rFN/Cad-11-Modified Collagen Type II Biomimetic Interface Promotes the Adhesion and Chondrogenic Differentiation of Mesenchymal Stem Cells

Science.gov (United States)

Guo, Hongfeng; Zhang, Yuan; Li, Zhengsheng; Kang, Fei; Yang, Bo; Kang, Xia; Wen, Can; Yan, Yanfei; Jiang, Bo; Fan, Yujiang

2013-01-01

Properties of the cell-material interface are determining factors in the successful function of cells for cartilage tissue engineering. Currently, cell adhesion is commonly promoted through the use of polypeptides; however, due to their lack of complementary or modulatory domains, polypeptides must be modified to improve their ability to promote adhesion. In this study, we utilized the principle of matrix-based biomimetic modification and a recombinant protein, which spans fragments 7–10 of fibronectin module III (heterophilic motif ) and extracellular domains 1–2 of cadherin-11 (rFN/Cad-11) (homophilic motif ), to modify the interface of collagen type II (Col II) sponges. We showed that the designed material was able to stimulate cell proliferation and promote better chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) in vitro than both the FN modified surfaces and the negative control. Further, the Col II/rFN/Cad-11-MSCs composite stimulated cartilage formation in vivo; the chondrogenic effect of Col II alone was much less significant. These results suggested that the rFN/Cad-11-modified collagen type II biomimetic interface has dual biological functions of promoting adhesion and stimulating chondrogenic differentiation. This substance, thus, may serve as an ideal scaffold material for cartilage tissue engineering, enhancing repair of injured cartilage in vivo. PMID:23919505

Is 'subthreshold' bipolar II disorder more difficult to differentiate from borderline personality disorder than formal bipolar II disorder?

Science.gov (United States)

Bayes, Adam; Graham, Rebecca K; Parker, Gordon B; McCraw, Stacey

2018-06-01

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy. Copyright © 2018 Elsevier B.V. All rights reserved.

Angiotensin II modulates interleukin-1β-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-κB crosstalk

International Nuclear Information System (INIS)

Xu, Shanqin; Zhi, Hui; Hou, Xiuyun; Jiang, Bingbing

2011-01-01

Highlights: → We examine how angiotensin II modulates ERK-NF-κB crosstalk and gene expression. → Angiotensin II suppresses IL-1β-induced prolonged ERK and NF-κB activation. → ERK-RSK1 signaling is required for IL-1β-induced prolonged NF-κB activation. → Angiotensin II modulates NF-κB responsive genes via regulating ERK-NF-κB crosstalk. → ERK-NF-κB crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. In cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1β-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-κB, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1β-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1β, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE -/- ) mice. VCAM-1 and iNOS expression were higher in ApoE -/- than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE -/- mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that angiotensin II can differentially modulate inflammatory gene expression in aortic smooth muscle cells

Multi-crystalline II-VI based multijunction solar cells and modules

Science.gov (United States)

Hardin, Brian E.; Connor, Stephen T.; Groves, James R.; Peters, Craig H.

2015-06-30

Multi-crystalline group II-VI solar cells and methods for fabrication of same are disclosed herein. A multi-crystalline group II-VI solar cell includes a first photovoltaic sub-cell comprising silicon, a tunnel junction, and a multi-crystalline second photovoltaic sub-cell. A plurality of the multi-crystalline group II-VI solar cells can be interconnected to form low cost, high throughput flat panel, low light concentration, and/or medium light concentration photovoltaic modules or devices.

Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells

Directory of Open Access Journals (Sweden)

Vaibhav Shinde

2016-04-01

Full Text Available Background/Aims: Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on the embryonic development processes we established an in vitro methodology allowing differentiation of mouse embryonic stem cells (mESCs under simulated microgravity within a fast-rotating clinostat (clinorotation and capture of microarray-based gene signatures. Methods: The differentiating mESCs were cultured in a 2D pipette clinostat. The microarray and bioinformatics tools were used to capture genes that are deregulated by simulated microgravity and their impact on developmental biological processes. Results: The data analysis demonstrated that differentiation of mESCs in pipettes for 3 days resultet to early germ layer differentiation and then to the different somatic cell types after further 7 days of differentiation in the Petri dishes. Clinorotation influences differentiation as well as non-differentiation related biological processes like cytoskeleton related 19 genes were modulated. Notably, simulated microgravity deregulated genes Cyr61, Thbs1, Parva, Dhrs3, Jun, Tpm1, Fzd2 and Dll1 are involved in heart morphogenesis as an acute response on day 3. If the stem cells were further cultivated under normal gravity conditions (1 g after clinorotation, the expression of cardiomyocytes specific genes such as Tnnt2, Rbp4, Tnni1, Csrp3, Nppb and Mybpc3 on day 10 was inhibited. This correlated well with a decreasing beating activity of the 10-days old embryoid bodies (EBs. Finally, we captured Gadd45g, Jun, Thbs1, Cyr61and Dll1 genes whose expressions were modulated by simulated microgravity and by real microgravity in various reported studies. Simulated microgravity also deregulated genes belonging to the MAP kinase and focal dhesion signal transduction pathways. Conclusion: One of the most prominent biological processes affected by simulated microgravity was the process of cardiomyogenesis. The

First large DEPFET pixel modules for the Belle II Pixel Detector

Energy Technology Data Exchange (ETDEWEB)

Mueller, Felix; Avella, Paola; Kiesling, Christian; Koffmane, Christian; Moser, Hans-Guenther; Valentan, Manfred [Max-Planck-Institut fuer Physik, Muenchen (Germany); Andricek, Ladislav; Richter, Rainer [Halbleiterlabor der Max-Planck-Gesellschaft, Muenchen (Germany); Collaboration: Belle II-Collaboration

2016-07-01

DEPFET pixel detectors offer excellent signal to noise ratio, resolution and low power consumption with a low material budget. They will be used at Belle II and are a candidate for an ILC vertex detector. The pixels are integrated in a monolithic piece of silicon which also acts as PCB providing the signal and control routings for the ASICs on top. The first prototype DEPFET sensor modules for Belle II have been produced. The modules have 192000 pixels and are equipped with SMD components and three different kinds of ASICs to control and readout the pixels. The entire readout chain has to be studied; the metal layer interconnectivity and routings need to be verified. The modules are fully characterized, and the operation voltages and control sequences of the ASICs are investigated. An overview of the DEPFET concept and first characterization results is presented.

Differentiable absorption of Hilbert C*-modules, connections and lifts of unbounded operators

DEFF Research Database (Denmark)

Kaad, Jens

2017-01-01

. The differentiable absorption theorem is then applied to construct densely defined connections (or correpondences) on Hilbert C∗C∗-modules. These connections can in turn be used to define selfadjoint and regular "lifts" of unbounded operators which act on an auxiliary Hilbert C∗C∗-module....

Two pore channel 2 differentially modulates neural differentiation of mouse embryonic stem cells.

Directory of Open Access Journals (Sweden)

Zhe-Hao Zhang

Full Text Available Nicotinic acid adenine dinucleotide phosphate (NAADP is an endogenous Ca(2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca(2+ from acidic organelles through two pore channel 2 (TPC2 in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation.

Thermal behavior and phase identification of Valsartan by standard and temperature-modulated differential scanning calorimetry.

Science.gov (United States)

Skotnicki, Marcin; Gaweł, Agnieszka; Cebe, Peggy; Pyda, Marek

2013-10-01

Thermal behavior of angiotensin II type 1 (AT1) receptor antagonist, Valsartan (VAL), was examined employing thermogravimetric analysis (TGA), standard differential scanning calorimetry (DSC) and temperature-modulated differential scanning calorimetry (TMDSC). The stability of VAL was measured by TGA from 25 to 600°C. Decomposition of Valsartan starts around 160°C. The DSC curve shows two endotherms, occurring around 80°C and 100°C, related to evaporation of water and enthalpy relaxation, respectively. Valsartan was identified by DSC as an amorphous material and it was confirmed by X-ray powder diffraction. The glass transition of fresh Valsartan appears around 76°C (fictive temperature). TMDSC allows separation of the total heat flow rate into reversing and nonreversing parts. The nonreversing curve corresponds to the enthalpy relaxation and the reversing curve shows changes of heat capacity around 94°C. In the second run, TMDSC curve shows the glass transition process occurring at around 74°C. Results from standard DSC and TMDSC of Valsartan were compared over the whole range of temperature.

Cholera Toxin Promotes Th17 Cell Differentiation by Modulating Expression of Polarizing Cytokines and the Antigen-Presenting Potential of Dendritic Cells.

Science.gov (United States)

Kang, Jung-Ok; Lee, Jee-Boong; Chang, Jun

2016-01-01

Cholera toxin (CT), an exotoxin produced by Vibrio cholera, acts as a mucosal adjuvant. In a previous study, we showed that CT skews differentiation of CD4 T cells to IL-17-producing Th17 cells. Here, we found that intranasal administration of CT induced migration of migratory dendritic cell (DC) populations, CD103+ DCs and CD11bhi DCs, to the lung draining mediastinal lymph nodes (medLN). Among those DC subsets, CD11bhi DCs that were relatively immature had a major role in Th17 cell differentiation after administration of CT. CT-treated BMDCs showed reduced expression of MHC class II and CD86, similar to CD11bhi DCs in medLN, and these BMDCs promoted Th17 cell differentiation more potently than other BMDCs expressing higher levels of MHC class II and CD86. By analyzing the expression of activation markers such as CD25 and CD69, proliferation and IL-2 production, we determined that CT-treated BMDCs showed diminished antigen-presenting potential to CD4+ T cells compared with normal BMDCs. We also found that CT-stimulated BMDCs promote activin A expression as well as IL-6 and IL-1β, and activin A had a synergic role with TGF-β1 in CT-mediated Th17 cell differentiation. Taken together, our results suggest that CT-stimulated DCs promote Th17 cell differentiation by not only modulating antigen-presenting potential but also inducing Th polarizing cytokines.

Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

Science.gov (United States)

Wei, Min; Li, Song; Le, Weidong

2017-10-25

Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

New hybrid reverse differential pulse position width modulation scheme for wireless optical communication

Science.gov (United States)

Liao, Renbo; Liu, Hongzhan; Qiao, Yaojun

2014-05-01

In order to improve the power efficiency and reduce the packet error rate of reverse differential pulse position modulation (RDPPM) for wireless optical communication (WOC), a hybrid reverse differential pulse position width modulation (RDPPWM) scheme is proposed, based on RDPPM and reverse pulse width modulation. Subsequently, the symbol structure of RDPPWM is briefly analyzed, and its performance is compared with that of other modulation schemes in terms of average transmitted power, bandwidth requirement, and packet error rate over ideal additive white Gaussian noise (AWGN) channels. Based on the given model, the simulation results show that the proposed modulation scheme has the advantages of improving the power efficiency and reducing the bandwidth requirement. Moreover, in terms of error probability performance, RDPPWM can achieve a much lower packet error rate than that of RDPPM. For example, at the same received signal power of -28 dBm, the packet error rate of RDPPWM can decrease to 2.6×10-12, while that of RDPPM is 2.2×10. Furthermore, RDPPWM does not need symbol synchronization at the receiving end. These considerations make RDPPWM a favorable candidate to select as the modulation scheme in the WOC systems.

On the Frequency Correction in Temperature-Modulated Differential Scanning Calorimetry of Glass Transition

DEFF Research Database (Denmark)

Guo, Xiaoju; Mauro, J.C.; Allan, D.C.

2012-01-01

Temperature-modulated differential scanning calorimetry (TMDSC) is based on conventional DSC but with a sinusoidally modulated temperature path. Simulations of TMDSC signals were performed for Corning EAGLE XG® glass over a wide range of modulation frequencies. Our results reveal that the frequency...... correction commonly used in the interpretation of TMDSC signals leads to a master nonreversing heat flow curve independent of modulation frequency, provided that sufficiently high frequencies are employed in the TMDSC measurement. A master reversing heat flow curve can also be generated through the frequency...

Wafer defect detection by a polarization-insensitive external differential interference contrast module.

Science.gov (United States)

Nativ, Amit; Feldman, Haim; Shaked, Natan T

2018-05-01

We present a system that is based on a new external, polarization-insensitive differential interference contrast (DIC) module specifically adapted for detecting defects in semiconductor wafers. We obtained defect signal enhancement relative to the surrounding wafer pattern when compared with bright-field imaging. The new DIC module proposed is based on a shearing interferometer that connects externally at the output port of an optical microscope and enables imaging thin samples, such as wafer defects. This module does not require polarization optics (such as Wollaston or Nomarski prisms) and is insensitive to polarization, unlike traditional DIC techniques. In addition, it provides full control of the DIC shear and orientation, which allows obtaining a differential phase image directly on the camera (with no further digital processing) while enhancing defect detection capabilities, even if the size of the defect is smaller than the resolution limit. Our technique has the potential of future integration into semiconductor production lines.

Polymeric membranes modulate human keratinocyte differentiation in specific epidermal layers.

Science.gov (United States)

Salerno, Simona; Morelli, Sabrina; Giordano, Francesca; Gordano, Amalia; Bartolo, Loredana De

2016-10-01

In vitro models of human bioengineered skin substitutes are an alternative to animal experimentation for testing the effects and toxicity of drugs, cosmetics and pollutants. For the first time specific and distinct human epidermal strata were engineered by using membranes and keratinocytes. To this purpose, biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT-PCL were prepared by phase-inversion technique and characterized in order to evaluate their morphological, physico-chemical and mechanical properties. The capability of membranes to modulate keratinocyte differentiation inducing specific interactions in epidermal membrane systems was investigated. The overall results demonstrated that the membrane properties strongly influence the cell morpho-functional behaviour of human keratinocytes, modulating their terminal differentiation, with the creation of specific epidermal strata or a fully proliferative epidermal multilayer system. In particular, human keratinocytes adhered on CHT and CHT-PCL membranes, forming the structure of the epidermal top layers, such as the corneum and granulosum strata, characterized by withdrawal or reduction from the cell cycle and cell proliferation. On the PCL membrane, keratinocytes developed an epidermal basal lamina, with high proliferating cells that stratified and migrated over time to form a complete differentiating epidermal multilayer system. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2006-03-15

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

Host regulation of lysogenic decision in bacteriophage lambda: transmembrane modulation of FtsH (HflB), the cII degrading protease, by HflKC (HflA).

Science.gov (United States)

Kihara, A; Akiyama, Y; Ito, K

1997-05-27

The cII gene product of bacteriophage lambda is unstable and required for the establishment of lysogenization. Its intracellular amount is important for the decision between lytic growth and lysogenization. Two genetic loci of Escherichia coli are crucial for these commitments of infecting lambda genome. One of them, hflA encodes the HflKC membrane protein complex, which has been believed to be a protease degrading the cII protein. However, both its absence and overproduction stabilized cII in vivo and the proposed serine protease-like sequence motif in HflC was dispensable for the lysogenization control. Moreover, the HflKC protein was found to reside on the periplasmic side of the plasma membrane. In contrast, the other host gene, ftsH (hflB) encoding an integral membrane ATPase/protease, is positively required for degradation of cII, since loss of its function stabilized cII and its overexpression accelerated the cII degradation. In vitro, purified FtsH catalyzed ATP-dependent proteolysis of cII and HflKC antagonized the FtsH action. These results, together with our previous finding that FtsH and HflKC form a complex, suggest that FtsH is the cII degrading protease and HflKC is a modulator of the FtsH function. We propose that this transmembrane modulation differentiates the FtsH actions to different substrate proteins such as the membrane-bound SecY protein and the cytosolic cII protein. This study necessitates a revision of the prevailing view about the host control over lambda lysogenic decision.

Effect of angiotensin II on proliferation and differentiation of mouse induced pluripotent stem cells into mesodermal progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Ishizuka, Toshiaki, E-mail: tishizu@ndmc.ac.jp [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan); Goshima, Hazuki; Ozawa, Ayako; Watanabe, Yasuhiro [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan)

2012-03-30

Highlights: Black-Right-Pointing-Pointer Treatment with angiotensin II enhanced LIF-induced DNA synthesis of mouse iPS cells. Black-Right-Pointing-Pointer Angiotensin II may enhance the DNA synthesis via induction of superoxide. Black-Right-Pointing-Pointer Treatment with angiotensin II significantly increased JAK/STAT3 phosphorylation. Black-Right-Pointing-Pointer Angiotensin II enhanced differentiation into mesodermal progenitor cells. Black-Right-Pointing-Pointer Angiotensin II may enhance the differentiation via activation of p38 MAPK. -- Abstract: Previous studies suggest that angiotensin receptor stimulation may enhance not only proliferation but also differentiation of undifferentiated stem/progenitor cells. Therefore, in the present study, we determined the involvement of the angiotensin receptor in the proliferation and differentiation of mouse induced pluripotent stem (iPS) cells. Stimulation with angiotensin II (Ang II) significantly increased DNA synthesis in mouse iPS cells cultured in a medium with leukemia inhibitory factor (LIF). Pretreatment of the cells with either candesartan (a selective Ang II type 1 receptor [AT{sub 1}R] antagonist) or Tempol (a cell-permeable superoxide scavenger) significantly inhibited Ang II-induced DNA synthesis. Treatment with Ang II significantly increased JAK/STAT3 phosphorylation. Pretreatment with candesartan significantly inhibited Ang II- induced JAK/STAT3 phosphorylation. In contrast, induction of mouse iPS cell differentiation into Flk-1-positive mesodermal progenitor cells was performed in type IV collagen (Col IV)- coated dishes in a differentiation medium without LIF. When Col IV-exposed iPS cells were treated with Ang II for 5 days, the expression of Flk-1 was significantly increased compared with that in the cells treated with the vehicle alone. Pretreatment of the cells with both candesartan and SB203580 (a p38 MAPK inhibitor) significantly inhibited the Ang II- induced increase in Flk-1 expression

Effect of angiotensin II on proliferation and differentiation of mouse induced pluripotent stem cells into mesodermal progenitor cells

International Nuclear Information System (INIS)

Ishizuka, Toshiaki; Goshima, Hazuki; Ozawa, Ayako; Watanabe, Yasuhiro

2012-01-01

Highlights: ► Treatment with angiotensin II enhanced LIF-induced DNA synthesis of mouse iPS cells. ► Angiotensin II may enhance the DNA synthesis via induction of superoxide. ► Treatment with angiotensin II significantly increased JAK/STAT3 phosphorylation. ► Angiotensin II enhanced differentiation into mesodermal progenitor cells. ► Angiotensin II may enhance the differentiation via activation of p38 MAPK. -- Abstract: Previous studies suggest that angiotensin receptor stimulation may enhance not only proliferation but also differentiation of undifferentiated stem/progenitor cells. Therefore, in the present study, we determined the involvement of the angiotensin receptor in the proliferation and differentiation of mouse induced pluripotent stem (iPS) cells. Stimulation with angiotensin II (Ang II) significantly increased DNA synthesis in mouse iPS cells cultured in a medium with leukemia inhibitory factor (LIF). Pretreatment of the cells with either candesartan (a selective Ang II type 1 receptor [AT 1 R] antagonist) or Tempol (a cell-permeable superoxide scavenger) significantly inhibited Ang II-induced DNA synthesis. Treatment with Ang II significantly increased JAK/STAT3 phosphorylation. Pretreatment with candesartan significantly inhibited Ang II- induced JAK/STAT3 phosphorylation. In contrast, induction of mouse iPS cell differentiation into Flk-1-positive mesodermal progenitor cells was performed in type IV collagen (Col IV)- coated dishes in a differentiation medium without LIF. When Col IV-exposed iPS cells were treated with Ang II for 5 days, the expression of Flk-1 was significantly increased compared with that in the cells treated with the vehicle alone. Pretreatment of the cells with both candesartan and SB203580 (a p38 MAPK inhibitor) significantly inhibited the Ang II- induced increase in Flk-1 expression. Treatment with Ang II enhanced the phosphorylation of p38 MAPK in Col IV- exposed iPS cells. These results suggest that the stimulation

Insights into glass transition and relaxation behavior using temperature-modulated differential scanning calorimetry

DEFF Research Database (Denmark)

Guo, Xiaoju; Mauro, J.C.; Allan, D.C.

Temperature-modulated differential scanning calorimetry (TMDSC) is based on conventional DSC but with a sinusoidally modulated temperature path. Our simulations of TMDSC signals prove that the frequency correction of non-reversing heat flow can give a master curve within a certain range...... of frequencies. This frequency range is dependent not only on the measurement parameters such as linear heating/cooling rate and frequency and amplitude of the modulation, but also on the previous thermal history before the TMDSC measurement. The frequency correction for the reversing heat flow gives more...

Angiotensin II potentiates adrenergic and muscarinic modulation of guinea pig intracardiac neurons.

Science.gov (United States)

Girasole, Allison E; Palmer, Christopher P; Corrado, Samantha L; Marie Southerland, E; Ardell, Jeffrey L; Hardwick, Jean C

2011-11-01

The intrinsic cardiac plexus represents a major peripheral integration site for neuronal, hormonal, and locally produced neuromodulators controlling efferent neuronal output to the heart. This study examined the interdependence of norepinephrine, muscarinic agonists, and ANG II, to modulate intrinsic cardiac neuronal activity. Intracellular voltage recordings from whole-mount preparations of the guinea pig cardiac plexus were used to determine changes in active and passive electrical properties of individual intrinsic cardiac neurons. Application of either adrenergic or muscarinic agonists induced changes in neuronal resting membrane potentials, decreased afterhyperpolarization duration of single action potentials, and increased neuronal excitability. Adrenergic responses were inhibited by removal of extracellular calcium ions, while muscarinic responses were inhibited by application of TEA. The adrenergic responses were heterogeneous, responding to a variety of receptor-specific agonists (phenylephrine, clonidine, dobutamine, and terbutaline), although α-receptor agonists produced the most frequent responses. Application of ANG II alone produced a significant increase in excitability, while application of ANG II in combination with either adrenergic or muscarinic agonists produced a much larger potentiation of excitability. The ANG II-induced modulation of firing was blocked by the angiotensin type 2 (AT(2)) receptor inhibitor PD 123319 and was mimicked by the AT(2) receptor agonist CGP-42112A. AT(1) receptor blockade with telmasartin did not alter neuronal responses to ANG II. These data demonstrate that ANG II potentiates both muscarinically and adrenergically mediated activation of intrinsic cardiac neurons, doing so primarily via AT(2) receptor-dependent mechanisms. These neurohumoral interactions may be fundamental to regulation of neuronal excitability within the intrinsic cardiac nervous system.

Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

Directory of Open Access Journals (Sweden)

Hidekazu Kuwayama

Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

Differential pulse amplitude modulation for multiple-input single-output OWVLC

Science.gov (United States)

Yang, S. H.; Kwon, D. H.; Kim, S. J.; Son, Y. H.; Han, S. K.

2015-01-01

White light-emitting diodes (LEDs) are widely used for lighting due to their energy efficiency, eco-friendly, and small size than previously light sources such as incandescent, fluorescent bulbs and so on. Optical wireless visible light communication (OWVLC) based on LED merges lighting and communications in applications such as indoor lighting, traffic signals, vehicles, and underwater communications because LED can be easily modulated. However, physical bandwidth of LED is limited about several MHz by slow time constant of the phosphor and characteristics of device. Therefore, using the simplest modulation format which is non-return-zero on-off-keying (NRZ-OOK), the data rate reaches only to dozens Mbit/s. Thus, to improve the transmission capacity, optical filtering and pre-, post-equalizer are adapted. Also, high-speed wireless connectivity is implemented using spectrally efficient modulation methods: orthogonal frequency division multiplexing (OFDM) or discrete multi-tone (DMT). However, these modulation methods need additional digital signal processing such as FFT and IFFT, thus complexity of transmitter and receiver is increasing. To reduce the complexity of transmitter and receiver, we proposed a novel modulation scheme which is named differential pulse amplitude modulation. The proposed modulation scheme transmits different NRZ-OOK signals with same amplitude and unit time delay using each LED chip, respectively. The `N' parallel signals from LEDs are overlapped and directly detected at optical receiver. Received signal is demodulated by power difference between unit time slots. The proposed scheme can overcome the bandwidth limitation of LEDs and data rate can be improved according to number of LEDs without complex digital signal processing.

CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

Science.gov (United States)

McNally, Alice; Hill, Geoffrey R.; Sparwasser, Tim; Thomas, Ranjeny; Steptoe, Raymond J.

2011-01-01

CD4+CD25+ regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8+ T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4+CD25+ Treg, by critically regulating IL-2 homeostasis, modulate CD8+ T-cell effector differentiation. Expansion and effector differentiation of CD8+ T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8+ effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8+ effector T cells, where IL-2 produced during CD8+ T-cell effector differentiation promotes Treg expansion. PMID:21502514

A Receiver for Differential Space-Time -Shifted BPSK Modulation Based on Scalar-MSDD and the EM Algorithm

Directory of Open Access Journals (Sweden)

Kim Jae H

2005-01-01

Full Text Available In this paper, we consider the issue of blind detection of Alamouti-type differential space-time (ST modulation in static Rayleigh fading channels. We focus our attention on a -shifted BPSK constellation, introducing a novel transformation to the received signal such that this binary ST modulation, which has a second-order transmit diversity, is equivalent to QPSK modulation with second-order receive diversity. This equivalent representation allows us to apply a low-complexity detection technique specifically designed for receive diversity, namely, scalar multiple-symbol differential detection (MSDD. To further increase receiver performance, we apply an iterative expectation-maximization (EM algorithm which performs joint channel estimation and sequence detection. This algorithm uses minimum mean square estimation to obtain channel estimates and the maximum-likelihood principle to detect the transmitted sequence, followed by differential decoding. With receiver complexity proportional to the observation window length, our receiver can achieve the performance of a coherent maximal ratio combining receiver (with differential decoding in as few as a single EM receiver iteration, provided that the window size of the initial MSDD is sufficiently long. To further demonstrate that the MSDD is a vital part of this receiver setup, we show that an initial ST conventional differential detector would lead to strange convergence behavior in the EM algorithm.

Research on channel characteristics of differential multi pulse position modulation without background noise

Science.gov (United States)

Gao, Zhuo; Zhan, Weida; Sun, Quan; Hao, Ziqiang

2018-04-01

Differential multi-pulse position modulation (DMPPM) is a new type of modulation technology. There is a fast transmission rate, high bandwidth utilization, high modulation rate characteristics. The study of DMPPM modulation has important scientific value and practical significance. Channel capacity is one of the important indexes to measure the communication capability of communication system, and studying the channel capacity of DMPPM without background noise is the key to analyze the characteristics of DMPPM. The DMPPM theoretical model is established. The symbol structure of DMPPM with guard time slot is analyzed, and the channel capacity expression of DMPPM is deduced. Simulation analysis by MATLAB. The curves of unit channel capacity and capacity efficiency at different pulse and photon counting rates are analyzed. The results show that DMPPM is more advantageous than multi-pulse position modulation (MPPM), and is more suitable for future wireless optical communication system.

Subthalamic stimulation differentially modulates declarative and nondeclarative memory.

Science.gov (United States)

Hälbig, Thomas D; Gruber, Doreen; Kopp, Ute A; Scherer, Peter; Schneider, Gerd-Helge; Trottenberg, Thomas; Arnold, Guy; Kupsch, Andreas

2004-03-01

Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems. Copyright 2004 Lippincott Williams & Wilkins

Development of Diamond Vacuum Differential Amplifier for Harsh Environment Power Electronics, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — In this proposed Phase II, Scientic and Vanderbilt University will develop a novel vacuum field emission differential amplifier (VFEDA) using low electron affinity...

The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling.

Science.gov (United States)

Martins, Torcato; Meghini, Francesco; Florio, Francesca; Kimata, Yuu

2017-01-09

The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, Drosophila Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Class II HLA interactions modulate genetic risk for multiple sclerosis

Science.gov (United States)

Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

2016-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

Modulating Function-Based Method for Parameter and Source Estimation of Partial Differential Equations

KAUST Repository

Asiri, Sharefa M.

2017-10-08

Partial Differential Equations (PDEs) are commonly used to model complex systems that arise for example in biology, engineering, chemistry, and elsewhere. The parameters (or coefficients) and the source of PDE models are often unknown and are estimated from available measurements. Despite its importance, solving the estimation problem is mathematically and numerically challenging and especially when the measurements are corrupted by noise, which is often the case. Various methods have been proposed to solve estimation problems in PDEs which can be classified into optimization methods and recursive methods. The optimization methods are usually heavy computationally, especially when the number of unknowns is large. In addition, they are sensitive to the initial guess and stop condition, and they suffer from the lack of robustness to noise. Recursive methods, such as observer-based approaches, are limited by their dependence on some structural properties such as observability and identifiability which might be lost when approximating the PDE numerically. Moreover, most of these methods provide asymptotic estimates which might not be useful for control applications for example. An alternative non-asymptotic approach with less computational burden has been proposed in engineering fields based on the so-called modulating functions. In this dissertation, we propose to mathematically and numerically analyze the modulating functions based approaches. We also propose to extend these approaches to different situations. The contributions of this thesis are as follows. (i) Provide a mathematical analysis of the modulating function-based method (MFBM) which includes: its well-posedness, statistical properties, and estimation errors. (ii) Provide a numerical analysis of the MFBM through some estimation problems, and study the sensitivity of the method to the modulating functions\\' parameters. (iii) Propose an effective algorithm for selecting the method\\'s design parameters

Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of α7 nicotinic acetylcholine receptors

DEFF Research Database (Denmark)

Thomsen, Morten Skøtt; Mikkelsen, Jens D

2012-01-01

Long-term treatment with nicotine or selective α7 nicotinic acetylcholine receptor (nAChR) agonists increases the number of α7 nAChRs and this up-regulation may be involved in the mechanism underlying the sustained procognitive effect of these compounds. Here, we investigate the influence of type I...... expressing human α7 nAChR, whereas the type I PAMs AVL-3288 or NS1738 do not. Contrarily, neither type I nor II PAMs affect 10 μM nicotine-induced receptor up-regulation, suggesting that nicotine and A-582941 induce up-regulation through different mechanisms. We further show in vivo that 3 mg/kg PNU-120596...... is involved in A-582941-induced up-regulation. Our results are the first to show an in vivo difference between type I and II α7 nAChR PAMs, and demonstrate an agonist-dependent effect of type II PAMs occurring on a much longer time scale than previously appreciated. Furthermore, our data suggest that nicotine...

Aspects of differential geometry II

CERN Document Server

Gilkey, Peter

2015-01-01

Differential Geometry is a wide field. We have chosen to concentrate upon certain aspects that are appropriate for an introduction to the subject; we have not attempted an encyclopedic treatment. Book II deals with more advanced material than Book I and is aimed at the graduate level. Chapter 4 deals with additional topics in Riemannian geometry. Properties of real analytic curves given by a single ODE and of surfaces given by a pair of ODEs are studied, and the volume of geodesic balls is treated. An introduction to both holomorphic and Kähler geometry is given. In Chapter 5, the basic properties of de Rham cohomology are discussed, the Hodge Decomposition Theorem, Poincaré duality, and the Künneth formula are proved, and a brief introduction to the theory of characteristic classes is given. In Chapter 6, Lie groups and Lie algebras are dealt with. The exponential map, the classical groups, and geodesics in the context of a bi-invariant metric are discussed. The de Rham cohomology of compact Lie groups an...

AUTOMOTIVE DIESEL MAINTENANCE 1. UNIT XXII, I--MAINTAINING THE FUEL SYSTEM (PART I)--CUMMINS DIESEL ENGINE, II--UNDERSTANDING THE DIFFERENTIAL.

Science.gov (United States)

Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF THE FUNCTION AND MAINTENANCE OF THE DIESEL ENGINE FUEL SYSTEM AND DIFFERENTIAL DRIVE UNITS USED IN DIESEL POWERED VEHICLES. TOPICS ARE (1) FUEL SYSTEM COMPARISONS, (2) FUEL SYSTEM SUPPLY COMPONENTS, (3) FUEL SUPPLY SECTION MAINTENANCE, (4) FUNCTION OF THE DIFFERENTIAL,…

Incorporation of Biomaterials in Multicellular Aggregates Modulates Pluripotent Stem Cell Differentiation

Science.gov (United States)

Bratt-Leal, Andrés M.; Carpenedo, Richard L.; Ungrin, Mark; Zandstra, Peter W.; McDevitt, Todd C.

2010-01-01

Biomaterials are increasingly being used to engineer the biochemical and biophysical properties of the extracellular stem cell microenvironment in order to tailor niche characteristics and direct cell phenotype. To date, stem cell-biomaterial interactions have largely been studied by introducing stem cells into artificial environments, such as 2D cell culture on biomaterial surfaces, encapsulation of cell suspensions within hydrogel materials, or cell seeding on 3D polymeric scaffolds. In this study, microparticles fabricated from different materials, such as agarose, PLGA and gelatin, were stably integrated, in a dose-dependent manner, within aggregates of pluripotent stem cells (PSCs) prior to differentiation as a means to directly examine stem cell-biomaterial interactions in 3D. Interestingly, the presence of the materials within the stem cell aggregates differentially modulated the gene and protein expression patterns of several differentiation markers without adversely affecting cell viability. Microparticle incorporation within 3D stem cell aggregates can control the spatial presentation of extracellular environmental cues (i.e. soluble factors, extracellular matrix and intercellular adhesion molecules) as a means to direct the differentiation of stem cells for tissue engineering and regenerative medicine applications. In addition, these results suggest that the physical presence of microparticles within stem cell aggregates does not compromise PSC differentiation, but in fact the choice of biomaterials can impact the propensity of stem cells to adopt particular differentiated cell phenotypes. PMID:20864164

Liquid metal blanket module testing and design for ITER/TIBER II

International Nuclear Information System (INIS)

Mattas, R.F.; Cha, Y.; Finn, P.A.; Majumdar, S.; Picologlou, B.; Stevens, H.; Turner, L.

1988-05-01

A major goal for ITER is the testing of nuclear components to demonstrate the integrated performance of the most attractive concepts that can lead to a commercial fusion reactor. As part of the ITER/TIBER II study, the test program and design of test models were examined for a number of blanket concepts. The work at Argonne National Laboratory focused on self-cooled liquid metal blankets. A test program for liquid metal blankets was developed based upon the ITER/TIBER II operating schedule and the specific data needs to resolve the key issues for liquid metals. Testing can begin early in reactor operation with liquid metal MHD tests to confirm predictive capability. Combined heat transfer/MHD tests can be performed during initial plasma operation. After acceptable heat transfer performance is verified, tests to determine the integrated high temperature performance in a neutron environment can begin. During the high availability phase operation, long term performance and reliability tests will be performed. It is envisioned that a companion test program will be conducted outside ITER to determine behavior under severe accident conditions and upper performance limits. A detailed design of a liquid metal test module and auxiliary equipment was also developed. The module followed the design of the TPSS blanket. Detailed analysis of the heat transfer and tritium systems were performed, and the overall layout of the systems was determined. In general, the blanket module appears to be capable of addressing most of the testing needs. 8 refs., 27 figs., 11 tabs

Modulating Functions Based Algorithm for the Estimation of the Coefficients and Differentiation Order for a Space-Fractional Advection-Dispersion Equation

KAUST Repository

Aldoghaither, Abeer

2015-12-01

In this paper, a new method, based on the so-called modulating functions, is proposed to estimate average velocity, dispersion coefficient, and differentiation order in a space-fractional advection-dispersion equation, where the average velocity and the dispersion coefficient are space-varying. First, the average velocity and the dispersion coefficient are estimated by applying the modulating functions method, where the problem is transformed into a linear system of algebraic equations. Then, the modulating functions method combined with a Newton\\'s iteration algorithm is applied to estimate the coefficients and the differentiation order simultaneously. The local convergence of the proposed method is proved. Numerical results are presented with noisy measurements to show the effectiveness and robustness of the proposed method. It is worth mentioning that this method can be extended to general fractional partial differential equations.

Modulating Functions Based Algorithm for the Estimation of the Coefficients and Differentiation Order for a Space-Fractional Advection-Dispersion Equation

KAUST Repository

Aldoghaither, Abeer; Liu, Da-Yan; Laleg-Kirati, Taous-Meriem

2015-01-01

In this paper, a new method, based on the so-called modulating functions, is proposed to estimate average velocity, dispersion coefficient, and differentiation order in a space-fractional advection-dispersion equation, where the average velocity and the dispersion coefficient are space-varying. First, the average velocity and the dispersion coefficient are estimated by applying the modulating functions method, where the problem is transformed into a linear system of algebraic equations. Then, the modulating functions method combined with a Newton's iteration algorithm is applied to estimate the coefficients and the differentiation order simultaneously. The local convergence of the proposed method is proved. Numerical results are presented with noisy measurements to show the effectiveness and robustness of the proposed method. It is worth mentioning that this method can be extended to general fractional partial differential equations.

Modulating functions-based method for parameters and source estimation in one-dimensional partial differential equations

KAUST Repository

Asiri, Sharefa M.; Laleg-Kirati, Taous-Meriem

2016-01-01

In this paper, modulating functions-based method is proposed for estimating space–time-dependent unknowns in one-dimensional partial differential equations. The proposed method simplifies the problem into a system of algebraic equations linear

HDAC inhibitors: modulating leukocyte differentiation, survival, proliferation and inflammation.

Science.gov (United States)

Sweet, Matthew J; Shakespear, Melanie R; Kamal, Nabilah A; Fairlie, David P

2012-01-01

Therapeutic effects of histone deacetylase (HDAC) inhibitors in cancer models were first linked to their ability to cause growth arrest and apoptosis of tumor cells. It is now clear that these agents also have pleiotropic effects on angiogenesis and the immune system, and some of these properties are likely to contribute to their anti-cancer activities. It is also emerging that inhibitors of specific HDACs affect the differentiation, survival and/or proliferation of distinct immune cell populations. This is true for innate immune cells such as macrophages, as well as cells of the acquired immune system, for example, T-regulatory cells. These effects may contribute to therapeutic profiles in some autoimmune and chronic inflammatory disease models. Here, we review our current understanding of how classical HDACs (HDACs 1-11) and their inhibitors impact on differentiation, survival and proliferation of distinct leukocyte populations, as well as the likely relevance of these effects to autoimmune and inflammatory disease processes. The ability of HDAC inhibitors to modulate leukocyte survival may have implications for the rationale of developing selective inhibitors as anti-inflammatory drugs.

miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity.

Science.gov (United States)

Li, Bo; Wang, Xi; Choi, In Young; Wang, Yu-Chen; Liu, Siyuan; Pham, Alexander T; Moon, Heesung; Smith, Drake J; Rao, Dinesh S; Boldin, Mark P; Yang, Lili

2017-10-02

Autoreactive CD4 T cells that differentiate into pathogenic Th17 cells can trigger autoimmune diseases. Therefore, investigating the regulatory network that modulates Th17 differentiation may yield important therapeutic insights. miR-146a has emerged as a critical modulator of immune reactions, but its role in regulating autoreactive Th17 cells and organ-specific autoimmunity remains largely unknown. Here, we have reported that miR-146a-deficient mice developed more severe experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). We bred miR-146a-deficient mice with 2D2 T cell receptor-Tg mice to generate 2D2 CD4 T cells that are deficient in miR-146a and specific for myelin oligodendrocyte glycoprotein (MOG), an autoantigen in the EAE model. miR-146a-deficient 2D2 T cells induced more severe EAE and were more prone to differentiate into Th17 cells. Microarray analysis revealed enhancements in IL-6- and IL-21-induced Th17 differentiation pathways in these T cells. Further study showed that miR-146a inhibited the production of autocrine IL-6 and IL-21 in 2D2 T cells, which in turn reduced their Th17 differentiation. Thus, our study identifies miR-146a as an important molecular brake that blocks the autocrine IL-6- and IL-21-induced Th17 differentiation pathways in autoreactive CD4 T cells, highlighting its potential as a therapeutic target for treating autoimmune diseases.

Modulating functions-based method for parameters and source estimation in one-dimensional partial differential equations

KAUST Repository

Asiri, Sharefa M.

2016-10-20

In this paper, modulating functions-based method is proposed for estimating space–time-dependent unknowns in one-dimensional partial differential equations. The proposed method simplifies the problem into a system of algebraic equations linear in unknown parameters. The well-posedness of the modulating functions-based solution is proved. The wave and the fifth-order KdV equations are used as examples to show the effectiveness of the proposed method in both noise-free and noisy cases.

E2F6: a member of the E2F family that does not modulate squamous differentiation

International Nuclear Information System (INIS)

Wong, C.F.; Barnes, Liam M.; Smith, Louise; Popa, Claudia; Serewko-Auret, Magdalena M.; Saunders, Nicholas A.

2004-01-01

The inhibition of E2F has been demonstrated to be important in the initiation of squamous differentiation by two independent manners: promotion of growth arrest and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is reported to behave as a transcriptional repressor of the E2F family. In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme. Results demonstrated that whilst E2F6 was able to suppress E2F activity in proliferating keratinocytes, it did not modulate squamous differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents. Significantly, although E2F6 could suppress E2F activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40 cells. These results demonstrate that E2F6 does not contain the domains required for modulation of squamous differentiation and imply isoform-specific functions for individual E2F family members

Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses.

Science.gov (United States)

Tchankouo-Nguetcheu, Stéphane; Khun, Huot; Pincet, Laurence; Roux, Pascal; Bahut, Muriel; Huerre, Michel; Guette, Catherine; Choumet, Valérie

2010-10-05

Arthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. The midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. A proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications that happen in the midgut for viral transmission to eventually take place. Using a proteomics differential approach with two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE), we defined the protein modulations in the midgut of Aedes aegypti that were triggered seven days after an oral infection (7 DPI) with dengue 2 (DENV-2) and chikungunya (CHIKV) viruses. Gel profile comparisons showed that the level of 18 proteins was modulated by DENV-2 only and 12 proteins were modulated by CHIKV only. Twenty proteins were regulated by both viruses in either similar or different ways. Both viruses caused an increase of proteins involved in the generation of reactive oxygen species, energy production, and carbohydrate and lipid metabolism. Midgut infection by DENV-2 and CHIKV triggered an antioxidant response. CHIKV infection produced an increase of proteins involved in detoxification. Our study constitutes the first analysis of the protein response of Aedes aegypti's midgut infected with viruses belonging to different families. It shows that the differentially regulated proteins in response to viral infection include structural, redox, regulatory proteins, and enzymes for several metabolic pathways. Some of these proteins like antioxidant are probably involved in cell protection. On the other hand, we propose that the modulation of other proteins like transferrin, hsp60 and alpha glucosidase, may favour virus survival, replication and transmission, suggesting a subversion of

Reactive oxygen species modulator 1, a novel protein, combined with carcinoembryonic antigen in differentiating malignant from benign pleural effusion.

Science.gov (United States)

Chen, Xianmeng; Zhang, Na; Dong, Jiahui; Sun, Gengyun

2017-05-01

The differential diagnosis of malignant pleural effusion and benign pleural effusion remains a clinical problem. Reactive oxygen species modulator 1 is a novel protein overexpressed in various human tumors. The objective of this study was to evaluate the diagnostic value of joint detection of reactive oxygen species modulator 1 and carcinoembryonic antigen in the differential diagnosis of malignant pleural effusion and benign pleural effusion. One hundred two consecutive patients with pleural effusion (including 52 malignant pleural effusion and 50 benign pleural effusion) were registered in this study. Levels of reactive oxygen species modulator 1 and carcinoembryonic antigen were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Results showed that the concentrations of reactive oxygen species modulator 1 both in pleural fluid and serum of patients with malignant pleural effusion were significantly higher than those of benign pleural effusion (both p pleural fluid reactive oxygen species modulator 1 were 61.54% and 82.00%, respectively, with the optimized cutoff value of 589.70 pg/mL. However, the diagnostic sensitivity and specificity of serum reactive oxygen species modulator 1 were only 41.38% and 86.21%, respectively, with the cutoff value of 27.22 ng/mL, indicating that serum reactive oxygen species modulator 1 may not be a good option in the differential diagnosis of malignant pleural effusion and benign pleural effusion. The sensitivity and specificity of pleural fluid carcinoembryonic antigen were 69.23% and 88.00%, respectively, at the cutoff value of 3.05 ng/mL, while serum carcinoembryonic antigen were 80.77% and 72.00% at the cutoff value of 2.60 ng/mL. The sensitivity could be raised to 88.17% in parallel detection of plural fluid reactive oxygen species modulator 1 and carcinoembryonic antigen concentration, and the specificity could be improved to 97.84% in serial detection.

Differential network analysis reveals genetic effects on catalepsy modules.

Directory of Open Access Journals (Sweden)

Ovidiu D Iancu

Full Text Available We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS formed by crossing four inbred strains (HS4 and a heterogeneous stock (HS-CC formed from the inbred strain founders of the Collaborative Cross (CC. All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections.

Mesenchymal Stem Cells Modulate Differentiation of Myeloid Progenitor Cells During Inflammation.

Science.gov (United States)

Amouzegar, Afsaneh; Mittal, Sharad K; Sahu, Anuradha; Sahu, Srikant K; Chauhan, Sunil K

2017-06-01

Mesenchymal stem cells (MSCs) possess distinct immunomodulatory properties and have tremendous potential for use in therapeutic applications in various inflammatory diseases. MSCs have been shown to regulate pathogenic functions of mature myeloid inflammatory cells, such as macrophages and neutrophils. Intriguingly, the capacity of MSCs to modulate differentiation of myeloid progenitors (MPs) to mature inflammatory cells remains unknown to date. Here, we report the novel finding that MSCs inhibit the expression of differentiation markers on MPs under inflammatory conditions. We demonstrate that the inhibitory effect of MSCs is dependent on direct cell-cell contact and that this intercellular contact is mediated through interaction of CD200 expressed by MSCs and CD200R1 expressed by MPs. Furthermore, using an injury model of sterile inflammation, we show that MSCs promote MP frequencies and suppress infiltration of inflammatory cells in the inflamed tissue. We also find that downregulation of CD200 in MSCs correlates with abrogation of their immunoregulatory function. Collectively, our study provides unequivocal evidence that MSCs inhibit differentiation of MPs in the inflammatory environment via CD200-CD200R1 interaction. Stem Cells 2017;35:1532-1541. © 2017 AlphaMed Press.

Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers.

Science.gov (United States)

Navarro, Gemma; Aguinaga, David; Moreno, Estefania; Hradsky, Johannes; Reddy, Pasham P; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Mikhaylova, Marina; Kreutz, Michael R; Lluís, Carme; Canela, Enric I; McCormick, Peter J; Ferré, Sergi

2014-11-20

The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

25 Gbit/s differential phase-shift-keying signal generation using directly modulated quantum-dot semiconductor optical amplifiers

International Nuclear Information System (INIS)

Zeghuzi, A.; Schmeckebier, H.; Stubenrauch, M.; Bimberg, D.; Meuer, C.; Schubert, C.; Bunge, C.-A.

2015-01-01

Error-free generation of 25-Gbit/s differential phase-shift keying (DPSK) signals via direct modulation of InAs quantum-dot (QD) based semiconductor optical amplifiers (SOAs) is experimentally demonstrated with an input power level of −5 dBm. The QD SOAs emit in the 1.3-μm wavelength range and provide a small-signal fiber-to-fiber gain of 8 dB. Furthermore, error-free DPSK modulation is achieved for constant optical input power levels from 3 dBm down to only −11 dBm for a bit rate of 20 Gbit/s. Direct phase modulation of QD SOAs via current changes is thus demonstrated to be much faster than direct gain modulation

Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses.

Directory of Open Access Journals (Sweden)

Stéphane Tchankouo-Nguetcheu

Full Text Available BACKGROUND: Arthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. The midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. A proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications that happen in the midgut for viral transmission to eventually take place. METHODOLOGY AND PRINCIPAL FINDINGS: Using a proteomics differential approach with two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE, we defined the protein modulations in the midgut of Aedes aegypti that were triggered seven days after an oral infection (7 DPI with dengue 2 (DENV-2 and chikungunya (CHIKV viruses. Gel profile comparisons showed that the level of 18 proteins was modulated by DENV-2 only and 12 proteins were modulated by CHIKV only. Twenty proteins were regulated by both viruses in either similar or different ways. Both viruses caused an increase of proteins involved in the generation of reactive oxygen species, energy production, and carbohydrate and lipid metabolism. Midgut infection by DENV-2 and CHIKV triggered an antioxidant response. CHIKV infection produced an increase of proteins involved in detoxification. CONCLUSION/SIGNIFICANCE: Our study constitutes the first analysis of the protein response of Aedes aegypti's midgut infected with viruses belonging to different families. It shows that the differentially regulated proteins in response to viral infection include structural, redox, regulatory proteins, and enzymes for several metabolic pathways. Some of these proteins like antioxidant are probably involved in cell protection. On the other hand, we propose that the modulation of other proteins like transferrin, hsp60 and alpha

A bonding study toward the quality assurance of Belle-II silicon vertex detector modules

Energy Technology Data Exchange (ETDEWEB)

Kang, K.H.; Jeon, H.B. [RSRI, Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Park, H., E-mail: sunshine@knu.ac.kr [RSRI, Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Uozumi, S. [RSRI, Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Adamczyk, K. [H. Niewodniczanski Institute of Nuclear Physics, Krakow 31-342 (Poland); Aihara, H. [Department of Physics, University of Tokyo, Tokyo 113-0033 (Japan); Angelini, C. [Dipartimento di Fisica, Universitá di Pisa, I-56127 Pisa (Italy); INFN Sezione di Pisa, I-56127 Pisa (Italy); Aziz, T.; Babu, V. [Tata Institute of Fundamental Research, Mumbai 400005 (India); Bacher, S. [H. Niewodniczanski Institute of Nuclear Physics, Krakow 31-342 (Poland); Bahinipati, S. [Indian Institute of Technology Bhubaneswar, Satya Nagar (India); Barberio, E.; Baroncelli, T. [School of Physics, University of Melbourne, Melbourne, Victoria 3010 (Australia); Basith, A.K. [Indian Institute of Technology Madras, Chennai 600036 (India); Batignani, G. [Dipartimento di Fisica, Universitá di Pisa, I-56127 Pisa (Italy); INFN Sezione di Pisa, I-56127 Pisa (Italy); Bauer, A. [Institute of High Energy Physics, Austrian Academy of Sciences, 1050 Vienna (Austria); Behera, P.K. [Indian Institute of Technology Madras, Chennai 600036 (India); Bergauer, T. [Institute of High Energy Physics, Austrian Academy of Sciences, 1050 Vienna (Austria); Bettarini, S. [Dipartimento di Fisica, Universitá di Pisa, I-56127 Pisa (Italy); INFN Sezione di Pisa, I-56127 Pisa (Italy); Bhuyan, B. [Indian Institute of Technology Guwahati, Assam 781039 (India); and others

2016-09-21

A silicon vertex detector (SVD) for the Belle-II experiment comprises four layers of double-sided silicon strip detectors (DSSDs), assembled in a ladder-like structure. Each ladder module of the outermost SVD layer has four rectangular and one trapezoidal DSSDs supported by two carbon-fiber ribs. In order to achieve a good signal-to-noise ratio and minimize material budget, a novel chip-on-sensor “Origami” method has been employed for the three rectangular sensors that are sandwiched between the backward rectangular and forward (slanted) trapezoidal sensors. This paper describes the bonding procedures developed for making electrical connections between sensors and signal fan-out flex circuits (i.e., pitch adapters), and between pitch adapters and readout chips as well as the results in terms of the achieved bonding quality and pull force. - Highlights: • Gluing and wire binding for Belle-II SVD are studied. • Gluing robot and Origami module are used. • QA are satisfied in terms of the achieved bonding throughput and the pull force. • Result will be applied for L6 ladder assembly.

A bonding study toward the quality assurance of Belle-II silicon vertex detector modules

International Nuclear Information System (INIS)

Kang, K.H.; Jeon, H.B.; Park, H.; Uozumi, S.; Adamczyk, K.; Aihara, H.; Angelini, C.; Aziz, T.; Babu, V.; Bacher, S.; Bahinipati, S.; Barberio, E.; Baroncelli, T.; Basith, A.K.; Batignani, G.; Bauer, A.; Behera, P.K.; Bergauer, T.; Bettarini, S.; Bhuyan, B.

2016-01-01

A silicon vertex detector (SVD) for the Belle-II experiment comprises four layers of double-sided silicon strip detectors (DSSDs), assembled in a ladder-like structure. Each ladder module of the outermost SVD layer has four rectangular and one trapezoidal DSSDs supported by two carbon-fiber ribs. In order to achieve a good signal-to-noise ratio and minimize material budget, a novel chip-on-sensor “Origami” method has been employed for the three rectangular sensors that are sandwiched between the backward rectangular and forward (slanted) trapezoidal sensors. This paper describes the bonding procedures developed for making electrical connections between sensors and signal fan-out flex circuits (i.e., pitch adapters), and between pitch adapters and readout chips as well as the results in terms of the achieved bonding quality and pull force. - Highlights: • Gluing and wire binding for Belle-II SVD are studied. • Gluing robot and Origami module are used. • QA are satisfied in terms of the achieved bonding throughput and the pull force. • Result will be applied for L6 ladder assembly.

MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

Directory of Open Access Journals (Sweden)

Judith A. James

2012-12-01

Full Text Available Anthrax Lethal Toxin consists of Protective Antigen (PA and Lethal Factor (LF, and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class II versus non-MHC class II genes in the humoral response to PA and LF immunization using three immunized strains of inbred mice: A/J (H-2k at the MHC class II locus, B6 (H-2b, and B6.H2k (H-2k. IgG antibody titers to LF were controlled primarily by the MHC class II locus, whereas IgG titers to PA were strongly influenced by the non-MHC class II genetic background. Conversely, the humoral fine specificity of reactivity to LF appeared to be controlled primarily through non-MHC class II genes, while the specificity of reactivity to PA was more dependent on MHC class II. Common epitopes, reactive in all strains, occurred in both LF and PA responses. These results demonstrate that MHC class II differentially influences humoral immune responses to LF and PA.

Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells.

Science.gov (United States)

Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin

2016-01-01

During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.

Neuronal differentiation modulates the dystrophin Dp71d binding to the nuclear matrix

International Nuclear Information System (INIS)

Rodriguez-Munoz, Rafael; Villarreal-Silva, Marcela; Gonzalez-Ramirez, Ricardo; Garcia-Sierra, Francisco; Mondragon, Monica; Mondragon, Ricardo; Cerna, Joel; Cisneros, Bulmaro

2008-01-01

The function of dystrophin Dp71 in neuronal cells remains unknown. To approach this issue, we have selected the PC12 neuronal cell line. These cells express both a Dp71f cytoplasmic variant and a Dp71d nuclear isoform. In this study, we demonstrated by electron and confocal microscopy analyses of in situ nuclear matrices and Western blotting evaluation of cell extracts that Dp71d associates with the nuclear matrix. Interestingly, this binding is modulated during NGF-induced neuronal differentiation of PC12 cells with a twofold increment in the differentiated cells, compared to control cells. Also, distribution of Dp71d along the periphery of the nuclear matrix observed in the undifferentiated cells is replaced by intense fluorescent foci localized in Center of the nucleoskeletal structure. In summary, we revealed that Dp71d is a dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation

Exogenous hydrogen sulfide promotes cell proliferation and differentiation by modulating autophagy in human keratinocytes

International Nuclear Information System (INIS)

Xie, Xin; Dai, Hui; Zhuang, Binyu; Chai, Li; Xie, Yanguang; Li, Yuzhen

2016-01-01

The effects and the underlying mechanisms of hydrogen sulfide (H 2 S) on keratinocyte proliferation and differentiation are still less known. In the current study, we investigated the effects and the underlying mechanisms of exogenous H 2 S on keratinocyte proliferation and differentiation. Human keratinocytes (HaCaT cells) were treated with various concentrations (0.05, 0.25, 0.5 and 1 mM) of sodium hydrosulfide (NaHS, a donor of H 2 S) for 24 h. A CCK-8 assay was used to assess cell viability. Western blot analysis was performed to determine the expression levels of proteins associated with differentiation and autophagy. Transmission electron microscopy was performed to observe autophagic vacuoles, and flow cytometry was applied to evaluate apoptosis. NaHS promoted the viability, induced the differentiation, and enhanced autophagic activity in a dose-dependent manner in HaCaT cells but had no effect on cell apoptosis. Blockage of autophagy by ATG5 siRNA inhibited NaHS-induced cell proliferation and differentiation. The current study demonstrated that autophagy in response to exogenous H 2 S treatment promoted keratinocyte proliferation and differentiation. Our results provide additional insights into the potential role of autophagy in keratinocyte proliferation and differentiation. - Highlights: • Exogenous H 2 S promotes keratinocyte proliferation and differentiation. • The effects of H 2 S on proliferation and differentiation is modulated by autophagy. • Exogenous H 2 S has no effect on keratinocyte apoptosis.

Solving Linear Differential Equations

NARCIS (Netherlands)

Nguyen, K.A.; Put, M. van der

2010-01-01

The theme of this paper is to 'solve' an absolutely irreducible differential module explicitly in terms of modules of lower dimension and finite extensions of the differential field K. Representations of semi-simple Lie algebras and differential Galo is theory are the main tools. The results extend

VXI based multibunch detector and QPSK modulator for the PEP-II/ALS/DAΦNE longitudinal feedback system

International Nuclear Information System (INIS)

Young, A.; Fox, J.; Teytelman, D.

1997-04-01

The PEP-II/ALS/DAΦNE feedback systems are complex systems implemented using analog, digital and microwave circuits. The VXI hardware implementation for the Front-end and Back-end analog processing modules is presented. The Front-end module produces a baseband beam phase signal from pickups using a microwave tone burst generator. The Back-end VXI module generates an AM/QPSK modulated signal from a baseband correction signal computed in a digital signal processor. These components are implemented in VXI packages that allow a wide spectrum of system functions including a 120 MHz bandwidth rms detector, reference phase servo, woofer link to the RF control system, standard VXI status/control, and user defined registers. The details of the design and implementation of the VXI modules including performance characteristics are presented

Differential on-on keying: A robust non-coherent digital modulation scheme

KAUST Repository

Kaddoum, Georges

2015-05-01

A robust digital modulation scheme, called differential on-on keying (DOOK), is presented in this paper which outperforms the conventional on-off keying (OOK). In this scheme, a sinusoidal signal is transmitted during the first half of the bit duration while a replica or an inverted version of the sinusoidal signal is transmitted during the second half for logic one or logic zero, respectively. Non-coherent receiver correlates the two halves of the received signal over half bit duration to construct a decision variable. Bit error performance is analyzed over AWGN and Rayleigh fading channels and compared to the conventional OOK.

Differential on-on keying: A robust non-coherent digital modulation scheme

KAUST Repository

Kaddoum, Georges; Ahmed, Mohammed F. A.; Al-Naffouri, Tareq Y.

2015-01-01

A robust digital modulation scheme, called differential on-on keying (DOOK), is presented in this paper which outperforms the conventional on-off keying (OOK). In this scheme, a sinusoidal signal is transmitted during the first half of the bit duration while a replica or an inverted version of the sinusoidal signal is transmitted during the second half for logic one or logic zero, respectively. Non-coherent receiver correlates the two halves of the received signal over half bit duration to construct a decision variable. Bit error performance is analyzed over AWGN and Rayleigh fading channels and compared to the conventional OOK.

Fucoidan, a Sulfated Polysaccharide, Inhibits Osteoclast Differentiation and Function by Modulating RANKL Signaling

Directory of Open Access Journals (Sweden)

Young Woo Kim

2014-10-01

Full Text Available Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1 expression, was alleviated in the fucoidan-treated cells. These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption.

A non-correlator-based digital communication system using interleaved chaotic differential peaks keying (I-CDPK) modulation and chaotic synchronization

International Nuclear Information System (INIS)

Chien, T.-I; Hung, Y.-C.; Liao, T.-L.

2006-01-01

This paper presents a novel non-correlator-based digital communication system with the application of interleaved chaotic differential peaks keying (I-CDPK) modulation technique. The proposed communication system consists of four major modules: I-CDPK modulator (ICM), frequency modulation (FM) transmitter, FM receiver and I-CDPK demodulator (ICDM). In the ICM module, there are four components: a chaotic circuit to generate the chaotic signals, A/D converter, D/A converter and a digital processing mechanism to control all signal flows and performs I-CDPK modulation corresponding to the input digital bits. For interleaving every input digital bit set, every state of the chaotic system is used to represent one portion of it, but only a scalar state variable (i.e. the system output) is sent to the ICDM's chaotic circuit through both FM transmitter and FM receiver. An observer-based chaotic synchronization scheme is designed to synchronize the chaotic circuits of the ICM and ICDM. Meanwhile, the bit detector in ICDM is devoted to recover the transmitted input digital bits. Some numerical simulations of an illustrative communication system are given to demonstrate its theoretical effectiveness. Furthermore, the performance of bit error rate of the proposed system is analyzed and compared with those of the correlator-based communication systems adopting coherent binary phase shift keying (BPSK) and coherent differential chaotic shift keying (DCSK) schemes

Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

Science.gov (United States)

Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

2017-03-01

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

Endogenous angiotensin II modulates nNOS expression in renovascular hypertension

Directory of Open Access Journals (Sweden)

T.M.C. Pereira

2009-07-01

Full Text Available Nitric oxide (NO influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS. Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight divided into 2K1C (N = 19 and sham-operated (N = 19 groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9 was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan (10 mg·kg-1·day-1; N = 5 or the superoxide scavenger tempol (0.2 mmol·kg-1·day-1; N = 5, which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.

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

Science.gov (United States)

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

2013-01-01

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

Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells

NARCIS (Netherlands)

Lu, Z.F.; Zandieh Doulabi, B.; Wuisman, P.I.; Bank, R.A.; Helder, M.N.

2008-01-01

Tissue microenvironment plays a critical role in guiding local stem cell differentiation. Within the intervertebral disc, collagen type II and nucleus pulposus (NP) cells are two major components. This study aimed to investigate how collagen type II and NP cells affect adipose tissue-derived stem

Exogenous hydrogen sulfide promotes cell proliferation and differentiation by modulating autophagy in human keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Xie, Xin [Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang Province (China); Dai, Hui [Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province (China); Zhuang, Binyu [Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang Province (China); Chai, Li; Xie, Yanguang [Institute of Dermatology of Heilongjiang Province, Harbin, 150001, Heilongjiang Province (China); Li, Yuzhen, E-mail: liyuzhen@medmail.com.cn [Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang Province (China)

2016-04-08

The effects and the underlying mechanisms of hydrogen sulfide (H{sub 2}S) on keratinocyte proliferation and differentiation are still less known. In the current study, we investigated the effects and the underlying mechanisms of exogenous H{sub 2}S on keratinocyte proliferation and differentiation. Human keratinocytes (HaCaT cells) were treated with various concentrations (0.05, 0.25, 0.5 and 1 mM) of sodium hydrosulfide (NaHS, a donor of H{sub 2}S) for 24 h. A CCK-8 assay was used to assess cell viability. Western blot analysis was performed to determine the expression levels of proteins associated with differentiation and autophagy. Transmission electron microscopy was performed to observe autophagic vacuoles, and flow cytometry was applied to evaluate apoptosis. NaHS promoted the viability, induced the differentiation, and enhanced autophagic activity in a dose-dependent manner in HaCaT cells but had no effect on cell apoptosis. Blockage of autophagy by ATG5 siRNA inhibited NaHS-induced cell proliferation and differentiation. The current study demonstrated that autophagy in response to exogenous H{sub 2}S treatment promoted keratinocyte proliferation and differentiation. Our results provide additional insights into the potential role of autophagy in keratinocyte proliferation and differentiation. - Highlights: • Exogenous H{sub 2}S promotes keratinocyte proliferation and differentiation. • The effects of H{sub 2}S on proliferation and differentiation is modulated by autophagy. • Exogenous H{sub 2}S has no effect on keratinocyte apoptosis.

Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells.

Directory of Open Access Journals (Sweden)

Ahmed A Mostafa

Full Text Available The coordinate regulation of HLA class II (HLA-II is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E₂ and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER⁻ and ER⁺ breast cancer cell lines, we showed that E₂ attenuated HLA-DR in two ER⁺ lines (MCF-7 and BT-474, but not in T47D, while it augmented expression in ER⁻ lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s, we used paired transfectants: ERα⁺ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene and ERα⁻ VC5 (MDA-MB-231 c10A transfected with the empty vector, treated or not with E₂ and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E₂ treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E₂ in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα⁻ breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα⁺ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

Gαq Regulates the Development of Rheumatoid Arthritis by Modulating Th1 Differentiation.

Science.gov (United States)

Wang, Dashan; Liu, Yuan; Li, Yan; He, Yan; Zhang, Jiyun; Shi, Guixiu

2017-01-01

The G α q-containing G protein, an important member of G q/11 class, is ubiquitously expressed in mammalian cells. G α q has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how G α q participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether G α q controls RA via regulation of Th1 differentiation. We observed that the expression of G α q was negatively correlated with the expression of signature Th1 cytokine (IFN- γ ) in RA patients, which suggests a negative role of G α q in differentiation of Th1 cells. By using G α q knockout ( Gnaq-/- ) mice, we demonstrated that loss of G α q led to enhanced Th1 cell differentiation. G α q negative regulated the differentiation of Th1 cell by modulating the expression of T-bet and the activity of STAT4. Furthermore, we detected the increased ratio of Th1 cells in Gnaq-/- bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of G α q promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA.

Detecting modulated signals in modulated noise: (II) neural thresholds in the songbird forebrain.

Science.gov (United States)

Bee, Mark A; Buschermöhle, Michael; Klump, Georg M

2007-10-01

Sounds in the real world fluctuate in amplitude. The vertebrate auditory system exploits patterns of amplitude fluctuations to improve signal detection in noise. One experimental paradigm demonstrating these general effects has been used in psychophysical studies of 'comodulation detection difference' (CDD). The CDD effect refers to the fact that thresholds for detecting a modulated, narrowband noise signal are lower when the envelopes of flanking bands of modulated noise are comodulated with each other, but fluctuate independently of the signal compared with conditions in which the envelopes of the signal and flanking bands are all comodulated. Here, we report results from a study of the neural correlates of CDD in European starlings (Sturnus vulgaris). We manipulated: (i) the envelope correlations between a narrowband noise signal and a masker comprised of six flanking bands of noise; (ii) the signal onset delay relative to masker onset; (iii) signal duration; and (iv) masker spectrum level. Masked detection thresholds were determined from neural responses using signal detection theory. Across conditions, the magnitude of neural CDD ranged between 2 and 8 dB, which is similar to that reported in a companion psychophysical study of starlings [U. Langemann & G.M. Klump (2007) Eur. J. Neurosci., 26, 1969-1978]. We found little evidence to suggest that neural CDD resulted from the across-channel processing of auditory grouping cues related to common envelope fluctuations and synchronous onsets between the signal and flanking bands. We discuss a within-channel model of peripheral processing that explains many of our results.

A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.

Directory of Open Access Journals (Sweden)

Daniela Annibali

Full Text Available The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.

Nouns referring to tools and natural objects differentially modulate the motor system.

Science.gov (United States)

Gough, Patricia M; Riggio, Lucia; Chersi, Fabian; Sato, Marc; Fogassi, Leonardo; Buccino, Giovanni

2012-01-01

While increasing evidence points to a critical role for the motor system in language processing, the focus of previous work has been on the linguistic category of verbs. Here we tested whether nouns are effective in modulating the motor system and further whether different kinds of nouns - those referring to artifacts or natural items, and items that are graspable or ungraspable - would differentially modulate the system. A Transcranial Magnetic Stimulation (TMS) study was carried out to compare modulation of the motor system when subjects read nouns referring to objects which are Artificial or Natural and which are Graspable or Ungraspable. TMS was applied to the primary motor cortex representation of the first dorsal interosseous (FDI) muscle of the right hand at 150 ms after noun presentation. Analyses of Motor Evoked Potentials (MEPs) revealed that across the duration of the task, nouns referring to graspable artifacts (tools) were associated with significantly greater MEP areas. Analyses of the initial presentation of items revealed a main effect of graspability. The findings are in line with an embodied view of nouns, with MEP measures modulated according to whether nouns referred to natural objects or artifacts (tools), confirming tools as a special class of items in motor terms. Additionally our data support a difference for graspable versus non graspable objects, an effect which for natural objects is restricted to initial presentation of items. Copyright © 2011 Elsevier Ltd. All rights reserved.

Differential pattern of semantic memory organization between bipolar I and II disorders.

Science.gov (United States)

Chang, Jae Seung; Choi, Sungwon; Ha, Kyooseob; Ha, Tae Hyon; Cho, Hyun Sang; Choi, Jung Eun; Cha, Boseok; Moon, Eunsoo

2011-06-01

Semantic cognition is one of the key factors in psychosocial functioning. The aim of this study was to explore the differences in pattern of semantic memory organization between euthymic patients with bipolar I and II disorders using the category fluency task. Study participants included 23 euthymic subjects with bipolar I disorder, 23 matched euthymic subjects with bipolar II disorder and 23 matched control subjects. All participants were assessed for verbal learning, recall, learning strategies, and fluency. The combined methods of hierarchical clustering and multidimensional scaling were used to compare the pattern of semantic memory organization among the three groups. Quantitative measures of verbal learning, recall, learning strategies, and fluency did not differ between the three groups. A two-cluster structure of semantic memory organization was identified for the three groups. Semantic structure was more disorganized in the bipolar I disorder group compared to the bipolar II disorder. In addition, patients with bipolar II disorder used less elaborate strategies of semantic memory organization than those of controls. Compared to healthy controls, strategies for categorization in semantic memory appear to be less knowledge-based in patients with bipolar disorders. A differential pattern of semantic memory organization between bipolar I and II disorders indicates a higher risk of cognitive abnormalities in patients with bipolar I disorder compared to patients with bipolar II disorder. Exploring qualitative nature of neuropsychological domains may provide an explanatory insight into the characteristic behaviors of patients with bipolar disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Dopamine receptors D3 and D5 regulate CD4(+)T-cell activation and differentiation by modulating ERK activation and cAMP production.

Science.gov (United States)

Franz, Dafne; Contreras, Francisco; González, Hugo; Prado, Carolina; Elgueta, Daniela; Figueroa, Claudio; Pacheco, Rodrigo

2015-07-15

Dopamine receptors have been described in T-cells, however their signalling pathways coupled remain unknown. Since cAMP and ERKs play key roles regulating T-cell physiology, we aim to determine whether cAMP and ERK1/2-phosphorylation are modulated by dopamine receptor 3 (D3R) and D5R, and how this modulation affects CD4(+) T-cell activation and differentiation. Our pharmacologic and genetic evidence shows that D3R-stimulation reduced cAMP levels and ERK2-phosphorylation, consequently increasing CD4(+) T-cell activation and Th1-differentiation, respectively. Moreover, D5R expression reinforced TCR-triggered ERK1/2-phosphorylation and T-cell activation. In conclusion, these findings demonstrate how D3R and D5R modulate key signalling pathways affecting CD4(+) T-cell activation and Th1-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Health Occupations Module. The Skeletal System--II.

Science.gov (United States)

Temple Univ., Philadelphia, PA. Div. of Vocational Education.

This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, two objectives (e.g., list the types of joints and movements, and give examples), and two learning…

A Simple Differential Modulation Scheme for Quasi-Orthogonal Space-Time Block Codes with Partial Transmit Diversity

Directory of Open Access Journals (Sweden)

Lingyang Song

2007-04-01

Full Text Available We report a simple differential modulation scheme for quasi-orthogonal space-time block codes. A new class of quasi-orthogonal coding structures that can provide partial transmit diversity is presented for various numbers of transmit antennas. Differential encoding and decoding can be simplified for differential Alamouti-like codes by grouping the signals in the transmitted matrix and decoupling the detection of data symbols, respectively. The new scheme can achieve constant amplitude of transmitted signals, and avoid signal constellation expansion; in addition it has a linear signal detector with very low complexity. Simulation results show that these partial-diversity codes can provide very useful results at low SNR for current communication systems. Extension to more than four transmit antennas is also considered.

Stability of skeletal changes induced by growth modulation procedures in the treatment of skeletal Class II malocclusion

Directory of Open Access Journals (Sweden)

Prashantha Govinakovi Shivamurthy

2016-01-01

Full Text Available Objective: Objective of this study, based on an evaluation of lateral cephalograms, was to evaluate the degree of skeletal changes produced by the various growth modulative procedures in the treatment of skeletal Class II malocclusion and to characterize the stability of these changes in the years after treatment. Materials and Methods: Total of 40 patients with Class II malocclusion was divided into three groups according to appliance used, i.e. removable or fixed functional appliances (n = 10, combination of functional appliance with headgear (n = 10, and only headgear (n = 10. In addition, almost a matched control group (n = 10 also characterized by skeletal Class II pattern and were under observation, for more than 2 years was also selected. Lateral cephalograms of each patient were taken at the start of treatment (T1, at its completion (T2, and long-term posttreatment (T3. Results: This study showed significant improvement in maxillomandibular relationship in treated group compared to control group, and the changes remained stable in posttreatment phase. Restriction of maxillary growth was evident in headgear and combination groups whereas significant forward movement of the mandible was seen in functional group. Conclusion: Analysis of lateral cephalograms indicates that growth modulation therapy in angle Class II malocclusion brings about desired skeletal changes which remain relatively stable over a long-term period.

Interaction of prostaglandins and angiotensin II in the modulation of renal function in congestive heart failure.

Science.gov (United States)

Packer, M

1988-06-01

Despite a dramatic fall in renal blood flow, glomerular filtration rate is usually preserved in patients with congestive heart failure until the terminal stages of the disease. This maintenance of renal function appears to be achieved in part by the synthesis of two vasoactive factors within the kidney--angiotensin II and prostaglandins--which are rapidly released whenever renal perfusion is compromised or sympathetic nerve traffic to the kidneys is increased. Although these two hormonal systems exert opposite effects on systemic and renal blood flow and sodium and water excretion, both act to preserve glomerular filtration rate: prostaglandins by a vasodilator action exerted primarily on the afferent arteriole and angiotensin II by a vasoconstrictor effect on the efferent arteriole. Consequently, when the synthesis of these hormones is experimentally blocked, renal function deteriorates, especially in subjects with marked renal hypoperfusion and sodium depletion; these two factors interact to determine the importance of intrarenal hormonal release in the modulation of renal function. Clinically, four specific factors have been identified that predispose patients with heart failure to the development of functional renal insufficiency after treatment with converting-enzyme or cyclo-oxygenase inhibitors: (1) marked renal hypoperfusion, (2) vigorous diuretic therapy, (3) diabetes mellitus, and (4) intensity of hormonal inhibition within the kidney. This last risk factor may provide the basis for differentiating among enzyme-inhibitory drugs and suggests that renal insufficiency in low-output states may be minimized by the development of therapeutic agents that block hormonal synthesis selectively at sites that are critical to the disease process but spare the homeostatic tissue-based enzyme systems that exist within the kidney.

Nuclear Technology. Course 32: Nondestructive Examination (NDE) II. Module 32-3, Fundamentals of Magnetic Particle Testing.

Science.gov (United States)

Groseclose, Richard

This third in a series of six modules for a course titled Nondestructive Examination (NDE) Techniques II explains the principles of magnets and magnetic fields and how they are applied in magnetic particle testing, describes the theory and methods of magnetizing test specimens, describes the test equipment used, discusses the principles and…

Stereotactic Image-Guided Intensity Modulated Radiotherapy Using the HI-ART II Helical Tomotherapy System

International Nuclear Information System (INIS)

Holmes, Timothy W.; Hudes, Richard; Dziuba, Sylwester; Kazi, Abdul; Hall, Mark; Dawson, Dana

2008-01-01

The highly integrated adaptive radiation therapy (HI-ART II) helical tomotherapy unit is a new radiotherapy machine designed to achieve highly precise and accurate treatments at all body sites. The precision and accuracy of the HI-ART II is similar to that provided by stereotactic radiosurgery systems, hence the historical distinction between external beam radiotherapy and stereotactic procedures based on differing precision requirements is removed for this device. The objectives of this work are: (1) to describe stereotactic helical tomotherapy processes (SRS, SBRT); (2) to show that the precision and accuracy of the HI-ART meet the requirements defined for SRS and SBRT; and (3) to describe the clinical implementation of a stereotactic image-guided intensity modulated radiation therapy (IG-IMRT) system that incorporates optical motion management

Local fractional variational iteration algorithm II for non-homogeneous model associated with the non-differentiable heat flow

Directory of Open Access Journals (Sweden)

Yu Zhang

2015-10-01

Full Text Available In this article, we begin with the non-homogeneous model for the non-differentiable heat flow, which is described using the local fractional vector calculus, from the first law of thermodynamics in fractal media point view. We employ the local fractional variational iteration algorithm II to solve the fractal heat equations. The obtained results show the non-differentiable behaviors of temperature fields of fractal heat flow defined on Cantor sets.

M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.

Directory of Open Access Journals (Sweden)

Linda Cambier

Full Text Available Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.

Study of gamma irradiated polyethylenes by temperature modulated differential scanning calorimetry

International Nuclear Information System (INIS)

Secerov, B.; Galovic, S.; Trifunovic, S.; Milicevic, D.; Suljovrujic, E.

2011-01-01

Complete text of publication follows. The various polyethylenes (PEs) and effects of high energy radiation on theirs structures were widely studied in the past using conventional Differential Scanning Calorimetry (DSC) measurements. In this work, we applied the Temperature Modulated Differential Scanning Calorimetry (TMDSC) technique in order to obtain more information about the influence of initial structural differences and gamma radiation on the evolution in structure and thermal properties of different polyethylenes. For this reason, low density polyethylene (LDPE), linear low density polyethylene (LLDPE) and high density polyethylene (HDPE) samples were exposed to gamma radiation, in air, to a wide range of absorbed doses (up to 2400 kGy). The separation of the total heat flow TMDSC signal into a reversing and nonreversing part enabled to observed the low temperature enthalpy relaxation (related to the existence of the 'rigid amorphous phase') and recrystallization processes as well as to follow their and/or radiation-induced evolution of melting in a more revealing manner compared to the case of the conventional DSC. Consequently, our results indicate that TMDSC could improve the understanding of radiation-induced effects in polymers.

Characterization of the phase transformations in shape-memory alloys by modulated differential scanning calorimetry

International Nuclear Information System (INIS)

Wei, Z.G.; Sandstroem, R.

1999-01-01

Modulated differential scanning calorimetry (MDSC) is a recently developed calorimetric technique, which has demonstrated some significant advantages over the conventional differential scanning calorimetry (DSC). By separating the reversing quantity from the non-reversing component in the total thermal events, it provides some new information that can not be obtained from the conventional DSC. The technique has been applied to various polycrystalline and single crystalline shape-memory alloys, including Cu-Zn-Al, Cu-Al-Ni, Ti-Ni(Cu), Ni-Mn-Ga and Fe-Mn-Si, to characterize the martensitic transformations, bainitic transformation, chemical and magnetic ordering transitions, atomic reordering and other kinetic relaxation processes in the alloys. The preliminary results of the MDSC measurements are summarized and the interpretation of the MDSC results and some factors affecting the results are discussed. (orig.)

Differential Relationships between WISC-IV and WIAT-II Scales: An Evaluation of Potentially Moderating Child Demographics

Science.gov (United States)

Konold, Timothy R.; Canivez, Gary L.

2010-01-01

Considerable debate exists regarding the accuracy of intelligence tests with members of different groups. This study investigated differential predictive validity of the "Wechsler Intelligence Scale for Children-Fourth Edition". Participants from the WISC-IV--WIAT-II standardization linking sample (N = 550) ranged in age from 6 through…

Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

Energy Technology Data Exchange (ETDEWEB)

Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada); Faure, Robert [Département de Pédiatrie, Université Laval and Centre de recherche du CHUQ (Centre Mère-Enfant), Québec, Qc, Canada G1V 4G2 (Canada); Marceau, Normand, E-mail: normand.marceau@crhdq.ulaval.ca [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada)

2013-02-15

As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

Three members of a peptide family are differentially distributed and elicit differential state-dependent responses in a pattern generator-effector system.

Science.gov (United States)

Dickinson, Patsy S; Armstrong, Matthew K; Dickinson, Evyn S; Fernandez, Rebecca; Miller, Alexandra; Pong, Sovannarath; Powers, Brian; Pupo Wiss, Alixander; Stanhope, Meredith E; Walsh, Patrick J; Wiwatpanit, Teerawat; Christie, Andrew E

2018-01-31

C-type allatostatins (AST-Cs) are pleiotropic neuropeptides that are broadly conserved within arthropods; the presence of three AST-C isoforms, encoded by paralog genes, is common. However, these peptides are hypothesized to act through a single receptor, thereby exerting similar bioactivities within each species. We investigated this hypothesis in the American lobster, Homarus americanus, mapping the distributions of AST-C isoforms within relevant regions of the nervous system and digestive tract, and comparing their modulatory influences on the cardiac neuromuscular system. Immunohistochemistry showed that in the pericardial organ, a neuroendocrine release site, AST-C I and/or III and AST-C II are contained within distinct populations of release terminals. Moreover, AST-C I/III-like immunoreactivity was seen in midgut epithelial endocrine cells and the cardiac ganglion (CG), whereas AST-C II-like immunoreactivity was not seen in these tissues. These data suggest that AST-C I and/or III can modulate the CG both locally and hormonally; AST-C II likely acts on the CG solely as a hormonal modulator. Physiological studies demonstrated that all three AST-C isoforms can exert differential effects, including both increases and decreases, on contraction amplitude and frequency when perfused through the heart. However, in contrast to many state-dependent modulatory changes, the changes in contraction amplitude and frequency elicited by the AST-Cs were not functions of the baseline parameters. The responses to AST-C I and III, neither of which is C-terminally amidated, are more similar to one another than they are to the responses elicited by AST-C II, which is C-terminally amidated. These results suggest that the three AST-C isoforms are differentially distributed in the lobster nervous system/midgut and can elicit distinct behaviors from the cardiac neuromuscular system, with particular structural features, e.g., C-terminal amidation, likely important in determining the

The overvoltage protection module for the power supply system for the pixel detector at Belle II experiment at KEK

International Nuclear Information System (INIS)

Kapusta, P.; Kisielewski, B.

2015-01-01

In this paper the overvoltage protection modules (OVP) for the power supply (PS) system of the Belle II pixel detector (PXD) are described. The aim of the OVP is to protect the detector and associated electronics against overvoltage conditions. Most critical in the system are voltages supplying the front-end ASICs. The PXD detector consists of the DEPFET sensor modules with integrated chips like the Drain Current Digitizer, the Switcher and the Data Handling Processor. These chips, implemented in modern sub-micron technologies, are quite vulnerable to variations in the supply voltages. The PXD will be placed in the Belle II experiment as close as possible to the interaction point, where access during experiment is very limited or even impossible, thus the PS and OVP systems exploit the remote-sensing method. Overvoltage conditions are due to failures of the PS itself, wrong setting of the output voltages or transient voltages coming out of hard noisy environment of the experiment. The OVP modules are parts of the PS modules. For powering the PXD 40 PS modules are placed 15 m outside the Belle II spectrometer. Each one is equipped with the OVP board. All voltages (22) are grouped in 4 domains: Analog, Digital, Steering and Gate which have independent grounds. The OVP boards are designed from integrated circuits from Linear Technology. All configurations were simulated with the Spice program. The control electronics is designed in a Xilinx CPLD. Two types of integrated circuits were used. LT4356 surge stopper protects loads from high voltage transients. The output voltages are limited to a safe value and also protect loads against over current faults. For less critical voltages, the LTC2912 voltage monitors are used that detect under-voltage and overvoltage events. It has to be noted that the OVP system is working independently of any other protection of the PS system, which increases its overall reliability. (authors)

The overvoltage protection module for the power supply system for the pixel detector at Belle II experiment at KEK

Energy Technology Data Exchange (ETDEWEB)

Kapusta, P.; Kisielewski, B. [Institute of Nuclear Physics PAN, ul.Radzikowskiego 152, 31-875 Krakow, (Poland)

2015-07-01

In this paper the overvoltage protection modules (OVP) for the power supply (PS) system of the Belle II pixel detector (PXD) are described. The aim of the OVP is to protect the detector and associated electronics against overvoltage conditions. Most critical in the system are voltages supplying the front-end ASICs. The PXD detector consists of the DEPFET sensor modules with integrated chips like the Drain Current Digitizer, the Switcher and the Data Handling Processor. These chips, implemented in modern sub-micron technologies, are quite vulnerable to variations in the supply voltages. The PXD will be placed in the Belle II experiment as close as possible to the interaction point, where access during experiment is very limited or even impossible, thus the PS and OVP systems exploit the remote-sensing method. Overvoltage conditions are due to failures of the PS itself, wrong setting of the output voltages or transient voltages coming out of hard noisy environment of the experiment. The OVP modules are parts of the PS modules. For powering the PXD 40 PS modules are placed 15 m outside the Belle II spectrometer. Each one is equipped with the OVP board. All voltages (22) are grouped in 4 domains: Analog, Digital, Steering and Gate which have independent grounds. The OVP boards are designed from integrated circuits from Linear Technology. All configurations were simulated with the Spice program. The control electronics is designed in a Xilinx CPLD. Two types of integrated circuits were used. LT4356 surge stopper protects loads from high voltage transients. The output voltages are limited to a safe value and also protect loads against over current faults. For less critical voltages, the LTC2912 voltage monitors are used that detect under-voltage and overvoltage events. It has to be noted that the OVP system is working independently of any other protection of the PS system, which increases its overall reliability. (authors)

Synthesis and structural characterization of nickel(II), cobalt(II), Zinc(II), manganese(II), cadmium(II) and uranium(VI) complexes of α-oximinoacetoacet-o/p-anisidide thiosemicarbazone

International Nuclear Information System (INIS)

Patel, P.S.; Patel, M.M.; Ray, R.M.

1993-01-01

A few metal complexes of α-oximinoacetoacet-o/p-anisidide thiosemicarbazones (OAOATS)/(OAPATS) with Ni(II), Co(II), Zn(II), Mn(II), Hg(II), Cd(II) and UO 2 (II) have been prepared and characterized by elemental analyses, conductivity, differential scanning calorimetry study, thermogravimetric analyses and infrared and electronic spectral measurements in conjunction with magnetic susceptibility measurements at room temperature. They have also been tested for their antimicrobial activities. (author). 24 refs., 2 tabs

Pressure-modulated differential scanning calorimetry. An approach to the continuous, simultaneous determination of heat capacities and expansion coefficients.

Science.gov (United States)

Boehm, K; Rösgen, J; Hinz, H-J

2006-02-15

A new method is described that permits the continuous and synchronous determination of heat capacity and expansibility data. We refer to it as pressure-modulated differential scanning calorimetry (PMDSC), as it involves a standard DSC temperature scan and superimposes on it a pressure modulation of preselected format. The power of the method is demonstrated using salt solutions for which the most accurate heat capacity and expansibility data exist in the literature. As the PMDSC measurements could reproduce the parameters with high accuracy and precision, we applied the method also to an aqueous suspension of multilamellar DSPC vesicles for which no expansibility data had been reported previously for the transition region. Excellent agreement was obtained between data from PMDSC and values from independent direct differential scanning densimetry measurements. The basic theoretical background of the method when using sawtooth-like pressure ramps is given under Supporting Information, and a complete statistical thermodynamic derivation of the general equations is presented in the accompanying paper.

Fringe Controls Naïve CD4+T Cells Differentiation through Modulating Notch Signaling in Asthmatic Rat Models

Science.gov (United States)

Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

2012-01-01

The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4+T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4+T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4+T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4+T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma. PMID:23071776

Fringe controls naïve CD4(+)T cells differentiation through modulating notch signaling in asthmatic rat models.

Science.gov (United States)

Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

2012-01-01

The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4(+)T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4(+)T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4(+)T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4(+)T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma.

Differential saturation study of radial and angular modulation mechanisms of electron spin--lattice relaxation for trapped hydrogen atoms in sulfuric acid glasses. [X radiation

Energy Technology Data Exchange (ETDEWEB)

Plonka, A; Kevan, L

1976-11-01

A differential ESR saturation study of allowed transitions and forbidden proton spin-flip satellite transitions for trapped hydrogen atoms in sulfuric acid glasses indicates that angular modulation dominates the spin-lattice relaxation mechanisms and suggests that the modulation arises from motion of the H atom.

A two-level voltage source inverter with differentially sinusoidal pulse width modulation used in the interconnection system of a wind turbine generator

Directory of Open Access Journals (Sweden)

Alexandros C. Charalampidis

2014-10-01

Full Text Available This study analyses an interconnection system based on differentially sinusoidal pulse width modulation, used for the interconnection to the grid of a variable speed wind turbine. The modulation technique used provides specific advantages in comparison with the commonly used sinusoidal pulse width modulation (SPWM technique, such as lower DC bus voltage requirements, smaller switching losses for the same switching frequency as well as less higher harmonic content in the voltage waveforms produced. The respective control system is also described in detail. Thus this study provides a guide enabling the design of any interconnection system based on this modulation technique.

Differential signaling spread-spectrum modulation of the LED visible light wireless communications using a mobile-phone camera

Science.gov (United States)

Chen, Shih-Hao; Chow, Chi-Wai

2015-02-01

Visible light communication (VLC) using spread spectrum modulation (SSM) and differential signaling (DS), detected by a mobile-phone camera is proposed and demonstrated for the first time to provide high immunity to background ambient light interference. The SSM signal provides the coding gain while the DS scheme enhances the clock recovery particular under high background ambient light. Experiment results confirm the feasibility of the proposed scheme, showing that the proposed system has 6-dB gain comparing with the traditional on-off keying (OOK) modulation under background ambient light of 3000 lux. The direct incident ambient light to the mobile-phone camera is 520 lux.

Nuclear Technology. Course 32: Nondestructive Examination (NDE) Techniques II. Module 32-4, Operation of Magnetic Particle Test Equipment.

Science.gov (United States)

Groseclose, Richard

This fourth in a series of six modules for a course titled Nondestructive Examination (NDE) Techniques II describes the specific technique variables and options which are available to the test technician, provides instructions for selecting and operating the appropriate test equipment, describes physical criteria for detectable discontinuities,…

The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE Pathway

Directory of Open Access Journals (Sweden)

Bo Zhang

2012-01-01

Full Text Available Among various cancer cell lines, the leukemia cell line HL-60 was most sensitive to Shikonin, with evidence showing both the prooxidative activities and proapoptotic effects of micromolar concentrations of Shikonin. However, the mechanism involved in the cytotoxicity of Shikonin in the submicromolar range has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the prodifferentiated profiles of Shikonin and evaluated the redox homeostasis during HL-60 differentiation. The data showed a strong dose-response relationship between Shikonin exposure and the characteristics of HL-60 differentiation in terms of morphology changes, nitroblue tetrazolium (NBT reductive activity, and the expression level of surface antigens CD11b/CD14. During drug exposure, intercellular redox homeostasis changes towards oxidation are necessary to support Shikonin-induced differentiation, which was proven by additional enzymatic and non-enzymatic redox modulators. A statistically significant and dose-dependent increase (P<0.05 was recorded with regard to the unique expression levels of the Nrf2/ARE downstream target genes in HL-60 cells undergoing late differentiation, which were restored with further antioxidants employed with the Shikonin treatment. Our research demonstrated that Shikonin is a differentiation-inducing agent, and its mechanisms involve the Nrf2/ARE pathway to modulate the intercellular redox homeostasis, thus facilitating differentiation.

Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection.

Science.gov (United States)

Tomosada, Yohsuke; Chiba, Eriko; Zelaya, Hortensia; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio

2013-08-15

Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. The aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. Nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible

A study of gamma-irradiated polyethylenes by temperature modulated differential scanning calorimetry

Science.gov (United States)

Galovic, S.; Secerov, B.; Trifunovic, S.; Milicevic, D.; Suljovrujic, E.

2012-09-01

Various polyethylenes (PEs) and the effects of high-energy radiation on their structures were widely studied in the past using conventional Differential Scanning Calorimetry (DSC) measurements. In this work, we used the Temperature Modulated Differential Scanning Calorimetry (TMDSC) technique in order to obtain more information about the influence of the initial structural differences and gamma radiation on the evolution in structure and thermal properties of different polyethylenes. For this reason, low density polyethylene (LDPE), linear low density polyethylene (LLDPE) and high density polyethylene (HDPE) samples were exposed to gamma radiation, in air, to a wide range of absorbed doses (up to 2400 kGy). The separation of the total heat flow TMDSC signal into a reversing and non-reversing part enabled us to observe the low-temperature enthalpy relaxation (related to the existence of the "rigid amorphous phase") and recrystallisation processes, as well as to follow their radiation-induced evolution and/or that of melting in a more revealing manner compared to the case of the conventional DSC. Consequently, our results indicate that TMDSC could improve the understanding of radiation-induced effects in polymers.

γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

Science.gov (United States)

D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.

2015-01-01

Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103

Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

Directory of Open Access Journals (Sweden)

Savage Paul

2002-05-01

Full Text Available Abstract Background 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. Methods Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression. Results The median age was 64 yrs (34–84 and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. Conclusions This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin are in progress and may prove encouraging.

Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30II-mediated repression of LTR transcriptional activity

International Nuclear Information System (INIS)

Michael, Bindhu; Nair, Amrithraj M.; Datta, Antara; Hiraragi, Hajime; Ratner, Lee; Lairmore, Michael D.

2006-01-01

Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13 II and p30 II , which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30 II , a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30 II motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100-179 of p30 II , a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30 II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30 II -dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30 II -mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30 II -mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30 II -mediated LTR repression. Collectively, our data indicate that HTLV-1 p30 II modulates viral gene expression in a cooperative manner with p300-mediated acetylation

Investigation of the impact of mechanical stress on the properties of silicon sensor modules for the ATLAS Phase II upgrade

Energy Technology Data Exchange (ETDEWEB)

Stegler, Martin; Polay, Luise; Spehrlich, Dennis; Bloch, Ingo [DESY, Zeuthen (Germany)

2016-07-01

The new ATLAS tracker for phase II will be composed of silicon pixel and strip sensor modules. Such a module consists of silicon sensors, boards and readout chips. In a currently ongoing study new adhesives to connect the modular components thermally and mechanically are examined. It was shown that the silicon sensor is exposed to mechanical stress when part of a module. Mechanical stress can cause damage to a sensor and can change the tensors of electrical properties. The study of the effects of mechanical stress on characteristics of the silicon sensor modules are the focus in this presentation. The thermal induced tensile stress near to the surface of a silicon sensor build in a module was simulated. A four point bending setup was used to measure the maximum tensile stress of silicon and to verify the piezoresistive effect on ATLAS07 sensors. The results of the electrical measurements and simulations of stressed silicon sensor modules are shown in the presentation.

Application of the modulated temperature differential scanning calorimetry technique for the determination of the specific heat of copper nanofluids

International Nuclear Information System (INIS)

De Robertis, E.; Cosme, E.H.H.; Neves, R.S.; Kuznetsov, A.Yu.; Campos, A.P.C.; Landi, S.M.; Achete, C.A.

2012-01-01

The purpose of this work is to investigate the applicability of the modulated temperature differential scanning calorimetry technique to measure specific heat of copper nanofluids by using the ASTM E2719 standard procedure, which is generally applied to thermally stable solids and liquids. The one-step method of preparation of copper nanofluid samples is described. The synthesized nanoparticles were separated from the base fluid and examined by X-ray diffraction and transmission electron microscopy in order to evaluate their structure, morphology and chemical nature. The presence of copper nanoparticles in the base fluid alters the characteristics of crystallization and melting processes and reduces the specific heat values of nanofluids in the whole studied temperature range. - Highlights: ► Copper nanofluids prepared by one-step method. ► Methodology of synthesis improved nanofluid stability. ► Specific heat determinations using modulated temperature differential scanning calorimetry. ► Good agreement between theoretical and experimental values.

Differentiation of Human Adipose Derived Stem Cells into Smooth Muscle Cells Is Modulated by CaMKIIγ

Directory of Open Access Journals (Sweden)

Kaisaier Aji

2016-01-01

Full Text Available The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII is known to participate in maintenance and switches of smooth muscle cell (SMC phenotypes. However, which isoform of CaMKII is involved in differentiation of adult mesenchymal stem cells into contractile SMCs remains unclear. In the present study, we detected γ isoform of CaMKII in differentiation of human adipose derived stem cells (hASCs into SMCs that resulted from treatment with TGF-β1 and BMP4 in combination for 7 days. The results showed that CaMKIIγ increased gradually during differentiation of hASCs as determined by real-time PCR and western blot analysis. The siRNA-mediated knockdown of CaMKIIγ decreased the protein levels and transcriptional levels of smooth muscle contractile markers (a-SMA, SM22a, calponin, and SM-MHC, while CaMKIIγ overexpression increases the transcriptional and protein levels of smooth muscle contractile markers. These results suggested that γ isoform of CaMKII plays a significant role in smooth muscle differentiation of hASCs.

MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy

Directory of Open Access Journals (Sweden)

Guang-yu Zhang

2015-01-01

Full Text Available MicroRNA-9 (miR-9 has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9 + group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

Method translation and full metadata transfer from thermal to differential flow modulated comprehensive two dimensional gas chromatography: Profiling of suspected fragrance allergens.

Science.gov (United States)

Cordero, Chiara; Rubiolo, Patrizia; Reichenbach, Stephen E; Carretta, Andrea; Cobelli, Luigi; Giardina, Matthew; Bicchi, Carlo

2017-01-13

The possibility to transfer methods from thermal to differential-flow modulated comprehensive two-dimensional gas chromatographic (GC×GC) platforms is of high interest to improve GC×GC flexibility and increase the compatibility of results from different platforms. The principles of method translation are here applied to an original method, developed for a loop-type thermal modulated GC×GC-MS/FID system, suitable for quali-quantitative screening of suspected fragrance allergens. The analysis conditions were translated to a reverse-injection differential flow modulated platform (GC×2GC-MS/FID) with a dual-parallel secondary column and dual detection. The experimental results, for a model mixture of suspected volatile allergens and for raw fragrance mixtures of different composition, confirmed the feasibility of translating methods by preserving 1 D elution order, as well as the relative alignment of resulting 2D peak patterns. A correct translation produced several benefits including an effective transfer of metadata (compound names, MS fragmentation pattern, response factors) by automatic template transformation and matching from the original/reference method to its translated counterpart. The correct translation provided: (a) 2D pattern repeatability, (b) MS fragmentation pattern reliability for identity confirmation, and (c) comparable response factors and quantitation accuracy within a concentration range of three orders of magnitude. The adoption of a narrow bore (i.e. 0.1mm d c ) first-dimension column to operate under close-to-optimal conditions with the differential-flow modulation GC×GC platform was also advantageous in halving the total analysis under the translated conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Modulation of type II TGF-β receptor degradation by integrin-linked kinase.

Science.gov (United States)

Vi, Linda; Boo, Stellar; Sayedyahossein, Samar; Singh, Randeep K; McLean, Sarah; Di Guglielmo, Gianni M; Dagnino, Lina

2015-03-01

Cutaneous responses to injury, infection, and tumor formation involve the activation of resident dermal fibroblasts and subsequent transition to myofibroblasts. The key for induction of myofibroblast differentiation is the activation of transforming growth factor-β (TGF-β) receptors and stimulation of integrins and their associated proteins, including integrin-linked kinase (ILK). Cross-talk processes between TGF-β and ILK are crucial for myofibroblast formation, as ILK-deficient dermal fibroblasts exhibit impaired responses to TGF-β receptor stimulation. We now show that ILK associates with type II TGF-β receptors (TβRII) in ligand- and receptor kinase activity-independent manners. In cells with targeted Ilk gene inactivation, cellular levels of TβRII are decreased, through mechanisms that involve enhanced ubiquitination and proteasomal degradation. Partitioning of TGF-β receptors into membrane has been linked to proteasome-dependent receptor degradation. We found that interfering with membrane raft formation in ILK-deficient cells restored TβRII levels and signaling. These observations support a model whereby ILK functions in fibroblasts to direct TβRII away from degradative pathways during their differentiation into myofibroblasts.

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS Inner Detector

OpenAIRE

Poley, Luise; Bloch, Ingo; Edwards, Sam; Friedrich, Conrad; Gregor, Ingrid-Maria; Jones, Tim; Lacker, Heiko; Pyatt, Simon; Rehnisch, Laura; Sperlich, Dennis; Wilson, John

2015-01-01

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive between readout chips and circuit board is a silver epoxy gl...

Developmental Decline in the MicroRNA 199a (miR-199a)/miR-214 Cluster in Human Fetal Lung Promotes Type II Cell Differentiation by Upregulating Key Transcription Factors.

Science.gov (United States)

Mishra, Ritu; Benlhabib, Houda; Guo, Wei; Lerma Cervantes, Connie B; Mendelson, Carole R

2018-06-01

The major surfactant protein, SP-A (a product of the SFTPA gene), serves as a marker of type II pneumocyte differentiation and surfactant synthesis. SFTPA expression in cultured human fetal lung (HFL) epithelial cells is upregulated by hormones that increase cyclic AMP (cAMP) and activate TTF-1/NKX2.1 and NF-κB. To further define mechanisms for type II cell differentiation and induction of SP-A, we investigated roles of microRNAs (miRNAs). Using microarray to identify differentially expressed miRNAs in HFL epithelial cells during type II cell differentiation in culture, we observed that members of the miRNA 199a (miR-199a)/miR-214 cluster were significantly downregulated during differentiation. Validated and predicted targets of miR-199a-3p/miR-199a-5p and miR-214, which serve roles in type II cell differentiation (COX-2, NF-κB p50/p65, and CREB1), and the CREB1 target, C/EBPβ, were coordinately upregulated. Accordingly, overexpression of miR-199a-5p, miR-199a-3p, or miR-214 mimics in cultured HFL epithelial cells decreased COX-2, NF-κB p50/p65, CREB1, and C/EBPβ proteins, with an associated inhibition of SP-A expression. Interestingly, overexpression of the EMT factor, ZEB1, which declines during cAMP-induced type II cell differentiation, increased pri-miR-199a and reduced the expression of the targets NF-κB/p50 and COX-2. Collectively, these findings suggest that the developmental decline in miR-199a/miR-214 in HFL causes increased expression of critical targets that enhance type II cell differentiation and SP-A expression. Copyright © 2018 American Society for Microbiology.

Testbeam evaluation of silicon strip modules for ATLAS Phase - II Strip Tracker Upgrade

CERN Document Server

Blue, Andrew; The ATLAS collaboration; Ai, Xiaocong; Allport, Phillip; Arling, Jan-Hendrik; Atkin, Ryan Justin; Bruni, Lucrezia Stella; Carli, Ina; Casse, Gianluigi; Chen, Liejian; Chisholm, Andrew; Cormier, Kyle James Read; Cunningham, William Reilly; Dervan, Paul; Diez Cornell, Sergio; Dolezal, Zdenek; Dopke, Jens; Dreyer, Etienne; Dreyling-Eschweiler, Jan Linus Roderik; Escobar, Carlos; Fabiani, Veronica; Fadeyev, Vitaliy; Fernandez Tejero, Javier; Fleta Corral, Maria Celeste; Gallop, Bruce; Garcia-Argos, Carlos; Greenall, Ashley; Gregor, Ingrid-Maria; Greig, Graham George; Guescini, Francesco; Hara, Kazuhiko; Hauser, Marc Manuel; Huang, Yanping; Hunter, Robert Francis Holub; Keller, John; Klein, Christoph; Kodys, Peter; Koffas, Thomas; Kotek, Zdenek; Kroll, Jiri; Kuehn, Susanne; Lee, Steven Juhyung; Liu, Yi; Lohwasser, Kristin; Meszarosova, Lucia; Mikestikova, Marcela; Mi\\~nano Moya, Mercedes; Mori, Riccardo; Moser, Brian; Nikolopoulos, Konstantinos; Peschke, Richard; Pezzullo, Giuseppe; Phillips, Peter William; Poley, Anne-luise; Queitsch-Maitland, Michaela; Ravotti, Federico; Rodriguez Rodriguez, Daniel

2018-01-01

The planned HL-LHC (High Luminosity LHC) is being designed to maximise the physics potential of the LHC with 10 years of operation at instantaneous luminosities of \\mbox{$7.5\\times10^{34}\\;\\mathrm{cm}^{-2}\\mathrm{s}^{-1}$}. A consequence of this increased luminosity is the expected radiation damage requiring the tracking detectors to withstand hadron equivalences to over $1x10^{15}$ 1 MeV neutron equivalent per $cm^{2}$ in the ATLAS Strips system. The silicon strip tracker exploits the concept of modularity. Fast readout electronics, deploying 130nm CMOS front-end electronics are glued on top of a silicon sensor to make a module. The radiation hard n-in-p micro-strip sensors used have been developed by the ATLAS ITk Strip Sensor collaboration and produced by Hamamatsu Photonics. A series of tests were performed at the DESY-II test beam facility to investigate the detailed performance of a strip module with both 2.5cm and 5cm length strips before irradiation. The DURANTA telescope was used to obtain a pointing...

Advanced Sine Wave Modulation of Continuous Wave Laser System for Atmospheric CO2 Differential Absorption Measurements

Science.gov (United States)

Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.

2014-01-01

NASA Langley Research Center in collaboration with ITT Exelis have been experimenting with Continuous Wave (CW) laser absorption spectrometer (LAS) as a means of performing atmospheric CO2 column measurements from space to support the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission.Because range resolving Intensity Modulated (IM) CW lidar techniques presented here rely on matched filter correlations, autocorrelation properties without side lobes or other artifacts are highly desirable since the autocorrelation function is critical for the measurements of lidar return powers, laser path lengths, and CO2 column amounts. In this paper modulation techniques are investigated that improve autocorrelation properties. The modulation techniques investigated in this paper include sine waves modulated by maximum length (ML) sequences in various hardware configurations. A CW lidar system using sine waves modulated by ML pseudo random noise codes is described, which uses a time shifting approach to separate channels and make multiple, simultaneous online/offline differential absorption measurements. Unlike the pure ML sequence, this technique is useful in hardware that is band pass filtered as the IM sine wave carrier shifts the main power band. Both amplitude and Phase Shift Keying (PSK) modulated IM carriers are investigated that exibit perfect autocorrelation properties down to one cycle per code bit. In addition, a method is presented to bandwidth limit the ML sequence based on a Gaussian filter implemented in terms of Jacobi theta functions that does not seriously degrade the resolution or introduce side lobes as a means of reducing aliasing and IM carrier bandwidth.

Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2).

Science.gov (United States)

Xu, Zheng; Li, Weixin; Han, Jibo; Zou, Chunpeng; Huang, Weijian; Yu, Weihui; Shan, Xiaoou; Lum, Hazel; Li, Xiaokun; Liang, Guang

2017-03-21

Growing evidence indicates that angiotensin II (Ang II), a potent biologically active product of RAS, is a key regulator of renal inflammation and fibrosis. In this study, we tested the hypothesis that Ang II induces renal inflammatory injury and fibrosis through interaction with myeloid differentiation protein-2 (MD2), the accessory protein of toll-like receptor 4 (TLR4) of the immune system. Results indicated that in MD2 -/- mice, the Ang II-induced renal fibrosis, inflammation and kidney dysfunction were significantly reduced compared to control Ang II-infused wild-type mice. Similarly, in the presence of small molecule MD2 specific inhibitor L6H21 or siRNA-MD2, the Ang II-induced increases of pro-fibrotic and pro-inflammatory molecules were prevented in tubular NRK-52E cells. MD2 blockade also inhibited activation of NF-κB and ERK. Moreover, MD2 blockade prevented the Ang II-stimulated formation of the MD2/TLR4/MyD88 signaling complex, as well as the increased surface binding of Ang II in NRK-52E cells. In addition, Ang II directly bound recombinant MD2 protein, rather than TLR4 protein. We conclude that MD2 is a significant contributor in the Ang II-induced kidney inflammatory injury in chronic renal diseases. Furthermore, MD2 inhibition could be a new and important therapeutic strategy for preventing progression of chronic renal diseases.

Neuronal Differentiation Modulated by Polymeric Membrane Properties.

Science.gov (United States)

Morelli, Sabrina; Piscioneri, Antonella; Drioli, Enrico; De Bartolo, Loredana

2017-01-01

In this study, different collagen-blend membranes were successfully constructed by blending collagen with chitosan (CHT) or poly(lactic-co-glycolic acid) (PLGA) to enhance their properties and thus create new biofunctional materials with great potential use for neuronal tissue engineering and regeneration. Collagen blending strongly affected membrane properties in the following ways: (i) it improved the surface hydrophilicity of both pure CHT and PLGA membranes, (ii) it reduced the stiffness of CHT membranes, but (iii) it did not modify the good mechanical properties of PLGA membranes. Then, we investigated the effect of the different collagen concentrations on the neuronal behavior of the membranes developed. Morphological observations, immunocytochemistry, and morphometric measures demonstrated that the membranes developed, especially CHT/Col30, PLGA, and PLGA/Col1, provided suitable microenvironments for neuronal growth owing to their enhanced properties. The most consistent neuronal differentiation was obtained in neurons cultured on PLGA-based membranes, where a well-developed neuronal network was achieved due to their improved mechanical properties. Our findings suggest that tensile strength and elongation at break are key material parameters that have potential influence on both axonal elongation and neuronal structure and organization, which are of fundamental importance for the maintenance of efficient neuronal growth. Hence, our study has provided new insights regarding the effects of membrane mechanical properties on neuronal behavior, and thus it may help to design and improve novel instructive biomaterials for neuronal tissue engineering. © 2017 S. Karger AG, Basel.

Interferon-γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO.

Directory of Open Access Journals (Sweden)

Juliana Croitoru-Lamoury

Full Text Available The kynurenine pathway (KP of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO and IDO2, that it is highly regulated by type I (IFN-β and II interferons (IFN-γ, and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.

SOLAR CYCLE VARIABILITY AND SURFACE DIFFERENTIAL ROTATION FROM Ca II K-LINE TIME SERIES DATA

Energy Technology Data Exchange (ETDEWEB)

Scargle, Jeffrey D.; Worden, Simon P. [NASA Ames Research Center, Moffett Field, CA, 94035 (United States); Keil, Stephen L. [National Solar Observatory, P.O. Box 57, Sunspot, NM 88349 (United States)

2013-07-01

Analysis of over 36 yr of time series data from the NSO/AFRL/Sac Peak K-line monitoring program elucidates 5 components of the variation of the 7 measured chromospheric parameters: (a) the solar cycle (period {approx} 11 yr), (b) quasi-periodic variations (periods {approx} 100 days), (c) a broadband stochastic process (wide range of periods), (d) rotational modulation, and (e) random observational errors, independent of (a)-(d). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these parameters. Time-frequency analysis illuminates periodic and quasi-periodic signals, details of frequency modulation due to differential rotation, and in particular elucidates the rather complex harmonic structure (a) and (b) at timescales in the range {approx}0.1-10 yr. These results using only full-disk data suggest that similar analyses will be useful for detecting and characterizing differential rotation in stars from stellar light curves such as those being produced by NASA's Kepler observatory. Component (c) consists of variations over a range of timescales, in the manner of a 1/f random process with a power-law slope index that varies in a systematic way. A time-dependent Wilson-Bappu effect appears to be present in the solar cycle variations (a), but not in the more rapid variations of the stochastic process (c). Component (d) characterizes differential rotation of the active regions. Component (e) is of course not characteristic of solar variability, but the fact that the observational errors are quite small greatly facilitates the analysis of the other components. The data analyzed in this paper can be found at the National Solar Observatory Web site http://nsosp.nso.edu/cak{sub m}on/, or by file transfer protocol at ftp://ftp.nso.edu/idl/cak.parameters.

Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.

Science.gov (United States)

Zhu, Wanqu; Yao, Xiao; Liang, Yan; Liang, Dan; Song, Lu; Jing, Naihe; Li, Jinsong; Wang, Gang

2015-02-01

Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. © 2015. Published by The Company of Biologists Ltd.

An absolute calibration method of an ethyl alcohol biosensor based on wavelength-modulated differential photothermal radiometry.

Science.gov (United States)

Liu, Yi Jun; Mandelis, Andreas; Guo, Xinxin

2015-11-01

In this work, laser-based wavelength-modulated differential photothermal radiometry (WM-DPTR) is applied to develop a non-invasive in-vehicle alcohol biosensor. WM-DPTR features unprecedented ethanol-specificity and sensitivity by suppressing baseline variations through a differential measurement near the peak and baseline of the mid-infrared ethanol absorption spectrum. Biosensor signal calibration curves are obtained from WM-DPTR theory and from measurements in human blood serum and ethanol solutions diffused from skin. The results demonstrate that the WM-DPTR-based calibrated alcohol biosensor can achieve high precision and accuracy for the ethanol concentration range of 0-100 mg/dl. The high-performance alcohol biosensor can be incorporated into ignition interlocks that could be fitted as a universal accessory in vehicles in an effort to reduce incidents of drinking and driving.

Spinal cord activation differentially modulates ischaemic electrical responses to different stressors in canine ventricles.

Science.gov (United States)

Cardinal, René; Ardell, Jeffrey L; Linderoth, Bengt; Vermeulen, Michel; Foreman, Robert D; Armour, J Andrew

2004-03-31

Spinal cord stimulation (SCS) represents an acceptable treatment modality for patients with chronic angina pectoris refractory to standard therapy, but its mechanism of action remains unclear. To develop an experimental paradigm to study this issue, ameroid (AM) constrictors were implanted around the left circumflex coronary artery (LCx) in canines. Six weeks later, unipolar electrograms were recorded from 191 sites in the LCx territory in the open-chest, anesthetized state under basal pacing at 150 beats/min. We investigated the effect of SCS on ST segment displacements induced in the collateral-dependent myocardium in response to two stressors: (i) transient bouts of rapid ventricular pacing (TRP: 240/min for 1 min) and (ii) angiotensin II administered to right atrial neurons via their coronary artery blood supply. ST segment responses to TRP consisted of ST segment elevation in central areas of the LCx territory and ST depression at more peripheral areas. Such responses were unchanged when TRP was applied under SCS. Shortening of repolarization intervals in the metabolically compromised myocardium in response to TRP was also unaffected by SCS. In contrast, ST segment responses to intracoronary angiotensin II, which consisted of increased ST elevation, were attenuated by SCS in 6/8 preparations. The modulator effects of SCS were greatest at sites at which the greatest responses to angiotensin II occurred in the absence of SCS. These data indicate that spinal cord stimulation may attenuate the deleterious effects that stressors exert on the myocardium with reduced coronary reserve, particularly stressors associated with chemical activation of the intrinsic cardiac nervous system. Copyright 2004 Elsevier B.V.

ATLAS ITk Short Strip Prototype Module with Integrated DCDC Powering and Control Phase II Upgrade of the ATLAS Inner Tracker detector at the HL - LHC

CERN Document Server

Greenall, Ashley; The ATLAS collaboration

2017-01-01

The prototype Barrel module design, for the Phase II upgrade of the of the new Inner Tracker (ITk) detector at the LHC, has adopted an integrated low mass assembly featuring single-sided flexible circuits, with readout ASICs, glued to the silicon strip sensor. Further integration has been achieved by the attachment of module DCDC powering, HV sensor biasing switch and autonomous monitoring and control to the sensor. This low mass, integrated module approach benefits further in a reduced width stave structure to which the modules are attached. The results of preliminary electrical tests of such an integrated module will be presented.

Sequential attack with intensity modulation on the differential-phase-shift quantum-key-distribution protocol

International Nuclear Information System (INIS)

Tsurumaru, Toyohiro

2007-01-01

In this paper, we discuss the security of the differential-phase-shift quantum-key-distribution (DPSQKD) protocol by introducing an improved version of the so-called sequential attack, which was originally discussed by Waks et al. [Phys. Rev. A 73, 012344 (2006)]. Our attack differs from the original form of the sequential attack in that the attacker Eve modulates not only the phases but also the amplitude in the superposition of the single-photon states which she sends to the receiver. Concentrating especially on the 'discretized Gaussian' intensity modulation, we show that our attack is more effective than the individual attack, which had been the best attack up to present. As a result of this, the recent experiment with communication distance of 100 km reported by Diamanti et al. [Opt. Express 14, 13073 (2006)] turns out to be insecure. Moreover, it can be shown that in a practical experimental setup which is commonly used today, the communication distance achievable by the DPSQKD protocol is less than 95 km

Differential Amplitude Pulse-Position Modulation for Indoor Wireless Optical Communications

Directory of Open Access Journals (Sweden)

Sethakaset Ubolthip

2005-01-01

Full Text Available We propose a novel differential amplitude pulse-position modulation (DAPPM for indoor optical wireless communications. DAPPM yields advantages over PPM, DPPM, and DH-PIM in terms of bandwidth requirements, capacity, and peak-to-average power ratio (PAPR. The performance of a DAPPM system with an unequalized receiver is examined over nondispersive and dispersive channels. DAPPM can provide better bandwidth and/or power efficiency than PAM, PPM, DPPM, and DH-PIM depending on the number of amplitude levels and the maximum length of a symbol. We also show that, given the same maximum length, DAPPM has better bandwidth efficiency but requires about and more power than PPM and DPPM, respectively, at high bit rates over a dispersive channel. Conversely, DAPPM requires less power than DH-PIM . When the number of bits per symbol is the same, PAM requires more power, and DH-PIM less power, than DAPPM. Finally, it is shown that the performance of DAPPM can be improved with MLSD, chip-rate DFE, and multichip-rate DFE.

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS Inner Detector

CERN Document Server

INSPIRE-00407830; Bloch, Ingo; Edwards, Sam; Friedrich, Conrad; Gregor, Ingrid M.; Jones, T; Lacker, Heiko; Pyatt, Simon; Rehnisch, Laura; Sperlich, Dennis; Wilson, John

2016-05-24

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). This glue has several disadvantages, which motivated the search for an alternative. This paper presents a study concerning the use of six ultra-violet (UV) cure glues and a glue pad for use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, the thermal conduction and shear strength, thermal cycling, radiation hardness, corrosion resistance and shear strength tests. These investigatio...

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS inner detector

International Nuclear Information System (INIS)

Poley, Luise; Bloch, Ingo; Edwards, Sam

2016-04-01

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). This glue has several disadvantages, which motivated the search for an alternative. This paper presents a study concerning the use of six ultra-violet (UV) cure glues and a glue pad for use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, the thermal conduction and shear strength, thermal cycling, radiation hardness, corrosion resistance and shear strength tests. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives. Results from electrical tests of first prototype modules constructed using these glues are presented.

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS inner detector

Energy Technology Data Exchange (ETDEWEB)

Poley, Luise [DESY, Zeuthen (Germany); Humboldt Univ. Berlin (Germany); Bloch, Ingo [DESY, Zeuthen (Germany); Edwards, Sam [Birmingham Univ. (United Kingdom); and others

2016-04-15

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). This glue has several disadvantages, which motivated the search for an alternative. This paper presents a study concerning the use of six ultra-violet (UV) cure glues and a glue pad for use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, the thermal conduction and shear strength, thermal cycling, radiation hardness, corrosion resistance and shear strength tests. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives. Results from electrical tests of first prototype modules constructed using these glues are presented.

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS Inner Detector

Science.gov (United States)

Poley, L.; Bloch, I.; Edwards, S.; Friedrich, C.; Gregor, I.-M.; Jones, T.; Lacker, H.; Pyatt, S.; Rehnisch, L.; Sperlich, D.; Wilson, J.

2016-05-01

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive used initially between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). However, this glue has several disadvantages, which motivated the search for an alternative. This paper presents a study of six ultra-violet (UV) cure glues and a glue pad for possible use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, thermal conduction and shear strength. Samples were thermally cycled, radiation hardness and corrosion resistance were also determined. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives than silver loaded glue. Results from electrical tests of first prototype modules constructed using these glues are presented.

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS Inner Detector

International Nuclear Information System (INIS)

Poley, L.; Bloch, I.; Friedrich, C.; Gregor, I.-M.; Edwards, S.; Pyatt, S.; Wilson, J.; Jones, T.; Lacker, H.; Rehnisch, L.; Sperlich, D.

2016-01-01

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive used initially between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). However, this glue has several disadvantages, which motivated the search for an alternative. This paper presents a study of six ultra-violet (UV) cure glues and a glue pad for possible use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, thermal conduction and shear strength. Samples were thermally cycled, radiation hardness and corrosion resistance were also determined. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives than silver loaded glue. Results from electrical tests of first prototype modules constructed using these glues are presented.

Magnesium sulfate differentially modulates fetal membrane inflammation in a time-dependent manner.

Science.gov (United States)

Cross, Sarah N; Nelson, Rachel A; Potter, Julie A; Norwitz, Errol R; Abrahams, Vikki M

2018-04-30

Chorioamnionitis and infection-associated inflammation are major causes of preterm birth. Magnesium sulfate (MgSO 4 ) is widely used in obstetrics as a tocolytic; however, its mechanism of action is unclear. This study sought to investigate how MgSO 4 modulates infection-associated inflammation in fetal membranes (FMs), and whether the response was time dependent. Human FM explants were treated with or without bacterial lipopolysaccharide (LPS); with or without MgSO 4 added either: 1 hour before LPS; at the same time as LPS; 1 hour post-LPS; or 2 hours post-LPS. Explants were also treated with or without viral dsRNA and LPS, alone or in combination; and MgSO 4 added 1 hour post-LPS After 24 hours, supernatants were measured for cytokines/chemokines; and tissue lysates measured for caspase-1 activity. Lipopolysaccharide-induced FM inflammation by upregulating the secretion of a number of inflammatory cytokines/chemokines. Magnesium sulfate administered 1-hour post-LPS inhibited FM secretion of IL-1β, IL-6, G-CSF, RANTES, and TNFα. Magnesium sulfate administered 2 hours post-LPS augmented FM secretion of these factors as well as IL-8, IFNγ, VEGF, GROα and IP-10. Magnesium sulfate delivered 1- hour post-LPS inhibited LPS-induced caspase-1 activity, and inhibited the augmented IL-1β response triggered by combination viral dsRNA and LPS. Magnesium sulfate differentially modulates LPS-induced FM inflammation in a time-dependent manner, in part through its modulation of caspase-1 activity. Thus, the timing of MgSO 4 administration may be critical in optimizing its anti-inflammatory effects in the clinical setting. MgSO 4 might also be useful at preventing FM inflammation triggered by a polymicrobial viral-bacterial infection. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

Directory of Open Access Journals (Sweden)

Usha Bughani

Full Text Available CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1 specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17 have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab'2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an

Oxytocin differentially modulates pavlovian cue and context fear acquisition.

Science.gov (United States)

Cavalli, Juliana; Ruttorf, Michaela; Pahi, Mario Rosero; Zidda, Francesca; Flor, Herta; Nees, Frauke

2017-06-01

Fear acquisition and extinction have been demonstrated as core mechanisms for the development and maintenance of mental disorders, with different contributions of processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a prominent role in this context, as it has been shown to affect fear learning. However, investigations have focused on cue conditioning, and fear extinction. Its differential role for cue and context fear acquisition is still not known. In a randomized, double-blind, placebo (PLC)-controlled design, we administered an intranasal dose of OXT or PLC before the acquisition of cue and context fear conditioning in healthy individuals (n = 52), and assessed brain responses, skin conductance responses and self-reports (valence/arousal/contingency). OXT compared with PLC significantly induced decreased responses in the nucleus accumbens during early cue and context acquisition, and decreased responses of the anterior cingulate cortex and insula during early as well as increased hippocampal response during late context, but not cue acquisition. The OXT group additionally showed significantly higher arousal in late cue and context acquisition. OXT modulates various aspects of cue and context conditioning, which is relevant from a mechanism-based perspective and might have implications for the treatment of fear and anxiety. © The Author (2017). Published by Oxford University Press.

A comparison of volumetric modulated arc therapy and sliding-window intensity-modulated radiotherapy in the treatment of Stage I-II nasal natural killer/T-cell lymphoma

Energy Technology Data Exchange (ETDEWEB)

Liu, Xianfeng [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China); Yang, Yong [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Jin, Fu; He, Yanan; Zhong, Mingsong; Luo, Huanli; Qiu, Da; Li, Chao; Yang, Han; He, Guanglei [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China); Wang, Ying, E-mail: zjajf@126.com [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China)

2016-04-01

This article is aimed to compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL). Ten patients with Stage I-II NNKTL treated with IMRT were replanned with VMAT (2 arcs). The prescribed dose of the planning target volume (PTV) was 50 Gy in 25 fractions. The VMAT plans with the Anisotropic Analytical Algorithm (Version 8.6.15) were based on an Eclipse treatment planning system; the monitor units (MUs) and treatment time (T) were scored to measure the expected treatment efficiency. All the 10 patients under the study were subject to comparisons regarding the quality of target coverage, the efficiency of delivery, and the exposure of normal adjacent organs at risk (OARs). The study shows that VMAT was associated with a better conformal index (CI) and homogeneity index (HI) (both p < 0.05) but slightly higher dose to OARs than IMRT. The MUs with VMAT (650.80 ± 24.59) were fewer than with IMRT (1300.10 ± 57.12) (relative reduction of 49.94%, p = 0.00) when using 2-Gy dose fractions. The treatment time with VMAT (3.20 ± 0.02 minutes) was shorter than with IMRT (7.38 ± 0.18 minutes) (relative reduction of 56.64%, p = 0.00). We found that VMAT and IMRT both provide satisfactory target dosimetric coverage and OARs sparing clinically. Likely to deliver a bit higher dose to OARs, VMAT in comparison with IMRT, is still a better choice for treatment of patients with Stage I-II NNKTL, thanks to better dose distribution, fewer MUs, and shorter delivery time.

Developing a service-learning module for oral health: A needs assessment

Directory of Open Access Journals (Sweden)

R Ebrahim

2017-03-01

Full Text Available Background. Service learning (SL as a pedagogy in higher education must be differentiated from other services with a primarily philanthropic intent. Dental therapy and oral hygiene students at Sefako Makgatho Health Sciences University, School of Oral Health Sciences, Pretoria, South Africa visit community sites during their 2nd year of study. However, the current curricula would need restructuring for alignment with the espoused pedagogy and standards of SL. Such an SL curriculum design would thus allow for the provision of meaningful services to communities as an integral component of these programmes. Objective. To explore (i perceptions of 2nd-year oral health students; and (ii opinions of academics with regard to the need for an SL module. Methods. Purposive sampling was used to conduct two focus group discussions with academics involved in curriculum development (n=11 and students who had previous exposure to communities (n=10. A survey containing open-ended questions was completed by 9 academics, who would implement the proposed SL module. Frequencies were calculated and data from the open questions were analysed for emergent themes. Results. Most academics (89%, n=8 indicated that working effectively with others as members of a team and developing cultural sensitivity were achievable from an SL module. Two themes emerged from the focus groups, i.e. (i enhanced teaching and learning – students could apply theoretical and clinical training in an authentic setting; and (ii standardisation of training – an SL module would ensure consistency when engaging with communities. Conclusion. The needs assessment was valuable to inform the development and implementation of the SL module.

Small-signal modulation and differential gain of red-emitting (λ = 630 nm) InGaN/GaN quantum dot lasers

Energy Technology Data Exchange (ETDEWEB)

Frost, Thomas; Banerjee, Animesh; Bhattacharya, Pallab, E-mail: pkb@eecs.umich.edu [Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109-2122 (United States)

2013-11-18

We report small-signal modulation bandwidth and differential gain measurements of a ridge waveguide In{sub 0.4}Ga{sub 0.6}N/GaN quantum dot laser grown by molecular beam epitaxy. The laser peak emission is at λ = 630 nm. The −3 dB bandwidth of an 800 μm long device was measured to be 2.4 GHz at 250 mA under pulsed biasing, demonstrating the possibility of high-speed operation of these devices. The differential gain was measured to be 5.3 × 10{sup −17} cm{sup 2}, and a gain compression factor of 2.87 × 10{sup −17} cm{sup 3} is also derived from the small-signal modulation response.

Compact Energy Conversion Module, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — This STTR project delivers a compact vibration-based Energy Conversion Module (ECM) that powers sensors for purposes such as structural health monitoring (SHM). NASA...

Developing a servicelearning module for oral health: A needs assessment

Directory of Open Access Journals (Sweden)

R Ebrahim

2017-03-01

Full Text Available Background. Service learning (SL as a pedagogy in higher education must be differentiated from other services with a primarily philanthropic intent. Dental therapy and oral hygiene students at Sefako Makgatho Health Sciences University, School of Oral Health Sciences, Pretoria, South Africa visit community sites during their 2nd year of study. However, the current curricula would need restructuring for alignment with the espoused pedagogy and standards of SL. Such an SL curriculum design would thus allow for the provision of meaningful services to communities as an integral component of these programmes.Objective. To explore (i perceptions of 2nd-year oral health students; and (ii opinions of academics with regard to the need for an SL module.Methods. Purposive sampling was used to conduct two focus group discussions with academics involved in curriculum development (n=11 and students who had previous exposure to communities (n=10. A survey containing open-ended questions was completed by 9 academics, who would implement the proposed SL module. Frequencies were calculated and data from the open questions were analysed for emergent themes.Results. Most academics (89%, n=8 indicated that working effectively with others as members of a team and developing cultural sensitivity were achievable from an SL module. Two themes emerged from the focus groups, i.e. (i enhanced teaching and learning – students could apply theoretical and clinical training in an authentic setting; and (ii standardisation of training – an SL module would ensure consistency when engaging with communities.Conclusion. The needs assessment was valuable to inform the development and implementation of the SL module.

An accurate modelling of the two-diode model of PV module using a hybrid solution based on differential evolution

International Nuclear Information System (INIS)

Chin, Vun Jack; Salam, Zainal; Ishaque, Kashif

2016-01-01

Highlights: • An accurate computational method for the two-diode model of PV module is proposed. • The hybrid method employs analytical equations and Differential Evolution (DE). • I PV , I o1 , and R p are computed analytically, while a 1 , a 2 , I o2 and R s are optimized. • This allows the model parameters to be computed without using costly assumptions. - Abstract: This paper proposes an accurate computational technique for the two-diode model of PV module. Unlike previous methods, it does not rely on assumptions that cause the accuracy to be compromised. The key to this improvement is the implementation of a hybrid solution, i.e. by incorporating the analytical method with the differential evolution (DE) optimization technique. Three parameters, i.e. I PV , I o1 , and R p are computed analytically, while the remaining, a 1 , a 2 , I o2 and R s are optimized using the DE. To validate its accuracy, the proposed method is tested on three PV modules of different technologies: mono-crystalline, poly-crystalline and thin film. Furthermore, its performance is evaluated against two popular computational methods for the two-diode model. The proposed method is found to exhibit superior accuracy for the variation in irradiance and temperature for all module types. In particular, the improvement in accuracy is evident at low irradiance conditions; the root-mean-square error is one order of magnitude lower than that of the other methods. In addition, the values of the model parameters are consistent with the physics of PV cell. It is envisaged that the method can be very useful for PV simulation, in which accuracy of the model is of prime concern.

Differential analysis of matrix convex functions II

DEFF Research Database (Denmark)

Hansen, Frank; Tomiyama, Jun

2009-01-01

We continue the analysis in [F. Hansen, and J. Tomiyama, Differential analysis of matrix convex functions. Linear Algebra Appl., 420:102--116, 2007] of matrix convex functions of a fixed order defined in a real interval by differential methods as opposed to the characterization in terms of divided...

Pitavastatin Differentially Modulates MicroRNA-Associated Cholesterol Transport Proteins in Macrophages.

Directory of Open Access Journals (Sweden)

Haijun Zhang

Full Text Available There is emerging evidence identifying microRNAs (miRNAs as mediators of statin-induced cholesterol efflux, notably through the ATP-binding cassette transporter A1 (ABCA1 in macrophages. The objective of this study was to assess the impact of an HMG-CoA reductase inhibitor, pitavastatin, on macrophage miRNAs in the presence and absence of oxidized-LDL, a hallmark of a pro-atherogenic milieu. Treatment of human THP-1 cells with pitavastatin prevented the oxLDL-mediated suppression of miR-33a, -33b and -758 mRNA in these cells, an effect which was not uniquely attributable to induction of SREBP2. Induction of ABCA1 mRNA and protein by oxLDL was inhibited (30% by pitavastatin, while oxLDL or pitavastatin alone significantly induced and repressed ABCA1 expression, respectively. These findings are consistent with previous reports in macrophages. miRNA profiling was also performed using a miRNA array. We identified specific miRNAs which were up-regulated (122 and down-regulated (107 in THP-1 cells treated with oxLDL plus pitavastatin versus oxLDL alone, indicating distinct regulatory networks in these cells. Moreover, several of the differentially expressed miRNAs identified are functionally associated with cholesterol trafficking (six miRNAs in cells treated with oxLDL versus oxLDL plus pitavastatin. Our findings indicate that pitavastatin can differentially modulate miRNA in the presence of oxLDL; and, our results provide evidence that the net effect on cholesterol homeostasis is mediated by a network of miRNAs.

Epac is required for exogenous and endogenous stimulation of adenosine A2B receptor for inhibition of angiotensin II-induced collagen synthesis and myofibroblast differentiation.

Science.gov (United States)

Phosri, Sarawuth; Bunrukchai, Kwanchai; Parichatikanond, Warisara; Sato, Vilasinee H; Mangmool, Supachoke

2018-01-10

Angiotensin II (Ang II) plays an important role on the pathogenesis of cardiac fibrosis. Prolong and overstimulation of angiotensin II type 1 receptor with Ang II-induced collagen synthesis and myofibroblast differentiation in cardiac fibroblasts, leading to cardiac fibrosis. Although adenosine and its analogues are known to have cardioprotective effects, the mechanistic by which adenosine A 2 receptors (A 2 Rs) inhibit Ang II-induced cardiac fibrosis is not clearly understood. In the present study, we examined the effects of exogenous adenosine and endogenous adenosine on Ang II-induced collagen and myofibroblast differentiation determined by α-smooth muscle action (α-SMA) overexpression and their underlying signal transduction. Elevation of endogenous adenosine levels resulted in the inhibition of Ang II-induced collagen type I and III and α-SMA synthesis in cardiac fibroblasts. Moreover, treatment with exogenous adenosine which selectively stimulated A 2 Rs also suppressed Ang II-induced collagen synthesis and α-SMA production. These antifibrotic effects of both endogenous and exogenous adenosines are mediated through the A 2B receptor (A 2B R) subtype. Stimulation of A 2B R exhibited antifibrotic effects via the cAMP-dependent and Epac-dependent pathways. Our results provide new mechanistic insights regarding the role for cAMP and Epac on A 2B R-mediated antifibrotic effects. Thus, A 2B R is one of the potential therapeutic targets against cardiac fibrosis.

Resolving glass transition in Te-based phase-change materials by modulated differential scanning calorimetry

Science.gov (United States)

Chen, Yimin; Mu, Sen; Wang, Guoxiang; Shen, Xiang; Wang, Junqiang; Dai, Shixun; Xu, Tiefeng; Nie, Qiuhua; Wang, Rongping

2017-10-01

Glass transitions of Te-based phase-change materials (PCMs) were studied by modulated differential scanning calorimetry. It was found that both Ge2Sb2Te5 and GeTe are marginal glass formers with ΔT (= T x - T g) less than 2.1 °C when the heating rate is below 3 °C min-1. The fragilities of Ge2Sb2Te5 and GeTe can be estimated as 46.0 and 39.7, respectively, around the glass transition temperature, implying that a fragile-to-strong transition would be presented in such Te-based PCMs. The above results provide direct experimental evidence to support the investigation of crystallization kinetics in supercooled liquid PCMs.

Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

Directory of Open Access Journals (Sweden)

Itsuro Kazama

2013-04-01

Full Text Available Background/Aims: Salicylate and chlorpromazine exert differential effects on the chemokine release from mast cells. Since these drugs are amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membranes, they would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate and chlorpromazine on the membrane capacitance (Cm during exocytosis in rat peritoneal mast cells. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on plasma membrane deformation of the cells. Results: Salicylate dramatically accelerated the GTP-γ-S-induced increase in the Cm immediately after its application, whereas chlorpromazine significantly suppressed the increase. Treatment with salicylate increased the trapping of the dye on the cell surface, while treatment with chlorpromazine completely washed it out, indicating that both drugs induced membrane surface deformation in mast cells. Conclusion: This study demonstrated for the first time that membrane amphipaths, such as salicylate and chlorpromazine, may oppositely modulate the process of exocytosis in mast cells, as detected by the changes in the Cm. The plasma membrane deformation induced by the drugs was thought to be responsible for their differential effects.

Mechanisms of masked evaluative priming: task sets modulate behavioral and electrophysiological priming for picture and words differentially.

Science.gov (United States)

Kiefer, Markus; Liegel, Nathalie; Zovko, Monika; Wentura, Dirk

2017-04-01

Research with the evaluative priming paradigm has shown that affective evaluation processes reliably influence cognition and behavior, even when triggered outside awareness. However, the precise mechanisms underlying such subliminal evaluative priming effects, response activation vs semantic processing, are matter of a debate. In this study, we determined the relative contribution of semantic processing and response activation to masked evaluative priming with pictures and words. To this end, we investigated the modulation of masked pictorial vs verbal priming by previously activated perceptual vs semantic task sets and assessed the electrophysiological correlates of priming using event-related potential (ERP) recordings. Behavioral and electrophysiological effects showed a differential modulation of pictorial and verbal subliminal priming by previously activated task sets: Pictorial priming was only observed during the perceptual but not during the semantic task set. Verbal priming, in contrast, was found when either task set was activated. Furthermore, only verbal priming was associated with a modulation of the N400 ERP component, an index of semantic processing, whereas a priming-related modulation of earlier ERPs, indexing visuo-motor S-R activation, was found for both picture and words. The results thus demonstrate that different neuro-cognitive processes contribute to unconscious evaluative priming depending on the stimulus format. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin-Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia.

Science.gov (United States)

Cabrera-Pastor, Andrea; Llansola, Marta; Felipo, Vicente

2016-12-21

Extracellular protein kinases, including cAMP-dependent protein kinase (PKA), modulate neuronal functions including N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation. NMDA receptor activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO), which activates guanylate cyclase, increasing cGMP, which is released to the extracellular fluid, allowing analysis of this glutamate-NO-cGMP pathway in vivo by microdialysis. The function of this pathway is impaired in hyperammonemic rats. The aims of this work were to assess (1) whether the glutamate-NO-cGMP pathway is modulated in cerebellum in vivo by an extracellular PKA, (2) the role of phosphorylation and activity of calcium/calmodulin-dependent protein kinase II (CaMKII) and NOS in the pathway modulation by extracellular PKA, and (3) whether the effects are different in hyperammonemic and control rats. The pathway was analyzed by in vivo microdialysis. The role of extracellular PKA was analyzed by inhibiting it with a membrane-impermeable inhibitor. The mechanisms involved were analyzed in freshly isolated cerebellar slices from control and hyperammonemic rats. In control rats, inhibiting extracellular PKA reduces the glutamate-NO-cGMP pathway function in vivo. This is due to reduction of CaMKII phosphorylation and activity, which reduces NOS phosphorylation at Ser1417 and NOS activity, resulting in reduced guanylate cyclase activation and cGMP formation. In hyperammonemic rats, under basal conditions, CaMKII phosphorylation and activity are increased, increasing NOS phosphorylation at Ser847, which reduces NOS activity, guanylate cyclase activation, and cGMP. Inhibiting extracellular PKA in hyperammonemic rats normalizes CaMKII phosphorylation and activity, NOS phosphorylation, NOS activity, and cGMP, restoring normal function of the pathway.

Usher syndrome clinical types I and II: could ocular symptoms and signs differentiate between the two types?

Science.gov (United States)

Tsilou, Ekaterini T; Rubin, Benjamin I; Caruso, Rafael C; Reed, George F; Pikus, Anita; Hejtmancik, James F; Iwata, Fumino; Redman, Joy B; Kaiser-Kupfer, Muriel I

2002-04-01

Usher syndrome types I and II are clinical syndromes with substantial genetic and clinical heterogeneity. We undertook the current study in order to identify ocular symptoms and signs that could differentiate between the two types. Sixty-seven patients with Usher syndrome were evaluated. Based on audiologic and vestibular findings, patients were classified as either Usher type I or II. The severity of the ocular signs and symptoms present in each type were compared. Visual acuity, visual field area, electroretinographic amplitude, incidence of cataract and macular lesions were not significantly different between Usher types I and II. However, the ages when night blindness was perceived and retinitis pigmentosa was diagnosed differed significantly between the two types. There seems to be some overlap between types I and II of Usher syndrome in regard to the ophthalmologic findings. However, night blindness appears earlier in Usher type I (although the difference in age of appearance appears to be less dramatic than previously assumed). Molecular elucidation of Usher syndrome may serve as a key to understanding these differences and, perhaps, provide a better tool for use in clinical diagnosis, prognosis and genetic counseling.

Differential sensor in front photopyroelectric technique: II. Experimental

International Nuclear Information System (INIS)

Ivanov, R; Moreno, I; Araujo-Andrade, C; MarIn, E; Cruz-Orea, A; Pichardo-Molina, J L

2009-01-01

We describe the differential cell design and the experimental (optical and electronic) setup for the differential front photopyroelectric technique, whose theory has been developed in the first part of this paper (Ivanov et al 2008 J. Phys. D: Appl. Phys. 41 085106). We will show first how the direct (non-differential) front photopyroelectric theory described in our previous paper reproduces well the experimental results. The usefulness of the differential technique is demonstrated by means of experimental measurements of the thermal effusivity in binary ethanol-water and glycerol-water mixtures, based on a theoretical methodology that simplifies the measurement procedure and diminishes the experimental uncertainty.

Differential sensor in front photopyroelectric technique: II. Experimental

Energy Technology Data Exchange (ETDEWEB)

Ivanov, R; Moreno, I; Araujo-Andrade, C [Facultad de Fisica, Universidad Autonoma de Zacatecas, Calz. Solidaridad Esquina Paseo de la Bufa s/n, CP 98060, Zacatecas, Zac. (Mexico); MarIn, E [Centro de Investigacion en Ciencia Aplicada y TecnologIa Avanzada-Instituto Politecnico Nacional, Legaria 694, Col. Irrigacion, CP 11500, Mexico D.F. (Mexico); Cruz-Orea, A [Departamento de Fisica, CINVESTAV-IPN, Av. IPN No. 2508, Col. San Pedro Zacatenco, CP 07360, Mexico D.F. (Mexico); Pichardo-Molina, J L, E-mail: rumen@fisica.uaz.edu.m [Centro de Investigaciones en Optica, Loma del Bosque 115, Loma del Campestre, CP 37150, Leon, Guanajuato (Mexico)

2009-06-21

We describe the differential cell design and the experimental (optical and electronic) setup for the differential front photopyroelectric technique, whose theory has been developed in the first part of this paper (Ivanov et al 2008 J. Phys. D: Appl. Phys. 41 085106). We will show first how the direct (non-differential) front photopyroelectric theory described in our previous paper reproduces well the experimental results. The usefulness of the differential technique is demonstrated by means of experimental measurements of the thermal effusivity in binary ethanol-water and glycerol-water mixtures, based on a theoretical methodology that simplifies the measurement procedure and diminishes the experimental uncertainty.

Polarized differential-phase laser scanning microscope

International Nuclear Information System (INIS)

Chou Chien; Lyu, C.-W.; Peng, L.-C.

2001-01-01

A polarized differential-phase laser scanning microscope, which combines a polarized optical heterodyne Mach-Zehnder interferometer and a differential amplifier to scan the topographic image of a surface, is proposed. In the experiment the differential amplifier, which acts as a PM-AM converter, in the experiment, converting phase modulation (PM) into amplitude modulation (AM). Then a novel, to our knowledge, phase demodulator was proposed and implemented for the differential-phase laser scanning microscope. An optical grating (1800 lp/mm) was imaged. The lateral and the depth resolutions of the imaging system were 0.5 μm and 1 nm, respectively. The detection accuracy, which was limited by the reflectivity variation of the test surface, is discussed

ODEion--a software module for structural identification of ordinary differential equations.

Science.gov (United States)

Gennemark, Peter; Wedelin, Dag

2014-02-01

In the systems biology field, algorithms for structural identification of ordinary differential equations (ODEs) have mainly focused on fixed model spaces like S-systems and/or on methods that require sufficiently good data so that derivatives can be accurately estimated. There is therefore a lack of methods and software that can handle more general models and realistic data. We present ODEion, a software module for structural identification of ODEs. Main characteristic features of the software are: • The model space is defined by arbitrary user-defined functions that can be nonlinear in both variables and parameters, such as for example chemical rate reactions. • ODEion implements computationally efficient algorithms that have been shown to efficiently handle sparse and noisy data. It can run a range of realistic problems that previously required a supercomputer. • ODEion is easy to use and provides SBML output. We describe the mathematical problem, the ODEion system itself, and provide several examples of how the system can be used. Available at: http://www.odeidentification.org.

αII-spectrin and βII-spectrin do not affect TGFβ1-induced myofibroblast differentiation.

Science.gov (United States)

Piersma, Bram; Wouters, Olaf Y; Bank, Ruud A

2018-05-03

Mechanosensing of fibroblasts plays a key role in the development of fibrosis. So far, no effective treatments are available to treat this devastating disorder. Spectrins regulate cell morphology and are potential mechanosensors in a variety of non-erythroid cells, but little is known about the role of spectrins in fibroblasts. We investigate whether αII- and βII-spectrin are required for the phenotypic properties of adult human dermal (myo)fibroblasts. Knockdown of αII- or βII-spectrin in fibroblasts did not affect cell adhesion, cell size and YAP nuclear/cytosolic localization. We further investigated whether αII- and βII-spectrin play a role in the phenotypical switch from fibroblasts to myofibroblasts under the influence of the pro-fibrotic cytokine TGFβ1. Knockdown of spectrins did not affect myofibroblast formation, nor did we observe changes in the organization of αSMA stress fibers. Focal adhesion assembly was unaffected by spectrin deficiency, as was collagen type I mRNA expression and protein deposition. Wound closure was unaffected as well, showing that important functional properties of myofibroblasts are unchanged without αII- or βII-spectrin. In fact, fibroblasts stimulated with TGFβ1 demonstrated significantly lower endogenous mRNA levels of αII- and βII-spectrin. Taken together, despite the diverse roles of spectrins in a variety of other cells, αII- and βII-spectrin do not regulate cell adhesion, cell size and YAP localization in human dermal fibroblasts and are not required for the dermal myofibroblast phenotypical switch.

Modulated Temperature Differential Scanning Calorimetry Theoretical and Practical Applications in Polymer Characterisation

CERN Document Server

Reading, Mike

2006-01-01

MTDSC provides a step-change increase in the power of calorimetry to characterize virtually all polymer systems including curing systems, blends and semicrystalline polymers. It enables hidden transitions to be revealed, miscibility to be accurately assessed, and phases and interfaces in complex blends to be quantified. It also enables crystallinity in complex systems to be measured and provides new insights into melting behaviour. All of this is achieved by a simple modification of conventional DSC. In 1992 a new calorimetric technique was introduced that superimposed a small modulation on top of the conventional linear temperature program typically used in differential scanning calorimetry. This was combined with a method of data analysis that enabled the sample’s response to the linear component of the temperature program to be separated from its response to the periodic component. In this way, for the first time, a signal equivalent to that of conventional DSC was obtained simultaneously with a measure ...

Differential preparation intervals modulate repetition processes in task switching: an ERP study

Directory of Open Access Journals (Sweden)

Min eWang

2016-02-01

Full Text Available In task-switching paradigms, reaction times (RTs switch cost (SC and the neural correlates underlying the SC are affected by different preparation intervals. However, little is known about the effect of the preparation interval on the repetition processes in task-switching. To examine this effect we utilized a cued task-switching paradigm with long sequences of repeated trials. Response-stimulus intervals (RSI and cue-stimulus intervals (CSI were manipulated in short and long conditions. Electroencephalography (EEG and behavioral data were recorded. We found that with increasing repetitions, RTs were faster in the short CSI conditions, while P3 amplitudes decreased in the LS (long RSI and short CSI conditions. Positive correlations between RT benefit and P3 activation decrease (repeat 1 minus repeat 5, and between the slope of the RT and P3 regression lines were observed only in the LS condition. Our findings suggest that differential preparation intervals modulate repetition processes in task switching.

Efficient and Compact Semiconductor Laser Transmitter Modules, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Continue development of a Compact Transmitter Module (CTM). Modules will be voltage controlled to adjust wavlength using temperature and drive current settings. The...

Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer.

Directory of Open Access Journals (Sweden)

Laxmidhar Das

Full Text Available Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.

Application of Box-Behnken designs in parameters optimization of differential pulse anodic stripping voltammetry for lead(II) determination in two electrolytes.

Science.gov (United States)

Yu, Xiao-Lan; He, Yong

2017-06-05

Box-Behnken design was advantageous to parameters optimization of differential pulse anodic stripping voltammetry (DPASV) for the analysis of lead(II) with its high efficiency and accuracy. Five Box-Behnken designs were designed and conducted in the electrolyte of 0.1 mol/L acetate buffer and 0.1 mol/L HCl without the removal of oxygen. Significant parameters and interactions in each electrolyte were found (P-value Box-Behnken designs in parameters optimization of DPASV for lead(II) determination regardless of the electrolyte kinds.

Tissue transglutaminase (TG2 activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

Directory of Open Access Journals (Sweden)

Xiaoxue Yin

2012-08-01

Full Text Available Tissue transglutaminase (type II, TG2 has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14 to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC mRNA, bone morphogenetic protein-2 (BMP-2 and collagen I, significantly high alkaline phosphatase (ALP activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2.

Local angiotensin II promotes adipogenic differentiation of human adipose tissue mesenchymal stem cells through type 2 angiotensin receptor

Directory of Open Access Journals (Sweden)

Veronika Y. Sysoeva

2017-12-01

Full Text Available Obesity is often associated with high systemic and local activity of renin-angiotensin system (RAS. Mesenchymal stem cells of adipose tissue are the main source of adipocytes. The aim of this study was to clarify how local RAS could control adipose differentiation of human adipose tissue derived mesenchymal stem cells (ADSCs. We examined the distribution of angiotensin receptor expressing cells in human adipose tissue and found that type 1 and type 2 receptors are co-expressed in its stromal compartment, which is known to contain mesenchymal stem cells. To study the expression of receptors specifically in ADSCs we have isolated them from adipose tissue. Up to 99% of cultured ADSCs expressed angiotensin II (AngII receptor type 1 (AT1. Using the analysis of Ca2+ mobilization in single cells we found that only 5.2 ± 2.7% of ADSCs specifically respond to serial Ang II applications via AT1 receptor and expressed this receptor constantly. This AT1const ADSCs subpopulation exhibited increased adipose competency, which was triggered by endogenous AngII. Inhibitory and expression analyses showed that AT1const ADSCs highly co-express AngII type 2 receptor (AT2, which was responsible for increased adipose competency of this ADSC subpopulation.

Electron spin resonance and electron spin echo modulation studies of Cu(II) ions in the aluminosilicate chabazite: A comparison of Cu(II) cation location and adsorbate interaction with isostructural silicoaluminophosphate-34

International Nuclear Information System (INIS)

Zamadics, M.; Kevan, L.

1992-01-01

This study focuses on Cu(II) ions exchanged in the aluminosilicate zeolite chabazite. The various Cu(II) species formed after dehydration, rehydration, and exposure to adsorbates are characterized by electron spin resonance and electron spin echo modulation spectroscopies. These results are interpreted in terms of Cu(II) ion location and adsorbate interaction. The results of this study are compared to the results found earlier for SAPO-34, chabazite's structural analog from the silicoaluminophosphate group. In a hydrated sample of chabazite the Cu(II) ions are found to be in a near octahedral environment coordinated to three nonequivalent water molecules and three framework oxygens. The most probable location of the Cu(II) ion in a hydrated sample is above the plane of the six-membered ring slightly displaced into the ellipsoidal cavity. A somewhat similar location and coordination is found for Cu(II) ions in H-SAPO-34. A feature common to both CuH-chabazite and CuH-SAPO-34 is the generation of two distinct Cu(II) species upon dehydration. It is found that Cu(II) cations in chabazite interact with the various adsorbate molecules in a similar manner as Cu(II) cation in H-chabazite and three molecules of ethanol and three propanol molecules. Only the Cu(II) ions located in the hexagonal rings after dehydration were found to complex with ethylene. The differences observed in the interaction of the Cu(II) in with water, propanol, and ehtylene between SAPO-34 and chabazite can be related to the differing cation densities of these two materials. 32 refs., 7 figs., 21 tabs

Application of TZERO calibrated modulated temperature differential scanning calorimetry to characterize model protein formulations.

Science.gov (United States)

Badkar, Aniket; Yohannes, Paulos; Banga, Ajay

2006-02-17

The objective of this study was to evaluate the feasibility of using T(ZERO) modulated temperature differential scanning calorimetry (MDSC) as a novel technique to characterize protein solutions using lysozyme as a model protein and IgG as a model monoclonal antibody. MDSC involves the application of modulated heating program, along with the standard heating program that enables the separation of overlapping thermal transitions. Although characterization of unfolding transitions for protein solutions requires the application of high sensitive DSC, separation of overlapping transitions like aggregation and other exothermic events may be possible only by use of MDSC. A newer T(ZERO) calibrated MDSC model from TA instruments that has improved sensitivity than previous models was used. MDSC analysis showed total, reversing and non-reversing heat flow signals. Total heat flow signals showed a combination of melting endotherms and overlapping exothermic events. Under the operating conditions used, the melting endotherms were seen in reversing heat flow signal while the exothermic events were seen in non-reversing heat flow signal. This enabled the separation of overlapping thermal transitions, improved data analysis and decreased baseline noise. MDSC was used here for characterization of lysozyme solutions, but its feasibility for characterizing therapeutic protein solutions needs further assessment.

Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells.

Science.gov (United States)

Johari, Behrooz; Ebrahimi-Rad, Mina; Maghsood, Faezeh; Lotfinia, Majid; Saltanatpouri, Zohreh; Teimoori-Toolabi, Ladan; Sharifzadeh, Zahra; Karimipoor, Morteza; Kadivar, Mehdi

2017-01-01

Myc (c-Myc) alone activates the embryonic stem cell-like transcriptional module in both normal and transformed cells. Its dysregulation might lead to increased cancer stem cells (CSCs) population in some tumor cells. In order to investigate the potential of Myc decoy oligodeoxynucleotides for differentiation therapy, mouse embryonic stem cells (mESCs) were used in this study as a model of CSCs. To our best of knowledge this is the first report outlining the application of Myc decoy in transcription factor decoy "TFD" strategy for inducing differentiation in mESCs. A 20-mer double-stranded Myc transcription factor decoy and scrambled oligodeoxynucleotides (ODNs) were designed, analyzed by electrophoretic mobility shift (EMSA) assay and transfected into the mESCs under 2 inhibitors (2i) condition. Further investigations were carried out using fluorescence and confocal microscopy, cell proliferation and apoptosis analysis, alkaline phosphatase and embryoid body formation assay, real-time PCR and western blotting. EMSA data showed that Myc decoy ODNs bound specifically to c-Myc protein. They were found to be localized in both cytoplasm and nucleus of mESCs. Our results revealed the potential capability of Myc decoy ODNs to decrease cell viability by (16.1±2%), to increase the number of cells arrested in G0/G1 phases and apoptosis by (14.2±3.1%) and (12.1±3.2%), respectively regarding the controls. Myc decoy could also modulate differentiation in mESCs despite the presence of 2i/LIF in our medium the presence of 2i/LIF in our medium. The optimized Myc decoy ODNs approach might be considered as a promising alternative strategy for differentiation therapy investigations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.

Directory of Open Access Journals (Sweden)

Leni Moldovan

Full Text Available Peripheral blood mononuclear cells (PBMCs, including rare circulating stem and progenitor cells (CSPCs, have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene, defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03 with age (R2 = -0.23, vascular stiffness (R2 = -0.24, and central aortic pressure (R2 = -0.19 and positively correlated with body mass index (R2 = 0.72, in women. The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional

An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

Science.gov (United States)

Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

2016-02-01

The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

Differential expression of secretogranin II and chromogranin A genes in the female rat pituitary through sexual maturation and estrous cycle

International Nuclear Information System (INIS)

Anouar, Y.; Duval, J.

1991-01-01

Secretogranin II (SgII) is a protein of pituitary secretory granules released by LHRH-stimulated gonadotrope cells. Estrogens and androgens are modulators of SgII release. Experiments were performed to determine the regulation of expression of the SgII gene in the female rat pituitary, during sexual maturation and according to the estrous cycle. Age- and cycle-related changes in SgII mRNA content were estimated through cytoplasmic slot blot; SgII content was determined by western blotting; maturation of the protein was controlled through [35S]sulfate labeling. Variations in chromogranin A (CgA), another protein of secretory granules, were analyzed in the same experimental conditions to assess the specificity of SgII regulation. The pituitary SgII concentration increased between days 7 and 21 (2.2-fold) and then declined to the initial 7-day-old value. Simultaneously, the CgA concentration went through a maximum between days 14 and 21 and then strongly dropped to barely detectable levels in the adult pituitary. The SgII mRNA concentration followed roughly the same pattern as the protein. Moreover, the sulfation level remained constant between days 14 and 60. These results demonstrated a regulatory mechanism operating, during sexual maturation, on the SgII gene and not on the protein processing or on storage/release steps. In the 4-day cycling females, the pituitary SgII mRNA and protein contents were the lowest during estrus. They then increased to their highest values in diestrus II. Moreover, the sulfation level of SgII was significantly higher during estrus than during any other stage. Due to its low content level, variations in pituitary CgA could not be demonstrated during the cycle

Progress on the RF Coupling Coil Module Design for the MICE Channel

International Nuclear Information System (INIS)

Li, D.; Green, M.A.; Virostek, S.P.; Zisman, M.S.; Lau, W.; White, A.E.; Yang, S.Q.

2005-01-01

We describe the progress on the design of the RF coupling coil (RFCC) module for the international Muon Ionization Cooling Experiment (MICE) at Rutherford Appleton Laboratory (RAL) in the UK. The MICE cooling channel design consists of one SFOFO cell that is similar to that of the US Study-II of a neutrino factory. The MICE RFCC module comprises a superconducting solenoid, mounted around four normal conducting 201.25-MHz RF cavities. Each cavity has a pair of thin curved beryllium windows to close the conventional open beam irises, which allows for independent control of the phase in each cavity and for the RF power to be fed separately. The coil package that surrounds the RF cavities is mounted on a vacuum vessel. The RF vacuum is shared between the cavities and the vacuum vessel around the cavities such that there is no differential pressure on the thin beryllium windows. This paper discusses the design progress of the RFCC module and the fabrication progress of a prototype 201.25-MHz cavity

Mediator kinase module and human tumorigenesis.

Science.gov (United States)

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

2015-01-01

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

Architecture of the RNA polymerase II-Mediator core initiation complex.

Science.gov (United States)

Plaschka, C; Larivière, L; Wenzeck, L; Seizl, M; Hemann, M; Tegunov, D; Petrotchenko, E V; Borchers, C H; Baumeister, W; Herzog, F; Villa, E; Cramer, P

2015-02-19

The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 Å resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.

Negative effect of cyclin D1 overexpression on recurrence-free survival in stage II-IIIA lung adenocarcinoma and its expression modulation by vorinostat in vitro.

Science.gov (United States)

Lee, Eunju; Jin, DongHao; Lee, Bo Bin; Kim, Yujin; Han, Joungho; Shim, Young Mog; Kim, Duk-Hwan

2015-12-17

This study was aimed at identifying prognostic biomarkers for stage II-IIIA non-small cell lung cancer (NSCLC) according to histology and at investigating the effect of vorinostat on the expression of these biomarkers. Expression levels of cyclin D1, cyclin A2, cyclin E, and p16 proteins that are involved in the G1-to-S phase progression of cell cycle were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 372 samples of stage II-IIIA NSCLC. The effect of vorinostat on the expression of these proteins, impacts on cell cycle, and histone modification was explored in lung cancer cells. Abnormal expression of cyclin A2, cyclin D1, cyclin E, and p16 was found in 66, 47, 34, and 51 % of 372 cases, respectively. Amongst the four proteins, only cyclin D1 overexpression was significantly associated with poor recurrence-free survival (adjusted hazard ratio = 1.87; 95 % confidence interval = 1.12 - 2.69, P = 0.02) in adenocarcinoma but not in squamous cell carcinoma (P = 0.44). Vorinostat inhibited cell cycle progression to the S-phase and induced down-regulation of cyclin D1 in vitro. The down-regulation of cyclin D1 by vorinostat was comparable to a siRNA-mediated knockdown of cyclin D1 in A549 cells, but vorinostat in the presence of benzo[a]pyrene showed a differential effect in different lung cancer cell lines. Cyclin D1 down-regulation by vorinostat was associated with the accumulation of dimethyl-H3K9 at the promoter of the gene. The present study suggests that cyclin D1 may be an independent prognostic factor for recurrence-free survival in stage II-IIIA adenocarcinoma of lung and its expression may be modulated by vorinostat.

Stochastic temperature modulation: A new technique in temperature-modulated DSC

International Nuclear Information System (INIS)

Schawe, J.E.K.; Huetter, T.; Heitz, C.; Alig, I.; Lellinger, D.

2006-01-01

A new temperature-modulated differential scanning calorimetry (TMDSC) technique is introduced. The technique is based on stochastic temperature modulation and has been developed as a consequence of a generalized theory of a temperature-modulated DSC. The quasi-static heat capacity and the frequency-dependent complex heat capacity can be determined over a wide frequency range in one single measurement without further calibration. Furthermore, the reversing and non-reversing heat flows are determined directly from the measured data. Examples show the frequency dependence of the glass transition, the isothermal curing of thermosets and a solid-solid transition

Glutathione S-transferase expression and isoenzyme composition during cell differentiation of Caco-2 cells

International Nuclear Information System (INIS)

Scharmach, E.; Hessel, S.; Niemann, B.; Lampen, A.

2009-01-01

The human colon adenocarcinoma cell line Caco-2 is frequently used to study human intestinal metabolism and transport of xenobiotica. Previous studies have shown that both Caco-2 cells and human colon cells constitutively express the multigene family of detoxifying enzymes glutathione S-transferases (GSTs), particularly GST alpha and GST pi. GSTs may play a fundamental role in the molecular interplay between phase I, II enzymes and ABC-transporters. The gut fermentation product, butyrate, can modulate the potential for detoxification. The aim of this study was to investigate the basal expression of further cytosolic GSTs in Caco-2 cells during cell differentiation. In addition, a comparison was made with expression levels in MCF-7 and HepG2, two other cell types with barrier functions. Finally, the butyrate-mediated modulation of gene and protein expression was determined by real time PCR and western blot analysis. In Caco-2, gene and protein expression levels of GST alpha increased during cell differentiation. High levels of GSTO1 and GSTP1 were constantly expressed. No expression of GSTM5 and GSTT1 was detected. HepG2 expressed GSTO1 and MCF-7 GSTZ1 most intensively. No expression of GSTA5, GSTM5, or GSTP1 was detected in either cell. Incubation of Caco-2 cells with butyrate (5 mM) significantly induced GSTA1 and GSTM2 in proliferating Caco-2 cells. In differentiated cells, butyrate tended to increase GSTO1 and GSTP1. The results of this study show that a differentiation-dependent expression of GSTs in Caco-2 cells may reflect the in vivo situation and indicate the potential of butyrate to modify intestinal metabolism. GSTA1-A4 have been identified as good markers for cell differentiation. The Caco-2 cell line is a useful model for assessing the potential of food-related substances to modulate the GST expression pattern.

Glutathione S-transferase expression and isoenzyme composition during cell differentiation of Caco-2 cells.

Science.gov (United States)

Scharmach, E; Hessel, S; Niemann, B; Lampen, A

2009-11-30

The human colon adenocarcinoma cell line Caco-2 is frequently used to study human intestinal metabolism and transport of xenobiotica. Previous studies have shown that both Caco-2 cells and human colon cells constitutively express the multigene family of detoxifying enzymes glutathione S-transferases (GSTs), particularly GST alpha and GST pi. GSTs may play a fundamental role in the molecular interplay between phase I, II enzymes and ABC-transporters. The gut fermentation product, butyrate, can modulate the potential for detoxification. The aim of this study was to investigate the basal expression of further cytosolic GSTs in Caco-2 cells during cell differentiation. In addition, a comparison was made with expression levels in MCF-7 and HepG2, two other cell types with barrier functions. Finally, the butyrate-mediated modulation of gene and protein expression was determined by real time PCR and western blot analysis. In Caco-2, gene and protein expression levels of GST alpha increased during cell differentiation. High levels of GSTO1 and GSTP1 were constantly expressed. No expression of GSTM5 and GSTT1 was detected. HepG2 expressed GSTO1 and MCF-7 GSTZ1 most intensively. No expression of GSTA5, GSTM5, or GSTP1 was detected in either cell. Incubation of Caco-2 cells with butyrate (5 mM) significantly induced GSTA1 and GSTM2 in proliferating Caco-2 cells. In differentiated cells, butyrate tended to increase GSTO1 and GSTP1. The results of this study show that a differentiation-dependent expression of GSTs in Caco-2 cells may reflect the in vivo situation and indicate the potential of butyrate to modify intestinal metabolism. GSTA1-A4 have been identified as good markers for cell differentiation. The Caco-2 cell line is a useful model for assessing the potential of food-related substances to modulate the GST expression pattern.

RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation

International Nuclear Information System (INIS)

Sundaram, Kumaran; Nishimura, Riko; Senn, Joseph; Youssef, Rimon F.; London, Steven D.; Reddy, Sakamuri V.

2007-01-01

the absence of RANKL. Taken together, our results suggest that RANKL signals through TRAF6 and that NFATc1 is a downstream effector of RANKL signaling to modulate MMP-9 gene expression during osteoclast differentiation

H + Ar collisions. II. Differential scattering calculations

International Nuclear Information System (INIS)

Neumann, H.; Le, T.Q.; van Zyl, B.

1977-01-01

Differential elastic scattering cross-section calculations have been made for H + Ar collisions using classical and eikonal techniques. The calculation procedures are described and compared with existing experimental data. It is shown that the angular distribution of the elastic cross section is similar to that obtained for proton production in such collisions at energies above about 200 eV. By combining the angular dependence of the computed elastic cross section with experimental measurements described in the preceding paper, absolute differential cross sections for proton production have been determined

Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs

Directory of Open Access Journals (Sweden)

Victoria A. Church

2017-09-01

Full Text Available The cellular abundance of mature microRNAs (miRNAs is dictated by the efficiency of nuclear processing of primary miRNA transcripts (pri-miRNAs into pre-miRNA intermediates. The Microprocessor complex of Drosha and DGCR8 carries this out, but it has been unclear what controls Microprocessor’s differential processing of various pri-miRNAs. Here, we show that Drosophila DGCR8 (Pasha directly associates with the C-terminal domain of the RNA polymerase II elongation complex when it is phosphorylated by the Cdk9 kinase (pTEFb. When association is blocked by loss of Cdk9 activity, a global change in pri-miRNA processing is detected. Processing of pri-miRNAs with a UGU sequence motif in their apical junction domain increases, while processing of pri-miRNAs lacking this motif decreases. Therefore, phosphorylation of RNA polymerase II recruits Microprocessor for co-transcriptional processing of non-UGU pri-miRNAs that would otherwise be poorly processed. In contrast, UGU-positive pri-miRNAs are robustly processed by Microprocessor independent of RNA polymerase association.

The Belle II DEPFET pixel vertex detector. Development of a full-scale module prototype

International Nuclear Information System (INIS)

Lemarenko, Mikhail

2013-11-01

The Belle II experiment, which will start after 2015 at the SuperKEKB accelerator in Japan, will focus on the precision measurement of the CP-violation mechanism and on the search for physics beyond the Standard Model. A new detection system with an excellent spatial resolution and capable of coping with considerably increased background is required. To address this challenge, a pixel detector based on DEPFET technology has been proposed. A new all silicon integrated circuit, called Data Handling Processor (DHP), is implemented in 65 nm CMOS technology. It is designed to steer the detector and preprocess the generated data. The scope of this thesis covers DHP tests and optimization as well the development of its test environment, which is the first Full-Scale Module Prototype of the DEPFET Pixel Vertex detector.

Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation

Energy Technology Data Exchange (ETDEWEB)

Ding, Ke, E-mail: dingke@med.uestc.edu.cn [Department of Pediatric Surgery, School of medicine, University of Electronic Science and Technology of China, Chengdu 610072 (China); Sichuan Academy of Medical Sciences & Sichuan Provincial People' s Hospital, Chengdu 610072 (China); Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Liu, Wen-ying; Zeng, Qiang; Hou, Fang [Department of Pediatric Surgery, School of medicine, University of Electronic Science and Technology of China, Chengdu 610072 (China); Sichuan Academy of Medical Sciences & Sichuan Provincial People' s Hospital, Chengdu 610072 (China); Xu, Jian-zhong, E-mail: xjzspine@163.com [Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Yang, Zhong, E-mail: zyang1999@163.com [Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

2017-03-01

Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering.

Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation

International Nuclear Information System (INIS)

Ding, Ke; Liu, Wen-ying; Zeng, Qiang; Hou, Fang; Xu, Jian-zhong; Yang, Zhong

2017-01-01

Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering.

Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation.

Science.gov (United States)

Ding, Ke; Liu, Wen-Ying; Zeng, Qiang; Hou, Fang; Xu, Jian-Zhong; Yang, Zhong

2017-03-01

Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuroprotective effects of metabotropic glutamate receptor group II and III activators against MPP(+)-induced cell death in human neuroblastoma SH-SY5Y cells: the impact of cell differentiation state.

Science.gov (United States)

Jantas, D; Greda, A; Golda, S; Korostynski, M; Grygier, B; Roman, A; Pilc, A; Lason, W

2014-08-01

Recent studies have documented that metabotropic glutamate receptors from group II and III (mGluR II/III) are a potential target in the symptomatic treatment of Parkinson's disease (PD), however, the neuroprotective effects of particular mGluR II/III subtypes in relation to PD pathology are recognized only partially. In the present study, we investigated the effect of various mGluR II/III activators in the in vitro model of PD using human neuroblastoma SH-SY5Y cell line and mitochondrial neurotoxin MPP(+). We demonstrated that all tested mGluR ligands: mGluR II agonist - LY354740, mGluR III agonist - ACPT-I, mGluR4 PAM - VU0361737, mGluR8 agonist - (S)-3,4-DCPG, mGluR8 PAM - AZ12216052 and mGluR7 allosteric agonist - AMN082 were protective against MPP(+)-evoked cell damage in undifferentiated (UN-) SH-SY5Y cells with the highest neuroprotection mediated by mGluR8-specific agents. However, in retinoic acid- differentiated (RA-) SH-SY5Y cells we found protection mediated only by mGluR8 activators. We also demonstrated the cell proliferation stimulating effect for mGluR4 and mGluR8 PAMs. Next, we showed that the protection mediated by mGluR II/III activators in UN-SH-SY5Y was not accompanied by the modulation of caspase-3 activity, however, a decrease in the number of apoptotic nuclei was found. Finally, we showed that the inhibitor of necroptosis, necrostatin-1 blocked the mGluR III-mediated protection. Altogether our comparative in vitro data add a further proof to neuroprotective effects of mGluR agonists or PAMs and point to mGluR8 as a promising target for neuroprotective interventions in PD. The results also suggest the participation of necroptosis-related molecular pathways in neuroprotective effects of mGluR III activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nitric oxide activation by distal redox modulation in tetranuclear iron nitrosyl complexes.

Science.gov (United States)

de Ruiter, Graham; Thompson, Niklas B; Lionetti, Davide; Agapie, Theodor

2015-11-11

A series of tetranuclear iron complexes displaying a site-differentiated metal center was synthesized. Three of the metal centers are coordinated to our previously reported ligand, based on a 1,3,5-triarylbenzene motif with nitrogen and oxygen donors. The fourth (apical) iron center is coordinatively unsaturated and appended to the trinuclear core through three bridging pyrazolates and an interstitial μ4-oxide moiety. Electrochemical studies of complex [LFe3(PhPz)3OFe][OTf]2 revealed three reversible redox events assigned to the Fe(II)4/Fe(II)3Fe(III) (-1.733 V), Fe(II)3Fe(III)/Fe(II)2Fe(III)2 (-0.727 V), and Fe(II)2Fe(III)2/Fe(II)Fe(III)3 (0.018 V) redox couples. Combined Mössbauer and crystallographic studies indicate that the change in oxidation state is exclusively localized at the triiron core, without changing the oxidation state of the apical metal center. This phenomenon is assigned to differences in the coordination environment of the two metal sites and provides a strategy for storing electron and hole equivalents without affecting the oxidation state of the coordinatively unsaturated metal. The presence of a ligand-binding site allowed the effect of redox modulation on nitric oxide activation by an Fe(II) metal center to be studied. Treatment of the clusters with nitric oxide resulted in binding of NO to the apical iron center, generating a {FeNO}(7) moiety. As with the NO-free precursors, the three reversible redox events are localized at the iron centers distal from the NO ligand. Altering the redox state of the triiron core resulted in significant change in the NO stretching frequency, by as much as 100 cm(-1). The increased activation of NO is attributed to structural changes within the clusters, in particular, those related to the interaction of the metal centers with the interstitial atom. The differences in NO activation were further shown to lead to differential reactivity, with NO disproportionation and N2O formation performed by the more

Differential Binding of Co(II) and Zn(II) to Metallo-beta-Lactamase Bla2 from Bacillus anthracis

Energy Technology Data Exchange (ETDEWEB)

Hawk, M.; Breece, R; Hajdin, C; Bender, K; Hu, Z; Costello, A; Bennett, B; Tierney, D; Crowder, M

2009-01-01

In an effort to probe the structure, mechanism, and biochemical properties of metallo-{beta}-lactamase Bla2 from Bacillus anthracis, the enzyme was overexpressed, purified, and characterized. Metal analyses demonstrated that recombinant Bla2 tightly binds 1 equiv of Zn(II). Steady-state kinetic studies showed that mono-Zn(II) Bla2 (1Zn-Bla2) is active, while di-Zn(II) Bla2 (ZnZn-Bla2) was unstable. Catalytically, 1Zn-Bla2 behaves like the related enzymes CcrA and L1. In contrast, di-Co(II) Bla2 (CoCo-Bla2) is substantially more active than the mono-Co(II) analogue. Rapid kinetics and UV-vis, 1H NMR, EPR, and EXAFS spectroscopic studies show that Co(II) binding to Bla2 is distributed, while EXAFS shows that Zn(II) binding is sequential. To our knowledge, this is the first documented example of a Zn enzyme that binds Co(II) and Zn(II) via distinct mechanisms, underscoring the need to demonstrate transferability when extrapolating results on Co(II)-substituted proteins to the native Zn(II)-containing forms.

The role of metallothionein II in neuronal differentiation and survival

DEFF Research Database (Denmark)

Køhler, Lene B; Berezin, Vladimir; Bock, Elisabeth

2003-01-01

-I+II can affect neurons directly. It is likely that MT isoforms could be beneficial also during neurodegenerative disorders. In this study, we have examined if MT-II affects survival and neurite extension of dopaminergic and hippocampal neurons. We show for the first time that MT-II treatment can....... Accordingly, treatment with MT-II may be of therapeutic value in neurodegenerative disorders....

Evaluating construct validity of the second version of the Copenhagen Psychosocial Questionnaire through analysis of differential item functioning and differential item effect

DEFF Research Database (Denmark)

Bjorner, Jakob Bue; Pejtersen, Jan Hyld

2010-01-01

AIMS: To evaluate the construct validity of the Copenhagen Psychosocial Questionnaire II (COPSOQ II) by means of tests for differential item functioning (DIF) and differential item effect (DIE). METHODS: We used a Danish general population postal survey (n = 4,732 with 3,517 wage earners) with a ...

The Bipolar II Depression Questionnaire: A Self-Report Tool for Detecting Bipolar II Depression.

Directory of Open Access Journals (Sweden)

Chi Ming Leung

Full Text Available Bipolar II (BP-II depression is often misdiagnosed as unipolar (UP depression, resulting in suboptimal treatment. Tools for differentiating between these two types of depression are lacking. This study aimed to develop a simple, self-report screening instrument to help distinguish BP-II depression from UP depressive disorder. A prototype BP-II depression questionnaire (BPIIDQ-P was constructed following a literature review, panel discussions and a field trial. Consecutively assessed patients with a diagnosis of depressive disorder or BP with depressive episodes completed the BPIIDQ-P at a psychiatric outpatient clinic in Hong Kong between October and December 2013. Data were analyzed using discriminant analysis and logistic regression. Of the 298 subjects recruited, 65 (21.8% were males and 233 (78.2% females. There were 112 (37.6% subjects with BP depression [BP-I = 42 (14.1%, BP-II = 70 (23.5%] and 182 (62.4% with UP depression. Based on family history, age at onset, postpartum depression, episodic course, attacks of anxiety, hypersomnia, social phobia and agoraphobia, the 8-item BPIIDQ-8 was constructed. The BPIIDQ-8 differentiated subjects with BP-II from those with UP depression with a sensitivity/specificity of 0.75/0.63 for the whole sample and 0.77/0.72 for a female subgroup with a history of childbirth. The BPIIDQ-8 can differentiate BP-II from UP depression at the secondary care level with satisfactory to good reliability and validity. It has good potential as a screening tool for BP-II depression in primary care settings. Recall bias, the relatively small sample size, and the high proportion of females in the BP-II sample limit the generalization of the results.

Differential Effect of Solution Conditions on the Conformation of the Actinoporins Sticholysin II and Equinatoxin II

Directory of Open Access Journals (Sweden)

EDSON V.F. FAUTH

2014-12-01

Full Text Available Actinoporins are a family of pore-forming proteins with hemolytic activity. The structural basis for such activity appears to depend on their correct folding. Such folding encompasses a phosphocholine binding site, a tryptophan-rich region and the activity-related N-terminus segment. Additionally, different solution conditions are known to be able to influence the pore formation by actinoporins, as for Sticholysin II (StnII and Equinatoxin II (EqtxII. In this context, the current work intends to characterize the influence of distinct solution conditions in the conformational behavior of these proteins through molecular dynamics (MD simulations. The obtained data offer structural insights into actinoporins dynamics in solution, characterizing its conformational behavior at the atomic level, in accordance with previous experimental data on StnII and EqtxII hemolytic activities.

Modulation of DNA base excision repair during neuronal differentiation

DEFF Research Database (Denmark)

Sykora, Peter; Yang, Jenq-Lin; Ferrarelli, Leslie K

2013-01-01

DNA damage susceptibility and base excision DNA repair (BER) capacity in undifferentiated and differentiated human neural cells. The results show that undifferentiated human SH-SY5Y neuroblastoma cells are less sensitive to oxidative damage than their differentiated counterparts, in part because...

Wavelength-Modulated Differential Photoacoustic (WM-DPA) imaging: a high dynamic range modality towards noninvasive diagnosis of cancer

Science.gov (United States)

Dovlo, Edem; Lashkari, Bahman; Choi, Sung soo Sean; Mandelis, Andreas

2016-03-01

This study explores wavelength-modulated differential photo-acoustic (WM-DPA) imaging for non-invasive early cancer detection via sensitive characterization of functional information such as hemoglobin oxygenation (sO2) levels. Well-known benchmarks of tumor formation such as angiogenesis and hypoxia can be addressed this way. While most conventional photo-acoustic imaging has almost entirely employed high-power pulsed lasers, frequency-domain photo-acoustic radar (FD-PAR) has seen significant development as an alternative technique. It employs a continuous wave laser source intensity-modulated and driven by frequency-swept waveforms. WM-DPA imaging utilizes chirp modulated laser beams at two distinct wavelengths for which absorption differences between oxy- and deoxygenated hemoglobin are minimum (isosbestic point, 805 nm) and maximum (680 nm) to simultaneously generate two signals detected using a standard commercial array transducer as well as a single-element transducer that scans the sample. Signal processing is performed using Lab View and Matlab software developed in-house. Minute changes in total hemoglobin concentration (tHb) and oxygenation levels are detectable using this method since background absorption is suppressed due to the out-of-phase modulation of the laser sources while the difference between the two signals is amplified, thus allowing pre-malignant tumors to become identifiable. By regulating the signal amplitude ratio and phase shift the system can be tuned to applications like cancer screening, sO2 quantification and hypoxia monitoring in stroke patients. Experimental results presented demonstrate WM-DPA imaging of sheep blood phantoms in comparison to single-wavelength FD-PAR imaging. Future work includes the functional PA imaging of small animals in vivo.

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation

Directory of Open Access Journals (Sweden)

Maricela Maldonado

2016-09-01

Full Text Available Robust control of human induced pluripotent stem cell (hIPSC differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36 h. Simultaneously, epithelial-to-mesenchymal (EMT transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632.

Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling.

Science.gov (United States)

Sun, X; Lu, B; Hu, B; Xiao, W; Li, W; Huang, Z

2014-03-28

12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was the major activator of C7ORF41 that in turn repressed NF-κB activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation.

Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling

International Nuclear Information System (INIS)

Sun, X; Lu, B; Hu, B; Xiao, W; Li, W; Huang, Z

2014-01-01

12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was the major activator of C7ORF41 that in turn repressed NF-κB activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation

Consolidation differentially modulates schema effects on memory for items and associations.

Science.gov (United States)

van Kesteren, Marlieke T R; Rijpkema, Mark; Ruiter, Dirk J; Fernández, Guillén

2013-01-01

Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongruent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always consistently supported in the literature, with differential schema effects reported for different types of memory, different retrieval cues, and the possibility of time-dependent effects related to consolidation processes. To examine these effects more directly, we tested participants on two different types of memory (item recognition and associative memory) for newly encoded visuo-tactile associations at different study-test intervals, thus probing memory retrieval accuracy for schema-congruent and schema-incongruent items and associations at different time points (t = 0, t = 20, and t = 48 hours) after encoding. Results show that the schema effect on visual item recognition only arises after consolidation, while the schema effect on associative memory is already apparent immediately after encoding, persisting, but getting smaller over time. These findings give further insight into different factors influencing the schema effect on memory, and can inform future schema experiments by illustrating the value of considering effects of memory type and consolidation on schema-modulated retrieval.

Consolidation differentially modulates schema effects on memory for items and associations.

Directory of Open Access Journals (Sweden)

Marlieke T R van Kesteren

Full Text Available Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongruent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always consistently supported in the literature, with differential schema effects reported for different types of memory, different retrieval cues, and the possibility of time-dependent effects related to consolidation processes. To examine these effects more directly, we tested participants on two different types of memory (item recognition and associative memory for newly encoded visuo-tactile associations at different study-test intervals, thus probing memory retrieval accuracy for schema-congruent and schema-incongruent items and associations at different time points (t = 0, t = 20, and t = 48 hours after encoding. Results show that the schema effect on visual item recognition only arises after consolidation, while the schema effect on associative memory is already apparent immediately after encoding, persisting, but getting smaller over time. These findings give further insight into different factors influencing the schema effect on memory, and can inform future schema experiments by illustrating the value of considering effects of memory type and consolidation on schema-modulated retrieval.

Test-beam evaluation of heavily irradiated silicon strip modules for ATLAS Phase-II Strip Tracker Upgrade

CERN Document Server

Blue, Andrew; The ATLAS collaboration

2018-01-01

The planned HL-LHC (High Luminosity LHC) is being designed to maximise the physics potential of the LHC with 10 years of operation at instantaneous luminosities of 7.5x1034cm−2s−1. A consequence of this increased luminosity is the expected radiation damage requiring the tracking detectors to withstand hadron equivalences to over 1x1015 1 MeV neutron equivalent per cm2 in the ATLAS Strips system. The silicon strip tracker exploits the concept of modularity. Fast readout electronics, deploying 130nm CMOS front-end electronics are glued on top of a silicon sensor to make a module. The radiation hard n-in-p micro-strip sensors used have been developed by the ATLAS ITk Strip Sensor collaboration and produced by Hamamatsu Photonics. A series of tests were performed at the DESY-II and CERN SPS test beam facilities to investigate the detailed performance of a strip module with both 2.5cm and 5cm length strips before and after irradiation with 8x1014neqcm−2 protons and a total ionising dose of 37.2MRad. The DURA...

Divergent modulation of neuronal differentiation by caspase-2 and -9.

Directory of Open Access Journals (Sweden)

Giuseppa Pistritto

Full Text Available Human Ntera2/cl.D1 (NT2 cells treated with retinoic acid (RA differentiate towards a well characterized neuronal phenotype sharing many features with human fetal neurons. In view of the emerging role of caspases in murine stem cell/neural precursor differentiation, caspases activity was evaluated during RA differentiation. Caspase-2, -3 and -9 activity was transiently and selectively increased in differentiating and non-apoptotic NT2-cells. SiRNA-mediated selective silencing of either caspase-2 (si-Casp2 or -9 (si-Casp9 was implemented in order to dissect the role of distinct caspases. The RA-induced expression of neuronal markers, i.e. neural cell adhesion molecule (NCAM, microtubule associated protein-2 (MAP2 and tyrosine hydroxylase (TH mRNAs and proteins, was decreased in si-Casp9, but markedly increased in si-Casp2 cells. During RA-induced NT2 differentiation, the class III histone deacetylase Sirt1, a putative caspase substrate implicated in the regulation of the proneural bHLH MASH1 gene expression, was cleaved to a ∼100 kDa fragment. Sirt1 cleavage was markedly reduced in si-Casp9 cells, even though caspase-3 was normally activated, but was not affected (still cleaved in si-Casp2 cells, despite a marked reduction of caspase-3 activity. The expression of MASH1 mRNA was higher and occurred earlier in si-Casp2 cells, while was reduced at early time points during differentiation in si-Casp9 cells. Thus, caspase-2 and -9 may perform opposite functions during RA-induced NT2 neuronal differentiation. While caspase-9 activation is relevant for proper neuronal differentiation, likely through the fine tuning of Sirt1 function, caspase-2 activation appears to hinder the RA-induced neuronal differentiation of NT2 cells.

The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part II (Differentiation

Directory of Open Access Journals (Sweden)

Kathryn Dorst

2014-02-01

Full Text Available Osseointegration of bone implants is a vital part of the recovery process. Numerous studies have shown that micropatterned geometries can promote cell-substrate associations and strengthen the bond between tissue and the implanted material. As demonstrated previously, exogenous zinc levels can influence the responsiveness of pre-osteoblasts to micropatterns and modify their migratory behavior. In this study, we sought to determine the effect of exogenous zinc on differentiation of osteoblasts cultured on micropatterned vs. planar substrates. Levels of activated metalloproteinase-2 (MMP-2 and transforming growth factor-beta 1 (TGF-β1, as well as early stage differentiation marker alkaline phosphatase, were altered with the addition of zinc. These results suggest that exogenous zinc concentration and micropatterning may interdependently modulate osteoblast differentiation.

Efficiently and easily integrating differential equations with JiTCODE, JiTCDDE, and JiTCSDE

Science.gov (United States)

Ansmann, Gerrit

2018-04-01

We present a family of Python modules for the numerical integration of ordinary, delay, or stochastic differential equations. The key features are that the user enters the derivative symbolically and it is just-in-time-compiled, allowing the user to efficiently integrate differential equations from a higher-level interpreted language. The presented modules are particularly suited for large systems of differential equations such as those used to describe dynamics on complex networks. Through the selected method of input, the presented modules also allow almost complete automatization of the process of estimating regular as well as transversal Lyapunov exponents for ordinary and delay differential equations. We conceptually discuss the modules' design, analyze their performance, and demonstrate their capabilities by application to timely problems.

Tensile loading modulates bone marrow stromal cell differentiation and the development of engineered fibrocartilage constructs.

Science.gov (United States)

Connelly, John T; Vanderploeg, Eric J; Mouw, Janna K; Wilson, Christopher G; Levenston, Marc E

2010-06-01

Mesenchymal progenitors such as bone marrow stromal cells (BMSCs) are an attractive cell source for fibrocartilage tissue engineering, but the types or combinations of signals required to promote fibrochondrocyte-specific differentiation remain unclear. The present study investigated the influences of cyclic tensile loading on the chondrogenesis of BMSCs and the development of engineered fibrocartilage. Cyclic tensile displacements (10%, 1 Hz) were applied to BMSC-seeded fibrin constructs for short (24 h) or extended (1-2 weeks) periods using a custom loading system. At early stages of chondrogenesis, 24 h of cyclic tension stimulated both protein and proteoglycan synthesis, but at later stages, tension increased protein synthesis only. One week of intermittent cyclic tension significantly increased the total sulfated glycosaminoglycan and collagen contents in the constructs, but these differences were lost after 2 weeks of loading. Constraining the gels during the extended culture periods prevented contraction of the fibrin matrix, induced collagen fiber alignment, and increased sulfated glycosaminoglycan release to the media. Cyclic tension specifically stimulated collagen I mRNA expression and protein synthesis, but had no effect on collagen II, aggrecan, or osteocalcin mRNA levels. Overall, these studies suggest that the combination of chondrogenic stimuli and tensile loading promotes fibrochondrocyte-like differentiation of BMSCs and has the potential to direct fibrocartilage development in vitro.

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation.

Science.gov (United States)

Maldonado, Maricela; Luu, Rebeccah J; Ramos, Michael E P; Nam, Jin

2016-09-01

Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632. Copyright © 2016 Helmholtz Zentrum München. Published by Elsevier B.V. All rights reserved.

Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice

Directory of Open Access Journals (Sweden)

Weina Cao

2018-02-01

Full Text Available Background/Aims: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms. Methods: Quantitative real-time PCR (qPCR and western blot were performed to determine Hoxa5 expression in primary adipocytes and in adipose tissues from mice. Lipid accumulation was evaluated by bodipy staining. Dual luciferase assay was applied to explore the transcription factor of Hoxa5 and the transcriptional target gene modulated by Hoxa5. All measurements were performed at least for three times at least. Results: A significant reduction of Hoxa5 expression was observed in adipose tissue of High Fat Diet (HFD induced obesity mice. We determined Hoxa5 increased adipocytes differentiation and mitochondrial biogenesis in adipocytes in vitro. CEBPβ was determined a transcription factor of Hoxa5 and inhibited methylation level of Hoxa5 by combining on the promoter of Hoxa5. Importantly, we found Fabp4, a known positive regulator of adipocytes differentiation, was transcriptional activation by Hoxa5. In addition, Hoxa5 promotes adipocytes differentiation by inhibiting PKA/HSL pathway. Conclusion: Our study demonstrated the promoting role of Hoxa5 in adipocytes differentiation and therefore bringing a new therapeutic mean to the treatment of obesity and type II diabetes.

A modulated differential scanning calorimetry and small-angle x-ray scattering study of the interfacial region in structured latices

Directory of Open Access Journals (Sweden)

Hourston Douglas J.

2001-01-01

Full Text Available The interfacial structure of poly(styrene (PS-poly(methyl acrylate (PMA structured latices has been investigated by means of modulated-temperature differential scanning calorimetry (M-TDSC and small-angle x-ray scattering (SAXS. The differential of heat capacity, dCp/dT, signal from M-TDSC was used to quantify the weight fraction of interface in these latices. For PS-PMA (50:50 by weight structured latices in which the PS component had different crosslink densities (0, 1, 3, 5 and 10 mol% of crosslinking agent, the weight fraction of interface was about 13%. With increasing crosslink density, the fraction of interface increased only slightly. A core-shell model has been used to analyse SAXS data for these PS-PMA latices. M-TDSC can only provide information about the weight fraction of interface, but the combination of M-TDSC and SAXS can provide much more information on the morphology of such structured latices.

Differential modulation of auditory responses to attended and unattended speech in different listening conditions.

Science.gov (United States)

Kong, Ying-Yee; Mullangi, Ala; Ding, Nai

2014-10-01

This study investigates how top-down attention modulates neural tracking of the speech envelope in different listening conditions. In the quiet conditions, a single speech stream was presented and the subjects paid attention to the speech stream (active listening) or watched a silent movie instead (passive listening). In the competing speaker (CS) conditions, two speakers of opposite genders were presented diotically. Ongoing electroencephalographic (EEG) responses were measured in each condition and cross-correlated with the speech envelope of each speaker at different time lags. In quiet, active and passive listening resulted in similar neural responses to the speech envelope. In the CS conditions, however, the shape of the cross-correlation function was remarkably different between the attended and unattended speech. The cross-correlation with the attended speech showed stronger N1 and P2 responses but a weaker P1 response compared to the cross-correlation with the unattended speech. Furthermore, the N1 response to the attended speech in the CS condition was enhanced and delayed compared with the active listening condition in quiet, while the P2 response to the unattended speaker in the CS condition was attenuated compared with the passive listening in quiet. Taken together, these results demonstrate that top-down attention differentially modulates envelope-tracking neural activity at different time lags and suggest that top-down attention can both enhance the neural responses to the attended sound stream and suppress the responses to the unattended sound stream. Copyright © 2014 Elsevier B.V. All rights reserved.

Multiple-Symbol Differential Detection Of MPSK

Science.gov (United States)

Divsalar, Dariush; Simon, Marvin K.

1991-01-01

Multiple-symbol differential detection proposed for reception of radio-frequency signals modulated by mutliple-phase-shift keying (MPSK). Offers advantage of less complexity in not requiring equipment to acquire and track carrier signal. Performance approaches that of ideal coherent detection. Applicable to coded as well as uncoded MPSK, and to other forms of modulation.

Post-stimulus endogenous and exogenous oscillations are differentially modulated by task difficulty.

Science.gov (United States)

Li, Yun; Lou, Bin; Gao, Xiaorong; Sajda, Paul

2013-01-01

We investigate the modulation of post-stimulus endogenous and exogenous oscillations when a visual discrimination is made more difficult. We use exogenous frequency tagging to induce steady-state visually evoked potentials (SSVEP) while subjects perform a face-car discrimination task, the difficulty of which varies on a trial-to-trial basis by varying the noise (phase coherence) in the image. We simultaneously analyze amplitude modulations of the SSVEP and endogenous alpha activity as a function of task difficulty. SSVEP modulation can be viewed as a neural marker of attention toward/away from the primary task, while modulation of post-stimulus alpha is closely related to cortical information processing. We find that as the task becomes more difficult, the amplitude of SSVEP decreases significantly, approximately 250-450 ms post-stimulus. Significant changes in endogenous alpha amplitude follow SSVEP modulation, occurring at approximately 400-700 ms post-stimulus and, unlike the SSVEP, the alpha amplitude is increasingly suppressed as the task becomes less difficult. Our results demonstrate simultaneous measurement of endogenous and exogenous oscillations that are modulated by task difficulty, and that the specific timing of these modulations likely reflects underlying information processing flow during perceptual decision-making.

Paracrine and autocrine signals promoting full chondrogenic differentiation of a mesoblastic cell line.

Science.gov (United States)

Locker, Morgane; Kellermann, Odile; Boucquey, Marie; Khun, Huot; Huerre, Michel; Poliard, Anne

2004-01-01

The pluripotent mesoblastic C1 cell line was used under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to drive chondrogenesis. Sequential addition of two systemic hormones, dexamethasone and triiodothyronine, permits full chondrogenic differentiation. The cell intrinsic activation of the BMP signaling pathway and Sox9 expression occurring on mesoblastic condensation is insufficient for recruitment of the progenitors. Dexamethasone-dependent Sox9 upregulation is essential for chondrogenesis. Differentiation of lineage stem cells relies on cell autonomous regulations modulated by external signals. We used the pluripotent mesoblastic C1 cell line under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to induce differentiation of a precursor clone along the chondrogenic lineage. C1 cells, cultured as aggregates, were induced toward chondrogenesis by addition of 10(-7) M dexamethasone in serum-free medium. After 30 days, dexamethasone was replaced by 10 nM triiodothyronine to promote final hypertrophic conversion. Mature and hypertrophic phenotypes were characterized by immunocytochemistry using specific antibodies against types II and X collagens, respectively. Type II collagen, bone morphogenetic proteins (BMPs), BMP receptors, Smads, and Sox9 expression were monitored by reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot, and/or Western blot analysis. Once C1 cells have formed nodules, sequential addition of two systemic hormones is sufficient to promote full chondrogenic differentiation. In response to dexamethasone, nearly 100% of the C1 precursors engage in chondrogenesis and convert within 30 days into mature chondrocytes, which triggers a typical cartilage matrix. On day 25, a switch in type II procollagen mRNA splicing acted as a limiting step in the acquisition of the mature chondrocyte phenotype. On day 30, substitution of dexamethasone with

Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Directory of Open Access Journals (Sweden)

Manda V Sasidhar

Full Text Available CD147 is an activation induced glycoprotein that promotes the secretion and activation of matrix metalloproteinases (MMPs and is upregulated during the differentiation of macrophages. Interestingly, some of the molecular functions of CD147 rely on its glycosylation status: the highly glycosylated forms of CD147 induce MMPs whereas the lowly glycosylated forms inhibit MMP activation. Statins are hydroxy-methylglutaryl coenzyme A reductase inhibitors that block the synthesis of mevalonate, thereby inhibiting all mevalonate-dependent pathways, including isoprenylation, N-glycosylation and cholesterol synthesis. In this study, we investigated the role of statins in the inhibition of macrophage differentiation and the associated process of MMP secretion through modulation of CD147. We observed that differentiation of the human monocytic cell line THP-1 to a macrophage phenotype led to upregulation of CD147 and CD14 and that this effect was inhibited by statins. At the molecular level, statins altered CD147 expression, structure and function by inhibiting isoprenylation and N-glycosylation. In addition, statins induced a shift of CD147 from its highly glycosylated form to its lowly glycosylated form. This shift in N-glycosylation status was accompanied by a decrease in the production and functional activity of MMP-2 and MMP-9. In conclusion, these findings describe a novel molecular mechanism of immune regulation by statins, making them interesting candidates for autoimmune disease therapy.

Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Science.gov (United States)

Sasidhar, Manda V; Chevooru, Sai Krishnaveni; Eickelberg, Oliver; Hartung, Hans-Peter; Neuhaus, Oliver

2017-01-01

CD147 is an activation induced glycoprotein that promotes the secretion and activation of matrix metalloproteinases (MMPs) and is upregulated during the differentiation of macrophages. Interestingly, some of the molecular functions of CD147 rely on its glycosylation status: the highly glycosylated forms of CD147 induce MMPs whereas the lowly glycosylated forms inhibit MMP activation. Statins are hydroxy-methylglutaryl coenzyme A reductase inhibitors that block the synthesis of mevalonate, thereby inhibiting all mevalonate-dependent pathways, including isoprenylation, N-glycosylation and cholesterol synthesis. In this study, we investigated the role of statins in the inhibition of macrophage differentiation and the associated process of MMP secretion through modulation of CD147. We observed that differentiation of the human monocytic cell line THP-1 to a macrophage phenotype led to upregulation of CD147 and CD14 and that this effect was inhibited by statins. At the molecular level, statins altered CD147 expression, structure and function by inhibiting isoprenylation and N-glycosylation. In addition, statins induced a shift of CD147 from its highly glycosylated form to its lowly glycosylated form. This shift in N-glycosylation status was accompanied by a decrease in the production and functional activity of MMP-2 and MMP-9. In conclusion, these findings describe a novel molecular mechanism of immune regulation by statins, making them interesting candidates for autoimmune disease therapy.

Quantitative Analysis of Proteome Modulations in Alveolar Epithelial Type II Cells in Response to Pulmonary Aspergillus fumigatus Infection.

Science.gov (United States)

Seddigh, Pegah; Bracht, Thilo; Molinier-Frenkel, Válerie; Castellano, Flavia; Kniemeyer, Olaf; Schuster, Marc; Weski, Juliane; Hasenberg, Anja; Kraus, Andreas; Poschet, Gernot; Hager, Thomas; Theegarten, Dirk; Opitz, Christiane A; Brakhage, Axel A; Sitek, Barbara; Hasenberg, Mike; Gunzer, Matthias

2017-12-01

The ubiquitous mold Aspergillus fumigatus threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. A. fumigatus conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Previous studies reported the importance of the surfactant-producing AEC II during A. fumigatus infection via in vitro experiments using cell lines. We established a negative isolation protocol yielding untouched primary murine AEC II with a purity >90%, allowing ex vivo analyses of the cells, which encountered the mold in vivo By label-free proteome analysis of AEC II isolated from mice 24h after A. fumigatus or mock infection we quantified 2256 proteins and found 154 proteins to be significantly differentially abundant between both groups (ANOVA p value ≤ 0.01, ratio of means ≥1.5 or ≤0.67, quantified with ≥2 peptides). Most of these proteins were higher abundant in the infected condition and reflected a comprehensive activation of AEC II on interaction with A. fumigatus This was especially represented by proteins related to oxidative phosphorylation, hence energy production. However, the most strongly induced protein was the l-amino acid oxidase (LAAO) Interleukin 4 induced 1 (IL4I1) with a 42.9 fold higher abundance (ANOVA p value 2.91 -10 ). IL4I1 has previously been found in B cells, macrophages, dendritic cells and rare neurons. Increased IL4I1 abundance in AEC II was confirmed by qPCR, Western blot and immunohistology. Furthermore, A. fumigatus infected lungs showed high levels of IL4I1 metabolic products. Importantly, higher IL4I1 abundance was also confirmed in lung tissue from human aspergilloma. Because LAAO are key enzymes for bactericidal product generation, AEC II might actively participate in pathogen defense. We provide insights into proteome changes of primary AEC II thereby opening new avenues to analyze the molecular changes of this central lung cell on infectious threats. Data are available via Proteome

Attenuation of myocardial fibrosis with curcumin is mediated by modulating expression of angiotensin II AT1/AT2 receptors and ACE2 in rats

Directory of Open Access Journals (Sweden)

Pang XF

2015-11-01

Full Text Available Xue-Fen Pang,1 Li-Hui Zhang,2 Feng Bai,1 Ning-Ping Wang,3 Ron E Garner,3 Robert J McKallip,4 Zhi-Qing Zhao1,3 1Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Cardiology, Shanxi Academy of Medical Sciences and Shanxi Dayi Hospital, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA; 4Division of Basic Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USA Abstract: Curcumin is known to improve cardiac function by balancing degradation and synthesis of collagens after myocardial infarction. This study tested the hypothesis that inhibition of myocardial fibrosis by curcumin is associated with modulating expression of angiotensin II (Ang II receptors and angiotensin-converting enzyme 2 (ACE2. Male Sprague Dawley rats were subjected to Ang II infusion (500 ng/kg/min using osmotic minipumps for 2 and 4 weeks, respectively, and curcumin (150 mg/kg/day was fed by gastric gavage during Ang II infusion. Compared to the animals with Ang II infusion, curcumin significantly decreased the mean arterial blood pressure during the course of the observation. The protein level of the Ang II type 1 (AT1 receptor was reduced, and the Ang II type 2 (AT2 receptor was up-regulated, evidenced by an increased ratio of the AT2 receptor over the AT1 receptor in the curcumin group (1.2±0.02% vs in the Ang II group (0.7±0.03%, P<0.05. These changes were coincident with less locally expressed AT1 receptor and enhanced AT2 receptor in the intracardiac vessels and intermyocardium. Along with these modulations, curcumin significantly decreased the populations of macrophages and alpha smooth muscle actin-expressing myofibroblasts, which were accompanied by reduced expression of transforming growth factor beta 1 and phosphorylated-Smad2/3. Collagen I synthesis was

Modulation of differentiation and self-renewal of tissue specific stem cells for effective mitigation of radiation injury

International Nuclear Information System (INIS)

Bandekar, Mayuri; Patwardhan, R.S.; Maurya, Dharmendra K.; Bhilwade, Hari N.; Sharma, Deepak; Sandur, Santosh Kumar

2017-01-01

The use of stem cells in regenerative medicine for the treatment of various human diseases is one of the active research areas. The aim of regenerative medicine is to restore normal tissue functions by replenishing injured tissues using either cell-based therapy or by inducing certain factors that can aid endogenous repair and regeneration. The approach for inducing endogenous repair and regeneration requires in vivo modulation of tissue-specific stem cells by therapeutic agents and enhance their abundance through activation, proliferation, differentiation, or reprogramming. Here we describe three different approaches to enhance the abundance of hematopoietic stem cells in vivo for mitigation of radiation induced toxicity. Baicalein, a flavonoid derived from Chinese and Indian medicinal plants like Scutellaria baicalensis and Terminalia ariuna enhanced the abundance of hematopoietic stem cells through activation of Nrf-2 in the lineage negative cells. Another anti-oxidant, chlorophyllin derived from green plant pigment, chlorophyll also enhanced the abundance of hematopoietic stem cells through modulation of cell cycle in cells of the bone marrow. Treatment of mice with Cobaltus chloride (CoCl_2), a well-known activator of hypoxia inducible factor-1α (HIP-1α), also led to increase in the number of hematopoietic stem cells in the bone marrow. Whereas chlorophyllin offered up to 100 % protection against whole body irradiation (WBI, 8 Gy) induced mortality in mice, baicalein offered up to70%protection. Cobaltus chloride treatment offered 40% protection against 8 Gy of WBI. These studies indicate potential use of stem cell modulating agents as effective mitigators of radiation induced toxicity in vivo. (author)

Supernatant from bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells.

Directory of Open Access Journals (Sweden)

Cyrille Hoarau

Full Text Available BACKGROUND: Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK, glycogen synthase kinase-3 (GSK3 and phosphatidylinositol 3-kinase (PI3K pathways on biological functions of human monocyte-derived DCs treated with BbC50sn. METHODOLOGY/PRINCIPAL FINDINGS: DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS or Zymosan, with or without specific inhibitors of p38MAPK (SB203580, ERK (PD98059, PI3K (LY294002 and GSK3 (SB216763. We found that 1 the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2 p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3 ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4 BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS. CONCLUSION/SIGNIFICANCE: We report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria.

NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.

Science.gov (United States)

Anastasia, Luigi; Papini, Nadia; Colazzo, Francesca; Palazzolo, Giacomo; Tringali, Cristina; Dileo, Loredana; Piccoli, Marco; Conforti, Erika; Sitzia, Clementina; Monti, Eugenio; Sampaolesi, Maurilio; Tettamanti, Guido; Venerando, Bruno

2008-12-26

Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.

Modulation of Rhamm (CD168) for selective adipose tissue development

Science.gov (United States)

Turley, Eva A; Bissell, Mina J

2014-05-06

Herein is described the methods and compositions for modulation of Rhamm, also known as CD 186, and its effects on wound repair, muscle differentiation, bone density and adipogeneisis through its ability to regulate mesenchymal stem cell differentiation. Compositions and methods are provided for blocking Rhamm function for selectively increasing subcutaneous, but not, visceral fat. Compositions and methods for modulating Rhamm in wound repair are also described.

NOV/CCN3 impairs muscle cell commitment and differentiation

International Nuclear Information System (INIS)

Calhabeu, Frederico; Lafont, Jerome; Le Dreau, Gwenvael; Laurent, Maryvonne; Kazazian, Chantal; Schaeffer, Laurent; Martinerie, Cecile; Dubois, Catherine

2006-01-01

NOV (nephroblastoma overexpressed) is a member of a family of proteins which encodes secreted matrix-associated proteins. NOV is expressed during development in dermomyotome and limb buds, but its functions are still poorly defined. In order to understand the role of NOV in myogenic differentiation, C2C12 cells overexpressing NOV (C2-NOV) were generated. These cells failed to engage into myogenic differentiation, whereas they retained the ability to differentiate into osteoblasts. In differentiating conditions, C2-NOV cells remained proliferative, failed to express differentiation markers and lost their ability to form myotubes. Inhibition of differentiation by NOV was also observed with human primary muscle cells. Further examination of C2-NOV cells revealed a strong downregulation of the myogenic determination genes MyoD and Myf5 and of IGF-II expression. MyoD forced expression in C2-NOV was sufficient to restore differentiation and IGF-II induction whereas 10 -6 M insulin treatment had no effects. NOV therefore acts upstream of MyoD and does not affect IGF-II induction and signaling. HES1, a target of Notch, previously proposed to mediate NOV action, was not implicated in the inhibition of differentiation. We propose that NOV is a specific cell fate regulator in the myogenic lineage, acting negatively on key myogenic genes thus controlling the transition from progenitor cells to myoblasts

Differential SPR immunosensing

NARCIS (Netherlands)

Berger, Charles E.H.; Berger, C.E.H.; Greve, Jan

2000-01-01

In this work we describe a surface plasmon resonance (SPR) sensor with a differential detection of the SPR angle, and demonstrate it. The angle of incidence is modulated by a simple piezo-electric actuator, and the reflectance signal is measured with a lockin-amplifier. When the conditions for SPR

HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways.

Science.gov (United States)

Guo, Fang; Zhao, Qiong; Sheraz, Muhammad; Cheng, Junjun; Qi, Yonghe; Su, Qing; Cuconati, Andrea; Wei, Lai; Du, Yanming; Li, Wenhui; Chang, Jinhong; Guo, Ju-Tao

2017-09-01

Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or "empty" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.

HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways.

Directory of Open Access Journals (Sweden)

Fang Guo

2017-09-01

Full Text Available Hepatitis B virus (HBV core protein assembles viral pre-genomic (pg RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs and sulfamoylbenzamides (SBAs, have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or "empty" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.

HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways

Science.gov (United States)

Guo, Fang; Zhao, Qiong; Cheng, Junjun; Qi, Yonghe; Su, Qing; Wei, Lai; Li, Wenhui; Chang, Jinhong

2017-01-01

Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or “empty” capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B. PMID:28945802

Crystallization and preliminary X-ray analysis of Acetivibrio cellulolyticus cellulosomal type II cohesin module: two versions having different linker lengths

International Nuclear Information System (INIS)

Noach, Ilit; Alber, Orly; Bayer, Edward A.; Lamed, Raphael; Levy-Assaraf, Maly; Shimon, Linda J. W.; Frolow, Felix

2007-01-01

The cloning, expression, purification, crystallization and preliminary X-ray characterization of two protein constructs of the second type II cohesin module from A. cellulolyticus ScaB are described. Both constructs contain the native N-terminal linker, but only one of them contains the full-length 45-residue C-terminal linker; the other contains a five-residue segment of this linker. The second type II cohesin module of the cellulosomal scaffoldin polypeptide ScaB from Acetivibrio cellulolyticus (CohB2) was cloned into two constructs: one containing a short (five-residue) C-terminal linker (CohB2-S) and the second incorporating the full native 45-residue linker (CohB2-L). Both constructs encode proteins that also include the full native six-residue N-terminal linker. The CohB2-S and CohB2-L proteins were expressed, purified and crystallized in the orthorhombic crystal system, but with different unit cells and symmetries: space group P2 1 2 1 2 1 with unit-cell parameters a = 90.36, b = 68.65, c = 111.29 Å for CohB2-S and space group P2 1 2 1 2 with unit-cell parameters a = 68.76, b = 159.22, c = 44.21 Å for CohB2-L. The crystals diffracted to 2.0 and 2.9 Å resolution, respectively. The asymmetric unit of CohB2-S contains three cohesin molecules, while that of CohB2-L contains two molecules

A status report on the PBFA II construction project

International Nuclear Information System (INIS)

Barr, G.W.; Furaus, J.P.; Cook, D.L.; Shirley, C.G.

1985-01-01

The Particle Beam Fusion Accelerator II (PBFA II) is under construction at Sandia National Laboratories (SNL). PBFA II contains 36 individual power modules configured in a stacked radial geometry and synchronized to provide greater than 3.5 MJ of energy into the vacuum section in a single 55-ns-wide 90-TW peak power pulse. This R and D construction project is being implemented in a fast track schedule mode in which final design of the accelerator components occurs in parallel with the construction of the laboratory building and the accelerator tank. PBFA II is scheduled to become operational in January 1986 with its first multi-module shot into an applied-B ion diode that will generate and transport a beam of lithium ions. Plans are now being made for experimental work on PBFA II beyond the construction phase

Nonlinear self-modulation of ion-acoustic waves

International Nuclear Information System (INIS)

Ikezi, H.; Schwarzenegger, K.; Simons, A.L.; Ohsawa, Y.; Kamimura, T.

1978-01-01

The nonlinear evolution of an ion-acoustic wave packet is studied. Experimentally, it is found that (i) nonlinear phase modulation develops in the wave packet; (ii) the phase modulation, together with the dispersion effect, causes expansion and breaking of the wave packet; (iii) the ions trapped in the troughs of the wave potential introduce self-phase modulation; and (iv) the ion-acoustic wave is stable with respect to the modulational instability. Computer simulations have reproduced the experimental results. The physical picture and the model equation describing the wave evolution are discussed

Preliminary PBFA II design

International Nuclear Information System (INIS)

Johnson, D.L.; VanDevender, J.P.; Martin, T.H.

1980-01-01

The upgrade of Sandia National Laboratories particle beam fusion accelerator, PBFA I, to PBFA II presents several interesting and challenging pulsed power design problems. PBFA II requires increasing the PBFA I output parameters from 2 MV, 30 TW, 1 MJ to 4 MV, 100 TW, 3.5 MJ with the constraint of using much of the same PBFA I hardware. The increased PBFA II output will be obtained by doubling the number of modules (from 36 to 72), increasing the primary energy storage (from 4 MJ to 15 MJ), lowering the pulse forming line (PFL) output impedance, and adding a voltage doubling network

The self shielding module of Apollo.II; Module d`autoprotection du code Apollo.II

Energy Technology Data Exchange (ETDEWEB)

Sanchez, R.

1994-06-01

This note discusses the methods used in the APOLLO.II code for the calculation of self shielded multigroup cross sections. Basically, the calculation consists in characterizing a heterogenous medium with a single parameter: the background cross section, which is in then used to interpolate reaction rates from pre tabulated values. Very fine multigroup slowing down calculations in homogenous media are used to generate these tables, which contain absorption, diffusion and production reaction rates per group, resonant isotope, temperature and background cross section. Multigroup self shielded cross sections are determined from an equivalence that preserves absorption rates at a slowing down problem with given sources. This article gives a detailed description of the PIC and ``dilution matrix`` formalisms that are used in the homogenization step, as well as the utilization of Bell macro-groups and the different quadrature formulas that may be used in the calculations. Self shielding techniques for isotopic resonant mixtures are also discussed. (author). 2 refs., 193 figs., 2 tabs.

Identification of differentially expressed proteins during human urinary bladder cancer progression

DEFF Research Database (Denmark)

Memon, Ashfaque Ahmed; chang, Jong. w; Oh, Bong R.

2005-01-01

and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder...... cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may...

A Differential Evolution Based MPPT Method for Photovoltaic Modules under Partial Shading Conditions

Directory of Open Access Journals (Sweden)

Kok Soon Tey

2014-01-01

Full Text Available Partially shaded photovoltaic (PV modules have multiple peaks in the power-voltage (P-V characteristic curve and conventional maximum power point tracking (MPPT algorithm, such as perturbation and observation (P&O, which is unable to track the global maximum power point (GMPP accurately due to its localized search space. Therefore, this paper proposes a differential evolution (DE based optimization algorithm to provide the globalized search space to track the GMPP. The direction of mutation in the DE algorithm is modified to ensure that the mutation always converges to the best solution among all the particles in the generation. This helps to provide the rapid convergence of the algorithm. Simulation of the proposed PV system is carried out in PSIM and the results are compared to P&O algorithm. In the hardware implementation, a high step-up DC-DC converter is employed to verify the proposed algorithm experimentally on partial shading conditions, load variation, and solar intensity variation. The experimental results show that the proposed algorithm is able to converge to the GMPP within 1.2 seconds with higher efficiency than P&O.

E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway

International Nuclear Information System (INIS)

Contreras-Paredes, Adriana; Cruz-Hernandez, Erick de la; Martinez-Ramirez, Imelda; Duenas-Gonzalez, Alfonso; Lizano, Marcela

2009-01-01

Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation

Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study.

Science.gov (United States)

Gao, Patrick P; Zhang, Jevin W; Fan, Shu-Juan; Sanes, Dan H; Wu, Ed X

2015-12-01

gain modulation is mediated primarily through direct projections and they point to future investigations of the differential roles of the direct and indirect projections in corticofugal modulation. In summary, our imaging findings demonstrate the large-scale descending influences, from both the auditory and visual cortices, on sound processing in different IC subdivisions. They can guide future studies on the coordinated activity across multiple regions of the auditory network, and its dysfunctions. Copyright © 2015 Elsevier Inc. All rights reserved.

Type II cytokeratin gene expression is indicative of early cell differentiation in the chick embryo

International Nuclear Information System (INIS)

Charlebois, T.S.

1988-01-01

Embryonic development in vertebrates appears to involve a series of inductive tissue interactions that lead to regional specializations, which eventually become elaborated in the basic body plan of the embryo. The inductive interactions leading to early regionalization of the embryo are often particularly difficult to evaluate because of the absence of available morphological or biochemical evidence that such events have occurred. In the 36 hour chick embryo, the regional subdivision of the early ectoderm is evidence by a marked lens-forming bias in the head ectoderm, which is absent in the presumptive dorsal epidermis of the trunk region. As a strategy for isolating genes whose differential expression might reflect this regional subdivision, a cDNA library from 36 hour embryos was prepared and screened for differential hybridization to [ 32 P]cDNA probes synthesized using template RNA isolated from 36 hour head ectoderm and trunk ectoderm. A cDNA clone (T4) was isolated which hybridizes to transcripts present at much higher levels in trunk ectoderm than in head ectoderm. Partial nucleotide and deduced amino acid sequences of this clone indicate that it represents a gene encoding a type II cytokeratin. The distribution of transcripts complementary to the T4 probe was evaluated in early embryos using RNA gel blot analysis and in situ hybridization to tissue sections

Sustained release of melatonin from TiO2 nanotubes for modulating osteogenic differentiation of mesenchymal stem cells in vitro.

Science.gov (United States)

Lai, Min; Jin, Ziyang; Tang, Qiang; Lu, Min

2017-10-01

To control the sustained release of melatonin and modulate the osteogenic differentiation of mesenchymal stem cells (MSCs), melatonin was firstly loaded onto TiO 2 nanotubes by direct dropping method, and then a multilayered film was coated by a spin-assisted layer-by-layer technique, which was composed of chitosan (Chi) and gelatin (Gel). Successful fabrication was characterized by field emission scanning electron microscopy, atomic force microscope, X-ray photoelectron spectroscopy and contact angle measurement, respectively. The efficient sustained release of melatonin was measured by UV-visible-spectrophotometer. After 2 days of culture, well-spread morphology was observed in MSCs grown on the Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates as compared to different groups. After 4, 7, 14 and 21 days of culture, the multilayered-coated melatonin-loaded TiO 2 nanotube substrates increased cell proliferation, increased alkaline phosphatase (ALP) and mineralization, increased expression of mRNA levels for runt-related transcription factor 2 (Runx2), ALP, osteopontin (OPN) and osteocalcin (OC), indicative of osteoblastic differentiation. These results demonstrated that Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates promoted cell adhesion, spreading, proliferation and differentiation and could provide an alternative fabrication method for titanium-based implants to enhance the osteointegration between bone tissues and implant surfaces.

Data management in the TJ-II multi-layer database

International Nuclear Information System (INIS)

Vega, J.; Cremy, C.; Sanchez, E.; Portas, A.; Fabregas, J.A.; Herrera, R.

2000-01-01

The handling of TJ-II experimental data is performed by means of several software modules. These modules provide the resources for data capture, data storage and management, data access as well as general-purpose data visualisation. Here we describe the module related to data storage and management. We begin by introducing the categories in which data can be classified. Then, we describe the TJ-II data flow through the several file systems involved, before discussing the architecture of the TJ-II database. We review the concept of the 'discharge file' and identify the drawbacks that would result from a direct application of this idea to the TJ-II data. In order to overcome these drawbacks, we propose alternatives based on our concepts of signal family, user work-group and data priority. Finally, we present a model for signal storage. This model is in accordance with the database architecture and provides a proper framework for managing the TJ-II experimental data. In the model, the information is organised in layers and is distributed according to the generality of the information, from the common fields of all signals (first layer), passing through the specific records of signal families (second layer) and reaching the particular information of individual signals (third layer)

FGF-2b and h-PL Transform Duct and Non-Endocrine Human Pancreatic Cells into Endocrine Insulin Secreting Cells by Modulating Differentiating Genes

Directory of Open Access Journals (Sweden)

Giulia Donadel

2017-10-01

Full Text Available Background: Diabetes mellitus (DM is a multifactorial disease orphan of a cure. Regenerative medicine has been proposed as novel strategy for DM therapy. Human fibroblast growth factor (FGF-2b controls β-cell clusters via autocrine action, and human placental lactogen (hPL-A increases functional β-cells. We hypothesized whether FGF-2b/hPL-A treatment induces β-cell differentiation from ductal/non-endocrine precursor(s by modulating specific genes expression. Methods: Human pancreatic ductal-cells (PANC-1 and non-endocrine pancreatic cells were treated with FGF-2b plus hPL-A at 500 ng/mL. Cytofluorimetry and Immunofluorescence have been performed to detect expression of endocrine, ductal and acinar markers. Bromodeoxyuridine incorporation and annexin-V quantified cells proliferation and apoptosis. Insulin secretion was assessed by RIA kit, and electron microscopy analyzed islet-like clusters. Results: Increase in PANC-1 duct cells de-differentiation into islet-like aggregates was observed after FGF-2b/hPL-A treatment showing ultrastructure typical of islets-aggregates. These clusters, after stimulation with FGF-2b/hPL-A, had significant (p < 0.05 increase in insulin, C-peptide, pancreatic and duodenal homeobox 1 (PDX-1, Nkx2.2, Nkx6.1, somatostatin, glucagon, and glucose transporter 2 (Glut-2, compared with control cells. Markers of PANC-1 (Cytokeratin-19, MUC-1, CA19-9 were decreased (p < 0.05. These aggregates after treatment with FGF-2b/hPL-A significantly reduced levels of apoptosis. Conclusions: FGF-2b and hPL-A are promising candidates for regenerative therapy in DM by inducing de-differentiation of stem cells modulating pivotal endocrine genes.

Wavelength-modulated spectroscopy of the sub-bandgap response of solar cell devices

Energy Technology Data Exchange (ETDEWEB)

Mandanirina, N.H., E-mail: s213514095@nmmu.ac.za; Botha, J.R.; Wagener, M.C.

2016-01-01

A wavelength-modulation setup for measuring the differential photo-response of a GaSb/GaAs quantum ring solar cell structure is reported. The pseudo-monochromatic wavelength is modulated at the output of a conventional monochromator by means of a vibrating slit mechanism. The vibrating slit was able to modulate the excitation wavelength up to 33 nm. The intensity of the light beam was kept constant through a unique flux correction module, designed and built in-house. The setup enabled measurements in the near-infrared range (from 1000 to 1300 nm), which is specifically used to probe the sub-band gap differential photo-response of GaAs solar cells.

Differential Equations Compatible with KZ Equations

International Nuclear Information System (INIS)

Felder, G.; Markov, Y.; Tarasov, V.; Varchenko, A.

2000-01-01

We define a system of 'dynamical' differential equations compatible with the KZ differential equations. The KZ differential equations are associated to a complex simple Lie algebra g. These are equations on a function of n complex variables z i taking values in the tensor product of n finite dimensional g-modules. The KZ equations depend on the 'dual' variable in the Cartan subalgebra of g. The dynamical differential equations are differential equations with respect to the dual variable. We prove that the standard hypergeometric solutions of the KZ equations also satisfy the dynamical equations. As an application we give a new determinant formula for the coordinates of a basis of hypergeometric solutions

Modulation of transcription factors by curcumin.

Science.gov (United States)

Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

2007-01-01

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

Optimization of flavanones extraction by modulating differential solvent densities and centrifuge temperatures.

Science.gov (United States)

Chebrolu, Kranthi K; Jayaprakasha, G K; Jifon, J; Patil, Bhimanagouda S

2011-07-15

Understanding the factors influencing flavonone extraction is critical for the knowledge in sample preparation. The present study was focused on the extraction parameters such as solvent, heat, centrifugal speed, centrifuge temperature, sample to solvent ratio, extraction cycles, sonication time, microwave time and their interactions on sample preparation. Flavanones were analyzed in a high performance liquid chromatography (HPLC) and later identified by liquid chromatography and mass spectrometry (LC-MS). The five flavanones were eluted by a binary mobile phase with 0.03% phosphoric acid and acetonitrile in 20 min and detected at 280 nm, and later identified by mass spectral analysis. Dimethylsulfoxide (DMSO) and dimethyl formamide (DMF) had optimum extraction levels of narirutin, naringin, neohesperidin, didymin and poncirin compared to methanol (MeOH), ethanol (EtOH) and acetonitrile (ACN). Centrifuge temperature had a significant effect on flavanone distribution in the extracts. The DMSO and DMF extracts had homogeneous distribution of flavanones compared to MeOH, EtOH and ACN after centrifugation. Furthermore, ACN showed clear phase separation due to differential densities in the extracts after centrifugation. The number of extraction cycles significantly increased the flavanone levels during extraction. Modulating the sample to solvent ratio increased naringin quantity in the extracts. Current research provides critical information on the role of centrifuge temperature, extraction solvent and their interactions on flavanone distribution in extracts. Published by Elsevier B.V.

The differentiation of the character of solid lesions in the breast in the compression sonoelastography. Part II: Diagnostic value of BIRADS-US classification, Tsukuba score and FLR ratio

OpenAIRE

Dobruch-Sobczak, Katarzyna

2013-01-01

Sonoelastography is a dynamically developing method of ultrasound examination used to differentiate the character of focal lesions in the breasts. The aim of the Part II of the study is to determine the usefulness of sonoelastography in the differentiation diagnosis of focal breast lesions including the evaluation of the diagnostic value of Tsukuba score and FLR ratio in characterizing solid lesions in the breasts. Furthermore, the paper provides a comparison of classic B-mode imaging and son...

PBFA II energy storage section design

International Nuclear Information System (INIS)

Wilson, J.M.

1983-01-01

PBFA II will be the second thirty-six module accelerator built at Sandia National Laboratories for particle beam fusion feasibility studies. Each module of the machine will deliver 2.8 terawatts to a central experimental chamber. The total power delivered (100 terawatts) is expected to permit ignition scaling studies beginning in 1986. The PBFA II energy storage system consists of thirty-six 6.0 mv, 400 kj. Marx generators with their high voltage trigger and charging systems, and electromechanical output switching system. The paper describes the current design of this section of the machine. Constraints imposed by the existing tank and building are presented, as they relate to locating support systems in the oil section of PBFA II. The charging system and output switches have been designed and are described. A conceptual design for the Marx triggering system is also presented. Additional hardware (monitors, grounding connections, etc.) is discussed briefly with design details given where available

IKKα/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation.

Directory of Open Access Journals (Sweden)

Eleonora Olivotto

Full Text Available BACKGROUND: The non-canonical NF-κB activating kinase IKKα, encoded by CHUK (conserved-helix-loop-helix-ubiquitous-kinase, has been reported to modulate pro- or anti- inflammatory responses, cellular survival and cellular differentiation. Here, we have investigated the mechanism of action of IKKα as a novel effector of human and murine chondrocyte extracellular matrix (ECM homeostasis and differentiation towards hypertrophy. METHODOLOGY/PRINCIPAL FINDINGS: IKKα expression was ablated in primary human osteoarthritic (OA chondrocytes and in immature murine articular chondrocytes (iMACs derived from IKKα(f/f:CreERT2 mice by retroviral-mediated stable shRNA transduction and Cre recombinase-dependent Lox P site recombination, respectively. MMP-10 was identified as a major target of IKKα in chondrocytes by mRNA profiling, quantitative RT-PCR analysis, immunohistochemistry and immunoblotting. ECM integrity, as assessed by type II collagen (COL2 deposition and the lack of MMP-dependent COL2 degradation products, was enhanced by IKKα ablation in mice. MMP-13 and total collagenase activities were significantly reduced, while TIMP-3 (tissue inhibitor of metalloproteinase-3 protein levels were enhanced in IKKα-deficient chondrocytes. IKKα deficiency suppressed chondrocyte differentiation, as shown by the quantitative inhibition of.Alizarin red staining and the reduced expression of multiple chondrocyte differentiation effectors, including Runx2, Col10a1 and Vegfa,. Importantly, the differentiation of IKKα-deficient chondrocytes was rescued by a kinase-dead IKKα protein mutant. CONCLUSIONS/SIGNIFICANCE: IKKα acts independent of its kinase activity to help drive chondrocyte differentiation towards a hypertrophic-like state. IKKα positively modulates ECM remodeling via multiple downstream targets (including MMP-10 and TIMP-3 at the mRNA and post-transcriptional levels, respectively to maintain maximal MMP-13 activity, which is required for ECM

Optical spectral reshaping for directly modulated 4-pulse amplitude modulation signals

DEFF Research Database (Denmark)

Ozolins, Oskars; Da Ros, Francesco; Cristofori, Valentina

2017-01-01

The tremendous traffic growth in intra/inter-datacenters requires low-cost high-speed integrated solutions [1]. To enable a significantly reduced footprint directly modulated lasers (DMLs) have been proposed instead of large external modulators. However, it is challenging to use DMLs due to their......The tremendous traffic growth in intra/inter-datacenters requires low-cost high-speed integrated solutions [1]. To enable a significantly reduced footprint directly modulated lasers (DMLs) have been proposed instead of large external modulators. However, it is challenging to use DMLs due...... (PAM) [3] signals. However, moving to 4-PAM,many of the impressive demonstrations reported so far rely heavily on off-line digital signal processing (DSP), which increases latency, power consumption and cost. In this talk, we report on (i) a detailed numerical analysis on the complex transfer function...... of the optical filter for optical spectral reshaping in case of pulse amplitude modulation and(ii) an experimental demonstration of real-time dispersion-uncompensated transmission of 10-GBd and 14-GBd 4-PAM signals up to 10- and 26-km SSMF. This is achieved by combining a commercial 10-Gb/s DML with optical...

Finite Element calculations of heat transfer for the Forward SCT ModulesPart II - the Inner Module ATL-COM-INDET-2000-015

CERN Document Server

Blocki, J

2000-01-01

A status report on the thermal performance of the baseline SCT inner forward modules is presented. In order to understand improvements of the thermal behaviour, design changes that have been proposed elsewhere for the outer module, and which lead to significant improvements of the thermal characteristics of the modules, have been applied to the inner module.

Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme*

Science.gov (United States)

Sato, Shigeo; Tomomori-Sato, Chieri; Tsai, Kuang-Lei; Yu, Xiaodi; Sardiu, Mihaela; Saraf, Anita; Washburn, Michael P.; Florens, Laurence; Asturias, Francisco J.; Conaway, Ronald C.

2016-01-01

Mediator plays an integral role in activation of RNA polymerase II (Pol II) transcription. A key step in activation is binding of Mediator to Pol II to form the Mediator-Pol II holoenzyme. Here, we exploit a combination of biochemistry and macromolecular EM to investigate holoenzyme assembly. We identify a subset of human Mediator head module subunits that bind Pol II independent of other subunits and thus probably contribute to a major Pol II binding site. In addition, we show that binding of human Mediator to Pol II depends on the integrity of a conserved “hinge” in the middle module MED21-MED7 heterodimer. Point mutations in the hinge region leave core Mediator intact but lead to increased disorder of the middle module and markedly reduced affinity for Pol II. These findings highlight the importance of Mediator conformation for holoenzyme assembly. PMID:27821593

Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1.

Science.gov (United States)

Hawkins, Brian T; Grego, Sonia; Sellgren, Katelyn L

2015-05-22

Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. Brain endothelial cells were grown alone or in co-culture with astrocytes. Astrocytes were grown either as conventional (2D) monolayers, or in a collagen-based gel which allows them to grow in a three-dimensional (3D) construct. Astrocytes were viable in 3D conditions, and displayed a marked reduction in their expression of glial fibrillary acidic protein (GFAP), suggesting reduced activation. Stimulation of astrocytes with transforming growth factor (TGF)β1 decreased transendothelial electrical resistance (TEER) and reduced expression of claudin-5 in co-cultures, whereas treatment of endothelial cells in the absence of astrocytes was without effect. The effect of TGFβ1 on TEER was significantly more pronounced in endothelial cells cultured with 3D astrocytes compared to 2D astrocytes. These results demonstrate that astrocyte culture conditions differentially affect their ability to modulate brain endothelial barrier function, and suggest a direct relationship between reactive gliosis and BBB permeability. Moreover, these studies demonstrate the potential importance of physiologically relevant culture conditions to in vitro modeling of disease processes that affect the neurovascular unit. Copyright © 2015 Elsevier B.V. All rights reserved.

Performance comparison of binary modulation schemes for visible light communication

KAUST Repository

Park, Kihong; Li, Changping; Alouini, Mohamed-Slim

2015-01-01

communication with dimming control. We also propose a novel slope-based modulation called differential chip slope modulation (DCSM) and develop a chip-based hard-decision receiver to demodulate the resulting signal, detect the chip sequence, and decode the input

Rat vas deferens SERCA2 is modulated by Ca2+/calmodulin protein kinase II-mediated phosphorylation

International Nuclear Information System (INIS)

Rodriguez, J.B.R.; Muzi-Filho, H.; Valverde, R.H.F.; Quintas, L.E.M.; Noel, F.; Einicker-Lamas, M.; Cunha, V.M.N.

2013-01-01

Ca 2+ pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca 2+ -ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca 2+ -ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (∼115 kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca 2+ (Ca 0.5 = 780 nM) and a low sensitivity to vanadate (IC 50 = 41 µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca 2+ and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca 2+ accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca 2+ and CaM, possibly via CaMKII, in a process that results in stimulation of Ca 2+ pumping activity

Index modulation for 5G wireless communications

CERN Document Server

Wen, Miaowen; Yang, Liuqing

2017-01-01

This book presents a thorough examination of index modulation, an emerging 5G modulation technique. It includes representative transmitter and receiver design, optimization, and performance analysis of index modulation in various domains. First, the basic spatial modulation system for the spatial domain is introduced. Then, the development of a generalized pre-coding aided quadrature spatial modulation system as well as a virtual spatial modulation system are presented. For the space-time domain, a range of differential spatial modulation systems are examined, along with the pre-coding design. Both basic and enhanced index modulated OFDM systems for the frequency domain are discussed, focusing on the verification of their strong capabilities in inter-carrier interference mitigation. Finally, key open problems are highlighted and future research directions are considered. Designed for researchers and professionals, this book is essential for anyone working in communications networking, 5G, and system design. A...

TALE-PvuII fusion proteins--novel tools for gene targeting.

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

Visual attention to food cues is differentially modulated by gustatory-hedonic and post-ingestive attributes.

Science.gov (United States)

Garcia-Burgos, David; Lao, Junpeng; Munsch, Simone; Caldara, Roberto

2017-07-01

Although attentional biases towards food cues may play a critical role in food choices and eating behaviours, it remains largely unexplored which specific food attribute governs visual attentional deployment. The allocation of visual attention might be modulated by anticipatory postingestive consequences, from taste sensations derived from eating itself, or both. Therefore, in order to obtain a comprehensive understanding of the attentional mechanisms involved in the processing of food-related cues, we recorded the eye movements to five categories of well-standardised pictures: neutral non-food, high-calorie, good taste, distaste and dangerous food. In particular, forty-four healthy adults of both sexes were assessed with an antisaccade paradigm (which requires the generation of a voluntary saccade and the suppression of a reflex one) and a free viewing paradigm (which implies the free visual exploration of two images). The results showed that observers directed their initial fixations more often and faster on items with high survival relevance such as nutrient and possible dangers; although an increase in antisaccade error rates was only detected for high-calorie items. We also found longer prosaccade fixation duration and initial fixation duration bias score related to maintained attention towards high-calorie, good taste and danger categories; while shorter reaction times to correct an incorrect prosaccade related to less difficulties in inhibiting distasteful images. Altogether, these findings suggest that visual attention is differentially modulated by both the accepted and rejected food attributes, but also that normal-weight, non-eating disordered individuals exhibit enhanced approach to food's postingestive effects and avoidance of distasteful items (such as bitter vegetables or pungent products). Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study

International Nuclear Information System (INIS)

Junius, Sara; Haustermans, Karin; Bussels, Barbara; Oyen, Raymond; Vanstraelen, Bianca; Depuydt, Tom; Verstraete, Jan; Joniau, Steven; Van Poppel, Hendrik

2007-01-01

To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC). 38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT. Acute toxicity was evaluated weekly during radiotherapy (RT), at 1–3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria. Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse. None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4–5 and resolved within 4 weeks after RT in 82%. Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24–36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1–6 months showed similar values but rose slowly 2–3 years after RT. Nadir of sexual symptom scores was reached 1–6 months after RT but improved 2–3 years later as well as physical, cognitive and role functional scales. Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized. This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of

Effect of resveratrol on proliferation and differentiation of embryonic cardiomyoblasts

International Nuclear Information System (INIS)

Leong, C.-W.; Wong, C.H.; Lao, S.-C.; Leong, Emilia Conceicao; Lao, Iok Fong; Law, Patrick Tik Wan; Fung, Kwok Pui; Tsang, Kam Sze; Waye, Mary Miu-Yee; Tsui, Stephen Kwok-Wing; Wang Yitao; Lee, Simon Ming-Yuen

2007-01-01

Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found largely in the skins of red grapes, has been used as a nutritional supplement or an investigational new drug for prevention of cardiovascular diseases. Previous reports showed that resveratrol had a protective effect against oxidative agent-induced cell injury. Our studies indicate that resveratrol plays a role in the differentiation of cardiomyoblasts. The cardiomyoblast cell line, H9c2, was exposed to 30-120 μM resveratrol for up to 5 days. Resveratrol inhibits cardiomyoblast proliferation without causing cells injury. Moreover, resveratrol treatment modulated the differentiation of morphological characteristics including elongation and cell fusion in cardiomyoblasts. Proliferation and differentiation of H9c2 cells were further revealed by measurement of the mRNA expression of a cell cycle marker (CDK2), a differentiation marker (myogenin), and a contractile apparatus protein (MLC-2). Gene expression analysis revealed that resveratrol promoted entry into cell cycle arrest but extended the myogenic differentiation progress. These results have implications for the role of resveratrol in modulating cell cycle control and differentiation in cardiomyoblasts

Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration

Directory of Open Access Journals (Sweden)

Sajjad Ashraf

2017-04-01

Full Text Available Advances in mesenchymal stem cells (MSCs and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs, and type II collagen (COL2. RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2 with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y-box 9 (SOX9 and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPβ. Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments.

The Bus Extension Module Design and Verification of POSAFE-Q Using LVDS

International Nuclear Information System (INIS)

Lee, Youn Sang; Song, Seung Whan; No, Young Hun; Yoo, Kwan Woo

2012-01-01

This paper described the Bus Extension Module using Low Voltage Differential Signal (LVDS). A Bus Extension Module use Safety-Related PLC (Programmable Logic Controller), called POSAFE-Q (made by POSCO ICT), for handling many data (I/O) extension rack. A processor module of POSAFE-Q can control I/O Module installed another rack. This paper explains Bus Extension Module and Data transfer technology using LVDS. (author)

Hypoxia modulates the differentiation potential of stem cells of the apical papilla.

Science.gov (United States)

Vanacker, Julie; Viswanath, Aiswarya; De Berdt, Pauline; Everard, Amandine; Cani, Patrice D; Bouzin, Caroline; Feron, Olivier; Diogenes, Anibal; Leprince, Julian G; des Rieux, Anne

2014-09-01

Stem cells from the apical papilla (SCAP) are a population of mesenchymal stem cells likely involved in regenerative endodontic procedures and have potential use as therapeutic agents in other tissues. In these situations, SCAP are exposed to hypoxic conditions either within a root canal devoid of an adequate blood supply or in a scaffold material immediately after implantation. However, the effect of hypoxia on SCAP proliferation and differentiation is largely unknown. Therefore, the objective of this study was to evaluate the effect of hypoxia on the fate of SCAP. SCAP were cultured under normoxia (21% O2) or hypoxia (1% O2) in basal or differentiation media. Cellular proliferation, gene expression, differentiation, and protein secretion were analyzed by live imaging, quantitative reverse-transcriptase polymerase chain reaction, cellular staining, and enzyme-linked immunosorbent assay, respectively. Hypoxia had no effect on SCAP proliferation, but it evoked the up-regulation of genes specific for osteogenic differentiation (runt-related transcription factor 2, alkaline phosphatase, and transforming growth factor-β1), neuronal differentiation ( 2'-3'-cyclic nucleotide 3' phosphodiesterase, SNAIL, neuronspecific enolase, glial cell-derived neurotrophic factor and neurotrophin 3), and angiogenesis (vascular endothelial growth factor A and B). Hypoxia also increased the sustained production of VEGFa by SCAP. Moreover, hypoxia augmented the neuronal differentiation of SCAP in the presence of differentiation exogenous factors as detected by the up-regulation of NSE, VEGFB, and GDNF and the expression of neuronal markers (PanF and NeuN). This study shows that hypoxia induces spontaneous differentiation of SCAP into osteogenic and neurogenic lineages while maintaining the release of the proangiogenic factor VEGFa. This highlights the potential of SCAP to promote pulp-dentin regeneration. Moreover, SCAP may represent potential therapeutic agents for neurodegenerative

Recent advances and potential applications of modulated differential scanning calorimetry (mDSC) in drug development.

Science.gov (United States)

Knopp, Matthias Manne; Löbmann, Korbinian; Elder, David P; Rades, Thomas; Holm, René

2016-05-25

Differential scanning calorimetry (DSC) is frequently the thermal analysis technique of choice within preformulation and formulation sciences because of its ability to provide detailed information about both the physical and energetic properties of a substance and/or formulation. However, conventional DSC has shortcomings with respect to weak transitions and overlapping events, which could be solved by the use of the more sophisticated modulated DSC (mDSC). mDSC has multiple potential applications within the pharmaceutical field and the present review provides an up-to-date overview of these applications. It is aimed to serve as a broad introduction to newcomers, and also as a valuable reference for those already practising in the field. Complex mDSC was introduced more than two decades ago and has been an important tool for the quantification of amorphous materials and development of freeze-dried formulations. However, as discussed in the present review, a number of other potential applications could also be relevant for the pharmaceutical scientist. Copyright © 2015 Elsevier B.V. All rights reserved.

Apollo 16 astronauts in Apollo Command Module Mission Simulator

Science.gov (United States)

1972-01-01

Astronaut Thomas K. Mattingly II, command module pilot of the Apollo 16 lunar landing mission, participates in extravehicular activity (EVA) training in bldg 5 at the Manned Spacecraft Center (MSC). In the right background is Astronaut Charles M. Duke Jr., lunar module pilot. They are inside the Apollo Command Module Mission Simulator (31046); Mattingly (right foreground) and Duke (right backgroung) in the Apollo Command Module Mission Simulator for EVA simulation and training. Astronaut John W. Young, commander, can be seen in the left background (31047).

Identification of differentially expressed proteins during human urinary bladder cancer progression.

Science.gov (United States)

Memon, Ashfaque A; Chang, Jong W; Oh, Bong R; Yoo, Yung J

2005-01-01

Comparative proteome analysis was performed between RT4 (grade-1) and T24 (grade-3) bladder cancer cell lines, in an attempt to identify differentially expressed proteins during bladder cancer progression. Among those relatively abundant proteins, seven spots changed more than two-fold reproducibly and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis. However, additional investigations are needed on large number of human samples to further verify these findings.

Engineering mathematics-II

CERN Document Server

Ganesh, A

2009-01-01

About the Book: This book Engineering Mathematics-II is designed as a self-contained, comprehensive classroom text for the second semester B.E. Classes of Visveswaraiah Technological University as per the Revised new Syllabus. The topics included are Differential Calculus, Integral Calculus and Vector Integration, Differential Equations and Laplace Transforms. The book is written in a simple way and is accompanied with explanatory figures. All this make the students enjoy the subject while they learn. Inclusion of selected exercises and problems make the book educational in nature. It shou

Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

Directory of Open Access Journals (Sweden)

Patrick eHecht

2015-10-01

Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

Evaluation of modulators and electron-capture detectors for comprehensive two-dimensional GC of halogenated organic compounds

NARCIS (Netherlands)

Kristenson, E.M.; Korytar, P.; Danielsson, C.; Kallio, M.; Brandt, M.; Makela, J.; Vreuls, R.J.J.; Beens, J.; Brinkman, U.A.T.

2003-01-01

Different cryogenic and a heated GC×GC modulator(s) were evaluated and compared for the analysis of high-boiling halogenated compounds. The cryogenic modulators investigated were: (i) the longitudinally modulated cryogenic system; (ii) the liquid-nitrogen-cooled jet modulator (KT2001); (iii) a

The Class II trehalose 6-phosphate synthase gene PvTPS9 modulates trehalose metabolism in Phaseolus vulgaris nodules.

Directory of Open Access Journals (Sweden)

Aarón Barraza

2016-11-01

Full Text Available Legumes form symbioses with rhizobia, producing nitrogen-fixing nodules on the roots of the plant host. The network of plant signaling pathways affecting carbon metabolism may determine the final number of nodules. The trehalose biosynthetic pathway regulates carbon metabolism and plays a fundamental role in plant growth and development, as well as in plant-microbe interactions. The expression of genes for trehalose synthesis during nodule development suggests that this metabolite may play a role in legume-rhizobia symbiosis. In this work, PvTPS9, which encodes a Class II trehalose-6-phosphate synthase (TPS of common bean (Phaseolus vulgaris, was silenced by RNA interference in transgenic nodules. The silencing of PvTPS9 in root nodules resulted in a reduction of 85% (± 1% of its transcript, which correlated with a 30% decrease in trehalose contents of transgenic nodules and in untransformed leaves. Composite transgenic plants with PvTPS9 silenced in the roots showed no changes in nodule number and nitrogen fixation, but a severe reduction in plant biomass and altered transcript profiles of all Class II TPS genes. Our data suggest that PvTPS9 plays a key role in modulating trehalose metabolism in the symbiotic nodule and, therefore, in the whole plant.

Angiotensin II accelerates functional recovery in the rat sciatic nerve in vivo: role of the AT2 receptor and the transcription factor NF-kappaB.

Science.gov (United States)

Reinecke, Kirstin; Lucius, Ralph; Reinecke, Alexander; Rickert, Uta; Herdegen, Thomas; Unger, Thomas

2003-11-01

The AT2 receptor regulates several functions of nerve cells, e.g., ionic fluxes, cell differentiation, and axonal regeneration, but also modulates programmed cell death. We tested the hypothesis that angiotensin II (ANG II) via its AT2 receptor not only promotes regeneration but also functional recovery after sciatic nerve crush in adult rats. ANG II (10(-7), 10(-9), 10(-11) M) applied locally via osmotic minipumps promoted functional recovery with maximal effects after the lowest concentration. The toe spread distance as a parameter for re-innervation after 20 days was significantly (Pelectrical stimulation (return of sensorimotor function) was reduced to 14.6 days vs. 17.9 days in the control group (PSchwann cells. Histological criteria, morphometric analyses, and electron microscopy confirmed the functional data. These results are the first to present direct evidence for an involvement of the AT2 receptor and NF-kappaB in peripheral nerve regeneration.

Quantitative determination of the specific heat and the glass transition of moist samples by temperature modulated differential scanning calorimetry.

Science.gov (United States)

Schubnell, M; Schawe, J E

2001-04-17

In differential scanning calorimetry (DSC), remnant moisture loss in samples often overlaps and distorts other thermal events, e.g. glass transitions. To separate such overlapping processes, temperature modulated DSC (TMDSC) has been widely used. In this contribution we discuss the quantitative determination of the heat capacity of a moist sample from TMDSC measurements. The sample was a spray-dried pharmaceutical compound run in different pans (hermetically-sealed pan, pierced lid pan [50 microm] and open pan). The apparent heat capacity was corrected for the remaining amount of moisture. Using this procedure we could clearly identify the glass transition of the dry and the moist sample. We found that a moisture content of about 6.2% shifts the glass transition by about 50 degrees C.

NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

Directory of Open Access Journals (Sweden)

Fabio eCavaliere

2013-12-01

Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

Modulation of chromatin access during adipocyte differentiation

DEFF Research Database (Denmark)

Mandrup, Susanne; Hager, Gordon L

2012-01-01

identified; however, it is not until recently that we have begun to understand how these factors act at a genome-wide scale. In a recent publication we have mapped the genome-wide changes in chromatin structure during differentiation of 3T3-L1 preadipocytes and shown that a major reorganization...... of the chromatin landscape occurs within few hours following the addition of the adipogenic cocktail. In addition, we have mapped the genome-wide profiles of several of the early adipogenic transcription factors and shown that they act in a highly cooperative manner to drive this dramatic remodeling process....

Differential absorption lidar measurements of atmospheric water vapor using a pseudonoise code modulated AlGaAs laser. Thesis

Science.gov (United States)

Rall, Jonathan A. R.

1994-01-01

Lidar measurements using pseudonoise code modulated AlGaAs lasers are reported. Horizontal path lidar measurements were made at night to terrestrial targets at ranges of 5 and 13 km with 35 mW of average power and integration times of one second. Cloud and aerosol lidar measurements were made to thin cirrus clouds at 13 km altitude with Rayleigh (molecular) backscatter evident up to 9 km. Average transmitter power was 35 mW and measurement integration time was 20 minutes. An AlGaAs laser was used to characterize spectral properties of water vapor absorption lines at 811.617, 816.024, and 815.769 nm in a multipass absorption cell using derivative spectroscopy techniques. Frequency locking of an AlGaAs laser to a water vapor absorption line was achieved with a laser center frequency stability measured to better than one-fifth of the water vapor Doppler linewidth over several minutes. Differential absorption lidar measurements of atmospheric water vapor were made in both integrated path and range-resolved modes using an externally modulated AlGaAs laser. Mean water vapor number density was estimated from both integrated path and range-resolved DIAL measurements and agreed with measured humidity values to within 6.5 percent and 20 percent, respectively. Error sources were identified and their effects on estimates of water vapor number density calculated.

TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

Numerical analysis II essentials

CERN Document Server

REA, The Editors of; Staff of Research Education Association

1989-01-01

REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.

Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

Science.gov (United States)

Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

2014-01-01

Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

Dissection of regulatory networks that are altered in disease via differential co-expression.

Directory of Open Access Journals (Sweden)

David Amar

Full Text Available Comparing the gene-expression profiles of sick and healthy individuals can help in understanding disease. Such differential expression analysis is a well-established way to find gene sets whose expression is altered in the disease. Recent approaches to gene-expression analysis go a step further and seek differential co-expression patterns, wherein the level of co-expression of a set of genes differs markedly between disease and control samples. Such patterns can arise from a disease-related change in the regulatory mechanism governing that set of genes, and pinpoint dysfunctional regulatory networks. Here we present DICER, a new method for detecting differentially co-expressed gene sets using a novel probabilistic score for differential correlation. DICER goes beyond standard differential co-expression and detects pairs of modules showing differential co-expression. The expression profiles of genes within each module of the pair are correlated across all samples. The correlation between the two modules, however, differs markedly between the disease and normal samples. We show that DICER outperforms the state of the art in terms of significance and interpretability of the detected gene sets. Moreover, the gene sets discovered by DICER manifest regulation by disease-specific microRNA families. In a case study on Alzheimer's disease, DICER dissected biological processes and protein complexes into functional subunits that are differentially co-expressed, thereby revealing inner structures in disease regulatory networks.

An algorithm of computing inhomogeneous differential equations for definite integrals

OpenAIRE

Nakayama, Hiromasa; Nishiyama, Kenta

2010-01-01

We give an algorithm to compute inhomogeneous differential equations for definite integrals with parameters. The algorithm is based on the integration algorithm for $D$-modules by Oaku. Main tool in the algorithm is the Gr\\"obner basis method in the ring of differential operators.

Sambot II: A self-assembly modular swarm robot

Science.gov (United States)

Zhang, Yuchao; Wei, Hongxing; Yang, Bo; Jiang, Cancan

2018-04-01

The new generation of self-assembly modular swarm robot Sambot II, based on the original generation of self-assembly modular swarm robot Sambot, adopting laser and camera module for information collecting, is introduced in this manuscript. The visual control algorithm of Sambot II is detailed and feasibility of the algorithm is verified by the laser and camera experiments. At the end of this manuscript, autonomous docking experiments of two Sambot II robots are presented. The results of experiments are showed and analyzed to verify the feasibility of whole scheme of Sambot II.

A Voltage Modulated DPC Approach for Three-Phase PWM Rectifier

DEFF Research Database (Denmark)

Gui, Yonghao; Li, Mingshen; Lu, Jinghang

2018-01-01

In this paper, a voltage modulated direct power control for three-phase pulse-width modulated rectifier is proposed. With the suggested method, the differential equations describing the rectifier dynamics are changing from a linear time-varying system into a linear time-invariant one. In this way...

Differential scanning calorimetry techniques: applications in biology and nanoscience.

Science.gov (United States)

Gill, Pooria; Moghadam, Tahereh Tohidi; Ranjbar, Bijan

2010-12-01

This paper reviews the best-known differential scanning calorimetries (DSCs), such as conventional DSC, microelectromechanical systems-DSC, infrared-heated DSC, modulated-temperature DSC, gas flow-modulated DSC, parallel-nano DSC, pressure perturbation calorimetry, self-reference DSC, and high-performance DSC. Also, we describe here the most extensive applications of DSC in biology and nanoscience.

Differential Scanning Calorimetry Techniques: Applications in Biology and Nanoscience

OpenAIRE

Gill, Pooria; Moghadam, Tahereh Tohidi; Ranjbar, Bijan

2010-01-01

This paper reviews the best-known differential scanning calorimetries (DSCs), such as conventional DSC, microelectromechanical systems-DSC, infrared-heated DSC, modulated-temperature DSC, gas flow-modulated DSC, parallel-nano DSC, pressure perturbation calorimetry, self-reference DSC, and high-performance DSC. Also, we describe here the most extensive applications of DSC in biology and nanoscience.

Simvastatin enhances bone morphogenetic protein receptor type II expression

International Nuclear Information System (INIS)

Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N.

2006-01-01

Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function

Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells

Science.gov (United States)

Rios, Carmen; D'Ippolito, Gianluca; Curtis, Kevin M.; Delcroix, Gaëtan J.-R.; Gomez, Lourdes A.; El Hokayem, Jimmy; Rieger, Megan; Parrondo, Ricardo; de las Pozas, Alicia; Perez-Stable, Carlos; Howard, Guy A.

2016-01-01

Human bone marrow multipotent mesenchymal stromal cell (hMSC) number decreases with aging. Subpopulations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues and participate in their repair. Maintaining throughout adult life such cell subpopulations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain, notch target genes, neuronal transcriptional repressor element 1 (RE1)-silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1α), and additionally, by decreasing the expression of (i) the proapoptotic proteins, apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity. Furthermore, low oxygen increases canonical Wnt pathway signaling coreceptor Lrp5 expression, and PI3K/Akt pathway activation. Lrp5 inhibition decreases self-renewal marker Sox2 mRNA, Oct4a nuclear accumulation, and cell numbers. Wortmannin-mediated PI3K/Akt pathway inhibition leads to increased osteoblastic differentiation at both low and high oxygen tension. We demonstrate that low oxygen stimulates a complex signaling network involving PI3K/Akt, Notch, and canonical Wnt pathways, which mediate the observed increase in nuclear Oct4a and REST, with simultaneous decrease in p53, AIF, and Bak. Collectively, these pathway activations contribute to increased self-renewal with concomitant decreased differentiation, cell cycle arrest, apoptosis, and/or senescence in MIAMI cells. Importantly, the PI3K/Akt pathway plays a central mechanistic role in the oxygen tension-regulated self-renewal versus osteoblastic differentiation of progenitor cells. PMID:27059084

AUTOMOTIVE DIESEL MAINTENANCE 2. UNIT XV, UNDERSTANDING DC GENERATOR PRINCIPLES (PART II).

Science.gov (United States)

Human Engineering Inst., Cleveland, OH.

THIS MODULE OF A 25-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF MAINTENANCE PROCEDURES FOR DIRECT CURRENT GENERATORS USED ON DIESEL POWERED EQUIPMENT. TOPICS ARE SPECIAL GENERATOR CIRCUITS, GENERATOR TESTING, AND GENERATOR POLARITY. THE MODULE CONSISTS OF A SELF-INSTRUCTIONAL PROGRAMED TRAINING FILM "DC GENERATORS II--GENERATOR…

Differential electron scattering cross sections for the 3 (2)S to 3 (2)P0 h, k transitions in Mg II - Comparison of experiment and theory

Science.gov (United States)

Williams, I. D.; Chutjian, A.; Msezane, A. Z.; Henry, R. J. W.

1985-01-01

Angular differential electron scattering cross sections are reported for the unresolved inelastic 3s (2)S to 3p (2)P0 h, k transitions in Mg II for the first time. Relative differential cross sections have been measured at 35 eV and 50 eV in the angular range of Theta between 6 and 17 deg using the newly developed electron energy loss technique in a crossed electron-ion beam geometry. Theoretical values have been calculated in a five-state close-coupling approximation in which 3s, 3p, 3d, 4s, and 4p states were included, and to which measurements were normalized at Theta = 12 deg.

Cranial CT signs of the Chiari II malformation

International Nuclear Information System (INIS)

Naidich, T.P.; Pudlowski, R.M.

1980-01-01

Serial CT scans of 32 patients with proved Chiari II malformations and 19 patients with hydrocephalus and meningomyelocele (presumed to have Chiari II malformation) were reviewed and compared with CT scans from 30 patients with non-chiari aqueductal stenosis to develop criteria for identifying the Chiari II malformation and for differentiating it from other forms of hydrocephalus. Correlation with post-mortem specimens of Chiari II brains provided a pathologic basis for the CT signs observed. (orig.) [de

The MARX Modulator Development Program for the International Linear Collider

International Nuclear Information System (INIS)

Leyh, G.E.

2006-01-01

The International Linear Collider (ILC) Marx Modulator Development Program at SLAC is working towards developing a full-scale ILC Marx ''Reference Design'' modulator prototype, with the goal of significantly reducing the size and cost of the ILC modulator while improving overall modulator efficiency and availability. The ILC Reference Design prototype will provide a proof-of-concept model to industry in advance of Phase II SBIR funding, and also allow operation of the new 10MW L-Band Klystron prototypes immediately upon their arrival at SLAC

Rat vas deferens SERCA2 is modulated by Ca{sup 2+}/calmodulin protein kinase II-mediated phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Rodriguez, J.B.R.; Muzi-Filho, H. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Valverde, R.H.F. [Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Quintas, L.E.M. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Noel, F. [Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Einicker-Lamas, M. [Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ (Brazil); Cunha, V.M.N. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil)

2013-03-19

Ca{sup 2+} pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca{sup 2+}-ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (∼115 kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca{sup 2+} (Ca{sub 0.5} = 780 nM) and a low sensitivity to vanadate (IC{sub 50} = 41 µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca{sup 2+} and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca{sup 2+} accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca{sup 2+} and CaM, possibly via CaMKII, in a process that results in stimulation of Ca{sup 2+} pumping activity.

Industrial Special Wastes Generated in Iowa and Manpower Characteristics of Employee Handlers, Volume II.

Science.gov (United States)

Pierce, David R.

This document, Vol. II in a set, presents the results of the development and instruction of two pilot modules. The first module deals with pesticide container recycling. The second module deals with hazardous substances, especially paints and solvents. Each module contains background information, instructor narrative, student activities, and…

The CRESST-III detector module

Energy Technology Data Exchange (ETDEWEB)

Wuestrich, Marc [Max-Planck-Institut f. Physik (Werner-Heisenberg-Institut) (Germany); Collaboration: CRESST-Collaboration

2016-07-01

The direct dark matter experiment CRESST uses scintillating calorimeters to detected WIMP induced nuclear scattering in CaWO{sub 4} single crystals. Equipped with transition edge sensors (TESs), these detectors can achieve detection thresholds well below 1 keV. The last physics run of CRESST-II proved the high potential of the experiment especially for small WIMP masses and triggered the development of a new detector module using much smaller CaWO{sub 4} main absorbers. The upcoming CRESST-III run will mainly be equipped with these newly developed modules, which combine a fully scintillating detector housing with an improved detection threshold (<100 keV). While many features of the new module were adapted from previous module designs in an improved way, also new features are implemented like instrumented sticks (iSticks) holding the crystals and optimized TES structures for phonon and light detectors. First tests above ground validated the improved performance of these detector modules and promise to explore new regions in the WIMP parameter space in the next CRESST-III run.

Hepatic farnesoid X-receptor isoforms α2 and α4 differentially modulate bile salt and lipoprotein metabolism in mice.

Directory of Open Access Journals (Sweden)

Marije Boesjes

Full Text Available The nuclear receptor FXR acts as an intracellular bile salt sensor that regulates synthesis and transport of bile salts within their enterohepatic circulation. In addition, FXR is involved in control of a variety of crucial metabolic pathways. Four FXR splice variants are known, i.e. FXRα1-4. Although these isoforms show differences in spatial and temporal expression patterns as well as in transcriptional activity, the physiological relevance hereof has remained elusive. We have evaluated specific roles of hepatic FXRα2 and FXRα4 by stably expressing these isoforms using liver-specific self-complementary adeno-associated viral vectors in total body FXR knock-out mice. The hepatic gene expression profile of the FXR knock-out mice was largely normalized by both isoforms. Yet, differential effects were also apparent; FXRα2 was more effective in reducing elevated HDL levels and transrepressed hepatic expression of Cyp8b1, the regulator of cholate synthesis. The latter coincided with a switch in hydrophobicity of the bile salt pool. Furthermore, FXRα2-transduction caused an increased neutral sterol excretion compared to FXRα4 without affecting intestinal cholesterol absorption. Our data show, for the first time, that hepatic FXRα2 and FXRα4 differentially modulate bile salt and lipoprotein metabolism in mice.

Differential modulation of FXR activity by chlorophacinone and ivermectin analogs

Energy Technology Data Exchange (ETDEWEB)

Hsu, Chia-Wen [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Hsieh, Jui-Hua [National Toxicology Program, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (United States); Huang, Ruili [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Pijnenburg, Dirk [PamGene International B.V., Wolvenhoek 10, 5211 HH ' s-Hertogenbosch (Netherlands); Khuc, Thai [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Hamm, Jon [Integrated Laboratory System, Inc., Morrisville, NC (United States); Zhao, Jinghua; Lynch, Caitlin [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Beuningen, Rinie van [PamGene International B.V., Wolvenhoek 10, 5211 HH ' s-Hertogenbosch (Netherlands); Chang, Xiaoqing [Integrated Laboratory System, Inc., Morrisville, NC (United States); Houtman, René [PamGene International B.V., Wolvenhoek 10, 5211 HH ' s-Hertogenbosch (Netherlands); Xia, Menghang, E-mail: mxia@mail.nih.gov [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States)

2016-12-15

Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10 K chemical collection. In the present study, we validated the FXR antagonist activity of selected structural classes, including avermectin anthelmintics, dihydropyridine calcium channel blockers, 1,3-indandione rodenticides, and pyrethroid pesticides, using in vitro assay and quantitative structural-activity relationship (QSAR) analysis approaches. (Z)-Guggulsterone, chlorophacinone, ivermectin, and their analogs were profiled for their ability to alter CDCA-mediated FXR binding using a panel of 154 coregulator motifs and to induce or inhibit transactivation and coactivator recruitment activities of constitutive androstane receptor (CAR), liver X receptor alpha (LXRα), or pregnane X receptor (PXR). Our results showed that chlorophacinone and ivermectin had distinct modes of action (MOA) in modulating FXR-coregulator interactions and compound selectivity against the four aforementioned functionally-relevant nuclear receptors. These findings collectively provide mechanistic insights regarding compound activities against FXR and possible explanations for in vivo toxicological observations of chlorophacinone, ivermectin, and their analogs. - Highlights: • A subset of Tox21 chemicals was investigated for FXR antagonism. • In vitro and computational approaches were used to evaluate FXR antagonists. • Chlorophacinone and ivermectin had distinct patterns in modulating FXR activity.

Dimethyl sulfoxide-inducible cytoplasmic factor involved in erythroid differentiation in mouse erythroleukemia (Friend) cells

International Nuclear Information System (INIS)

Watanabe, T.; Oishi, M.

1987-01-01

A previous report described an intracellular factor (differentiation-inducing factor I, or DIF-I) that seem to play a role in erythroid differentiation in mouse erythroleukemia (MEL) cells. The authors have detected another erythroid-inducing factor in cell-free extracts from dimethyl sulfoxide- or hexamethylenebis(acetamide)-treated MEL cells, which acts synergistically with DIF-I. The partially purified factor (termed DIF-II) triggered erythroid differentiation when introduced into undifferentiated MEL cells that had been potentiated by the induction of DIF-I. The activity in the extracts appeared in an inducible manner after addition of dimethyl sulfoxide or hexamethylenebis(acetamide), reached a maximum at 6 hr, and then rapidly decreased. The induction was inhibited by phorbol 12-myristate 13-acetate and also by cycloheximide. No induction was observed in a mutant MEL cell line defective in erythroid differentiation. These characteristics are consistent with the supposition that DIF-II is one of the putative dimethyl sulfoxide-inducible factors detected in previously reported cell-fusion and cytoplast-fusion experiments. The role of DIF-II in MEL-cell differentiation and in vitro differentiation in general is discussed

Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr and modulates cardiac action potential characteristics.

Directory of Open Access Journals (Sweden)

Anders Peter Larsen

Full Text Available BACKGROUND: The repolarizing cardiac rapid delayed rectifier current, I(Kr, is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr. Marked heterogeneity in the kinetic properties of native I(Kr has been described. We hypothesized that the heterogeneity of native I(Kr can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD and restitution. METHODOLOGY/PRINCIPAL FINDINGS: The results show that the heterogeneity of native I(Kr can be reproduced in heterologous expression systems by differential expression of ERG1a and ERG1b isoforms. Characterization of the macroscopic kinetics of ERG1 currents demonstrated that these were dependent on the relative abundance of ERG1a and ERG1b. Furthermore, we used a computational model of the ventricular cardiomyocyte to show that both APD and the slope of the restitution curve may be modulated by varying the relative abundance of ERG1a and ERG1b. As the relative abundance of ERG1b was increased, APD was gradually shortened and the slope of the restitution curve was decreased. CONCLUSIONS/SIGNIFICANCE: Our results show that differential expression of ERG1 isoforms may explain regional heterogeneity of I(Kr kinetics. The data demonstrate that subunit dependent changes in channel kinetics are important for the functional properties of ERG1 currents and hence I(Kr. Importantly, our results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts.

Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

Energy Technology Data Exchange (ETDEWEB)

Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Efstathiou, Theo [Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex (France); Saligaut, Christian [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Pakdel, Farzad, E-mail: farzad.pakdel@univ-rennes1.fr [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France)

2017-06-15

Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and

Differential display-mediated identification of three drought

Indian Academy of Sciences (India)

L.) O. Kuntze], a woody and perennial plant of commercial importance. Using differential display of mRNA, three drought-modulated expressed sequence tags (ESTs) were identified. Northern and BLAST analysis revealed that clone dr1 ...

An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.

Science.gov (United States)

Tasseff, Ryan; Jensen, Holly A; Congleton, Johanna; Dai, David; Rogers, Katharine V; Sagar, Adithya; Bunaciu, Rodica P; Yen, Andrew; Varner, Jeffrey D

2017-10-30

In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.

Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Masataka Kikuchi

Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs, we identified the PINs expressed in three brain regions: the entorhinal cortex (EC, hippocampus (HIP and superior frontal gyrus (SFG. Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system.

The Effect of Soy Isoflavone on the Proliferation and Differentiation of Adipose-Derived Mesenchymal Stem Cells into Chondrocytes and Expression of Collagen II and Aggrecan Genes

Directory of Open Access Journals (Sweden)

Fatemeh Bamdadpasand Shekarsarayi

2017-03-01

Full Text Available Background and Objectives: Due to the lack of blood vessels in cartilage tissue, its damage is not repairable. This study was conducted to investigate the effect of soy isoflavone on proliferation and differentiation of adipose-derived mesenchymal stem cells into chondrocytes and expression of collagen II and aggrecan genes. Methods: In this experimental study, human subcutaneous fat was obtained during liposuction and incubated with collagenase enzyme (type 1 for the breakdown of collagen, and collagenase was deactivated by DMEM medium, and was cultured in the cell sediment after centrifugation, the cells were isolated after the third passage, were placed in chondrogenic medium for differentiate into the cartilage, and were divided into three groups, including control, treatment with TGF-β1, and treatment with soy isoflavones tablets. The tablets were dissolved in distilled water, sterilized by passing through a 0.2 um filter and were added to the culture medium. After 48 hours, cell viability was determined by MTT assay, and after 14 days, collagen II and aggrecan gene expressions were assessed by real-time PCR technique. Data were statistically analyzed by one-way ANOVA and Tukey's post-hoc test using SPSS 20 and p<0.05. Results: The results of MTT assay showed a significant increase in viability in the TGF-β1 group compared to the control and soy isoflavone groups (p<0.05. The RT-PCR indicated a significant increase in the expression of collagen II and aggrecan genes in isoflavones and TGF-β1 groups compared to the control group, and also, the mean CT associated with collagen II gene had a significant increase in isoflavone and TGF-β1groups compared to the control group (p<0.05. Conclusion: Soy in culture medium increases the expression of collagen II and aggrecan genes and cell proliferation, but this increase is not high compared to the TGF-β1 group.

Unstart Coupling Mechanism Analysis of Multiple-Modules Hypersonic Inlet

Directory of Open Access Journals (Sweden)

Jichao Hu

2013-01-01

Full Text Available The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.

Science.gov (United States)

Hu, Jichao; Chang, Juntao; Wang, Lei; Cao, Shibin; Bao, Wen

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

Differential recurrence formulae for orthogonal polynomials

Directory of Open Access Journals (Sweden)

Anton L. W. von Bachhaus

1995-11-01

Full Text Available Part I - By combining a general 2nd-order linear homogeneous ordinary differential equation with the three-term recurrence relation possessed by all orthogonal polynomials, it is shown that sequences of orthogonal polynomials which satisfy a differential equation of the above mentioned type necessarily have a differentiation formula of the type: gn(xY'n(x=fn(xYn(x+Yn-1(x. Part II - A recurrence formula of the form: rn(xY'n(x+sn(xY'n+1(x+tn(xY'n-1(x=0, is derived using the result of Part I.

Thermal Studies of Zn(II, Cd(II and Hg(II Complexes of Some N-Alkyl-N-Phenyl-Dithiocarbamates

Directory of Open Access Journals (Sweden)

Peter A. Ajibade

2012-07-01

Full Text Available The thermal decomposition of Zn(II, Cd(II and Hg(II complexes of N-ethyl-N-phenyl and N-butyl-N-phenyl dithiocarbamates have been studied using thermogravimetric analysis (TGA and differential scanning calorimetry (DSC. The products of the decomposition, at two different temperatures, were further characterized by scanning electron microscopy (SEM and energy-dispersive X-ray spectroscopy (EDX. The results show that while the zinc and cadmium complexes undergo decomposition to form metal sulphides, and further undergo oxidation forming metal oxides as final products, the mercury complexes gave unstable volatiles as the final product.

Fully Digital Chaotic Differential Equation-based Systems And Methods

KAUST Repository

Radwan, Ahmed Gomaa Ahmed; Zidan, Mohammed A.; Salama, Khaled N.

2012-01-01

Various embodiments are provided for fully digital chaotic differential equation-based systems and methods. In one embodiment, among others, a digital circuit includes digital state registers and one or more digital logic modules configured to obtain a first value from two or more of the digital state registers; determine a second value based upon the obtained first values and a chaotic differential equation; and provide the second value to set a state of one of the plurality of digital state registers. In another embodiment, a digital circuit includes digital state registers, digital logic modules configured to obtain outputs from a subset of the digital shift registers and to provide the input based upon a chaotic differential equation for setting a state of at least one of the subset of digital shift registers, and a digital clock configured to provide a clock signal for operating the digital shift registers.

Fully Digital Chaotic Differential Equation-based Systems And Methods

KAUST Repository

Radwan, Ahmed Gomaa Ahmed

2012-09-06

Various embodiments are provided for fully digital chaotic differential equation-based systems and methods. In one embodiment, among others, a digital circuit includes digital state registers and one or more digital logic modules configured to obtain a first value from two or more of the digital state registers; determine a second value based upon the obtained first values and a chaotic differential equation; and provide the second value to set a state of one of the plurality of digital state registers. In another embodiment, a digital circuit includes digital state registers, digital logic modules configured to obtain outputs from a subset of the digital shift registers and to provide the input based upon a chaotic differential equation for setting a state of at least one of the subset of digital shift registers, and a digital clock configured to provide a clock signal for operating the digital shift registers.

Directed neuronal differentiation of human embryonic stem cells

Directory of Open Access Journals (Sweden)

Noggle Scott A

2003-10-01

Full Text Available Abstract Background We have developed a culture system for the efficient and directed differentiation of human embryonic stem cells (HESCs to neural precursors and neurons. HESC were maintained by manual passaging and were differentiated to a morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum free conditions, in the presence of 50% conditioned medium from the human hepatocarcinoma cell line HepG2 (MedII. Results A neural precursor population was observed within HESC derived serum free embryoid bodies cultured in MedII conditioned medium, around 7–10 days after derivation. The neural precursors were organized into rosettes comprised of a central cavity surrounded by ring of cells, 4 to 8 cells in width. The central cells within rosettes were proliferating, as indicated by the presence of condensed mitotic chromosomes and by phosphoHistone H3 immunostaining. When plated and maintained in adherent culture, the rosettes of neural precursors were surrounded by large interwoven networks of neurites. Immunostaining demonstrated the expression of nestin in rosettes and associated non-neuronal cell types, and a radial expression of Map-2 in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker for dopaminergic neurons. Conclusion This novel directed differentiation approach led to the efficient derivation of neuronal cultures from HESCs, including the differentiation of tyrosine hydroxylase expressing neurons. HESC were morphologically differentiated to a monolayer OCT-4+ cell type, which was used to derive embryoid bodies directly into serum free conditions. Exposure to the MedII conditioned medium enhanced the derivation of neural precursors, the first example of the effect of this conditioned medium on HESC.

Crystallization of Polymers Investigated by Temperature-Modulated DSC

Directory of Open Access Journals (Sweden)

Maria Cristina Righetti

2017-04-01

Full Text Available The aim of this review is to summarize studies conducted by temperature-modulated differential scanning calorimetry (TMDSC on polymer crystallization. This technique can provide several advantages for the analysis of polymers with respect to conventional differential scanning calorimetry. Crystallizations conducted by TMDSC in different experimental conditions are analysed and discussed, in order to illustrate the type of information that can be deduced. Isothermal and non-isothermal crystallizations upon heating and cooling are examined separately, together with the relevant mathematical treatments that allow the evolution of the crystalline, mobile amorphous and rigid amorphous fractions to be determined. The phenomena of ‘reversing’ and ‘reversible‘ melting are explicated through the analysis of the thermal response of various semi-crystalline polymers to temperature modulation.

Random and systematic beam modulator errors in dynamic intensity modulated radiotherapy

International Nuclear Information System (INIS)

Parsai, Homayon; Cho, Paul S; Phillips, Mark H; Giansiracusa, Robert S; Axen, David

2003-01-01

This paper reports on the dosimetric effects of random and systematic modulator errors in delivery of dynamic intensity modulated beams. A sliding-widow type delivery that utilizes a combination of multileaf collimators (MLCs) and backup diaphragms was examined. Gaussian functions with standard deviations ranging from 0.5 to 1.5 mm were used to simulate random positioning errors. A clinical example involving a clival meningioma was chosen with optic chiasm and brain stem as limiting critical structures in the vicinity of the tumour. Dose calculations for different modulator fluctuations were performed, and a quantitative analysis was carried out based on cumulative and differential dose volume histograms for the gross target volume and surrounding critical structures. The study indicated that random modulator errors have a strong tendency to reduce minimum target dose and homogeneity. Furthermore, it was shown that random perturbation of both MLCs and backup diaphragms in the order of σ = 1 mm can lead to 5% errors in prescribed dose. In comparison, when MLCs or backup diaphragms alone was perturbed, the system was more robust and modulator errors of at least σ = 1.5 mm were required to cause dose discrepancies greater than 5%. For systematic perturbation, even errors in the order of ±0.5 mm were shown to result in significant dosimetric deviations

Ihh enhances differentiation of CFK-2 chondrocytic cells and antagonizes PTHrP-mediated activation of PKA.

Science.gov (United States)

Deckelbaum, Ron A; Chan, George; Miao, Dengshun; Goltzman, David; Karaplis, Andrew C

2002-07-15

Indian Hedgehog (Ihh), a member of the hedgehog (HH) family of secreted morphogens, and parathyroid hormone-related peptide (PTHrP) are key regulators of cartilage cell (chondrocyte) differentiation. We have investigated, in vitro, the actions of HH signalling and its possible interplay with PTHrP using rat CFK-2 chondrocytic cells. Markers of chondrocyte differentiation [alkaline phosphatase (ALP) activity, and type II (Col2a1) and type X collagen (Col10a1) expression] were enhanced by overexpression of Ihh or its N-terminal domain (N-Ihh), effects mimicked by exogenous administration of recombinant N-terminal HH peptide. Moreover, a missense mutation mapping to the N-terminal domain of Ihh (W160G) reduces the capacity of N-Ihh to induce differentiation. Prolonged exposure of CFK-2 cells to exogenous N-Shh (5x10(-9) M) in the presence of PTHrP (10(-8) M) or forskolin (10(-7) M) resulted in perturbation of HH-mediated differentiation. In addition, overexpression of a constitutively active form of the PTHrP receptor (PTHR1 H223R) inhibited Ihh-mediated differentiation, implicating activation of protein kinase A (PKA) by PTHR1 as a probable mediator of the antagonistic effects of PTHrP. Conversely, overexpression of Ihh/N-Ihh or exogenous treatment with N-Shh led to dampening of PTHrP-mediated activation of PKA. Taken together, our data suggest that Ihh harbors the capacity to induce rather than inhibit chondrogenic differentiation, that PTHrP antagonizes HH-mediated differentiation through a PKA-dependent mechanism and that HH signalling, in turn, modulates PTHrP action through functional inhibition of signalling by PTHR1 to PKA.

Symmetry, phase modulation and nonlinear waves

CERN Document Server

Bridges, Thomas J

2017-01-01

Nonlinear waves are pervasive in nature, but are often elusive when they are modelled and analysed. This book develops a natural approach to the problem based on phase modulation. It is both an elaboration of the use of phase modulation for the study of nonlinear waves and a compendium of background results in mathematics, such as Hamiltonian systems, symplectic geometry, conservation laws, Noether theory, Lagrangian field theory and analysis, all of which combine to generate the new theory of phase modulation. While the build-up of theory can be intensive, the resulting emergent partial differential equations are relatively simple. A key outcome of the theory is that the coefficients in the emergent modulation equations are universal and easy to calculate. This book gives several examples of the implications in the theory of fluid mechanics and points to a wide range of new applications.

Informed Conjecturing of Solutions for Differential Equations in a Modeling Context

Science.gov (United States)

Winkel, Brian

2015-01-01

We examine two differential equations. (i) first-order exponential growth or decay; and (ii) second order, linear, constant coefficient differential equations, and show the advantage of learning differential equations in a modeling context for informed conjectures of their solution. We follow with a discussion of the complete analysis afforded by…

Crystallization of Polymers Investigated by Temperature-Modulated DSC

OpenAIRE

Maria Cristina Righetti

2017-01-01

The aim of this review is to summarize studies conducted by temperature-modulated differential scanning calorimetry (TMDSC) on polymer crystallization. This technique can provide several advantages for the analysis of polymers with respect to conventional differential scanning calorimetry. Crystallizations conducted by TMDSC in different experimental conditions are analysed and discussed, in order to illustrate the type of information that can be deduced. Isothermal and non-isothermal crystal...

Hardware modules of the RSA algorithm

Directory of Open Access Journals (Sweden)

Škobić Velibor

2014-01-01

Full Text Available This paper describes basic principles of data protection using the RSA algorithm, as well as algorithms for its calculation. The RSA algorithm is implemented on FPGA integrated circuit EP4CE115F29C7, family Cyclone IV, Altera. Four modules of Montgomery algorithm are designed using VHDL. Synthesis and simulation are done using Quartus II software and ModelSim. The modules are analyzed for different key lengths (16 to 1024 in terms of the number of logic elements, the maximum frequency and speed.

Differential geometry based solvation model II: Lagrangian formulation.

Science.gov (United States)

Chen, Zhan; Baker, Nathan A; Wei, G W

2011-12-01

Solvation is an elementary process in nature and is of paramount importance to more sophisticated chemical, biological and biomolecular processes. The understanding of solvation is an essential prerequisite for the quantitative description and analysis of biomolecular systems. This work presents a Lagrangian formulation of our differential geometry based solvation models. The Lagrangian representation of biomolecular surfaces has a few utilities/advantages. First, it provides an essential basis for biomolecular visualization, surface electrostatic potential map and visual perception of biomolecules. Additionally, it is consistent with the conventional setting of implicit solvent theories and thus, many existing theoretical algorithms and computational software packages can be directly employed. Finally, the Lagrangian representation does not need to resort to artificially enlarged van der Waals radii as often required by the Eulerian representation in solvation analysis. The main goal of the present work is to analyze the connection, similarity and difference between the Eulerian and Lagrangian formalisms of the solvation model. Such analysis is important to the understanding of the differential geometry based solvation model. The present model extends the scaled particle theory of nonpolar solvation model with a solvent-solute interaction potential. The nonpolar solvation model is completed with a Poisson-Boltzmann (PB) theory based polar solvation model. The differential geometry theory of surfaces is employed to provide a natural description of solvent-solute interfaces. The optimization of the total free energy functional, which encompasses the polar and nonpolar contributions, leads to coupled potential driven geometric flow and PB equations. Due to the development of singularities and nonsmooth manifolds in the Lagrangian representation, the resulting potential-driven geometric flow equation is embedded into the Eulerian representation for the purpose of

PASC-1, Petten AMPX-II/SCALE-3 Code System for Reactor Neutronics Calculation

International Nuclear Information System (INIS)

Yaoqing, W.; Oppe, J.; Haas, J.B.M. de; Gruppelaar, H.; Slobben, J.

1995-01-01

1 - Description of program or function: The Petten AMPX-II/SCALE-3 Code System PASC-1 is a reactor neutronics calculation programme system consisting of well known IBM-oriented codes, that have been translated into FORTRAN-77, for calculations on a CDC-CYBER computer. Thus, the portability of these codes has been increased. In this system, some AMPX-II and SCALE-3 modules, the one-dimensional transport code ANISN and the 1 to 3-dimensional diffusion code CITATION are linked together on the CDC-CYBER/855 computer. The new cell code XSDRNPM-S and the old XSDRN code are included in the system. Starting from an AMPX fine group library up to CITATION, calculations can be performed for each individual module. Existing AMPX master interface format libraries, such as CSRL-IV, JEF-1, IRI and SCALE-45, and the old XSDRN-formatted libraries such as the COBB library can be used for the calculations. The code system contains the following modules and codes at present: AIM, AJAX, MALOCS, NITAWL-S, REVERT-I, ICE-2, CONVERT, JUAN, OCTAGN, XSDRNPM-S, XSDRN, ANISN and CITATION. The system will be extended with other SCALE modules and transport codes. 2 - Method of solution: The PASC-1 system is based on AMPX-II/SCALE-3 modules. Except for some SCALE-3 modules taken from the SCALIAS package, the original AMPX-II modules were IBM versions written in FORTRAN IV. These modules have been translated into CDC FORTRAN V. In order to test these modules and link them with some codes, some of the sample problem calculations have been performed for the whole PASC-1 system. During these calculations, some FORTRAN-77 errors were found in MALOCS, REVERT, CONVERT and some subroutines of SUBLIB (FORTRAN-77 subroutine library). These errors have been corrected. Because many corrections were made for the REVERT module, it is renamed as REVERT-I (improved version of REVERT). After these corrections, the whole system is running on a CDC-CYBER Computer (NOS-BE operating system). 3 - Restrictions on the

Confinement Sensing and Signal Optimization via Piezo1/PKA and Myosin II Pathways

Directory of Open Access Journals (Sweden)

Wei-Chien Hung

2016-05-01

Full Text Available Summary: Cells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca2+ level is increased, leading to phosphodiesterase 1 (PDE1-dependent suppression of PKA activity. This Ca2+ elevation requires Piezo1, a stretch-activated cation channel. Moreover, differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II, indicating that these proteins can independently mediate confinement sensing. Signals activated by Piezo1 and myosin II in response to confinement both feed into a signaling circuit that optimizes cell motility. This study provides a mechanism by which confinement-induced signaling enables cells to sense and adapt to different physical microenvironments. : Hung et al. demonstrate that a Piezo1-dependent intracellular calcium increase negatively regulates protein kinase A (PKA as cells transit from unconfined to confined spaces. The Piezo1/PKA and myosin II signaling modules constitute two confinement-sensing mechanisms. This study provides a paradigm by which signaling enables cells to sense and adapt to different microenvironments.

Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

Directory of Open Access Journals (Sweden)

Xiaoke Ma

2015-06-01

Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

Receptors for insulin-like growth factor II (IGF-II) in the rat kidney glomerulus

International Nuclear Information System (INIS)

Haskell, J.F.; Pillion, D.J.; Meezan, E.

1986-01-01

Renal glomeruli were isolated by a technique involving renal perfusion with a solution containing magnetic iron oxide particles, followed by homogenization, sieving and isolation over a strong magnet. Isolated glomeruli were treated with 1% Triton X-100 to solubilize plasma membrane components while insoluble basement membrane components were removed by centrifugation. [ 125 I]Insulin-like growth factor-II (IGF-II) binding to this preparation was competitively inhibited by increasing amounts of unlabelled IGF-II, with 50% inhibition of binding observed at an IGF-II concentration of 1 ng/ml. [ 125 I]IGF-II was covalently cross-linked to its receptor with disuccinimidyl suberate in two tissues known to contain IGF-II receptors, the rat chondrosarcoma chondrocyte and the rat kidney tubule, as well as in rat renal glomeruli. In all three cases, a specific high-molecular weight (Mr = 255,000) band could be identified on autoradiograms of dodecyl sulfate polyacrylamide gels. These results indicate that the rat glomerulus contains a high-affinity receptor for IGF-II. This finding is consistent with the hypothesis that IGF-II plays a role in glomerular growth and differentiation

The biometric-based module of smart grid system

Science.gov (United States)

Engel, E.; Kovalev, I. V.; Ermoshkina, A.

2015-10-01

Within Smart Grid concept the flexible biometric-based module base on Principal Component Analysis (PCA) and selective Neural Network is developed. The formation of the selective Neural Network the biometric-based module uses the method which includes three main stages: preliminary processing of the image, face localization and face recognition. Experiments on the Yale face database show that (i) selective Neural Network exhibits promising classification capability for face detection, recognition problems; and (ii) the proposed biometric-based module achieves near real-time face detection, recognition speed and the competitive performance, as compared to some existing subspaces-based methods.

Differential Fecundity, Markets and Gender Roles

OpenAIRE

Aloysius Siow

1996-01-01

Women are fecund for a shorter period of their lives than men. This paper investigates how differential fecundity interacts with marriage, labor and financial markets to affect gender roles. The main findings of the paper are: (i) Differential fecundity does not have any market invariant gender effect. (ii) Gender roles depend on competition for mates in the marriage market and the way in which ex-post differences in earnings affect that competition. (iii) Gender differences in the labor mark...

Performance comparison of binary modulation schemes for visible light communication

KAUST Repository

Park, Kihong

2015-09-11

In this paper, we investigate the power spectral density of several binary modulation schemes including variable on-off keying, variable pulse position modulation, and pulse dual slope modulation which were previously proposed for visible light communication with dimming control. We also propose a novel slope-based modulation called differential chip slope modulation (DCSM) and develop a chip-based hard-decision receiver to demodulate the resulting signal, detect the chip sequence, and decode the input bit sequence. We show that the DCSM scheme can exploit spectrum density more efficiently than the reference schemes while providing an error rate performance comparable to them. © 2015 IEEE.

Design, modeling and performance analysis of dual channel semitransparent photovoltaic thermal hybrid module in the cold environment

International Nuclear Information System (INIS)

Singh, Sonveer; Agrawal, Sanjay; Avasthi, D.V.

2016-01-01

Highlights: • Thermal modeling of novel dual channel semitransparent PVT hybrid module. • Exergy and carbon credit analysis has been performed. • Annual performance has been evaluated for Srinagar (India). • There are improvements in results for case-I as compared to case-II. - Abstract: In this work, thermal modeling and performance analysis of the dual channel semitransparent photovoltaic thermal (DCSPVT) module has been carried out. For extracting heat associated with the lower and upper surface of the solar cell, two channels have been proposed; (i) one is above the solar cell called upper channel and (ii) second is below the solar cell called lower channel. Firstly, thermal modeling of DCSPVT module has been developed. After that, performance analysis of the above system has been carried out for Srinagar, Indian climatic condition. Performance in terms of electrical gain (EG), thermal gain (TG), overall exergy gain (OEG), overall thermal gain (OTG), electrical efficiency (EE) and overall exergy efficiency (OEE) of the DCSPVT module (case-I) have been compared with single channel semitransparent photovoltaic thermal (SCSPVT) hybrid module (case-II). The average improvement in EG, TG, OEG, OTG of the case-I have been observed by 71.51%, 34.57%, 5.78% and 35.41% respectively as compared to case-II.

Rack assembly for mounting solar modules

Science.gov (United States)

Plaisted, Joshua Reed; West, Brian

2010-12-28

A rack assembly is provided for mounting solar modules over an underlying body. The rack assembly may include a plurality of rail structures that are arrangeable over the underlying body to form an overall perimeter for the rack assembly. One or more retention structures may be provided with the plurality of rail structures, where each retention structure is configured to support one or more solar modules at a given height above the underlying body. At least some of the plurality of rail structures are adapted to enable individual rail structures o be sealed over the underlying body so as to constrain air flow underneath the solar modules. Additionally, at least one of (i) one or more of the rail structures, or (ii) the one or more retention structures are adjustable so as to adapt the rack assembly to accommodate solar modules of varying forms or dimensions.

Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms

Directory of Open Access Journals (Sweden)

Alexandra Clemente-Perez

2017-06-01

Full Text Available Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV and somatostatin (SOM expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms.

Dopamine modulates memory consolidation of discrimination learning in the auditory cortex.

Science.gov (United States)

Schicknick, Horst; Reichenbach, Nicole; Smalla, Karl-Heinz; Scheich, Henning; Gundelfinger, Eckart D; Tischmeyer, Wolfgang

2012-03-01

In Mongolian gerbils, the auditory cortex is critical for discriminating rising vs. falling frequency-modulated tones. Based on our previous studies, we hypothesized that dopaminergic inputs to the auditory cortex during and shortly after acquisition of the discrimination strategy control long-term memory formation. To test this hypothesis, we studied frequency-modulated tone discrimination learning of gerbils in a shuttle box GO/NO-GO procedure following differential treatments. (i) Pre-exposure of gerbils to the frequency-modulated tones at 1 day before the first discrimination training session severely impaired the accuracy of the discrimination acquired in that session during the initial trials of a second training session, performed 1 day later. (ii) Local injection of the D1/D5 dopamine receptor antagonist SCH-23390 into the auditory cortex after task acquisition caused a discrimination deficit of similar extent and time course as with pre-exposure. This effect was dependent on the dose and time point of injection. (iii) Injection of the D1/D5 dopamine receptor agonist SKF-38393 into the auditory cortex after retraining caused a further discrimination improvement at the beginning of subsequent sessions. All three treatments, which supposedly interfered with dopamine signalling during conditioning and/or retraining, had a substantial impact on the dynamics of the discrimination performance particularly at the beginning of subsequent training sessions. These findings suggest that auditory-cortical dopamine activity after acquisition of a discrimination of complex sounds and after retrieval of weak frequency-modulated tone discrimination memory further improves memory consolidation, i.e. the correct association of two sounds with their respective GO/NO-GO meaning, in support of future memory recall. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Differential Aging Trajectories of Modulation of Activation to Cognitive Challenge in APOE ε4 Groups: Reduced Modulation Predicts Poorer Cognitive Performance.

Science.gov (United States)

Foster, Chris M; Kennedy, Kristen M; Rodrigue, Karen M

2017-07-19

The present study was designed to investigate the effect of a genetic risk factor for Alzheimer's disease (AD), ApolipoproteinE ε4 (APOEε4), on the ability of the brain to modulate activation in response to cognitive challenge in a lifespan sample of healthy human adults. A community-based sample of 181 cognitively intact, healthy adults were recruited from the Dallas-Fort Worth metroplex. Thirty-one APOEε4+ individuals (48% women), derived from the parent sample, were matched based on sex, age, and years of education to 31 individuals who were APOEε4-negative (APOEε4-). Ages ranged from 20 to 86 years of age. Blood oxygen level-dependent functional magnetic resonance imaging was collected during the performance of a visuospatial distance judgment task with three parametric levels of difficulty. Multiple regression was used in a whole-brain analysis with age, APOE group, and their interaction predicting functional brain modulation in response to difficulty. Results revealed an interaction between age and APOE in a large cluster localized primarily to the bilateral precuneus. APOEε4- individuals exhibited age-invariant modulation in response to task difficulty, whereas APOEε4+ individuals showed age-related reduction of modulation in response to increasing task difficulty compared with ε4- individuals. Decreased modulation in response to cognitive challenge was associated with reduced task accuracy as well as poorer name-face associative memory performance. Findings suggest that APOEε4 is associated with a reduction in the ability of the brain to dynamically modulate in response to cognitive challenge. Coupled with a significant genetic risk factor for AD, changes in modulation may provide additional information toward identifying individuals potentially at risk for cognitive decline associated with preclinical AD. SIGNIFICANCE STATEMENT Understanding how risk factors for Alzheimer's disease (AD) affect brain function and cognition in healthy adult samples

Development of a new lower hybrid antenna module using a poloidal power divider

International Nuclear Information System (INIS)

Maebara, S.; Imai, T.; Seki, M.; Suganuma, K.; Goniche, M.; Bibet, Ph.; Berio, S.; Brossaud, J.; Rey, G.; Tonon, G.

1997-03-01

A realistic antenna module using a poloidal divider for lower hybrid current drive (LHCD) experiment, is modelled and fabricated. In this antenna module test II, three types of poloidal dividers, which split the power in 3, are tested. (author)

[Research of dual-photoelastic-modulator-based beat frequency modulation and Fourier-Bessel transform imaging spectrometer].

Science.gov (United States)

Wang, Zhi-Bin; Zhang, Rui; Wang, Yao-Li; Huang, Yan-Fei; Chen, You-Hua; Wang, Li-Fu; Yang, Qiang

2014-02-01

As the existing photoelastic-modulator(PEM) modulating frequency in the tens of kHz to hundreds of kHz between, leading to frequency of modulated interference signal is higher, so ordinary array detector cannot effectively caprure interference signal..A new beat frequency modulation method based on dual-photoelastic-modulator (Dual-PEM) and Fourier-Bessel transform is proposed as an key component of dual-photoelastic-modulator-based imaging spectrometer (Dual-PEM-IS) combined with charge coupled device (CCD). The dual-PEM are operated as an electro-optic circular retardance modulator, Operating the PEMs at slightly different resonant frequencies w1 and w2 respectively, generates a differential signal at a much lower heterodyne frequency that modulates the incident light. This method not only retains the advantages of the existing PEM, but also the frequency of modulated photocurrent decreased by 2-3 orders of magnitude (10-500 Hz) and can be detected by common array detector, and the incident light spectra can be obtained by Fourier-Bessel transform of low frequency component in the modulated signal. The method makes the PEM has the dual capability of imaging and spectral measurement. The basic principle is introduced, the basic equations is derived, and the feasibility is verified through the corresponding numerical simulation and experiment. This method has' potential applications in imaging spectrometer technology, and analysis of the effect of deviation of the optical path difference. This work provides the necessary theoretical basis for remote sensing of new Dual-PEM-IS and for engineering implementation of spectra inversion.

The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention

Science.gov (United States)

Bekisz, Marek; Bogdan, Wojciech; Ghazaryan, Anaida; Waleszczyk, Wioletta J.; Kublik, Ewa; Wróbel, Andrzej

2016-01-01

Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation. PMID:26730705

Optics modules for circular accelerator design

International Nuclear Information System (INIS)

Brown, K.L.; Servranckx, R.V.

1986-05-01

The first-order differential equations of motion for a single particle in a closed circular machine are solved, introducing the concepts of phase shift, beta functions, and the Courant-Snyder invariant. The transfer matrix between two points in the machine is derived as a function of the phase shift and the parameters contained in the Courant-Snyder invariant. Typical optical modules used in circular machine designs are introduced and related to their characteristic transfer matrix elements, the phase shift through them, and the Courant-Snyder-Twiss parameters. The systematics of some elementary phase ellipse matching problems between optical modules are discussed. Second-order optical modules are discussed, including how they are used to provide the momentum bandwidth needed for the design of a typical circular machine

dE/dx electronics for MARK II experiment at SLAC

International Nuclear Information System (INIS)

Bernstein, D.; Boyarski, A.; Coupal, D.; Feldman, G.; Paffrath, L.

1985-10-01

This paper describes a 100 MHz pulse digitizer for dE/dx measurements on the MARK II drift chamber at SLAC. The electronics provides the read-out of the detector's 5832 sense based on a 16-channel FASTBUS module. The basic element of the module is the TRW 6-bit Flash-ADC

DUMAND-II progress report

International Nuclear Information System (INIS)

Wilkes, R.J.; Alexander, C.M.; Aoki, T.; Berson, U.; Bosetti, P.; Bolesta, J.; Boynton, P.E.; Bradner, H.; Camerini, U.; Dye, S.T.; Gergin, E.; Gorham, P.W.; Grieder, P.K.F.; Grogan, W.; Hanada, H.; Harris, D.; Hayashino, T.; Hazen, E.; Ito, M.; Jaworski, M.; Jenko, M.; Kawamoto, H.; Kitamura, T.; Kobayakawa, K.; Kondo, S.; Koske, P.; Learned, J.G.; Ley, C.; Lord, J.J.; Lord, R.; Lozic, T.; March, R.; Matsumoto, T.; Matsuno, S.; Mavretic, A.; McCourry, L.; Mignard, M.; Miller, K.; Minkowski, P.; Mitiguy, R.; Mitsui, K.; Narita, S.; Nicklaus, D.

1993-01-01

The design, scientific goals, and capabilities of the DUMAND II detector system are described. Construction was authorized by DOE in 1990, and construction of various detector subsystems is under way. Current plans include deployment of the shore cable, junction box and three strings of optical detector modules in 1993, with expansion to the full 9-string configuration about one year later

Design and Implementation of an Embedded NIOS II System for JPEG2000 Tier II Encoding

Directory of Open Access Journals (Sweden)

John M. McNichols

2013-01-01

Full Text Available This paper presents a novel implementation of the JPEG2000 standard as a system on a chip (SoC. While most of the research in this field centers on acceleration of the EBCOT Tier I encoder, this work focuses on an embedded solution for EBCOT Tier II. Specifically, this paper proposes using an embedded softcore processor to perform Tier II processing as the back end of an encoding pipeline. The Altera NIOS II processor is chosen for the implementation and is coupled with existing embedded processing modules to realize a fully embedded JPEG2000 encoder. The design is synthesized on a Stratix IV FPGA and is shown to out perform other comparable SoC implementations by 39% in computation time.

Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

Directory of Open Access Journals (Sweden)

Eichbaum Michael H

2011-01-01

Full Text Available Abstract Background The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. Methods/design The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border, heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Discussion Intensity-modulated WAR provides

Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

International Nuclear Information System (INIS)

Rochet, Nathalie; Debus, Juergen; Kieser, Meinhard; Sterzing, Florian; Krause, Sonja; Lindel, Katja; Harms, Wolfgang; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof

2011-01-01

The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border), heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Intensity-modulated WAR provides a new promising option in the consolidation treatment of

Class II HLA interactions modulate genetic risk for multiple sclerosis

DEFF Research Database (Denmark)

Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H

2015-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17...

Optical encryption using pseudorandom complex spatial modulation.

Science.gov (United States)

Sarkadi, Tamás; Koppa, Pál

2012-12-01

In this paper we propose a new (to our knowledge) complex spatial modulation method to encode data pages applicable in double random phase encryption (DRPE) to make the system more resistant to brute-force attack. The proposed modulation method uses data page pixels with random phase and amplitude values with the condition that the intensity of the interference of light from two adjacent pixels should correspond to the encoded information. A differential phase contrast technique is applied to recover the data page at the output of the system. We show that the proposed modulation method can enhance the robustness of the DRPE technique using point spread function analysis. Key space expansion is determined by numeric model calculations.

Handbook of differential equations stationary partial differential equations

CERN Document Server

Chipot, Michel

2006-01-01

This handbook is volume III in a series devoted to stationary partial differential quations. Similarly as volumes I and II, it is a collection of self contained state-of-the-art surveys written by well known experts in the field. The topics covered by this handbook include singular and higher order equations, problems near critically, problems with anisotropic nonlinearities, dam problem, T-convergence and Schauder-type estimates. These surveys will be useful for both beginners and experts and speed up the progress of corresponding (rapidly developing and fascinating) areas of mathematics. Ke

Heme oxygenase-1 gene expression modulates angiotensin II-induced increase in blood pressure.

Science.gov (United States)

Yang, Liming; Quan, Shuo; Nasjletti, Alberto; Laniado-Schwartzman, Michal; Abraham, Nader G

2004-06-01

The heme-heme oxygenase (HO) system has been implicated in the regulation of vascular reactivity and blood pressure. This study examines the notion that overexpression of HO decreases pressor responsiveness to angiotensin II (Ang II). Five-day-old Sprague-Dawley rats received an intraleft ventricular injection of approximately 5x10(9) cfu/mL of retroviruses containing human HO-1 sense (LSN-HHO-1), rat HO-1 antisense (LSN-RHO-1-AS), or control retrovirus (LXSN). Three months later, rats were instrumented with femoral arterial and venous catheters for mean arterial pressure (MAP) determination and Ang II administration, respectively. Rats injected with LSN-HHO-1, but not with LXSN, expressed human HO-1 mRNA and protein in several tissues. BP increased with administration of Ang II in rats expressing and not expressing human HO-1. However, the Ang II-induced pressor response (mm Hg) in LSN-HHO-1 rats (16+/-3, 27+/-3, and 38+/-3 at 0.5, 2, and 10 ng) was surpassed (PHHO-1 rats with the HO inhibitor tin mesoporphyrin (SnMP) enhanced (P<0.05) the Ang II-induced pressor response to a level not different from that observed in LXSN rats. Rats injected with LSN-RHO-1-AS showed a decrease in renal HO-1 protein expression and HO activity relative to control LXSN rats. Administration of Ang II (0.1 to 2 ng) caused small (4 to 5 mm Hg) but significant increases in MAP in rats injected with LSN-RHO-1-AS (P<0.05) compared with rats injected with LXSN. These data demonstrate that overexpression of HO-1 brings about a reduction in pressor responsiveness to Ang II, which is most likely due to increased generation of an HO-1 product, presumably CO, with the ability to inhibit vascular reactivity to constrictor stimuli.

Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells

International Nuclear Information System (INIS)

Dartel, Dorien A.M. van; Pennings, Jeroen L.A.; Schooten, Frederik J. van; Piersma, Aldert H.

2010-01-01

The embryonic stem cell test (EST) predicts developmental toxicity based on the inhibition of cardiomyocyte differentiation of embryonic stem cells (ESC). The subjective endpoint, the long culture duration together with the undefined applicability domain and related predictivity need further improvement to facilitate implementation of the EST into regulatory strategies. These aspects may be improved by studying gene expression changes in the ESC differentiation cultures and their modulation by compound exposure using transcriptomics. Here, we tested the developmental toxicants monobutyl phthalate and 6-aminonicotinamide. ESC were allowed to differentiated, and cardiomyocyte differentiation was assessed after 10 days of culture. RNA of solvent controls was collected after 0, 24, 48, 72 and 96 h of exposure, and RNA of developmental-toxicant-exposed cultures was collected after 24 and 96 h. Samples were hybridized to DNA microarrays, and 1355 genes were found differentially expressed among the unexposed experimental groups. These regulated genes were involved in differentiation-related processes, and Principal Component Analysis (PCA) based on these genes showed that the unexposed experimental groups appeared in chronological order in the PCA, which can therefore be regarded as a continuous representation of the differentiation track. The developmental-toxicant-exposed cultures appeared to deviate significantly from this differentiation track, which confirms the compound-modulating effects on the differentiation process. The incorporation of transcriptomics in the EST is expected to provide a more informative and improved endpoint in the EST as compared with morphology, allowing early detection of differentiation modulation. Furthermore, this approach may improve the definition of the applicability domain and predictivity of the EST.

Modulation of human dendritic cell activity by Giardia and helminth antigens

DEFF Research Database (Denmark)

Summan, Anneka; Nejsum, Peter; Williams, Andrew R

2018-01-01

by modulating cytokine secretion and/or inducing apoptosis, which may be a parasite driven mechanism to dampen host immunity and establish chronic infections. The differential mechanisms of DC modulation by intestinal parasites warrant further attention. This article is protected by copyright. All rights...

Reversible differentiation of myofibroblasts by MyoD

International Nuclear Information System (INIS)

Hecker, Louise; Jagirdar, Rajesh; Jin, Toni; Thannickal, Victor J.

2011-01-01

Myofibroblasts participate in tissue repair processes in diverse mammalian organ systems. The deactivation of myofibroblasts is critical for termination of the reparative response and restoration of tissue structure and function. The current paradigm on normal tissue repair is the apoptotic clearance of terminally differentiated myofibroblasts; while, the accumulation of activated myofibroblasts is associated with progressive human fibrotic disorders. The capacity of myofibroblasts to undergo de-differentiation as a potential mechanism for myofibroblast deactivation has not been examined. In this report, we have uncovered a role for MyoD in the induction of myofibroblast differentiation by transforming growth factor-β1 (TGF-β1). Myofibroblasts demonstrate the capacity for de-differentiation and proliferation by modulation of endogenous levels of MyoD. We propose a model of reciprocal signaling between TGF-β1/ALK5/MyoD and mitogen(s)/ERK-MAPK/CDKs that regulate myofibroblast differentiation and de-differentiation, respectively. Our studies provide the first evidence for MyoD in controlling myofibroblast activation and deactivation. Restricted capacity for de-differentiation of myofibroblasts may underlie the progressive nature of recalcitrant human fibrotic disorders.

A portable data acquisition system on J.I.P.P. T-II ICRF experiment

International Nuclear Information System (INIS)

Hidekuma, S.

1982-03-01

This system has been developed for the data acquisition in the J.I.P.P. T-II ICRF experiment. It is composed of the LSI-11/2(56KB), a dual floppy disk drive, CAMAC modules, a graphic display and an interface module to the HITAC 10-II system. The operating system is RT-11. This system has functions of the data acquisition through A-D converters (max.32ch), the transfer of the data to the HITAC 10-II system and the preservation of them in its floppy disk. Furthermore, a user can easily develop his application programs with this system. The operating procedures of this system are described. (author)

Serotonin receptors expressed in Drosophila mushroom bodies differentially modulate larval locomotion.

Directory of Open Access Journals (Sweden)

Bryon Silva

Full Text Available Drosophila melanogaster has been successfully used as a simple model to study the cellular and molecular mechanisms underlying behaviors, including the generation of motor programs. Thus, it has been shown that, as in vertebrates, CNS biogenic amines (BA including serotonin (5HT participate in motor control in Drosophila. Several evidence show that BA systems innervate an important association area in the insect brain previously associated to the planning and/or execution of motor programs, the Mushroom Bodies (MB. The main objective of this work is to evaluate the contribution of 5HT and its receptors expressed in MB to motor behavior in fly larva. Locomotion was evaluated using an automated tracking system, in Drosophila larvae (3(rd-instar exposed to drugs that affect the serotonergic neuronal transmission: alpha-methyl-L-dopa, MDMA and fluoxetine. In addition, animals expressing mutations in the 5HT biosynthetic enzymes or in any of the previously identified receptors for this amine (5HT1AR, 5HT1BR, 5HT2R and 5HT7R were evaluated in their locomotion. Finally, RNAi directed to the Drosophila 5HT receptor transcripts were expressed in MB and the effect of this manipulation on motor behavior was assessed. Data obtained in the mutants and in animals exposed to the serotonergic drugs, suggest that 5HT systems are important regulators of motor programs in fly larvae. Studies carried out in animals pan-neuronally expressing the RNAi for each of the serotonergic receptors, support this idea and further suggest that CNS 5HT pathways play a role in motor control. Moreover, animals expressing an RNAi for 5HT1BR, 5HT2R and 5HT7R in MB show increased motor behavior, while no effect is observed when the RNAi for 5HT1AR is expressed in this region. Thus, our data suggest that CNS 5HT systems are involved in motor control, and that 5HT receptors expressed in MB differentially modulate motor programs in fly larvae.

Cell proliferation and migration are modulated by Cdk-1-phosphorylated endothelial-monocyte activating polypeptide II.

Directory of Open Access Journals (Sweden)

Margaret A Schwarz

Full Text Available Endothelial-Monocyte Activating Polypeptide (EMAP II is a secreted protein with well-established anti-angiogenic activities. Intracellular EMAP II expression is increased during fetal development at epithelial/mesenchymal boundaries and in pathophysiologic fibroproliferative cells of bronchopulmonary dysplasia, emphysema, and scar fibroblast tissue following myocardial ischemia. Precise function and regulation of intracellular EMAP II, however, has not been explored to date.Here we show that high intracellular EMAP II suppresses cellular proliferation by slowing progression through the G2M cell cycle transition in epithelium and fibroblast. Furthermore, EMAP II binds to and is phosphorylated by Cdk1, and exhibits nuclear/cytoplasmic partitioning, with only nuclear EMAP II being phosphorylated. We observed that extracellular secreted EMAP II induces endothelial cell apoptosis, where as excess intracellular EMAP II facilitates epithelial and fibroblast cells migration.Our findings suggest that EMAP II has specific intracellular effects, and that this intracellular function appears to antagonize its extracellular anti-angiogenic effects during fetal development and pulmonary disease progression.

Identification and Characterization of Novel Immunomodulatory Bursal-derived Pentapeptide-II (BPP-II)*

Science.gov (United States)

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-01-01

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement. PMID:22184121

Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).

Science.gov (United States)

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-02-03

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.

Impedance-Source Networks for Electric Power Conversion Part II

DEFF Research Database (Denmark)

Siwakoti, Yam P.; Peng, Fang Zheng; Blaabjerg, Frede

2015-01-01

Impedance-source networks cover the entire spectrum of electric power conversion applications (dc-dc, dc-ac, ac-dc, ac-ac) controlled and modulated by different modulation strategies to generate the desired dc or ac voltage and current at the output. A comprehensive review of various impedance......-source-network-based power converters has been covered in a previous paper and main topologies were discussed from an application point of view. Now Part II provides a comprehensive review of the most popular control and modulation strategies for impedance-source network-based power converters/inverters. These methods...

Differential diagnosis of sensory modulation dysfunction (SMD and attention deficit hyperactivity disorder (ADHD: participation, sensation and attention

Directory of Open Access Journals (Sweden)

Aviva eYochman

2013-12-01

Full Text Available Differential diagnosis between sensory modulation disorder (SMD and attention deficit hyperactivity disorder (ADHD is often challenging, since these disorders occur at a high rate of co-morbidity and share several clinical characteristics. Preliminary studies providing evidence that these are distinct disorders have focused solely on body functions, using sophisticated laboratory measurements. Moreover, no studies have compared participation profiles of these populations. This study is the first to compare the profiles of these populations regarding both ‘body functions’(attention and sensation and ‘participation,’ using measures applicable for clinical use. The study included 19 children with ADHD without SMD and 19 with SMD without ADHD (diagnosed by both pediatric neurologists and occupational therapists, aged 6 to 9, and matched by age and gender. All children underwent a broad battery of evaluations: The Evaluation of Sensory Processing, Fabric Prickliness Test and Von Frey Test to evaluate sensory processing, and Test of Everyday Attention to evaluate attention components. The Participation in Childhood Occupations Questionnaire was used to evaluate participation. Results support significant group differences in all sensory components, including pain intensity to suprathreshold stimuli and pain 'after sensation', as well as in tactile, vestibular, taste and olfactory processing. No differences were found in attention components and participation. This study has both theoretical and clinical importance, inter alia, providing further evidence of two distinct disorders as well as indications of specific clinical instruments that might enable clinicians to implement differential diagnoses. In addition, results accord with other previous statements, which indicate that the clinical diagnosis of children with disabilities may not be a major factor in determining their participation profile.

Analysis of hepatocellular carcinoma and metastatic hepatic carcinoma via functional modules in a protein-protein interaction network

Directory of Open Access Journals (Sweden)

Jun Pan

2014-01-01

Full Text Available Introduction: This study aims to identify protein clusters with potential functional relevance in the pathogenesis of hepatocellular carcinoma (HCC and metastatic hepatic carcinoma using network analysis. Materials and Methods: We used human protein interaction data to build a protein-protein interaction network with Cytoscape and then derived functional clusters using MCODE. Combining the gene expression profiles, we calculated the functional scores for the clusters and selected statistically significant clusters. Meanwhile, Gene Ontology was used to assess the functionality of these clusters. Finally, a support vector machine was trained on the gold standard data sets. Results: The differentially expressed genes of HCC were mainly involved in metabolic and signaling processes. We acquired 13 significant modules from the gene expression profiles. The area under the curve value based on the differentially expressed modules were 98.31%, which outweighed the classification with DEGs. Conclusions: Differentially expressed modules are valuable to screen biomarkers combined with functional modules.

Differential modulation of thresholds for intracranial self-stimulation by mGlu5 positive and negative allosteric modulators: implications for effects on drug self-administration

Directory of Open Access Journals (Sweden)

M. Foster eOlive

2012-01-01

Full Text Available Pharmacological manipulation of the type 5 metabotropic glutamate (mGlu5 receptor alters various addiction related behaviors such as drug self-administration and the extinction and reinstatement of drug-seeking behavior. However, the effects of pharmacological modulation of mGlu5 receptors on brain reward function have not been widely investigated. We examined the effects of acute administration of positive and negative allosteric modulators (PAMs and NAMs, respectively on brain reward function by assessing thresholds for intracranial self-stimulation (ICSS. In addition, when acute effects were observed, we examined potential changes in altered ICSS thresholds following repeated administration. Male Sprague-Dawley rats were implanted with bipolar electrodes into the medial forebrain bundle and trained to respond for ICSS, followed by assessment of effects of mGlu5 ligands on ICSS thresholds using a discrete trials current intensity threshold determination procedure. Acute administration of the selective mGlu5 NAMs MTEP (0, 0.3, 1 or 3 mg/kg and fenobam (0, 3, 10, or 30 mg/kg dose-dependently increased ICSS thresholds (~70% at the highest dose tested, suggesting a deficit in brain reward function. Acute administration of the mGlu5 PAMs CDPPB (0, 10, 30 and 60 mg/kg or ADX47273 (0, 10, 30 and 60 mg/kg was without effect at any dose tested. When administered once daily for 5 consecutive days, the development of tolerance to the ability of threshold-elevating doses of MTEP and fenobam to increase ICSS thresholds was observed. We conclude that mGlu5 PAMs and NAMs differentially affect brain reward function, and that tolerance to the ability of mGlu5 NAMs to reduce brain reward function develops with repeated administration. These brain reward deficits should be taken into consideration when interpreting acute effects of mGlu5 NAMs on drug self-administration, and repeated administration may be an effective method to reduce these deficits.

H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response

Science.gov (United States)

Bland, David A; Suarez, Giovanni; Beswick, Ellen J; Sierra, Johanna C; Reyes, Victor E

2006-01-01

AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells. PMID:16981259

IGF-II Promotes Stemness of Neural Restricted Precursors

Science.gov (United States)

Ziegler, Amber N.; Schneider, Joel S.; Qin, Mei; Tyler, William A.; Pintar, John E.; Fraidenraich, Diego; Wood, Teresa L.; Levison, Steven W.

2016-01-01

Insulin-like growth factor (IGF)-I and IGF-II regulate brain development and growth through the IGF type 1 receptor (IGF-1R). Less appreciated is that IGF-II, but not IGF-I, activates a splice variant of the insulin receptor (IR) known as IR-A. We hypothesized that IGF-II exerts distinct effects from IGF-I on neural stem/progenitor cells (NSPs) via its interaction with IR-A. Immunofluorescence revealed high IGF-II in the medial region of the subventricular zone (SVZ) comprising the neural stem cell niche, with IGF-II mRNA predominant in the adjacent choroid plexus. The IGF-1R and the IR isoforms were differentially expressed with IR-A predominant in the medial SVZ, whereas the IGF-1R was more abundant laterally. Similarly, IR-A was more highly expressed by NSPs, whereas the IGF-1R was more highly expressed by lineage restricted cells. In vitro, IGF-II was more potent in promoting NSP expansion than either IGF-I or standard growth medium. Limiting dilution and differentiation assays revealed that IGF-II was superior to IGF-I in promoting stemness. In vivo, NSPs propagated in IGF-II migrated to and took up residence in periventricular niches while IGF-I-treated NSPs predominantly colonized white matter. Knockdown of IR or IGF-1R using shRNAs supported the conclusion that the IGF-1R promotes progenitor proliferation, whereas the IR is important for self-renewal. Q-PCR revealed that IGF-II increased Oct4, Sox1, and FABP7 mRNA levels in NSPs. Our data support the conclusion that IGF-II promotes the self-renewal of neural stem/progenitors via the IR. By contrast, IGF-1R functions as a mitogenic receptor to increase precursor abundance. PMID:22593020

Crystal structure of the commensurately modulated ζ phase of PAMC

DEFF Research Database (Denmark)

Harris, P.; Larsen, F.K.; Lebech, B.

1994-01-01

phase, indicating a 'lock-in' and phase shift between adjacent modulated layers. The modulation waves do not change much from the values of the epsilon phase, which confirms the lock-in of the modulation vector; only some components of the modulations of the propylammonium chains appear......The commensurately modulated zeta low-temperature phase of bis(propylammonium) tetrachloromanganate(II), [NH3(C3H7)]2MnCl4, has been determined at 8 K. a = 7.437 (5), b = 7.082 (5), c = 13.096 (8) Angstrom, alpha = 105.59 (1)degrees. Superspace group P2(1)/b(0 beta 0)(1) over bar s, with beta = 1...... to be significantly different, these chains appear to be responsible for the phase shift across the layers....

Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation.

Directory of Open Access Journals (Sweden)

Priyadarsini Kumar

Full Text Available Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2 and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts and a villous pathway (giving rise to multinucleated syncytiotrophoblast. Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries. We tested the idea that sodium butyrate (an epigenetic modulator induces trophoblast differentiation in early gestation rhesus monkey trophoblasts through activation of the Wnt/β-catenin pathway. The results show that syncytiotrophoblast formation was increased by butyrate, accompanied by nuclear accumulation of β-catenin, and increased expression of EnvV2 and galectin-1 (two factors thought to be involved in trophoblast fusion. Surprisingly, the expression of GCM1 and syncytin-2 was not affected by sodium butyrate. When trophoblasts were incubated with lithium chloride, a GSK3 inhibitor that mimics Wnt activation, nuclear accumulation of β-catenin also occurred but differentiation into syncytiotrophoblast was not observed. Instead the cells differentiated to mononucleated spindle-shaped cells and showed molecular and behavioral characteristics of endovascular trophoblasts. Another highly specific inhibitor of GSK3, CHIR99021, failed to induce endovascular trophoblast characteristics. These observations suggest that activation of the Wnt/β-catenin pathway correlates with both trophoblast differentiation pathways, but that additional factors determine specific cell fate decisions. Other experiments suggested that the differential effects of sodium butyrate and lithium chloride might be explained by their effects on TNF�

Perturbative Heat Transport Experiments on TJ-II

International Nuclear Information System (INIS)

Eguilor, S.; Castejon, F.; Luna, E. de la; Cappa, A.; Likin, K.; Fernandez, A.; Tj-II, T.

2002-01-01

Heat wave experiments are performed on TJ-II stellarator plasmas to estimate both heat diffusivity and power deposition profiles. High frequency ECRH modulation experiments are used to obtain the power deposition profiles, which is observed to be wider and duller than estimated by tracing techniques. The causes of this difference are discussed in the paper. Fourier analysis techniques are used to estimate the heat diffusivity in low frequency ECRH modulation experiments. This include the power deposition profile as a new ingredient. ECHR switch on/off experiments are exploited to obtain power deposition and heat diffusivities profile. Those quantities are compared with the obtained by modulation experiments and transport analysis, showing a good agreement. (Author) 18 refs

Perturbative Heat Transport Experiments on TJ-II

Energy Technology Data Exchange (ETDEWEB)

Eguilor, S.; Castejon, F.; Luna, E. de la; Cappa, A.; Likin, K.; Fernandez, A.; Tj-II, T.

2002-07-01

Heat wave experiments are performed on TJ-II stellarator plasmas to estimate both heat diffusivity and power deposition profiles. High frequency ECRH modulation experiments are used to obtain the power deposition profiles, which is observed to be wider and duller than estimated by tracing techniques. The causes of this difference are discussed in the paper. Fourier analysis techniques are used to estimate the heat diffusivity in low frequency ECRH modulation experiments. This include the power deposition profile as a new ingredient. ECHR switch on/off experiments are exploited to obtain power deposition and heat diffusivities profile. Those quantities are compared with the obtained by modulation experiments and transport analysis, showing a good agreement. (Author) 18 refs.

Real-time RT-PCR high-resolution melting curve analysis and multiplex RT-PCR to detect and differentiate grapevine leafroll-associated associated virus 3 variant groups I, II, III and VI

Directory of Open Access Journals (Sweden)

Bester Rachelle

2012-09-01

Full Text Available Abstract Background Grapevine leafroll-associated virus 3 (GLRaV-3 is the main contributing agent of leafroll disease worldwide. Four of the six GLRaV-3 variant groups known have been found in South Africa, but their individual contribution to leafroll disease is unknown. In order to study the pathogenesis of leafroll disease, a sensitive and accurate diagnostic assay is required that can detect different variant groups of GLRaV-3. Methods In this study, a one-step real-time RT-PCR, followed by high-resolution melting (HRM curve analysis for the simultaneous detection and identification of GLRaV-3 variants of groups I, II, III and VI, was developed. A melting point confidence interval for each variant group was calculated to include at least 90% of all melting points observed. A multiplex RT-PCR protocol was developed to these four variant groups in order to assess the efficacy of the real-time RT-PCR HRM assay. Results A universal primer set for GLRaV-3 targeting the heat shock protein 70 homologue (Hsp70h gene of GLRaV-3 was designed that is able to detect GLRaV-3 variant groups I, II, III and VI and differentiate between them with high-resolution melting curve analysis. The real-time RT-PCR HRM and the multiplex RT-PCR were optimized using 121 GLRaV-3 positive samples. Due to a considerable variation in melting profile observed within each GLRaV-3 group, a confidence interval of above 90% was calculated for each variant group, based on the range and distribution of melting points. The intervals of groups I and II could not be distinguished and a 95% joint confidence interval was calculated for simultaneous detection of group I and II variants. An additional primer pair targeting GLRaV-3 ORF1a was developed that can be used in a subsequent real-time RT-PCR HRM to differentiate between variants of groups I and II. Additionally, the multiplex RT-PCR successfully validated 94.64% of the infections detected with the real-time RT-PCR HRM

DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells.

Science.gov (United States)

Le, Hanh; Arnold, Julia T; McFann, Kimberly K; Blackman, Marc R

2006-05-01

Prostate cancer is one of the four most common cancers in the United States, affecting one of six men. Increased serum levels of androgens and IGF-I are associated with an augmented risk of prostate cancer. Dihydrotestosterone (DHT) and testosterone (T) stimulate prostate cancer cell growth, development, and function, whereas the effects of DHT and T in prostate stromal cells, and of dehydroepiandrosterone (DHEA) in prostate cancer or stromal cells, are uncertain. We investigated the actions of DHT, T, DHEA, and estradiol (E2) on insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor (R), IGF-binding protein (IGFBP)-2, IGFBP-3, and IGFBP-5 in primary cultures of human prostatic stromal cells by assessing cell proliferation, mRNA expression, and protein secretion by MTT growth assay, quantitative real-time PCR, and ELISA, respectively. DHT and T each increased IGF-I (7-fold) and decreased IGFBP-3 (2-fold) mRNA expression and protein secretion in a dose- and time-dependent manner and increased IGFBP-2 (2-fold) mRNA in a dose- and time-dependent manner. DHEA and E2 did not significantly alter these measures. Flutamide abolished the DHT-modulated increases in IGF-I and IGFBP-2, suggesting that the influences of DHT and T on these measures were androgen receptor mediated. None of the four steroids significantly affected IGF-IR, IGF-II, or IGFBP-5 mRNA levels or stromal cell proliferation. The effects of DHT on IGF-I, IGFBP-2, and IGFBP-3 were more pronounced in stromal cultures that did not express desmin. These data suggest that DHT and T promote prostate growth partly via modulation of the stromal cell IGF axis, with potential paracrine effects on prostate epithelial cells.

Solving Differential Equations Analytically. Elementary Differential Equations. Modules and Monographs in Undergraduate Mathematics and Its Applications Project. UMAP Unit 335.

Science.gov (United States)

Goldston, J. W.

This unit introduces analytic solutions of ordinary differential equations. The objective is to enable the student to decide whether a given function solves a given differential equation. Examples of problems from biology and chemistry are covered. Problem sets, quizzes, and a model exam are included, and answers to all items are provided. The…

Differentially Encoded LDPC Codes—Part II: General Case and Code Optimization

Directory of Open Access Journals (Sweden)

Li (Tiffany Jing

2008-01-01

Full Text Available This two-part series of papers studies the theory and practice of differentially encoded low-density parity-check (DE-LDPC codes, especially in the context of noncoherent detection. Part I showed that a special class of DE-LDPC codes, product accumulate codes, perform very well with both coherent and noncoherent detections. The analysis here reveals that a conventional LDPC code, however, is not fitful for differential coding and does not, in general, deliver a desirable performance when detected noncoherently. Through extrinsic information transfer (EXIT analysis and a modified "convergence-constraint" density evolution (DE method developed here, we provide a characterization of the type of LDPC degree profiles that work in harmony with differential detection (or a recursive inner code in general, and demonstrate how to optimize these LDPC codes. The convergence-constraint method provides a useful extension to the conventional "threshold-constraint" method, and can match an outer LDPC code to any given inner code with the imperfectness of the inner decoder taken into consideration.

Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) – Pilot trial of a phase I/II study: study protocol

International Nuclear Information System (INIS)

Rochet, Nathalie; Jensen, Alexandra D; Sterzing, Florian; Munter, Marc W; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

2007-01-01

The prognosis for patients with advanced epithelial ovarian cancer remains poor despite aggressive surgical resection and platinum-based chemotherapy. More than 60% of patients will develop recurrent disease, principally intraperitoneal, and die within 5 years. The use of whole abdominal irradiation (WAI) as consolidation therapy would appear to be a logical strategy given its ability to sterilize small tumour volumes. Despite the clinically proven efficacy of whole abdominal irradiation, the use of radiotherapy in ovarian cancer has profoundly decreased mainly due to high treatment-related toxicity. Modern intensity-modulated radiation therapy (IMRT) could allow to spare kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. The OVAR-IMRT-01 study is a single center pilot trial of a phase I/II study. Patients with advanced ovarian cancer stage FIGO III (R1 or R2< 1 cm) after surgical resection and platinum-based chemotherapy will be treated with whole abdomen irradiation as consolidation therapy using intensity modulated radiation therapy (IMRT) to a total dose of 30 Gy in 1.5 Gy fractions. A total of 8 patients will be included in this trial. For treatment planning bone marrow, kidneys, liver, spinal cord, vertebral bodies and pelvic bones are defined as organs at risk. The planning target volume includes the entire peritoneal cavity plus pelvic and para-aortic node regions. The primary endpoint of the study is the evaluation of the feasibility of intensity-modulated WAI and the evaluation of the study protocol. Secondary endpoint is evaluation of the toxicity of intensity modulated WAI before continuing with the phase I/II study. The aim is to explore the potential of IMRT as a new method for WAI to decrease the dose to kidneys, liver, bone marrow while covering the peritoneal cavity with a homogenous dose, and to implement whole abdominal intensity-modulated radiotherapy into the adjuvant multimodal

Sibling rivalry: competition between MHC class II family members inhibits immunity.

Science.gov (United States)

Denzin, Lisa K; Cresswell, Peter

2013-01-01

Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation.

Scintillation counter and wire chamber front end modules for high energy physics experiments

International Nuclear Information System (INIS)

Baldin, Boris; DalMonte, Lou

2011-01-01

This document describes two front-end modules developed for the proposed MIPP upgrade (P-960) experiment at Fermilab. The scintillation counter module was developed for the Plastic Ball detector time and charge measurements. The module has eight LEMO 00 input connectors terminated with 50 ohms and accepts negative photomultiplier signals in the range 0.25...1000 pC with the maximum input voltage of 4.0 V. Each input has a passive splitter with integration and differentiation times of ∼20 ns. The integrated portion of the signal is digitized at 26.55 MHz by Analog Devices AD9229 12-bit pipelined 4-channel ADC. The differentiated signal is discriminated for time measurement and sent to one of the four TMC304 inputs. The 4-channel TMC304 chip allows high precision time measurement of rising and falling edges with ∼100 ps resolution and has internal digital pipeline. The ADC data is also pipelined which allows deadtime-less operation with trigger decision times of ∼4 (micro)s. The wire chamber module was developed for MIPP EMCal detector charge measurements. The 32-channel digitizer accepts differential analog signals from four 8-channel integrating wire amplifiers. The connection between wire amplifier and digitizer is provided via 26-wire twist-n-flat cable. The wire amplifier integrates input wire current and has sensitivity of 275 mV/pC and the noise level of ∼0.013 pC. The digitizer uses the same 12-bit AD9229 ADC chip as the scintillator counter module. The wire amplifier has a built-in test pulser with a mask register to provide testing of the individual channels. Both modules are implemented as a 6Ux220 mm VME size board with 48-pin power connector. A custom europack (VME) 21-slot crate is developed for housing these front-end modules.

Stuttering adults' lack of pre-speech auditory modulation normalizes when speaking with delayed auditory feedback.

Science.gov (United States)

Daliri, Ayoub; Max, Ludo

2018-02-01

Auditory modulation during speech movement planning is limited in adults who stutter (AWS), but the functional relevance of the phenomenon itself remains unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a potential relationship between pre-speech auditory modulation and auditory feedback contributions to speech motor learning and (b) the effect on pre-speech auditory modulation of real-time versus delayed auditory feedback. Experiment I used a sensorimotor adaptation paradigm to estimate auditory-motor speech learning. Using acoustic speech recordings, we quantified subjects' formant frequency adjustments across trials when continually exposed to formant-shifted auditory feedback. In Experiment II, we used electroencephalography to determine the same subjects' extent of pre-speech auditory modulation (reductions in auditory evoked potential N1 amplitude) when probe tones were delivered prior to speaking versus not speaking. To manipulate subjects' ability to monitor real-time feedback, we included speaking conditions with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory-motor learning was limited for AWS versus AWNS, and the extent of learning was negatively correlated with stuttering frequency. Experiment II yielded several key findings: (a) our prior finding of limited pre-speech auditory modulation in AWS was replicated; (b) DAF caused a decrease in auditory modulation for most AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory modulation when speaking with DAF was positively correlated with stuttering frequency. Lastly, AWNS showed no correlation between pre-speech auditory modulation (Experiment II) and extent of auditory-motor learning (Experiment I) whereas AWS showed a negative correlation between these measures. Thus, findings suggest that AWS show deficits in both pre-speech auditory modulation and auditory-motor learning; however, limited pre

Identification of Transcriptional Modules and Key Genes in Chickens Infected with Salmonella enterica Serovar Pullorum Using Integrated Coexpression Analyses

Directory of Open Access Journals (Sweden)

Bao-Hong Liu

2017-01-01

Full Text Available Salmonella enterica Pullorum is one of the leading causes of mortality in poultry. Understanding the molecular response in chickens in response to the infection by S. enterica is important in revealing the mechanisms of pathogenesis and disease progress. There have been studies on identifying genes associated with Salmonella infection by differential expression analysis, but the relationships among regulated genes have not been investigated. In this study, we employed weighted gene coexpression network analysis (WGCNA and differential coexpression analysis (DCEA to identify coexpression modules by exploring microarray data derived from chicken splenic tissues in response to the S. enterica infection. A total of 19 modules from 13,538 genes were associated with the Jak-STAT signaling pathway, the extracellular matrix, cytoskeleton organization, the regulation of the actin cytoskeleton, G-protein coupled receptor activity, Toll-like receptor signaling pathways, and immune system processes; among them, 14 differentially coexpressed modules (DCMs and 2,856 differentially coexpressed genes (DCGs were identified. The global expression of module genes between infected and uninfected chickens showed slight differences but considerable changes for global coexpression. Furthermore, DCGs were consistently linked to the hubs of the modules. These results will help prioritize candidate genes for future studies of Salmonella infection.

Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

Energy Technology Data Exchange (ETDEWEB)

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

2013-11-15

Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment. �

Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

International Nuclear Information System (INIS)

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

2013-01-01

Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment. �

Re-modulated technology of WDM-PON employing different DQPSK downstream signals

Science.gov (United States)

Gao, Chao; Xin, Xiang-jun; Yu, Chong-xiu

2012-11-01

This paper proposes a kind of modulation architecture for wavelength-division-multiplexing passive optical network (WDMPON) employing optical differential quadrature phase shift keying (DQPSK) downstream signals and two different modulation formats of re-modulated upstream signals. At the optical line terminal (OLT), 10 Gbit/s signal is modulated with DQPSK. At the optical network unit (ONU), part of the downstream signal is re-modulated with on-off keying (OOK) or inverse-return-to-zero (IRZ). Simulation results show the impact on the system employing NRZ, RZ and carrier-suppressed return-to-zero (CSRZ). The analyses also reflect that the architecture can restrain chromatic dispersion and channel crosstalk, which makes it the best architecture of access network in the future.

The role of surface microtopography in the modulation of osteoblast differentiation

Directory of Open Access Journals (Sweden)

JS Hayes

2010-07-01

Full Text Available The osteoinductive and conductive capabilities of commercially pure titanium and its alloys is well documented, as is their ability to provide long-term stability for permanent implantable devices. Fracture fixation in paediatric and trauma patients generally requires transient fixation after which the implant becomes redundant and requires removal. Removal can be complicated due to excessive bony over-growth which is encouraged by the standard micro-rough implant surface. We have shown in vivo that removal related morbidity can be significantly reduced with surface polishing, a technique which reduces the micro-roughness of clinically available materials. However, tissue integration at the bone-implant interface requires activation of key regulatory pathways which influences osteoblastic differentiation and maturation therefore we do not believe this effect to be purely mechanical. To elucidate potential mechanisms by which surface polishing exerts its effect on bone regeneration this study assessed in vitro the effect of surface polishing commercially pure titanium on cell growth, morphology and on the regulation of core binding factor 1, osterix, collagen I, alkaline phosphatase, bone sialoprotein and osteocalcin for primary rat calvarial osteoblasts. Results indicate that polishing differentially influences osteoblast differentiation in a surface dependent manner and that these changes are potentially linked to surface dependent morphology, but not to differences in cell proliferation.

Detection and processing of phase modulated optical signals at 40 Gbit/s and beyond

DEFF Research Database (Denmark)

Geng, Yan

the amplitude regeneration capability based on FWM in a highly nonlinear fiber (HNLF). The first reported experimental demonstration of amplitude equalization of 40 Gbit/s RZ-DPSK signals using a 500 m long HNLF is presented. Using four possible phase levels to carry the information, DQPSK allows generation......This thesis addresses demodulation in direct detection systems and signal processing of high speed phase modulated signals in future all-optical wavelength division multiplexing (WDM) communication systems where differential phase shift keying (DPSK) or differential quadrature phase shift keying...... (DQPSK) are used to transport information. All-optical network functionalities -such as optical labeling, wavelength conversion and signal regeneration- are experimentally investigated. Direct detection of phase modulated signals requires phase-to-intensity modulation conversion in a demodulator...

Extreme electronic modulation of the cofacial porphyrin structural motif.

Science.gov (United States)

Fletcher, James T; Therien, Michael J

2002-04-24

The synthesis, electrochemistry, and optical spectroscopy of an extensive series of cofacial bis[(porphinato)zinc(II)] compounds are reported. These species were synthesized using sequential palladium-catalyzed cross-coupling and cobalt-mediated [2+2+2] cycloaddition reactions. This modular methodology enables facile control of the nature of macrocycle-to-macrocycle connectivity and allows unprecedented modulation of the redox properties of face-to-face porphyrin species. We report the synthesis of 5,6-bis[(5',5''-10',20'-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (1), 5,6-bis[(2'-5',10',15',20'-tetraphenylporphinato)zinc(II)]indane (2), 5-([2'-5',10',15',20'-tetraphenylporphinato]zinc(II))-6-[(5"-10'',20''-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (3), 5-([2'-5',10',15',20'-tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(5' '-10' ',20' '-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (4), 5-(2'-5',10',15',20'-[tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(2''-5'',10'',15'',20''-tetraphenylporphinato)zinc(II)]indane (5), 5,6-bis([2'-5',15'-diphenyl-10',20'-(trifluoromethyl)porphinato]zinc(II))indane (6), and 5,6-bis([2'-5',10',15',20'-tetrakis(trifluoromethyl)porphinato]zinc(II))indane (7); 4-7 define the first examples of cofacial bis[(porphinato)metal] compounds in which sigma-electron-withdrawing perfluoroalkyl groups serve as macrocycle substituents, while 2, 6, and 7 constitute the first such structures that possess a beta-to-beta linkage topology. Cyclic voltammetric studies show that the electrochemically determined HOMO and LUMO energy levels of these cofacial bis(porphinato) complexes can be lowered by 780 and 945 mV, respectively, relative to the archetypal members of this class of compounds; importantly, these orbital energy levels can be modulated over well-defined increments throughout these wide potentiometric domains. Analyses of these cofacial bis

Ca II H and K emission from late-type stars

International Nuclear Information System (INIS)

Middlekoop, F.

1982-01-01

This thesis is based on a study of the Ca II H and K emission features of late main-sequence stars. In Chapter II it is shown that rotation periods can be determined from a modulation in the Ca II H and K signal for many stars in a broad range of spectral types. In Chapter III it is shown that a clear correlation exists between Ca II H and K emission and rotational velocity in active main-sequence stars. There is an indication for a (probably colour-dependent) critical velocity at which the Ca II H and K emission suddenly drops. Chapter IV discusses the dependence of Ca II H and K emission on the rotation rate for evolved stars. (Auth./C.F.)

Modulation Technique for Four-Leg Voltage Source Inverter without a Look-Up Table

DEFF Research Database (Denmark)

Ebrahimzadeh, Esmaeil; Farhangi, Shahrokh; Iman-Eini, Hossein

2016-01-01

Three-dimensional space-vector modulation (3D SVM) has more popularity among the other modulation techniques of the four-leg inverter due to higher DC-link voltage utilisation. Sequencing schemes of the switching vectors in the 3D SVM are divided into Class I and II categories. Each of these clas...

Industry wage differentials, rent sharing and gender: three empirical essays

OpenAIRE

Tojerow, Ilan

2008-01-01

This thesis focuses on the industry wage differentials, rent-sharing and the gender wage gap. I empirically investigate: i) the interaction between inter-industry wage differentials and the gender wage gap in six European countries, ii) how rent sharing interacts with the gender wage gap in the Belgian private sector and iii) the existence of inter-industry wage differentials in Belgium, through the unobserved ability hypothesis.The first chapter is devoted to the analysis of the interaction ...

Development of photovoltaic array and module safety requirements

Science.gov (United States)

1982-01-01

Safety requirements for photovoltaic module and panel designs and configurations likely to be used in residential, intermediate, and large-scale applications were identified and developed. The National Electrical Code and Building Codes were reviewed with respect to present provisions which may be considered to affect the design of photovoltaic modules. Limited testing, primarily in the roof fire resistance field was conducted. Additional studies and further investigations led to the development of a proposed standard for safety for flat-plate photovoltaic modules and panels. Additional work covered the initial investigation of conceptual approaches and temporary deployment, for concept verification purposes, of a differential dc ground-fault detection circuit suitable as a part of a photovoltaic array safety system.

Differential scanning calorimetry (DSC) and temperature-modulated DSC study of three mouthguard materials.

Science.gov (United States)

Meng, Frank H; Schricker, Scott R; Brantley, William A; Mendel, Deborah A; Rashid, Robert G; Fields, Henry W; Vig, Katherine W L; Alapati, Satish B

2007-12-01

Employ differential scanning calorimetry (DSC) and temperature-modulated DSC (TMDSC) to investigate thermal transformations in three mouthguard materials and provide insight into their previously investigated energy absorption. Samples (13-21mg) were obtained from (a) conventional ethylene vinyl acetate (EVA), (b) Pro-form, another EVA polymer, and (c) PolyShok, an EVA polymer containing polyurethane. Conventional DSC (n=5) was first performed from -80 to 150 degrees C at a heating rate of 10 degrees C/min to determine the temperature range for structural transformations. Subsequently, TMDSC (n=5) was performed from -20 to 150 degrees C at a heating rate of 1 degrees C/min. Onset and peak temperatures were compared using ANOVA and the Tukey-Kramer HSD test. Other samples were coated with a gold-palladium film and examined with an SEM. DSC and TMDSC curves were similar for both conventional EVA and Pro-form, showing two endothermic peaks suggestive of melting processes, with crystallization after the higher-temperature peak. Evidence for crystallization and the second endothermic peak were much less prominent for PolyShok, which had no peaks associated with the polyurethane constituent. The onset of the lower-temperature endothermic transformation is near body temperature. No glass transitions were observed in the materials. SEM examination revealed different surface morphology and possible cushioning effect for PolyShok, compared to Pro-form and EVA. The difference in thermal behavior for PolyShok is tentatively attributed to disruption of EVA crystal formation, which may contribute to its superior impact resistance. The lower-temperature endothermic peak suggests that impact testing of these materials should be performed at 37 degrees C.

wALADin benzimidazoles differentially modulate the function of porphobilinogen synthase orthologs.

Science.gov (United States)

Lentz, Christian S; Halls, Victoria S; Hannam, Jeffrey S; Strassel, Silke; Lawrence, Sarah H; Jaffe, Eileen K; Famulok, Michael; Hoerauf, Achim; Pfarr, Kenneth M

2014-03-27

The heme biosynthesis enzyme porphobilinogen synthase (PBGS) is a potential drug target in several human pathogens. wALADin1 benzimidazoles have emerged as species-selective PBGS inhibitors against Wolbachia endobacteria of filarial worms. In the present study, we have systematically tested wALADins against PBGS orthologs from bacteria, protozoa, metazoa, and plants to elucidate the inhibitory spectrum. However, the effect of wALADin1 on different PBGS orthologs was not limited to inhibition: several orthologs were stimulated by wALADin1; others remained unaffected. We demonstrate that wALADins allosterically modulate the PBGS homooligomeric equilibrium with inhibition mediated by favoring low-activity oligomers, while 5-aminolevulinic acid, Mg(2+), or K(+) stabilized high-activity oligomers. Pseudomonas aeruginosa PBGS could be inhibited or stimulated by wALADin1 depending on these factors and pH. We have defined the wALADin chemotypes responsible for either inhibition or stimulation, facilitating the design of tailored PBGS modulators for potential application as antimicrobial agents, herbicides, or drugs for porphyric disorders.

Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.

Science.gov (United States)

Grilli, A; Sciandra, M; Terracciano, M; Picci, P; Scotlandi, K

2015-06-30

microRNAs (miRs) are small non-coding RNAs involved in the fine regulation of several cellular processes by inhibiting their target genes at post-transcriptional level. Osteosarcoma (OS) is a tumor thought to be related to a molecular blockade of the normal process of osteoblast differentiation. The current paper explores temporal transcriptional modifications comparing an osteosarcoma cell line, Saos-2, and clones stably transfected with CD99, a molecule which was found to drive OS cells to terminally differentiate. Parental cell line and CD99 transfectants were cultured up to 14 days in differentiating medium. In this setting, OS cells were profiled by gene and miRNA expression arrays. Integration of gene and miRNA profiling was performed by both sequence complementarity and expression correlation. Further enrichment and network analyses were carried out to focus on the modulated pathways and on the interactions between transcriptome and miRNome. To track the temporal transcriptional modification, a PCA analysis with differentiated human MSC was performed. We identified a strong (about 80 %) gene down-modulation where reversion towards the osteoblast-like phenotype matches significant enrichment in TGFbeta signaling players like AKT1 and SMADs. In parallel, we observed the modulation of several cancer-related microRNAs like miR-34a, miR-26b or miR-378. To decipher their impact on the modified transcriptional program in CD99 cells, we correlated gene and microRNA time-series data miR-34a, in particular, was found to regulate a distinct subnetwork of genes with respect to the rest of the other differentially expressed miRs and it appeared to be the main mediator of several TGFbeta signaling genes at initial and middle phases of differentiation. Integration studies further highlighted the involvement of TGFbeta pathway in the differentiation of OS cells towards osteoblasts and its regulation by microRNAs. These data underline that the expression of miR-34a and down-modulation

Increasing the bit rate in OCDMA systems using pulse position modulation techniques.

Science.gov (United States)

Arbab, Vahid R; Saghari, Poorya; Haghi, Mahta; Ebrahimi, Paniz; Willner, Alan E

2007-09-17

We have experimentally demonstrated two novel pulse position modulation techniques, namely Double Pulse Position Modulation (2-PPM) and Differential Pulse Position Modulation (DPPM) in Time-Wavelength OCDMA systems that will operate at a higher bit rate compared to traditional OOK-OCDMA systems with the same bandwidth. With 2-PPM technique, the number of active users will be more than DPPM while their bit rate is almost the same. Both techniques provide variable quality of service in OCDMA networks.

Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

DEFF Research Database (Denmark)

Chen, Li; Hu, Huimin; Qiu, Weimin

2018-01-01

Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte...

Differential modulation of nitric oxide synthases in aging: therapeutic opportunities

Directory of Open Access Journals (Sweden)

Stêfany Bruno De Assis Cau

2012-06-01

Full Text Available Vascular aging is the term that describes the structural and functional disturbances of the vasculature with advancing aging. The molecular mechanisms of aging-associated endothelial dysfunction are complex, but reduced nitric oxide (NO bioavailability and altered vascular expression and activity of NO synthase (NOS enzymes have been implicated as major players. Impaired vascular relaxation in aging has been attributed to reduced endothelial NOS (eNOS-derived NO, while increased inducible NOS (iNOS expression seems to account for nitrosative stress and disrupted vascular homeostasis. Although eNOS is considered the main source of NO in the vascular endothelium, neuronal NOS (nNOS also contributes to endothelial cells-derived NO, a mechanism that is reduced in aging. Pharmacological modulation of NO generation and expression/activity of NOS isoforms may represent a therapeutic alternative to prevent the progression of cardiovascular diseases. Accordingly, this review will focus on drugs that modulate NO bioavailability, such as nitrite anions and NO-releasing non-steroidal anti-inflammatory drugs, hormones (dehydroepiandrosterone and estrogen, statins, resveratrol and folic acid, since they may be useful to treat/to prevent aging-associated vascular dysfunction. The impact of these therapies on life quality in elderly and longevity will be discussed.

Multilevel photonic modules for millimeter-wave phased-array antennas

Science.gov (United States)

Paolella, Arthur C.; Bauerle, Athena; Joshi, Abhay M.; Wright, James G.; Coryell, Louis A.

2000-09-01

Millimeter wave phased array systems have antenna element sizes and spacings similar to MMIC chip dimensions by virtue of the operating wavelength. Designing modules in traditional planar packaing techniques are therefore difficult to implement. An advantageous way to maintain a small module footprint compatible with Ka-Band and high frequency systems is to take advantage of two leading edge technologies, opto- electronic integrated circuits (OEICs) and multilevel packaging technology. Under a Phase II SBIR these technologies are combined to form photonic modules for optically controlled millimeter wave phased array antennas. The proposed module, consisting of an OEIC integrated with a planar antenna array will operate on the 40GHz region. The OEIC consists of an InP based dual-depletion PIN photodetector and distributed amplifier. The multi-level module will be fabricated using an enhanced circuit processing thick film process. Since the modules are batch fabricated using an enhanced circuit processing thick film process. Since the modules are batch fabricated, using standard commercial processes, it has the potential to be low cost while maintaining high performance, impacting both military and commercial communications systems.

Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

OpenAIRE

Souza, Patrícia Reis de; Sales-Campos, Helioswilton; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda; Alves, Vanessa Beatriz Freitas; Chica, Javier Emílio Lazo; Nomizo, Auro; Cardoso, Cristina Ribeiro de Barros

2016-01-01

The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score...

Local inversions in ultrasound-modulated optical tomography

International Nuclear Information System (INIS)

Bal, Guillaume; Moskow, Shari

2014-01-01

Ultrasound-modulated optical tomography is a hybrid imaging modality that aims to combine the high contrast of optical waves with the high resolution of ultrasound. We follow the model of the influence of ultrasound modulation on the light intensity measurements developed in Bal and Schotland (2010 Phys. Rev. Lett. 104 043902). We present sufficient conditions ensuring that the absorption and diffusion coefficients modeling light propagation can locally be uniquely and stably reconstructed from the corresponding available information. We present an iterative procedure to solve such a problem based on the analysis of linear elliptic systems of redundant partial differential equations. (paper)

Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells

International Nuclear Information System (INIS)

Vaca, Pilar; Berna, Genoveva; Araujo, Raquel; Carneiro, Everardo M.; Bedoya, Francisco J.; Soria, Bernat; Martin, Franz

2008-01-01

The poly(ADP-ribose) polymerase (PARP) inhibitor, nicotinamide, induces differentiation and maturation of fetal pancreatic cells. In addition, we have previously reported evidence that nicotinamide increases the insulin content of cells differentiated from embryonic stem (ES) cells, but the possibility of nicotinamide acting as a differentiating agent on its own has never been completely explored. Islet cell differentiation was studied by: (i) X-gal staining after neomycin selection; (ii) BrdU studies; (iii) single and double immunohistochemistry for insulin, C-peptide and Glut-2; (iv) insulin and C-peptide content and secretion assays; and (v) transplantation of differentiated cells, under the kidney capsule, into streptozotocin (STZ)-diabetic mice. Here we show that undifferentiated mouse ES cells treated with nicotinamide: (i) showed an 80% decrease in cell proliferation; (ii) co-expressed insulin, C-peptide and Glut-2; (iii) had values of insulin and C-peptide corresponding to 10% of normal mouse islets; (iv) released insulin and C-peptide in response to stimulatory glucose concentrations; and (v) after transplantation into diabetic mice, normalized blood glucose levels over 7 weeks. Our data indicate that nicotinamide decreases ES cell proliferation and induces differentiation into insulin-secreting cells. Both aspects are very important when thinking about cell therapy for the treatment of diabetes based on ES cells

Single or combined treatment with L-DOPA and quinpirole differentially modulate expression and phosphorylation of key regulatory kinases in neuroblastoma cells.

Science.gov (United States)

Fuzzati-Armentero, Marie Therese; Ghezzi, Cristina; Nisticò, Robert; Oda, Adriano; Blandini, Fabio

2013-09-27

In the past decades, the clinical use of dopamine agonists has expanded from adjunct therapy in patients with a deteriorating response to L-3,4-dihydroxyphenylalanine (L-DOPA) to monotherapy for the treatment of early PD. Dopamine agonists provide their antiparkinsonian benefit through stimulation of brain postsynaptic type 2 dopamine receptors that exert their effect through classical cAMP-dependent mechanisms, as well as cAMP-independent cellular signaling cascades, including the Akt/glycogen synthase kinase 3 (GSK3) pathway. Alterations of Akt/GSK3 have been observed and may contribute to the neurodegenerative processes and the development of L-DOPA-induced dyskinesia. The effects L-DOPA and quinpirole, a dopamine agonist, on the two key regulatory kinases, Akt and GSK3, were evaluated in neuroblastoma cell line. L-DOPA and dopamine agonist dose-dependently and differentially modulated Akt and GSK3 expression and phosphorylation when added alone or combined. The combined treatment inverted or potentiated the modulatory properties of the single compound. The drug- and concentration-dependent balance of dopamine receptor stimulation over auto-oxidation may distinctively modulate GSK3 isoforms and Akt. Our results indicate that particular attention must be given to drug concentration and combination when multiple therapies are applied for the clinical treatment of PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

Science.gov (United States)

Seo, Seung In; Kim, Hyoung Su; Kim, Won Jin; Shin, Woon Geon; Kim, Doo Jin; Kim, Kyung Ho; Jang, Myoung Kuk; Lee, Jin Heon; Kim, Joo Seop; Kim, Hak Yang; Kim, Dong Joon; Lee, Myung Seok; Park, Choong Kee

2015-01-01

AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB). METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their combination were calculated and compared. RESULTS: The optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-II and AFP were not significantly different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB (P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION: Serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB. PMID:25852278

Grid-connected of photovoltaic module using nonlinear control

DEFF Research Database (Denmark)

El Fadil, H.; Giri, F.; Guerrero, Josep M.

2012-01-01

The problem of controlling single-phase grid connected photovoltaic (PV) system is considered. The control objective is fourfold: (i) asymptotic stability of the closed loop system, (ii) maximum power point tracking (MPPT) of PV module (iii) tight regulation of the DC bus voltage, and (iv) unity...

A cryogenic multichannel electronically scanned pressure module

Science.gov (United States)

Shams, Qamar A.; Fox, Robert L.; Adcock, Edward E.; Kahng, Seun K.

1992-01-01

Consideration is given to a cryogenic multichannel electronically scanned pressure (ESP) module developed and tested over an extended temperature span from -184 to +50 C and a pressure range of 0 to 5 psig. The ESP module consists of 32 pressure sensor dice, four analog 8 differential-input multiplexers, and an amplifier circuit, all of which are packaged in a physical volume of 2 x 1 x 5/8 in with 32 pressure and two reference ports. Maximum nonrepeatability is measured at 0.21 percent of full-scale output. The ESP modules have performed consistently well over 15 times over the above temperature range and continue to work without any sign of degradation. These sensors are also immune to repeated thermal shock tests over a temperature change of 220 C/sec.

Digital logic circuit design with ALTERA MAX+PLUS II

International Nuclear Information System (INIS)

Lee, Seung Ho; Park, Yong Su; Park, Gun Jong; Lee, Ju Heon

2006-09-01

This book is composed of five parts. The first part has introduction of ALTERA MAX+PLUS II and graphic editor, text editor, compiler, waveform editor simulator and timing analyzer of it. The second part is about direction of digital logic circuit design with training kit. The third part has grammar and practice of VHDL in ALTERA MAX+PLUS II including example and history of VHDL. The fourth part shows the design example of digital logic circuit by VHDL of ALTERA MAX+PLUS II which lists designs of adder and subtractor, code converter, counter, state machine and LCD module. The last part explains design example of digital logic circuit by graphic editor in ALTERA MAX+PLUS II.

Hyponormal differential operators with discrete spectrum

Directory of Open Access Journals (Sweden)

Zameddin I. Ismailov

2010-01-01

Full Text Available In this work, we first describe all the maximal hyponormal extensions of a minimal operator generated by a linear differential-operator expression of the first-order in the Hilbert space of vector-functions in a finite interval. Next, we investigate the discreteness of the spectrum and the asymptotical behavior of the modules of the eigenvalues for these maximal hyponormal extensions.

The diabetogenic mouse MHC class II molecule I-A[subscript g7] is endowed with a switch that modulates TCR affinity

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Kenji; Corper, Adam L.; Herro, Rana; Jabri, Bana; Wilson, Ian A.; Teyton, Luc (Scripps); (UC)

2011-11-16

Genetic susceptibility to autoimmunity is frequently associated with specific MHC alleles. Diabetogenic MHC class II molecules, such as human HLA-DQ8 and mouse I-A{sub g7}, typically have a small, uncharged amino acid residue at position 57 of their {beta} chain ({beta}57); this results in the absence of a salt bridge between {beta}57 and Arg{alpha}76, which is adjacent to the P9 pocket of the peptide-binding groove. However, the influence of Arg{alpha}76 on the selection of the TCR repertoire remains unknown, particularly when the MHC molecule binds a peptide with a neutral amino acid residue at position P9. Here, we have shown that diabetogenic MHC class II molecules bound to a peptide with a neutral P9 residue primarily selected and expanded cells expressing TCRs bearing a negatively charged residue in the first segment of their complementarity determining region 3{beta}. The crystal structure of one such TCR in complex with I-A{sub g7} bound to a peptide containing a neutral P9 residue revealed that a network of favorable long-range (greater than 4 {angstrom}) electrostatic interactions existed among Arg{alpha}76, the neutral P9 residue, and TCR, which supported the substantially increased TCR/peptide-MHC affinity. This network could be modulated or switched to a lower affinity interaction by the introduction of a negative charge at position P9 of the peptide. Our results support the existence of a switch at residue {beta}57 of the I-Ag7 and HLA-DQ8 class II molecules and potentially link normal thymic TCR selection with abnormal peripheral behavior.

Heat capacity measurements on ThO2 by temperature modulated differential scanning calorimetry (TMDSC)

International Nuclear Information System (INIS)

Venkatakrishnan, R.; Nagarajan, K.; Vasudeva Rao, P.R.

2001-01-01

Heat capacity measurements were carried out on ThO 2 in the temperature range 330-820 K by using temperature modulated DSC. An underlying heating rate of 5 K. min -1 , a temperature modulation with an amplitude of 0.398K and a period of 150s were used for these measurements. The heat capacity values are within ± 2-4% of the literature data. (author)

Cu(II AND Zn(II COMPLEX COMPOUNDS WITH BIGUANIDES AROMATIC DERIVATIVES. SYNTHESIS, CHARACTERIZATION, BIOLOGICAL ACTIVITY

Directory of Open Access Journals (Sweden)

Ticuţa Negreanu-Pîrjol

2011-05-01

Full Text Available In this paper we report the synthesis, physical-chemical characterization and antimicrobial activity of some new complex compounds of hetero-aromatic biguanides ligands, chlorhexidine base (CHX and chlorhexidine diacetate (CHXac2 with metallic ions Cu(II and Zn(II, in different molar ratio. The synthesized complexes were characterized by elemental chemical analysis and differential thermal analysis. The stereochemistry of the metallic ions was determined by infrared spectra, UV-Vis, EPR spectroscopy and magnetic susceptibility in the aim to establish the complexes structures. The biological activity of the new complex compounds was identified in solid technique by measuring minimum inhibition diameter of bacterial and fungal culture, against three standard pathogen strains, Escherichia coli ATCC 25922, Staphilococcus aureus ATCC 25923 and Candida albicans ATCC 10231. The results show an increased specific antimicrobial activity for the complexes chlorhexidine:Cu(II 1:1 and 1:2 compared with the one of the Zn(II complexes.

Digital logic circuit design with ALTERA MAX+PLUS II

International Nuclear Information System (INIS)

Lee, Seung Ho; Park, Yong Su; Lee, Ju Heon

2006-03-01

Contents of this book are the kinds of integrated circuit, design process of integrated circuit, introduction of ALTERA MAX+PLUS II, designing logic circuit with VHDL of ALTERA MAX+PLUS II, grammar and practice of VHDL of ALTERA MAX+PLUS II, design for adder, subtractor, parallel binary subtractor, BCD design, CLA design, code converter design, ALU design, register design, counter design, accumulator design, state machine design, frequency divider design, circuit design with TENMILLION counter, LCD module, circuit design for control the outside RAM in training kit and introduction for HEB-DTK-20K-240/HBE-DTK-IOK.

Combination of the LEP II ffbar Results

CERN Document Server

Geweniger, C; Elsing, M; Goy, C; Holt, J; Liebig, W; Minard, M N; Renton, P B; Riemann, S; Sachs, K; Ward, P; Wynhoff, S

2002-01-01

Preliminary combinations of measurements of the 4 LEP collaborations of the process e+e-->ffbar at LEP-II are presented, using data from the full LEP-II data set where available. Cross-sections and forward-backward asymmetry measurements are combined for the full LEP-II data set. Combined differential cross-sections $\\frac{{\\rm d}\\sigma}{{\\rm d}\\cos\\theta}$ for electron-pairs, muon pair and tau-pair final states are presented. Measurements of the production of heavy flavours are combined. The combined results are interpreted in terms of contact interactions and the exchange Z' bosons and leptoquarks, and within models of low scale gravity in large extra dimensions.

Vertically mounted bifacial photovoltaic modules: A global analysis

International Nuclear Information System (INIS)

Guo, Siyu; Walsh, Timothy Michael; Peters, Marius

2013-01-01

Bifacial PV (photovoltaic) modules have recently come to increasing attention and various system designs have been investigated. In this paper, a global comparison is made between vertically mounted bifacial modules facing East–West and conventionally mounted mono-facial modules. An analytical method is used to calculate the radiation received by these two module configurations. It is found that the answer to the question which of these two module configurations performs better strongly depends on three factors: (i) the latitude, (ii) the local diffuse fraction and (iii) the albedo. In a subsequent part of the paper, the minimum albedo required to result in a better performance for vertically mounted bifacial modules is calculated for every place in the world. The calculation is based on measured data of the diffuse light fraction and the results are shown in the form of a global map. Finally, the albedo requirements are compared with the measured global albedo distribution. The calculation allows a distinct decision which module configuration is more suitable for a certain place in the world. The result is also shown as a map defining the corresponding areas. - Highlights: • Vertically mounted bifacial module and conventionally monofacial module are compared. • The key factors affecting the performance of the two configurations are investigated. • Which module configuration is more suitable for each place is shown in a world map. • The minimum albedo for bifacial modules to have a better performance is calculated

An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

Science.gov (United States)

Ruge, Diane; Muggleton, Neil; Hoad, Damon; Caronni, Antonio; Rothwell, John C

2014-09-01

The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Multi-level trellis coded modulation and multi-stage decoding

Science.gov (United States)

Costello, Daniel J., Jr.; Wu, Jiantian; Lin, Shu

1990-01-01

Several constructions for multi-level trellis codes are presented and many codes with better performance than previously known codes are found. These codes provide a flexible trade-off between coding gain, decoding complexity, and decoding delay. New multi-level trellis coded modulation schemes using generalized set partitioning methods are developed for Quadrature Amplitude Modulation (QAM) and Phase Shift Keying (PSK) signal sets. New rotationally invariant multi-level trellis codes which can be combined with differential encoding to resolve phase ambiguity are presented.

bHLH-O proteins balance the self-renewal and differentiation of Drosophila neural stem cells by regulating Earmuff expression.

Science.gov (United States)

Li, Xiaosu; Chen, Rui; Zhu, Sijun

2017-11-15

Balancing self-renewal and differentiation of stem cells requires differential expression of self-renewing factors in two daughter cells generated from the asymmetric division of the stem cells. In Drosophila type II neural stem cell (or neuroblast, NB) lineages, the expression of the basic helix-loop-helix-Orange (bHLH-O) family proteins, including Deadpan (Dpn) and E(spl) proteins, is required for maintaining the self-renewal and identity of type II NBs, whereas the absence of these self-renewing factors is essential for the differentiation of intermediate neural progenitors (INPs) generated from type II NBs. Here, we demonstrate that Dpn maintains type II NBs by suppressing the expression of Earmuff (Erm). We provide evidence that Dpn and E(spl) proteins suppress Erm by directly binding to C-sites and N-boxes in the cis-regulatory region of erm. Conversely, the absence of bHLH-O proteins in INPs allows activation of erm and Erm-mediated maturation of INPs. Our results further suggest that Pointed P1 (PntP1) mediates the dedifferentiation of INPs resulting from the loss of Erm or overexpression of Dpn or E(spl) proteins. Taken together, these findings reveal mechanisms underlying the regulation of the maintenance of type II NBs and differentiation of INPs through the differential expression of bHLH-O family proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Csk regulates angiotensin II-induced podocyte apoptosis.

Science.gov (United States)

Zhang, Lu; Ren, Zhilong; Yang, Qian; Ding, Guohua

2016-07-01

Increasing data have shown that angiotensin II (Ang II) perpetuates podocyte injury and promotes progression to end-stage kidney disease. The mechanism underlying Ang II-induced podocyte apoptosis has not been established. C-terminal Src kinase (Csk) is a cytoplasmic kinase that interacts with scaffolding proteins involved in cell growth, adhesion, and polarization, and the role of Csk in regulating cellular apoptosis has gradually attracted attention. This study evaluates the role of Csk in Ang II-induced podocyte apoptosis. In vivo, Wistar rats were randomly subjected to a normal saline or Ang II infusion. In vitro, we exposed differentiated mouse podocytes to Ang II. Ang II increased Csk expression and induced podocyte apoptosis, stimulated Csk translocation and binding to Caveolin-1, and stimulated decreased Fyn pY416, increased Fyn pY529, and nephrin dephosphorylation. Csk knockdown prevented Ang II-induced podocyte apoptosis, reduced Fyn kinase inactivation, and increased the interaction between nephrin and the activated form of Fyn, accompanied by a reduced interaction between Csk and Caveolin-1. These findings indicate that Ang II induces podocyte injury via a Csk-dependent pathway.

ATLAS ITk short-strip stave prototype module with integrated DCDC powering and control

CERN Document Server

AUTHOR|(SzGeCERN)397167; The ATLAS collaboration

2017-01-01

During the Phase II upgrade, the ATLAS detector at the LHC will be upgraded with a new Inner Tracker (ITk) detector. The ITk prototype barrel module design has adopted an integrated low mass assembly featuring single-sided flexible circuits, with readout ASICs, glued to the silicon strip sensor. Further integration has been achieved by the attachment of module DCDC powering, a HV sensor biasing switch and autonomous monitoring and control to the sensor. This low mass integrated module approach benefits further in a reduced width stave structure to which the modules are attached. The results of preliminary electrical tests of such an integrated module are presented.

Repression of BLADE-ON-PETIOLE genes by KNOX homeodomain protein BREVIPEDICELLUS is essential for differentiation of secondary xylem in Arabidopsis root.

Science.gov (United States)

Woerlen, Natalie; Allam, Gamalat; Popescu, Adina; Corrigan, Laura; Pautot, Véronique; Hepworth, Shelley R

2017-06-01

Repression of boundary genes by KNOTTED1-like homeodomain transcription factor BREVIPEDICELLUS promotes the differentiation of phase II secondary xylem in Arabidopsis roots. Plant growth and development relies on the activity of meristems. Boundaries are domains of restricted growth that separate forming organs and the meristem. Class I KNOX homeodomain transcription factors are important regulators of meristem maintenance. Members of this class including BREVIDICELLUS also called KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (BP/KNAT1) fulfill this function in part by spatially regulating boundary genes. The vascular cambium is a lateral meristem that allows for radial expansion of organs during secondary growth. We show here that BP/KNAT1 repression of boundary genes plays a crucial role in root secondary growth. In particular, exclusion of BLADE-ON-PETIOLE1/2 (BOP1/2) and other members of this module from xylem is required for the differentiation of lignified fibers and vessels during the xylem expansion phase of root thickening. These data reveal a previously undiscovered role for boundary genes in the root and shed light on mechanisms controlling wood development in trees.

Socio-Cognitive Phenotypes Differentially Modulate Large-Scale Structural Covariance Networks.

Science.gov (United States)

Valk, Sofie L; Bernhardt, Boris C; Böckler, Anne; Trautwein, Fynn-Mathis; Kanske, Philipp; Singer, Tania

2017-02-01

Functional neuroimaging studies have suggested the existence of 2 largely distinct social cognition networks, one for theory of mind (taking others' cognitive perspective) and another for empathy (sharing others' affective states). To address whether these networks can also be dissociated at the level of brain structure, we combined behavioral phenotyping across multiple socio-cognitive tasks with 3-Tesla MRI cortical thickness and structural covariance analysis in 270 healthy adults, recruited across 2 sites. Regional thickness mapping only provided partial support for divergent substrates, highlighting that individual differences in empathy relate to left insular-opercular thickness while no correlation between thickness and mentalizing scores was found. Conversely, structural covariance analysis showed clearly divergent network modulations by socio-cognitive and -affective phenotypes. Specifically, individual differences in theory of mind related to structural integration between temporo-parietal and dorsomedial prefrontal regions while empathy modulated the strength of dorsal anterior insula networks. Findings were robust across both recruitment sites, suggesting generalizability. At the level of structural network embedding, our study provides a double dissociation between empathy and mentalizing. Moreover, our findings suggest that structural substrates of higher-order social cognition are reflected rather in interregional networks than in the the local anatomical markup of specific regions per se. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Real-time data exchange system in CSRe and RIBBLL II

International Nuclear Information System (INIS)

Liu Wufeng; Xu Yang; Li Guohua; Guo Yuhui; Chinese Academy of Sciences, Beijing; Qiao Weimin; Jing Lan; Wang Yongping; Gou Shizhe

2008-01-01

The design of real-time data exchange system in HIRFL-CSR's CSRe and RIBLL II has been introduced, including it's design of software and hardware. This system realizes controlling power devices at the same time. In system, data is from web browser to center Oracle database. And then, it arrives at sqlite database in ARM module by way of front-server's Oracle database by COM module. Finally, ARM module transmits data to DSP module's memory to control power devices when event is same. At the same time, ADC can acquire device's current value or voltage value which is saved in center Oracle data-base. Practice shows that this system has the character of high reliability and stability. (authors)

Head position modulates optokinetic nystagmus.

Science.gov (United States)

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

2011-08-01

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

Rho GTPases in ameloblast differentiation

Directory of Open Access Journals (Sweden)

Keishi Otsu

2016-05-01

Full Text Available During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

New insights into redox regulation of stem cell self-renewal and differentiation.

Science.gov (United States)

Ren, Fenglian; Wang, Kui; Zhang, Tao; Jiang, Jingwen; Nice, Edouard Collins; Huang, Canhua

2015-08-01

Reactive oxygen species (ROS), the natural byproducts of aerobic metabolism, are precisely orchestrated to evoke diverse signaling pathways. To date, studies have focused mainly on the detrimental effects of ROS in stem cells. Recently, accumulating evidence has suggested that ROS also function as second messengers that modulate stem cell self-renewal and differentiation by regulating intricate signaling networks. Although many efforts have been made to clarify the general effects of ROS on signal transduction in stem cells, less is known about the initial and direct executors of ROS signaling, which are known as 'redox sensors'. Modifications of cysteine residues in redox sensors are of significant importance in the modulation of protein function in response to different redox conditions. Intriguingly, most key molecules in ROS signaling and cell cycle regulation (including transcriptional factors and kinases) that are crucial in the regulation of stem cell self-renewal and differentiation have the potential to be redox sensors. We highlight herein the importance of redox regulation of these key regulators in stem cell self-renewal and differentiation. Understanding the mechanisms of redox regulation in stem cell self-renewal and differentiation will open exciting new perspectives for stem cell biology. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy analysis of LDPC coded APSK modulated differential space-time-frequency coded for wireless body area network using MB-pulsed OFDM UWB technology.

Science.gov (United States)

Manimegalai, C T; Gauni, Sabitha; Kalimuthu, K

2017-12-04

Wireless body area network (WBAN) is a breakthrough technology in healthcare areas such as hospital and telemedicine. The human body has a complex mixture of different tissues. It is expected that the nature of propagation of electromagnetic signals is distinct in each of these tissues. This forms the base for the WBAN, which is different from other environments. In this paper, the knowledge of Ultra Wide Band (UWB) channel is explored in the WBAN (IEEE 802.15.6) system. The measurements of parameters in frequency range from 3.1-10.6 GHz are taken. The proposed system, transmits data up to 480 Mbps by using LDPC coded APSK Modulated Differential Space-Time-Frequency Coded MB-OFDM to increase the throughput and power efficiency.

The Tocotrienol-Rich Fraction Is Superior to Tocopherol in Promoting Myogenic Differentiation in the Prevention of Replicative Senescence of Myoblasts.

Directory of Open Access Journals (Sweden)

Shy Cian Khor

Full Text Available Aging results in a loss of muscle mass and strength. Myoblasts play an important role in maintaining muscle mass through regenerative processes, which are impaired during aging. Vitamin E potentially ameliorates age-related phenotypes. Hence, this study aimed to determine the effects of the tocotrienol-rich fraction (TRF and α-tocopherol (ATF in protecting myoblasts from replicative senescence and promoting myogenic differentiation. Primary human myoblasts were cultured into young and senescent stages and were then treated with TRF or ATF for 24 h, followed by an analysis of cell proliferation, senescence biomarkers, cellular morphology and differentiation. Our data showed that replicative senescence impaired the normal regenerative processes of myoblasts, resulting in changes in cellular morphology, cell proliferation, senescence-associated β-galactosidase (SA-β-gal expression, myogenic differentiation and myogenic regulatory factors (MRFs expression. Treatment with both TRF and ATF was beneficial to senescent myoblasts in reclaiming the morphology of young cells, improved cell viability and decreased SA-β-gal expression. However, only TRF treatment increased BrdU incorporation in senescent myoblasts, as well as promoted myogenic differentiation through the modulation of MRFs at the mRNA and protein levels. MYOD1 and MYOG gene expression and myogenin protein expression were modulated in the early phases of myogenic differentiation. In conclusion, the tocotrienol-rich fraction is superior to α-tocopherol in ameliorating replicative senescence-related aberration and promoting differentiation via modulation of MRFs expression, indicating vitamin E potential in modulating replicative senescence of myoblasts.

Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

Science.gov (United States)

Tahimic, Candice; Bahl, Disha; Shirazi-Fard, Yasaman; Marsh, Timothy; Schreurs, Anne-Sofie; Rael, Victoria E.; Glikbarg, Chloe; Debnath, Jayantha; Globus, Ruth K.

2016-01-01

Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. This bone loss is attributed to increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our long-term goal is to identify signaling pathways that may be targeted to mitigate bone loss in scenarios of space exploration, radiotherapy and accidental radiation exposure. We have previously shown that exposure of MLO-Y4 osteocyte-like cells to simulated space radiation (56Fe) increased the expression of the pro-osteoclastogenic gene rankl and decreased protein levels of LC3B-II, a key player in autophagy. In this current study, we aimed to further elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis we performed global postnatal deletion of Atg12 using tamoxifeninducible Cre recombinase under the control of the CAG promoter. Six-week-old CAGCreERT2/ FloxAtg12 animals were treated daily with Tamoxifen or Vehicle (Control, oil only) for five days and euthanasia performed two weeks after the onset of treatment. Percent change in body weights (prior to treatment and at euthanasia) was not significantly different between treatment groups within the same gender. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. Quantitative PCR revealed increased expression of proosteoclastogenic cytokines mcp1 and rankl in bone and marrow respectively in male iKOs compared to male controls. Expression levels of these genes were not significantly altered in the Atg12 iKO females compared to females controls. Microcomputed tomography of tibiae revealed decreased cortical bone volume, cortical

2-Bromopalmitate modulates neuronal differentiation through the regulation of histone acetylation

Directory of Open Access Journals (Sweden)

Xueran Chen

2014-03-01

Full Text Available In order to evaluate the functional significance of palmitoylation during multi-potent neural stem/progenitor cell proliferation and differentiation, retinoic acid-induced P19 cells were used in this study as a model system. Cell behaviour was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BP. Here, we observed a significant reduction in neuronal differentiation in the 2BP-treated cell model. We further explored the underlying mechanisms and found that 2BP resulted in the decreased acetylation of histones H3 and H4 and interfered with cell cycle withdrawal and neural stem/progenitor cells' renewal. Our results established a direct link between palmitoylation and the regulation of neural cell fate specification and revealed the epigenetic regulatory mechanisms that are involved in the effects of palmitoylation during neural development.

Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.

Directory of Open Access Journals (Sweden)

Alejandro Cerrada

Full Text Available Lung alveolar type II (ATII cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs have been differentiated into Alveolar Type II- Like Cells (ATII-LCs, which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.

Development of pyridine-containing macrocyclic copper(II) complexes: potential role in the redox modulation of oxaliplatin toxicity in human breast cells.

Science.gov (United States)

Fernandes, Ana S; Costa, Judite; Gaspar, Jorge; Rueff, José; Cabral, M Fátima; Cipriano, Madalena; Castro, Matilde; Oliveira, Nuno G

2012-09-01

The unique redox and catalytic chemistry of Cu has justified the development of novel Cu complexes for different therapeutic uses including cancer therapy. In this work, four pyridine-containing aza-macrocyclic copper(II) complexes were prepared (CuL1-CuL4) varying in ring size and/or substituents and their superoxide scavenging activity evaluated. CuL3, the most active superoxide scavenger, was further studied as a modulator of the cytotoxicity of oxaliplatin in epithelial breast MCF10A cells and in MCF7 breast cancer cells. Our results show that CuL3 enhances the therapeutic window of oxaliplatin, by both protecting non-tumour cells and increasing its cytotoxic effect in breast carcinoma cells. CuL3 is thus a promising complex to be further studied and to be used as a lead compound for the optimization of novel chemotherapy sensitizers.

Control of photon correlations in type II parametric down-conversion

International Nuclear Information System (INIS)

Andrews, R; Joseph, A T; Pike, E R; Sarkar, Sarben

2005-01-01

In this paper we describe theoretically quantum control of temporal correlations of entangled photons produced by collinear type II spontaneous parametric down-conversion. We examine the effect of spectral phase modulation of the signal or idler photons arriving at a 50/50 beam splitter on the temporal shape of the entangled-photon wavepacket. The coincidence count rate is calculated analytically for photon pairs in terms of the modulation depth applied to either the signal or idler beam with a spectral phase filter. It is found that the two-photon coincidence rate can be controlled by varying the modulation depth of the spectral filter

Cell-Intrinsic Roles for Autophagy in Modulating CD4 T Cell Functions

Directory of Open Access Journals (Sweden)

Elise Jacquin

2018-05-01

Full Text Available The catabolic process of autophagy plays important functions in inflammatory and immune responses by modulating innate immunity and adaptive immunity. Over the last decade, a cell-intrinsic role for autophagy in modulating CD4 T cell functions and differentiation was revealed. After the initial observation of autophagosomes in effector CD4 T cells, further work has shown that not only autophagy levels are modulated in CD4 T cells in response to environmental signals but also that autophagy critically affects the biology of these cells. Mouse models of autophagy deletion in CD4 T cells have indeed shown that autophagy is essential for CD4 T cell survival and homeostasis in peripheral lymphoid organs. Furthermore, autophagy is required for CD4 T cell proliferation and cytokine production in response to T cell receptor activation. Recent developments have uncovered that autophagy controls CD4 T cell differentiation and functions. While autophagy is required for the maintenance of immunosuppressive functions of regulatory T cells, it restrains the differentiation of TH9 effector cells, thus limiting their antitumor and pro-inflammatory properties. We will here discuss these findings that collectively suggest that therapeutic strategies targeting autophagy could be exploited for the treatment of cancer and inflammatory diseases.

Probing HeII Reionization at z>3.5 with Resolved HeII Lyman Alpha Forest Spectra

Science.gov (United States)

Worseck, Gabor

2017-08-01

The advent of GALEX and COS have revolutionized our view of HeII reionization, the final major phase transition of the intergalactic medium. COS spectra of the HeII Lyman alpha forest have confirmed with high confidence the high HeII transmission that signifies the completion of HeII reionization at z 2.7. However, the handful of z>3.5 quasars observed to date show a set of HeII transmission 'spikes' and larger regions with non-zero transmission that suggest HeII reionization was well underway by z=4. This is in striking conflict with predictions from state-of-the-art radiative transfer simulations of a HeII reionization driven by bright quasars. Explaining these measurements may require either faint quasars or more exotic sources of hard photons at z>4, with concomitant implications for HI reionization. However, many of the observed spikes are unresolved in G140L spectra and are significantly impacted by Poisson noise. Current data cannot reliably probe the ionization state of helium at z>3.5.We request 41 orbits to obtain science-grade G130M spectra of the two UV-brightest HeII-transmitting QSOs at z>3.5 to confirm and resolve their HeII transmission spikes as an unequivocal test of early HeII reionization. These spectra are complemented by recently obtained data from 8m telescopes: (1) Echelle spectra of the coeval HI Lya forest to map the underlying density field that modulates the HeII absorption, and (2) Our dedicated survey for foreground QSOs that may source the HeII transmission. Our recent HST programs revealed the only two viable targets to resolve the z>3.5 HeII Lyman alpha forest, and to conclusively solve this riddle.

Modeling of Pulses Having Arbitrary Amplitude and Frequency Modulation.

Science.gov (United States)

1980-03-01

function, fi(t), has been discussed in great detail in Section II. The linearized amplitude modulation, 1(t), is given by: (IV-6) vo A +h( -) TO’ # where "A...10. LCDR Francis Martin Lunney, USN 6143 Gatsby Green Columbia, Maryland 21045 149

Differential harmony search algorithm to optimize PWRs loading pattern

Energy Technology Data Exchange (ETDEWEB)

Poursalehi, N., E-mail: npsalehi@yahoo.com [Engineering Department, Shahid Beheshti University, G.C, P.O.Box: 1983963113, Tehran (Iran, Islamic Republic of); Zolfaghari, A.; Minuchehr, A. [Engineering Department, Shahid Beheshti University, G.C, P.O.Box: 1983963113, Tehran (Iran, Islamic Republic of)

2013-04-15

Highlights: ► Exploit of DHS algorithm in LP optimization reveals its flexibility, robustness and reliability. ► Upshot of our experiments with DHS shows that the search approach to optimal LP is quickly. ► On the average, the final band width of DHS fitness values is narrow relative to HS and GHS. -- Abstract: The objective of this work is to develop a core loading optimization technique using differential harmony search algorithm in the context of obtaining an optimal configuration of fuel assemblies in pressurized water reactors. To implement and evaluate the proposed technique, differential harmony search nodal expansion package for 2-D geometry, DHSNEP-2D, is developed. The package includes two modules; in the first modules differential harmony search (DHS) is implemented and nodal expansion code which solves two dimensional-multi group neutron diffusion equations using fourth degree flux expansion with one node per a fuel assembly is in the second module. For evaluation of DHS algorithm, classical harmony search (HS) and global-best harmony search (GHS) algorithms are also included in DHSNEP-2D in order to compare the outcome of techniques together. For this purpose, two PWR test cases have been investigated to demonstrate the DHS algorithm capability in obtaining near optimal loading pattern. Results show that the convergence rate of DHS and execution times are quite promising and also is reliable for the fuel management operation. Moreover, numerical results show the good performance of DHS relative to other competitive algorithms such as genetic algorithm (GA), classical harmony search (HS) and global-best harmony search (GHS) algorithms.

Differential harmony search algorithm to optimize PWRs loading pattern

International Nuclear Information System (INIS)

Poursalehi, N.; Zolfaghari, A.; Minuchehr, A.

2013-01-01

Highlights: ► Exploit of DHS algorithm in LP optimization reveals its flexibility, robustness and reliability. ► Upshot of our experiments with DHS shows that the search approach to optimal LP is quickly. ► On the average, the final band width of DHS fitness values is narrow relative to HS and GHS. -- Abstract: The objective of this work is to develop a core loading optimization technique using differential harmony search algorithm in the context of obtaining an optimal configuration of fuel assemblies in pressurized water reactors. To implement and evaluate the proposed technique, differential harmony search nodal expansion package for 2-D geometry, DHSNEP-2D, is developed. The package includes two modules; in the first modules differential harmony search (DHS) is implemented and nodal expansion code which solves two dimensional-multi group neutron diffusion equations using fourth degree flux expansion with one node per a fuel assembly is in the second module. For evaluation of DHS algorithm, classical harmony search (HS) and global-best harmony search (GHS) algorithms are also included in DHSNEP-2D in order to compare the outcome of techniques together. For this purpose, two PWR test cases have been investigated to demonstrate the DHS algorithm capability in obtaining near optimal loading pattern. Results show that the convergence rate of DHS and execution times are quite promising and also is reliable for the fuel management operation. Moreover, numerical results show the good performance of DHS relative to other competitive algorithms such as genetic algorithm (GA), classical harmony search (HS) and global-best harmony search (GHS) algorithms

Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

Science.gov (United States)

Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

2017-01-01

The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

The Ubiquitin-Conjugating Enzyme E2-EPF Is Overexpressed in Primary Breast Cancer and Modulates Sensitivity to Topoisomerase II Inhibition

Directory of Open Access Journals (Sweden)

Donato Tedesco

2007-07-01

Full Text Available We identified the ubiquitin-conjugating enzyme E2EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER negativity in breast cancer specimens and that its expression is cell cycleregulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER- MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G2/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G2 checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo II inhibitors etoposide and doxorubicin and also increased topo IIα protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.

The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition.

Science.gov (United States)

Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

2007-07-01

We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER(-) MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G(2)/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G(2) checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIalpha protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.

Performance of the Soudan II honeycomb drift chambers

International Nuclear Information System (INIS)

Ambats, I.; Ayres, D.; Barrett, W.

1987-01-01

The Soudan II nucleon decay project is in the process of building 260 identical 5-ton fine grained calorimeter modules for the study of nucleon decay and cosmic ray physics in the Soudan Iron Mine in Minnesota. Several of these modules have been studied on a cosmic ray test stand on the surface at Argonne National Lab. Several have been installed on location in the mine, 700 m under the surface (2200 mwe overburden). In addition, many studies of trigger efficiency, pattern recognition and background rejection have been done using Monte Carlo techniques

DUMAND-II (Deep Underwater Muon and Neutrino Detector) PROGRESS Report