlated with prediction errors for both pleasant and unpleasant pictures. Copyright © 2015 the American Physiological Society.
Taouki, Ioanna; Tasiudi, Eve; Lalioti, Maria-Eleni; Kyrousi, Christina; Skavatsou, Eleni; Kaplani, Konstantina; Lygerou, Zoi; Kouvelas, Elias D; Mitsacos, Adamantia; Giompres, Panagiotis; Taraviras, Stavros
2017-08-15
Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. In this article, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6-OHDA hemiparkinsonian mouse model. Our results indicate that, in the absence of Geminin, grafted cells differentiating into dopaminergic neurons were decreased, while an increased number of oligodendrocytes were detected. The number of proliferating multipotent cells was not modified by the absence of Geminin. These findings encourage research related to the impact of Geminin on transplantations for neurodegenerative disorders, as an important molecule in influencing differentiation decisions of the cells composing the graft.
ERIC Educational Resources Information Center
Klapwijk, Eduard T.; Aghajani, Moji; Lelieveld, Gert-Jan; van Lang, Natasja D. J.; Popma, Arne; van der Wee, Nic J. A.; Colins, Olivier F.; Vermeiren, Robert R. J. M.
2017-01-01
Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD…
Li, Chunhe; Wang, Jin
2013-01-01
Cellular reprogramming has been recently intensively studied experimentally. We developed a global potential landscape and kinetic path framework to explore a human stem cell developmental network composed of 52 genes. We uncovered the underlying landscape for the stem cell network with two basins of attractions representing stem and differentiated cell states, quantified and exhibited the high dimensional biological paths for the differentiation and reprogramming process, connecting the stem cell state and differentiated cell state. Both the landscape and non-equilibrium curl flux determine the dynamics of cell differentiation jointly. Flux leads the kinetic paths to be deviated from the steepest descent gradient path, and the corresponding differentiation and reprogramming paths are irreversible. Quantification of paths allows us to find out how the differentiation and reprogramming occur and which important states they go through. We show the developmental process proceeds as moving from the stem cell basin of attraction to the differentiation basin of attraction. The landscape topography characterized by the barrier heights and transition rates quantitatively determine the global stability and kinetic speed of cell fate decision process for development. Through the global sensitivity analysis, we provided some specific predictions for the effects of key genes and regulation connections on the cellular differentiation or reprogramming process. Key links from sensitivity analysis and biological paths can be used to guide the differentiation designs or reprogramming tactics. PMID:23935477
Dynamical crossover in a stochastic model of cell fate decision
NASA Astrophysics Data System (ADS)
Yamaguchi, Hiroki; Kawaguchi, Kyogo; Sagawa, Takahiro
2017-07-01
We study the asymptotic behaviors of stochastic cell fate decision between proliferation and differentiation. We propose a model of a self-replicating Langevin system, where cells choose their fate (i.e., proliferation or differentiation) depending on local cell density. Based on this model, we propose a scenario for multicellular organisms to maintain the density of cells (i.e., homeostasis) through finite-ranged cell-cell interactions. Furthermore, we numerically show that the distribution of the number of descendant cells changes over time, thus unifying the previously proposed two models regarding homeostasis: the critical birth death process and the voter model. Our results provide a general platform for the study of stochastic cell fate decision in terms of nonequilibrium statistical mechanics.
Ilin, Yelena; Choi, Ji Sun; Harley, Brendan A C; Kraft, Mary L
2015-11-17
A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely related short-term repopulating HSCs (ST-HSCs) and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four subpopulations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that elicited them.
Hawse, William F; Boggess, William C; Morel, Penelope A
2017-07-15
The Akt/mTOR pathway is a key driver of murine CD4 + T cell differentiation, and induction of regulatory T (Treg) cells results from low TCR signal strength and low Akt/mTOR signaling. However, strong TCR signals induce high Akt activity that promotes Th cell induction. Yet, it is unclear how Akt controls alternate T cell fate decisions. We find that the strength of the TCR signal results in differential Akt enzymatic activity. Surprisingly, the Akt substrate networks associated with T cell fate decisions are qualitatively different. Proteomic profiling of Akt signaling networks during Treg versus Th induction demonstrates that Akt differentially regulates RNA processing and splicing factors to drive T cell differentiation. Interestingly, heterogeneous nuclear ribonucleoprotein (hnRNP) L or hnRNP A1 are Akt substrates during Treg induction and have known roles in regulating the stability and splicing of key mRNAs that code for proteins in the canonical TCR signaling pathway, including CD3ζ and CD45. Functionally, inhibition of Akt enzymatic activity results in the dysregulation of splicing during T cell differentiation, and knockdown of hnRNP L or hnRNP A1 results in the lower induction of Treg cells. Together, this work suggests that a switch in substrate specificity coupled to the phosphorylation status of Akt may lead to alternative cell fates and demonstrates that proteins involved with alternative splicing are important factors in T cell fate decisions. Copyright © 2017 by The American Association of Immunologists, Inc.
ERIC Educational Resources Information Center
Morgan, Debra; Funk, Melanie; Crossley, Margaret; Basran, Jenny; Kirk, Andrew; Bello-Haas, Vanina Dal
2007-01-01
Early differential diagnosis of dementia is becoming increasingly important as new pharmacologic therapies are developed, as these treatments are not equally effective for all types of dementia. Early detection and differential diagnosis also facilitates informed family decision making and timely access to appropriate services. Information about…
ERIC Educational Resources Information Center
Kluth, Paula; Danaher, Sheila
2010-01-01
Differentiated instruction engages students of all abilities as active learners, decision-makers, and problem solvers--making educational experiences more meaningful for all. This one-of-a-kind book proves that designing differentiated instruction can be simple and fun! Packed with creative adaptation ideas like fidget bags, doodle notes, and…
Quantitative Analysis of TDLUs using Adaptive Morphological Shape Techniques
Rosebrock, Adrian; Caban, Jesus J.; Figueroa, Jonine; Gierach, Gretchen; Linville, Laura; Hewitt, Stephen; Sherman, Mark
2014-01-01
Within the complex branching system of the breast, terminal duct lobular units (TDLUs) are the anatomical location where most cancer originates. With aging, TDLUs undergo physiological involution, reflected in a loss of structural components (acini) and a reduction in total number. Data suggest that women undergoing benign breast biopsies that do not show age appropriate involution are at increased risk of developing breast cancer. To date, TDLU assessments have generally been made by qualitative visual assessment, rather than by objective quantitative analysis. This paper introduces a technique to automatically estimate a set of quantitative measurements and use those variables to more objectively describe and classify TDLUs. To validate the accuracy of our system, we compared the computer-based morphological properties of 51 TDLUs in breast tissues donated for research by volunteers in the Susan G. Komen Tissue Bank and compared results to those of a pathologist, demonstrating 70% agreement. Secondly, in order to show that our method is applicable to a wider range of datasets, we analyzed 52 TDLUs from biopsies performed for clinical indications in the National Cancer Institute’s Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project and obtained 82% correlation with visual assessment. Lastly, we demonstrate the ability to uncover novel measures when researching the structural properties of the acini by applying machine learning and clustering techniques. Through our study we found that while the number of acini per TDLU increases exponentially with the TDLU diameter, the average elongation and roundness remain constant. PMID:25722829
Periglacial process and Pleistocene environment in northern China
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guo Xudong; Liu Dongsheng; Yan Fuhua
1991-03-01
In the present time, five kinds of periglacial phenomena have been defined: ice wedges, periglacial involutions, congelifolds, congeliturbations, and loess dunes. From the stratigraphical and geochronological data, the periglacial process is divided into six stages. (1) Guanting periglacial stage, characterized by the congeliturbative deposits that have developed in early Pleistocene Guanting loess-like formation. Paleomagnetic dating gives 2.43 Ma B.P. (2) Yanchi periglacial stage, characterized by the congelifold that has developed in middle Pleistocene Yanchi Lishi loess formation. Paleomagnetic dating gives 0.50 Ma B.P. (3) Zhaitang periglacial stage (II), characterized by the periglacial involutions that have developed in lower middle Pleistocenemore » Lishi loess formation. Paleomagnetic dating gives 0.30 Ma B.P. (4) Zhaitang periglacial state (I), characterized by the ice (soil) wedge that has developed in upper-middle Pleistocene Lishi loess formation. Paleomagnetic dating gives 0.20 Ma B.P. (5) Qiansangyu periglacial stage (II), characterized by the ice (sand) wedges that has developed in late Pleistocene Malan loess formation. Paleomagnetic dating gives 0.13 Ma B.P. (6) Qiansangyu periglacial stage (I), characterized by the ice (soil) wedge that has developed in late Pleistocene Malan loess-like formation. Thermoluminescent dating gives 0.018 Ma B.P. Spore-pollen composition analysis shows that the savannah steppe environment prevailed in northern China during Pleistocene periglacial periods. These fossilized periglacial phenomena indicate a rather arid and windy periglacial environment with a mean annual temperature estimated some 12-15C colder than that in the present.« less
Thymic alterations in GM2 gangliosidoses model mice.
Kanzaki, Seiichi; Yamaguchi, Akira; Yamaguchi, Kayoko; Kojima, Yoshitsugu; Suzuki, Kyoko; Koumitsu, Noriko; Nagashima, Yoji; Nagahama, Kiyotaka; Ehara, Michiko; Hirayasu, Yoshio; Ryo, Akihide; Aoki, Ichiro; Yamanaka, Shoji
2010-08-10
Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb(-/-) mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies. In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb(-/-) mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4(+)/CD8(+) T cells and a significantly increased number of CD4(+)/CD8(-) T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb(-/-) mice. These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13.
Association between histological alterations in the thymus and sudden infant death syndrome.
Varga, Ivan; Bódi, Ildikó; Mešťanová, Veronika; Kováč, Martin; Klein, Martin
2018-04-01
Sudden infant death syndrome (SIDS) involves the death of an infant during the first year of life and it is among the leading causes of infant mortality worldwide. One hypothesis regarding the pathogenesis of SIDS is that it results from a combination of three independent factors: endogenous vulnerability, a critical time window during postnatal development, and exogenous stressors. This hypothesis is known as the "triple-risk model". In this study, we used an immunohistological approach to compare the cellular microenvironments of thymuses from 19 infants whose sudden death was classified as SIDS and a control group, which consisted of thymuses from age-matched children undergoing surgery for various congenital heart defects. We hypothesized that morphological signs of stress-related thymic involution would be present. Based on our observations, we found evidence that the proliferation and maturation of T-lymphocytes in the thymuses of infants with SIDS were suppressed. We observed enhanced macrophage activity, suggesting an increase in the apoptosis of lymphocytes and decrease in number of thymic dendritic cells and myoid cells. Significant apoptosis of thymic lymphocytes without cell regeneration typically leads to atrophy of the thymus. All cellular events we observed resemble the initial stage of stress-related thymic involution. These results support the "triple-risk model," suggesting that certain exogenous stressors might be involved in the pathogenesis of SIDS. This was probably not recognized during the autopsies of infants who died suddenly. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Browlift--a South East Asian experience.
Almousa, Radwan; Amrith, Shantha; Sundar, Gangadhara
2009-01-01
To describe the indications, techniques and outcomes of various browlift procedures in a predominantly East-Asian community. Retrospective review of patients who underwent browlift procedures performed by 2 oculoplastic surgeons or under their direct supervision, in a tertiary referral hospital in South East Asia from 2002 to 2007. Forty-six patients (30 female, 16 male) had browlift surgery for 89 sides from 2002 to 2007. Mean follow-up period was 10 months (6 to 44 months). 43 patients had bilateral browlift, 3 patients had unilateral browlift, 2 of whom had underlying facial nerve palsy and one had involutional brow ptosis. involutional brow ptosis (42), mitochondrial myopathy (2), and facial palsy (2). Ethnicity of patients: Chinese (40), Indian (4) and Malay (2). direct browlift (18), transblepharoplasty browpexy (6), midforehead lift (3), coronal browlift (2) and pretrichial browlift (4), endoscopic browlift (7), limited incision nonendoscopic browlift (5) and temporal browlift (3). Adjuvant procedures included upper blepharoplasty (26), blepharoptosis correction (4), midface lift (2), upper eyelid entropion correction (1), lacrimal gland fixation (1), and upper lid gold implant (1). Encountered complications included: undercorrection 6 (12%), segmental facial nerve palsy 1(2%), visible scar 2 (5%), paraesthesia 2 (5%), suture granuloma 1 (2%). Overall 94% of our patients were satisfied. Browlift provides satisfactory results for both patient and surgeon. A comprehensive knowledge and proper surgical technique, along with a thorough discussion with patients about the pros and cons of each procedure are essential to obtain optimal outcomes.
The world is not fair: an examination of innocent and guilty suspects' waiver decisions.
Scherr, Kyle C; Franks, Andrew S
2015-04-01
Suspects' decisions to waive or invoke their interrogation rights can have a considerable impact on their eventual legal fate. Although innocent and guilty suspects show differences in waiver rates, research has yet to examine whether innocent and guilty individuals' waiver decisions are differentially influenced by dispositional and situational factors. The current research examined the relationship among a dispositional factor (just world beliefs), a situational factor (social proof pressures-i.e., influencing others to believe that certain behaviors are normative) and innocent and guilty individuals' waiver decisions. Social proof pressures influenced the preinterrogation decisions of guilty individuals holding strong just world beliefs but not guilty individuals holding weak just world beliefs. However, social proof pressures influenced the preinterrogation decisions of innocent individuals holding weak just world beliefs but not innocent individuals holding strong just world beliefs. Results also indicated that strong just world beliefs are associated with attenuated stress responses to an accusation among innocent individuals but exacerbated stress responses among guilty individuals, thereby helping to explain why guilty and innocent individuals are differentially influenced by situational and dispositional factors. The theoretical and applied implications of these effects are discussed with an emphasis on the consequences of suspects' mindset during the preinterrogation decision-making process. (c) 2015 APA, all rights reserved).
de Jong, Christien G W; Van De Voorde, Séverine; Roeyers, Herbert; Raymaekers, Ruth; Allen, Albert J; Knijff, Simone; Verhelst, Helene; Temmink, Alfons H; Smit, Leo M E; Rodriques-Pereira, Rob; Vandenberghe, Dirk; van Welsen, Inge; ter Schuren, Liesbeth; Al-Hakim, Mazim; Amin, Azad; Vlasveld, Laurens; Oosterlaan, Jaap; Sergeant, Joseph A
2009-12-01
The effects of a promising pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), atomoxetine, were studied on executive functions in both ADHD and reading disorder (RD) because earlier research demonstrated an overlap in executive functioning deficits in both disorders. In addition, the effects of atomoxetine were explored on lexical decision. Sixteen children with ADHD, 20 children with ADHD + RD, 21 children with RD, and 26 normal controls were enrolled in a randomized placebo-controlled crossover study. Children were measured on visuospatial working memory, inhibition, and lexical decision on the day of randomization and following two 28-day medication periods. Children with ADHD + RD showed improved visuospatial working memory performance and, to a lesser extent, improved inhibition following atomoxetine treatment compared to placebo. No differential effects of atomoxetine were found for lexical decision in comparison to placebo. In addition, no effects of atomoxetine were demonstrated in the ADHD and RD groups. Atomoxetine improved visuospatial working memory and to a lesser degree inhibition in children with ADHD + RD, which suggests differential developmental pathways for co-morbid ADHD + RD as compared to ADHD and RD alone. B4Z-MC-LYCK, NCT00191906; http://clinicaltrials.gov/ct2/show/NCT00191906.
NASA Astrophysics Data System (ADS)
Holmes, Philip; Eckhoff, Philip; Wong-Lin, K. F.; Bogacz, Rafal; Zacksenhouse, Miriam; Cohen, Jonathan D.
2010-03-01
We describe how drift-diffusion (DD) processes - systems familiar in physics - can be used to model evidence accumulation and decision-making in two-alternative, forced choice tasks. We sketch the derivation of these stochastic differential equations from biophysically-detailed models of spiking neurons. DD processes are also continuum limits of the sequential probability ratio test and are therefore optimal in the sense that they deliver decisions of specified accuracy in the shortest possible time. This leaves open the critical balance of accuracy and speed. Using the DD model, we derive a speed-accuracy tradeoff that optimizes reward rate for a simple perceptual decision task, compare human performance with this benchmark, and discuss possible reasons for prevalent sub-optimality, focussing on the question of uncertain estimates of key parameters. We present an alternative theory of robust decisions that allows for uncertainty, and show that its predictions provide better fits to experimental data than a more prevalent account that emphasises a commitment to accuracy. The article illustrates how mathematical models can illuminate the neural basis of cognitive processes.
Rhee, Catherine; Lee, Bum-Kyu; Beck, Samuel; Anjum, Azeen; Cook, Kendra R.; Popowski, Melissa
2014-01-01
Despite their origin from the inner cell mass, embryonic stem (ES) cells undergo differentiation to the trophectoderm (TE) lineage by repression of the ES cell master regulator Oct4 or activation of the TE master regulator Caudal-type homeobox 2 (Cdx2). In contrast to the in-depth studies of ES cell self-renewal and pluripotency, few TE-specific regulators have been identified, thereby limiting our understanding of mechanisms underlying the first cell fate decision. Here we show that up-regulation and nuclear entry of AT-rich interactive domain 3a (Arid3a) drives TE-like transcriptional programs in ES cells, maintains trophoblast stem (TS) cell self-renewal, and promotes further trophoblastic differentiation both upstream and independent of Cdx2. Accordingly, Arid3a−/− mouse post-implantation placental development is severely impaired, resulting in early embryonic death. We provide evidence that Arid3a directly activates TE-specific and trophoblast lineage-specific genes while directly repressing pluripotency genes via differential regulation of epigenetic acetylation or deacetylation. Our results identify Arid3a as a critical regulator of TE and placental development through execution of the commitment and differentiation phases of the first cell fate decision. PMID:25319825
Zhao, Jingyao; Chen, Xufeng; Song, Guangrong; Zhang, Jiali; Liu, Haifeng; Liu, Xiaolong
2017-01-01
Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate. However, how individual HSC makes the decision between self-renewal and differentiation remains largely unknown. Here we report that ablation of the key epigenetic regulator Uhrf1 in the hematopoietic system depletes the HSC pool, leading to hematopoietic failure and lethality. Uhrf1-deficient HSCs display normal survival and proliferation, yet undergo erythroid-biased differentiation at the expense of self-renewal capacity. Notably, Uhrf1 is required for the establishment of DNA methylation patterns of erythroid-specific genes during HSC division. The expression of these genes is enhanced in the absence of Uhrf1, which disrupts the HSC-division modes by promoting the symmetric differentiation and suppressing the symmetric self-renewal. Moreover, overexpression of one of the up-regulated genes, Gata1, in HSCs is sufficient to phenocopy Uhrf1-deficient HSCs, which show impaired HSC symmetric self-renewal and increased differentiation commitment. Taken together, our findings suggest that Uhrf1 controls the self-renewal versus differentiation of HSC through epigenetically regulating the cell-division modes, thus providing unique insights into the relationship among Uhrf1-mediated DNA methylation, cell-division mode, and HSC fate decision. PMID:27956603
Jena, Manas Kumar; Samantaray, Subhransu Ranjan
2016-01-01
This paper presents a data-mining-based intelligent differential relaying scheme for transmission lines, including flexible ac transmission system device, such as unified power flow controller (UPFC) and wind farms. Initially, the current and voltage signals are processed through extended Kalman filter phasor measurement unit for phasor estimation, and 21 potential features are computed at both ends of the line. Once the features are extracted at both ends, the corresponding differential features are derived. These differential features are fed to a data-mining model known as decision tree (DT) to provide the final relaying decision. The proposed technique has been extensively tested for single-circuit transmission line, including UPFC and wind farms with in-feed, double-circuit line with UPFC on one line and wind farm as one of the substations with wide variations in operating parameters. The test results obtained from simulation as well as in real-time digital simulator testing indicate that the DT-based intelligent differential relaying scheme is highly reliable and accurate with a response time of 2.25 cycles from the fault inception.
Staff Differentiation; An Annotated Bibliography Addendum.
ERIC Educational Resources Information Center
Marin County Public Schools, Corte Madera, CA.
Differentiated staffing has emphasized development of teacher leadership roles, the importance of shared decision making in schools, and the constructive ways in which paid instructional aides and volunteer aides can support the professional teaching staff. Eighteen annotated bibliographic citations concerning the various aspects of differentiated…
Generation of a crowned pinion tooth surface by a surface of revolution
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Zhang, J.; Handschuh, R. F.
1988-01-01
A method of generating crowned pinion tooth surfaces using a surface of revolution is developed. The crowned pinion meshes with a regular involute gear and has a prescribed parabolic type of transmission errors when the gears operate in the aligned mode. When the gears are misaligned the transmission error remains parabolic with the maximum level still remaining very small (less than 0.34 arc sec for the numerical examples). Tooth contact analysis (TCA) is used to simulate the conditions of meshing, determine the transmission error, and determine the bearing contact.
Pseudotumor of the pituitary due to PROP-1 deletion.
Teinturier, C; Vallette, S; Adamsbaum, C; Bendaoud, M; Brue, T; Bougnères, P F
2002-01-01
Hypopituitarism associated with pituitary mass in childhood is most frequently the consequence of craniopharyngioma or Rathke's cleft cyst. We report a patient with an intrasellar pseudotumor associated with hypopituitarism, which led us to a misdiagnosis of intrasellar craniopharyngioma. After spontaneous involution of the mass, diagnosis was revised. DNA analysis showed a deletion in the Prophet of Pit-1 (PROP-1) gene, a pituitary transcription factor. It is important to recognize that a PROP-1 deletion can cause pituitary pseudotumor that can be mistaken for a craniopharyngioma or Rathke's pouch cyst.
2014-07-01
in rodents versus humans and whether the same isolation technique will yield exosomes that are equally useful in subsequent functional assays...exosome isolation by PEG based precipitation method, equal amounts of plasma and PEG 6000 were incubated overnight at 4°C on a rotating shaker followed by...Blotting: Equal amounts of proteins from Exosome samples (20 μg) were loaded onto 10% Tris gels in. Gels were run at an initial voltage of 60V thought eh
Mental health problems of aging and the aged from the viewpoint of analytical psychology*
Bash, K. W.
1959-01-01
According to Jung's analytical psychology man is either predominantly extravert or predominantly introvert. Whichever he is, he must in most cases, in order to satisfy the biological drives of the earlier part of his life, adapt himself to an extraverted culture and thus become largely extravert. In the later part of life, as biological involution sets in, this attitude and the values attached thereto no longer suffice. The strains set up by the resulting need for a reorientation in life are a fruitful source of mental disorder. PMID:20604058
Chierchia, G; Lesemann, F H Parianen; Snower, D; Vogel, M; Singer, T
2017-09-11
Standard economic theory postulates that decisions are driven by stable context-insensitive preferences, while motivation psychology suggests they are driven by distinct context-sensitive motives with distinct evolutionary goals and characteristic psycho-physiological and behavioral patterns. To link these fields and test how distinct motives could differentially predict different types of economic decisions, we experimentally induced participants with either a Care or a Power motive, before having them take part in a suite of classic game theoretical paradigms involving monetary exchange. We show that the Care induction alone raised scores on a latent factor of cooperation-related behaviors, relative to a control condition, while, relative to Care, Power raised scores on a punishment-related factor. These findings argue against context-insensitive stable preferences and theories of strong reciprocity and in favor of a motive-based approach to economic decision making: Care and Power motivation have a dissociable fingerprint in shaping either cooperative or punishment behaviors.
Decision-making Strategies and Performance among Seniors1
Besedeš, Tibor; Deck, Cary; Sarangi, Sudipta; Shor, Mikhael
2011-01-01
Using paper and pencil experiments administered in senior centers, we examine decision-making performance in multi-attribute decision problems. We differentiate the effects of declining cognitive performance and changing cognitive process on decision-making performance of seniors as they age. We find a significant decline in performance with age due to reduced reliance on common heuristics and increased decision-making randomness among our oldest subjects. However, we find that increasing the number of options in a decision problem increases the number of heuristics brought to the task. This challenges the choice overload view that people give up when confronted with too much choice. PMID:22408282
The design of patient decision support interventions: addressing the theory-practice gap.
Elwyn, Glyn; Stiel, Mareike; Durand, Marie-Anne; Boivin, Jacky
2011-08-01
Although an increasing number of decision support interventions for patients (including decision aids) are produced, few make explicit use of theory. We argue the importance of using theory to guide design. The aim of this work was to address this theory-practice gap and to examine how a range of selected decision-making theories could inform the design and evaluation of decision support interventions. We reviewed the decision-making literature and selected relevant theories. We assessed their key principles, theoretical pathways and predictions in order to determine how they could inform the design of two core components of decision support interventions, namely, information and deliberation components and to specify theory-based outcome measures. Eight theories were selected: (1) the expected utility theory; (2) the conflict model of decision making; (3) prospect theory; (4) fuzzy-trace theory; (5) the differentiation and consolidation theory; (6) the ecological rationality theory; (7) the rational-emotional model of decision avoidance; and finally, (8) the Attend, React, Explain, Adapt model of affective forecasting. Some theories have strong relevance to the information design (e.g. prospect theory); some are more relevant to deliberation processes (conflict theory, differentiation theory and ecological validity). None of the theories in isolation was sufficient to inform the design of all the necessary components of decision support interventions. It was also clear that most work in theory-building has focused on explaining or describing how humans think rather than on how tools could be designed to help humans make good decisions. It is not surprising therefore that a large theory-practice gap exists as we consider decision support for patients. There was no relevant theory that integrated all the necessary contributions to the task of making good decisions in collaborative interactions. Initiatives such as the International Patient Decision Aids Standards Collaboration influence standards for the design of decision support interventions. However, this analysis points to the need to undertake more work in providing theoretical foundations for these interventions. © 2010 Blackwell Publishing Ltd.
Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence
Reske, Martina; Stewart, Jennifer L.; Flagan, Taru M.; Paulus, Martin P.
2015-01-01
Objective Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing. Methods 158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a “risky gains” decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, “risky decisions”). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed. Results There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options. Discussion Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring, reward processing and interoceptive awareness. Marijuana had additive effects by diminishing neural risk differentiation. PMID:26076493
NASA Astrophysics Data System (ADS)
Aubert, Benoit; Léger, Pierre-Majorique; Larocque, Denis
2012-05-01
Enterprise resource planning (ERP) systems represent a major IT adoption decision. ERP adoption decisions, in the chemicals and allied products sectors, were examined between 1994 and 2005. Networks of strong ties and weak ties partners are investigated. Results show that neighbouring companies linked with strong ties can have an influence on organisations making such adoption decision. Past decisions made by major trading partners have a significant influence on the decision to adopt an ERP system for a given organisation. This reflects the complex nature of the knowledge required for such adoption.
Boesch, I
2013-04-01
This study aimed to determine key attributes of milk that drive a processor's supply decisions and possibilities for differentiation based on these product attributes. Feedback-driven exploration was applied to derive product attributes relevant to the buying decision. Conjoint analysis with hierarchical Bayes estimation methods was used to determine the relative importance of attributes. Results show that the technical aspects of milk, as well as the price and country of origin, dominate the buying decision. Potential for differentiation was found for environmental and societal attributes as well as freedom from genetically modified products. Product and supplier criteria also provide the potential to segment the market if the price premium is held within limits. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Korucu, M Kemal; Karademir, Aykan
2014-02-01
The procedure of a multi-criteria decision analysis supported by the geographic information systems was applied to the site selection process of a planning municipal solid waste management practice based on twelve different scenarios. The scenarios included two different decision tree modes and two different weighting models for three different area requirements. The suitability rankings of the suitable sites obtained from the application of the decision procedure for the scenarios were assessed by a factorial experimental design concerning the effect of some external criteria on the final decision of the site selection process. The external criteria used in the factorial experimental design were defined as "Risk perception and approval of stakeholders" and "Visibility". The effects of the presence of these criteria in the decision trees were evaluated in detail. For a quantitative expression of the differentiations observed in the suitability rankings, the ranking data were subjected to ANOVA test after a normalization process. Then the results of these tests were evaluated by Tukey test to measure the effects of external criteria on the final decision. The results of Tukey tests indicated that the involvement of the external criteria into the decision trees produced statistically meaningful differentiations in the suitability rankings. Since the external criteria could cause considerable external costs during the operation of the disposal facilities, the presence of these criteria in the decision tree in addition to the other criteria related to environmental and legislative requisites could prevent subsequent external costs in the first place.
Forgetting the Past: Individual Differences in Recency in Subjective Valuations from Experience
ERIC Educational Resources Information Center
Ashby, Nathaniel J. S.; Rakow, Tim
2014-01-01
Recent research investigating decisions from experience suggests that not all information is treated equally in the decision process, with more recently encountered information having a greater impact. We report 2 studies investigating how this differential treatment of sequentially encountered information affects subjective valuations of risky…
Selected Legal Considerations Bearing upon Alternative Salary Plans for Teachers. Revised.
ERIC Educational Resources Information Center
O'Reilly, Robert C.
Although employment decisions must be in harmony with existing case laws and statutes, such decisions allow for more flexibility than is sometimes supposed. Increasingly, state legislators and other public officials (including Secretary of Education T. H. Bell and Tennessee Governor Lamar Alexander) are working to establish differentiated pay…
Factors, Correlates, Emotional Barriers Affecting Career Decisions of College Students.
ERIC Educational Resources Information Center
O'Neil, James M.; And Others
The correlates of career choice and the problem areas affecting career decisions are important to counseling psychologists. They are important to understanding the complexities of vocational behavior, facilitating differential treatment in counseling, and developing preventive career programs for men, women, and special groups. The effects of the…
Personal Influence on the Decision to Join Voluntary Associations.
ERIC Educational Resources Information Center
Booth, Alan James
A longitudinal study (1961-1965) was planned to obtain information on the pervasiveness of personal influence with respect to decisions to join formal voluntary associations; examine the characteristics of opinion leaders and the individuals they influence; discover the differential patterns of joiners' exposure to mass communicated messages about…
Ettlin, Florence; Bröder, Arndt
2015-05-01
Adaptive strategy selection implies that a decision strategy is chosen based on its fit to the task and situation. However, other aspects, such as the way information is presented, can determine information search behavior; especially when the application of certain strategies over others is facilitated. But are such display effects on multi-attribute decisions also at work when the manipulation does not entail differential costs for different decision strategies? Three Mouselab experiments with hidden information and one eye tracking experiment with an open information board revealed that decision behavior is unaffected by purely perceptual manipulations of the display based on Gestalt principles; that is, based on manipulations that induce no noteworthy processing costs for different information search patterns. We discuss our results in the context of previous findings on display effects; specifically, how the combination of these findings and our results reveal the crucial role of differential processing costs for different strategies for the emergence of display effects. This finding describes a boundary condition of the commonly acknowledged influence of information displays and is in line with the ideas of adaptive strategy selection and cost-benefit tradeoffs. Copyright © 2015. Published by Elsevier B.V.
Tooth-meshing-harmonic static-transmission-error amplitudes of helical gears
NASA Astrophysics Data System (ADS)
Mark, William D.
2018-01-01
The static transmission errors of meshing gear pairs arise from deviations of loaded tooth working surfaces from equispaced perfect involute surfaces. Such deviations consist of tooth-pair elastic deformations and geometric deviations (modifications) of tooth working surfaces. To a very good approximation, the static-transmission-error tooth-meshing-harmonic amplitudes of helical gears are herein expressed by superposition of Fourier transforms of the quantities: (1) the combination of tooth-pair elastic deformations and geometric tooth-pair modifications and (2) fractional mesh-stiffness fluctuations, each quantity (1) and (2) expressed as a function of involute "roll distance." Normalization of the total roll-distance single-tooth contact span to unity allows tooth-meshing-harmonic amplitudes to be computed for different shapes of the above-described quantities (1) and (2). Tooth-meshing harmonics p = 1, 2, … are shown to occur at Fourier-transform harmonic values of Qp, p = 1, 2, …, where Q is the actual (total) contact ratio, thereby verifying its importance in minimizing transmission-error tooth-meshing-harmonic amplitudes. Two individual shapes and two series of shapes of the quantities (1) and (2) are chosen to illustrate a wide variety of shapes. In most cases representative of helical gears, tooth-meshing-harmonic values p = 1, 2, … are shown to occur in Fourier-transform harmonic regions governed by discontinuities arising from tooth-pair-contact initiation and termination, thereby showing the importance of minimizing such discontinuities. Plots and analytical expressions for all such Fourier transforms are presented, thereby illustrating the effects of various types of tooth-working-surface modifications and tooth-pair stiffnesses on transmission-error generation.
Martin, Amy C; Thornton, J Derek; Liu, Jiewiu; Wang, XiaoFei; Zuo, Jian; Jablonski, Monica M; Chaum, Edward; Zindy, Frederique; Skapek, Stephen X
2004-10-01
Persistent hyperplastic primary vitreous (PHPV) is an idiopathic developmental eye disease associated with failed involution of the hyaloid vasculature. The present work addressed the pathogenesis of PHPV in a mouse model that replicates many aspects of the human disease. Ophthalmoscopic and histologic analyses documented pathologic processes in eyes of mice lacking the Arf gene compared with Ink4a-deficient and wild-type control animals. Immunohistochemical staining, in situ hybridization, and RT-PCR demonstrated the expression of relevant gene products. Arf gene expression was determined by in situ hybridization using wholemounts of wild-type mouse eyes and by immunofluorescence staining for green fluorescent protein (GFP) in Arf(+/GFP) heterozygous knock-in mouse eyes. Abnormalities in Arf(-/-) mice mimicked those found in patients with severe PHPV. The mice had microphthalmia; fibrovascular, retrolental tissue containing retinal pigment epithelial cells and remnants of the hyaloid vascular system; posterior lens capsule destruction with lens degeneration and opacity; and severe retinal dysplasia and detachment. Eyes of mice lacking the overlapping Ink4a gene were normal. Arf was selectively expressed in perivascular cells within the vitreous of the postnatal eye. Cells composing the retrolental mass in Arf(-/-) mice expressed the Arf promoter. The remnant hyaloid vessels expressed Flk-1. Its ligand, vascular endothelial growth factor (Vegf), was expressed in the retrolental tissue and the adjacent dysplastic neuroretina. Arf(-/-) mice have features that accurately mimic severe PHPV. In the HVS, Arf expression in perivascular cells may block their accumulation or repress Vegf expression to promote HVS involution and prevent PHPV.
Martin, Amy C.; Thornton, J. Derek; Liu, Jiewiu; Wang, XiaoFei; Zuo, Jian; Jablonski, Monica M.; Chaum, Edward; Zindy, Frederique; Skapek, Stephen X.
2006-01-01
Purpose Persistent hyperplastic primary vitreous (PHPV) is an idiopathic developmental eye disease associated with failed involution of the hyaloid vasculature. The present work addressed the pathogenesis of PHPV in a mouse model that replicates many aspects of the human disease. Methods Ophthalmoscopic and histologic analyses documented pathologic processes in eyes of mice lacking the Arf gene compared with Ink4a-deficient and wild-type control animals. Immunohistochemical staining, in situ hybridization, and RT-PCR demonstrated the expression of relevant gene products. Arf gene expression was determined by in situ hybridization using wholemounts of wild-type mouse eyes and by immunofluorescence staining for green fluores-cent protein (GFP) in Arf+/GFP heterozygous knock-in mouse eyes. Results Abnormalities in Arf−/− mice mimicked those found in patients with severe PHPV. The mice had microphthalmia; fibrovascular, retrolental tissue containing retinal pigment epithelial cells and remnants of the hyaloid vascular system; posterior lens capsule destruction with lens degeneration and opacity; and severe retinal dysplasia and detachment. Eyes of mice lacking the overlapping Ink4a gene were normal. Arf was selectively expressed in perivascular cells within the vitreous of the postnatal eye. Cells composing the retrolental mass in Arf−/− mice expressed the Arf promoter. The remnant hyaloid vessels expressed Flk-1. Its ligand, vascular endothelial growth factor (Vegf), was expressed in the retrolental tissue and the adjacent dysplastic neuroretina. Conclusions Arf−/− mice have features that accurately mimic severe PHPV. In the HVS, Arf expression in perivascular cells may block their accumulation or repress Vegf expression to promote HVS involution and prevent PHPV. PMID:15452040
Molecular regulation of the mitosis/meiosis decision in multicellular organisms.
Kimble, Judith
2011-08-01
A major step in the journey from germline stem cell to differentiated gamete is the decision to leave the mitotic cell cycle and begin progression through the meiotic cell cycle. Over the past decade, molecular regulators of the mitosis/meiosis decision have been discovered in most of the major model multicellular organisms. Historically, the mitosis/meiosis decision has been closely linked with controls of germline self-renewal and the sperm/egg decision, especially in nematodes and mice. Molecular explanations of those linkages clarify our understanding of this fundamental germ cell decision, and unifying themes have begun to emerge. Although the complete circuitry of the decision is not known in any organism, the recent advances promise to impact key issues in human reproduction and agriculture.
Buse, Eberhard; Habermann, Gunnar; Vogel, Friedhelm
2006-05-01
Thymus development was studied in the cynomolgus monkey from day 35 of gestation (gd 35) to the stage of advanced involution in a 21-year-old monkey. Special emphasis was placed on thymus cell generation and cellular pattern formation. At gd 35, the epithelial bud of the thymus was visible in a sagittal position at the level of the thoracic aperture. At gd 50, first lymphocyte-like cells and few Human Leukocyte Antigen-D Region (HLA-DR) immunoreactive cells appeared. The cortico-medullary differentiation, Hassall's body precursors and faint immunoreactivity for T-lymphocytes (CD 3-positive) were detected from gd 60 onwards. First macrophages (CD 68 positive) were apparent at day 70, first CD 20 immunoreactive cells (B-lymphocyte-like cells) at gd 85, and natural killer cells (M1014 immunoreactive) at gd 100. At gd 100 all evaluated cell populations present in the adult cynomolgus monkey thymus were in place, whereas no B- and T-cell precursors or (CD 34 and CD 117, respectively) dendritic cells (CD 35 positive cells) were present. All these immunopositive cells persisted, partly with changing distribution patterns, until the advanced age of 21 years with the exception of natural killer cells, which were present only until adult ages (evaluation at 4-7 years). The rationale of this study was to analyse thymic development in the cynomolgus monkey and to evaluate the relevance of the development of thymus in non-human primate as a model for corresponding human targeted toxicological research.
Reyes, R. A.; Canfield, Don R.; Esser, Ursula; Adamson, Lourdes A.; Brown, Charles R.; Cheng-Mayer, Cecilia; Gardner, Murray B.; Harouse, Janet M.; Luciw, Paul A.
2004-01-01
Newborn rhesus macaques were infected with two chimeric simian-human immunodeficiency virus (SHIV) strains which contain unique human immunodeficiency virus type 1 (HIV-1) env genes and exhibit distinct phenotypes. Infection with either the CCR5-specific SHIVSF162P3 or the CXCR4-utilizing SHIVSF33A resulted in clinical manifestations consistent with simian AIDS. Most prominent in this study was the detection of severe thymic involution in all SHIVSF33A-infected infants, which is very similar to HIV-1-induced thymic dysfunction in children who exhibit a rapid pattern of disease progression. In contrast, SHIVSF162P3 induced only a minor disruption in thymic morphology. Consistent with the distribution of the coreceptors CXCR4 and CCR5 within the thymus, the expression of SHIVSF162P3 was restricted to the thymic medulla, whereas SHIVSF33A was preferentially detected in the cortex. This dichotomy of tissue tropism is similar to the differential tropism of HIV-1 isolates observed in the reconstituted human thymus in SCID-hu mice. Accordingly, our results show that the SHIV-monkey model can be used for the molecular dissection of cell and tissue tropisms controlled by the HIV-1 env gene and for the analysis of mechanisms of viral immunopathogenesis in AIDS. Furthermore, these findings could help explain the rapid progression of disease observed in some HIV-1-infected children. PMID:14747577
Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G
2009-09-01
The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.
Li, Xin; Gonzalez, Maria E.; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D.; Kleer, Celina G.
2009-01-01
The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with β-catenin, inducing β-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/β-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with β-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma. PMID:19661437
Wu, Xiufeng; Wan, Shengqin; Pujar, Shashikant; Haskins, Mark E.; Schlafer, Donald H.; Lee, Mary M.; Meyers-Wallen, Vicki N.
2008-01-01
Müllerian Inhibiting Substance (MIS), a secreted glycoprotein in the Transforming Growth Factor-beta (TGF-beta) family of growth factors, mediates regression of the Müllerian ducts during embryonic sex differentiation in males. In Persistent Müllerian Duct Syndrome (PMDS), rather than undergoing involution, the Müllerian ducts persist in males, giving rise to the uterus, Fallopian tubes, and upper vagina. Genetic defects in MIS or its receptor (MISRII) have been identified in patients with PMDS. The phenotype in the canine model of PMDS derived from the miniature schnauzer breed is strikingly similar to that of human patients. In this model, PMDS is inherited as a sex-limited autosomal recessive trait. Previous studies indicated that a defect in the MIS receptor or its downstream signaling pathway was likely to be causative of the canine syndrome. In this study the canine PMDS phenotype and clinical sequelae are described in detail. Affected and unaffected members of this pedigree are genotyped, identifying a single base pair substitution in MISRII that introduces a stop codon in exon 3. The homozygous mutation terminates translation at 80 amino acids, eliminating much of the extracellular domain and the entire transmembrane and intracellular signaling domains. Findings in this model may enable insights to be garnered from correlation of detailed clinical descriptions with molecular defects, which are not otherwise possible in the human syndrome. PMID:18723470
Dynamics of early planetary gear trains
NASA Technical Reports Server (NTRS)
August, R.; Kasuba, R.; Frater, J. L.; Pintz, A.
1984-01-01
A method to analyze the static and dynamic loads in a planetary gear train was developed. A variable-variable mesh stiffness (VVMS) model was used to simulate the external and internal spur gear mesh behavior, and an equivalent conventional gear train concept was adapted for the dynamic studies. The analysis can be applied either involute or noninvolute spur gearing. By utilizing the equivalent gear train concept, the developed method may be extended for use for all types of epicyclic gearing. The method is incorporated into a computer program so that the static and dynamic behavior of individual components can be examined. Items considered in the analysis are: (1) static and dynamic load sharing among the planets; (2) floating or fixed Sun gear; (3) actual tooth geometry, including errors and modifications; (4) positioning errors of the planet gears; (5) torque variations due to noninvolute gear action. A mathematical model comprised of power source, load, and planetary transmission is used to determine the instantaneous loads to which the components are subjected. It considers fluctuating output torque, elastic behavior in the system, and loss of contact between gear teeth. The dynamic model has nine degrees of freedom resulting in a set of simultaneous second order differential equations with time varying coefficients, which are solved numerically. The computer program was used to determine the effect of manufacturing errors, damping and component stiffness, and transmitted load on dynamic behavior. It is indicated that this methodology offers the designer/analyst a comprehensive tool with which planetary drives may be quickly and effectively evaluated.
Allavena, Giulia; Marotta, Roberto; Catelani, Tiziano; Bertolini, Marta; Paus, Ralf
2018-01-01
Autophagy plays a crucial role in health and disease, regulating central cellular processes such as adaptive stress responses, differentiation, tissue development, and homeostasis. However, the role of autophagy in human physiology is poorly understood, highlighting a need for a model human organ system to assess the efficacy and safety of strategies to therapeutically modulate autophagy. As a complete, cyclically remodelled (mini-)organ, the organ culture of human scalp hair follicles (HFs), which, after massive growth (anagen), spontaneously enter into an apoptosis-driven organ involution (catagen) process, may provide such a model. Here, we reveal that in anagen, hair matrix keratinocytes (MKs) of organ-cultured HFs exhibit an active autophagic flux, as documented by evaluation of endogenous lipidated Light Chain 3B (LC3B) and sequestosome 1 (SQSTM1/p62) proteins and the ultrastructural visualization of autophagosomes at all stages of the autophagy process. This autophagic flux is altered during catagen, and genetic inhibition of autophagy promotes catagen development. Conversely, an anti–hair loss product markedly enhances intrafollicular autophagy, leading to anagen prolongation. Collectively, our data reveal a novel role of autophagy in human hair growth. Moreover, we show that organ-cultured scalp HFs are an excellent preclinical research model for exploring the role of autophagy in human tissue physiology and for evaluating the efficacy and tissue toxicity of candidate autophagy-modulatory agents in a living human (mini-)organ. PMID:29590104
Factors Used by Accounting Students in Differentiating among Prospective Employers
ERIC Educational Resources Information Center
Phillips, Carl R.; Phillips, Antoinette S.
2006-01-01
Past research has revealed a number of determinants that employers use in making selection decisions about college students. However, few studies have examined those factors students use in differentiating among prospective employers and to date no studies have examined Accounting student preferences. Increased scrutiny of corporate accounting…
Boccia, Maria L; Campbell, Frances A; Goldman, Barbara D; Skinner, Martie
2009-01-01
In the present simulation research, the authors examined the relations between the type of information that low-income parents (N = 116) recalled from informed-consent materials and their hypothetical decision to enroll a child in a clinical study. The authors gave parents or guardians of Head Start children information about a medical protocol involving high risk and significant potential benefit to child participants. Differential recall of the various categories of information (procedures, benefits, risks and costs, rights, and other) showed that relative to all consent information conveyed to them, participants recalled most about procedures and least about their child's rights as a study participant. Relative to their own recall, they also recounted most about procedures, slightly more about benefits than risks, and least about research rights. The pattern of recall differed among those who agreed to enroll and those who declined. The ratio of recalled risks to benefits predicted enrollment decisions.
Purtle, Jonathan
2015-07-01
Racial health disparities in the United States are produced and perpetuated through public policies that differentially allocate risks and resources for health. Elected officials have the ability modify the structural determinants of racial health disparities through policy decisions and, through voting, the electorate can influence the extent to which these policy decisions promote health equity. In this commentary, I synthesize research on the voting behavior of electorates and policy decisions and present strategies to foster sociopolitical environments that are conducive to the implementation and enforcement of racial health disparity reduction initiatives. There is a need for research that contributes to a more comprehensive understanding of the role of voting in health policy making processes and further development of empirically-based policy advocacy strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.
75 FR 17605 - Federal Motor Vehicle Safety Standards; Roof Crush Resistance
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-07
...-weight ratio requirement to heavier light vehicles, i.e., ones with a gross vehicle weight rating greater... of that decision as well as the agency's decision not to adopt a dynamic rollover test requirement as.... Petitioner's Claim That Quasi-Static Test and Criteria Do Not Reasonably Differentiate Between the Injury...
Students as Rational Decision-Makers: The Question of Beliefs and Attitudes
ERIC Educational Resources Information Center
Sullivan, Alice
2006-01-01
Rational choice theorists have analysed rates of participation in post-compulsory education, and, in particular, class differentials in these rates. Various claims have been made about the motivations of student decision-makers, but these claims have not been grounded empirically. This paper will assess the question of whether students' attitudes…
Improved Decision Making for School Organization. What and What for
ERIC Educational Resources Information Center
Myers, Donald A.; Sinclair, Robert
1973-01-01
A framework of 13 decision criteria to give educators help in comparing the relative merits of different forms of school organization. The methods of school organization judged to be in widespread use and defined in the article are (1) the self-contained classroom, team teaching, departmentalization, modular scheduling, differentiated staffing,…
ERIC Educational Resources Information Center
Breidenbach, Daniel H.; French, Brian F.
2011-01-01
Many factors can influence a student's decision to withdraw from college. Intervention programs aimed at retention can benefit from understanding the factors related to such decisions, especially in underrepresented groups. The Institutional Integration Scale (IIS) has been suggested as a predictor of student persistence. Accurate prediction of…
Khacho, Mireille; Clark, Alysen; Svoboda, Devon S; Azzi, Joelle; MacLaurin, Jason G; Meghaizel, Cynthia; Sesaki, Hiromi; Lagace, Diane C; Germain, Marc; Harper, Mary-Ellen; Park, David S; Slack, Ruth S
2016-08-04
Regulated mechanisms of stem cell maintenance are key to preventing stem cell depletion and aging. While mitochondrial morphology plays a fundamental role in tissue development and homeostasis, its role in stem cells remains unknown. Here, we uncover that mitochondrial dynamics regulates stem cell identity, self-renewal, and fate decisions by orchestrating a transcriptional program. Manipulation of mitochondrial structure, through OPA1 or MFN1/2 deletion, impaired neural stem cell (NSC) self-renewal, with consequent age-dependent depletion, neurogenesis defects, and cognitive impairments. Gene expression profiling revealed ectopic expression of the Notch self-renewal inhibitor Botch and premature induction of transcription factors that promote differentiation. Changes in mitochondrial dynamics regulate stem cell fate decisions by driving a physiological reactive oxygen species (ROS)-mediated process, which triggers a dual program to suppress self-renewal and promote differentiation via NRF2-mediated retrograde signaling. These findings reveal mitochondrial dynamics as an upstream regulator of essential mechanisms governing stem cell self-renewal and fate decisions through transcriptional programming. Copyright © 2016 Elsevier Inc. All rights reserved.
Farrell, Anne M.; Goh, Joshua O. S.; White, Brian J.
2018-01-01
Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events. PMID:29487519
Farrell, Anne M; Goh, Joshua O S; White, Brian J
2018-01-01
Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.
The influence of differential response on decision-making in child protective service agencies.
Janczewski, Colleen E
2015-01-01
Differential response (DR) profoundly changes the decision pathways of public child welfare systems, yet little is known about how DR shapes the experiences of children whose reports receive an investigation rather than an alternate response. Using data from the National Child Abuse and Neglect Data System (NCANDS), this study examined the relationship between DR implementation and decision outcomes in neglect cases, as measured by investigation, substantiation, and removal rates in 297 U.S. counties. Multivariate regression models included county-level measures of child poverty and proportions of African American children. Path analyses were also conducted to identify mediating effects of prior decision points and moderating effects of DR on poverty and race's influence on decision outcomes. Results indicate that compared to non-DR counties, those implementing DR have significantly lower investigation and substantiation rates within county populations but higher substantiation rates among investigated cases. Regression models showed significant reductions in removal rates associated with DR implementation, but these effects became insignificant in path models that accounted for mediation effects of previous decision points. Findings also suggest that DR implementation may reduce the positive association between child poverty rates and investigation rates, but additional studies with larger samples are needed to confirm this moderation effect. Two methods of calculating decision outcomes, population- and decision-based enumeration, were used, and policy and research implications of each are discussed. This study demonstrates that despite their inherit complexity, large administrative datasets such as NCANDS can be used to assess the impact of wide-scale system change across jurisdictions. Copyright © 2014 Elsevier Ltd. All rights reserved.
Making lineage decisions with biological noise: Lessons from the early mouse embryo.
Simon, Claire S; Hadjantonakis, Anna-Katerina; Schröter, Christian
2018-04-30
Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types. Using the early mouse embryo as a model we review recent developments that have allowed the quantification of molecular intercellular heterogeneity during cell differentiation. We first discuss the relationship between these heterogeneities and developmental cellular potential. We then review recent theoretical approaches that formalize the mechanisms underlying fate decisions in the inner cell mass of the blastocyst stage embryo. These models build on our extensive knowledge of the genetic control of fate decisions in this system and will become essential tools for a rigorous understanding of the connection between noisy molecular processes and reproducible outcomes at the multicellular level. We conclude by suggesting that cell-to-cell communication provides a mechanism to exploit and buffer intercellular variability in a self-organized process that culminates in the reproducible formation of the mature mammalian blastocyst stage embryo that is ready for implantation into the maternal uterus. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Quantitative Methods and Models. © 2018 Wiley Periodicals, Inc.
1986-03-01
pin is along the escape wheel tooth, and is a measure of the distance along the plane of the tooth to its end. [Again, parameter g has a negative...Reference 2, appendix C gives the details of how thes." parameters are evaluated.) The parameter f is a measure of the distance between the pallet pin... measures the distance from the pallet pin center tO the escape wheel tooth tip along the plane of the tooth. First the parameter f is monitored. If f
[Changes in the manifestation of guilt perception in endogenous depression in advanced age].
Bron, B; Wetter-Parasie, J
1989-05-01
The manifestation of endogenous depressions has clearly changed in the last decades. Ideas of guilt and sin have decreased or changed their contents, whereas feelings of insufficiency, physical complaints and hypochondriac ideas have clearly increased. The importance of the experience of guilt in the case of endogenous depressions and transcultural aspects of the guilt phenomenon are pointed out. By means of 301 case-histories of depressive patients at the involutional period the change in the manifestation of the depression within four periods of time is pointed out and its possible causal relationships are discussed.
Generation of helical gears with new surfaces topology by application of CNC machines
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Chen, N. X.; Hsiao, C. L.; Handschuh, Robert F.
1993-01-01
Analysis of helical involute gears by tooth contact analysis shows that such gears are very sensitive to angular misalignment that leads to edge contact and the potential for high vibration. A new topology of tooth surfaces of helical gears that enables a favorable bearing contact and a reduced level of vibration is described. Methods for grinding of the helical gears with the new topology are proposed. A TCA (tooth contact analysis) program for simulation of meshing and contact of helical gears with the new topology has been developed. Numerical examples that illustrate the proposed ideas are discussed.
Generation of helical gears with new surfaces, topology by application of CNC machines
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Chen, N. X.; Hsiao, C. L.; Handschuh, R. F.
1993-01-01
Analysis of helical involute gears by tooth contact analysis shows that such gears are very sensitive to angular misalignment that leads to edge contact and the potential for high vibration. A new topology of tooth surfaces of helical gears that enables a favorable bearing contact and a reduced level of vibration is described. Methods for grinding of the helical gears with the new topology are proposed. A TCA (tooth contact analysis) program for simulation of meshing and contact of helical gears with the new topology has been developed. Numerical examples that illustrate the proposed ideas are discussed.
Virasoro algebra in the KN algebra; Bosonic string with fermionic ghosts on Riemann surfaces
DOE Office of Scientific and Technical Information (OSTI.GOV)
Koibuchi, H.
1991-10-10
In this paper the bosonic string model with fermionic ghosts is considered in the framework of the KN algebra. The authors' attentions are paid to representations of KN algebra and a Clifford algebra of the ghosts. The authors show that a Virasoro-like algebra is obtained from KN algebra when KN algebra has certain antilinear anti-involution, and that it is isomorphic to the usual Virasoro algebra. The authors show that there is an expected relation between a central charge of this Virasoro-like algebra and an anomaly of the combined system.
Weak Lie symmetry and extended Lie algebra
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goenner, Hubert
2013-04-15
The concept of weak Lie motion (weak Lie symmetry) is introduced. Applications given exhibit a reduction of the usual symmetry, e.g., in the case of the rotation group. In this context, a particular generalization of Lie algebras is found ('extended Lie algebras') which turns out to be an involutive distribution or a simple example for a tangent Lie algebroid. Riemannian and Lorentz metrics can be introduced on such an algebroid through an extended Cartan-Killing form. Transformation groups from non-relativistic mechanics and quantum mechanics lead to such tangent Lie algebroids and to Lorentz geometries constructed on them (1-dimensional gravitational fields).
Successful management of airway hemangioma with propranolol.
Mendiratta, Vibhu; Varghese, Bincy; Chander, Ram; Parakh, Ankit; Solanki, Ravi S
2013-06-01
Airway hemangiomas can be difficult to manage and cause anxiety in both the parents and the treating physician. Propranolol, a nonselective beta-blocker, has recently been used for treating proliferating infantile hemangiomas. We report successful management of a proliferating, large, mixed infantile hemangioma with subglottic extension in an Indian infant using oral propranolol in a dose of 2mg/kg/day without any side effects. Induction of early involution and freedom from the side effects of steroid therapy seem encouraging for using propranolol as a first line treatment modality in the management of troublesome hemangiomas. © 2013 The International Society of Dermatology.
From revolution to involution: the disappearance of the gay movement in France.
Duyvendak, J W
1995-01-01
This essay sketches the development of the modern French gay movement in relation to its political context, in particular to the French Socialist Party. The author argues that its curvilinear development the movement started very modestly in the 1950s, spread within small, radical left-wing circles in the late 1960s and early 1970s, peaked around 1980, and declined rapidly in the course of the 1980s can be explained by the ups and downs in political repression on the one hand and political support and success on the other.
Mikels, Joseph A; Löckenhoff, Corinna E; Maglio, Sam J; Goldstein, Mary K; Garber, Alan; Carstensen, Laura L
2010-03-01
Research on aging has indicated that whereas deliberative cognitive processes decline with age, emotional processes are relatively spared. To examine the implications of these divergent trajectories in the context of health care choices, we investigated whether instructional manipulations emphasizing a focus on feelings or details would have differential effects on decision quality among younger and older adults. We presented 60 younger and 60 older adults with health care choices that required them to hold in mind and consider multiple pieces of information. Instructional manipulations in the emotion-focus condition asked participants to focus on their emotional reactions to the options, report their feelings about the options, and then make a choice. In the information-focus condition, participants were instructed to focus on the specific attributes, report the details about the options, and then make a choice. In a control condition, no directives were given. Manipulation checks indicated that the instructions were successful in eliciting different modes of processing. Decision quality data indicate that younger adults performed better in the information-focus than in the control condition whereas older adults performed better in the emotion-focus and control conditions than in the information-focus condition. Findings support and extend extant theorizing on aging and decision making as well as suggest that interventions to improve decision-making quality should take the age of the decision maker into account.
Hostettler, Isabel Charlotte; Muroi, Carl; Richter, Johannes Konstantin; Schmid, Josef; Neidert, Marian Christoph; Seule, Martin; Boss, Oliver; Pangalu, Athina; Germans, Menno Robbert; Keller, Emanuela
2018-01-19
OBJECTIVE The aim of this study was to create prediction models for outcome parameters by decision tree analysis based on clinical and laboratory data in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS The database consisted of clinical and laboratory parameters of 548 patients with aSAH who were admitted to the Neurocritical Care Unit, University Hospital Zurich. To examine the model performance, the cohort was randomly divided into a derivation cohort (60% [n = 329]; training data set) and a validation cohort (40% [n = 219]; test data set). The classification and regression tree prediction algorithm was applied to predict death, functional outcome, and ventriculoperitoneal (VP) shunt dependency. Chi-square automatic interaction detection was applied to predict delayed cerebral infarction on days 1, 3, and 7. RESULTS The overall mortality was 18.4%. The accuracy of the decision tree models was good for survival on day 1 and favorable functional outcome at all time points, with a difference between the training and test data sets of < 5%. Prediction accuracy for survival on day 1 was 75.2%. The most important differentiating factor was the interleukin-6 (IL-6) level on day 1. Favorable functional outcome, defined as Glasgow Outcome Scale scores of 4 and 5, was observed in 68.6% of patients. Favorable functional outcome at all time points had a prediction accuracy of 71.1% in the training data set, with procalcitonin on day 1 being the most important differentiating factor at all time points. A total of 148 patients (27%) developed VP shunt dependency. The most important differentiating factor was hyperglycemia on admission. CONCLUSIONS The multiple variable analysis capability of decision trees enables exploration of dependent variables in the context of multiple changing influences over the course of an illness. The decision tree currently generated increases awareness of the early systemic stress response, which is seemingly pertinent for prognostication.
Molecular Regulation of the Mitosis/Meiosis Decision in Multicellular Organisms
Kimble, Judith
2011-01-01
A major step in the journey from germline stem cell to differentiated gamete is the decision to leave the mitotic cell cycle and begin progression through the meiotic cell cycle. Over the past decade, molecular regulators of the mitosis/meiosis decision have been discovered in most of the major model multicellular organisms. Historically, the mitosis/meiosis decision has been closely linked with controls of germline self-renewal and the sperm/egg decision, especially in nematodes and mice. Molecular explanations of those linkages clarify our understanding of this fundamental germ cell decision, and unifying themes have begun to emerge. Although the complete circuitry of the decision is not known in any organism, the recent advances promise to impact key issues in human reproduction and agriculture. PMID:21646377
ERIC Educational Resources Information Center
Benathen, Isaiah A.
1991-01-01
Alternatives to the traditional unknown tests that permit a clear and unequivocal differential identification decision between Bacillus subtilis and Bacillus megaterium are presented. Plates of Phenylethyl Alcohol agar with Blood (PEAB), slants of Bile Esculin agar and plates of DNA agar are used. The materials, methods, results, and conclusions…
The Manifest and Latent Functions of Differential Response in Child Welfare
ERIC Educational Resources Information Center
Ji, Daniel; Sullivan, Richard
2016-01-01
Although previous research has explored the efficacy of differential response (DR) programs in child welfare, there have been no studies to date about coding decisions between designations by child protection service agencies. Research has explored client satisfaction with DR as well as rates of recidivism and removal/placement but with limited…
Do Processing Patterns of Strengths and Weaknesses Predict Differential Treatment Response?
Miciak, Jeremy; Williams, Jacob L; Taylor, W Pat; Cirino, Paul T; Fletcher, Jack M; Vaughn, Sharon
2016-08-01
No previous empirical study has investigated whether the LD identification decisions of proposed methods to operationalize processing strengths and weaknesses (PSW) approaches for LD identification are associated with differential treatment response. We investigated whether the identification decisions of the concordance/discordance model (C/DM; Hale & Fiorello, 2004) and Cross Battery Assessment approach (XBA method; Flanagan, Ortiz, & Alfonso, 2007) were consistent and whether they predicted intervention response beyond that accounted for by pretest performance on measures of reading. Psychoeducational assessments were administered at pretest to 203 4 th graders with low reading comprehension and individual results were utilized to identify students who met LD criteria according to the C/DM and XBA methods and students who did not. Resulting group status permitted an investigation of agreement for identification methods and whether group status at pretest (LD or not LD) was associated with differential treatment response to an intensive reading intervention. The LD identification decisions of the XBA and C/DM demonstrated poor agreement with one another (κ = -.10). Comparisons of posttest performance for students who met LD criteria and those who did not meet were largely null, with small effect sizes across all measures. LD status, as identified through the C/DM and XBA approaches, was not associated with differential treatment response and did not contribute educationally meaningful information about how students would respond to intensive reading intervention. These results do not support the value of cognitive assessment utilized in this way as part of the LD identification process.
Affective biasing of choices in gambling task decision making.
Hinson, John M; Whitney, Paul; Holben, Heather; Wirick, Aaron K
2006-09-01
The proponents of the somatic marker hypothesis presume that rational decision making is guided by emotional reactions that are developed from prior experience. Supporting evidence for the hypothesis comes almost exclusively from the short-term affective reactions that are learned during the course of a hypothetical decision-making task--the gambling task (GT). We examined GT performance and affective reactions to choices when those choices were biased by words that had preexisting affective value. In one experiment, affectively valued words directly signaled good and bad choices. A congruent relation between affective value of word and choice outcome improved GT performance, whereas an incongruent relation greatly interfered with performance. In another experiment, affectively valued words were maintained as a working memory (WM) load between GT choices. A WM load with affectively positive words somewhat improved GT performance, whereas affectively negative words interfered with performance. Somatic markers-indicated by differential anticipatory skin conductance response (SCR) amplitude for good and bad choices-appeared at a point in the GT session when choice performance was superior. However, differential SCR developed during the session after good choice performance was already established. These results indicate that preexisting affective biases can influence GT decision making. In addition, the somatic markers that are regular accompaniments of GT decision making appeared to be temporally lagging indicators of choice performance.
Lelieveld, Gert-Jan; Aghajani, Moji; Boon, Albert E.; van der Wee, Nic J. A.; Popma, Arne; Vermeiren, Robert R. J. M.; Colins, Olivier F.
2016-01-01
Research suggests that individuals with conduct disorder (CD) are marked by social impairments, such as difficulties in processing the affective reactions of others. Little is known, though, about how they make decisions during social interactions in response to emotional expressions of others. In this study, we therefore investigated the neural mechanisms underlying fairness decisions in response to communicated emotions of others in aggressive, criminal justice-involved boys with CD (N = 32) compared with typically developing (TD) boys (N = 33), aged 15–19 years. Participants received written emotional responses (angry, disappointed or happy) from peers in response to a previous offer and then had to make fairness decisions in a version of the Dictator Game. Behavioral results showed that CD boys did not make differential fairness decisions in response to the emotions, whereas the TD boys did show a differentiation and also responded more unfair to happy reactions than the CD boys. Neuroimaging results revealed that when receiving happy vs disappointed and angry reactions, the CD boys showed less activation than the TD boys in the temporoparietal junction and supramarginal gyrus, regions involved in perspective taking and attention. These results suggest that boys with CD have difficulties with processing explicit emotional cues from others on behavioral and neural levels. PMID:26926604
Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe
2014-03-01
This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.
ERIC Educational Resources Information Center
Lutz, Wolfgang; Saunders, Stephen M.; Leon, Scott C.; Martinovich, Zoran; Kosfelder, Joachim; Schulte, Dietmar; Grawe, Klaus; Tholen, Sven
2006-01-01
In the delivery of clinical services, outcomes monitoring (i.e., repeated assessments of a patient's response to treatment) can be used to support clinical decision making (i.e., recurrent revisions of outcome expectations on the basis of that response). Outcomes monitoring can be particularly useful in the context of established practice research…
ERIC Educational Resources Information Center
Torres, Mario S., Jr.
2012-01-01
This study examined federal and state court decisions related to student Fourth Amendment rights following the "New Jersey v. T.L.O." ruling in 1985. There has been minimal research in judicial treatment of students' Fourth Amendment rights across regions of the country and less to what extent regional rulings implicitly or explicitly…
ERIC Educational Resources Information Center
Miller, Duane I.
Failure to establish a strong relationship between attitudes and buying behavior may indicate that the personality-consumer behavior link is mediated by some social mechanism, such as differential propensities toward advice-seeking. Undergraduates (N=75) completed two measures of attitudes, a questionnaire consisting of 10 consumer decisions and…
Enhancing Adolescent Girls' Argument Skills in Reasoning about Personal and Non-Personal Decisions
ERIC Educational Resources Information Center
Udell, Wadiya
2007-01-01
The present study sought to evaluate (a) the effectiveness of an intervention in developing adolescents' argument skills regarding a decision on a topic of high potential personal relevance (teen pregnancy) or one of general social relevance (capital punishment), and (b) differential effects of the two topics in promoting the generalization of…
The Effects of Enhanced Informed Consent in a Pro-Life Pregnancy Counseling Center.
ERIC Educational Resources Information Center
Mardirosian, Kathryn; And Others
1990-01-01
Investigated effects of enhanced informed consent condition on attitudes of female clients (n=60) toward a counselor, counseling situation, and decision making in a pro-life pregnancy center. Results suggest enhanced consent did not lead to increased or decreased decisions to abort nor to differential attitudes toward counselor or setting.…
Research of grinding process of gears with involute profile to increase its efficiency
NASA Astrophysics Data System (ADS)
Ivanova, T. N.; Korshunov, A. I.; Sannikov, I. N.; Tyukpiekov, V. N.
2018-03-01
Grinding as final processing exerts great influence on quality and accuracy of a surface layer of gears. Gear grinding is the most productive method of abrasive processing providing gears of 3 - 8 degrees of accuracy. However violation of the temperature condition of grinding leads to emergence of burns on the surfaces of gears. Therefore the research of the reasons generating defects and finding the ways of their elimination are relevant. The work presents the research of involute tooth profile grinding by wheels of different types with different ways to form a surface. For every way the movements of a tool and a workpiece in order to receive a contour of the tooth socket are simulated. The advantages and the shortcomings of the tooth grinding using form wheels in a grinding method and using dish, worm wheels in generating the grinding method are revealed. The experience of gear production shows that availability of burns in the certain part of a tooth profile is caused by features of the gear grinding process. Theoretical and experimental researches of the thermal phenomena of gear grinding with different configurations of spots in a contact zone and a trajectory of their movement are conducted. There are recommendations how to choose grinding modes, characteristics of abrasive tools taking into account a non-burnt condition of a working surface of a gear. The right choice of lubricating fluid and the way of its supply greatly affect the efficiency of the gear grinding process. It is established that lubricating fluid with special additives gives the best results to obtain desired roughness of a processed surface. The recommendations of effective fluids and their foreign analogs are made.
Cheng, Zhangrui; Oguejiofor, Chike F; Swangchan-Uthai, Theerawat; Carr, Susan; Wathes, D Claire
2015-08-14
Both high and low circulating urea concentrations, a product of protein metabolism, are associated with decreased fertility in dairy cows through poorly defined mechanisms. The rate of involution and the endometrial ability to mount an adequate innate immune response after calving are both critical for subsequent fertility. Study 1 used microarray analysis to identify genes whose endometrial expression 2 weeks postpartum correlated significantly with the mean plasma urea per cow, ranging from 3.2 to 6.6 mmol/L. The biological functions of 781 mapped genes were analysed using Ingenuity Pathway Analysis. These were predominantly associated with tissue turnover (e.g., BRINP1, FOXG1), immune function (e.g., IL17RB, CRISPLD2), inflammation (e.g., C3, SERPINF1, SERPINF2) and lipid metabolism (e.g., SCAP, ACBD5, SLC10A). Study 2 investigated the relationship between urea concentration and expression of 6 candidate genes (S100A8, HSP5A, IGF1R, IL17RB, BRINP1, CRISPLD2) in bovine endometrial cell culture. These were treated with 0, 2.5, 5.0 or 7.5 mmol/L urea, equivalent to low, medium and high circulating values with or without challenge by bacterial lipopolysaccharide (LPS). LPS increased S100A8 expression as expected but urea treatment had no effect on expression of any tested gene. Examination of the genes/pathways involved suggests that plasma urea levels may reflect variations in lipid metabolism. Our results suggest that it is the effects of lipid metabolism rather than the urea concentration which probably alter the rate of involution and innate immune response, in turn influencing subsequent fertility.
Swangchan-Uthai, Theerawat; Chen, Qiusheng; Kirton, Sally E; Fenwick, Mark A; Cheng, Zhangrui; Patton, Joe; Fouladi-Nashta, Ali A; Wathes, D Claire
2013-05-01
Uterine inflammation occurs after calving in association with extensive endometrial remodelling and bacterial contamination. If the inflammation persists, it leads to reduced fertility. Chronic endometritis is highly prevalent in high-yielding cows that experience negative energy balance (NEB) in early lactation. This study investigated the effect of NEB on the antimicrobial peptides S100A8 and S100A9 in involuting uteri collected 2 weeks post partum. Holstein-Friesian cows (six per treatment) were randomly allocated to two interventions designed to produce mild or severe NEB (MNEB and SNEB) status. Endometrial samples were examined histologically, and the presence of neutrophils, macrophages, lymphocytes and natural killer cells was confirmed using haematoxylin and eosin and immunostaining. SNEB cows had greater signs of uterine inflammation. Samples of previously gravid uterine horn were used to localise S100A8 and S100A9 by immunohistochemistry. Both S100 proteins were present in bovine endometrium with strong staining in epithelial and stromal cells and in infiltrated leucocytes. Immunostaining was significantly higher in SNEB cows along with increased numbers of segmented neutrophils. These results suggest that the metabolic changes of a post-partum cow suffering from NEB delay uterine involution and promote a chronic state of inflammation. We show that upregulation of S100A8 and S100A9 is clearly a key component of the early endometrial response to uterine infection. Further studies are warranted to link the extent of this response after calving to the likelihood of cows developing endometritis and to their subsequent fertility.
Bollig-Fischer, Aliccia; Thakur, Archana; Sun, Yuan; Wu, Jiusheng; Liao, D Joshua
2012-03-01
There are many estrogen receptor α (ERα) antibodies available but few of them target a rodent ERα. Using the MC-20 antibody raised against the C-terminus of mouse ERα, we show in this communication that in the mammary gland of female mice and rats, the wild type (wt) ERα was detected on immunoblots as a dominant protein only during lactation, and the protein was lactating specific as it migrated slightly faster than the 67-kD wt ERα in the uterus, likely due to a different phosphorylation status. In contrast, in the nulliparous, pregnant, involuting and involuted mammary glands, the dominant protein recognized by MC-20 was about 61-kD, which is dubbed herein as "MC-20 reactive protein" or MC20RP in abbreviation as its identity is unknown. Our results showed that it was not derived from proteolysis or de-phosphorylation of the 67-kD ERα and was unlikely to be translated from an ERα mRNA variant. Ovariectomy decreased the lactating specific wt ERα but increased the 61-kD MC20RP in the mammary tumors from MMTV-c-myc transgenic mice but these two proteins in the uterus were unaffected. The 61-kD MC20RP was decreased in the mammary tumors, compared with proliferating mammary glands, in estrogen-treated ACI rats. These results suggest that while the lactating specific wt ERα alone or together with the MC20RP may sustain lactation, the MC20RP may support proliferation of the mammary gland and some mammary tumors.
Yamada, Toshiyuki; Nanashima, Naoki; Shimizu, Takeshi; Nakazawa, Yosuke; Nakazawa, Mitsuru; Tsuchida, Shigeki
2015-10-15
From our stock of SDRs (Sprague-Dawley rats), we established a mutant strain having small opaque eyes and named it HiSER (Hirosaki small-eye rat). The HiSER phenotype is progressive and autosomal recessive. In HiSER eyes, disruption and involution of the lens, thickening of the inner nuclear layer, detachment and aggregation of the retina, rudimentary muscle in the ciliary body and cell infiltration in the vitreous humour were observed. Genetic linkage analysis using crossing with Brown Norway rat suggested that the causative gene(s) is located on chromosome 10. Microarray analysis showed that the expression level of the Cryba1 gene encoding βA3/A1-crystallin on chromosome 10 was markedly decreased in HiSER eyes. Genomic PCR revealed deletion of a 3.6-kb DNA region encompassing exons 4-6 of the gene in HiSERs. In HiSER eyes, a chimaeric transcript of the gene containing exons 1-3 and an approximately 250-bp sequence originating from the 3'-UTR of the Nufip2 gene, located downstream of the breakpoint in the opposite direction, was present. Whereas the chimaeric transcript was expressed in HiSER eyes, neither normal nor chimaeric βA3/A1-crystallin proteins were detected by Western blot analysis. Real-time RT (reverse transcription)-PCR analysis revealed that expression level of the Nufip2 gene in the HiSER eye was 40% of that in the SDR eye. These results suggest that the disappearance of the βA3/A1-crystallin protein and, in addition, down-regulation of the Nufip2 gene as a consequence of gene rearrangement causes the HiSER phenotype. © 2015 Authors; published by Portland Press Limited.
Swangchan-Uthai, Theerawat; Chen, Qiusheng; Kirton, Sally E; Fenwick, Mark A; Cheng, Zhangrui; Patton, Joe; Fouladi-Nashta, Ali A; Wathes, D Claire
2013-01-01
Uterine inflammation occurs after calving in association with extensive endometrial remodelling and bacterial contamination. If the inflammation persists, it leads to reduced fertility. Chronic endometritis is highly prevalent in high-yielding cows that experience negative energy balance (NEB) in early lactation. This study investigated the effect of NEB on the antimicrobial peptides S100A8 and S100A9 in involuting uteri collected 2 weeks post partum. Holstein-Friesian cows (six per treatment) were randomly allocated to two interventions designed to produce mild or severe NEB (MNEB and SNEB) status. Endometrial samples were examined histologically, and the presence of neutrophils, macrophages, lymphocytes and natural killer cells was confirmed using haematoxylin and eosin and immunostaining. SNEB cows had greater signs of uterine inflammation. Samples of previously gravid uterine horn were used to localise S100A8 and S100A9 by immunohistochemistry. Both S100 proteins were present in bovine endometrium with strong staining in epithelial and stromal cells and in infiltrated leucocytes. Immunostaining was significantly higher in SNEB cows along with increased numbers of segmented neutrophils. These results suggest that the metabolic changes of a post-partum cow suffering from NEB delay uterine involution and promote a chronic state of inflammation. We show that upregulation of S100A8 and S100A9 is clearly a key component of the early endometrial response to uterine infection. Further studies are warranted to link the extent of this response after calving to the likelihood of cows developing endometritis and to their subsequent fertility. PMID:23533291
Rodríguez-Fernández, Lucía; Ferrer-Vicens, Iván; García, Concha; Oltra, Sara S; Zaragozá, Rosa; Viña, Juan R; García-Trevijano, Elena R
2016-09-15
Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca(2+)-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification. In both models, E-cadherin, β-catenin, p-120, and talin-1 were cleaved as assessed by western blot analysis. Both CAPNs were able to cleave adhesion proteins from lactating mammary gland in vitro Nevertheless, CAPN2 was the only isoform found to co-localize with E-cadherin in cell junctions at the peak of lactation. CAPN2/E-cadherin in vivo interaction, analyzed by proximity ligation assay, was dramatically increased during involution. Calpain inhibitor administration prevented the cytosolic accumulation of truncated E-cadherin cleaved by CAPN2. Conversely, in breast cancer cells, CAPN2 was restricted to the nuclear compartment. The isoform-specific expression of CAPNs and CAPN activity was dependent on the breast cancer subtype. However, CAPN1 and CAPN2 knockdown cells showed that cleavage of adhesion proteins and cell migration was mediated by CAPN1, independently of the breast cancer cell line used. Data presented here suggest that the subcellular distribution of CAPN1 and CAPN2 is a major issue in target-substrate recognition; therefore, it determines the isoform-specific role of CAPNs during disruption of cell adhesion in either a physiological or a pathological context. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.
Right ventricular involution: What can we learn from nature's model of compensated hypertrophy?
Bowen, Megan E; Liu, Xiaoqing; Sundwall, Peter M; Drakos, Stavros G; Li, Dean Y; Selzman, Craig H; McKellar, Stephen H
2018-05-01
Right ventricular (RV) failure (RVF) is a vexing problem facing patients with various disease processes and carries a high mortality. RVF is a poorly understood phenomenon with limited treatment options. In mammalian fetal circulation, the right ventricle is the systemic ventricle. In neonates, however, the left ventricle assumes that role and gradually thickens compared with the right ventricle. This process, known as right ventricular involution (RVI), is poorly understood. We sought to define the time course and identify mechanisms involved in RVI. Wild-type mice were bred and sacrificed on day of life (DOL) 1, 4, 8, 16, and 30 to evaluate left ventricular (LV) and RV wall thickness and apoptosis. A terminal deoxynucleotidyl transferase nick-end labeling assay and RNA sequencing were performed to measure changes during RVI. Morphometric analysis demonstrated the changes in RV and LV wall thickness occurring between DOL 1 and DOL 16 (RV:LV, 0.53:0.44; P = .03). In addition, apoptosis was most active early, with the highest percentage of apoptotic cells on DOL 1 (1.0%) and a significant decrease by DOL 30 (0.23%) (P = .02). Similarly, expression of the proapoptotic genes BCL2l11 and Pawr were increased at DOL 1, and the antiapoptotic genes Nol3 and Naip2 were significantly increased at DOL 30. RVI is a misnomer, but significant changes occur early (by DOL 16) in neonatal mouse hearts. Apoptosis plays a role in RVI, but whether manipulation of apoptotic pathways can prevent or reverse RVI is unknown and warrants further investigation. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Lorenzo, Laureanne P E; Shatynski, Kristen E; Clark, Sarah; Yarowsky, Paul J; Williams, Mark S
2013-01-01
In addition to archetypal cognitive defects, Down syndrome (DS) is characterized by altered lymphocyte development and function, including premature thymic involution and increased incidence of infections. However, the potential mechanisms for these changes have not been fully elucidated. The current study used the Ts65Dn mouse model of DS to assess deficiencies in T-cell development and possible molecular alterations. Ts65Dn mice exhibited premature thymic involution and a threefold to fourfold decrease in the number and proportion of immature, double-negative thymocyte progenitors. In addition, there were twofold fewer double-positive and CD4 single-positive thymocytes in Ts65Dn thymuses. Reflecting this deficient thymic function, there were fewer naive T cells in the spleen and polyclonal stimulation of peripheral T cells exhibited a marked reduction in proliferation, suggesting a senescent phenotype. In contrast, B-cell progenitors were unchanged in the bone marrow of Ts65Dn mice, but in the spleen, there were decreased transitional and follicular B cells and these cells proliferated less upon antigen receptor stimulus but not in response to lipopolysaccharide. As a potential mechanism for diminished thymic function, immature thymocyte populations expressed diminished levels of the cytokine receptor interleukin-7Rα, which was associated with decreased proliferation and increased apoptosis. Increased oxidative stress and inhibition of the Notch pathway were identified as possible mediators of decreased interleukin-7Rα expression in Ts65Dn mice. The data suggest that immature thymocyte defects underlie immune dysfunction in DS and that increased oxidative stress and reduced cytokine signalling may alter lymphocyte development in Ts65Dn mice. PMID:23432468
DOE Office of Scientific and Technical Information (OSTI.GOV)
Costa-Silva, Bruno; Programa de Pos-graduacao em Neurociencias, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C.; Coelho da Costa, Meline
The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effectmore » was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells.« less
Neurofunctional Correlates of Ethical, Food-Related Decision-Making
Cherry, J. Bradley C.; Bruce, Jared M.; Lusk, Jayson L.; Crespi, John M.; Lim, Seung-Lark; Bruce, Amanda S.
2015-01-01
For consumers today, the perceived ethicality of a food’s production method can be as important a purchasing consideration as its price. Still, few studies have examined how, neurofunctionally, consumers are making ethical, food-related decisions. We examined how consumers’ ethical concern about a food’s production method may relate to how, neurofunctionally, they make decisions whether to purchase that food. Forty-six participants completed a measure of the extent to which they took ethical concern into consideration when making food-related decisions. They then underwent a series of functional magnetic resonance imaging (fMRI) scans while performing a food-related decision-making (FRDM) task. During this task, they made 56 decisions whether to purchase a food based on either its price (i.e., high or low, the “price condition”) or production method (i.e., with or without the use of cages, the “production method condition”), but not both. For 23 randomly selected participants, we performed an exploratory, whole-brain correlation between ethical concern and differential neurofunctional activity in the price and production method conditions. Ethical concern correlated negatively and significantly with differential neurofunctional activity in the left dorsolateral prefrontal cortex (dlPFC). For the remaining 23 participants, we performed a confirmatory, region-of-interest (ROI) correlation between the same variables, using an 8-mm3 volume situated in the left dlPFC. Again, the variables correlated negatively and significantly. This suggests, when making ethical, food-related decisions, the more consumers take ethical concern into consideration, the less they may rely on neurofunctional activity in the left dlPFC, possibly because making these decisions is more routine for them, and therefore a more perfunctory process requiring fewer cognitive resources. PMID:25830288
Neurofunctional correlates of ethical, food-related decision-making.
Cherry, J Bradley C; Bruce, Jared M; Lusk, Jayson L; Crespi, John M; Lim, Seung-Lark; Bruce, Amanda S
2015-01-01
For consumers today, the perceived ethicality of a food's production method can be as important a purchasing consideration as its price. Still, few studies have examined how, neurofunctionally, consumers are making ethical, food-related decisions. We examined how consumers' ethical concern about a food's production method may relate to how, neurofunctionally, they make decisions whether to purchase that food. Forty-six participants completed a measure of the extent to which they took ethical concern into consideration when making food-related decisions. They then underwent a series of functional magnetic resonance imaging (fMRI) scans while performing a food-related decision-making (FRDM) task. During this task, they made 56 decisions whether to purchase a food based on either its price (i.e., high or low, the "price condition") or production method (i.e., with or without the use of cages, the "production method condition"), but not both. For 23 randomly selected participants, we performed an exploratory, whole-brain correlation between ethical concern and differential neurofunctional activity in the price and production method conditions. Ethical concern correlated negatively and significantly with differential neurofunctional activity in the left dorsolateral prefrontal cortex (dlPFC). For the remaining 23 participants, we performed a confirmatory, region-of-interest (ROI) correlation between the same variables, using an 8-mm3 volume situated in the left dlPFC. Again, the variables correlated negatively and significantly. This suggests, when making ethical, food-related decisions, the more consumers take ethical concern into consideration, the less they may rely on neurofunctional activity in the left dlPFC, possibly because making these decisions is more routine for them, and therefore a more perfunctory process requiring fewer cognitive resources.
Differential Diagnosis of Hispanic Children Referred for Autism Spectrum Disorders: Complex Issues
ERIC Educational Resources Information Center
Overton, Terry; Fielding, Cheryl; Alba, Roman
2007-01-01
This study examines the decision-making process used for differential diagnosis of a sample of Hispanic children referred for autism spectrum disorders (ASDs). Of the sample of 28 children, 18 were diagnosed with ASDs. Of the 10 children who were not diagnosed with ASDs, 80% were found to have multiple diagnostic labels or comorbidities.…
Weiss, Cary N.; Ito, Keisuke
2015-01-01
In the adult, the source of functionally diverse, mature blood cells are hematopoietic stem cells, a rare population of quiescent cells that reside in the bone marrow niche. Like stem cells in other tissues, hematopoietic stem cells are defined by their ability to self-renew, in order to maintain the stem cell population for the lifetime of the organism, and to differentiate, in order to give rise to the multiple lineages of the hematopoietic system. In recent years, increasing evidence has suggested a role for the accumulation of reactive oxygen species and DNA damage in the decision for hematopoietic stem cells to exit quiescence and to differentiate. In this review, we will examine recent work supporting the idea that detection of cell stressors, such as oxidative and genetic damage, is an important mediator of cell fate decisions in hematopoietic stem cells. We will explore the benefits of such a system in avoiding the development and progression of malignancies, and in avoiding tissue exhaustion and failure. Additionally, we will discuss new work that examines the accumulation of DNA damage and replication stress in aging hematopoietic stem cells and causes us to rethink ideas of genoprotection in the bone marrow niche. PMID:25789504
Shankar, Swetha; Kayser, Andrew S
2017-06-01
To date it has been unclear whether perceptual decision making and rule-based categorization reflect activation of similar cognitive processes and brain regions. On one hand, both map potentially ambiguous stimuli to a smaller set of motor responses. On the other hand, decisions about perceptual salience typically concern concrete sensory representations derived from a noisy stimulus, while categorization is typically conceptualized as an abstract decision about membership in a potentially arbitrary set. Previous work has primarily examined these types of decisions in isolation. Here we independently varied salience in both the perceptual and categorical domains in a random dot-motion framework by manipulating dot-motion coherence and motion direction relative to a category boundary, respectively. Behavioral and modeling results suggest that categorical (more abstract) information, which is more relevant to subjects' decisions, is weighted more strongly than perceptual (more concrete) information, although they also have significant interactive effects on choice. Within the brain, BOLD activity within frontal regions strongly differentiated categorical salience and weakly differentiated perceptual salience; however, the interaction between these two factors activated similar frontoparietal brain networks. Notably, explicitly evaluating feature interactions revealed a frontal-parietal dissociation: parietal activity varied strongly with both features, but frontal activity varied with the combined strength of the information that defined the motor response. Together, these data demonstrate that frontal regions are driven by decision-relevant features and argue that perceptual decisions and rule-based categorization reflect similar cognitive processes and activate similar brain networks to the extent that they define decision-relevant stimulus-response mappings. NEW & NOTEWORTHY Here we study the behavioral and neural dynamics of perceptual categorization when decision information varies in multiple domains at different levels of abstraction. Behavioral and modeling results suggest that categorical (more abstract) information is weighted more strongly than perceptual (more concrete) information but that perceptual and categorical domains interact to influence decisions. Frontoparietal brain activity during categorization flexibly represents decision-relevant features and highlights significant dissociations in frontal and parietal activity during decision making. Copyright © 2017 the American Physiological Society.
Kayser, Andrew S.
2017-01-01
To date it has been unclear whether perceptual decision making and rule-based categorization reflect activation of similar cognitive processes and brain regions. On one hand, both map potentially ambiguous stimuli to a smaller set of motor responses. On the other hand, decisions about perceptual salience typically concern concrete sensory representations derived from a noisy stimulus, while categorization is typically conceptualized as an abstract decision about membership in a potentially arbitrary set. Previous work has primarily examined these types of decisions in isolation. Here we independently varied salience in both the perceptual and categorical domains in a random dot-motion framework by manipulating dot-motion coherence and motion direction relative to a category boundary, respectively. Behavioral and modeling results suggest that categorical (more abstract) information, which is more relevant to subjects’ decisions, is weighted more strongly than perceptual (more concrete) information, although they also have significant interactive effects on choice. Within the brain, BOLD activity within frontal regions strongly differentiated categorical salience and weakly differentiated perceptual salience; however, the interaction between these two factors activated similar frontoparietal brain networks. Notably, explicitly evaluating feature interactions revealed a frontal-parietal dissociation: parietal activity varied strongly with both features, but frontal activity varied with the combined strength of the information that defined the motor response. Together, these data demonstrate that frontal regions are driven by decision-relevant features and argue that perceptual decisions and rule-based categorization reflect similar cognitive processes and activate similar brain networks to the extent that they define decision-relevant stimulus-response mappings. NEW & NOTEWORTHY Here we study the behavioral and neural dynamics of perceptual categorization when decision information varies in multiple domains at different levels of abstraction. Behavioral and modeling results suggest that categorical (more abstract) information is weighted more strongly than perceptual (more concrete) information but that perceptual and categorical domains interact to influence decisions. Frontoparietal brain activity during categorization flexibly represents decision-relevant features and highlights significant dissociations in frontal and parietal activity during decision making. PMID:28250149
Navigating the Decision Space: Shared Medical Decision Making as Distributed Cognition.
Lippa, Katherine D; Feufel, Markus A; Robinson, F Eric; Shalin, Valerie L
2017-06-01
Despite increasing prominence, little is known about the cognitive processes underlying shared decision making. To investigate these processes, we conceptualize shared decision making as a form of distributed cognition. We introduce a Decision Space Model to identify physical and social influences on decision making. Using field observations and interviews, we demonstrate that patients and physicians in both acute and chronic care consider these influences when identifying the need for a decision, searching for decision parameters, making actionable decisions Based on the distribution of access to information and actions, we then identify four related patterns: physician dominated; physician-defined, patient-made; patient-defined, physician-made; and patient-dominated decisions. Results suggests that (a) decision making is necessarily distributed between physicians and patients, (b) differential access to information and action over time requires participants to transform a distributed task into a shared decision, and (c) adverse outcomes may result from failures to integrate physician and patient reasoning. Our analysis unifies disparate findings in the medical decision-making literature and has implications for improving care and medical training.
A Decision Analysis Perspective on Multiple Response Robust Optimization
2012-03-01
the utility function in question is monotonically increasing and is twice differentiable . If γ(y) = 0, the utility function is describing risk neutral...twice differentiable , the risk aversion function with respect to a single attribute, yi, i = 1, . . . , n, is given in Equation 2.9, γUyi = − U ′′yi U...UV (V (y1, y2)) and fol- lowing the chain rule of differentiation , Matheson and Abbas [31] show that the risk aversion with respect to a single
MRI-based decision tree model for diagnosis of biliary atresia.
Kim, Yong Hee; Kim, Myung-Joon; Shin, Hyun Joo; Yoon, Haesung; Han, Seok Joo; Koh, Hong; Roh, Yun Ho; Lee, Mi-Jung
2018-02-23
To evaluate MRI findings and to generate a decision tree model for diagnosis of biliary atresia (BA) in infants with jaundice. We retrospectively reviewed features of MRI and ultrasonography (US) performed in infants with jaundice between January 2009 and June 2016 under approval of the institutional review board, including the maximum diameter of periportal signal change on MRI (MR triangular cord thickness, MR-TCT) or US (US-TCT), visibility of common bile duct (CBD) and abnormality of gallbladder (GB). Hepatic subcapsular flow was reviewed on Doppler US. We performed conditional inference tree analysis using MRI findings to generate a decision tree model. A total of 208 infants were included, 112 in the BA group and 96 in the non-BA group. Mean age at the time of MRI was 58.7 ± 36.6 days. Visibility of CBD, abnormality of GB and MR-TCT were good discriminators for the diagnosis of BA and the MRI-based decision tree using these findings with MR-TCT cut-off 5.1 mm showed 97.3 % sensitivity, 94.8 % specificity and 96.2 % accuracy. MRI-based decision tree model reliably differentiates BA in infants with jaundice. MRI can be an objective imaging modality for the diagnosis of BA. • MRI-based decision tree model reliably differentiates biliary atresia in neonatal cholestasis. • Common bile duct, gallbladder and periportal signal changes are the discriminators. • MRI has comparable performance to ultrasonography for diagnosis of biliary atresia.
Singh, Varsha
2013-01-01
The Iowa Gambling Task (IGT) is based on the assumption that a decision maker is equally motivated to seek reward and avoid punishment, and that decision making is governed solely by the intertemporal attribute (i.e., preference for an option that produces an immediate outcome instead of one that yields a delayed outcome is believed to reflect risky decision making and is considered a deficit). It was assumed in the present study that the emotion- and cognition-based processing dichotomy manifests in the IGT as reward and punishment frequency and the intertemporal attribute. It was further proposed that the delineation of emotion- and cognition-based processing is contingent upon reward and punishment as manifested in the frame of the task (variant type) and task motivation (instruction type). The effects of IGT variant type (reward vs. punishment) and instruction type (task motivation induced by instruction types: reward, punishment, reward and punishment, or no hint) on the intertemporal and frequency attributes of IGT decision-making were analyzed. Decision making in the reward variant was equally governed by both attributes, and significantly affected by instruction type, while decision making in the punishment variant was differentially affected by the two attributes and not significantly impacted by instruction type. These results suggest that reward and punishment manifested via task frame as well as the task motivation may facilitate the differentiation of emotion- and cognition-based processing in the IGT.
Singh, Varsha
2013-01-01
The Iowa Gambling Task (IGT) is based on the assumption that a decision maker is equally motivated to seek reward and avoid punishment, and that decision making is governed solely by the intertemporal attribute (i.e., preference for an option that produces an immediate outcome instead of one that yields a delayed outcome is believed to reflect risky decision making and is considered a deficit). It was assumed in the present study that the emotion- and cognition-based processing dichotomy manifests in the IGT as reward and punishment frequency and the intertemporal attribute. It was further proposed that the delineation of emotion- and cognition-based processing is contingent upon reward and punishment as manifested in the frame of the task (variant type) and task motivation (instruction type). The effects of IGT variant type (reward vs. punishment) and instruction type (task motivation induced by instruction types: reward, punishment, reward and punishment, or no hint) on the intertemporal and frequency attributes of IGT decision-making were analyzed. Decision making in the reward variant was equally governed by both attributes, and significantly affected by instruction type, while decision making in the punishment variant was differentially affected by the two attributes and not significantly impacted by instruction type. These results suggest that reward and punishment manifested via task frame as well as the task motivation may facilitate the differentiation of emotion- and cognition-based processing in the IGT. PMID:24381567
Reconstructing blood stem cell regulatory network models from single-cell molecular profiles
Hamey, Fiona K.; Nestorowa, Sonia; Kinston, Sarah J.; Kent, David G.; Wilson, Nicola K.
2017-01-01
Adult blood contains a mixture of mature cell types, each with specialized functions. Single hematopoietic stem cells (HSCs) have been functionally shown to generate all mature cell types for the lifetime of the organism. Differentiation of HSCs toward alternative lineages must be balanced at the population level by the fate decisions made by individual cells. Transcription factors play a key role in regulating these decisions and operate within organized regulatory programs that can be modeled as transcriptional regulatory networks. As dysregulation of single HSC fate decisions is linked to fatal malignancies such as leukemia, it is important to understand how these decisions are controlled on a cell-by-cell basis. Here we developed and applied a network inference method, exploiting the ability to infer dynamic information from single-cell snapshot expression data based on expression profiles of 48 genes in 2,167 blood stem and progenitor cells. This approach allowed us to infer transcriptional regulatory network models that recapitulated differentiation of HSCs into progenitor cell types, focusing on trajectories toward megakaryocyte–erythrocyte progenitors and lymphoid-primed multipotent progenitors. By comparing these two models, we identified and subsequently experimentally validated a difference in the regulation of nuclear factor, erythroid 2 (Nfe2) and core-binding factor, runt domain, alpha subunit 2, translocated to, 3 homolog (Cbfa2t3h) by the transcription factor Gata2. Our approach confirms known aspects of hematopoiesis, provides hypotheses about regulation of HSC differentiation, and is widely applicable to other hierarchical biological systems to uncover regulatory relationships. PMID:28584094
Operating principles of tristable circuits regulating cellular differentiation
NASA Astrophysics Data System (ADS)
Jia, Dongya; Jolly, Mohit Kumar; Harrison, William; Boareto, Marcelo; Ben-Jacob, Eshel; Levine, Herbert
2017-06-01
Many cell-fate decisions during embryonic development are governed by a motif comprised of two transcription factors (TFs) A and B that mutually inhibit each other and may self-activate. This motif, called as a self-activating toggle switch (SATS), can typically have three stable states (phenotypes)—two corresponding to differentiated cell fates, each of which has a much higher level of one TF than the other—≤ft(A,~B\\right)=≤ft(1,~0\\right) or ≤ft(0,~1\\right) —and the third state corresponding to an ‘undecided’ stem-like state with similar levels of both A and B—≤ft(A,~B\\right)=≤ft(1/2,1/2\\right) . Furthermore, two or more SATSes can be coupled together in various topologies in different contexts, thereby affecting the coordination between multiple cellular decisions. However, two questions remain largely unanswered: (a) what governs the co-existence and relative stability of these three stable states? (b) What orchestrates the decision-making of coupled SATSes? Here, we first demonstrate that the co-existence and relative stability of the three stable states in an individual SATS can be governed by the relative strength of self-activation, external signals activating and/or inhibiting A and B, and mutual degradation between A and B. Simultaneously, we investigate the effects of these factors on the decision-making of two coupled SATSes. Our results offer novel understanding into the operating principles of individual and coupled tristable self-activating toggle switches (SATSes) regulating cellular differentiation and can yield insights into synthesizing three-way genetic circuits and understanding of cellular reprogramming.
Livingston, Jennifer I; Deprey, Sara M; Hensley, Craig P
2015-10-01
differential diagnosis and clinical decision making. Young adults with lateral hip pain are often referred to physical therapy (PT). A thorough examination is required to obtain a diagnosis and guide management. The purpose of this case report is to describe the physical therapist's differential diagnostic process and clinical decision making for a subject with the referring diagnosis of trochanteric bursitis. A 29-year-old female presented to PT with limited sitting and running tolerance secondary to right lateral hip pain. Her symptoms began three months prior when she abruptly changed her running intensity and frequency of weight bearing activities, including running and low impact plyometrics for the lower extremity. Physical examination revealed a positive Trendelenburg sign, manual muscle test that was weak and painless of the right hip abductors, and pain elicited when performing a vertical hop on a concrete surface (+single leg hop test), but pain-free when performing the same single leg hop on a foam surface. Examination findings warranted discussion with the referring physician for further diagnostic imaging. Magnetic resonance imaging revealed a focus of edema in the posterior acetabulum, suspicious for an acetabular stress fracture. The subject was subsequently diagnosed with an acetabular stress fracture and restricted from running and plyometrics for four weeks. Thorough examination and appropriate clinical decision making by the physical therapist at the initial examination led to the diagnosis of an acetabular stress fracture in this subject. Clinicians must be aware of symptoms and signs which place the subject at risk for stress fracture for timely referral and management. 4.
Social Influences in Sequential Decision Making
Schöbel, Markus; Rieskamp, Jörg; Huber, Rafael
2016-01-01
People often make decisions in a social environment. The present work examines social influence on people’s decisions in a sequential decision-making situation. In the first experimental study, we implemented an information cascade paradigm, illustrating that people infer information from decisions of others and use this information to make their own decisions. We followed a cognitive modeling approach to elicit the weight people give to social as compared to private individual information. The proposed social influence model shows that participants overweight their own private information relative to social information, contrary to the normative Bayesian account. In our second study, we embedded the abstract decision problem of Study 1 in a medical decision-making problem. We examined whether in a medical situation people also take others’ authority into account in addition to the information that their decisions convey. The social influence model illustrates that people weight social information differentially according to the authority of other decision makers. The influence of authority was strongest when an authority's decision contrasted with private information. Both studies illustrate how the social environment provides sources of information that people integrate differently for their decisions. PMID:26784448
Social Influences in Sequential Decision Making.
Schöbel, Markus; Rieskamp, Jörg; Huber, Rafael
2016-01-01
People often make decisions in a social environment. The present work examines social influence on people's decisions in a sequential decision-making situation. In the first experimental study, we implemented an information cascade paradigm, illustrating that people infer information from decisions of others and use this information to make their own decisions. We followed a cognitive modeling approach to elicit the weight people give to social as compared to private individual information. The proposed social influence model shows that participants overweight their own private information relative to social information, contrary to the normative Bayesian account. In our second study, we embedded the abstract decision problem of Study 1 in a medical decision-making problem. We examined whether in a medical situation people also take others' authority into account in addition to the information that their decisions convey. The social influence model illustrates that people weight social information differentially according to the authority of other decision makers. The influence of authority was strongest when an authority's decision contrasted with private information. Both studies illustrate how the social environment provides sources of information that people integrate differently for their decisions.
Illuminating hospital discharge planning: staff nurse decision making.
Rhudy, Lori M; Holland, Diane E; Bowles, Kathryn H
2010-11-01
This qualitative study proposed to examine staff RN's decision making related to discharge planning and perceptions of their role. Themes resulting from interviews were "following the script" and "RN as coordinator." The decision to consult a discharge planner occurred when the patient's situation did not follow the RN's expectations. Discharge planning for nonroutine situations was considered disruptive to the RN's workflow. The RN's role was limited to oversight when a discharge planner was involved. Understanding RNs' decision making in this key process provides valuable insights into differentiating routine from nonroutine patient situations and deploying appropriate resources in a timely fashion. Copyright © 2010 Elsevier Inc. All rights reserved.
Binary Cell Fate Decisions and Fate Transformation in the Drosophila Larval Eye
Rister, Jens; Ng, June; Celik, Arzu; Sprecher, Simon G.
2013-01-01
The functionality of sensory neurons is defined by the expression of specific sensory receptor genes. During the development of the Drosophila larval eye, photoreceptor neurons (PRs) make a binary choice to express either the blue-sensitive Rhodopsin 5 (Rh5) or the green-sensitive Rhodopsin 6 (Rh6). Later during metamorphosis, ecdysone signaling induces a cell fate and sensory receptor switch: Rh5-PRs are re-programmed to express Rh6 and become the eyelet, a small group of extraretinal PRs involved in circadian entrainment. However, the genetic and molecular mechanisms of how the binary cell fate decisions are made and switched remain poorly understood. We show that interplay of two transcription factors Senseless (Sens) and Hazy control cell fate decisions, terminal differentiation of the larval eye and its transformation into eyelet. During initial differentiation, a pulse of Sens expression in primary precursors regulates their differentiation into Rh5-PRs and repression of an alternative Rh6-cell fate. Later, during the transformation of the larval eye into the adult eyelet, Sens serves as an anti-apoptotic factor in Rh5-PRs, which helps in promoting survival of Rh5-PRs during metamorphosis and is subsequently required for Rh6 expression. Comparably, during PR differentiation Hazy functions in initiation and maintenance of rhodopsin expression. Hazy represses Sens specifically in the Rh6-PRs, allowing them to die during metamorphosis. Our findings show that the same transcription factors regulate diverse aspects of larval and adult PR development at different stages and in a context-dependent manner. PMID:24385925
Binary cell fate decisions and fate transformation in the Drosophila larval eye.
Mishra, Abhishek Kumar; Tsachaki, Maria; Rister, Jens; Ng, June; Celik, Arzu; Sprecher, Simon G
2013-01-01
The functionality of sensory neurons is defined by the expression of specific sensory receptor genes. During the development of the Drosophila larval eye, photoreceptor neurons (PRs) make a binary choice to express either the blue-sensitive Rhodopsin 5 (Rh5) or the green-sensitive Rhodopsin 6 (Rh6). Later during metamorphosis, ecdysone signaling induces a cell fate and sensory receptor switch: Rh5-PRs are re-programmed to express Rh6 and become the eyelet, a small group of extraretinal PRs involved in circadian entrainment. However, the genetic and molecular mechanisms of how the binary cell fate decisions are made and switched remain poorly understood. We show that interplay of two transcription factors Senseless (Sens) and Hazy control cell fate decisions, terminal differentiation of the larval eye and its transformation into eyelet. During initial differentiation, a pulse of Sens expression in primary precursors regulates their differentiation into Rh5-PRs and repression of an alternative Rh6-cell fate. Later, during the transformation of the larval eye into the adult eyelet, Sens serves as an anti-apoptotic factor in Rh5-PRs, which helps in promoting survival of Rh5-PRs during metamorphosis and is subsequently required for Rh6 expression. Comparably, during PR differentiation Hazy functions in initiation and maintenance of rhodopsin expression. Hazy represses Sens specifically in the Rh6-PRs, allowing them to die during metamorphosis. Our findings show that the same transcription factors regulate diverse aspects of larval and adult PR development at different stages and in a context-dependent manner.
Decision Making in Paediatric Cardiology. Are We Prone to Heuristics, Biases and Traps?
Ryan, Aedin; Duignan, Sophie; Kenny, Damien; McMahon, Colin J
2018-01-01
Hidden traps in decision making have been long recognised in the behavioural economics community. Yet we spend very limited, if any time, analysing our decision-making processes in medicine and paediatric cardiology. Systems 1 and 2 thought processes differentiate between rapid emotional thoughts and slow deliberate rational thoughts. For fairly clear cut medical decisions, in-depth analysis may not be needed, but in our field of paediatric cardiology it is not uncommon for challenging cases and occasionally 'simple' cases to generate significant debate and uncertainty as to the best decision. Although morbidity and mortality meetings frequently highlight poor outcomes for our patients, they often neglect to analyse the process of thought which underlined those decisions taken. This article attempts to review commonly acknowledged traps in decision making in the behavioural economics world to ascertain whether these heuristics translate to decision making in the paediatric cardiology environment. We also discuss potential individual and collective solutions to pitfalls in decision making.
Small Unit Decision Making (SUDM) Assessment Battery
2014-11-21
largest contribution towards differentiating between the performance level of the NCO and Lt groups participating in the project. Two additional...Situational Judgment Test, made the largest contribution towards differentiating between the performance level of NCOs and Lts. Additionally, two other...basic perceptual skills. For the construct of cognitive flexibility we suggest the development of a performance instrument in line with our definition
Diffusion pseudotime robustly reconstructs lineage branching.
Haghverdi, Laleh; Büttner, Maren; Wolf, F Alexander; Buettner, Florian; Theis, Fabian J
2016-10-01
The temporal order of differentiating cells is intrinsically encoded in their single-cell expression profiles. We describe an efficient way to robustly estimate this order according to diffusion pseudotime (DPT), which measures transitions between cells using diffusion-like random walks. Our DPT software implementations make it possible to reconstruct the developmental progression of cells and identify transient or metastable states, branching decisions and differentiation endpoints.
Selecting decision strategies: the differential role of affect.
Scheibehenne, Benjamin; von Helversen, Bettina
2015-01-01
Many theories on cognition assume that people adapt their decision strategies depending on the situation they face. To test if and how affect guides the selection of decision strategies, we conducted an online study (N = 166), where different mood states were induced through video clips. Results indicate that mood influenced the use of decision strategies. Negative mood, in particular anger, facilitated the use of non-compensatory strategies, whereas positive mood promoted compensatory decision rules. These results are in line with the idea that positive mood broadens the focus of attention and thus increases the use of compensatory decision strategies that take many pieces of information into account, whereas negative mood narrows the focus of attention and thus fosters non-compensatory strategies that rely on a selective use of information. The results further indicate that gaining a deeper theoretical understanding of the cognitive mechanisms that govern decision processes requires taking emotions into account.
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Handschuh, R. F.; Zhang, J.
1988-01-01
A method for generation of crowned pinion tooth surfaces using a surface of revolution is developed. The crowned pinion meshes with a regular involute gear and has a prescribed parabolic type of transmission errors when the gears operate in the aligned mode. When the gears are misaligned the transmission error remains parabolic with the maximum level still remaining very small (less than 0.34 arc second for the numerical examples). Tooth Contact Analysis (TCA) is used to simulate the conditions of meshing, determine the transmission error, and the bearing contact.
NASA Astrophysics Data System (ADS)
Batalin, Igor; Marnelius, Robert
Open groups whose generators are in arbitrary involutions may be quantized within a ghost extended framework in terms of a nilpotent BFV-BRST charge operator. Previously we have shown that generalized quantum Maurer-Cartan equations for arbitrary open groups may be extracted from the quantum connection operators and that they also follow from a simple quantum master equation involving an extended nilpotent BFV-BRST charge and a master charge. Here we give further details of these results. In addition we establish the general structure of the solutions of the quantum master equation. We also construct an extended formulation whose properties are determined by the extended BRST charge in the master equation.
Improving applied roughness measurement of involute helical gears
NASA Astrophysics Data System (ADS)
Koulin, G.; Zhang, J.; Frazer, R. C.; Wilson, S. J.; Shaw, B. A.
2017-12-01
With improving gear design and manufacturing technology, improvement in metrology is necessary to provide reliable feedback to the designer and manufacturer. A recommended gear roughness measurement method is applied to a micropitting contact fatigue test gear. The development of wear and micropitting is reliably characterised at the sub-micron roughness level. Changes to the features of the localised surface texture are revealed and are related to key gear meshing positions. The application of the recommended methodology is shown to provide informative feedback to the gear designer in reference to the fundamental gear coordinate system, which is used in gear performance simulations such as tooth contact analysis.
The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals
Appay, Victor; Sauce, Delphine; Prelog, Martina
2010-01-01
The thymus is the major site of T cell production and a key organ of the immune system. Its natural involution during the course of life has cast doubts as to its importance for the integrity of our immunity in adulthood. We provide here an overview of the recent works focusing on the immunological evaluation of subjects thymectomized during early childhood due to cardiac surgery of congenital heart defects. These studies represent new advances in our appreciation of the role of the thymus in humans and more generally in our understanding of the development of immunosenescence. PMID:20354268
New non-naturally reductive Einstein metrics on exceptional simple Lie groups
NASA Astrophysics Data System (ADS)
Chen, Huibin; Chen, Zhiqi; Deng, Shaoqiang
2018-01-01
In this article, we construct several non-naturally reductive Einstein metrics on exceptional simple Lie groups, which are found through the decomposition arising from generalized Wallach spaces. Using the decomposition corresponding to the two involutions, we calculate the non-zero coefficients in the formulas of the components of Ricci tensor with respect to the given metrics. The Einstein metrics are obtained as solutions of a system of polynomial equations, which we manipulate by symbolic computations using Gröbner bases. In particular, we discuss the concrete numbers of non-naturally reductive Einstein metrics for each case up to isometry and homothety.
Kinematic precision of gear trains
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Goldrich, R. N.; Coy, J. J.; Zaretsky, E. V.
1982-01-01
Kinematic precision is affected by errors which are the result of either intentional adjustments or accidental defects in manufacturing and assembly of gear trains. A method for the determination of kinematic precision of gear trains is described. The method is based on the exact kinematic relations for the contact point motions of the gear tooth surfaces under the influence of errors. An approximate method is also explained. Example applications of the general approximate methods are demonstrated for gear trains consisting of involute (spur and helical) gears, circular arc (Wildhaber-Novikov) gears, and spiral bevel gears. Gear noise measurements from a helicopter transmission are presented and discussed with relation to the kinematic precision theory.
Isoflavones: Anti-Inflammatory Benefit and Possible Caveats
Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen
2016-01-01
Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks. PMID:27294954
Isoflavones: Anti-Inflammatory Benefit and Possible Caveats.
Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen
2016-06-10
Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks.
Klapwijk, Eduard T; Lelieveld, Gert-Jan; Aghajani, Moji; Boon, Albert E; van der Wee, Nic J A; Popma, Arne; Vermeiren, Robert R J M; Colins, Olivier F
2016-04-01
Research suggests that individuals with conduct disorder (CD) are marked by social impairments, such as difficulties in processing the affective reactions of others. Little is known, though, about how they make decisions during social interactions in response to emotional expressions of others. In this study, we therefore investigated the neural mechanisms underlying fairness decisions in response to communicated emotions of others in aggressive, criminal justice-involved boys with CD (N = 32) compared with typically developing (TD) boys (N = 33), aged 15-19 years. Participants received written emotional responses (angry, disappointed or happy) from peers in response to a previous offer and then had to make fairness decisions in a version of the Dictator Game. Behavioral results showed that CD boys did not make differential fairness decisions in response to the emotions, whereas the TD boys did show a differentiation and also responded more unfair to happy reactions than the CD boys. Neuroimaging results revealed that when receiving happy vs disappointed and angry reactions, the CD boys showed less activation than the TD boys in the temporoparietal junction and supramarginal gyrus, regions involved in perspective taking and attention. These results suggest that boys with CD have difficulties with processing explicit emotional cues from others on behavioral and neural levels. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
Toledano, Adolfo; Álvarez, María-Isabel; Toledano-Díaz, Adolfo; Merino, José-Joaquín; Rodríguez, José Julio
2016-01-01
From birth to death, neurons are dynamically accompanied by neuroglial cells in a very close morphological and functional relationship. Three families have been classically considered within the CNS: astroglia, oligodendroglia and microglia. Many types/subtypes (including NGR2+ cells), with a wide variety of physiological and pathological effects on neurons, have been described using morphological and immunocytochemical criteria. Glio-glial, glio-neuronal and neuro-glial cell signaling and gliotransmission are phenomena that are essential to support brain functions. Morphofunctional changes resulting from the plasticity of all the glial cell types parallel the plastic neuronal changes that optimize the functionality of neuronal circuits. Moreover, neuroglia possesses the ability to adopt a reactive status (gliosis) in which, generally, new functions arise to improve and restore if needed the neural functionality. All these features make neuroglial cells elements of paramount importance when attempting to explain any physiological or pathological processes in the CNS, because they are involved in both, neuroprotection/neurorepair and neurodegeneration. There exist diverse and profound, regional and local, neuroglial changes in all involutive processes (physiological and pathological aging; neurodegenerative disorders, including Alzheimer ´s disease -AD-), but today, the exact meaning of such modifications (the modifications of the different neuroglial types, in time and place), is not well understood. In this review we consider the different neuroglial cells and their responses in order to understand the possible role they fulfill in pathogenesis, diagnosis and treatment (preventive or palliative) of AD. The existence of differentiated and/or concurrent pathogenic and neuro-protective/neuro-restorative astroglial and microglial responses is highlighted.
Sarjan, H N; Divyashree, S; Yajurvedi, H N
2017-12-01
Chronic stress is an inevitable factor in the modern day society which affects cell mediated as well as humoral immunity. There is a need to prevent stress effects with traditionally used herbs. The present study was undertaken to investigate the immunoprotective effect of Vacha (Acorus calamus L. Acoraceae) rhizome under stressful condition. Soxlet extraction of Vacha rhizome was performed with increasing polarity of solvents, i.e., petroleum ether to ethanol. The extract was concentrated by distilling off the solvent in flash evaporator and dried in desiccators. The benzene extract was found to have anti-stress property in our earlier studies and hence it was used in the present experiment. Extract was administered every day for 4 weeks orally to adult female rats prior to exposure to stress, restraint (1 h) and forced swimming exercise (15 min). Vacha rhizome extract significantly prevented the stress induced reduction in total and differential leukocytes count, immunoglobulin content, bone marrow cellularity and viability, lymphocytes counts in lymphoid organs, islands of white pulp of spleen (ED 50 = 10 mg, p < 0.001) and a significant increase in circulating immune complexes and apoptotic index of lymphoid organs (ED 50 = 10 mg, p < 0.001) compared to controls. The present study clearly indicates that Vacha extract not only prevents stress-induced suppression of immunity and structural involution of lymphoid organs, but also boosts immunity in normal rats. Therefore, it is suggested that Vacha extract administration maintains normal immunity despite the body experiencing stress.
The pitfalls of premature closure: clinical decision-making in a case of aortic dissection
Kumar, Bharat; Kanna, Balavenkatesh; Kumar, Suresh
2011-01-01
Premature closure is a type of cognitive error in which the physician fails to consider reasonable alternatives after an initial diagnosis is made. It is a common cause of delayed diagnosis and misdiagnosis borne out of a faulty clinical decision-making process. The authors present a case of aortic dissection in which premature closure was avoided by the aggressive pursuit of the appropriate differential diagnosis, and discuss the importance of disciplined clinical decision-making in the setting of chest pain. PMID:22679162
Data-driven Modelling for decision making under uncertainty
NASA Astrophysics Data System (ADS)
Angria S, Layla; Dwi Sari, Yunita; Zarlis, Muhammad; Tulus
2018-01-01
The rise of the issues with the uncertainty of decision making has become a very warm conversation in operation research. Many models have been presented, one of which is with data-driven modelling (DDM). The purpose of this paper is to extract and recognize patterns in data, and find the best model in decision-making problem under uncertainty by using data-driven modeling approach with linear programming, linear and nonlinear differential equation, bayesian approach. Model criteria tested to determine the smallest error, and it will be the best model that can be used.
Offset quadrature communications with decision-feedback carrier synchronization
NASA Technical Reports Server (NTRS)
Simon, M. K.; Smith, J. G.
1974-01-01
In order to accommodate a quadrature amplitude-shift-keyed (QASK) signal, Simon and Smith (1974) have modified the decision-feedback loop which tracks a quadrature phase-shift-keyed (QPSK). In the investigation reported approaches are considered to modify the loops in such a way that offset QASK signals can be tracked, giving attention to the special case of an offset QPSK. The development of the stochastic integro-differential equation of operation for a decision-feedback offset QASK loop is discussed along with the probability density function of the phase error process.
ERIC Educational Resources Information Center
Schifter, Catherine C.; Natarajan, Uma; Ketelhut, Diane Jass; Kirchgessner, Amanda
2014-01-01
Data-driven decision making is essential in K-12 education today, but teachers often do not know how to make use of extensive data sets. Research shows that teachers are not taught how to use extensive data (i.e., multiple data sets) to reflect on student progress or to differentiate instruction. This paper presents a process used in an National…
Ramnarayan, Padmanabhan; Kapoor, Ritika R; Coren, Michael; Nanduri, Vasantha; Tomlinson, Amanda L; Taylor, Paul M; Wyatt, Jeremy C; Britto, Joseph F
2003-01-01
Few previous studies evaluating the benefits of diagnostic decision support systems have simultaneously measured changes in diagnostic quality and clinical management prompted by use of the system. This report describes a reliable and valid scoring technique to measure the quality of clinical decision plans in an acute medical setting, where diagnostic decision support tools might prove most useful. Sets of differential diagnoses and clinical management plans generated by 71 clinicians for six simulated cases, before and after decision support from a Web-based pediatric differential diagnostic tool (ISABEL), were used. A composite quality score was calculated separately for each diagnostic and management plan by considering the appropriateness value of each component diagnostic or management suggestion, a weighted sum of individual suggestion ratings, relevance of the entire plan, and its comprehensiveness. The reliability and validity (face, concurrent, construct, and content) of these two final scores were examined. Two hundred fifty-two diagnostic and 350 management suggestions were included in the interrater reliability analysis. There was good agreement between raters (intraclass correlation coefficient, 0.79 for diagnoses, and 0.72 for management). No counterintuitive scores were demonstrated on visual inspection of the sets. Content validity was verified by a consultation process with pediatricians. Both scores discriminated adequately between the plans of consultants and medical students and correlated well with clinicians' subjective opinions of overall plan quality (Spearman rho 0.65, p < 0.01). The diagnostic and management scores for each episode showed moderate correlation (r = 0.51). The scores described can be used as key outcome measures in a larger study to fully assess the value of diagnostic decision aids, such as the ISABEL system.
Bean, Christopher G; Winefield, Helen R; Sargent, Charli; Hutchinson, Amanda D
2015-10-01
The Job Demand-Control-Support (JDCS) model is commonly used to investigate associations between psychosocial work factors and employee health, yet research considering obesity using the JDCS model remains inconclusive. This study investigates which parts of the JDCS model are associated with measures of obesity and provides a comparison between waist circumference (higher values imply central obesity) and body mass index (BMI, higher values imply overall obesity). Contrary to common practice, in this study the JDCS components are not reduced into composite or global scores. In light of emerging evidence that the two components of job control (skill discretion and decision authority) could have differential associations with related health outcomes, components of the JDCS model were analysed at the subscale level. A cross-sectional design with a South Australian cohort (N = 450) combined computer-assisted telephone interview data and clinic-measured height, weight and waist circumference. After controlling for sex, age, household income, work hours and job nature (blue vs. white-collar), the two components of job control were the only parts of the JDCS model to hold significant associations with measures of obesity. Notably, the associations between skill discretion and waist circumference (b = -.502, p = .001), and skill discretion and BMI (b = -.163, p = .005) were negative. Conversely, the association between decision authority and waist circumference (b = .282, p = .022) was positive. These findings are significant since skill discretion and decision authority are typically combined into a composite measure of job control or decision latitude. Our findings suggest skill discretion and decision authority should be treated separately since combining these theoretically distinct components may conceal their differential associations with measures of obesity, masking their individual importance. Psychosocial work factors displayed stronger associations and explained greater variance in waist circumference compared with BMI, and possible reasons for this are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Minashima, Takeshi; Quirno, Martin; Lee, You Jin; Kirsch, Thorsten
2017-01-01
The progressive ankylosis protein (ANK) is a transmembrane protein that transports intracellular pyrophosphate (PPi) to the extracellular milieu. In this study we show increased fatty degeneration of the bone marrow of adult ank/ank mice, which lack a functional ANK protein. In addition, isolated bone marrow stromal cells (BMSCs) isolated from ank/ank mice showed a decreased proliferation rate and osteogenic differentiation potential, and an increased adipogenic differentiation potential compared to BMSCs isolated from wild type (WT) littermates. Wnt signaling pathway PCR array analysis revealed that Wnt ligands, Wnt receptors and Wnt signaling proteins that stimulate osteoblast differentiation were expressed at markedly lower levels in ank/ank BMSCs than in WT BMSCs. Lack of ANK function also resulted in impaired bone fracture healing, as indicated by a smaller callus formed and delayed bone formation in the callus site. Whereas 5 weeks after fracture, the fractured bone in WT mice was further remodeled and restored to original shape, the fractured bone in ank/ank mice was not fully restored and remodeled to original shape. In conclusion, our study provides evidence that ANK plays a critical role in the adipogenic/osteogenic fate decision of adult mesenchymal precursor cells. ANK functions in precursor cells are required for osteogenic differentiation of these cells during adult bone homeostasis and repair, whereas lack of ANK functions favors adipogenic differentiation. PMID:28286238
Simann, Meike; Le Blanc, Solange; Schneider, Verena; Zehe, Viola; Lüdemann, Martin; Schütze, Norbert; Jakob, Franz; Schilling, Tatjana
2017-02-01
Controlling the adipo-osteogenic lineage decision of trabecular human bone marrow stromal cells (hBMSCs) in favor of osteogenesis represents a promising approach for osteoporosis therapy and prevention. Previously, Fibroblast Growth Factor 1 (FGF1) and its subfamily member FGF2 were scored as leading candidates to exercise control over skeletal precursor commitment and lineage decision albeit literature results are highly inconsistent. We show here that FGF1 and 2 strongly prevent the osteogenic commitment and differentiation of hBMSCs. Mineralization of extracellular matrix (ECM) and mRNA expression of osteogenic marker genes Alkaline Phosphatase (ALP), Collagen 1A1 (COL1A1), and Integrin-Binding Sialoprotein (IBSP) were significantly reduced. Furthermore, master regulators of osteogenic commitment like Runt-Related Transcription Factor 2 (RUNX2) and Bone Morphogenetic Protein 4 (BMP4) were downregulated. When administered under adipogenic culture conditions, canonical FGFs did not support osteogenic marker expression. Moreover despite the presence of osteogenic differentiation factors, FGFs even disabled the pro-osteogenic lineage decision of pre-differentiated adipocytic cells. In contrast to FGF Receptor 2 (FGFR2), FGFR1 was stably expressed throughout osteogenic and adipogenic differentiation and FGF addition. Moreover, FGFR1 and Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2) were found to be responsible for underlying signal transduction using respective inhibitors. Taken together, we present new findings indicating that canonical FGFR-ERK1/2 signaling entrapped hBMSCs in a pre-committed state and arrested further maturation of committed precursors. Our results might aid in unraveling and controlling check points relevant for ageing-associated aberrant adipogenesis with consequences for the treatment of degenerative diseases such as osteoporosis and for skeletal tissue engineering strategies. J. Cell. Biochem. 118: 263-275, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Oxygen and Cell Fate Decisions
2009-05-27
mesenchymal stem cells may still be able to commit to chondro- genic differentiation under hypoxic conditions in vivo. Surprisingly, Malladi et al. have...are induced to undergo differentiation in vitro at 2% O2 ( Malladi et al. 2006). Nonetheless, targeted deletion of HIF-1α in adipose-derived adult... Malladi et al. 2007). These dis- crepancies could potentially be appreciated from at least two perspectives. (1) Chondrogenic dif- ferentiation is
ERIC Educational Resources Information Center
Skowron, Janice
This booklet helps teachers understand how to increase student motivation and interest and how to design lively, creative, and interactive lessons that will enrich learning. Chapter 1, "The Differences That Impact Learning," describes the differentiated classroom and provides teachers with an understanding of the many variations of how…
Dynamics of Sequential Decision Making
NASA Astrophysics Data System (ADS)
Rabinovich, Mikhail I.; Huerta, Ramón; Afraimovich, Valentin
2006-11-01
We suggest a new paradigm for intelligent decision-making suitable for dynamical sequential activity of animals or artificial autonomous devices that depends on the characteristics of the internal and external world. To do it we introduce a new class of dynamical models that are described by ordinary differential equations with a finite number of possibilities at the decision points, and also include rules solving this uncertainty. Our approach is based on the competition between possible cognitive states using their stable transient dynamics. The model controls the order of choosing successive steps of a sequential activity according to the environment and decision-making criteria. Two strategies (high-risk and risk-aversion conditions) that move the system out of an erratic environment are analyzed.
ERIC Educational Resources Information Center
Sukin, Tia M.
2010-01-01
The presence of outlying anchor items is an issue faced by many testing agencies. The decision to retain or remove an item is a difficult one, especially when the content representation of the anchor set becomes questionable by item removal decisions. Additionally, the reason for the aberrancy is not always clear, and if the performance of the…
[Forecast of costs of ecodependent cancer treatment for the development of management decisions].
Krasovskiy, V O
2014-01-01
The methodical approach for probabilistic forecasting and differentiation of treatment of costs of ecodependent cancer cases has been elaborated. The modality is useful in the organization of medical aid to cancer patients, in developing management decisions for the reduction the occupational load on the population, as well as in solutions problems in compensation to the population economic and social loss from industrial plants.
Wise, Richard J; Phung, Alissa L; Labuschagne, Izelle; Stout, Julie C
2015-01-01
Urgency is the tendency to make impulsive decisions under extreme positive or negative emotional states. Stress, gender and impulsive personality traits are all known to influence decision-making, but no studies have examined the interplay of all of these factors. We exposed 78 men and women to a stress or a non-stress condition, and then administered the Balloon Analogue Risk Task. We found that stress effects varied as a function of gender and urgency traits. Under stress, women low in negative urgency and men high in negative urgency made fewer risky decisions. Positive urgency yielded a similar pattern. Thus, decisions under stress depend on a complex interplay between gender and impulsive personality traits. These findings have implications for clinical disorders, such as substance use disorders, in which there are known deficits in decision-making and high levels of impulsive traits.
Collins, Loel; Collins, Dave
2015-01-01
This study examined the integration of professional judgement and decision-making processes in adventure sports coaching. The study utilised a thematic analysis approach to investigate the decision-making practices of a sample of high-level adventure sports coaches over a series of sessions. Results revealed that, in order to make judgements and decisions in practice, expert coaches employ a range of practical and pedagogic management strategies to create and opportunistically use time for decision-making. These approaches include span of control and time management strategies to facilitate the decision-making process regarding risk management, venue selection, aims, objectives, session content, and differentiation of the coaching process. The implication for coaches, coach education, and accreditation is the recognition and training of the approaches that "create time" for the judgements in practice, namely "creating space to think". The paper concludes by offering a template for a more expertise-focused progression in adventure sports coaching.
Induction of CD4 T cell memory by local cellular collectivity.
Polonsky, Michal; Rimer, Jacob; Kern-Perets, Amos; Zaretsky, Irina; Miller, Stav; Bornstein, Chamutal; David, Eyal; Kopelman, Naama Meira; Stelzer, Gil; Porat, Ziv; Chain, Benjamin; Friedman, Nir
2018-06-15
Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naïve CD4 + T cells into memory precursors. We found that differentiation of precursor memory T cells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses. Copyright © 2018, American Association for the Advancement of Science.
Mitochondrial activity in the regulation of stem cell self-renewal and differentiation.
Khacho, Mireille; Slack, Ruth S
2017-12-01
Mitochondria are classically known as the essential energy producers in cells. As such, the activation of mitochondrial metabolism upon cellular differentiation was deemed a necessity to fuel the high metabolic needs of differentiated cells. However, recent studies have revealed a direct role for mitochondrial activity in the regulation of stem cell fate and differentiation. Several components of mitochondrial metabolism and respiration have now been shown to regulate different aspects of stem cell differentiation through signaling, transcriptional, proteomic and epigenetic modulations. In light of these findings mitochondrial metabolism is no longer considered a consequence of cellular differentiation, but rather a key regulatory mechanism of this process. This review will focus on recent progress that defines mitochondria as the epicenters for the regulation of stem cell fate decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.
Assessing ethical problem solving by reasoning rather than decision making.
Tsai, Tsuen-Chiuan; Harasym, Peter H; Coderre, Sylvain; McLaughlin, Kevin; Donnon, Tyrone
2009-12-01
The assessment of ethical problem solving in medicine has been controversial and challenging. The purposes of this study were: (i) to create a new instrument to measure doctors' decisions on and reasoning approach towards resolving ethical problems; (ii) to evaluate the scores generated by the new instrument for their reliability and validity, and (iii) to compare doctors' ethical reasoning abilities between countries and among medical students, residents and experts. This study used 15 clinical vignettes and the think-aloud method to identify the processes and components involved in ethical problem solving. Subjects included volunteer ethics experts, postgraduate Year 2 residents and pre-clerkship medical students. The interview data were coded using the instruments of the decision score and Ethical Reasoning Inventory (ERI). The ERI assessed the quality of ethical reasoning for a particular case (Part I) and for an individual globally across all the vignettes (Part II). There were 17 Canadian and 32 Taiwanese subjects. Based on the Canadian standard, the decision scores between Taiwanese and Canadian subjects differed significantly, but made no discrimination among the three levels of expertise. Scores on the ERI Parts I and II, which reflect doctors' reasoning quality, differed between countries and among different levels of expertise in Taiwan, providing evidence of construct validity. In addition, experts had a greater organised knowledge structure and considered more relevant variables in the process of arriving at ethical decisions than did residents or students. The reliability of ERI scores was 0.70-0.99 on Part I and 0.75-0.80 on Part II. Expertise in solving ethical problems could not be differentiated by the decisions made, but could be differentiated according to the reasoning used to make those decisions. The difference between Taiwanese and Canadian experts suggests that cultural considerations come into play in the decisions that are made in the course of providing humane care to patients.
Applying evidence to support ethical decisions: is the placebo really powerless?.
Porzsolt, Franz; Schlotz-Gorton, Nicole; Biller-Andorno, Nikola; Thim, Anke; Meissner, Karin; Roeckl-Wiedmann, Irmgard; Herzberger, Barbara; Ziegler, Renatus; Gaus, Wilhelm; Pöppe, Ernst
2004-01-01
Using placebos in day-to-day practice is an ethical problem. This paper summarises the available epidemiological evidence to support this difficult decision. Based on these data we propose to differentiate between placebo and "knowledge framing". While the use of placebo should be confined to experimental settings in clinical trials, knowledge framing--which is only conceptually different from placebo--is a desired, expected and necessary component of any doctor-patient encounter. Examples from daily practice demonstrate both, the need to investigate the effects of knowledge framing and its impact on ethical, medical, economical and legal decisions.
2017-01-01
In the classic gain/loss framing effect, describing a gamble as a potential gain or loss biases people to make risk-averse or risk-seeking decisions, respectively. The canonical explanation for this effect is that frames differentially modulate emotional processes, which in turn leads to irrational choice behavior. Here, we evaluate the source of framing biases by integrating functional magnetic resonance imaging data from 143 human participants performing a gain/loss framing task with meta-analytic data from >8000 neuroimaging studies. We found that activation during choices consistent with the framing effect were most correlated with activation associated with the resting or default brain, while activation during choices inconsistent with the framing effect was most correlated with the task-engaged brain. Our findings argue against the common interpretation of gain/loss framing as a competition between emotion and control. Instead, our study indicates that this effect results from differential cognitive engagement across decision frames. SIGNIFICANCE STATEMENT The biases frequently exhibited by human decision makers have often been attributed to the presence of emotion. Using a large fMRI sample and analysis of whole-brain networks defined with the meta-analytic tool Neurosynth, we find that neural activity during frame-biased decisions was more significantly associated with default behaviors (and the absence of executive control) than with emotion. These findings point to a role for neuroscience in shaping long-standing psychological theories in decision science. PMID:28264981
Li, Rosa; Smith, David V; Clithero, John A; Venkatraman, Vinod; Carter, R McKell; Huettel, Scott A
2017-03-29
In the classic gain/loss framing effect, describing a gamble as a potential gain or loss biases people to make risk-averse or risk-seeking decisions, respectively. The canonical explanation for this effect is that frames differentially modulate emotional processes, which in turn leads to irrational choice behavior. Here, we evaluate the source of framing biases by integrating functional magnetic resonance imaging data from 143 human participants performing a gain/loss framing task with meta-analytic data from >8000 neuroimaging studies. We found that activation during choices consistent with the framing effect were most correlated with activation associated with the resting or default brain, while activation during choices inconsistent with the framing effect was most correlated with the task-engaged brain. Our findings argue against the common interpretation of gain/loss framing as a competition between emotion and control. Instead, our study indicates that this effect results from differential cognitive engagement across decision frames. SIGNIFICANCE STATEMENT The biases frequently exhibited by human decision makers have often been attributed to the presence of emotion. Using a large fMRI sample and analysis of whole-brain networks defined with the meta-analytic tool Neurosynth, we find that neural activity during frame-biased decisions was more significantly associated with default behaviors (and the absence of executive control) than with emotion. These findings point to a role for neuroscience in shaping long-standing psychological theories in decision science. Copyright © 2017 the authors 0270-6474/17/373588-11$15.00/0.
Pefani, Dafni-Eleutheria; Dimaki, Maria; Spella, Magda; Karantzelis, Nickolas; Mitsiki, Eirini; Kyrousi, Christina; Symeonidou, Ioanna-Eleni; Perrakis, Anastassis; Taraviras, Stavros; Lygerou, Zoi
2011-01-01
Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development. PMID:21543332
Pefani, Dafni-Eleutheria; Dimaki, Maria; Spella, Magda; Karantzelis, Nickolas; Mitsiki, Eirini; Kyrousi, Christina; Symeonidou, Ioanna-Eleni; Perrakis, Anastassis; Taraviras, Stavros; Lygerou, Zoi
2011-07-01
Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development.
Nogueira, Jeane de Souza; Canto, Fábio Barrozo do; Nunes, Caroline Fraga Cabral Gomes; Vianna, Pedro Henrique Oliveira; Paiva, Luciana de Souza; Nóbrega, Alberto; Bellio, Maria; Fucs, Rita
2016-02-01
CD4(+) Foxp3(+) regulatory T (Treg) cells are necessary for the maintenance of self-tolerance and T-cell homeostasis. This population is kept at stable frequencies in secondary lymphoid organs for the majority of the lifetime, despite permanent thymic emigration or in the face of thymic involution. Continuous competition is expected to occur between recently thymus-emigrated and resident Treg cells (either natural or post-thymically induced). In the present work, we analysed the renewal dynamics of Treg cells compared with CD4(+) Foxp3- conventional T cells (Tconv), using protocols of single or successive T-cell transfers into syngeneic euthymic or lymphopenic (nu/nu or RAG2(-/-)) mice, respectively. Our results show a higher turnover for Treg cells in the peripheral compartment, compared with Tconv cells, when B cell-sufficient euthymic or nude hosts are studied. This increased renewal within the Treg pool, shown by the greater replacement of resident Treg cells by donor counterparts, correlates with augmented rates of proliferation and is not modified following temporary environmental perturbations induced by inflammatory state or microbiota alterations. Notably, the preferential substitution of Treg lymphocytes was not observed in RAG2(-/-) hosts. We showed that limited B-cell replenishment in the RAG2(-/-) hosts decisively contributed to the altered peripheral T-cell homeostasis. Accordingly, weekly transfers of B cells to RAG2(-/-) hosts rescued the preferential substitution of Treg lymphocytes. Our study discloses a new aspect of T-cell homeostasis that depends on the presence of B lymphocytes to regulate the relative incorporation of recently arrived Treg and Tconv cells in the peripheral compartment. © 2015 John Wiley & Sons Ltd.
Materials property definition and generation for carbon-carbon and carbon phenolic materials
NASA Technical Reports Server (NTRS)
Canfield, A. R.; Mathis, J. R.; Starrett, H. S.; Koenig, J. R.
1987-01-01
A data base program to generate statistically significant material-property data for carbon-carbon and carbon phenolic materials to be used in designs of Space Shuttle is described. The program, which will provide data necessary for thermal and stress modeling of Shuttle nozzle and exit cone structures, includes evaluation of tension, compression, shear strength, shear modulus, thermal expansion, thermal conductivity, permeability, and emittance for both materials; the testing of carbon phenolic materials also includes CTE, off-gassing, pyrolysis, and RTG. Materials to be tested will be excised from Space Shuttle inlet, throat, and exit cone billets and modified involute carbon-carbon exit cones; coprocessed blocks, panels, and cylinders will also be tested.
Reflection Positive Stochastic Processes Indexed by Lie Groups
NASA Astrophysics Data System (ADS)
Jorgensen, Palle E. T.; Neeb, Karl-Hermann; Ólafsson, Gestur
2016-06-01
Reflection positivity originates from one of the Osterwalder-Schrader axioms for constructive quantum field theory. It serves as a bridge between euclidean and relativistic quantum field theory. In mathematics, more specifically, in representation theory, it is related to the Cartan duality of symmetric Lie groups (Lie groups with an involution) and results in a transformation of a unitary representation of a symmetric Lie group to a unitary representation of its Cartan dual. In this article we continue our investigation of representation theoretic aspects of reflection positivity by discussing reflection positive Markov processes indexed by Lie groups, measures on path spaces, and invariant gaussian measures in spaces of distribution vectors. This provides new constructions of reflection positive unitary representations.
Congenital hemangioma in spondylocostal dysostosis: a novel association*
Salinas-Torres, Victor Michael
2016-01-01
Congenital hemangioma is a benign tumor caused by dysfunction in embryogenesis and vasculogenesis, which progresses during fetal life to manifest as fully developed at birth. Although hemangiomas are the most common tumor of infancy, rapidly involuting congenital hemangioma has not been described in spondylocostal dysostosis. I report the novel association of congenital hemangioma and spondylocostal dysostosis in a Mexican newborn female patient with neural tube defects. Given the embryological relationship between skin and nervous system, I surmise that this association is not coincidental. I also propose that these morphologic alterations be incorporated to the spondylocostal dysostosis phenotype and specifically looked for in other affected children, in order to provide appropriate medical management and genetic counseling. PMID:28300884
Kinematic precision of gear trains
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Goldrich, R. N.; Coy, J. J.; Zaretsky, E. V.
1983-01-01
Kinematic precision is affected by errors which are the result of either intentional adjustments or accidental defects in manufacturing and assembly of gear trains. A method for the determination of kinematic precision of gear trains is described. The method is based on the exact kinematic relations for the contact point motions of the gear tooth surfaces under the influence of errors. An approximate method is also explained. Example applications of the general approximate methods are demonstrated for gear trains consisting of involute (spur and helical) gears, circular arc (Wildhaber-Novikov) gears, and spiral bevel gears. Gear noise measurements from a helicopter transmission are presented and discussed with relation to the kinematic precision theory. Previously announced in STAR as N82-32733
Congenital hemangioma in spondylocostal dysostosis: a novel association.
Salinas-Torres, Victor Michael
2016-01-01
Congenital hemangioma is a benign tumor caused by dysfunction in embryogenesis and vasculogenesis, which progresses during fetal life to manifest as fully developed at birth. Although hemangiomas are the most common tumor of infancy, rapidly involuting congenital hemangioma has not been described in spondylocostal dysostosis. I report the novel association of congenital hemangioma and spondylocostal dysostosis in a Mexican newborn female patient with neural tube defects. Given the embryological relationship between skin and nervous system, I surmise that this association is not coincidental. I also propose that these morphologic alterations be incorporated to the spondylocostal dysostosis phenotype and specifically looked for in other affected children, in order to provide appropriate medical management and genetic counseling.
Calvarial Plasmacytoma Mimicking Meningioma as the Initial Presentation of Multiple Myeloma
Pisapia, David; Ramakrishna, Rohan
2017-01-01
Plasmacytoma of the calvarium is a well-described feature of multiple myeloma and in some cases has been reported as a solitary lesion. However, when associated with multiple myeloma these are typically identified after the initial diagnosis is made. This case is unusual in that the diagnosis of plasmacytoma was first suspected in a patient thought to have a meningioma on the day of surgery, when a magnetic resonance imaging (MRI) demonstrated spontaneous involution of the mass. Recognition of evolving changes in a calvarial or dural-based lesion should prompt the practitioner to consider alternative diagnoses other than meningioma prior to proceeding with surgical resection. PMID:28465873
Kwek, Joly H L; Wynne, Alicia; Lefèvre, Christophe; Familari, Mary; Nicholas, Kevin R; Sharp, Julie A
2013-10-01
S100 proteins are calcium-binding proteins involved in controlling diverse intracellular and extracellular processes such as cell growth, differentiation, and antimicrobial function. We recently identified a S100-like cDNA from the tammar wallaby (Macropus eugenii) stomach. Phylogentic analysis shows wallaby S100A19 forms a new clade with other marsupial and monotreme S100A19, while this group shows similarity to eutherian S100A7 and S100A15 genes. This is also supported by amino acid and domain comparisons. We show S100A19 is developmentally-regulated in the tammar wallaby gut by demonstrating the gene is expressed in the forestomach of young animals at a time when the diet consists of only milk, but is absent in older animals when the diet is supplemented with herbage. During this transition the forestomach phenotype changes from a gastric stomach into a fermentation sac and intestinal flora changes with diet. We also show that S100A19 is expressed in the mammary gland of the tammar wallaby only during specific stages of lactation; the gene is up-regulated during pregnancy and involution and not expressed during the milk production phase of lactation. Comparison of the tammar wallaby S100A19 protein sequence with S100 protein sequences from eutherian, monotreme and other marsupial species suggest the marsupial S100A19 has two functional EF hand domains, and an extended His tail. An evolutionary analysis of S100 family proteins was carried out to gain a better understanding of the relationship between the S100 family member functions. We propose that S100A19 gene/protein is the ancestor of the eutherian S100A7 gene/protein, which has subsequently modified its original function in eutherians. This modified function may have arisen due to differentiation of evolutionary pressures placed on gut and mammary gland developmental during mammal evolution. The highly regulated differential expression patterns of S100A19 in the tammar wallaby suggests that S100A19 may play a role in gut development, which differs between metatherians and eutherians, and/or include a potential antibacterial role in order to establish the correct flora and protect against spiral bacteria in the immature forestomach. In the mammary gland it may protect the tissue from infection at times of vulnerability during the lactation cycle. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.
Ramond, Cyrille; Glaser, Nicolas; Berthault, Claire; Ameri, Jacqueline; Kirkegaard, Jeannette Schlichting; Hansson, Mattias; Honoré, Christian; Semb, Henrik; Scharfmann, Raphaël
2017-07-21
Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2 + population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3 , a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.
A Qualitative Analysis of Power Differentials in Ethical Situations in Academia
Gibson, Carter; Medeiros, Kelsey E.; Giorgini, Vincent; Mecca, Jensen T.; Devenport, Lynn D.; Connelly, Shane; Mumford, Michael D.
2014-01-01
Power and organizational hierarchies are ubiquitous to social institutions that form the foundation of modern society. Power differentials may act to constrain or enhance people's ability to make good ethical decisions. However, little scholarly work has examined perceptions of this important topic. The present effort seeks to address this issue by interviewing academics about hypothetical ethical problems that involve power differences among those involved. Academics discussed what they would do in these scenarios, often drawing on their own experiences. Using a think-aloud protocol, participants were prompted to discuss their reasoning and thinking behind their ethical decisions. These interview data were content analyzed using a semantic analysis program that identified a number of distinct ways that academics think about power differences and abuses in ethical situations. Implications of these findings are discussed. PMID:25356066
Brukner-Wertman, Yael; Laor, Nathaniel; Golan, Ofer
2016-08-01
DSM-5 introduced two diagnoses describing neurodevelopmental deficits in social communication (SC); Autism Spectrum Disorder (ASD) and Social (Pragmatic) Communication Disorder (SPCD). These diagnoses are differentiated by Repetitive and Restricted Behaviors (RRB), required for an ASD diagnosis and absent in SPCD. We highlight the gaps between the research into SPCD and DSM-5's diagnostic criteria, and discuss the clinical implications of this diagnostic decision. We argue that DSM-5's demand for full manifestation of both SC and RRB axes when diagnosing ASD, prematurely forced a categorical view on the continual nature of the potentially dependent SC and RRB phenotypes. We conclude by highlighting the implications of this differential diagnostic decision on public health policies, designated therapy, and the need for further research regarding SPCD.
Attributions of responsibility and affective reactions to decision outcomes.
Zeelenberg, M; van der Pligt, J; de Vries, N K
2000-06-01
Immediate affective reactions to outcomes are more intense following decisions to act than following decisions not to act. This finding holds for both positive and negative outcomes. We relate this "actor-effect" to attribution theory and argue that decision makers are seen as more responsible for outcomes when these are the result of a decision to act as compared to a decision not to act. Experiment 1 (N = 80) tests the main assumption underlying our reasoning and shows that affective reactions to decision outcomes are indeed more intense when the decision maker is seen as more responsible. Experiment 2 (N = 40) tests whether the actor effect can be predicted on the basis of differential attributions following action and inaction. Participants read vignettes in which active and passive actors obtained a positive or negative outcome. Action resulted in more intense affect than inaction, and positive outcomes resulted in more intense affect than negative outcomes. Experiment 2 further shows that responsibility attributions and affective reactions to outcomes are highly correlated; that is, more extreme affective reactions are associated with more internal attributions. We discuss the implications for research on post-decisional reactions.
Disease of the year: juvenile idiopathic arthritis--differential diagnosis.
Hu-Torres, Sandra; Foster, C Stephen
2014-02-01
The purpose of this review is to comprehensively explain the differential diagnosis of juvenile idiopathic arthritis-associated uveitis. Web-based literature review. Main diagnostic decisions are made through a thorough anterior segment exam and a comprehensive exploration of past medical and family history. High clinical suspicion of other uveitic entities occurring in children is necessary and must be excluded by the practitioner before immediate diagnosis of juvenile idiopathic arthritis is made.
Generalized Quantum Theory and Mathematical Foundations of Quantum Field Theory
NASA Astrophysics Data System (ADS)
Maroun, Michael Anthony
This dissertation is divided into two main topics. The first is the generalization of quantum dynamics when the Schrodinger partial differential equation is not defined even in the weak mathematical sense because the potential function itself is a distribution in the spatial variable, the same variable that is used to define the kinetic energy operator, i.e. the Laplace operator. The procedure is an extension and broadening of the distributional calculus and offers spectral results as an alternative to the only other two known methods to date, namely a) the functional calculi; and b) non-standard analysis. Furthermore, the generalizations of quantum dynamics presented within give a resolution to the time asymmetry paradox created by multi-particle quantum mechanics due to the time evolution still being unitary. A consequence is the randomization of phases needed for the fundamental justification Pauli master equation. The second topic is foundations of the quantum theory of fields. The title is phrased as ``foundations'' to emphasize that there is no claim of uniqueness but rather a proposal is put forth, which is markedly different than that of constructive or axiomatic field theory. In particular, the space of fields is defined as a space of generalized functions with involutive symmetry maps (the CPT invariance) that affect the topology of the field space. The space of quantum fields is then endowed the Frechet property and interactions change the topology in such a way as to cause some field spaces to be incompatible with others. This is seen in the consequences of the Haag theorem. Various examples and discussions are given that elucidate a new view of the quantum theory of fields and its (lack of) mathematical structure.
Generation of gear tooth surfaces by application of CNC machines
NASA Technical Reports Server (NTRS)
Litvin, F. L.; Chen, N. X.
1994-01-01
This study will demonstrate the importance of application of computer numerically controlled (CNC) machines in generation of gear tooth surfaces with new topology. This topology decreases gear vibration and will extend the gear capacity and service life. A preliminary investigation by a tooth contact analysis (TCA) program has shown that gear tooth surfaces in line contact (for instance, involute helical gears with parallel axes, worm gear drives with cylindrical worms, etc.) are very sensitive to angular errors of misalignment that cause edge contact and an unfavorable shape of transmission errors and vibration. The new topology of gear tooth surfaces is based on the localization of bearing contact, and the synthesis of a predesigned parabolic function of transmission errors that is able to absorb a piecewise linear function of transmission errors caused by gear misalignment. The report will describe the following topics: description of kinematics of CNC machines with six degrees of freedom that can be applied for generation of gear tooth surfaces with new topology. A new method for grinding of gear tooth surfaces by a cone surface or surface of revolution based on application of CNC machines is described. This method provides an optimal approximation of the ground surface to the given one. This method is especially beneficial when undeveloped ruled surfaces are to be ground. Execution of motions of the CNC machine is also described. The solution to this problem can be applied as well for the transfer of machine tool settings from a conventional generator to the CNC machine. The developed theory required the derivation of a modified equation of meshing based on application of the concept of space curves, space curves represented on surfaces, geodesic curvature, surface torsion, etc. Condensed information on these topics of differential geometry is provided as well.
Wang, C D; Long, K; Jin, L; Huang, S; Li, D H; Ma, X P; Wei, M; Gu, Y; Ma, J D; Zhang, H
2015-11-13
The giant panda (Ailuropoda melanoleuca) is one of the world's most endangered mammals, and it has evolved several unusual biological and behavioral traits. During puberty, pregnancy, lactation, and involution, the mammary gland undergoes profound morphological and functional changes. A large number of microRNAs (miRNAs) have been identified to be involved in mammary gland development and lactation. In this study, we identified 202 conserved mature miRNAs, corresponding to 147 pre-miRNAs, in giant panda peripheral blood using a small RNA-sequencing approach. In addition, 27 miRNA families and 29 miRNA clusters were identified. We analyzed the arm selection preference of pre-miRNAs and found that: 1) most giant panda pre-miRNAs generated one-strand miRNAs, and the 5p-arm only miRNAs have a higher expression level than 3p-arm only miRNAs; 2) there were more 5p-arm dominant miRNAs than 3p-arm dominant miRNAs; and 3) 5p-arm dominant miRNAs have a larger fold change within miRNA pairs than 3p-arm dominant miRNAs. Expression of 12 lactation-related miRNAs was detected across late pregnancy and early lactation stages by qPCR, and seven miRNAs were identified as clustered in one significant model. Most of these clustered miRNAs exhibited inhibitory roles in proliferation and differentiation of mammary epithelial cells. Functional analysis highlighted important roles of the seven as signed miRNAs in mammary development and metabolic changes, including blood vessel morphogenesis, macromolecule biosynthesis, cell cycle regulation, and protein transport.
Shynlova, Oksana; Nedd-Roderique, Tamara; Li, Yunqing; Dorogin, Anna; Nguyen, Tina; Lye, Stephen J
2013-01-01
Leucocyte infiltration in the decidua (maternal–foetal interface) before, during and after term (TL) and preterm labour (PTL) was studied in mouse. We also investigated the mechanism of peripheral leucocyte recruitment into decidua by analysing the tissue cytokine profiles. Decidual tissues were collected during late gestation, TL and post-partum (PP). PTL was initiated on gestational day 15 by intrauterine injection of Lipopolysaccharide (LPS, 125 μg) or progesterone signalling antagonism by RU486. Animals were killed during PTL or PP. Decidua basalis was analysed using FACS and immunohistochemistry. Markers of myeloid cell differentiation (Gr1, Ly6G, Neu7/4, F4/80) were assessed to define tissue monocytes (M), neutrophils (N) and macrophages (Macs). Flow cytometry revealed a significant (P < 0.05) increase in decidual Macs prior to TL; M and N numbers increased during TL and further increased during PP, which correlated with immunohistochemistry data. Massive influx of N, but not Macs and M, was detected by FACS during LPS-PTL (P < 0.05) but not RU486-PTL. Highest levels of N infiltration into the decidua occurred PP in both LPS and RU486 groups. Decidual infiltration during TL and RU486-PTL was accompanied by an increase in pro-inflammatory cytokines (IL1b and IL6) and CCL2 chemokine; LPS-PTL showed increases in multiple cytokines. PP period following TL and PTL was associated with further up-regulation of multiple cytokines/chemokines (P < 0.05). Our data suggest a programme of myeloid cells involvement in parturition with the pre-partum influx of Macs into the decidua contributing to the progression of labour, whereas the later influx of M and N contribute to PP decidual involution. PMID:23379349
Liu, Danya; Burd, Eileen M.; Coopersmith, Craig M.; Ford, Mandy L.
2016-01-01
Following T cell encounter with antigen, multiple signals are integrated to collectively induce distinct differentiation programs within antigen-specific CD8+ T cell populations. Several factors contribute to these cell fate decisions including the amount and duration of antigen, exposure to inflammatory cytokines, and degree of ligation of cosignaling molecules. The inducible costimulator (ICOS) is not expressed on resting T cells but is rapidly upregulated upon encounter with antigen. However, the impact of ICOS signaling on programmed differentiation is not well understood. In this study we therefore sought to determine the role of ICOS signaling on CD8+ T cell programmed differentiation. Through the creation of novel ICOS retrogenic antigen-specific TCR transgenic CD8+ T cells, we interrogated the phenotype, functionality, and recall potential of CD8+ T cells that receive early and sustained ICOS signaling during antigen exposure. Our results reveal that these ICOS signals critically impacted cell fate decisions of antigen-specific CD8+ T cells, resulting in increased frequencies of KLRG-1hiCD127lo cells, altered BLIMP-1, T-bet, and eomesodermin expression, and increased cytolytic capacity as compared to empty vector controls. Interestingly, however, ICOS retrogenic CD8+ T cells also preferentially homed to non-lymphoid organs, and exhibited reduced multi-cytokine functionality and reduced ability to mount secondary recall responses upon challenge in vivo. In sum, our results suggest that an altered differentiation program is induced following early and sustained ICOS expression, resulting in the generation of more cytolyticly potent, terminally differentiated effectors that possess limited capacity for recall response. PMID:26729800
Liu, Danya; Burd, Eileen M; Coopersmith, Craig M; Ford, Mandy L
2016-02-01
Following T cell encounter with Ag, multiple signals are integrated to collectively induce distinct differentiation programs within Ag-specific CD8(+) T cell populations. Several factors contribute to these cell fate decisions, including the amount and duration of Ag, exposure to inflammatory cytokines, and degree of ligation of cosignaling molecules. The ICOS is not expressed on resting T cells but is rapidly upregulated upon encounter with Ag. However, the impact of ICOS signaling on programmed differentiation is not well understood. In this study, we therefore sought to determine the role of ICOS signaling on CD8(+) T cell programmed differentiation. Through the creation of novel ICOS retrogenic Ag-specific TCR-transgenic CD8(+) T cells, we interrogated the phenotype, functionality, and recall potential of CD8(+) T cells that receive early and sustained ICOS signaling during Ag exposure. Our results reveal that these ICOS signals critically impacted cell fate decisions of Ag-specific CD8(+) T cells, resulting in increased frequencies of KLRG-1(hi)CD127(lo) cells, altered BLIMP-1, T-bet, and eomesodermin expression, and increased cytolytic capacity as compared with empty vector controls. Interestingly, however, ICOS retrogenic CD8(+) T cells also preferentially homed to nonlymphoid organs and exhibited reduced multicytokine functionality and reduced ability to mount secondary recall responses upon challenge in vivo. In sum, our results suggest that an altered differentiation program is induced following early and sustained ICOS expression, resulting in the generation of more cytolyticly potent, terminally differentiated effectors that possess limited capacity for recall response. Copyright © 2016 by The American Association of Immunologists, Inc.
MicroRNAs in the development and neoplasia of the mammary gland.
Jena, Manoj Kumar
2017-01-01
Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2) signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes. Oncogenic miRs like miR-21, miR-221, and miR-210 are overexpressed in triple negative breast cancer cases which can be diagnostic biomarker for this subtype of cancer. This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages) and their involvement in breast cancer progression. Further studies in this area will help us to understand the molecular details of mammary gland biology, as well as miRs that could be therapeutic targets of breast cancer.
Attardo, Geoffrey M.; Medlock, Jan; Aksoy, Serap
2014-01-01
Impact of reproductive processes upon female health has yielded conflicting results; particularly in relation to the role of reproduction-associated stress. We used the viviparous tsetse fly to determine if lactation, birth and involution lead to damage from oxidative stress (OS) that impairs subsequent reproductive cycles. Tsetse females carry an intrauterine larva to full term at each pregnancy cycle, and lactate to nourish them with milk secretions produced by the accessory gland ( = milk gland) organ. Unlike most K-strategists, tsetse females lack an apparent period of reproductive senescence allowing the production of 8–10 progeny over their entire life span. In a lactating female, over 47% of the maternal transcriptome is associated with the generation of milk proteins. The resulting single larval offspring weighs as much as the mother at birth. In studying this process we noted an increase in specific antioxidant enzyme (AOE) transcripts and enzymatic activity at critical times during lactation, birth and involution in the milk gland/fat body organ and the uterus. Suppression of superoxide dismutase (sod) decreased fecundity in subsequent reproductive cycles in young mothers and nearly abolished fecundity in geriatric females. Loss of fecundity was in part due to the inability of the mother to produce adequate milk to support larval growth. Longevity was also impaired after sod knockdown. Generation of OS in virgin females through exogenous treatment with hydrogen peroxide at times corresponding to pregnancy intervals reduced survival, which was exacerbated by sod knockdown. AOE expression may prevent oxidative damage associated with the generation of nutrients by the milk gland, parturition and milk gland breakdown. Our results indicate that prevention of OS is essential for females to meet the growing nutritional demands of juveniles during pregnancy and to repair the damage that occurs at birth. This process is particularly important for females to remain fecund during the latter portion of their lifetime. PMID:24763119
Shared temptations: An fMRI study of dishonest profit maximization.
Simmank, Fabian
2017-12-01
A single case of a tempting-decision task involving financial gain is reported. The subject showed a prosocial Social Value Orientation and applied a profit-maximizing strategy. Differential brain activation patterns for self-serving and other-serving decisions were observed. Results provide new insight into the design of paradigms on bounded ethicality and self- and group-serving behavior. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.
Radke, Sina; Schäfer, Ina C; Müller, Bernhard W; de Bruijn, Ellen R A
2013-12-15
Although 'irrational' decision-making has been linked to depression, the contribution of biases in information processing to these findings remains unknown. To investigate the impact of cognitive biases and aberrant processing of facial emotions on social decision-making, we manipulated both context-related and emotion-related information in a modified Ultimatum Game. Unfair offers were (1) paired with different unselected alternatives, establishing the context in which an offer was made, and (2) accompanied by emotional facial expressions of proposers. Responder behavior was assessed in patients with major depressive disorder and healthy controls. In both groups alike, rejection rates were highest following unambiguous signals of unfairness, i.e. an angry proposer face or when an unfair distribution had deliberately been chosen over an equal split. However, depressed patients showed overall higher rejection rates than healthy volunteers, without exhibiting differential processing biases. This suggests that depressed patients were, as healthy individuals, basing their decisions on informative, salient features and differentiating between (i) fair and unfair offers, (ii) alternatives to unfair offers and (iii) proposers' facial emotions. Although more fundamental processes, e.g. reduced reward sensitivity, might underlie increased rejection in depression, the current study provides insight into mechanisms that shape fairness considerations in both depressed and healthy individuals. © 2013 Elsevier Ireland Ltd. All rights reserved.
Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making
Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.
2008-01-01
The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more ‘bankruptcies’. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage. PMID:18390562
Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making.
Clark, L; Bechara, A; Damasio, H; Aitken, M R F; Sahakian, B J; Robbins, T W
2008-05-01
The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage.
Landsbergis, Paul A.; Diez-Roux, Ana V.; Fujishiro, Kaori; Baron, Sherry; Kaufman, Joel D.; Meyer, John D.; Koutsouras, George; Shimbo, Daichi; Shrager, Sandi; Stukovsky, Karen Hinckley; Szklo, Moyses
2015-01-01
Objective To assess associations of occupational categories and job characteristics with prevalent hypertension. Methods We analyzed 2,517 Multi-Ethnic Study of Atherosclerosis (MESA) participants, working 20+ hours per week, in 2002–4. Results Higher job decision latitude was associated with a lower prevalence of hypertension, prevalence ratio (PR)=0.78 (95% CI 0.66–0.91) for the top vs. bottom quartile of job decision latitude. However, associations differed by occupation: decision latitude was associated with a higher prevalence of hypertension in healthcare support occupations (interaction p=.02). Occupation modified associations of gender with hypertension: a higher prevalence of hypertension in women (vs men) was observed in healthcare support and in blue-collar occupations (interaction p=.03). Conclusions Lower job decision latitude is associated with hypertension prevalence in many occupations. Further research is needed to determine reasons for differential impact of decision latitude and gender on hypertension across occupations. PMID:26539765
TMS affects moral judgment, showing the role of DLPFC and TPJ in cognitive and emotional processing.
Jeurissen, Danique; Sack, Alexander T; Roebroeck, Alard; Russ, Brian E; Pascual-Leone, Alvaro
2014-01-01
Decision-making involves a complex interplay of emotional responses and reasoning processes. In this study, we use TMS to explore the neurobiological substrates of moral decisions in humans. To examining the effects of TMS on the outcome of a moral-decision, we compare the decision outcome of moral-personal and moral-impersonal dilemmas to each other and examine the differential effects of applying TMS over the right DLPFC or right TPJ. In this comparison, we find that the TMS-induced disruption of the DLPFC during the decision process, affects the outcome of the moral-personal judgment, while TMS-induced disruption of TPJ affects only moral-impersonal conditions. In other words, we find a double-dissociation between DLPFC and TPJ in the outcome of a moral decision. Furthermore, we find that TMS-induced disruption of the DLPFC during non-moral, moral-impersonal, and moral-personal decisions lead to lower ratings of regret about the decision. Our results are in line with the dual-process theory and suggest a role for both the emotional response and cognitive reasoning process in moral judgment. Both the emotional and cognitive processes were shown to be involved in the decision outcome.
Separate neural mechanisms underlie choices and strategic preferences in risky decision making.
Venkatraman, Vinod; Payne, John W; Bettman, James R; Luce, Mary Frances; Huettel, Scott A
2009-05-28
Adaptive decision making in real-world contexts often relies on strategic simplifications of decision problems. Yet, the neural mechanisms that shape these strategies and their implementation remain largely unknown. Using an economic decision-making task, we dissociate brain regions that predict specific choices from those predicting an individual's preferred strategy. Choices that maximized gains or minimized losses were predicted by functional magnetic resonance imaging activation in ventromedial prefrontal cortex or anterior insula, respectively. However, choices that followed a simplifying strategy (i.e., attending to overall probability of winning) were associated with activation in parietal and lateral prefrontal cortices. Dorsomedial prefrontal cortex, through differential functional connectivity with parietal and insular cortex, predicted individual variability in strategic preferences. Finally, we demonstrate that robust decision strategies follow from neural sensitivity to rewards. We conclude that decision making reflects more than compensatory interaction of choice-related regions; in addition, specific brain systems potentiate choices depending on strategies, traits, and context.
Separate neural mechanisms underlie choices and strategic preferences in risky decision making
Venkatraman, Vinod; Payne, John W.; Bettman, James R.; Luce, Mary Frances; Huettel, Scott A.
2011-01-01
Adaptive decision making in real-world contexts often relies on strategic simplifications of decision problems. Yet, the neural mechanisms that shape these strategies and their implementation remain largely unknown. Using a novel economic decision-making task, we dissociate brain regions that predict specific choices from those predicting an individual’s preferred strategy. Choices that maximized gains or minimized losses were predicted by fMRI activation in ventromedial prefrontal cortex or anterior insula, respectively. However, choices that followed a simplifying strategy (i.e., attending to overall probability of winning) were associated with activation in parietal and lateral prefrontal cortices. Dorsomedial prefrontal cortex, through differential functional connectivity with parietal and insular cortex, predicted individual variability in strategic preferences. Finally, we demonstrate that robust decision strategies follow from neural sensitivity to rewards. We conclude that decision making reflects more than compensatory interaction of choice-related regions; in addition, specific brain systems potentiate choices depending upon strategies, traits, and context. PMID:19477159
Emotion expression, decision-making and well-being.
Xiao, Erte
2008-01-01
This chapter discusses the role of emotion expression in decision-making. To understand connections between emotion and decision it is helpful first to differentiate between emotion experience and emotion expression. Understanding how emotion expression influences decision-making is important as a practical matter. However, in contrast to emotion experience, economic research has paid little attention to the significance of emotion expression in decision-making. I review recent studies on emotion expression, paying specific attention to possible connections between emotion expression, punishment, fair economic exchange, and well-being. In contrast to emotions, which are typically difficult to control, I suggest that opportunities for emotion expression can feasibly be manipulated through appropriately designed policies. I further suggest that this approach may have the ability to positively affect well-being and economic outcomes. VALUE OF THE CHAPTER: The chapter provides new perspectives on how policy-makers can benefit by understanding the effect of emotion expression in decision-making. The chapter also suggests future research to improve our understanding of emotion expression.
Evidence Accumulation and Choice Maintenance Are Dissociated in Human Perceptual Decision Making
Pedersen, Mads Lund; Endestad, Tor; Biele, Guido
2015-01-01
Perceptual decision making in monkeys relies on decision neurons, which accumulate evidence and maintain choices until a response is given. In humans, several brain regions have been proposed to accumulate evidence, but it is unknown if these regions also maintain choices. To test if accumulator regions in humans also maintain decisions we compared delayed and self-paced responses during a face/house discrimination decision making task. Computational modeling and fMRI results revealed dissociated processes of evidence accumulation and decision maintenance, with potential accumulator activations found in the dorsomedial prefrontal cortex, right inferior frontal gyrus and bilateral insula. Potential maintenance activation spanned the frontal pole, temporal gyri, precuneus and the lateral occipital and frontal orbital cortices. Results of a quantitative reverse inference meta-analysis performed to differentiate the functions associated with the identified regions did not narrow down potential accumulation regions, but suggested that response-maintenance might rely on a verbalization of the response. PMID:26510176
The inaction effect in the psychology of regret.
Zeelenberg, Marcel; van de Bos, Kees; van Dijk, Eric; Pieters, Rik
2002-03-01
Previous research showed that decisions to act (i.e., actions) produce more regret than decisions not to act (i.e., inactions). This previous research focused on decisions made in isolation and ignored that decisions are often made in response to earlier outcomes. The authors show in 4 experiments that these prior outcomes may promote action and hence make inaction more abnormal. They manipulated information about a prior outcome. As hypothesized, when prior outcomes were positive or absent, people attributed more regret to action than to inaction. However, as predicted and counter to previous research, following negative prior outcomes, more regret was attributed to inaction, a finding that the authors label the inaction effect. Experiment 4, showing differential effects for regret and disappointment, demonstrates the need for emotion-specific predictions.
Framing discrimination: effects of inclusion versus exclusion mind-sets on stereotypic judgments.
Hugenberg, Kurt; Bodenhausen, Galen V; McLain, Melissa
2006-12-01
Three studies investigated how inclusion versus exclusion strategies differentially lead to stereotypic decisions. In inclusion strategies, suitable targets are selected from a list of candidates, whereas in exclusion strategies, unsuitable candidates are eliminated. Across 2 separate target domains (Study 1: male and female politicians; Studies 2 and 3: African American and European American basketball players), exclusion strategies, as compared with inclusion strategies, elicited higher levels of both sensitivity stereotyping (i.e., greater difficulty distinguishing among members of stereotyped groups) and criterion stereotyping (i.e., setting different decision thresholds for judging members of different groups; see M. R. Banaji & A. G. Greenwald, 1995). Thus, the strategy used during decision making can influence the final decision via 2 theoretically distinct stereotyping mechanisms. (c) 2006 APA, all rights reserved.
Social Impact of Facial Infantile Hemangiomas in Preteen Children.
Costa, Victoria A; Haimowitz, Rachel; Cheng, Yao I; Wang, Jichuan; Silverman, Robert A; Bauman, Nancy M
2016-01-01
Involuted infantile facial hemangiomas (IHs) may adversely affect the social skills of children. To assess the social impact of involuted facial IHs, with or without prior treatment, in preteen children. An observational, cross-sectional study of social anxiety and skills in preteen children with facial IHs diagnosed during infancy. The study took place in an academic institution and a community dermatology practice between January 1, 2013, and July 30, 2014. Records on 236 children with IHs located in a cosmetically sensitive area were identified; of those, 144 potential participants (parents) were reached by telephone and mailed study packets. Thirty completed questionnaires were returned. Data analysis was performed from August 1, 2014, to September 7, 2015. The questionnaires included the following psychiatric scales: (1) Social Anxiety Scale for Children-Revised (SASC-R), completed by parents and children, including the domains of Fear of Negative Evaluation and Social Avoidance/Distress in New Situations (SAD-New) (higher scores indicate greater social anxiety), and (2) Social Competency Inventory (SCI), completed by parents, including the domains of Prosocial Behavior and Social Initiative (lower scores indicate poorer social competency). Demographics, clinical details, and survey responses were collected. Analysis was conducted using t tests to compare scores for each survey domain with established normative data and between sex as well as between treatment vs nontreatment groups. Of the 144 potential participants, 30 (21%) responded. The mean age of the preteen subjects was 10.0 years (range, 5.4-12.9 years) with a 2:1 female to male ratio. Twenty-five children (83%) had a single IH, and the remaining 5 participants (17%) had multiple IHs, with at least 1 IH in a cosmetically sensitive area. The periocular region was the most common site of the IH (10 [33%]), followed by the nose (6 [20%]), cheek (5 [17%]), forehead (4 [13%]), lip or perioral region (4 [13%]), and ear (1 [3%]). Eighteen children (60%) had received treatment for their IH. With results reported as mean (SD), the SASC-R test showed that social anxiety of the children was not increased over normative data; however, those who did not receive IH treatment had significantly greater anxiety for new situations compared with those who received treatment (SAD-New: 15.5 [5.1] vs 11.5 [3.8]; P = .02). Results of the SCI scale indicated that the Prosocial Orientation domain score for the children was similar to normative data (3.96 [0.48] vs 3.89 [0.55], P = .50). Social Initiative domain scores were significantly poorer in children who did not receive treatment vs those who received treatment (3.45 [0.43] vs 4.03 [0.55]; P = .006). Preteen children with involuted, untreated facial IHs have higher Social Anxiety domain scores in new situations and decreased Social Initiative domain scores compared with children who receive treatment for facial IH. Although this study is limited by a small sample size, it raises important considerations for whether early treatment of facial IHs in cosmetically sensitive areas has a beneficial effect on social skills in preteens.
Decision-Making Guide for the Proposed Coast Guard Differential Global Positioning System
1991-06-01
DIFFERENTIAL GLOBAL POSITIONING SYSTEM by Robert J. Wilson June, 1991 Thesis Co-Advisors: Dan C. Boger Kurt Schnebele Approved for public release; distribution...Wilson Approved by: -Dan C. Boger, Thesis Co dvisor Kurt Scnebele, CaIn, NOAA, Thesis Co-Advisor -4v David R. Whipple, Chairman Department of...Group, 9 April 1990, Coast Guard Research and Development Center, Groton, CT. 20. Kremer , G.T., and others, ’The Effect of Selective Availability on
Xavier, Joana M; Morgado, Ana L; Rodrigues, Cecília MP; Solá, Susana
2014-01-01
The low survival and differentiation rates of stem cells after either transplantation or neural injury have been a major concern of stem cell-based therapy. Thus, further understanding long-term survival and differentiation of stem cells may uncover new targets for discovery and development of novel therapeutic approaches. We have previously described the impact of mitochondrial apoptosis-related events in modulating neural stem cell (NSC) fate. In addition, the endogenous bile acid, tauroursodeoxycholic acid (TUDCA) was shown to be neuroprotective in several animal models of neurodegenerative disorders by acting as an anti-apoptotic and anti-oxidant molecule at the mitochondrial level. Here, we hypothesize that TUDCA might also play a role on NSC fate decision. We found that TUDCA prevents mitochondrial apoptotic events typical of early-stage mouse NSC differentiation, preserves mitochondrial integrity and function, while enhancing self-renewal potential and accelerating cell cycle exit of NSCs. Interestingly, TUDCA prevention of mitochondrial alterations interfered with NSC differentiation potential by favoring neuronal rather than astroglial conversion. Finally, inhibition of mitochondrial reactive oxygen species (mtROS) scavenger and adenosine triphosphate (ATP) synthase revealed that the effect of TUDCA is dependent on mtROS and ATP regulation levels. Collectively, these data underline the importance of mitochondrial stress control of NSC fate decision and support a new role for TUDCA in this process. PMID:25483094
Chiou, Wen-Bin; Chang, Ming-Hsu; Chen, Chien-Lung
2009-04-01
Raghunathan and Pham conducted a pioneer study in 1999 on the motivational influences of anxiety and sadness on decision making and indicated that anxiety would motivate individuals to be risk averse, whereas sadness would motivate individuals to be risk taking. A replication study was employed in the domain of perceived travel risk. Compared to participants in a neutral mood, anxious participants showed higher perceived travel risk than sad participants. Moreover, the differential effect of anxiety and sadness on perceived travel risk was only pronounced under the high personal relevance condition, in which participants made personal decisions and expected that they would be affected by the outcomes. In general, the results extend the notion proposed by Raghunathan and Pham suggesting that travelers' implicit goals primed by anxiety or sadness used for mood-repair purposes appear to be moderated by personal relevance.
Mechanisms of fate decision and lineage commitment during haematopoiesis.
Cvejic, Ana
2016-03-01
Blood stem cells need to both perpetuate themselves (self-renew) and differentiate into all mature blood cells to maintain blood formation throughout life. However, it is unclear how the underlying gene regulatory network maintains this population of self-renewing and differentiating stem cells and how it accommodates the transition from a stem cell to a mature blood cell. Our current knowledge of transcriptomes of various blood cell types has mainly been advanced by population-level analysis. However, a population of seemingly homogenous blood cells may include many distinct cell types with substantially different transcriptomes and abilities to make diverse fate decisions. Therefore, understanding the cell-intrinsic differences between individual cells is necessary for a deeper understanding of the molecular basis of their behaviour. Here we review recent single-cell studies in the haematopoietic system and their contribution to our understanding of the mechanisms governing cell fate choices and lineage commitment.
Neural encoding of competitive effort in the anterior cingulate cortex.
Hillman, Kristin L; Bilkey, David K
2012-09-01
In social environments, animals often compete to obtain limited resources. Strategically electing to work against another animal represents a cost-benefit decision. Is the resource worth an investment of competitive effort? The anterior cingulate cortex (ACC) has been implicated in cost-benefit decision-making, but its role in competitive effort has not been examined. We recorded ACC neurons in freely moving rats as they performed a competitive foraging choice task. When at least one of the two choice options demanded competitive effort, the majority of ACC neurons exhibited heightened and differential firing between the goal trajectories. Inter- and intrasession manipulations revealed that differential firing was not attributable to effort or reward in isolation; instead ACC encoding patterns appeared to indicate net utility assessments of available choice options. Our findings suggest that the ACC is important for encoding competitive effort, a cost-benefit domain that has received little neural-level investigation despite its predominance in nature.
Asymmetric cell division during T cell development controls downstream fate
Pham, Kim; Shimoni, Raz; Charnley, Mirren; Ludford-Menting, Mandy J.; Hawkins, Edwin D.; Ramsbottom, Kelly; Oliaro, Jane; Izon, David; Ting, Stephen B.; Reynolds, Joseph; Lythe, Grant; Molina-Paris, Carmen; Melichar, Heather; Robey, Ellen; Humbert, Patrick O.; Gu, Min
2015-01-01
During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and α-Adaptin. ACD occurs specifically during the β-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the β-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal. PMID:26370500
Medical sieve: a cognitive assistant for radiologists and cardiologists
NASA Astrophysics Data System (ADS)
Syeda-Mahmood, T.; Walach, E.; Beymer, D.; Gilboa-Solomon, F.; Moradi, M.; Kisilev, P.; Kakrania, D.; Compas, C.; Wang, H.; Negahdar, R.; Cao, Y.; Baldwin, T.; Guo, Y.; Gur, Y.; Rajan, D.; Zlotnick, A.; Rabinovici-Cohen, S.; Ben-Ari, R.; Guy, Amit; Prasanna, P.; Morey, J.; Boyko, O.; Hashoul, S.
2016-03-01
Radiologists and cardiologists today have to view large amounts of imaging data relatively quickly leading to eye fatigue. Further, they have only limited access to clinical information relying mostly on their visual interpretation of imaging studies for their diagnostic decisions. In this paper, we present Medical Sieve, an automated cognitive assistant for radiologists and cardiologists designed to help in their clinical decision-making. The sieve is a clinical informatics system that collects clinical, textual and imaging data of patients from electronic health records systems. It then analyzes multimodal content to detect anomalies if any, and summarizes the patient record collecting all relevant information pertinent to a chief complaint. The results of anomaly detection are then fed into a reasoning engine which uses evidence from both patient-independent clinical knowledge and large-scale patient-driven similar patient statistics to arrive at potential differential diagnosis to help in clinical decision making. In compactly summarizing all relevant information to the clinician per chief complaint, the system still retains links to the raw data for detailed review providing holistic summaries of patient conditions. Results of clinical studies in the domains of cardiology and breast radiology have already shown the promise of the system in differential diagnosis and imaging studies summarization.
NASA Astrophysics Data System (ADS)
Pietrzyk, Mariusz W.; Manning, David; Donovan, Tim; Dix, Alan
2010-02-01
Aim: To investigate the impact on visual sampling strategy and pulmonary nodule recognition of image-based properties of background locations in dwelled regions where the first overt decision was made. . Background: Recent studies in mammography show that the first overt decision (TP or FP) has an influence on further image reading including the correctness of the following decisions. Furthermore, the correlation between the spatial frequency properties of the local background following decision sites and the first decision correctness has been reported. Methods: Subjects with different radiological experience were eye tracked during detection of pulmonary nodules from PA chest radiographs. Number of outcomes and the overall quality of performance are analysed in terms of the cases where correct or incorrect decisions were made. JAFROC methodology is applied. The spatial frequency properties of selected local backgrounds related to a certain decisions were studied. ANOVA was used to compare the logarithmic values of energy carried by non redundant stationary wavelet packet coefficients. Results: A strong correlation has been found between the number of TP as a first decision and the JAFROC score (r = 0.74). The number of FP as a first decision was found negatively correlated with JAFROC (r = -0.75). Moreover, the differential spatial frequency profiles outcomes depend on the first choice correctness.
1982-08-01
8217 , . .. +: Lyle E. lawm. Jr. Departmnoto P hlg University of Colorado Technical Report No. 115 -ONR This research was sponsored’by the Personnel...Technical Report of Facts Due to Instructions and the Passage of Time 6. PERFORMING ORG. REPORT N UMPER ICS Tech Rept. 115 . 7. AUTHOR(a) S. CONTRACT OR...2) no difference in decision accuracy would be noted between the intentional and incidental learning groups, and (3) differential decisional accuracy
Feldman‐Stewart, Deb; Brundage, Michael D.; Van Manen, Lori
2008-01-01
Background We developed a decision aid for patients with curable prostate cancer based on Svenson’s DiffCon Theory of Decision Making. This study was designed to determine if surrogate patients using the aid could understand the information presented, complete all tasks, show evidence of differentiation, and arrive at a preferred treatment choice. Methods Men, at least 50 years old and never diagnosed with prostate cancer, were recruited through local advertisements. Participants were asked to imagine that they were a case‐scenario patient. Then they completed the decision aid interview, which included three components: (i) information presentation, with comprehension questions, (ii) exercises to help identify attributes important to the decision, and (iii) value‐clarification exercises. Results Sixty‐nine men volunteered. They had a mean age of 61.2 (range 50–83) years, 37% had no formal education beyond high school, and 87% were living with a partner. All participants completed all aspects of the interview. They answered an average of 10 comprehension questions each, with a mean of 94.7% correct without a prompt. Each attribute in the information presented was identified by at least one participant as important to his decision. Participants identified a median of five attributes as important (ranges 1–14) at each of three points during the interview; 75% changed at least one important attribute during the interview. Forty‐nine per cent of participants also identified attributes as important that were not included in the presented information. Participants showed a wide range of values in each of seven trade‐off exercises. Eighty‐eight per cent of participants showed evidence of differentiation; 75% had a clear treatment preference by the end of the interview. Conclusions Our decision aid appears to meet its goals for surrogate patients and illustrates the strengths of the DiffCon theory. The ability of the aid to accommodate wide variability, both in information needs and in important attributes, is a particular strength of the decision aid. It now requires testing in patients with prostate cancer. PMID:11703496
[Aging of the respiratory system: anatomical changes and physiological consequences].
Ketata, W; Rekik, W K; Ayadi, H; Kammoun, S
2012-10-01
The respiratory system undergoes progressive involution with age, resulting in anatomical and functional changes that are exerted on all levels. The rib cage stiffens and respiratory muscles weaken. Distal bronchioles have reduced diameter and tend to be collapsed. Mobilized lung volumes decrease with age while residual volume increases. Gas exchanges are modified with a linear decrease of PaO(2) up to the age of 70 years and a decreased diffusing capacity of carbon monoxide. Ventilatory responses to hypercapnia, hypoxia and exercise decrease in the elderly. Knowledge of changes in the respiratory system related to advancing age is a medical issue of great importance in order to distinguish the effects of aging from those of diseases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
A cephalometric study of velar stretch in adolescent subjects.
Simpson, R K; Colton, J
1980-01-01
Cephalometric x-rays were used to evaluate velar stretch in 20 normal adolescents during the production of /s/. Radiopaque markers were used so that the behaviors of both the anterior and posterior portions and the total velum cound be evaluated. Velar stretch was found in each of the subjects with the average stretch (15.19%) greater than the amount reported for 10-year-old subjects but less than the average stretch for adults. The correlation between amount of velar stretch and need ratio was not significant. The different stages of involution of adenoid tissue, which is characteristic of this age group, resulted in varying configurations of the naso-pharynx were postulated as one possible explanation for this unexpected finding. Normative data and clinical implications are presented.
Inverse eigenproblem for R-symmetric matrices and their approximation
NASA Astrophysics Data System (ADS)
Yuan, Yongxin
2009-11-01
Let be a nontrivial involution, i.e., R=R-1[not equal to]±In. We say that is R-symmetric if RGR=G. The set of all -symmetric matrices is denoted by . In this paper, we first give the solvability condition for the following inverse eigenproblem (IEP): given a set of vectors in and a set of complex numbers , find a matrix such that and are, respectively, the eigenvalues and eigenvectors of A. We then consider the following approximation problem: Given an n×n matrix , find such that , where is the solution set of IEP and ||[dot operator]|| is the Frobenius norm. We provide an explicit formula for the best approximation solution by means of the canonical correlation decomposition.
Spherical type integrable classical systems in a magnetic field
NASA Astrophysics Data System (ADS)
Marchesiello, A.; Šnobl, L.; Winternitz, P.
2018-04-01
We show that four classes of second order spherical type integrable classical systems in a magnetic field exist in the Euclidean space {E}3 , and construct the Hamiltonian and two second order integrals of motion in involution for each of them. For one of the classes the Hamiltonian depends on four arbitrary functions of one variable. This class contains the magnetic monopole as a special case. Two further classes have Hamiltonians depending on one arbitrary function of one variable and four or six constants, respectively. The magnetic field in these cases is radial. The remaining system corresponds to a constant magnetic field and the Hamiltonian depends on two constants. Questions of superintegrability—i.e. the existence of further integrals—are discussed.
Thymic Fatness and Approaches to Enhance Thymopoietic Fitness in Aging
Dixit, Vishwa Deep
2010-01-01
Summary With advancing age, the thymus undergoes striking fibrotic and fatty changes that culminate in its transformation into adipose tissue. As the thymus involutes, reduction in thymocytes and thymic epithelial cells precede the emergence of mature lipid-laden adipocytes. Dogma dictates that adipocytes are ‘passive’ cells that occupy non-epithelial thymic space or ‘infiltrate’ the non cellular thymic niches. The provenance and purpose of ectopic thymic adipocytes during aging in an organ that is required for establishment and maintenance of T cell repertoire remains an unsolved puzzle. Nonetheless, tantalizing clues about elaborate reciprocal relationship between thymic fatness and thymopoietic fitness are emerging. Blocking or bypassing the route towards thymic adiposity may complement the approaches to rejuvenate thymopoiesis and immunity in elderly. PMID:20650623
[Enhanced resistance to emotional stress through the use of D-phenylalanine].
Iumatov, E A; Sarychev, E I; Kozlovskiĭ, I I; Mineeva, M F; Demidov, V M; Morozov, I S; Kozlovskaia, M M
1991-01-01
Stress-protective action was studied of D-phenylalanine, having an ability to decrease destruction of endogenic enkefalins. In the experiments stability of the experimental (receiving D-phenylalanine) and control groups of male rats of August line to emotional stress was compared in conditions of immobilization stress by parameters of animals survival rate, adrenal glands hypertrophy development, involution of thymus, pathologic changes in lungs (abscesses development), ulcero-dystrophic disturbances in stomach, and also the activity and kinetic properties of enzyme tyrosin-hydroxylase in the hypothalamus were determined. It was shown that by several of the mentioned physiological parameters the D-phenylalanine significantly increased the animals stability to the emotional stress and decreased tyrosinhydroxylase activity which participates in activation of katecholaminergic processes.
A critical narrative analysis of shared decision-making in acute inpatient mental health care.
Stacey, Gemma; Felton, Anne; Morgan, Alastair; Stickley, Theo; Willis, Martin; Diamond, Bob; Houghton, Philip; Johnson, Beverley; Dumenya, John
2016-01-01
Shared decision-making (SDM) is a high priority in healthcare policy and is complementary to the recovery philosophy in mental health care. This agenda has been operationalised within the Values-Based Practice (VBP) framework, which offers a theoretical and practical model to promote democratic interprofessional approaches to decision-making. However, these are limited by a lack of recognition of the implications of power implicit within the mental health system. This study considers issues of power within the context of decision-making and examines to what extent decisions about patients' care on acute in-patient wards are perceived to be shared. Focus groups were conducted with 46 mental health professionals, service users, and carers. The data were analysed using the framework of critical narrative analysis (CNA). The findings of the study suggested each group constructed different identity positions, which placed them as inside or outside of the decision-making process. This reflected their view of themselves as best placed to influence a decision on behalf of the service user. In conclusion, the discourse of VBP and SDM needs to take account of how differentials of power and the positioning of speakers affect the context in which decisions take place.
Decision-making capacity should not be decisive in emergencies.
Hubbeling, Dieneke
2014-05-01
Examples of patients with anorexia nervosa, depression or borderline personality disorder who have decision-making capacity as currently operationalized, but refuse treatment, are discussed. It appears counterintuitive to respect their treatment refusal because their wish seems to be fuelled by their illness and the consequences of their refusal of treatment are severe. Some proposed solutions have focused on broadening the criteria for decision-making capacity, either in general or for specific patient groups, but these adjustments might discriminate against particular groups of patients and render the process less transparent. Other solutions focus on preferences expressed when patients are not ill, but this information is often not available. The reason for such difficulties with assessing decision-making capacity is that the underlying psychological processes of normal decision-making are not well known and one cannot differentiate between unwise decisions caused by an illness or other factors. The proposed alternative, set out in this paper, is to allow compulsory treatment of patients with decision-making capacity in cases of an emergency, if the refusal is potentially life threatening, but only for a time-limited period. The argument is also made for investigating hindsight agreement, in particular after compulsory measures.
Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A
2017-04-11
Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .
2010-09-01
differentiated between source codes and input/output files. The text makes references to a REMChlor-GoldSim model. The text also refers to the REMChlor...To the extent possible, the instructions should be accurate and precise. The documentation should differentiate between describing what is actually...Windows XP operating system Model Input Paran1eters. · n1e input parameters were identical to those utilized and reported by CDM (See Table .I .from
A Tutorial on RxODE: Simulating Differential Equation Pharmacometric Models in R.
Wang, W; Hallow, K M; James, D A
2016-01-01
This tutorial presents the application of an R package, RxODE, that facilitates quick, efficient simulations of ordinary differential equation models completely within R. Its application is illustrated through simulation of design decision effects on an adaptive dosing regimen. The package provides an efficient, versatile way to specify dosing scenarios and to perform simulation with variability with minimal custom coding. Models can be directly translated to Rshiny applications to facilitate interactive, real-time evaluation/iteration on simulation scenarios.
A Hierarchy of Proof Rules for Checking Differential Invariance of Algebraic Sets
2014-11-01
linear hybrid systems by linear algebraic methods. In SAS, volume 6337 of LNCS, pages 373–389. Springer, 2010. [19] E. W. Mayr. Membership in polynomial...383–394, 2009. [31] A. Tarski. A decision method for elementary algebra and geometry. Bull. Amer. Math. Soc., 59, 1951. [32] A. Tiwari. Abstractions...A Hierarchy of Proof Rules for Checking Differential Invariance of Algebraic Sets Khalil Ghorbal1 Andrew Sogokon2 André Platzer1 November 2014 CMU
Smith, S M; Clark, M
1990-09-01
The research confirms the coexistence of different images for hospitals, service centers within the same hospitals, and service programs offered by each of the service centers. The images of individual service centers are found not to be tied to the image of the host facility. Further, service centers and host facilities have differential rankings on the same service decision attributes. Managerial recommendations are offered for "image differentiation" between a hospital and its care centers.
Ramond, Cyrille; Glaser, Nicolas; Berthault, Claire; Ameri, Jacqueline; Kirkegaard, Jeannette Schlichting; Hansson, Mattias; Honoré, Christian; Semb, Henrik; Scharfmann, Raphaël
2017-01-01
Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated. DOI: http://dx.doi.org/10.7554/eLife.27564.001 PMID:28731406
The value of electrocardiography for differential diagnosis in wide QRS complex tachycardia.
Sousa, Pedro A; Pereira, Salomé; Candeias, Rui; de Jesus, Ilídio
2014-03-01
Correct diagnosis in wide QRS complex tachycardia remains a challenge. Differential diagnosis between ventricular and supraventricular tachycardia has important therapeutic and prognostic implications, and although data from clinical history and physical examination may suggest a particular origin, it is the 12-lead surface electrocardiogram that usually enables this differentiation. Since 1978, various electrocardiographic criteria have been proposed for the differential diagnosis of wide complex tachycardias, particularly the presence of atrioventricular dissociation, and the axis, duration and morphology of QRS complexes. Despite the wide variety of criteria, diagnosis is still often difficult, and errors can have serious consequences. To reduce such errors, several differential diagnosis algorithms have been proposed since 1991. However, in a small percentage of wide QRS tachycardias the diagnosis remains uncertain and in these the wisest decision is to treat them as ventricular tachycardias. The authors' objective was to review the main electrocardiographic criteria and differential diagnosis algorithms of wide QRS tachycardia. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.
Decision making in high-velocity environments: implications for healthcare.
Stepanovich, P L; Uhrig, J D
1999-01-01
Healthcare can be considered a high-velocity environment and, as such, can benefit from research conducted in other industries regarding strategic decision making. Strategic planning is not only relevant to firms in high-velocity environments, but is also important for high performance and survival. Specifically, decision-making speed seems to be instrumental in differentiating between high and low performers; fast decision makers outperform slow decision makers. This article outlines the differences between fast and slow decision makers, identifies five paralyses that can slow decision making in healthcare, and outlines the role of a planning department in circumventing these paralyses. Executives can use the proposed planning structure to improve both the speed and quality of strategic decisions. The structure uses planning facilitators to avoid the following five paralyses: 1. Analysis. Decision makers can no longer afford the luxury of lengthy, detailed analysis but must develop real-time systems that provide appropriate, timely information. 2. Alternatives. Many alternatives (beyond the traditional two or three) need to be considered and the alternatives must be evaluated simultaneously. 3. Group Think. Decision makers must avoid limited mind-sets and autocratic leadership styles by seeking out independent, knowledgeable counselors. 4. Process. Decision makers need to resolve conflicts through "consensus with qualification," as opposed to waiting for everyone to come on board. 5. Separation. Successful implementation requires a structured process that cuts across disciplines and levels.
Floresco, Stan B; Montes, David R; Tse, Maric M T; van Holstein, Mieke
2018-02-21
The nucleus accumbens (NAc) is a key node within corticolimbic circuitry for guiding action selection and cost/benefit decision making in situations involving reward uncertainty. Preclinical studies have typically assessed risk/reward decision making using assays where decisions are guided by internally generated representations of choice-outcome contingencies. Yet, real-life decisions are often influenced by external stimuli that inform about likelihoods of obtaining rewards. How different subregions of the NAc mediate decision making in such situations is unclear. Here, we used a novel assay colloquially termed the "Blackjack" task that models these types of situations. Male Long-Evans rats were trained to choose between one lever that always delivered a one-pellet reward and another that delivered four pellets with different probabilities [either 50% (good-odds) or 12.5% (poor-odds)], which were signaled by one of two auditory cues. Under control conditions, rats selected the large/risky option more often on good-odds versus poor-odds trials. Inactivation of the NAc core caused indiscriminate choice patterns. In contrast, NAc shell inactivation increased risky choice, more prominently on poor-odds trials. Additional experiments revealed that both subregions contribute to auditory conditional discrimination. NAc core or shell inactivation reduced Pavlovian approach elicited by an auditory CS+, yet shell inactivation also increased responding during presentation of a CS-. These data highlight distinct contributions for NAc subregions in decision making and reward seeking guided by discriminative stimuli. The core is crucial for implementation of conditional rules, whereas the shell refines reward seeking by mitigating the allure of larger, unlikely rewards and reducing expression of inappropriate or non-rewarded actions. SIGNIFICANCE STATEMENT Using external cues to guide decision making is crucial for adaptive behavior. Deficits in cue-guided behavior have been associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder and schizophrenia, which in turn has been linked to aberrant processing in the nucleus accumbens. However, many preclinical studies have often assessed risk/reward decision making in the absence of explicit cues. The current study fills that gap by using a novel task that allows for the assessment of cue-guided risk/reward decision making in rodents. Our findings identified distinct yet complementary roles for the medial versus lateral portions of this nucleus that provide a broader understanding of the differential contributions it makes to decision making and reward seeking guided by discriminative stimuli. Copyright © 2018 the authors 0270-6474/18/381901-14$15.00/0.
A special vegetation index for the weed detection in sensor based precision agriculture.
Langner, Hans-R; Böttger, Hartmut; Schmidt, Helmut
2006-06-01
Many technologies in precision agriculture (PA) require image analysis and image- processing with weed and background differentiations. The detection of weeds on mulched cropland is one important image-processing task for sensor based precision herbicide applications. The article introduces a special vegetation index, the Difference Index with Red Threshold (DIRT), for the weed detection on mulched croplands. Experimental investigations in weed detection on mulched areas point out that the DIRT performs better than the Normalized Difference Vegetation Index (NDVI). The result of the evaluation with four different decision criteria indicate, that the new DIRT gives the highest reliability in weed/background differentiation on mulched areas. While using the same spectral bands (infrared and red) as the NDVI, the new DIRT is more suitable for weed detection than the other vegetation indices and requires only a small amount of additional calculation power. The new vegetation index DIRT was tested on mulched areas during automatic ratings with a special weed camera system. The test results compare the new DIRT and three other decision criteria: the difference between infrared and red intensity (Diff), the soil-adjusted quotient between infrared and red intensity (Quotient) and the NDVI. The decision criteria were compared with the definition of a worse case decision quality parameter Q, suitable for mulched croplands. Although this new index DIRT needs further testing, the index seems to be a good decision criterion for the weed detection on mulched areas and should also be useful for other image processing applications in precision agriculture. The weed detection hardware and the PC program for the weed image processing were developed with funds from the German Federal Ministry of Education and Research (BMBF).
A Diagnostic Taxonomy of Adult Career Problems.
ERIC Educational Resources Information Center
Campbell, Robert E.; Cellini, James V.
1981-01-01
Developed a taxonomy for the differential diagnosis of adult career development problems. Problem categories identified were: (1) problems in career decision making; (2) problems in implementing career plans; (3) problems in organizational/institutional performance; and (4) problems in organizational/institutional adaption. (Author)
Normative evidence accumulation in unpredictable environments
Glaze, Christopher M; Kable, Joseph W; Gold, Joshua I
2015-01-01
In our dynamic world, decisions about noisy stimuli can require temporal accumulation of evidence to identify steady signals, differentiation to detect unpredictable changes in those signals, or both. Normative models can account for learning in these environments but have not yet been applied to faster decision processes. We present a novel, normative formulation of adaptive learning models that forms decisions by acting as a leaky accumulator with non-absorbing bounds. These dynamics, derived for both discrete and continuous cases, depend on the expected rate of change of the statistics of the evidence and balance signal identification and change detection. We found that, for two different tasks, human subjects learned these expectations, albeit imperfectly, then used them to make decisions in accordance with the normative model. The results represent a unified, empirically supported account of decision-making in unpredictable environments that provides new insights into the expectation-driven dynamics of the underlying neural signals. DOI: http://dx.doi.org/10.7554/eLife.08825.001 PMID:26322383
Dynamic Divisive Normalization Predicts Time-Varying Value Coding in Decision-Related Circuits
LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W.
2014-01-01
Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. PMID:25429145
The role of emotion expectancies in adolescents' moral decision making.
Krettenauer, Tobias; Jia, Fanli; Mosleh, Maureen
2011-02-01
This study investigated the impact of emotion expectancies on adolescents' moral decision making in hypothetical situations. The sample consisted of 160 participants from three different grade levels (mean age=15.79 years, SD=2.96). Participants were confronted with a set of scenarios that described various emotional outcomes of (im)moral actions and needed to decide what they would do if they were in the protagonist's shoes. Findings demonstrate that emotion expectancies differentially influenced adolescents' hypothetical decision making in antisocial versus prosocial behavioral contexts. Whereas negatively charged self-evaluative emotions over failing to act morally (e.g., guilt) were the strongest predictor for moral choice in antisocial behavioral contexts, positively charged self-evaluative emotions over acting morally (e.g., pride) most strongly predicted moral choice in prosocial contexts. Older adolescents paid greater attention to outcome-oriented emotions that make the decision to act morally less attractive (e.g., regret). Overall, the study suggests that emotion expectancies influence moral decision making in unique and meaningful ways. Copyright © 2010 Elsevier Inc. All rights reserved.
Bioinspired decision architectures containing host and microbiome processing units.
Heyde, K C; Gallagher, P W; Ruder, W C
2016-09-27
Biomimetic robots have been used to explore and explain natural phenomena ranging from the coordination of ants to the locomotion of lizards. Here, we developed a series of decision architectures inspired by the information exchange between a host organism and its microbiome. We first modeled the biochemical exchanges of a population of synthetically engineered E. coli. We then built a physical, differential drive robot that contained an integrated, onboard computer vision system. A relay was established between the simulated population of cells and the robot's microcontroller. By placing the robot within a target-containing a two-dimensional arena, we explored how different aspects of the simulated cells and the robot's microcontroller could be integrated to form hybrid decision architectures. We found that distinct decision architectures allow for us to develop models of computation with specific strengths such as runtime efficiency or minimal memory allocation. Taken together, our hybrid decision architectures provide a new strategy for developing bioinspired control systems that integrate both living and nonliving components.
Chen, Meizhen; Takano-Maruyama, Masumi; Pereira-Smith, Olivia M; Gaufo, Gary O; Tominaga, Kaoru
2009-05-15
Neurogenesis during development depends on the coordinated regulation of self-renewal and differentiation of neural precursor cells (NPCs). Chromatin regulation is a key step in self-renewal activity and fate decision of NPCs. However, the molecular mechanism or mechanisms of this regulation is not fully understood. Here, we demonstrate for the first time that MRG15, a chromatin regulator, is important for proliferation and neural fate decision of NPCs. Neuroepithelia from Mrg15-deficient embryonic brain are much thinner than those from control, and apoptotic cells increase in this region. We isolated NPCs from Mrg15-deficient and wild-type embryonic whole brains and produced neurospheres to measure the self-renewal and differentiation abilities of these cells in vitro. Neurospheres culture from Mrg15-deficient embryo grew less efficiently than those from wild type. Measurement of proliferation by means of BrdU (bromodeoxyuridine) incorporation revealed that Mrg15-deficient NPCs have reduced proliferation ability and apoptotic cells do not increase during in vitro culture. The reduced proliferation of Mrg15-deficient NPCs most likely accounts for the thinner neuroepithelia in Mrg15-deficient embryonic brain. Moreover, we also demonstrate Mrg15-deficient NPCs are defective in differentiation into neurons in vitro. Our results demonstrate that MRG15 has more than one function in neurogenesis and defines a novel role for this chromatin regulator that integrates proliferation and cell-fate determination in neurogenesis during development. Copyright 2008 Wiley-Liss, Inc.
Yu, Rong; Zhong, Weifeng; Xie, Shengli; Zhang, Yan; Zhang, Yun
2016-02-01
As the next-generation power grid, smart grid will be integrated with a variety of novel communication technologies to support the explosive data traffic and the diverse requirements of quality of service (QoS). Cognitive radio (CR), which has the favorable ability to improve the spectrum utilization, provides an efficient and reliable solution for smart grid communications networks. In this paper, we study the QoS differential scheduling problem in the CR-based smart grid communications networks. The scheduler is responsible for managing the spectrum resources and arranging the data transmissions of smart grid users (SGUs). To guarantee the differential QoS, the SGUs are assigned to have different priorities according to their roles and their current situations in the smart grid. Based on the QoS-aware priority policy, the scheduler adjusts the channels allocation to minimize the transmission delay of SGUs. The entire transmission scheduling problem is formulated as a semi-Markov decision process and solved by the methodology of adaptive dynamic programming. A heuristic dynamic programming (HDP) architecture is established for the scheduling problem. By the online network training, the HDP can learn from the activities of primary users and SGUs, and adjust the scheduling decision to achieve the purpose of transmission delay minimization. Simulation results illustrate that the proposed priority policy ensures the low transmission delay of high priority SGUs. In addition, the emergency data transmission delay is also reduced to a significantly low level, guaranteeing the differential QoS in smart grid.
Nature of collective decision-making by simple yes/no decision units.
Hasegawa, Eisuke; Mizumoto, Nobuaki; Kobayashi, Kazuya; Dobata, Shigeto; Yoshimura, Jin; Watanabe, Saori; Murakami, Yuuka; Matsuura, Kenji
2017-10-31
The study of collective decision-making spans various fields such as brain and behavioural sciences, economics, management sciences, and artificial intelligence. Despite these interdisciplinary applications, little is known regarding how a group of simple 'yes/no' units, such as neurons in the brain, can select the best option among multiple options. One prerequisite for achieving such correct choices by the brain is correct evaluation of relative option quality, which enables a collective decision maker to efficiently choose the best option. Here, we applied a sensory discrimination mechanism using yes/no units with differential thresholds to a model for making a collective choice among multiple options. The performance corresponding to the correct choice was shown to be affected by various parameters. High performance can be achieved by tuning the threshold distribution with the options' quality distribution. The number of yes/no units allocated to each option and its variability profoundly affects performance. When this variability is large, a quorum decision becomes superior to a majority decision under some conditions. The general features of this collective decision-making by a group of simple yes/no units revealed in this study suggest that this mechanism may be useful in applications across various fields.
A CONCEPT MAP FOR INTEGRATED ENVIRONMENTAL ASSESSMENT AND FUTURES MODELING
Integrated assessment models are differentiated from other models by their explicit concern for results that are useful to decision makers. While the details will differ greatly for each particular integrated assessments project, there are certain concepts that will be present f...
Family Influences on College Students' Occupational Identity
ERIC Educational Resources Information Center
Berrios-Allison, Ana C.
2005-01-01
The occupational identity statuses of 232 college students were analyzed by examining their family emotional environment and the identity control processes that drive career decision making. Results of multivariate analysis showed that each family differentiation construct, family tolerance for connectedness, and separateness explained significant…
Explanation and Categorization: How "Why?" Informs "What?"
ERIC Educational Resources Information Center
Lombrozo, Tania
2009-01-01
Recent theoretical and empirical work suggests that explanation and categorization are intimately related. This paper explores the hypothesis that explanations can help structure conceptual representations, and thereby influence the relative importance of features in categorization decisions. In particular, features may be differentially important…
Complexity reduction of rate-equations models for two-choice decision-making.
Carrillo, José Antonio; Cordier, Stéphane; Deco, Gustavo; Mancini, Simona
2013-01-01
We are concerned with the complexity reduction of a stochastic system of differential equations governing the dynamics of a neuronal circuit describing a decision-making task. This reduction is based on the slow-fast behavior of the problem and holds on the whole phase space and not only locally around the spontaneous state. Macroscopic quantities, such as performance and reaction times, computed applying this reduction are in agreement with previous works in which the complexity reduction is locally performed at the spontaneous point by means of a Taylor expansion.
High-predation habitats affect the social dynamics of collective exploration in a shoaling fish.
Ioannou, Christos C; Ramnarine, Indar W; Torney, Colin J
2017-05-01
Collective decisions play a major role in the benefits that animals gain from living in groups. Although the mechanisms of how groups collectively make decisions have been extensively researched, the response of within-group dynamics to ecological conditions is virtually unknown, despite adaptation to the environment being a cornerstone in biology. We investigate how within-group interactions during exploration of a novel environment are shaped by predation, a major influence on the behavior of prey species. We tested guppies ( Poecilia reticulata ) from rivers varying in predation risk under controlled laboratory conditions and find the first evidence of differences in group interactions between animals adapted to different levels of predation. Fish from high-predation habitats showed the strongest negative relationship between initiating movements and following others, which resulted in less variability in the total number of movements made between individuals. This relationship between initiating movements and following others was associated with differentiation into initiators and followers, which was only observed in fish from high-predation rivers. The differentiation occurred rapidly, as trials lasted 5 min, and was related to shoal cohesion, where more diverse groups from high-predation habitats were more cohesive. Our results show that even within a single species over a small geographical range, decision-making in a social context can vary with local ecological factors.
Judson, Robert N.; Tremblay, Annie M.; Knopp, Paul; White, Robert B.; Urcia, Roby; De Bari, Cosimo; Zammit, Peter S.; Camargo, Fernando D.; Wackerhage, Henning
2012-01-01
Summary Satellite cells are the resident stem cells of skeletal muscle. Mitotically quiescent in mature muscle, they can be activated to proliferate and generate myoblasts to supply further myonuclei to hypertrophying or regenerating muscle fibres, or self-renew to maintain the resident stem cell pool. Here, we identify the transcriptional co-factor Yap as a novel regulator of satellite cell fate decisions. Yap expression increases during satellite cell activation and Yap remains highly expressed until after the differentiation versus self-renewal decision is made. Constitutive expression of Yap maintains Pax7+ and MyoD+ satellite cells and satellite cell-derived myoblasts, promotes proliferation but prevents differentiation. In contrast, Yap knockdown reduces the proliferation of satellite cell-derived myoblasts by ≈40%. Consistent with the cellular phenotype, microarrays show that Yap increases expression of genes associated with Yap inhibition, the cell cycle, ribosome biogenesis and that it represses several genes associated with angiotensin signalling. We also identify known regulators of satellite cell function such as BMP4, CD34 and Myf6 (Mrf4) as genes whose expression is dependent on Yap activity. Finally, we confirm in myoblasts that Yap binds to Tead transcription factors and co-activates MCAT elements which are enriched in the proximal promoters of Yap-responsive genes. PMID:23038772
Muraskin, Jordan; Sherwin, Jason; Sajda, Paul
2015-12-01
Given a decision that requires less than half a second for evaluating the characteristics of the incoming pitch and generating a motor response, hitting a baseball potentially requires unique perception-action coupling to achieve high performance. We designed a rapid perceptual decision-making experiment modeled as a Go/No-Go task yet tailored to reflect a real scenario confronted by a baseball hitter. For groups of experts (Division I baseball players) and novices (non-players), we recorded electroencephalography (EEG) while they performed the task. We analyzed evoked EEG single-trial variability, contingent negative variation (CNV), and pre-stimulus alpha power with respect to the expert vs. novice groups. We found strong evidence for differences in inhibitory processes between the two groups, specifically differential activity in supplementary motor areas (SMA), indicative of enhanced inhibitory control in the expert (baseball player) group. We also found selective activity in the fusiform gyrus (FG) and orbital gyrus in the expert group, suggesting an enhanced perception-action coupling in baseball players that differentiates them from matched controls. In sum, our results show that EEG correlates of decision formation can be used to identify neural markers of high-performance athletes. Copyright © 2015 Elsevier Inc. All rights reserved.
Abadie, Marlène; Waroquier, Laurent; Terrier, Patrice
2017-05-01
Previous research showed that the unconscious-thought effect , which refers to an improvement in complex decision making following a distraction period, was moderated by the presentation format of pieces of information about different options. The aim of the current study was to replicate this finding and further examine the memory representations underlying decision making following a distraction or a deliberation period. Results showed that, when the information was presented blocked per option, participants were better able to differentiate the best option from the others after a distraction period than immediately after the information presentation or after a deliberation period. In addition, distracted participants retrieved more gist representations of the options when the information was presented per option. By contrast, participants were better able to differentiate the best option from the others after a deliberation period when the information was presented per attribute. Participants who deliberated also retrieved more verbatim representations when the information was presented per attribute. Finally, mediation analyses indicated that the accuracy of the evaluations of the options depends on gist memory when distracted but on verbatim memory when deliberating. These findings suggest that the effectiveness of distraction or deliberation depends on the memory representations of the different options. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Multi-objective optimisation and decision-making of space station logistics strategies
NASA Astrophysics Data System (ADS)
Zhu, Yue-he; Luo, Ya-zhong
2016-10-01
Space station logistics strategy optimisation is a complex engineering problem with multiple objectives. Finding a decision-maker-preferred compromise solution becomes more significant when solving such a problem. However, the designer-preferred solution is not easy to determine using the traditional method. Thus, a hybrid approach that combines the multi-objective evolutionary algorithm, physical programming, and differential evolution (DE) algorithm is proposed to deal with the optimisation and decision-making of space station logistics strategies. A multi-objective evolutionary algorithm is used to acquire a Pareto frontier and help determine the range parameters of the physical programming. Physical programming is employed to convert the four-objective problem into a single-objective problem, and a DE algorithm is applied to solve the resulting physical programming-based optimisation problem. Five kinds of objective preference are simulated and compared. The simulation results indicate that the proposed approach can produce good compromise solutions corresponding to different decision-makers' preferences.
Health versus money. Value judgments in the perspective of decision analysis.
Thompson, M S
1983-01-01
An important, but largely uninvestigated, value trade-off balances marginal nonhealth consumption against marginal medical care. Benefit-cost analysts have traditionally, if not fully satisfactorily, dealt with this issue by valuing health gains by their effects on productivity. Cost-effectiveness analysts compare monetary and health effects and leave their relative valuations to decision makers. A decision-analytic model using the satisfaction or utility gained from nonhealth consumption and the level of health enables one to calculate willingness to pay--a theoretically superior way of assigning monetary values to effects for benefit-cost analysis-and to determine minimally acceptable cost-effectiveness ratios. Examples show how a decision-analytic model of utility can differentiate medical actions so essential that failure to take them would be considered negligent from actions so expensive as to be unjustifiable, and can help to determine optimal legal arrangements for compensation for medical malpractice.
Two sides of the same coin: Monetary incentives concurrently improve and bias confidence judgments.
Lebreton, Maël; Langdon, Shari; Slieker, Matthijs J; Nooitgedacht, Jip S; Goudriaan, Anna E; Denys, Damiaan; van Holst, Ruth J; Luigjes, Judy
2018-05-01
Decisions are accompanied by a feeling of confidence, that is, a belief about the decision being correct. Confidence accuracy is critical, notably in high-stakes situations such as medical or financial decision-making. We investigated how incentive motivation influences confidence accuracy by combining a perceptual task with a confidence incentivization mechanism. By varying the magnitude and valence (gains or losses) of monetary incentives, we orthogonalized their motivational and affective components. Corroborating theories of rational decision-making and motivation, our results first reveal that the motivational value of incentives improves aspects of confidence accuracy. However, in line with a value-confidence interaction hypothesis, we further show that the affective value of incentives concurrently biases confidence reports, thus degrading confidence accuracy. Finally, we demonstrate that the motivational and affective effects of incentives differentially affect how confidence builds on perceptual evidence. Together, these findings may provide new hints about confidence miscalibration in healthy or pathological contexts.
Toma, Claudia; Butera, Fabrizio
2009-06-01
Two experiments investigated the differential impact of cooperation and competition on strategic information sharing and use in a three-person group decision-making task. Information was distributed in order to create a hidden profile so that disconfirmation of group members' initial preferences was required to solve the task. Experiment 1 revealed that competition, compared to cooperation, led group members to withhold unshared information, a difference that was not significant for shared information. In competition, compared to cooperation, group members were also more reluctant to disconfirm their initial preferences. Decision quality was lower in competition than in cooperation, this effect being mediated by disconfirmation use and not by information sharing. Experiment 2 replicated these findings and revealed the role of mistrust in predicting strategic information sharing and use in competition. These results support a motivated information processing approach of group decision making.
Mussel, Patrick; Hewig, Johannes; Allen, John J B; Coles, Michael G H; Miltner, Wolfgang
2014-04-01
Facial expressions are an important aspect of social interaction, conveying not only information regarding emotional states, but also regarding intentions, personality, and complex social characteristics. The present research investigates how a smiling, compared to a nonsmiling, expression impacts decision making and underlying cognitive and emotional processes in economic bargaining. Our results using the ultimatum game show that facial expressions have an impact on decision making as well as the feedback-related negativity following the offer. Furthermore, a moderating effect of sex on decision making was observed, with differential effects of facial expressions from male compared to female proposers. It is concluded that predictions of bargaining behavior must account for aspects of social interactions as well as sex effects to obtain more precise estimates of behavior. Copyright © 2014 Society for Psychophysiological Research.
Menditto, Anthony A; Linhorst, Donald M; Coleman, James C; Beck, Niels C
2006-04-01
Development of policies and procedures to contend with the risks presented by elopement, aggression, and suicidal behaviors are long-standing challenges for mental health administrators. Guidance in making such judgments can be obtained through the use of a multivariate statistical technique known as logistic regression. This procedure can be used to develop a predictive equation that is mathematically formulated to use the best combination of predictors, rather than considering just one factor at a time. This paper presents an overview of logistic regression and its utility in mental health administrative decision making. A case example of its application is presented using data on elopements from Missouri's long-term state psychiatric hospitals. Ultimately, the use of statistical prediction analyses tempered with differential qualitative weighting of classification errors can augment decision-making processes in a manner that provides guidance and flexibility while wrestling with the complex problem of risk assessment and decision making.
Shavit, Oren
2009-10-01
Innovative health technologies are often the focus of attention. However, in the allocation of public resources for improving health, the focus should be on the health needs of the population. It is the need that should be analyzed first, and decision makers should then evaluate the full range of interventions available, whether new or old, to meet this need. This is in contrast to analyzing the technology first and then characterizing the need it meets, which is the current practice in reimbursement decision-making in several countries. The identified health need should define national health goals, and these goals should be proactively assimilated into the reimbursement decision-making process. Differential reimbursement rates could reflect the relative contribution of the technology to the unmet health need.
Shahjehan, Khurram; Li, Guangxi; Dhokarh, Rajanigandha; Kashyap, Rahul; Janish, Christopher; Alsara, Anas; Jaffe, Allan S.; Hubmayr, Rolf D.; Gajic, Ognjen
2012-01-01
Background: At the onset of acute hypoxic respiratory failure, critically ill patients with acute lung injury (ALI) may be difficult to distinguish from those with cardiogenic pulmonary edema (CPE). No single clinical parameter provides satisfying prediction. We hypothesized that a combination of those will facilitate early differential diagnosis. Methods: In a population-based retrospective development cohort, validated electronic surveillance identified critically ill adult patients with acute pulmonary edema. Recursive partitioning and logistic regression were used to develop a decision support tool based on routine clinical information to differentiate ALI from CPE. Performance of the score was validated in an independent cohort of referral patients. Blinded post hoc expert review served as gold standard. Results: Of 332 patients in a development cohort, expert reviewers (κ, 0.86) classified 156 as having ALI and 176 as having CPE. The validation cohort had 161 patients (ALI = 113, CPE = 48). The score was based on risk factors for ALI and CPE, age, alcohol abuse, chemotherapy, and peripheral oxygen saturation/Fio2 ratio. It demonstrated good discrimination (area under curve [AUC] = 0.81; 95% CI, 0.77-0.86) and calibration (Hosmer-Lemeshow [HL] P = .16). Similar performance was obtained in the validation cohort (AUC = 0.80; 95% CI, 0.72-0.88; HL P = .13). Conclusions: A simple decision support tool accurately classifies acute pulmonary edema, reserving advanced testing for a subset of patients in whom satisfying prediction cannot be made. This novel tool may facilitate early inclusion of patients with ALI and CPE into research studies as well as improve and rationalize clinical management and resource use. PMID:22030803
Neural reactivation links unconscious thought to decision-making performance.
Creswell, John David; Bursley, James K; Satpute, Ajay B
2013-12-01
Brief periods of unconscious thought (UT) have been shown to improve decision making compared with making an immediate decision (ID). We reveal a neural mechanism for UT in decision making using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Participants (N = 33) encoded information on a set of consumer products (e.g. 48 attributes describing four different cars), and we manipulated whether participants (i) consciously thought about this information (conscious thought), (ii) completed a difficult 2-back working memory task (UT) or (iii) made an immediate decision about the consumer products (ID) in a within-subjects blocked design. To differentiate UT neural activity from 2-back working memory neural activity, participants completed an independent 2-back task and this neural activity was subtracted from neural activity occurring during the UT 2-back task. Consistent with a neural reactivation account, we found that the same regions activated during the encoding of complex decision information (right dorsolateral prefrontal cortex and left intermediate visual cortex) continued to be activated during a subsequent 2-min UT period. Moreover, neural reactivation in these regions was predictive of subsequent behavioral decision-making performance after the UT period. These results provide initial evidence for post-encoding unconscious neural reactivation in facilitating decision making.