Synthesis of 1,4-anhydro-D-fructose and 1,4-anhydro-D-tagatose

DEFF Research Database (Denmark)

Dekany, Gyula; Lundt, Inge; Steiner, Andreas J.

2006-01-01

1,4-Anhydro-D-fructose and 1,4-anhydro-D-tagatose were prepared from 1,2-O-isopropylidene-D-glucofuranose via the common intermediate 3,5,6-tri-O-benzyl-D-glucitol. The title compounds may be interesting anti-oxidants and feature activities akin to their natural pyranoid counterpart, 1,5-anhydro-D-fructose....

Prompt-gamma neutron activation analysis system design: Effects of D-T versus D-D neutron generator source selection

Science.gov (United States)

Prompt-gamma neutron activation (PGNA) analysis is used for the non-invasive measurement of human body composition. Advancements in portable, compact neutron generator design have made those devices attractive as neutron sources. Two distinct generators are available: D-D with 2.5 MeV and D-T with...

CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human.

Science.gov (United States)

Wu, Yu-Jing; Chen, Heng-Shi; Chen, Wen-Sheng; Dong, Jin; Dong, Xiao-Jie; Dai, Xing; Huang, Qiong; Wei, Wei

2018-01-01

Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6'- O -benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4 + T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4 + T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4 + T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr 394 ). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4 + T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr 394 ) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4 + T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation.

Science.gov (United States)

Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C

2009-07-01

The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.

Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

Directory of Open Access Journals (Sweden)

Richard Andersson

Full Text Available BACKGROUND: Gamma oscillations are electric activity patterns of the mammalian brain hypothesized to serve attention, sensory perception, working memory and memory encoding. They are disrupted or altered in schizophrenic patients with associated cognitive deficits, which persist in spite of treatment with antipsychotics. Because cognitive symptoms are a core feature of schizophrenia it is relevant to explore signaling pathways that potentially regulate gamma oscillations. Dopamine has been reported to decrease gamma oscillation power via D1-like receptors. Based on the expression pattern of D4 receptors (D4R in hippocampus, and pharmacological effects of D4R ligands in animals, we hypothesize that they are in a position to regulate gamma oscillations as well. METHODOLOGY/PRINCIPAL FINDINGS: To address this hypothesis we use rat hippocampal slices and kainate-induced gamma oscillations. Local field potential recordings as well as intracellular recordings of pyramidal cells, fast-spiking and non-fast-spiking interneurons were carried out. We show that D4R activation with the selective ligand PD168077 increases gamma oscillation power, which can be blocked by the D4R-specific antagonist L745,870 as well as by the antipsychotic drug Clozapine. Pyramidal cells did not exhibit changes in excitatory or inhibitory synaptic current amplitudes, but inhibitory currents became more coherent with the oscillations after application of PD168077. Fast-spiking, but not non-fast spiking, interneurons, increase their action potential phase-coupling and coherence with regard to ongoing gamma oscillations in response to D4R activation. Among several possible mechanisms we found that the NMDA receptor antagonist AP5 also blocks the D4R mediated increase in gamma oscillation power. CONCLUSIONS/SIGNIFICANCE: We conclude that D4R activation affects fast-spiking interneuron synchronization and thereby increases gamma power by an NMDA receptor-dependent mechanism. This

Non-Higgsable clusters for 4D F-theory models

International Nuclear Information System (INIS)

Morrison, David R.; Taylor, Washington

2015-01-01

We analyze non-Higgsable clusters of gauge groups and matter that can arise at the level of geometry in 4D F-theory models. Non-Higgsable clusters seem to be generic features of F-theory compactifications, and give rise naturally to structures that include the nonabelian part of the standard model gauge group and certain specific types of potential dark matter candidates. In particular, there are nine distinct single nonabelian gauge group factors, and only five distinct products of two nonabelian gauge group factors with matter, including SU(3)×SU(2), that can be realized through 4D non-Higgsable clusters. There are also more complicated configurations involving more than two gauge factors; in particular, the collection of gauge group factors with jointly charged matter can exhibit branchings, loops, and long linear chains.

Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Directory of Open Access Journals (Sweden)

Lin Sen

2012-03-01

Full Text Available Abstract Background Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH-induced neurological deficits; however, the signaling pathways are not apparent by which the upstream cellular events trigger innate immune and inflammatory responses that contribute to neurological impairments. Toll-like receptor 4 (TLR4 plays a role in inflammatory damage caused by brain disorders. Methods In this study, we investigate the role of TLR4 signaling in ICH-induced inflammation. In the ICH model, a significant upregulation of TLR4 expression in reactive microglia has been demonstrated using real-time RT-PCR. Activation of microglia was detected by immunohistochemistry, cytokines were measured by ELISA, MyD88, TRIF and NF-κB were measured by Western blot and EMSA, animal behavior was evaluated by animal behavioristics. Results Compared to WT mice, TLR4−/− mice had restrained ICH-induced brain damage showing in reduced cerebral edema and lower neurological deficit scores. Quantification of cytokines including IL-6, TNF-α and IL-1β and assessment of macrophage infiltration in perihematoma tissues from TLR4−/−, MyD88−/− and TRIF−/− mice showed attenuated inflammatory damage after ICH. TLR4−/− mice also exhibited reduced MyD88 and TRIF expression which was accompanied by decreased NF-κB activity. This suggests that after ICH both MyD88 and TRIF pathways might be involved in TLR4-mediated inflammatory injury possibly via NF-κB activation. Exogenous hemin administration significantly increased TLR4 expression and microglial activation in cultures and also exacerbated brain injury in WT mice but not in TLR4−/− mice. Anti-TLR4 antibody administration suppressed hemin-induced microglial activation in cultures and in the mice model of ICH. Conclusions Our findings suggest that heme potentiates microglial activation via TLR4, in turn inducing NF-κB activation via the MyD88/TRIF signaling pathway, and ultimately

Removal of 2,4-Dichlorophenolyxacetic acid (2,4-D) herbicide in the aqueous phase using modified granular activated carbon

OpenAIRE

Dehghani, Mansooreh; Nasseri, Simin; Karamimanesh, Mojtaba

2014-01-01

Background Low cost 2,4-Dichlorophenolyxacetic acid (2,4-D) widely used in controlling broad-leafed weeds is frequently detected in water resources. The main objectives of this research were focused on evaluating the feasibility of using granular activated carbon modified with acid to remove 2,4-D from aqueous phase, determining its removal efficiency and assessing the adsorption kinetics. Results The present study was conducted at bench-scale method. The influence of different pH (3–9), the ...

Distinct patterns of brain activity characterise lexical activation and competition in spoken word production.

Directory of Open Access Journals (Sweden)

Vitória Piai

Full Text Available According to a prominent theory of language production, concepts activate multiple associated words in memory, which enter into competition for selection. However, only a few electrophysiological studies have identified brain responses reflecting competition. Here, we report a magnetoencephalography study in which the activation of competing words was manipulated by presenting pictures (e.g., dog with distractor words. The distractor and picture name were semantically related (cat, unrelated (pin, or identical (dog. Related distractors are stronger competitors to the picture name because they receive additional activation from the picture relative to other distractors. Picture naming times were longer with related than unrelated and identical distractors. Phase-locked and non-phase-locked activity were distinct but temporally related. Phase-locked activity in left temporal cortex, peaking at 400 ms, was larger on unrelated than related and identical trials, suggesting differential activation of alternative words by the picture-word stimuli. Non-phase-locked activity between roughly 350-650 ms (4-10 Hz in left superior frontal gyrus was larger on related than unrelated and identical trials, suggesting differential resolution of the competition among the alternatives, as reflected in the naming times. These findings characterise distinct patterns of activity associated with lexical activation and competition, supporting the theory that words are selected by competition.

NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

Science.gov (United States)

Darias, V; Abdallah, S S; Tello, M L; Delgado, L D; Vega, S

1994-12-01

A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti-inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity.

MyoD undergoes a distinct G2/M-specific regulation in muscle cells

International Nuclear Information System (INIS)

Batonnet-Pichon, Sabrina; Tintignac, Lionel J.; Castro, Anna; Sirri, Valentina; Leibovitch, Marie Pierre; Lorca, Thierry; Leibovitch, Serge A.

2006-01-01

The transcription factors MyoD and Myf5 present distinct patterns of expression during cell cycle progression and development. In contrast to the mitosis-specific disappearance of Myf5, which requires a D-box-like motif overlapping the basic domain, here we describe a stable and inactive mitotic form of MyoD phosphorylated on its serine 5 and serine 200 residues by cyclin B-cdc2. In mitosis, these modifications are required for releasing MyoD from condensed chromosomes and inhibiting its DNA-binding and transcriptional activation ability. Then, nuclear MyoD regains instability in the beginning of G1 phase due to rapid dephosphorylation events. Moreover, a non-phosphorylable MyoD S5A/S200A is not excluded from condensed chromatin and alters mitotic progression with apparent abnormalities. Thus, the drop of MyoD below a threshold level and its displacement from the mitotic chromatin could present another window in the cell cycle for resetting the myogenic transcriptional program and to maintain the myogenic determination of the proliferating cells

MyoD undergoes a distinct G2/M-specific regulation in muscle cells.

Science.gov (United States)

Batonnet-Pichon, Sabrina; Tintignac, Lionel J; Castro, Anna; Sirri, Valentina; Leibovitch, Marie Pierre; Lorca, Thierry; Leibovitch, Serge A

2006-12-10

The transcription factors MyoD and Myf5 present distinct patterns of expression during cell cycle progression and development. In contrast to the mitosis-specific disappearance of Myf5, which requires a D-box-like motif overlapping the basic domain, here we describe a stable and inactive mitotic form of MyoD phosphorylated on its serine 5 and serine 200 residues by cyclin B-cdc2. In mitosis, these modifications are required for releasing MyoD from condensed chromosomes and inhibiting its DNA-binding and transcriptional activation ability. Then, nuclear MyoD regains instability in the beginning of G1 phase due to rapid dephosphorylation events. Moreover, a non-phosphorylable MyoD S5A/S200A is not excluded from condensed chromatin and alters mitotic progression with apparent abnormalities. Thus, the drop of MyoD below a threshold level and its displacement from the mitotic chromatin could present another window in the cell cycle for resetting the myogenic transcriptional program and to maintain the myogenic determination of the proliferating cells.

Catecholic amides as potential selective phosphodiesterase 4D inhibitors: Design, synthesis, pharmacological evaluation and structure-activity relationships.

Science.gov (United States)

Zhou, Zhong-Zhen; Ge, Bing-Chen; Chen, Yu-Fang; Shi, Xiu-Dong; Yang, Xue-Mei; Xu, Jiang-Ping

2015-11-15

In this study, a series of catechol-based amides (8a-n) with different amide linkers linking the catecholic moiety to the terminal phenyl ring was designed and synthesized as potent phosphodiesterase (PDE) 4D inhibitors. The inhibitory activities of these compounds were evaluated against the core catalytic domains of human PDE4 (PDE4CAT), full-length PDE4B1 and PDE4D7 enzymes, and other PDE family members. The results indicated the majority of compounds 8a-n displayed moderate to good inhibitory activities against PDE4CAT. Among these compounds, compound 8 j with a short amide linker (-CONHCH2-) displayed comparable PDE4CAT inhibitory activity (IC50=410 nM) with rolipram. More interestingly, compound 8 g, a potent and selective PDE4D inhibitor (IC50=94 nM), exhibited a 10-fold selectivity over the PDE4B subtypes and an over 1000-fold selectivity against other PDE family members. Docking simulations suggested that 8 g forms three extra H-bonds with the N-H of residue Asn487 and two water molecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

2,4-D and IAA Amino Acid Conjugates Show Distinct Metabolism in Arabidopsis

Czech Academy of Sciences Publication Activity Database

Eyer, L.; Vain, T.; Pařízková, Barbora; Oklešťková, Jana; Barbez, E.; Kozubíková, H.; Pospíšil, T.; Wierzbicka, R.; Kleine-Vehn, J.; Fránek, M.; Strnad, Miroslav; Robert, S.; Novák, Ondřej

2016-01-01

Roč. 11, č. 7 (2016), e0159269 E-ISSN 1932-6203 R&D Projects: GA ČR GA14-34792S; GA MŠk(CZ) LO1204; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : PERFORMANCE LIQUID - CHROMATOGRAPHY * TANDEM MASS-SPECTROMETRY * 2,4-DICHLOROPHENOXYACETIC ACID Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.806, year: 2016

Salinity reduces 2,4-D efficacy in Echinochloa crusgalli by affecting redox balance, nutrient acquisition, and hormonal regulation.

Science.gov (United States)

Islam, Faisal; Xie, Yuan; Farooq, Muhammad A; Wang, Jian; Yang, Chong; Gill, Rafaqat A; Zhu, Jinwen; Zhou, Weijun

2018-05-01

Distinct salinity levels have been reported to enhance plants tolerance to different types of stresses. The aim of this research is to assess the interaction of saline stress and the use of 2,4-D as a means of controlling the growth of Echinochloa crusgalli. The resultant effect of such interaction is vital for a sustainable approach of weed management and food production. The results showed that 2,4-D alone treatment reduces the chlorophyll contents, photosynthetic capacity, enhanced MDA, electrolyte leakage, and ROS production (H 2 O 2 , O 2 ·- ) and inhibited the activities of ROS scavenging enzymes. Further analysis of the ultrastructure of chloroplasts indicated that 2,4-D induced severe damage to the ultrastructure of chloroplasts and thylakoids. Severe saline stress (8 dS m -1 ) followed by mild saline stress treatments (4 dS m -1 ) also reduced the E. crusgalli growth, but had the least impact as compared to the 2,4-D alone treatment. Surprisingly, under combined treatments (salinity + 2,4-D), the phytotoxic effect of 2,4-D was reduced on saline-stressed E. crusgalli plants, especially under mild saline + 2,4-D treatment. This stimulated growth of E. crusgalli is related to the higher activities of enzymatic and non-enzymatic antioxidants and dynamic regulation of IAA, ABA under mild saline + 2,4-D treatment. This shows that 2,4-D efficacy was affected by salinity in a stress intensity-dependent manner, which may result in the need for greater herbicide application rates, additional application times, or more weed control operations required for controlling salt-affected weed.

(3,5-Dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone

Directory of Open Access Journals (Sweden)

Rania B. Bakr

2016-11-01

Full Text Available In an attempt to enhance cytotoxic activity of pyrazolo[3,4-d]pyrimidine core, we synthesized (3,5-dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone (4 by reacting 4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminobenzohydrazide (3 with acetylacetone. Antiproliferative activity of this compound was screened against breast (MCF-7, colon (HCT-116, and liver (HEPG-2 cancer cell lines. The tested compound exhibited cytotoxic activity with IC50 = 5.00–32.52 μM. Moreover, inhibitory activity of this compound was evaluated against the epidermal growth factor receptor (EGFR, the fibroblast growth factor receptor (FGFR, the insulin receptor (IR, and the vascular endothelial growth factor receptor (VEGFR. This target compound showed potent inhibitory activity, especially against FGFR with IC50 = 5.18 μM.

(D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity

Energy Technology Data Exchange (ETDEWEB)

Knapp, R.J.; Sharma, S.D.; Toth, G.; Duong, M.T.; Fang, L.; Bogert, C.L.; Weber, S.J.; Hunt, M.; Davis, T.P.; Wamsley, J.K. (Department of Pharmacology, University of Arizona, College of Medicine, Tucson (United States))

1991-09-01

(D-Pen2,4{prime}-125I-Phe4,D-Pen5)enkephalin ((125I)DPDPE) is a highly selective radioligand for the delta opioid receptor with a specific activity (2200 Ci/mmol) that is over 50-fold greater than that of tritium-labeled DPDPE analogs. (125I)DPDPE binds to a single site in rat brain membranes with an equilibrium dissociation constant (Kd) value of 421 {plus minus} 67 pM and a receptor density (Bmax) value of 36.4 {plus minus} 2.7 fmol/mg protein. The high affinity of this site for delta opioid receptor ligands and its low affinity for mu or kappa receptor-selective ligands are consistent with its being a delta opioid receptor. The distribution of these sites in rat brain, observed by receptor autoradiography, is also consistent with that of delta opioid receptors. Association and dissociation binding kinetics of 1.0 nM (125I) DPDPE are monophasic at 25 degrees C. The association rate (k + 1 = 5.80 {plus minus} 0.88 {times} 10(7) M-1 min-1) is about 20- and 7-fold greater than that measured for 1.0 nM (3H) DPDPE and 0.8 nM (3H) (D-Pen2,4{prime}-Cl-Phe4, D-Pen5)enkephalin, respectively. The dissociation rate of (125I)DPDPE (0.917 {plus minus} 0.117 {times} 10(-2) min-1) measured at 1.0 nM is about 3-fold faster than is observed for either of the other DPDPE analogs. The rapid binding kinetics of (125I)DPDPE is advantageous because binding equilibrium is achieved with much shorter incubation times than are required for other cyclic enkephalin analogs. This, in addition to its much higher specific activity, makes (125I)DPDPE a valuable new radioligand for studies of delta opioid receptors.

GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

International Nuclear Information System (INIS)

Zhu Zhiming; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin

2005-01-01

We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, β-myosin heavy chain, and α-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway

Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images

International Nuclear Information System (INIS)

Park, Sang-June; Ionascu, Dan; Killoran, Joseph; Chin, Lee; Berbeco, Ross; Mamede, Marcelo; Gerbaudo, Victor H

2008-01-01

Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with 18 F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D

BAFF induces spleen CD4+ T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

International Nuclear Information System (INIS)

Ji, Fang; Chen, Rongjing; Liu, Baojun; Zhang, Xiaoping; Han, Junli; Wang, Haining; Shen, Gang; Tao, Jiang

2012-01-01

Highlights: ► Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4 + T cells. ► Carrying out siRNA technology to study FOXO3A protein function. ► Helpful to understand the T cell especially CD4 + T cell‘s role in immunological reaction. -- Abstract: The TNF ligand family member “B cell-activating factor belonging to the TNF family” (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4 + spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4 + T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4 + spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4 + T cell proliferation.

Synthesis of MoS_2/g-C_3N_4 nanosheets as 2D heterojunction photocatalysts with enhanced visible light activity

International Nuclear Information System (INIS)

Li, Juan; Liu, Enzhou; Ma, Yongning; Hu, Xiaoyun; Wan, Jun; Sun, Lin; Fan, Jun

2016-01-01

Graphical abstract: TEM image and schematic diagram of photocatalytic mechanism of 2D MoS_2/g-C_3N_4 composites. - Highlights: • g-C_3N_4 nanosheets coupled with MoS_2 nanosheets as 2D heterojunction photocatalysts were synthesized successfully. • The 2D MoS_2/g-C_3N_4 heterojunctions show higher photocatalytic activity than pure g-C_3N_4. • The photocatalytic mechanism of the 2D MoS_2/g-C_3N_4 heterojunction was described. - Abstract: g-C_3N_4 nanosheets coupled with MoS_2 nanosheets as 2D heteroconjuction were prepared via a facile impregnation and calcination method. The structure characterization clearly indicated that MoS_2 nanosheets were successfully horizontal loaded on g-C_3N_4 nanosheets. The investigation indicated that the formation of 2D heterojunction between the g-C_3N_4 nanosheets and MoS_2 nanosheets promoted the charge transfer and enhanced separation efficiency of photoinduced electron–hole pairs. Furthermore, the measurement of photocatalytic activity for the degradation of rhodamine B and methyl orange revealed that the as-prepared 2D MoS_2/g-C_3N_4 heterojunction exhibited the significantly enhanced photocatalytic activity and considerable stability under visible light irradiation. The 2D MoS_2/g-C_3N_4 heterojunction prepared with 3 wt% of MoS_2 exhibited the optimal photodegradable efficiency. The present work shows that the formation of 2D heterojunction should be a good strategy to design efficient photocatalysts.

Interleukin 4 signals through two related pathways.

Science.gov (United States)

Pernis, A; Witthuhn, B; Keegan, A D; Nelms, K; Garfein, E; Ihle, J N; Paul, W E; Pierce, J H; Rothman, P

1995-08-15

The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors.

Multimeric and trimeric subunit SP-D are interconvertible structures with distinct ligand interaction

DEFF Research Database (Denmark)

Sørensen, Grith Lykke; Hoegh, Silje V; Leth-Larsen, Rikke

2009-01-01

-D compared to Met11 SP-D. Multimerization has proven important for enhancement of microbial phagocytosis. In the present study defined multimeric forms of Met11Thr SP-D were isolated from human amniotic fluid. Implementation of ManNAc-affinity chromatography allowed high recovery of natural trimeric SP......-D multimers. Trimeric SP-D subunits also showed greater binding to endogenous lipoproteins: LDL, oxLDL, and HDL, than multimeric SP-D. In conclusion, purified trimeric and multimeric SP-D represent separate and only partly interconvertible molecular populations with distinct biochemical properties....

dsRNA binding properties of RDE-4 and TRBP reflect their distinct roles in RNAi.

Science.gov (United States)

Parker, Greg S; Maity, Tuhin Subhra; Bass, Brenda L

2008-12-26

Double-stranded RNA (dsRNA)-binding proteins facilitate Dicer functions in RNA interference. Caenorhabditis elegans RDE-4 facilitates cleavage of long dsRNA to small interfering RNA (siRNA), while human trans-activation response RNA-binding protein (TRBP) functions downstream to pass siRNA to the RNA-induced silencing complex. We show that these distinct in vivo roles are reflected in in vitro binding properties. RDE-4 preferentially binds long dsRNA, while TRBP binds siRNA with an affinity that is independent of dsRNA length. These properties are mechanistically based on the fact that RDE-4 binds cooperatively, via contributions from multiple domains, while TRBP binds noncooperatively. Our studies offer a paradigm for how dsRNA-binding proteins, which are not sequence specific, discern dsRNA length. Additionally, analyses of the ability of RDE-4 deletion constructs and RDE-4/TRBP chimeras to reconstitute Dicer activity suggest RDE-4 promotes activity using its dsRNA-binding motif 2 to bind dsRNA, its linker region to interact with Dicer, and its C-terminus for Dicer activation.

Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.

Directory of Open Access Journals (Sweden)

Gabriela Galicia-Vázquez

Full Text Available Gene expression during muscle cell differentiation is tightly regulated at multiple levels, including translation initiation. The PI3K/mTOR signalling pathway exerts control over protein synthesis by regulating assembly of eukaryotic initiation factor (eIF 4F, a heterotrimeric complex that stimulates recruitment of ribosomes to mRNA templates. One of the subunits of eIF4F, eIF4A, supplies essential helicase function during this phase of translation. The presence of two cellular eIF4A isoforms, eIF4AI and eIF4AII, has long thought to impart equivalent functions to eIF4F. However, recent experiments have alluded to distinct activities between them. Herein, we characterize distinct regulatory mechanisms between the eIF4A isoforms during muscle cell differentiation. We find that eIF4AI levels decrease during differentiation whereas eIF4AII levels increase during myofiber formation in a MyoD-dependent manner. This study characterizes a previously undefined mechanism for eIF4AII regulation in differentiation and highlights functional differences between eIF4AI and eIF4AII. Finally, RNAi-mediated alterations in eIF4AI and eIF4AII levels indicate that the myogenic process can tolerate short term reductions in eIF4AI or eIF4AII levels, but not both.

Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

Directory of Open Access Journals (Sweden)

Norio Takata

Full Text Available The dorsal and ventral hippocampal regions (dHP and vHP are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP and multi unit activities (MUA upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2. Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP, which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

The D Domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells

Directory of Open Access Journals (Sweden)

Zeyou Wang

2016-11-01

Full Text Available Abstract Background As a well-characterized key player in various signal transduction networks, extracellular-signal-regulated kinase (ERK1/2 has been widely implicated in the development of many malignancies. We previously found that Leucine-rich repeat containing 4 (LRRC4 was a tumor suppressor and a negative regulator of the ERK/MAPK pathway in glioma tumorigenesis. However, the precise molecular role of LRRC4 in ERK signal transmission is unclear. Methods The interaction between LRRC4 and ERK1/2 was assessed by co-immunoprecipitation and GST pull-down assays in vivo and in vitro. We also investigated the interaction of LRRC4 and ERK1/2 and the role of the D domain in ERK activation in glioma cells. Results Here, we showed that LRRC4 and ERK1/2 interact via the D domain and CD domain, respectively. Following EGF stimuli, the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and abrogates ERK1/2 activation and nuclear translocation. In glioblastoma cells, ectopic LRRC4 expression competitively inhibited the interaction of endogenous mitogen-activated protein kinase (MEK and ERK1/2. Mutation of the D domain decreased the LRRC4-mediated inhibition of MAPK signaling and its anti-proliferation and anti-invasion roles. Conclusions Our results demonstrated that the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells. These findings identify a new mechanism underlying glioblastoma progression and suggest a novel therapeutic strategy by restoring the activity of LRRC4 to decrease MAPK cascade activation.

Auxin-activated NADH oxidase activity of soybean plasma membranes is distinct from the constitutive plasma membrane NADH oxidase and exhibits prion-like properties

Science.gov (United States)

Morre, D. James; Morre, Dorothy M.; Ternes, Philipp

2003-01-01

The hormone-stimulated and growth-related cell surface hydroquinone (NADH) oxidase activity of etiolated hypocotyls of soybeans oscillates with a period of about 24 min or 60 times per 24-h day. Plasma membranes of soybean hypocotyls contain two such NADH oxidase activities that have been resolved by purification on concanavalin A columns. One in the apparent molecular weight range of 14-17 kDa is stimulated by the auxin herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The other is larger and unaffected by 2,4-D. The 2,4-D-stimulated activity absolutely requires 2,4-D for activity and exhibits a period length of about 24 min. Also exhibiting 24-min oscillations is the rate of cell enlargement induced by the addition of 2,4-D or the natural auxin indole-3-acetic acid (IAA). Immediately following 2,4-D or IAA addition, a very complex pattern of oscillations is frequently observed. However, after several hours a dominant 24-min period emerges at the expense of the constitutive activity. A recruitment process analogous to that exhibited by prions is postulated to explain this behavior.

4D Applications of GIS in Construction Management

Directory of Open Access Journals (Sweden)

A. Chaitanya Kumar

2017-01-01

Full Text Available Construction industries broadly involve different set of construction activities which are to be executed as per schedule and the major software used for scheduling is PRIMAVERA and Microsoft Project (MSP. But the software still lacks a feature of providing spatial aspects of information in construction schedule. Recently, advanced technology like 4D GIS plays a major role in overcoming the limitation of the software. 4D GIS technology includes integration of 2D drawings from AutoCAD and schedules prepared in PRIMAVERA software. In the present study, a multistair residential building has been selected. ARCMAP 10.2 is used for interlinking of schedules as well as drawings and ARCSCENE has been used for developing 4D view. This linkage between scheduled activities and respective drawings in GIS helps in identifying construction sequences and also in detecting logical errors that occur in project schedules. The developed 4D view provides better visualization of construction progress of a project.

BAFF induces spleen CD4{sup +} T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

Energy Technology Data Exchange (ETDEWEB)

Ji, Fang; Chen, Rongjing [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Liu, Baojun [Laboratory of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai (China); Zhang, Xiaoping [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Han, Junli; Wang, Haining [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Shen, Gang [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Tao, Jiang, E-mail: taojiang2012@yahoo.cn [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China)

2012-09-07

Highlights: Black-Right-Pointing-Pointer Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4{sup +} T cells. Black-Right-Pointing-Pointer Carrying out siRNA technology to study FOXO3A protein function. Black-Right-Pointing-Pointer Helpful to understand the T cell especially CD4{sup +} T cell's role in immunological reaction. -- Abstract: The TNF ligand family member 'B cell-activating factor belonging to the TNF family' (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4{sup +} spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4{sup +} T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4{sup +} spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4{sup +} T cell proliferation.

D-6-Deoxy-myo-inositol 1,3,4,5-tetrakisphosphate, a mimic of D-myo-inositol 1,3,4,5-tetrakisphosphate: biological activity and pH-dependent conformational properties

International Nuclear Information System (INIS)

Horne, Graeme; Maechling, Clarisse; Fleig, Andrea; Hirata, Masato; Penner, Reinhold; Spiess, Bernard; Potter, Barry V.L.

2004-01-01

D-6-Deoxy-myo-inositol 1,3,4,5-tetrakisphosphate [D-6-deoxy-Ins(1,3,4,5)P 4 ] 3 is a novel deoxygenated analogue of D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P 4 ] 2, a central and enigmatic molecule in the polyphosphoinositide pathway of cellular signalling. D-6-Deoxy-Ins(1,3,4,5)P 4 is a moderate inhibitor of Ins(1,4,5)P 3 5-phosphatase [1.8 μM] compared to Ins(1,3,4,5)P 4 [0.15 μM] and similar to that of L-Ins(1,3,4,5)P 4 [1.8 μM]. In displacement of [ 3 H] Ins(1,4,5)P 3 from the rat cerebellar Ins(1,4,5)P 3 receptor, while slightly weaker [IC 50 =800 nM] than that of D-Ins(1,3,4,5)P 4 [IC 50 =220 nM], 3 is less markedly different and again similar to that of L-Ins(1,3,4,5)P 4 [IC 50 =660 nM]. 3 is an activator of I CRAC when inward currents are measured in RBL-2H3-M1 cells using patch-clamp electrophysiological techniques with a facilitation curve different to that of Ins(1,3,4,5)P 4 . Physicochemical properties were studied by potentiometric 31 P and 1 H NMR titrations and were similar to those of Ins(1,3,4,5)P 4 apart from the observation of a biphasic titration curve for the P1 phosphate group. A novel vicinal phosphate charge-induced conformational change of the inositol ring above pH 10 was observed for D-6-deoxy-Ins(1,3,4,5)P 4 that would normally be hindered because of the central stabilising role played by the 6-OH group in Ins(1,3,4,5)P 4 . We conclude that the 6-OH group in Ins(1,3,4,5)P 4 is crucial for its physicochemical behaviour and biological properties of this key inositol phosphate

Complete genomic sequences for hepatitis C virus subtypes 4b, 4c, 4d, 4g, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r and 4t.

Science.gov (United States)

Li, Chunhua; Lu, Ling; Wu, Xianghong; Wang, Chuanxi; Bennett, Phil; Lu, Teng; Murphy, Donald

2009-08-01

In this study, we characterized the full-length genomic sequences of 13 distinct hepatitis C virus (HCV) genotype 4 isolates/subtypes: QC264/4b, QC381/4c, QC382/4d, QC193/4g, QC383/4k, QC274/4l, QC249/4m, QC97/4n, QC93/4o, QC139/4p, QC262/4q, QC384/4r and QC155/4t. These were amplified, using RT-PCR, from the sera of patients now residing in Canada, 11 of which were African immigrants. The resulting genomes varied between 9421 and 9475 nt in length and each contains a single ORF of 9018-9069 nt. The sequences showed nucleotide similarities of 77.3-84.3 % in comparison with subtypes 4a (GenBank accession no. Y11604) and 4f (EF589160) and 70.6-72.8 % in comparison with genotype 1 (M62321/1a, M58335/1b, D14853/1c, and 1?/AJ851228) reference sequences. These similarities were often higher than those currently defined by HCV classification criteria for subtype (75.0-80.0 %) and genotype (67.0-70.0 %) division, respectively. Further analyses of the complete and partial E1 and partial NS5B sequences confirmed these 13 'provisionally assigned subtypes'.

Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free Fatty Acid Receptor 4/G Protein-Coupled Receptor 120

DEFF Research Database (Denmark)

Prihandoko, Rudi; Alvarez-Curto, Elisa; Hudson, Brian D

2016-01-01

of these phosphoacceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to extracellular signal regulated protein kinase 1 and 2 (ERK1/2) activation. Rather, an inhibitor of Gq/11proteins completely prevented receptor signaling to ERK1/2. By contrast, the recruitment...... activation. These unique observations define differential effects on signaling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signaling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode...

CD4 T cell activation and disease activity at onset of multiple sclerosis

DEFF Research Database (Denmark)

Jensen, J; Langkilde, Annika Reynberg; Fenst, C

2004-01-01

We studied CD4 T cell activation in patients with clinically isolated syndromes (CIS) suggesting an initial attack of multiple sclerosis. The percentage of blood CD26+ CD4 T cells was increased in these patients, and correlated with magnetic resonance imaging disease activity and clinical disease...... severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

Analysis of the 4d9-(4d86p + 4p54d10) transitions of Sb VII and the strongest transitions of the 4d9-4d84f array of Sb VII and Te VIII

International Nuclear Information System (INIS)

Kildiyarova, R.R.; Churilov, S.S.; Joshi, Y.N.; Ryabtsev, A.N.

1995-01-01

The spectra of antimony and tellurium were photographed in the 100-200 A region on grazing incidence spectrographs at Moscow, Russia and NIST, U.S.A. laboratories. The 4d 9 -[4d 8 6p + 4p 5 4d 10 ] transition array of Sb VII was analyzed. 31 levels in Sb VII were established. 41 new lines in Sb VII belonging to the 4d 9 -(4p 5 4d 10 + 4d 8 6p) transition array have been classified. Seven lines each in Sb VII and Te VIII belonging to the 4d 9 -4d 8 4f transition array have been classified. Parametric least-squares-fitted calculations involving configuration interaction have been carried out to interpret the spectrum satisfactorily. (orig.)

Development of an immunoassay for determination of 2,4-dichlorophenoxyacetic acid (2,4-D) based upon the recombinant Fab fragment of 2,4-D specific antibody

Science.gov (United States)

Nguyen, Van C.; Nguyen, Thi D. T.; Dau, Hung A.; Tham, Thu N.; Quyen, Dinh T.; Bachmman, Till; Schmid, Rolf D.

2001-09-01

To develop an immunoassay and further an immunosensor for 2,4-D based upon recombinant antibody, the Fab fragments of 2,4-D specific antibody were expressed in E. coli. Western blotting analysis of the periplasmic cell fractions shown that under the non-reducing condition only a single protein band at a molecular mass of 45-kDa, corresponding to the whole Fab fragment was detected. Antigen binding activity for 2,4-D was found only in the extract of cells bearing the 2,4-D plasmid. An immunoassay based on the competitive reaction of 2,4-D and enzyme tracer with 2,4-D Fab fragments immobilized on micro titer plates via rabbit anti-mouse IgC was developed. Using this assay, 2,4-D could be detected at concentration range of 0.5 (mu) g/1 to 10(mu) g/1. The center point of the 2,4-D test was found at a concentration of 5 (mu) g/l. The assay was applied for detection of 2,4-D in spiked orange samples, resulting in recovery rate of 90 percent. The immunoassay could be applied to monitor human exposure to 2,4-D from contamination in fruit samples.

Testis-expressed profilins 3 and 4 show distinct functional characteristics and localize in the acroplaxome-manchette complex in spermatids

Directory of Open Access Journals (Sweden)

Rothkegel Martin

2009-05-01

Full Text Available Abstract Background Multiple profilin isoforms exist in mammals; at least four are expressed in the mammalian testis. The testis-specific isoforms profilin-3 (PFN3 and profilin-4 (PFN4 may have specialized roles in spermatogenic cells which are distinct from known functions fulfilled by the "somatic" profilins, profilin-1 (PFN1 and profilin-2 (PFN2. Results Ligand interactions and spatial distributions of PFN3 and PFN4 were compared by biochemical, molecular and immunological methods; PFN1 and PFN2 were employed as controls. β-actin, phosphoinositides, poly-L-proline and mDia3, but not VASP, were confirmed as in vitro interaction partners of PFN3. In parallel experiments, PFN4 bound to selected phosphoinositides but not to poly-L-proline, proline-rich proteins, or actin. Immunofluorescence microscopy of PFN3 and PFN4 revealed distinct subcellular locations in differentiating spermatids. Both were associated first with the acroplaxome and later with the transient manchette. Predicted 3D structures indicated that PFN3 has the actin-binding site conserved, but retains only approximately half of the common poly-L-proline binding site. PFN4, in comparison, has lost both, polyproline and actin binding sites completely, which is well in line with the experimental data. Conclusion The testis-specific isoform PFN3 showed major hallmarks of the well characterized "somatic" profilin isoforms, albeit with distinct binding affinities. PFN4, on the other hand, did not interact with actin or polyproline in vitro. Rather, it seemed to be specialized for phospholipid binding, possibly providing cellular functions which are distinct from actin dynamics regulation.

Evaluation and structure-activity relationship analysis of a new series of 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines as potential antibacterial agents

Science.gov (United States)

Beyzaei, Hamid; Aryan, Reza; Moghaddam-Manesh, Mohammadreza; Ghasemi, Behzad; Karimi, Pouya; Samareh Delarami, Hojat; Sanchooli, Mahmood

2017-09-01

The synthesis of pyrazolo[3,4-d]pyrimidine derivatives is important due to their presence in various biologically active compounds such as anticancer, antimicrobial, antiparasitic, anti-inflammatory and antidiabetic agents. In this project, a new and efficient approach for the synthesis of some novel 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines from reaction of 5-amino-pyrazole-4-carbonitrile with various hydrazides in ethanolic sodium ethoxide medium was reported. Antimicrobial activities of all synthesized derivatives were evaluated against eight Gram-positive and five Gram-negative pathogenic bacteria. The moderate to good inhibitory effects were observed based on inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. In order to determine the reasonable relationship between antibacterial activities and physiochemical properties of the derivatives, computational studies were carried out in terms of geometry optimization, short-range van der Waals forces, dipole moments, atomic charges and frontier orbital energies. It was found that both short-range forces and covalent bonds are important in the observed inhibitory effects of the molecules. The results suggested that pyrazolo[3,4-d]pyrimidine derivatives prefer a soft nucleophilic attack on bio-macromolecular targets. Furthermore, our models proposed that the antibacterial activities of these derivatives can be improved by substituting large electron donating groups on the 6-phenyl rings.

The TLR4 D299G and T399I SNPs are constitutively active to up-regulate expression of Trif-dependent genes.

Directory of Open Access Journals (Sweden)

Georgina L Hold

Full Text Available Dysregulated Toll-Like Receptor (TLR signalling and genetic polymorphisms in these proteins are linked to many human diseases. We investigated TLR4 functional variants D299G and T399I to assess the impact on LPS-induced responsiveness in comparison to wild-type TLR4. The mechanism by which this occurs in unclear as these SNPs do not lie within the lipid A binding domain or dimerisation sites of the LPS-TLR4/MD2 receptor complexes. Transfection of TLR4D299G, TLR4T399I or TLR4D299G. T399I into HEK cells resulted in constitutive activation of an NF-κB reporter gene and a blunting of the LPS-induced reporter activation compared to WT-TLR4. Unstimulated human monocyte/macrophages, from patients with the D299G and T399I SNPs demonstrated a downregulation of many genes, particularly Tram/Trif signalling pathway constitutents compared to the TLR4 wild-type subjects supporting the concept of basal receptor activity. Monocyte/macrophages from carriers of the TLR4 D299G and T399I polymorphisms stimulated with LPS showed >6 fold lower levels of NF-κB and ∼12 fold higher IFN-β gene expression levels compared to wild-type subjects (P<0.05; MWU test and dramatically altered resultant cytokine profiles. We conclude that these TLR4 SNPs affect constitutive receptor activity which impacts on the hosts ability to respond to LPS challenge leading to a dysregulated sub-optimal immune response to infection.

Using 2D: 4D digit ratios to determine motor skills in children.

Science.gov (United States)

Wang, Y; Wang, H-L; Li, Y-H; Zhu, F-L; Li, S-J; Ni, H

2016-03-01

In past few decades, there has an outburst of research surrounding second to fourth finger digit ratio (2D:4D) and its relation to prenatal sex steroids including both testosterone and estrogen. In utero, testosterone and estrogen are responsible for the differences in digit ratio between the genders. Recent research has tried to extend past the influence of steroids and look at the potential effect of digit ratios on fine and gross motor skills in children. We compiled the current understanding of the connection between sex hormones and the development of the 2D:4D ratio as well as the effect the ratio has on motor skills. There seems to be a significant positive correlation between 2D:4D digit ratio and precision of fine motor skill. In addition, there is a negative correlation between 2D:4D ratio and speed of fine motor activity. In this review, we will outline the use of 2D:4D ratio as a biomarker for prenatal sex steroids and through that, a proxy marker for fine and gross motor skills.

Synthesis of tritium labeled Ac-[Nle4, D-Phe7]-α-MSH/sub 4-11/-NH2: a superpotent melanotropin with prolonged biological activity

International Nuclear Information System (INIS)

Wilkes, B.D.; Hruby, V.J.; Yamamura, H.I.; Akiyama, K.; Castrucci, A.M. de; Hadley, M.E.; Andrews, J.R.; Wan, Y.P.

1984-01-01

Ac-[Nle 4 , D-Phe 7 ]-α-MSH/sub 4-11/-NH 2 an octapeptide, is a melanotropin analogue (Ac-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-NH 2 ), which is a superpotent agonist of frog and lizard skin melanocytes and mouse S 91 (Cloudman) melanoma cells. This melanotropin possesses ultraprolonged activity on melanocytes, both in vitro and in vivo, and the peptide is resistant to inactivation by serum enzymes. The tritium-labeled congener was prepared by direct incorporation of [ 3 H]-labeled norleucine into the peptide. The melanotropic activity of the labeled peptide is identical to the unlabeled analogue. This labeled peptide should be useful for studies on the localization and characterization of melanotropin receptors

Special report: workshop on 4D-treatment planning in actively scanned particle therapy--recommendations, technical challenges, and future research directions.

Science.gov (United States)

Knopf, Antje; Bert, Christoph; Heath, Emily; Nill, Simeon; Kraus, Kim; Richter, Daniel; Hug, Eugen; Pedroni, Eros; Safai, Sairos; Albertini, Francesca; Zenklusen, Silvan; Boye, Dirk; Söhn, Matthias; Soukup, Martin; Sobotta, Benjamin; Lomax, Antony

2010-09-01

This article reports on a 4D-treatment planning workshop (4DTPW), held on 7-8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D-treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state-of-the-art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically.

Direct-write fabrication of 4D active shape-changing behavior based on a shape memory polymer and its nanocomposite (Conference Presentation)

Science.gov (United States)

Wei, Hongqiu; Zhang, Qiwei; Yao, Yongtao; Liu, Liwu; Liu, Yanju; Leng, Jinsong

2017-04-01

Shape memory polymers (SMPs), a typical class of smart materials, have been witnessed significant advances in the past decades. Based on the unique performance to recover the initial shape after going through a shape deformation, the applications of SMPs have aroused growing interests. However, most of the researches are hindered by traditional processing technologies which limit the design space of SMPs-based structures. Three-dimension (3D) printing as an emerging technology endows design freedom to manufacture materials with complex structures. In present article, we show that by employing direct-write printing method; one can realize the printing of SMPs to achieve 4D active shape-changing structures. We first fabricated a kind of 3D printable polylactide (PLA)-based SMPs and characterized the overall properties of such materials. Results demonstrated the prepared PLA-based SMPs presenting excellent shape memory effect. In what follows, the rheological properties of such PLA-based SMP ink during printing process were discussed in detail. Finally, we designed and printed several 3D configurations for investigation. By combining 3D printing with shape memory behavior, these printed structures achieve 4D active shape-changing performance under heat stimuli. This research presents a high flexible method to realize the fabrication of SMP-based 4D active shape-changing structures, which opens the way for further developments and improvements of high-tech fields like 4D printing, soft robotics, micro-systems and biomedical devices.

Training Extract. AFSC 4D0X1 Diet Therapy (Active Duty)

Science.gov (United States)

2002-07-01

17 22 43 19 24 25 4.28 D0115 Clean broilers 23 10 12 27 9...5.89 L0334 Perform patient carries using hand or litter method 6 2 14 4 7 22 10 5.35 L0335 Prepare...0089 6.4. Use cleaning agents +3c - - D0115 Clean broilers

Digit Ratio (2D:4D) Predicts Self-Reported Measures of General Competitiveness, but Not Behavior in Economic Experiments.

Science.gov (United States)

Bönte, Werner; Procher, Vivien D; Urbig, Diemo; Voracek, Martin

2017-01-01

The ratio of index finger length to ring finger length (2D:4D) is considered to be a putative biomarker of prenatal androgen exposure (PAE), with previous research suggesting that 2D:4D is associated with human behaviors, especially sex-typical behaviors. This study empirically examines the relationship between 2D:4D and individual competitiveness, a behavioral trait that is found to be sexually dimorphic. We employ two related, but distinct, measures of competitiveness, namely behavioral measures obtained from economic experiments and psychometric self-reported measures. Our analyses are based on two independent data sets obtained from surveys and economic experiments with 461 visitors of a shopping mall (Study I) and 617 university students (Study II). The correlation between behavior in the economic experiment and digit ratios of both hands is not statistically significant in either study. In contrast, we find a negative and statistically significant relationship between psychometric self-reported measures of competitiveness and right hand digit ratios (R2D:4D) in both studies. This relationship is especially strong for younger people. Hence, this study provides some robust empirical evidence for a negative association between R2D:4D and self-reported competitiveness. We discuss potential reasons why digit ratio may relate differently to behaviors in specific economics experiments and to self-reported general competitiveness.

Digit Ratio (2D:4D Predicts Self-Reported Measures of General Competitiveness, but Not Behavior in Economic Experiments

Directory of Open Access Journals (Sweden)

Werner Bönte

2017-12-01

Full Text Available The ratio of index finger length to ring finger length (2D:4D is considered to be a putative biomarker of prenatal androgen exposure (PAE, with previous research suggesting that 2D:4D is associated with human behaviors, especially sex-typical behaviors. This study empirically examines the relationship between 2D:4D and individual competitiveness, a behavioral trait that is found to be sexually dimorphic. We employ two related, but distinct, measures of competitiveness, namely behavioral measures obtained from economic experiments and psychometric self-reported measures. Our analyses are based on two independent data sets obtained from surveys and economic experiments with 461 visitors of a shopping mall (Study I and 617 university students (Study II. The correlation between behavior in the economic experiment and digit ratios of both hands is not statistically significant in either study. In contrast, we find a negative and statistically significant relationship between psychometric self-reported measures of competitiveness and right hand digit ratios (R2D:4D in both studies. This relationship is especially strong for younger people. Hence, this study provides some robust empirical evidence for a negative association between R2D:4D and self-reported competitiveness. We discuss potential reasons why digit ratio may relate differently to behaviors in specific economics experiments and to self-reported general competitiveness.

Npas4: Linking Neuronal Activity to Memory.

Science.gov (United States)

Sun, Xiaochen; Lin, Yingxi

2016-04-01

Immediate-early genes (IEGs) are rapidly activated after sensory and behavioral experience and are believed to be crucial for converting experience into long-term memory. Neuronal PAS domain protein 4 (Npas4), a recently discovered IEG, has several characteristics that make it likely to be a particularly important molecular link between neuronal activity and memory: it is among the most rapidly induced IEGs, is expressed only in neurons, and is selectively induced by neuronal activity. By orchestrating distinct activity-dependent gene programs in different neuronal populations, Npas4 affects synaptic connections in excitatory and inhibitory neurons, neural circuit plasticity, and memory formation. It may also be involved in circuit homeostasis through negative feedback and psychiatric disorders. We summarize these findings and discuss their implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Grb2 mediates semaphorin-4D-dependent RhoA inactivation.

Science.gov (United States)

Sun, Tianliang; Krishnan, Rameshkumar; Swiercz, Jakub M

2012-08-01

Signaling through the semaphorin 4D (Sema4D) receptor plexin-B1 is modulated by its interaction with tyrosine kinases ErbB-2 and Met. In cells expressing the plexin-B1-ErbB-2 receptor complex, ligand stimulation results in the activation of small GTPase RhoA and stimulation of cellular migration. By contrast, in cells expressing plexin-B1 and Met, ligand stimulation results in an association with the RhoGTPase-activating protein p190 RhoGAP and subsequent RhoA inactivation--a process that involves the tyrosine phosphorylation of plexin-B1 by Met. Inactivation of RhoA is necessary for Sema4D-mediated inhibition of cellular migration. It is, however, unknown how plexin-B1 phosphorylation regulates RhoGAP interaction and activity. Here we show that the activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation by Met creates a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Grb2 is thereby recruited into the plexin-B1 receptor complex and, through its SH3 domain, interacts with p190 RhoGAP and mediates RhoA deactivation. Phosphorylation of plexin-B1 by Met and the recruitment of Grb2 have no effect on the R-RasGAP activity of plexin-B1, but are required for Sema4D-induced, RhoA-dependent antimigratory effects of Sema4D on breast cancer cells. These data show Grb2 as a direct link between plexin and p190-RhoGAP-mediated downstream signaling.

Burden of Influenza in 4 Ecologically Distinct Regions of Peru: Household Active Surveillance of a Community Cohort, 2009-2015.

Science.gov (United States)

Tinoco, Yeny O; Azziz-Baumgartner, Eduardo; Uyeki, Timothy M; Rázuri, Hugo R; Kasper, Matthew R; Romero, Candice; Silva, Maria E; Simons, Mark P; Soto, Giselle M; Widdowson, Marc-Alain; Gilman, Robert H; Bausch, Daniel G; Montgomery, Joel M

2017-10-16

There are limited data on the burden of disease posed by influenza in low- and middle-income countries. Furthermore, most estimates of influenza disease burden worldwide rely on passive sentinel surveillance at health clinics and hospitals that lack accurate population denominators. We documented influenza incidence, seasonality, health-system utilization with influenza illness, and vaccination coverage through active community-based surveillance in 4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people in 1500 randomly selected households were visited 3 times per week. Naso- and oropharyngeal swabs were collected from persons with influenza-like illness and tested for influenza virus by real-time reverse-transcription polymerase chain reaction. We followed participants for 35353 person-years (PY). The overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI], 97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236-277]). Seasonal incidence trends were similar across sites, with 61% of annual influenza cases occurring during the austral winter (May-September). Of all participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100000 PY). Influenza vaccine coverage was 27% among children aged 6-23 months and 26% among persons aged ≥65 years. Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Structures and Biogenesis of Fallaxosides D4, D5, D6 and D7, Trisulfated Non-Holostane Triterpene Glycosides from the Sea Cucumber Cucumaria fallax

Directory of Open Access Journals (Sweden)

Alexandra S. Silchenko

2016-07-01

Full Text Available Four new trisulfated triterpene glycosides, fallaxosides D4 (1, D5 (2, D6 (3 and D7 (4 have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida. The structures of the glycosides have been elucidated by 2D NMR spectroscopy and HRESIMS. All the glycosides have the lanostane aglycones of a rare non-holostane type with 7(8-, 8(9- or 9(11-double bonds, one or two hydroxyl groups occupying unusual positions in the polycyclic nucleus and shortened or normal side chains. The pentasaccharide carbohydrate moieties of 1–4 have three sulfate groups. The cytotoxic activity of glycosides 1–4 against the ascite form of mouse Ehrlich carcinoma cells and mouse spleen lymphocytes and hemolytic activity against mouse erythrocytes have been studied.

Electrochemically active nanocomposites of Li4Ti5O12 2D nanosheets and SnO2 0D nanocrystals with improved electrode performance

International Nuclear Information System (INIS)

Han, Song Yi; Kim, In Young; Lee, Sang-Hyup; Hwang, Seong-Ju

2012-01-01

Electrochemically active nanocomposites consisting of Li 4 Ti 5 O 12 2D nanosheets and SnO 2 0D nanocrystals are synthesized by the crystal growth of tin dioxide on the surface of 2D nanostructured lithium titanate. According to powder X-ray diffraction and electron microscopic analyses, the rutile-structured SnO 2 nanocrystals are stabilized on the surface of spinel-structured Li 4 Ti 5 O 12 2D nanosheets. The homogeneous hybridization of tin dioxide with lithium titanate is confirmed by elemental mapping analysis. Ti K-edge X-ray absorption near-edge structure and Sn 3d X-ray photoelectron spectroscopy indicate the stabilization of tetravalent titanium ions in the spinel lattice of Li 4 Ti 5 O 12 and the formation of SnO 2 phase with tetravalent Sn oxidation state. The electrochemical measurements clearly demonstrate the promising functionality of the present nanocomposites as anode for lithium secondary batteries. The Li 4 Ti 5 O 12 –SnO 2 nanocomposites show larger discharge capacity and better cyclability than do the uncomposited Li 4 Ti 5 O 12 and SnO 2 phases, indicating the synergistic effect of nanocomposite formation on the electrode performance of Li 4 Ti 5 O 12 and SnO 2 . The present experimental findings underscore the validity of 2D nanostructured lithium titanate as a useful platform for the stabilization of nanocrystalline electrode materials and also for the improvement of their functionality.

Return of D4 Dopamine Receptor Antagonists in Drug Discovery.

Science.gov (United States)

Lindsley, Craig W; Hopkins, Corey R

2017-09-14

The dopamine D 4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D 4 , relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Unfortunately, D 4 antagonists that were developed for schizophrenia failed in the clinic. Thus, D 4 fell out of favor as a therapeutic target, and work in this area was silent for decades. Recently, D 4 ligands with improved selectivity for D 4 against not only D 1-3,5 but also other biogenic amine targets have emerged, and D 4 is once again in the spotlight as a novel target for both addiction and Parkinson's disease (PD), as well as other emerging diseases. This report will review the historical data for D 4 , review the known D 4 ligands, and then highlight new data supporting a role for D 4 inhibition in addiction, PD, and cancer.

Crystal and magnetic structures of CaCu3Fe4O12 and LaCu3Fe4O12: distinct charge transitions of unusual high valence Fe

International Nuclear Information System (INIS)

Shimakawa, Yuichi

2015-01-01

New 134-type perovskites, CaCu 3 Fe 4 O 12 (CCFO) and LaCu 3 Fe 4 O 12 (LCFO), were prepared by means of high-pressure synthesis. The compounds contain unusual high valence Fe 4+ in CCFO and Fe 3.75+ in LCFO at high temperatures. With decreasing temperature, the instabilities of the high valence states of Fe are relieved by distinct charge transitions, which are charge disproportionation (4Fe 4+   →  2Fe 3+   +  2Fe 5+ ) in CCFO and intermetallic charge transfer (3Cu 2+   +  4Fe 3.75+   →  3Cu 3+   +  4Fe 3+ ) in LCFO. Crystal structure analysis with synchrotron x-ray diffraction and magnetic structure analysis with neutron diffraction revealed the nature of the transitions. Although the two behaviors look completely different from each other in simple ionic models, they can both be explained by the localization of ligand holes, which are produced by the strong hybridization of low-lying Fe-d and oxygen p orbitals in the oxides. The ligand holes in the charge disproportionated CCFO are localized at the Fe–O sites alternately (4d 5 L  →  2d 5   +  2d 5 L 2 ) and the ligand holes in the charge transferred LCFO are localized at the Cu–O sites (3d 9   +  4d 5 L 0.75   →  3d 9 L  +  4d 5 ). (review)

Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.

Directory of Open Access Journals (Sweden)

Mirjam E Belderbos

Full Text Available Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP or soluble CD14 (sCD14. The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.

Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

Science.gov (United States)

Belderbos, Mirjam E.; Levy, Ofer; Stalpers, Femke; Kimpen, Jan L.; Meyaard, Linde; Bont, Louis

2012-01-01

Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. PMID:22442690

Intrinsic functional brain mapping in reconstructed 4D magnetic susceptibility (χ) data space.

Science.gov (United States)

Chen, Zikuan; Calhoun, Vince

2015-02-15

By solving an inverse problem of T2*-weighted magnetic resonance imaging for a dynamic fMRI study, we reconstruct a 4D magnetic susceptibility source (χ) data space for intrinsic functional mapping. A 4D phase dataset is calculated from a 4D complex fMRI dataset. The background field and phase wrapping effect are removed by a Laplacian technique. A 3D χ source map is reconstructed from a 3D phase image by a computed inverse MRI (CIMRI) scheme. A 4D χ data space is reconstructed by repeating the 3D χ source reconstruction for each time point. A functional map is calculated by a temporal correlation between voxel signals in the 4D χ space and the timecourse of the task paradigm. With a finger-tapping experiment, we obtain two 3D functional mappings in the 4D magnitude data space and in the reconstructed 4D χ data space. We find that the χ-based functional mapping reveals co-occurrence of bidirectional responses in a 3D activation map that is different from the conventional magnitude-based mapping. The χ-based functional mapping can also be achieved by a 3D deconvolution of a phase activation map. Based on a subject experimental comparison, we show that the 4D χ tomography method could produce a similar χ activation map as obtained by the 3D deconvolution method. By removing the dipole effect and other fMRI technological contaminations, 4D χ tomography provides a 4D χ data space that allows a more direct and truthful functional mapping of a brain activity. Published by Elsevier B.V.

Design, Synthesis, Antibacterial and Antifungal Activity of Novel 2-[(E-2-aryl-1-ethenyl]-3-(2-sulfanyl-1H-benzo[d]imidazole-5-yl-3,4- dihydro-4-quinolinones

Directory of Open Access Journals (Sweden)

Anisetti Ravinder Nath

2012-01-01

Full Text Available The novel 2-[(E-2-aryl-1-ethenyl]-3-(2-sulfanyl-1H-benzo[d]imidazole-5-yl-3,4- dihydro-4-quinolinones (4a-j analogs were synthesized by Knoevenagel condensation of a solution of 2-methyl-3-(2-sulfanyl-1H-benzo[d]imidazole-5-yl-3,4-dihydro-4-quinazolinone (3 with aromatic aldehyde in presence of catalytic amount of piperidine. Compounds (4a-j showed significant biological activity against all the standard strains. All the synthesized compounds were characterized on the basis of their IR, 1H NMR, MASS spectroscopic data and elemental analyses. All the compounds have been tested for antimicrobial and antifungal activity by the cup-plate method.

Exercise versus Nonexercise Activity: E-diaries Unravel Distinct Effects on Mood.

Science.gov (United States)

Reichert, Markus; Tost, Heike; Reinhard, Iris; Schlotz, Wolff; Zipf, Alexander; Salize, Hans-Joachim; Meyer-Lindenberg, Andreas; Ebner-Priemer, Ulrich W

2017-04-01

The association between physical activity and mood is of major importance to increase physical activity as a prevention strategy for noncommunicable diseases and to improve mental health. Unfortunately, existing studies examining how physical activity and mood wax and wane within persons over time in everyday life do show ambiguous findings. Taking a closer look at these studies reveals that the aggregation levels differ tremendously. Whereas mood is conceptualized as a three-dimensional construct, physical activity is treated as a global construct not taking into account its distinct components like exercise (such as jogging) and nonexercise activity (NEA; such as climbing stairs). To overcome these limitations, we conducted an ambulatory assessment study on the everyday life of 106 adults over 7 d continuously measuring NEA via accelerometers and repeatedly querying for mood in real time via GPS-triggered e-diaries. We used multilevel modeling to derive differential within-subject effects of exercise versus NEA on mood and to conduct analyses on the temporal course of effects. Analyses revealed that exercise increased valence (beta = 0.023; P Exercise and NEA differed regarding their within-subject effects on mood, whereas exercise increased valence and calmness, NEA increased energetic arousal and decreased calmness. Therefore, it appears necessary to clearly differentiate between exercise and NEA regarding their within-subject effects on mood dimensions in both research and treatment.

Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

Energy Technology Data Exchange (ETDEWEB)

Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

2010-07-16

Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

Analytical methods for 2,4-D (Dichlorophenoxyacetic acid) determination; Metodos analiticos para la determinacion del 2,4-D (Acido diclorofenoxiacetico)

Energy Technology Data Exchange (ETDEWEB)

Martinez G, M.S.M

1999-06-01

The 2,4-D herbicide is one of the main pesticides for controlling the bad grass in crops such as the water undergrowth. In Mexico the allowed bound of this pesticide is 0.05 mg/l in water of 2,4-D so it is required to have methods trusts and exacts, which can used in order to detected low concentration of it. In this work we show some for the conventional techniques and for establishing the 2,4-D concentrations. The UV-Vis spectrometer and liquids chromatography due that they are the most common used nowadays. Beside, we introduce a now developed technique, which is based on the neutronic activation analysis. Though use of the UV-Vis spectrometer technique it was possible target the concentrations interval between 1 and 200 mg/l. In the liquids chromatography interval was between 0.1 and 0.9, and by the neutronic activation analysis the interval was between 0.01 and 200 mg/l. (Author)

Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

Science.gov (United States)

Xie, Jianfeng; Robertson, Jennifer M; Chen, Ching-Wen; Zhang, Wenxiao; Coopersmith, Craig M; Ford, Mandy L

2018-01-01

The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy

Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

Directory of Open Access Journals (Sweden)

Jianfeng Xie

Full Text Available The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre

The site of 2,4-D accumulation in Euphorbia helioscopia L

International Nuclear Information System (INIS)

Sakri, F.A.

1990-01-01

The distribution and accumulation of the herbicide 2,4-D have been studied by 14 C labelling and by tracing due to the autoradiographic method in young plants of Euphorbia helioscopia L. (milkweed). Milkweed plants were grown in a greenhouse at 30deg C under 16 hrs. photoperiod for about two weeks. The two lower opposite leaves, the cotyledons, were used as sites for 14 C-labelled 2,4-D application. The autoradiograph of the whole plants revealed that labelled 2,4-D movement was predominantly basipetal into the root as well as acropetal into the shoot apex. The 2,4-D movement has by-passed all the matured leaves in its movement from active sources to active sinks. The microautoradiography indicated that 2,4-D can accumulate to a considerable amount both in the parenchyma of the pith and in the cortical cells. It is concluded that 2,4-D is transported through phloem cells when applied to the healthy long leaves. (author)

On the relation between 2D:4D and sex-dimorphic personality traits.

Science.gov (United States)

Hampson, Elizabeth; Ellis, Connie L; Tenk, Christine M

2008-02-01

Several personality traits, including aggressiveness and sensation seeking, have been hypothesized to be influenced by prenatal androgen exposure, though evidence for this proposition is limited. We investigated whether individual differences in aggressiveness, sensation seeking, and several prosocial personality traits can be predicted from differences in the 2D:4D digit ratio, a putative marker of prenatal androgen activity. A total of 164 undergraduates (87 men, 77 women) completed self-report measures of physical and verbal aggression, as well as a standardized measure of sensation seeking, and five scales to assess empathy, nurturance, expressivity/femininity, instrumentality/masculinity, and assertiveness. Two sex-dimorphic tests of spatial ability also were included. Men had a lower 2D:4D ratio than women, confirming the typical sex difference in digit proportions. Significant sex differences were observed on 10 of the 11 personality scales purported to show sex differences and on both tests of spatial ability. The 2D:4D ratio was a significant predictor of scores on three of the four aggression subscales, total aggression, thrill and adventure seeking, and total sensation-seeking, in the sample as a whole and in women. In men, correlations with 2D:4D were significant only for total sensation-seeking and verbal aggression. In both sexes, lower 2D:4D ratios were associated with increased aggressiveness and sensation seeking. For the spatial tests, there was no evidence of any association with 2D:4D in either men or women. The 2D:4D digit ratio may be a valid, though weak, predictor of selective sex-dependent traits that are sensitive to testosterone.

Evaluation of 2,4-D removal via activated carbon from pomegranate husk/polymer composite hydrogel: Optimization of process parameters through face centered composite design

International Nuclear Information System (INIS)

Taktak, Fulya; Ilbay, Zeynep; Sahin, Selin

2015-01-01

A new type of polymer composite hydrogel was prepared by introducing activated carbons from pomegranate husk into poly ((2-dimethylamino) ethyl methacrylate) network. The removal of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous solution was studied with respect to pH of the media, initial 2,4-D concentration and activated carbon content into the polymeric network. Face centered composite design (FCCD) through response surface methodology (RSM) was used for designing the experiments as well as for studying the effects of the process parameters. A quadratic model and a two factor interaction design model were developed for the removal of 2,4-D and adsorption capacity, respectively. The optimum pH of the pesticide solution, activated carbon content into the polymeric network and initial concentration of 2,4-D were found as 3, 2.5 wt% and 100mg/L. 63.245% and 68.805 (mg/g) for the removal of 2,4-D and adsorption capacity were obtained by using Simplex optimization method. Furthermore, the surface characteristics of the adsorbent prepared under optimized conditions were examined by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR).

Evaluation of 2,4-D removal via activated carbon from pomegranate husk/polymer composite hydrogel: Optimization of process parameters through face centered composite design

Energy Technology Data Exchange (ETDEWEB)

Taktak, Fulya; Ilbay, Zeynep [Usak Univ, Usak (Turkmenistan); Sahin, Selin [Istanbul University, Istanbul (Turkmenistan)

2015-09-15

A new type of polymer composite hydrogel was prepared by introducing activated carbons from pomegranate husk into poly ((2-dimethylamino) ethyl methacrylate) network. The removal of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous solution was studied with respect to pH of the media, initial 2,4-D concentration and activated carbon content into the polymeric network. Face centered composite design (FCCD) through response surface methodology (RSM) was used for designing the experiments as well as for studying the effects of the process parameters. A quadratic model and a two factor interaction design model were developed for the removal of 2,4-D and adsorption capacity, respectively. The optimum pH of the pesticide solution, activated carbon content into the polymeric network and initial concentration of 2,4-D were found as 3, 2.5 wt% and 100mg/L. 63.245% and 68.805 (mg/g) for the removal of 2,4-D and adsorption capacity were obtained by using Simplex optimization method. Furthermore, the surface characteristics of the adsorbent prepared under optimized conditions were examined by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR).

KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules.

Science.gov (United States)

Miah, S M Shahjahan; Hughes, Tracey L; Campbell, Kerry S

2008-03-01

KIR2DL4 (2DL4) is a member of the killer cell Ig-like receptor (KIR) family in human NK cells. It can stimulate potent cytokine production and weak cytolytic activity in resting NK cells, but the mechanism for 2DL4-mediated signaling remains unclear. In this study we characterized the signaling pathways stimulated by 2DL4 engagement. In a human NK-like cell line, KHYG-1, cross-linking of 2DL4 activated MAPKs including JNK, ERK, and p38. Furthermore, 2DL4 cross-linking resulted in phosphorylation of IkappaB kinase beta (IKKbeta) and the phosphorylation and degradation of IkappaBalpha, which indicate activation of the classical NF-kappaB pathway. Engagement of 2DL4 was also shown to activate the transcription and translation of a variety of cytokine genes, including TNF-alpha, IFN-gamma, MIP1alpha, MIP1beta, and IL-8. Pharmacological inhibitors of JNK, MEK1/2 and p38, blocked IFN-gamma, IL-8, and MIP1alpha production, suggesting that MAPKs are regulating 2DL4-mediated cytokine production in a nonredundant manner. Activation of both p38 and ERK appear to be upstream of the stimulation of NF-kappaB. Mutation of a transmembrane arginine in 2DL4 to glycine (R/G mutant) abrogated FcepsilonRI-gamma association, as well as receptor-mediated cytolytic activity and calcium responses. Surprisingly, the R/G mutant still activated MAPKs and the NF-kappaB pathway and selectively stimulated the production of MIP1alpha, but not that of IFN-gamma or IL-8. In conclusion, we provide evidence that the activating functions of 2DL4 can be compartmentalized into two distinct structural modules: 1) through transmembrane association with FcepsilonRI-gamma; and 2) through another receptor domain independent of the transmembrane arginine.

UDP-galactose 4'-epimerase activities toward UDP-Gal and UDP-GalNAc play different roles in the development of Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Jennifer M I Daenzer

Full Text Available In both humans and Drosophila melanogaster, UDP-galactose 4'-epimerase (GALE catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal and UDP-glucose (UDP-glc in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc and UDP-N-acetylglucosamine (UDP-glcNAc. All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans.

Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells

DEFF Research Database (Denmark)

Kongsbak, Martin; von Essen, Marina R; Boding, Lasse

2014-01-01

The active form of vitamin D3, 1,25(OH)2D3, has significant immunomodulatory properties and is an important determinant in the differentiation of CD4+ effector T cells. The biological actions of 1,25(OH)2D3 are mediated by the vitamin D receptor (VDR) and are believed to correlate with the VDR...... protein expression level in a given cell. The aim of this study was to determine if and how 1,25(OH)2D3 by itself regulates VDR expression in human CD4+ T cells. We found that activated CD4+ T cells have the capacity to convert the inactive 25(OH)D3 to the active 1,25(OH)2D3 that subsequently up......-regulates VDR protein expression approximately 2-fold. 1,25(OH)2D3 does not increase VDR mRNA expression but increases the half-life of the VDR protein in activated CD4+ T cells. Furthermore, 1,25(OH)2D3 induces a significant intracellular redistribution of the VDR. We show that 1,25(OH)2D3 stabilizes the VDR...

Estimating the magnitude of near-membrane PDE4 activity in living cells.

Science.gov (United States)

Xin, Wenkuan; Feinstein, Wei P; Britain, Andrea L; Ochoa, Cristhiaan D; Zhu, Bing; Richter, Wito; Leavesley, Silas J; Rich, Thomas C

2015-09-15

Recent studies have demonstrated that functionally discrete pools of phosphodiesterase (PDE) activity regulate distinct cellular functions. While the importance of localized pools of enzyme activity has become apparent, few studies have estimated enzyme activity within discrete subcellular compartments. Here we present an approach to estimate near-membrane PDE activity. First, total PDE activity is measured using traditional PDE activity assays. Second, known cAMP concentrations are dialyzed into single cells and the spatial spread of cAMP is monitored using cyclic nucleotide-gated channels. Third, mathematical models are used to estimate the spatial distribution of PDE activity within cells. Using this three-tiered approach, we observed two pharmacologically distinct pools of PDE activity, a rolipram-sensitive pool and an 8-methoxymethyl IBMX (8MM-IBMX)-sensitive pool. We observed that the rolipram-sensitive PDE (PDE4) was primarily responsible for cAMP hydrolysis near the plasma membrane. Finally, we observed that PDE4 was capable of blunting cAMP levels near the plasma membrane even when 100 μM cAMP were introduced into the cell via a patch pipette. Two compartment models predict that PDE activity near the plasma membrane, near cyclic nucleotide-gated channels, was significantly lower than total cellular PDE activity and that a slow spatial spread of cAMP allowed PDE activity to effectively hydrolyze near-membrane cAMP. These results imply that cAMP levels near the plasma membrane are distinct from those in other subcellular compartments; PDE activity is not uniform within cells; and localized pools of AC and PDE activities are responsible for controlling cAMP levels within distinct subcellular compartments. Copyright © 2015 the American Physiological Society.

Prompt-gamma neutron activation analysis system design. Effects of D-T versus D-D neutron generator source selection

International Nuclear Information System (INIS)

Shypailo, R.J.; Ellis, K.J.

2008-01-01

Prompt-gamma neutron activation (PGNA) analysis is used for the non-invasive measurement of human body composition. Advancements in portable, compact neutron generator design have made those devices attractive as neutron sources. Two distinct generators are available: D-D with 2.5 MeV and D-T with 14.2 MeV neutrons. To compare the performance of these two units in our present PGNA system, we performed Monte Carlo simulations (MCNP-5; Los Alamos National Laboratory) evaluating the nitrogen reactions produced in tissue-equivalent phantoms and the effects of background interference on the gamma-detectors. Monte Carlo response curves showed increased gamma production per unit dose when using the D-D generator, suggesting that it is the more suitable choice for smaller sized subjects. The increased penetration by higher energy neutrons produced by the D-T generator supports its utility when examining larger, especially obese, subjects. A clinical PGNA analysis design incorporating both neutron generator options may be the best choice for a system required to measure a wide range of subject phenotypes. (author)

Synthesis and Evaluation of the Anticonvulsant Activities of 4-(2-(Alkylthiobenzo[d]oxazol-5-yl-2,4-dihydro-3H-1,2,4-triazol-3-ones

Directory of Open Access Journals (Sweden)

Ming-Xia Song

2018-03-01

Full Text Available In this study, a novel series of 4-(2-(alkylthiobenzo[d]oxazol-5-yl-2,4-dihydro-3H-1,2,4-triazol-3-ones (4a–m was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES and subcutaneous pentylenetetrazole (scPTZ seizure models in mice. The neurotoxicity of these compounds was evaluated using the rotarod neurotoxicity test. The majority of compounds showed anti-MES activities at 100 or 300 mg/kg. Compound 4g was considered to be the most promising, based on its potency against MES- and PTZ-induced seizures with ED50 values of 23.7 and 18.9 mg/kg, respectively. The TD50 value of 4g was 284.0 mg/kg, which resulted in a higher protective index (PI = TD50/ED50 value than that of carbamazepine and valproate. In an ELISA test, compound 4g significantly increased the γ-aminobutyric acid (GABA content in mouse brain. In addition, pretreatment with thiosemicarbazide (an inhibitor of the GABA synthesizing enzyme significantly decreased the activity of 4g in the MES model, which suggests that the mechanism through which compound 4g elicits its anticonvulsive action is at least in part through increasing the GABA level in the brain.

Discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers.

Science.gov (United States)

Kemnitzer, William; Sirisoma, Nilantha; May, Chris; Tseng, Ben; Drewe, John; Cai, Sui Xiong

2009-07-01

We report the discovery of N-((benzo[d][1,3]dioxol-5-yl)methyl)-6-phenylthieno[3,2-d]pyrimidin-4-amine (2a) as an apoptosis inducer using our proprietary cell- and caspase-based ASAP HTS assay, and SAR study of HTS hit 2a which led to the discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers. Compounds 5d and 5e were the most potent with EC(50) values of 0.008 and 0.004microM in T47D human breast cancer cells, respectively. Compound 5d was found to be highly active in the MX-1 breast cancer model. Functionally, compounds 5d and 5e both induced apoptosis through inhibition of tubulin polymerization.

A cluster of aspartic residues in the extracellular loop II of PAR 4 is important for thrombin interaction and activation of platelets.

Science.gov (United States)

Sánchez Centellas, Daniel; Gudlur, Sushanth; Vicente-Carrillo, Alejandro; Ramström, Sofia; Lindahl, Tomas L

2017-06-01

Thrombin activates platelets via proteolytic cleavage of protease-activated receptors (PARs) 1 and 4. The two PARs have distinct but complementary roles. The mechanisms responsible for PAR1 activation by thrombin have been extensively studied. However, much less is known regarding thrombin activation of PAR4, especially the potential involvement of regions of PAR4 other than the N-terminal, which is bound to the catalytic site of thrombin. We have studied PAR4 in S. cerevisiae strain MMY12, an expression system in which the GPCR receptors are connected to a Lac Z reporter gene resulting in increased β-galactosidase activity. This approach was used to assess PAR4 mutants to evaluate the contribution of different aspartic residues in facilitating PAR4 activation. Furthermore, peptides mimicking parts of the PAR4 N-terminal and the second extracellular loop (ECLII) were tested for their ability to inhibit platelet activation by thrombin. Binding of these peptides to γ-thrombin was studied by monitoring the decrease in tryptophan fluorescence intensity of thrombin. We conclude that not only the N-terminal but also the electronegative aspartic residues D224, D230 and D235 (located in ECLII) are be important for PAR4 binding to thrombin. We further suggest that they play a role for the tethered ligand binding to the receptor, as mutations also affected activation in response to a PAR4-activating peptide mimicking the new N-terminal formed after cleavage. This agrees with previous results on PAR1 and thrombin binding. We suggest that the ECLII of PAR4 could be a potential target for antithrombotic drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Digit Ratio (2D:4D): A Biomarker for Prenatal Sex Steroids and Adult Sex Steroids in Challenge Situations.

Science.gov (United States)

Manning, John; Kilduff, Liam; Cook, Christian; Crewther, Blair; Fink, Bernhard

2014-01-01

Digit ratio (2D:4D) denotes the relative length of the second and fourth digits. This ratio is considered to be a biomarker of the balance between fetal testosterone (T) and estrogen (E) in a narrow window of early ontogeny. Evidence for this assertion is derived from direct and indirect measures of prenatal hormonal exposure (in experimental animals, via amniotic fluid samples and in the study of sex-typical traits) in relation to 2D:4D. In contrast, the relationships between 2D:4D and levels of sex steroids in adults are less clear, as many correlational studies of 2D:4D and adult sex steroids have concluded that this association is statistically non-significant. Here, we suggest that in order to understand the link between 2D:4D and sex hormones, one must consider both fetal organizing and adult activating effects of T and E. In particular, we hypothesize that 2D:4D correlates with organizing effects on the endocrine system that moderate activating effects in adulthood. We argue that this is particularly evident in "challenging" conditions such as aggressive and sexual encounters, in which individuals show increased levels of T. We discuss this refinement of the 2D:4D paradigm in relation to the links between 2D:4D and sports performance, and aggression.

Distinctive Left Ventricular Activations Associated With ECG Pattern in Heart Failure Patients.

Science.gov (United States)

Derval, Nicolas; Duchateau, Josselin; Mahida, Saagar; Eschalier, Romain; Sacher, Frederic; Lumens, Joost; Cochet, Hubert; Denis, Arnaud; Pillois, Xavier; Yamashita, Seigo; Komatsu, Yuki; Ploux, Sylvain; Amraoui, Sana; Zemmoura, Adlane; Ritter, Philippe; Hocini, Mélèze; Haissaguerre, Michel; Jaïs, Pierre; Bordachar, Pierre

2017-06-01

In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps. Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P =0.0004; NICD versus LBBB, 4±2 versus 1±1; P =0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity. In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy. © 2017 American Heart Association, Inc.

Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle

DEFF Research Database (Denmark)

Treebak, Jonas Thue; Taylor, Eric B.; Witczak, Carol A.

2010-01-01

TBC1D4 (also known as AS160) regulates GLUT4 translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of Serine (S)/Threonine (T) residues by upstream kinases resulting in inactivation of Rab-GAP activity leading to GLUT4 mobilization...

Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth.

Science.gov (United States)

Soong, Joanne; Chen, Yulin; Shustef, Elina M; Scott, Glynis A

2012-04-01

Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.

Synthesis and Herbicidal Activities of Novel 4-(4-(5-methyl-3-arylisoxazol-4-ylthiazol-2-ylpiperidyl Carboxamides and Thiocarboxamides

Directory of Open Access Journals (Sweden)

Ai-Dong Zhang

2009-03-01

Full Text Available A series of novel 4-(4-(5-methyl-3-arylisoxazol-4-ylthiazol-2-ylpiperidyl carboxamides and thiocarboxamides were synthesized as potential lead compounds of inhibitors targeting D1 protease in plants. These compounds were designed on the basis of a D1 protease inhibitor hit structure identified by homology modeling and virtual screening. The syntheses of these compounds were accomplished via a four-step procedure including the isoxazole ring formation, a-bromination of acetyl group, thiazole ring formation, and carboxamide/thiocarboxamide attachment. The in vivo herbicidal activity tests show that most compounds possess moderate to good herbicidal activities. The enzyme activity of one compound against the native spinach D1 protease exhibits a competitive inhibition. The results suggest that these compounds are indeed potential inhibitors for targeting D1 protease in plants.

Toxicology Study No. S.0024589d 15, Human Cell Line Activation Test of the Novel Energetic, 3,4 -Dinitropyrazole (DNP)

Science.gov (United States)

2016-04-01

Assay 1 0.259 0.278 Assay 2 0.299 6.3 CD54 and CD86 expression in response to DNP exposure of THP -1 cells Three independent tests were...2 Toxicology Study No. S.0024589d-15, April 2016 Toxicology Directorate Human Cell Line Activation Test of the Novel Energetic 3,4...report. 17-05-2016 Technical Report March 2016-April 2016 Toxicology Study No. S.0024589d-15 Human Cell Line Activation Test of the Novel

Special report : Workshop on 4D-treatment planning in actively scanned particle therapy-Recommendations, technical challenges, and future research directions

NARCIS (Netherlands)

Knopf, Antje; Bert, Christoph; Heath, Emily; Nill, Simeon; Kraus, Kim; Richter, Daniel; Hug, Eugen B.; Pedroni, Eros; Safai, Sairos; Albertini, Francesca; Zenklusen, Silvan; Boye, Dirk; Söhn, Matthias; Soukup, Martin; Sobotta, Benjamin; Lomax, Antony

This article reports on a 4D-treatment planning workshop (4DTPW), held on 7-8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to

Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor.

Science.gov (United States)

Ryan, J J; McReynolds, L J; Keegan, A; Wang, L H; Garfein, E; Rothman, P; Nelms, K; Paul, W E

1996-02-01

IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.

Measurement of the hyperfine structure of the 4d2D3/2,5/2 levels and isotope shifts of the 4p2P3/2->4d2D3/2 and 4p2P3/2->4d2D5/2 transitions in gallium 69 and 71

International Nuclear Information System (INIS)

Rehse, Steven J.; Fairbank, William M.; Lee, Siu Au

2001-01-01

The hyperfine structure of the 4d 2 D 3/2,5/2 levels of 69,71 Ga is determined. The 4p 2 P 3/2 ->4d 2 D 3/2 (294.50-nm) and 4p 2 P 3/2 ->4d 2 D 5/2 (294.45-nm) transitions are studied by laser-induced fluorescence in an atomic Ga beam. The hyperfine A constant measured for the 4d 2 D 5/2 level is 77.3±0.9 MHz for 69 Ga and 97.9± 0.7 MHz for 71 Ga (3σ errors). The A constant measured for the 4d 2 D 3/2 level is -36.3±2.2 MHz for 69 Ga and -46.2±3.8 MHz for 71 Ga. These measurements correct sign errors in the previous determination of these constants. For 69 Ga the hyperfine B constants measured for the 4d 2 D 5/2 and the 4d 2 D 3/2 levels are 5.3±4.1 MHz and 4.6±4.2 MHz, respectively. The isotope shift is determined to be 114±8 MHz for the 4p 2 P 3/2 ->4d 2 D 3/2 transition and 115±7 MHz for the 4p 2 P 3/2 ->4d 2 D 5/2 transition. The lines of 71 Ga are shifted to the blue. This is in agreement with previous measurement. [copyright] 2001 Optical Society of America

Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response.

Science.gov (United States)

Ceruti, Julieta M; Scassa, María E; Marazita, Mariela C; Carcagno, Abel C; Sirkin, Pablo F; Cánepa, Eduardo T

2009-06-01

p19INK4d promotes survival of several cell lines after UV irradiation due to enhanced DNA repair, independently of CDK4 inhibition. To further understand the action of p19INK4d in the cellular response to DNA damage, we aimed to elucidate whether this novel regulator plays a role only in mechanisms triggered by UV or participates in diverse mechanisms initiated by different genotoxics. We found that p19INK4d is induced in cells injured with cisplatin or beta-amyloid peptide as robustly as with UV. The mentioned genotoxics transcriptionally activate p19INK4d expression as demonstrated by run-on assay without influencing its mRNA stability and with partial requirement of protein synthesis. It is not currently known whether DNA damage-inducible genes are turned on by the DNA damage itself or by the consequences of that damage. Experiments carried out in cells transfected with distinct damaged DNA structures revealed that the damage itself is not responsible for the observed up-regulation. It is also not known whether the increased expression of DNA-damage-inducible genes is related to immediate protective responses such as DNA repair or to more delayed responses such as cell cycle arrest or apoptosis. We found that ectopic expression of p19INK4d improves DNA repair ability and protects neuroblastoma cells from apoptosis caused by cisplatin or beta-amyloid peptide. Using clonal cell lines where p19INK4d levels can be modified at will, we show that p19INK4d expression correlates with increased survival and clonogenicity. The results presented here, prompted us to suggest that p19INK4d displays an important role in an early stage of cellular DNA damage response.

Phospholipase D family member 4, a transmembrane glycoprotein with no phospholipase D activity, expression in spleen and early postnatal microglia.

Directory of Open Access Journals (Sweden)

Fumio Yoshikawa

Full Text Available BACKGROUND: Phospholipase D (PLD catalyzes conversion of phosphatidylcholine into choline and phosphatidic acid, leading to a variety of intracellular signal transduction events. Two classical PLDs, PLD1 and PLD2, contain phosphatidylinositide-binding PX and PH domains and two conserved His-x-Lys-(x(4-Asp (HKD motifs, which are critical for PLD activity. PLD4 officially belongs to the PLD family, because it possesses two HKD motifs. However, it lacks PX and PH domains and has a putative transmembrane domain instead. Nevertheless, little is known regarding expression, structure, and function of PLD4. METHODOLOGY/PRINCIPAL FINDINGS: PLD4 was analyzed in terms of expression, structure, and function. Expression was analyzed in developing mouse brains and non-neuronal tissues using microarray, in situ hybridization, immunohistochemistry, and immunocytochemistry. Structure was evaluated using bioinformatics analysis of protein domains, biochemical analyses of transmembrane property, and enzymatic deglycosylation. PLD activity was examined by choline release and transphosphatidylation assays. Results demonstrated low to modest, but characteristic, PLD4 mRNA expression in a subset of cells preferentially localized around white matter regions, including the corpus callosum and cerebellar white matter, during the first postnatal week. These PLD4 mRNA-expressing cells were identified as Iba1-positive microglia. In non-neuronal tissues, PLD4 mRNA expression was widespread, but predominantly distributed in the spleen. Intense PLD4 expression was detected around the marginal zone of the splenic red pulp, and splenic PLD4 protein recovered from subcellular membrane fractions was highly N-glycosylated. PLD4 was heterologously expressed in cell lines and localized in the endoplasmic reticulum and Golgi apparatus. Moreover, heterologously expressed PLD4 proteins did not exhibit PLD enzymatic activity. CONCLUSIONS/SIGNIFICANCE: Results showed that PLD4 is a non

Two distinct E3 ubiquitin ligases have complementary functions in the regulation of delta and serrate signaling in Drosophila.

Directory of Open Access Journals (Sweden)

Roland Le Borgne

2005-04-01

Full Text Available Signaling by the Notch ligands Delta (Dl and Serrate (Ser regulates a wide variety of essential cell-fate decisions during animal development. Two distinct E3 ubiquitin ligases, Neuralized (Neur and Mind bomb (Mib, have been shown to regulate Dl signaling in Drosophila melanogaster and Danio rerio, respectively. While the neur and mib genes are evolutionarily conserved, their respective roles in the context of a single organism have not yet been examined. We show here that the Drosophila mind bomb (D-mib gene regulates a subset of Notch signaling events, including wing margin specification, leg segmentation, and vein determination, that are distinct from those events requiring neur activity. D-mib also modulates lateral inhibition, a neur- and Dl-dependent signaling event, suggesting that D-mib regulates Dl signaling. During wing development, expression of D-mib in dorsal cells appears to be necessary and sufficient for wing margin specification, indicating that D-mib also regulates Ser signaling. Moreover, the activity of the D-mib gene is required for the endocytosis of Ser in wing imaginal disc cells. Finally, ectopic expression of neur in D-mib mutant larvae rescues the wing D-mib phenotype, indicating that Neur can compensate for the lack of D-mib activity. We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila.

Effects of INH, DNP, 2,4-D and CMU on the photosynthetic activity of barley and maize plants

International Nuclear Information System (INIS)

Fernandez, J.; Prieto, M. P.

1979-01-01

Determinations of the rate of photosynthesis were made in barley and maize leaves treated with INH, DNP, 2,4-D or CMU. 1 ppm of the chemicals in nutritive solutions was absorbed by roots during 24 or 48 hours in both dark and light conditions. After this period, photosynthetic activity, compensation point and 14 C O 2 assimilation were determined. Results show that INH increases the rate of photosynthesis, DNP and 2,4-D do not alter it sensibly and CMU acts as a strong inhibitor of photosynthesis. Some possible applications for ths obtention of labelled compounds by biosynthesis are discussed. (Author) 87 refs

Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells

Directory of Open Access Journals (Sweden)

Manpreet S. Chahal

2010-07-01

Full Text Available Phospholipase D2 (PLD2 generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.

Science.gov (United States)

Chahal, Manpreet S; Brauner, Daniel J; Meier, Kathryn E

2010-07-02

Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

Establishing a framework to implement 4D XCAT Phantom for 4D radiotherapy research

Directory of Open Access Journals (Sweden)

Raj K Panta

2012-01-01

Conclusions: An integrated computer program has been developed to generate, review, analyse, process, and export the 4D XCAT images. A framework has been established to implement the 4D XCAT phantom for 4D RT research.

Clinical Utility of 4D FDG-PET/CT Scans in Radiation Treatment Planning

Energy Technology Data Exchange (ETDEWEB)

Aristophanous, Michalis, E-mail: maristophanous@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center and Harvard Medical School, Boston, MA (United States); Berbeco, Ross I.; Killoran, Joseph H. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center and Harvard Medical School, Boston, MA (United States); Yap, Jeffrey T. [Department of Radiology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States); Sher, David J.; Allen, Aaron M.; Larson, Elysia; Chen, Aileen B. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center and Harvard Medical School, Boston, MA (United States)

2012-01-01

Purpose: The potential role of four-dimensional (4D) positron emission tomography (PET)/computed tomography (CT) in radiation treatment planning, relative to standard three-dimensional (3D) PET/CT, was examined. Methods and Materials: Ten patients with non-small-cell lung cancer had sequential 3D and 4D [{sup 18}F]fluorodeoxyglucose PET/CT scans in the treatment position prior to radiation therapy. The gross tumor volume and involved lymph nodes were contoured on the PET scan by use of three different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; a technique with a constant threshold of standardized uptake value (SUV) greater than 2.5; and an automatic segmentation technique. For each technique, the tumor volume was defined on the 3D scan (VOL3D) and on the 4D scan (VOL4D) by combining the volume defined on each of the five breathing phases individually. The range of tumor motion and the location of each lesion were also recorded, and their influence on the differences observed between VOL3D and VOL4D was investigated. Results: We identified and analyzed 22 distinct lesions, including 9 primary tumors and 13 mediastinal lymph nodes. Mean VOL4D was larger than mean VOL3D with all three techniques, and the difference was statistically significant (p < 0.01). The range of tumor motion and the location of the tumor affected the magnitude of the difference. For one case, all three tumor definition techniques identified volume of moderate uptake of approximately 1 mL in the hilar region on the 4D scan (SUV maximum, 3.3) but not on the 3D scan (SUV maximum, 2.3). Conclusions: In comparison to 3D PET, 4D PET may better define the full physiologic extent of moving tumors and improve radiation treatment planning for lung tumors. In addition, reduction of blurring from free-breathing images may reveal additional information regarding regional disease.

Federal and state regulatory requirements for the D ampersand D of the Alpha-4 Building, Y-12 Plant, Oak Ridge, Tennessee

International Nuclear Information System (INIS)

Etnier, E.L.; Houlberg, L.M.; Bock, R.E.

1994-01-01

The US Department of Energy (DOE) has begun the decontamination and decommissioning (D ampersand D) of Building 9201-4 (Alpha-4) at the Oak Y-12 Plant, Oak Ridge, Tennessee, The Alpha-4 Building was used from 1953--1962 to house a column exchange (Colex) process for lithium isotope separation. This process involved electrochemical and solvent extraction processes that required substantial quantities of mercury. Presently there is no law or regulation mandating decommissioning at DOE facilites or setting de minimis or ''below regulatory concern'' (BRC) radioactivity levels to guide decommissioning activities at DOE facilities. However, DOE Order 5820.2A, Chap. V (Decommissioning of Radioactively Contaminated Facilities), requires that the regulatory status of each project be identified and that technical engineering planning must assure D ampersand D compliance with all environmental regulations during cleanup activities. To assist in the performance of this requirement, this paper gives a brief overview of potential federal and state regulatory requirements related to D ampersand D activities at Alpha-4. Compliance with other federal, state, and local regulations not addressed here may be required, depending on site characterization, actual D ampersand D activities, and wastes generated

Synthesis and Antitumor Activity of 3-Methyl-4-oxo-3,4-dihydroimidazo [5,1-d][1,2,3,5]tetrazine-8-carboxylates and -carboxamides

Directory of Open Access Journals (Sweden)

Lin-Xiang Zhao

2010-12-01

Full Text Available Seventeen novel 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate and -carboxamide derivatives were synthesized and evaluated for their growth inhibition in seven human solid tumor and a human leukemia HL-60 cell lines. Compound IVa showed more activity than the other compounds and the positive control temozolomide. In the presence of 40 mg/mL of IVa, the survival rate of all tested tumor cells was less than 10%. Esters displayed more potent antitumour activity than amides and temozolomide against HL-60 cells. These compounds also exhibited considerably enhanced water-solubility.

NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d.

Science.gov (United States)

Kuylenstierna, Carlotta; Björkström, Niklas K; Andersson, Sofia K; Sahlström, Peter; Bosnjak, Lidija; Paquin-Proulx, Dominic; Malmberg, Karl-Johan; Ljunggren, Hans-Gustaf; Moll, Markus; Sandberg, Johan K

2011-07-01

Invariant NKT cells are important in the activation and regulation of immune responses. They can also function as CD1d-restricted killer cells. However, the role of activating innate NK-cell receptors expressed on NKT cells in triggering cytolytic function is poorly characterized. Here, we initially confirmed that the cellular stress-ligand receptor NKG2D is expressed on CD4- NKT cells, whereas most CD4+ NKT cells lack this receptor. Interestingly, NKG2D+ NKT cells frequently expressed perforin, and both NKG2D and perforin localized at the site of contact with NKG2D ligand-expressing target cells. CD4- NKT cells degranulated in response to NKG2D engagement in a redirected activation assay independent of stimulation via their invariant TCR. NKT cells killed P815 cells coated with anti-NKG2D mAb and CD1d-negative K562 tumor target cells in an NKG2D-dependent manner. Furthermore, NKG2D engagement co-stimulated TCR-mediated NKT-cell activation in response to endogenous CD1d-presented ligands or suboptimal levels of anti-CD3 triggering. These data indicate that the CD4- subset of human NKT cells can mediate direct lysis of target cells via NKG2D engagement independent of CD1d, and that NKG2D also functions as a co-stimulatory receptor in these cells. NKG2D thus plays both a direct and a co-stimulatory role in the activation of NKT cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole, a potential dopamine D{sub 4} receptor radioligand

Energy Technology Data Exchange (ETDEWEB)

Li, Gu-Cai; Zhang, Ru [Hunan Institute of Engineering, Hunan Xiangtan (China). College of Chemistry and Chemical Engineering; Xia, Jiao-yun [Changsha Univ. of Science and Technology (China). School of Chemistry and Biology Engineering

2016-07-01

The dopamine D{sub 4} receptor has been shown to play important roles in some central nervous system pathologies. Specific radioligands for the D{sub 4} receptor may be useful to understand the function of the D{sub 4} receptor and its correlations with various disorders. 2-(3-(4-(4-[{sup 18}F]Fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole ([{sup 18}F]4) was synthesized through a one-pot two-step procedure with total yield 18.6% (decay corrected). The specific activity of the radioligand was 112 GBq/μmol and its radiochemical purity was >95.0%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding evaluation and the K{sub i} value for the D{sub 4} receptor was determined to be 2.9±0.2 nM, and its selectivity for the dopamine D{sub 4} receptor is 709-fold versus D{sub 2long} receptor, 823-fold versus D{sub 3} receptor. The partition coefficient (Log D) of it was determined to be 2.6±0.1 through octanol-water partition experiment. The ligand presents desirable combination of lipophilicity, affinity and selectivity for the dopamine D{sub 4} receptor. The results suggested that the radioligand shows promises for the in vivo study of the dopamine D{sub 4} receptor.

O-GlcNAc transferase regulates transcriptional activity of human Oct4.

Science.gov (United States)

Constable, Sandii; Lim, Jae-Min; Vaidyanathan, Krithika; Wells, Lance

2017-10-01

O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc. Octamer-binding protein 4 (Oct4) is one of the key transcription factors required for pluripotency of ES cells and more recently, the generation of induced pluripotent stem (iPS) cells. The action of Oct4 is modulated by the addition of several post-translational modifications, including O-GlcNAc. Previous studies in mice found a single site of O-GlcNAc addition responsible for transcriptional regulation. This study was designed to determine if this mechanism is conserved in humans. We mapped 10 novel sites of O-GlcNAc attachment on human Oct4, and confirmed a role for OGT in transcriptional activation of Oct4 at a site distinct from that found in mouse that allows distinction between different Oct4 target promoters. Additionally, we uncovered a potential new role for OGT that does not include its catalytic function. These results confirm that human Oct4 activity is being regulated by OGT by a mechanism that is distinct from mouse Oct4. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analytical methods for 2,4-D (Dichlorophenoxyacetic acid) determination

International Nuclear Information System (INIS)

Martinez G, M.S.M.

1999-01-01

The 2,4-D herbicide is one of the main pesticides for controlling the bad grass in crops such as the water undergrowth. In Mexico the allowed bound of this pesticide is 0.05 mg/l in water of 2,4-D so it is required to have methods trusts and exacts, which can used in order to detected low concentration of it. In this work we show some for the conventional techniques and for establishing the 2,4-D concentrations. The UV-Vis spectrometer and liquids chromatography due that they are the most common used nowadays. Beside, we introduce a now developed technique, which is based on the neutronic activation analysis. Though use of the UV-Vis spectrometer technique it was possible target the concentrations interval between 1 and 200 mg/l. In the liquids chromatography interval was between 0.1 and 0.9, and by the neutronic activation analysis the interval was between 0.01 and 200 mg/l. (Author)

Distinct distribution of specific members of protein 4.1 genefamily in the mouse nephron

Energy Technology Data Exchange (ETDEWEB)

Ramez, Mohamed; Blot-Chabaud, Marcel; Cluzeaud, Francoise; Chanan, Sumita; Patterson, Michael; Walensky, Loren D.; Marfatia, Shirin; Baines, Anthony J.; Chasis, Joel A.; Conboy, John G.; Mohandas, Narla; Gascard, Philippe

2002-12-11

Background: Protein 4.1 is an adapter protein which linksthe actin cytoskeleton to various transmembrane proteins. 4.1 proteinsare encoded by four homologous genes, 4.1R, 4.1G, 4.1N, and 4.1B, whichundergo complex alternative splicing. Here we performed a detailedcharacterization of the expression of specific 4.1 proteins in the mousenephron. Methods: Distribution of renal 4.1 proteins was investigated bystaining of paraformaldehyde fixed mouse kidney sections with antibodieshighly specific for each 4.1 protein. Major 4.1 splice forms, amplifiedfrom mouse kidney marathon cDNA, were expressed in transfected COS-7cells in order to assign species of known exon composition to proteinsdetected in kidney. Results: A 105kDa4.1R splice form, initiating atATG-2 translation initiation site and lacking exon 16, but including exon17B, was restricted to thick ascending limb of Henle's loop. A 95kDa 4.1Nspliceform,lacking exons 15 and 17D, was expressed in either descendingor ascending thin limb of Henle'sloop, distal convoluted tubule and allregions of the collecting duct system. A major 108kDa 4.1B spliceform,initiating at a newly characterized ATG translation initiation site, andlacking exons 15, 17B, and 21, was present only in Bowman's capsule andproximal convoluted tubule (PCT). There was no expression of 4.1G inkidney. Conclusion: Distinct distribution of 4.1 proteins along thenephron suggests their involvement in targeting of selected transmembraneproteins in kidney epithelium andtherefore in regulation of specifickidney functions.

Distinct roles of synaptic and extrasynaptic GABAA receptors in striatal inhibition dynamics

Directory of Open Access Journals (Sweden)

Ruixi eLuo

2013-11-01

Full Text Available Striatonigral and striatopallidal projecting medium spiny neurons (MSNs express dopamine D1 (D1+ and D2 receptors (D2+, respectively. Both classes receive extensive GABAergic input via expression of synaptic, perisynaptic and extrasynaptic GABAA receptors. The activation patterns of different presynaptic GABAergic neurons produce transient and sustained GABAA receptor-mediated conductance that fulfill distinct physiological roles. We performed single and dual whole cell recordings from striatal neurons in mice expressing fluorescent proteins in interneurons and MSNs. We report specific inhibitory dynamics produced by distinct activation patterns of presynaptic GABAergic neurons as source of synaptic, perisynaptic and extrasynaptic inhibition. Synaptic GABAA receptors in MSNs contain the α2, γ2 and a β subunit. In addition, there is evidence for the developmental increase of the α1 subunit that contributes to faster inhibitory postsynaptic current (IPSC. Tonic GABAergic currents in MSNs from adult mice are carried by extrasynaptic receptors containing the α4 and δ subunit, while in younger mice this current is mediated by receptors that contain the α5 subunit. Both forms of tonic currents are differentially expressed in D1+ and D2+ MSNs. This study extends these findings by relating presynaptic activation with pharmacological analysis of inhibitory conductance in mice where the β3 subunit is conditionally removed in fluorescently labeled D2+ MSNs and in mice with global deletion of the δ subunit. Our results show that responses to low doses of gaboxadol (2μM, a GABAA receptor agonist with preference to δ subunit, are abolished in the δ but not the β3 subunit knock out mice. This suggests that the β3 subunit is not a component of the adult extrasynaptic receptor pool, in contrast to what has been shown for tonic current in young mice. Deletion of the β3 subunit from D2+ MSNs however, removed slow spontaneous IPSCs, implicating its

Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

Directory of Open Access Journals (Sweden)

Weihong Zeng

2017-06-01

Full Text Available Decidual CD4+ T (dCD4 T cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.

Energy level properties of 4p64d3, 4p64d24f, and 4p54d4 configurations of the W35+ ion

International Nuclear Information System (INIS)

Bogdanovich, P.; Kisielius, R.

2014-01-01

The ab initio quasirelativistic Hartree–Fock method developed specifically for the calculation of spectroscopic parameters of heavy atoms and highly charged ions was used to derive spectral data for the multicharged tungsten ion W 35+ . The configuration interaction method was applied to include the electron-correlation effects. The relativistic effects were taken into account in the Breit–Pauli approximation for quasirelativistic Hartree–Fock radial orbitals. The energy level spectra, radiative lifetimes τ, and Lande g-factors have been calculated for the 4p 6 4d 3 , 4p 6 4d 2 4f, and 4p 5 4d 4 configurations of the W 35+ ion

Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers.

Science.gov (United States)

Markowitz, John S; Donovan, Jennifer L; Devane, C Lindsay; Taylor, Robin M; Ruan, Ying; Wang, Jun-Sheng; Chavin, Kenneth D

2003-12-01

Saw palmetto (Serenoa repens) is the most commonly used herbal preparation in the treatment of benign prostatic hyperplasia. The objective of this study was to determine whether a characterized saw palmetto product affects the activity of cytochrome P450 (CYP) 2D6 or 3A4 in healthy volunteers (6 men and 6 women). The probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again after exposure to saw palmetto (320-mg capsule once daily) for 14 days. Dextromethorphan metabolic ratios and alprazolam pharmacokinetics were determined at baseline and after saw palmetto treatment. The mean ratio of dextromethorphan to its metabolite was 0.038 +/- 0.044 at baseline and 0.048 +/- 0.080 after 14 days of saw palmetto administration (P =.704, not significant [NS]), indicating a lack of effect on CYP2D6 activity. The area under the plasma alprazolam concentration versus time curve was 476 +/- 178 h. ng. mL(-1) at baseline and 479 +/- 125 h. ng. mL(-1) after saw palmetto treatment (P =.923, NS), indicating a lack of effect on CYP3A4 activity. The elimination half-life of alprazolam was 11.4 +/- 3.1 hours at baseline and 11.6 +/- 2.7 hours after saw palmetto treatment (P =.770, NS), also indicating a lack of effect on CYP3A4 activity. Our results indicate that extracts of saw palmetto at generally recommended doses are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination. These conclusions must be weighed in the context of the study's limited assessments and regarded as only the initial investigation into the drug interaction potential of saw palmetto.

Exploiting the pyrazolo[3,4-d]pyrimidin-4-one ring system as a useful template to obtain potent adenosine deaminase inhibitors.

Science.gov (United States)

La Motta, Concettina; Sartini, Stefania; Mugnaini, Laura; Salerno, Silvia; Simorini, Francesca; Taliani, Sabrina; Marini, Anna Maria; Da Settimo, Federico; Lavecchia, Antonio; Novellino, Ettore; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado; Del Tacca, Mario

2009-03-26

A number of pyrazolo[3,4-d]pyrimidin-4-ones bearing either alkyl or arylalkyl substituents in position 2 of the nucleus were synthesized and tested for their ability to inhibit adenosine deaminase (ADA) from bovine spleen. The 2-arylalkyl derivatives exhibited excellent inhibitory activity, showing Ki values in the nanomolar/subnanomolar range. The most active compound, 1-(4-((4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidin-2-yl)methyl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea, 14d, was tested in rats with colitis induced by 2,4-dinitrobenzenesulfonic acid to assess its efficacy to attenuate bowel inflammation. The treatment with 14d induced a significant amelioration of both systemic and intestinal inflammatory alterations in animals with experimental colitis. Docking simulations of the synthesized compounds into the ADA catalytic site were also performed to rationalize the structure-activity relationships observed and to highlight the key pharmacophoric elements of these products, thus prospectively guiding the design of novel ADA inhibitors.

Interaction of the D-isomer of 4-methylene glutamate (4-MG) with an active site thiol group of γ-glutamylcysteine synthetase (γ-GCS)

International Nuclear Information System (INIS)

Simondsen, R.P.; Meister, A.

1986-01-01

γ-GCS has an SH-group at or close to the glutamate binding site. During efforts to find a covalently bound inhibitor, the authors examined interaction of the enzyme with 4-MG with the thought that a glutamate analog with an α,β-unsaturated moiety might bind to the glutamate site and react with the active site thiol. 4-MG is not a significant substrate, but inhibits in the usual assay. Preincubation of the enzyme with DL-4-MG inactivated markedly and to about the same extent as found after preincubation with half the concentration of D-4-MG (prepared by action of glutamate decarboxylase on DL-4-MG); L-4-MG did not inactivate. Inactivation by 4-MG was decreased in the presence of L-glutamate. Inactivation by 4-MG was prevented by prior treatment of the enzyme with cystamine, which forms a disulfide with the active site thiol. After inactivation of the enzyme with 4-[2- 14 C]MG followed by separation of the enzyme by gel filtration, 0.9 mole of label was found per mole of enzyme, amino acid analysis after acid hydrolysis of the labeled enzyme gave labeled products that include the expected adduct formed by reaction of cysteine with 4-MG

Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

Science.gov (United States)

Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

2007-12-01

Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.

Siloxane D4 capture by hydrophobic microporous materials

OpenAIRE

Mito-oka, Yasuko; Horike, Satoshi; Nishitani, Yusuke; Masumori, Tadao; Inukai, Munehiro; Hijikata, Yuh; Kitagawa, Susumu

2013-01-01

Porous substances, including crystalline coordination materials and an amorphous organic polymer, were studied for their selective adsorption of siloxane D4. The investigated materials demonstrated a level of uptake comparable to that of conventional activated carbon.

μ-τ symmetry and charged lepton mass hierarchy in a supersymmetric D4 model

International Nuclear Information System (INIS)

Hagedorn, C.; Ziegler, R.

2010-01-01

In this paper we discuss a supersymmetric D 4 xZ 5 model which leads to vanishing reactor mixing angle θ 13 =0 and maximal atmospheric mixing θ 23 =π/4 in the lepton sector at leading order, due to the preservation of nontrivial distinct D 4 subgroups in the charged lepton and neutrino sectors, respectively. The solar mixing angle θ 12 remains undetermined and is expected to be of order one. Since right-handed charged leptons transform as singlets under D 4 , the charged lepton mass hierarchy can be naturally accounted for. The model predicts inverted mass hierarchy for neutrinos. Additionally, we show that, unlike in most of the other models of this type, all vacuum expectation values of gauge singlets (flavons) can be determined through mass parameters of the superpotential. Next-to-leading order corrections to lepton masses and mixings are calculated and shown to be under control; in particular, the corrections to θ 23 =π/4 and θ 13 =0 are of the order of the generic expansion parameter ε≅0.04 and arise dominantly from the charged lepton sector.

Phase 1 report: the 4D seismic market from 2000 to 2003

International Nuclear Information System (INIS)

Sagary, C.

2004-01-01

This report synthesizes the phase 1 results of the joint industrial project, called ''4D Seismic: Technologies, Economics and Issues''. This project was conducted by IFP between November 2003 and April 2004, in collaboration with Compagnie Generale de Geophysique (CGG) and sponsored by Gaz de France and 4. Wave Imaging. Phase 1 offers an objective view of the 4D seismic market over the period 2000-2003. The market has been assessed from IFP extensive databases, gathering 115 4D projects conducted worldwide and from interviews of seven oil companies, both representing 90% of the activity in time-lapse seismic. This study provides sales estimation and sales/projects breakdown by: in-house/subcontracted activity, geography, onshore/offshore, reservoir rocks and recovery methods, technology/methodology, oil companies and service companies. The market of 4D seismic has been split into 4 segments: acquisition, processing, reservoir studies - feasibility, interpretation and seismic history matching -, borehole seismic (acquisition and processing). In addition, the market of passive seismic monitoring, another technique of seismic reservoir monitoring has also been estimated. The main sources, used to build the IFP databases, were: Worldwide Global E and P Service Reports from IHS Energy, World Geophysical News, an extensive bibliographic study through more than 200 articles, abstracts and summaries, a collaboration with CGG. For all market estimations, numbers computed from IFP databases and from interviews of oil companies were extrapolated from 90% to 100%, to quantify the total 4D activity. The estimations obtained were not rounded in order to preserve trends with a consistent computation from one year to another and from one market segment to another, despite uncertainties of about 10%. Quality controls were performed to validate the final estimations: volumes of 4D seismic data, computed from IFP databases, were checked by comparing processed data with acquired data

Tachyon condensation in the D0/D4 system

International Nuclear Information System (INIS)

David, Justin R.

2000-01-01

The D0/D4 system with a Neveu-Schwarz B-field in the spatial directions of the D4-brane has a tachyon in the spectrum of the (0,4) strings. The tachyon signals the instability of the system to form a bound state of the D0-brane with the D4-brane. We use the Wess-Zumino-Witten like open superstring field theory formulated by Berkovits to study the tachyon potential for this system. The tachyon potential lies outside the universality class of the D-brane anti-D-brane system. It is a function of the B-field. We calculate the tachyon potential at the zeroth level approximation. The minimum of the tachyon potential in this case is expected to reproduce the mass defect involved in the formation of the D0/D4 bound state. We compare the minimum of the tachyon potential with the mass defect in three cases. For small values of the B-field we obtain 70% of the expected mass defect. For large values of the B-field with Pf(2πα' B) > 0 the potential reduces to that of the D-brane anti-D-brane reproducing 62% of the expected mass defect. For large values of the B-field with Pf(2πα' B) < 0 the minimum of the tachyon potential gives 25% of the expected mass defect. At the tachyon condensate we show that the (0,4) strings decouple from the low energy dynamics. (author)

Deoxyfluoroketohexoses: 4-deoxy-4-fluoro-D-sorbose and -tagatose and 5-deoxy-5-fluoro-L-sorbose.

Science.gov (United States)

Rao, G V; Que, L; Hall, L D; Fondy, T P

1975-04-01

4-Deoxy-4-fluoro-alpha-D-sorbose (6) was prepared in crystalline form by the action of potassium hydrogen fluoride on 3,4-anhydro-1,2-O-isopropylidene-beta-D-psicopyranose (3) followed by deacetonation. Under identical conditions, 3,4-anhydro-1,2-O-isopropylidene-beta-D-tagatopyranose (7) underwent epoxide migration to give 4,5-anhydro-1,2-O-isopropylidene-beta-D-fructopyranose (12), which after deacetonation yielded 4-deoxy-4-fluoro-D-tagatose (15) and 5-deoxy-5-fluoro-alpha-L-sorbopyranose (16), the latter as the crystalline, free sugar. The action of glycol-cleavage reagents on the isopropylidene acetals of the deoxyfluoro sugars was consistent with the assigned structures. The structures were established by 13-C n.m.r. studies of the free deoxyfluoro sugars 6 and 16 and of the isopropylidene acetal 13, and by 1-H n.m.r. studies on the acetylated isopropylidene acetals 5 diacetate, 13 diacetate, and 14 diacetate. 5-Deoxy-5-fluoro-L-sorbose (16) was biologically active, producing in mice effects characteristic of deoxyfluorotrioses and of fluoroacetate. 4-Deoxy-4-fluoro-D-tagatose (15) and 4-deoxy-4-fluoro-D-sorbose (6) produced no apparent effects in mice up to a dose of 500mg/kg. The implications of these findings with respect to transport, phosphorylation, and the action of aldolase on ketohexoses are discussed.

4D modeling in high-rise construction

Science.gov (United States)

Balakina, Anastasiya; Simankina, Tatyana; Lukinov, Vitaly

2018-03-01

High-rise construction is a complex construction process, requiring the use of more perfected and sophisticated tools for design, planning and construction management. The use of BIM-technologies allows minimizing the risks associated with design errors and errors that occur during construction. This article discusses a visual planning method using the 4D model, which allows the project team to create an accurate and complete construction plan, which is much more difficult to achieve with the help of traditional planning methods. The use of the 4D model in the construction of a 70-story building allowed to detect spatial and temporal errors before the start of construction work. In addition to identifying design errors, 4D modeling has allowed to optimize the construction, as follows: to optimize the operation of cranes, the placement of building structures and materials at various stages of construction, to optimize the organization of work performance, as well as to monitor the activities related to the preparation of the construction site for compliance with labor protection and safety requirements, which resulted in saving money and time.

4D monitoring of actively failing rockslopes

Science.gov (United States)

Rosser, Nick; Williams, Jack; Hardy, Richard; Brain, Matthew

2017-04-01

Assessing the conditions which promote rockfall to collapse relies upon detailed monitoring, ideally before, during and immediately after failure. With standard repeat surveys it is common that surveys do not coincide with or capture precursors, or that surveys are widely spaced relative to the timing and duration of driving forces such as storms. As a result gaining insight into the controls on failure and the timescales over which precursors operate remains difficult to establish with certainty, and establishing direct links between environmental conditions and rock-falls, or sequences of events prior to rockfall, remain difficult to define. To address this, we present analysis of a high-frequency 3D laser scan dataset captured using a new permanently installed system developed to constantly monitor actively failing rock slopes. The system is based around a time of flight laser scanner, integrated with and remotely controlled by dedicated controls and analysis software. The system is configured to capture data at 0.1 m spacing across > 22,000 m3 at up to 30 minute intervals. Here we present results captured with this system over a period of 9 months, spanning spring to winter 2015. Our analysis is focussed upon improving the understanding of the nature of small (volumetric measurement of rock face erosion. The results hold implications for understanding of rockfall mechanics, but also for how actively eroding surfaces can be monitored at high temporal frequency. Whilst high frequency data is ideal for describing processes that evolve rapidly through time, the cumulative errors that accumulate when monitored changes are dominated by inverse power-law distributed volumes are significant. To conclude we consider the benefits of defining survey frequency on the basis of the changes being detected relative to the accumulation of errors that inevitably arises when comparing high numbers of sequential surveys.

Synthesis of cyclophosphamide-4,4,5,5-d4

International Nuclear Information System (INIS)

Walsh, S.P.; Chang, Y.H.; Ludeman, S.M.

1995-01-01

3-Hydroxypropionitrile was subjected to a base-catalyzed exchange reaction in D 2 O which provided 2,2-dideuterio-3-deuteroxypropionitrile (DOCH 2 CD 2 CN) in 70% yield. Reduction of the nitrile with LiAID 4 gave 3-amino-2,2,3,3-tetradeuteriopropan-1-ol (HOCH 2 CD 2 CD 2 NH 2 ) in a crude yield of 71%. Reaction of this intermediate with N,N-bis(2-chloroethyl)phosphoramidic dichloride [Cl 2 P(O)N(CH 2 CH 2 Cl) 2 ] followed by the combination of those chromatography fractions which contained only pure material gave cyclophosphamide-4,4,5,5-d 4 as a white oil in 13% yield. A portion of this oil was converted to the monohydrate by the addition of water (1.1 equivalents) and crystallization from ether/petroleum ether (62% yield). For the hydrate, MS analyses gave an average mole percent enrichment (with average deviation over 5 determinations) of 89.1 ± 0.5% d 4 . (author)

Elevation of D4 dopamine receptor mRNA in postmortem schizophrenic brain.

Science.gov (United States)

Stefanis, N C; Bresnick, J N; Kerwin, R W; Schofield, W N; McAllister, G

1998-01-01

The D4 dopamine (DA) receptor has been proposed to be a target for the development of a novel antipsychotic drug based on its pharmacological and distribution profile. There is much interest in whether D4 DA receptor levels are altered in schizophrenia, but the lack of an available receptor subtype-specific radioligand made this difficult to quantitate. In this study, we examined whether D4 mRNA levels are altered in different brain regions of schizophrenics compared to controls. Ribonuclease protection assays were carried out on total RNA samples isolated postmortem from frontal cortex and caudate brain regions of schizophrenics and matched controls. 32P-labelled RNA probes to the D4 DA receptor and to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), were hybridised with the RNA samples, digested with ribonucleases to remove unhybridised probe, and separated on 6% sequencing gels. Densitometer analysis on the subsequent autoradiogams was used to calculate the relative optical density of D4 mRNA compared to G3PDH mRNA. Statistical analysis of the data revealed a 3-fold higher level (P<0.011) of D4 mRNA in the frontal cortex of schizophrenics compared to controls. No increase was seen in caudate. D4 receptors could play a role in mediating dopaminergic activity in frontal cortex, an activity which may be malfunctioning in schizophrenia.

A self-assembled 2D/2D-type protonated carbon nitride-modified graphene oxide nanocomposite with improved photocatalytic activity

Science.gov (United States)

Xie, Linfang; Ni, Jie; Tang, Bo; He, Guangyu; Chen, Haiqun

2018-03-01

A surface charge modified g-C3N4 was successfully prepared by protonation of nitric acid. Combination of the protonated g-C3N4 (pCN) and graphene oxide (GO) layers created a 2D/2D-type composite (pCN/GO) under the synergistic effect of sonication-exfoliation and self-assembly. The obtained 2D nanostructure of pCN/GO was explored by electron microscopy analysis. The photocatalytic degradation of rhodamine B (RhB) and ciprofloxacin (CIP) showed a distinctly high efficiency of pCN/GO-5% with excellent stability, which is superior not only to that of g-C3N4, pCN and g-C3N4/GO-5% nanocomposites we prepared, but also to what was reported previously. The optimized combination of GO and pCN afforded the pCN/GO composite intimate interfacial contact within the heterojunction, which promoted the separation of photogenerated electron-hole pairs as evidenced by zeta potential, photoluminescence and photocurrent measurements. A visible-light photocatalytic degradation mechanism associated with pCN/GO nanocomposites was also proposed.

Biokinetic Analysis and Metabolic Fate of 2,4-D in 2,4-D-Resistant Soybean (Glycine max).

Science.gov (United States)

Skelton, Joshua J; Simpson, David M; Peterson, Mark A; Riechers, Dean E

2017-07-26

The Enlist weed control system allows the use of 2,4-D in soybean but slight necrosis in treated leaves may be observed in the field. The objectives of this research were to measure and compare uptake, translocation, and metabolism of 2,4-D in Enlist (E, resistant) and non-AAD-12 transformed (NT, sensitive) soybeans. The adjuvant from the Enlist Duo herbicide formulation (ADJ) increased 2,4-D uptake (36%) and displayed the fastest rate of uptake (U 50 = 0.2 h) among treatments. E soybean demonstrated a faster rate of 2,4-D metabolism (M 50 = 0.2 h) compared to NT soybean, but glyphosate did not affect 2,4-D metabolism. Metabolites of 2,4-D in E soybean were qualitatively different than NT. Applying 2,4-D-ethylhexyl ester instead of 2,4-D choline (a quaternary ammonium salt) eliminated visual injury to E soybean, likely due to the time required for initial de-esterification and bioactivation. Excessive 2,4-D acid concentrations in E soybean resulting from ADJ-increased uptake may significantly contribute to foliar injury.

An activity canyon characterization of the pharmacological topography.

Science.gov (United States)

Kulkarni, Varsha S; Wild, David J

2016-01-01

Highly chemically similar drugs usually possess similar biological activities, but sometimes, small changes in chemistry can result in a large difference in biological effects. Chemically similar drug pairs that show extreme deviations in activity represent distinctive drug interactions having important implications. These associations between chemical and biological similarity are studied as discontinuities in activity landscapes. Particularly, activity cliffs are quantified by the drop in similar activity of chemically similar drugs. In this paper, we construct a landscape using a large drug-target network and consider the rises in similarity and variation in activity along the chemical space. Detailed analysis of structure and activity gives a rigorous quantification of distinctive pairs and the probability of their occurrence. We analyze pairwise similarity (s) and variation (d) in activity of drugs on proteins. Interactions between drugs are quantified by considering pairwise s and d weights jointly with corresponding chemical similarity (c) weights. Similarity and variation in activity are measured as the number of common and uncommon targets of two drugs respectively. Distinctive interactions occur between drugs having high c and above (below) average d (s). Computation of predicted probability of distinctiveness employs joint probability of c, s and of c, d assuming independence of structure and activity. Predictions conform with the observations at different levels of distinctiveness. Results are validated on the data used and another drug ensemble. In the landscape, while s and d decrease as c increases, d maintains value more than s. c ∈ [0.3, 0.64] is the transitional region where rises in d are significantly greater than drops in s. It is fascinating that distinctive interactions filtered with high d and low s are different in nature. It is crucial that high c interactions are more probable of having above average d than s. Identification of

Syntheses of two potential dopamine D{sub 4} receptor radioligands: {sup 18}F labelled chromeno[3,4-c]pyridin-5-ones

Energy Technology Data Exchange (ETDEWEB)

Gu-Cai Li; Duan-Zhi Yin; Ming-Wei Wang; Deng-Feng Cheng; Yong-Xian Wang [Research Center of Radiopharmaceuticals, Shanghai Inst. of Applied Physics, Chinese Academy of Sciences, Shanghai, SH (China)

2006-07-01

The dopamine D{sub 4} receptor is hypothesized to relate with the pathophysiology and pharmacotherapy of schizophrenia while its level in brain regions is much lower and to date no suitable tracer is available for the study of D{sub 4} receptor in vivo. Therefore, selective imaging agents for the D{sub 4} subtype are badly needed. Based on the structure-activity analysis of chromeno[3,4-c]pyridin-5-ones as dopamine D{sub 4} receptor ligands, two fluorine-18 labelled chromeno[3,4-c] pyridin-5-one derivatives, 3-(4-[{sup 18}F]fluorobenzyl)-8-hydroxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one and 3-(4-[{sup 18}F]fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one were synthesized through a two-step one-pot method. Their radiochemical yields were around 19.7% (decay-corrected) and radiochemical purities were higher than 95% with specific activities of about 120 GBq/{mu}mol. (orig.)

Triple shape memory polymers by 4D printing

Science.gov (United States)

Bodaghi, M.; Damanpack, A. R.; Liao, W. H.

2018-06-01

This article aims at introducing triple shape memory polymers (SMPs) by four-dimensional (4D) printing technology and shaping adaptive structures for mechanical/bio-medical devices. The main approach is based on arranging hot–cold programming of SMPs with fused decomposition modeling technology to engineer adaptive structures with triple shape memory effect (SME). Experiments are conducted to characterize elasto-plastic and hyper-elastic thermo-mechanical material properties of SMPs in low and high temperatures at large deformation regime. The feasibility of the dual and triple SMPs with self-bending features is demonstrated experimentally. It is advantageous in situations either where it is desired to perform mechanical manipulations on the 4D printed objects for specific purposes or when they experience cold programming inevitably before activation. A phenomenological 3D constitutive model is developed for quantitative understanding of dual/triple SME of SMPs fabricated by 4D printing in the large deformation range. Governing equations of equilibrium are established for adaptive structures on the basis of the nonlinear Green–Lagrange strains. They are then solved by developing a finite element approach along with an elastic-predictor plastic-corrector return map procedure accomplished by the Newton–Raphson method. The computational tool is applied to simulate dual/triple SMP structures enabled by 4D printing and explore hot–cold programming mechanisms behind material tailoring. It is shown that the 4D printed dual/triple SMPs have great potential in mechanical/bio-medical applications such as self-bending gripers/stents and self-shrinking/tightening staples.

Sepsis Induces Hematopoietic Stem Cell Exhaustion and Myelosuppression through Distinct Contributions of TRIF and MYD88

Directory of Open Access Journals (Sweden)

Huajia Zhang

2016-06-01

Full Text Available Toll-like receptor 4 (TLR4 plays a central role in host responses to bacterial infection, but the precise mechanism(s by which its downstream signaling components coordinate the bone marrow response to sepsis is poorly understood. Using mice deficient in TLR4 downstream adapters MYD88 or TRIF, we demonstrate that both cell-autonomous and non-cell-autonomous MYD88 activation are major causes of myelosuppression during sepsis, while having a modest impact on hematopoietic stem cell (HSC functions. In contrast, cell-intrinsic TRIF activation severely compromises HSC self-renewal without directly affecting myeloid cells. Lipopolysaccharide-induced activation of MYD88 or TRIF contributes to cell-cycle activation of HSC and induces rapid and permanent changes in transcriptional programs, as indicated by persistent downregulation of Spi1 and CebpA expression after transplantation. Thus, distinct mechanisms downstream of TLR4 signaling mediate myelosuppression and HSC exhaustion during sepsis through unique effects of MyD88 and TRIF.

Temperature-controlled two new Co(II) compounds with distinct topological networks: Syntheses, crystal structures and catalytic properties

Science.gov (United States)

Meng, Qing-Hua; Long, Xu; Liu, Jing-Li; Zhang, Shuan; Zhang, Guang-Hui

2018-04-01

Two new Co(II) coordination compounds, namely [Co2(bptc)(bpp)2]n (1) and [Co(bptc)0.5(bpp)]n (2) (H4bptc = biphenyl-3,3‧,5,5‧-tetracarboxylic acid, bpp = 1,3-di(4-pyridyl)propane), have been hydrothermally synthesized from the same reactants via tuning the reaction temperature. Single crystal X-ray diffraction analyses revealed that both 1 and 2 feature 2D sheet motifs. Topological analyses revealed that compounds 1 and 2 show distinct topological networks. Under the weak Van der Waals interactions, the 2D sheet motifs of compounds 1 and 2 are further packed into 2D→3D interdigitated supramolecular frameworks. Moreover, the two Co(II) compounds show high catalytic activities for degradation of methyl orange (MO) in a Fenten-like process.

3D-printed optical active components

Science.gov (United States)

Suresh Nair, S.; Nuding, J.; Heinrich, A.

2018-02-01

Additive Manufacturing (AM) has the potential to become a powerful tool in the realization of complex optical components. The primary advantage that meets the eye, is that fabrication of geometrically complicated optical structures is made easier in AM as compared to the conventional fabrication methods (using molds for instance). But this is not the only degree of freedom that AM has to offer. With the multitude of materials suitable for AM in the market, it is possible to introduce functionality into the components one step before fabrication: by altering the raw material. A passive example would be to use materials with varying properties together, in a single manufacturing step, constructing samples with localized refractive indices for instance. An active approach is to blend in materials with distinct properties into the photopolymer resin and manufacturing with this composite material. Our research is currently focused in this direction, with the desired optical property to be introduced being Photoluminescence. Formation of nanocomposite mixtures to produce samples is the current approach. With this endeavor, new sensor systems can be realized, which may be used to measure the absorption spectra of biological samples. Thereby the sample compartment, the optics and the spectral light source (different quantum dots) are 3D-printed in one run. This component can be individually adapted to the biological sample with respect to wavelength, optical and mechanical properties. Here we would like to present our work on the additive manufacturing of an active optical component. Based on the stereolithography method, a monolithic optical component was 3D-printed, showing light emission at different defined wavelengths due to UV excited quantum dots inside the 3D-printed optics.

Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

International Nuclear Information System (INIS)

Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

2004-01-01

The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

Synthesis and Anti-hyperlipidemic Activity of 3H-benzo [4, 5] thieno [2, 3-d] [1, 2, 3] triazin-4-ones: Possible Mechanism of Altered Lipid Metabolism

Directory of Open Access Journals (Sweden)

Gollapalle L. Viswanatha

2012-09-01

Full Text Available Objectives: The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 (3-(methyl-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one, CP-2 (3-(ethyl- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno[2,3-d][1,2,3] triazin-4-one and CP-6 (3-(2-chloro phenyl-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one against dexamethasone and Triton WR-1339-induced hyper-lipidemia in rats.Methods: Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone (10 mg/kg, subcutaneous [s.c.] and Triton WR-1339 (200 mg/kg, intraperitoneal [i.p] induced hyperlipidemia in rats.Results: Administration of single dose of Triton WR-1339 (200 mg/kg i.p and dexamethasone (10 mg/kg s.c. for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compare to normal control. Pretreatment with Atorvastatin (10 mg/kg, p.o., CP-1 (25 & 50 mg/kg, CP-2 (25 & 50 mg/kg and CP-6 (25 & 50mg/kg showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2.Conclusion: These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia.

Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

Directory of Open Access Journals (Sweden)

Kristina Kirschner

2015-03-01

Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

4D modeling in high-rise construction

Directory of Open Access Journals (Sweden)

Balakina Anastasiya

2018-01-01

Full Text Available High-rise construction is a complex construction process, requiring the use of more perfected and sophisticated tools for design, planning and construction management. The use of BIM-technologies allows minimizing the risks associated with design errors and errors that occur during construction. This article discusses a visual planning method using the 4D model, which allows the project team to create an accurate and complete construction plan, which is much more difficult to achieve with the help of traditional planning methods. The use of the 4D model in the construction of a 70-story building allowed to detect spatial and temporal errors before the start of construction work. In addition to identifying design errors, 4D modeling has allowed to optimize the construction, as follows: to optimize the operation of cranes, the placement of building structures and materials at various stages of construction, to optimize the organization of work performance, as well as to monitor the activities related to the preparation of the construction site for compliance with labor protection and safety requirements, which resulted in saving money and time.

Accelerated 4D phase contrast MRI in skeletal muscle contraction.

Science.gov (United States)

Mazzoli, Valentina; Gottwald, Lukas M; Peper, Eva S; Froeling, Martijn; Coolen, Bram F; Verdonschot, Nico; Sprengers, Andre M; van Ooij, Pim; Strijkers, Gustav J; Nederveen, Aart J

2018-03-05

3D time-resolved (4D) phase contrast MRI can be used to study muscle contraction. However, 3D coverage with sufficient spatiotemporal resolution can only be achieved by interleaved acquisitions during many repetitions of the motion task, resulting in long scan times. The aim of this study was to develop a compressed sensing accelerated 4D phase contrast MRI technique for quantification of velocities and strain rate of the muscles in the lower leg during active plantarflexion/dorsiflexion. Nine healthy volunteers were scanned during active dorsiflexion/plantarflexion task. For each volunteer, we acquired a reference scan, as well as 4 different accelerated scans (k-space undersampling factors: 3.14X, 4.09X, 4.89X, and 6.41X) obtained using Cartesian Poisson disk undersampling schemes. The data was reconstructed using a compressed sensing pipeline. For each scan, velocity and strain rate values were quantified in the gastrocnemius lateralis, gastrocnemius medialis, tibialis anterior, and soleus. No significant differences in velocity values were observed as a function acceleration factor in the investigated muscles. The strain rate calculation resulted in one positive (s + ) and one negative (s - ) eigenvalue, whereas the third eigenvalue (s 3 ) was consistently 0 for all the acquisitions. No significant differences were observed for the strain rate eigenvalues as a function of acceleration factor. Data undersampling combined with compressed sensing reconstruction allowed obtainment of time-resolved phase contrast acquisitions with 3D coverage and quantitative information comparable to the reference scan. The 3D sensitivity of the method can help in understanding the connection between muscle architecture and muscle function in future studies. © 2018 International Society for Magnetic Resonance in Medicine.

Distinct and overlapping effector functions of expanded human CD4+, CD8α+ and CD4-CD8α- invariant natural killer T cells.

Directory of Open Access Journals (Sweden)

Vincent O'Reilly

Full Text Available CD1d-restricted invariant natural killer T (iNKT cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. Activation of iNKT cells can protect against multiple diseases in mice but clinical trials in humans have had limited impact. Clinical studies to date have targeted polyclonal mixtures of iNKT cells and we proposed that their subset compositions will influence therapeutic outcomes. We sorted and expanded iNKT cells from healthy donors and compared the phenotypes, cytotoxic activities and cytokine profiles of the CD4(+, CD8α(+ and CD4(-CD8α(- double-negative (DN subsets. CD4(+ iNKT cells expanded more readily than CD8α(+ and DN iNKT cells upon mitogen stimulation. CD8α(+ and DN iNKT cells most frequently expressed CD56, CD161 and NKG2D and most potently killed CD1d(+ cell lines and primary leukemia cells. All iNKT subsets released Th1 (IFN-γ and TNF-α and Th2 (IL-4, IL-5 and IL-13 cytokines. Relative amounts followed a CD8α>DN>CD4 pattern for Th1 and CD4>DN>CD8α for Th2. All iNKT subsets could simultaneously produce IFN-γ and IL-4, but single-positivity for IFN-γ or IL-4 was strikingly rare in CD4(+ and CD8α(+ fractions, respectively. Only CD4(+ iNKT cells produced IL-9 and IL-10; DN cells released IL-17; and none produced IL-22. All iNKT subsets upregulated CD40L upon glycolipid stimulation and induced IL-10 and IL-12 secretion by dendritic cells. Thus, subset composition of iNKT cells is a major determinant of function. Use of enriched CD8α(+, DN or CD4(+ iNKT cells may optimally harness the immunoregulatory properties of iNKT cells for treatment of disease.

Generalized Choriocapillaris Dystrophy, a Distinct Phenotype in the Spectrum of ABCA4-Associated Retinopathies

DEFF Research Database (Denmark)

Bertelsen, Mette; Zernant, Jana; Larsen, Michael

2014-01-01

PURPOSE: We describe a particular form of autosomal recessive generalized choriocapillaris dystrophy phenotype associated with ABCA4 mutations. METHODS: A cohort of 30 patients with identified ABCA4 mutations and a distinct phenotype was studied. A retrospective review of history, fundus photogra......PURPOSE: We describe a particular form of autosomal recessive generalized choriocapillaris dystrophy phenotype associated with ABCA4 mutations. METHODS: A cohort of 30 patients with identified ABCA4 mutations and a distinct phenotype was studied. A retrospective review of history, fundus...... photographs, electroretinography, visual field testing, dark adaptometry, and optical coherence tomography was performed. Genetic analyses were performed by ABCA4 microarray analysis, high resolution melting, and/or next generation sequencing of all protein-coding sequences of the ABCA4 gene. RESULTS...

Absolute measurement of a standard thermal-neutron flux using gold-detector activation; Mesure absolue d'un flux etalon de neutrons thermiques par activation de detecteurs d'or

Energy Technology Data Exchange (ETDEWEB)

Paternot, Y [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1967-02-15

The density of neutrons in a standard stacking is determined between the zero-energy and the cut-off energy of 1 mm thick cadmium unit using a gold detector. Its absolute activity is measured using a 4 {pi} {beta} counter calibrated for 4 {pi} {beta},{gamma} coincidence by counting strongly active sources. The correction factor F due to the disintegration process for the gold is determined experimentally. {phi}{sub 0} = N{sub 0} {sup E}Cd{sub V0} = 6495 {+-} 1.5 per cent n/cm{sup 2}/s. (author) [French] La densite de neutrons dans un empilement etalon est determinee entre l'energie zero et l'energie de coupure d'un boitier de cadmium de 1 mm d'epaisseur au moyen d'un detecteur d'or. Son activite absolue est mesuree a l'aide d'un compteur 4 {pi} {beta} etalonne en coincidence 4 {pi} {beta},{gamma} par comptage de sources fortement actives. Le facteur de correction F d au schema de desintegration de l'or est determine experimentalement. {phi}{sub 0} = N{sub 0} {sup E}Cd{sub V0} = 6495 {+-} 1.5 pour cent n/cm{sup 2}/s. (auteur)

Cyclin D3 interacts with vitamin D receptor and regulates its transcription activity

International Nuclear Information System (INIS)

Jian Yongzhi; Yan Jun; Wang Hanzhou; Chen Chen; Sun Maoyun; Jiang Jianhai; Lu Jieqiong; Yang Yanzhong; Gu Jianxin

2005-01-01

D-type cyclins are essential for the progression through the G1 phase of the cell cycle. Besides serving as cell cycle regulators, D-type cyclins were recently reported to have transcription regulation functions. Here, we report that cyclin D3 is a new interacting partner of vitamin D receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and the fat-soluble vitamins A and D. The interaction was confirmed with methods of yeast two-hybrid system, in vitro binding analysis and in vivo co-immunoprecipitation. Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction. Confocal microscopy analysis showed that ligand-activated VDR led to an accumulation of cyclin D3 in the nuclear region. Cyclin D3 up-regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. These findings provide us a new clue to understand the transcription regulation functions of D-type cyclins

Differences of statin activity in 2D and 3D pancreatic cancer cell cultures

Directory of Open Access Journals (Sweden)

Paškevičiūtė M

2017-11-01

Full Text Available Miglė Paškevičiūtė,1 Vilma Petrikaitė1,21Department of Drug Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, Kaunas, Lithuania; 2Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, LithuaniaPurpose: To evaluate the anticancer activity of lovastatin (LOVA, mevastatin (MEVA, pitavastatin (PITA, and simvastatin (SIMVA in 2D and 3D models of three human pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and PANC-1.Methods: The effect of statins on cell viability was estimated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide test. The activity of statins in 3D pancreatic cancer cell cultures was examined by measuring the size change of spheroids. The type of cell death was identified by cell staining with Hoechst 33342 and propidium iodide. The activity of statins on the clonogenicity of cancer cells was tested by evaluating the effect on the colony-forming ability of cells.Results: The rank order of the activity of tested statins on cell viability was as follows: PITA > SIMVA > LOVA > MEVA. Among the tested statins, PITA had the greatest effect on cell viability (half maximal effective concentration values after 72 h on BxPC-3, MIA PaCa-2, and PANC-1 cells were 1.4±0.4 µM, 1.0±0.2 µM, and 1.0±0.5 µM, respectively. PITA also showed the strongest effect on tumor spheroid growth. Statins suppressed the colony formation of cancer cells. PITA demonstrated the greatest reduction in colony size and number. Apoptosis and necrosis assay results showed that at lower concentrations statins mostly induced cell death through apoptosis, whereas higher concentrations of compounds activated also necrotic processes.Conclusion: Statins, especially PITA, demonstrate an anticancer activity against pancreatic cancer cell lines BxPC-3, MIA PaCa-2, and PANC-1 in both 2D and 3D models.Keywords: HMG-CoA reductase, cell viability, spheroid, apoptosis

Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum

Directory of Open Access Journals (Sweden)

Decker BS

2013-12-01

Full Text Available Brian S Decker,1,2 Kalisha D O'Neill,1,2 Mary A Chambers,1,2 James E Slaven,3 Zhangsheng Yu,3 David R Jones,2,4 Sharon M Moe1,21Division of Nephrology, 2Department of Medicine, 3Department of Biostatistics, 4Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USAAbstract: There is a paucity of studies evaluating the change in liver metabolism in subjects receiving hemodialysis. The purpose of this study was to compare the effect of uremic toxins on hepatic cytochrome P450 (CYP3A4 and CYP2D6 metabolism before and after a 4-hour hemodialysis session. Midazolam and dextromethorphan were incubated with uremic serum collected from subjects before and after the 4-hour hemodialysis session. Analysis and quantification of the 1'-OH-midazolam and 4-OH-midazolam and dextrorphan metabolites were performed by high-pressure liquid chromatography/mass spectrometry. Statistical analysis using the Student's t-test (paired was used to compare the amount of metabolite formed. The mean amount of 1'-OH-midazolam, 4-OH-midazolam, and dextrorphan metabolites formed before and after hemodialysis did not significantly differ. There was no significant difference in CYP3A4 and CYP2D6 metabolic activity in uremic serum before and after hemodialysis.Keywords: hemodialysis, uremia, CYP3A4, CYP2D6, metabolism

The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4B.

Science.gov (United States)

Lapinski, Philip E; Oliver, Jennifer A; Bodie, Jennifer N; Marti, Francesc; King, Philip D

2009-11-01

Adapter proteins play key roles in intracellular signal transduction through complex formation with catalytically active signaling molecules. In T lymphocytes, the role of several different types of adapter proteins in T-cell antigen receptor signal transduction is well established. An exception to this is the family of T-cell-specific adapter (TSAd) proteins comprising of TSAd, adapter protein of unknown function (ALX), SH2D4A, and SH2D4B. Only recently has the function of these adapters in T-cell signal transduction been explored. Here, we discuss advances in our understanding of the role of this family of adapter proteins in T cells. Their function as regulators of signal transduction in other cell types is also discussed.

Solvent-free microwave-assisted synthesis of novel pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines with potential antifungal activity

Directory of Open Access Journals (Sweden)

Paola Acosta

2016-05-01

Full Text Available Novel fused pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines 5 were prepared by a solvent-free microwave assisted reaction of heterocyclic o-aminonitriles 3 and cyanopyridines 4 in the presence of tBuOK as catalyst. This protocol provides a versatile procedure for the synthesis of the title compounds with the advantages of easy work-up, mild reaction conditions and good yields. All compounds were also tested for antifungal properties against two clinically important fungi; Candida albicans and Cryptococcus neoformans. Several compounds showed moderate activity against both fungi, being 5a the most active compound. Analysis of the antifungal behavior of properly grouped compounds allowed to determine that the position of the N in the pyrimidyl moiety per se does not play a role in the activity. In turn, the type of 4-R substituent appears to influence the activity. In addition to the above considerations, the lipophilicity of compounds measured as logP showed to be not related to the activity and regarding the dipole moment (D, no net correlation was observed, although it is the most active compounds (% inhibition >50% that have a D ⩾ 7.5, mainly against C. albicans.

The co-stimulatory effects of MyD88-dependent Toll-like receptor signaling on activation of murine γδ T cells.

Directory of Open Access Journals (Sweden)

Jinping Zhang

Full Text Available γδ T cells express several different toll-like receptor (TLRs. The role of MyD88- dependent TLR signaling in TCR activation of murine γδ T cells is incompletely defined. Here, we report that Pam3CSK4 (PAM, TLR2 agonist and CL097 (TLR7 agonist, but not lipopolysaccharide (TLR4 agonist, increased CD69 expression and Th1-type cytokine production upon anti-CD3 stimulation of γδ T cells from young adult mice (6-to 10-week-old. However, these agonists alone did not induce γδ T cell activation. Additionally, we noted that neither PAM nor CL097 synergized with anti-CD3 in inducing CD69 expression on γδ T cells of aged mice (21-to 22-month-old. Compared to young γδ T cells, PAM and CL097 increased Th-1 type cytokine production with a lower magnitude from anti-CD3- stimulated, aged γδ T cells. Vγ1+ and Vγ4+ cells are two subpopulations of splenic γδ T cells. PAM had similar effects in anti-CD3-activated control and Vγ4+ subset- depleted γδ T cells; whereas CL097 induced more IFN-γ production from Vγ4+ subset-depleted γδ T cells than from the control group. Finally, we studied the role of MyD88-dependent TLRs in γδ T cell activation during West Nile virus (WNV infection. γδ T cell, in particular, Vγ1+ subset expansion was significantly reduced in both MyD88- and TLR7- deficient mice. Treatment with TLR7 agonist induced more Vγ1+ cell expansion in wild-type mice during WNV infection. In summary, these results suggest that MyD88-dependent TLRs provide co-stimulatory signals during TCR activation of γδ T cells and these have differential effects on distinct subsets.

Summary report for ITER Task -- D4: Activation calculations for the stainless steel ITER design

International Nuclear Information System (INIS)

Attaya, H.

1995-02-01

Detailed activation analysis for ITER has been performed as a part of ITER Task D4. The calculations have been performed for the shielding blanket (SS/water) and for the breeding blanket (LiN) options. The activation code RACC-P, which has been modified under IFER Task-D-10 for pulsed operation, has been used in this analysis. The spatial distributions of the radioactive inventory, decay heat, biological hazard potential, and the contact dose were calculated for the two designs for different operation modes and targeted fluences. A one-dimensional toroidal geometrical model has been utilized to determine the neutron fluxes in the two designs. The results are normalized for an inboard and outboard neutron wall loadings of 0.91 and 1.2 MW/M 2 , respectively. The point-wise distributions of the decay gamma sources have been calculated everywhere in the reactor at several times after the shutdown of the two designs and are then used in the transport code ONEDANT to calculate the biological dose everywhere in the reactor. The point-wise distributions of all the responses have also been calculated. These calculations have been performed for neutron fluences of 3.0 MWa/M 2 , which corresponds to the target fluence of ITER, and 0.1 MWa/M 2 , which is anticipated to correspond to the beginning of an extended maintenance period

Effect of Garden Cress Seeds Powder and Its Alcoholic Extract on the Metabolic Activity of CYP2D6 and CYP3A4

Directory of Open Access Journals (Sweden)

Fahad I. Al-Jenoobi

2014-01-01

Full Text Available The powder and alcoholic extract of dried seeds of garden cress were investigated for their effect on metabolic activity of CYP2D6 and CYP3A4 enzymes. In vitro and clinical studies were conducted on human liver microsomes and healthy human subjects, respectively. Dextromethorphan was used as a common marker for measuring metabolic activity of CYP2D6 and CYP3A4 enzymes. In in vitro studies, microsomes were incubated with NADPH in presence and absence of different concentrations of seeds extract. Clinical investigations were performed in two phases. In phase I, six healthy female volunteers were administered a single dose of dextromethorphan and in phase II volunteers were treated with seeds powder for seven days and dextromethorphan was administered with last dose. The O-demethylated and N-demethylated metabolites of dextromethorphan were measured as dextrorphan (DOR and 3-methoxymorphinan (3-MM, respectively. Observations suggested that garden cress inhibits the formation of DOR and 3-MM metabolites. This inhibition of metabolite level was attributed to the inhibition of CYP2D6 and CYP3A4 activity. Garden cress decreases the level of DOR and 3-MM in urine and significantly increases the urinary metabolic ratio of DEX/DOR and DEX/3-MM. The findings suggested that garden cress seeds powder and ethanolic extract have the potential to interact with CYP2D6 and CYP3A4 substrates.

The clinical and genomic significance of donor-specific antibody-positive/C4d-negative and donor-specific antibody-negative/C4d-negative transplant glomerulopathy.

Science.gov (United States)

Hayde, Nicole; Bao, Yi; Pullman, James; Ye, Bin; Calder, R Brent; Chung, Monica; Schwartz, Daniel; Lubetzky, Michelle; Ajaimy, Maria; de Boccardo, Graciela; Akalin, Enver

2013-12-01

This study investigated the mechanisms involved in development of donor-specific antibody (DSA) and/or C4d-negative transplant glomerulopathy (TGP) by allograft gene expression profiles using microarrays. This cohort study was conducted in kidney transplant recipients. Patients were eligible for inclusion if they required a clinically indicated biopsy at any time point after their transplant. They were then classified according to their histopathology findings and DSA and C4d results. Eighteen chronic antibody-mediated rejection (CAMR), 14 DSA+/C4d- TGP, 25 DSA-/C4d- TGP, and 47 nonspecific interstitial fibrosis/tubular atrophy (IFTA) biopsy specimens were identified. In a subset of patients from the study population, biopsy specimens in each group and normal transplant kidney specimens were analyzed with Affymetrix Human Gene 1.0 ST Arrays. The mean sum score of glomerulitis and peritubular capillaritis increased from 0.28±0.78 in IFTA specimens to 0.75±0.85 in DSA-/C4d- TGP specimens, 1.71±1.49 in DSA+/C4d-/TGP specimens, and 2.11±1.74 in CAMR specimens (PTGP specimens (14.3%), and DSA-/C4d- TGP specimens (16%) (P=0.01). With use of microarrays, comparison of the gene expression profiles of DSA-/C4d- TGP specimens with glomerulitis + peritubular capillaritis scores > 0 to normal and IFTA biopsy specimens revealed higher expression of quantitative cytotoxic T cell-associated transcripts (QCAT). However, both CAMR and DSA+/C4d- TGP specimens had higher expression of not only QCAT but also IFN-γ and rejection-induced, constitutive macrophage-associated, natural killer cell-associated, and DSA-selective transcripts. Endothelial cell-associated transcript expression was upregulated only in CAMR biopsy specimens. These results suggested that DSA+/C4d- TGP biopsy specimens may be classified as CAMR. In contrast, DSA-/C4d- TGP specimens showed increased cytotoxic T cell-associated transcripts, suggesting T cell activation as a mechanism of injury.

4D Electron Tomography

Science.gov (United States)

Kwon, Oh-Hoon; Zewail, Ahmed H.

2010-06-01

Electron tomography provides three-dimensional (3D) imaging of noncrystalline and crystalline equilibrium structures, as well as elemental volume composition, of materials and biological specimens, including those of viruses and cells. We report the development of 4D electron tomography by integrating the fourth dimension (time resolution) with the 3D spatial resolution obtained from a complete tilt series of 2D projections of an object. The different time frames of tomograms constitute a movie of the object in motion, thus enabling studies of nonequilibrium structures and transient processes. The method was demonstrated using carbon nanotubes of a bracelet-like ring structure for which 4D tomograms display different modes of motion, such as breathing and wiggling, with resonance frequencies up to 30 megahertz. Applications can now make use of the full space-time range with the nanometer-femtosecond resolution of ultrafast electron tomography.

The 4p-5d, 6d and 4p-6s, 7s transitions of Mo IX

International Nuclear Information System (INIS)

Khatoon, S.; Chaghtai, M.S.Z.; Rahimullah, K.

1979-01-01

The transitions 4p-5d, 6d and 4p-6s, 7s have been studied for the first time in Mo IX. The authors have identified 42 4p-5d, 36 4p-6d, 22 4p-6s and 22 4p-7s transitions, establishing 16 4p 3 5d, 14 4p 3 6d and all the ten 4p 3 6s, 7s levels of the spectrum concerned. The ionization energy is estimated to be (1 323 700 +- 700)cm -1 or (164.11 +- 0.09)eV. The spectrum was recorded in sliding and open spark discharges with a 5 m grazing incidence spectrograph of Lund University (Sweden) from about 40 A to 440 A. (Auth.)

4-D OCT in Developmental Cardiology

Science.gov (United States)

Jenkins, Michael W.; Rollins, Andrew M.

Although strong evidence exists to suggest that altered cardiac function can lead to CHDs, few studies have investigated the influential role of cardiac function and biophysical forces on the development of the cardiovascular system due to a lack of proper in vivo imaging tools. 4-D imaging is needed to decipher the complex spatial and temporal patterns of biomechanical forces acting upon the heart. Numerous solutions over the past several years have demonstrated 4-D OCT imaging of the developing cardiovascular system. This chapter will focus on these solutions and explain their context in the evolution of 4-D OCT imaging. The first sections describe the relevant techniques (prospective gating, direct 4-D imaging, retrospective gating), while later sections focus on 4-D Doppler imaging and measurements of force implementing 4-D OCT Doppler. Finally, the techniques are summarized, and some possible future directions are discussed.

Antioxidant activity of salts of 2-(5-R-4-amino-1,2,4-triazole-3-ylthioacetic acid

Directory of Open Access Journals (Sweden)

Ye. S. Pruglo

2017-12-01

that the most active substances among the studied substances were the initial 2-(4-amino-5-(2-bromophenyl-1,2,4-triasole-3-ylthioacetic acid (1b which reduced TBK-AP level at 91,95% (p˂0,001 and its magnesium salt (3a which suppressed the formation of this final product of LPO at 94,13% (p˂0,001. Some regularities of the chemical structure and AOA of the investigated substances were established after analyzing the data of experimental studies. Replacement of the morpholine cation in the morpholine molecule of 2-(4-amino-5-phenyl-1,2,4-triazole-3-ylthioacetic acid (2d on piperidine (2c is accompanied by the appearance of AOA from 18,18% to 74,95%. Replacement of the same piperidine cation on the morpholine cation in the piperidine molecule of 2-(4-amino-5-(2-bromophenyl-1,2,4-triazole-3-ylthioacetic acid is accompanied by the expressive appearance of AOA, which is 90,27% (3f. Conclusions 8 compounds among the 12 which were studied were able to suppress the generation of free radicals in varying degrees of severity and possessed a distinct AOA. It was established that the introduction in the molecule of 2-(4-amino-5-phenyl-1,2,4-triazole-3-ylthioacetic acid by С2 carbon atom of the phenyl nucleus of bromine atom was accompanied by an increase in the AOA of the studied substances.

Regulation of proliferation in developing human tooth germs by MSX homeodomain proteins and cyclin-dependent kinase inhibitor p19INK4d.

Science.gov (United States)

Kero, Darko; Vukojevic, Katarina; Stazic, Petra; Sundov, Danijela; Mardesic Brakus, Snjezana; Saraga-Babic, Mirna

2017-10-02

Before the secretion of hard dental tissues, tooth germs undergo several distinctive stages of development (dental lamina, bud, cap and bell). Every stage is characterized by specific proliferation patterns, which is regulated by various morphogens, growth factors and homeodomain proteins. The role of MSX homeodomain proteins in odontogenesis is rather complex. Expression domains of genes encoding for murine Msx1/2 during development are observed in tissues containing highly proliferative progenitor cells. Arrest of tooth development in Msx knockout mice can be attributed to impaired proliferation of progenitor cells. In Msx1 knockout mice, these progenitor cells start to differentiate prematurely as they strongly express cyclin-dependent kinase inhibitor p19 INK4d . p19 INK4d induces terminal differentiation of cells by blocking the cell cycle in mitogen-responsive G1 phase. Direct suppression of p19 INK4d by Msx1 protein is, therefore, important for maintaining proliferation of progenitor cells at levels required for the normal progression of tooth development. In this study, we examined the expression patterns of MSX1, MSX2 and p19 INK4d in human incisor tooth germs during the bud, cap and early bell stages of development. The distribution of expression domains of p19 INK4d throughout the investigated period indicates that p19 INK4d plays active role during human tooth development. Furthermore, comparison of expression domains of p19 INK4d with those of MSX1, MSX2 and proliferation markers Ki67, Cyclin A2 and pRb, indicates that MSX-mediated regulation of proliferation in human tooth germs might not be executed by the mechanism similar to one described in developing tooth germs of wild-type mouse.

Mineralization of 2,4-Dichlorophenoxyacetic Acid (2,4-D) and Mixtures of 2,4-D and 2,4,5-Trichlorophenoxyacetic Acid by Phanerochaete chrysosporium

Science.gov (United States)

Yadav, J. S.; Reddy, C. A.

1993-01-01

Evidence is presented for mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) in nutrient-rich media (high-nitrogen and malt extract media) by wild-type Phanerochaete chrysosporium and by a peroxidase-negative mutant of this organism. Mass balance analysis of [U-ring-14C]2,4-D mineralization in malt extract cultures showed 82.7% recovery of radioactivity. Of this, 38.6% was released as 14CO2 and 27.0, 11.2, and 5.9% were present in the aqueous, methylene chloride, and mycelial fractions, respectively. 2,4-D and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) were simultaneously mineralized when presented as a mixture, and mutual inhibition of degradation was not observed. In contrast, a relatively higher rate of mineralization of 2,4-D and 2,4,5-T was observed when these compounds were tested as mixtures than when they were tested alone. PMID:16349039

The APSEL4D Monolithic Active Pixel Sensor and its Usage in a Single Electron Interference Experiment

CERN Document Server

Alberghi, Gian Luigi

We have realized a Data Acquisition chain for the use and characterization of APSEL4D, a 32 x 128 Monolithic Active Pixel Sensor, developed as a prototype for frontier experiments in high energy particle physics. In particular a transition board was realized for the conversion between the chip and the FPGA voltage levels and for the signal quality enhancing. A Xilinx Spartan-3 FPGA was used for real time data processing, for the chip control and the communication with a Personal Computer through a 2.0 USB port. For this purpose a firmware code, developed in VHDL language, was written. Finally a Graphical User Interface for the online system monitoring, hit display and chip control, based on windows and widgets, was realized developing a C++ code and using Qt and Qwt dedicated libraries. APSEL4D and the full acquisition chain were characterized for the first time with the electron beam of the transmission electron microscope and with 55Fe and 90Sr radioactive sources. In addition, a beam test was performed at ...

Tagging like Humans: Diverse and Distinct Image Annotation

KAUST Repository

Wu, Baoyuan

2018-03-31

In this work we propose a new automatic image annotation model, dubbed {\\\\bf diverse and distinct image annotation} (D2IA). The generative model D2IA is inspired by the ensemble of human annotations, which create semantically relevant, yet distinct and diverse tags. In D2IA, we generate a relevant and distinct tag subset, in which the tags are relevant to the image contents and semantically distinct to each other, using sequential sampling from a determinantal point process (DPP) model. Multiple such tag subsets that cover diverse semantic aspects or diverse semantic levels of the image contents are generated by randomly perturbing the DPP sampling process. We leverage a generative adversarial network (GAN) model to train D2IA. Extensive experiments including quantitative and qualitative comparisons, as well as human subject studies, on two benchmark datasets demonstrate that the proposed model can produce more diverse and distinct tags than the state-of-the-arts.

4D-Var Developement at GMAO

Science.gov (United States)

Pelc, Joanna S.; Todling, Ricardo; Akkraoui, Amal El

2014-01-01

The Global Modeling and Assimilation Offce (GMAO) is currently using an IAU-based 3D-Var data assimilation system. GMAO has been experimenting with a 3D-Var-hybrid version of its data assimilation system (DAS) for over a year now, which will soon become operational and it will rapidly progress toward a 4D-EnVar. Concurrently, the machinery to exercise traditional 4DVar is in place and it is desirable to have a comparison of the traditional 4D approach with the other available options, and evaluate their performance in the Goddard Earth Observing System (GEOS) DAS. This work will also explore the possibility for constructing a reduced order model (ROM) to make traditional 4D-Var computationally attractive for increasing model resolutions. Part of the research on ROM will be to search for a suitably acceptable space to carry on the corresponding reduction. This poster illustrates how the IAU-based 4D-Var assimilation compares with our currently used IAU-based 3D-Var.

Distinct ontogenic patterns of overt and latent DGAT activities of rat liver microsomes.

Science.gov (United States)

Waterman, Ian J; Price, Nigel T; Zammit, Victor A

2002-09-01

We have studied the ontogeny of the two functional diacylglycerol acyltransferase (DGAT) activities (overt and latent) during postnatal development in rat liver. We find that the ontogenic patterns of the two are highly distinct. Overt DGAT shows a transient rise in activity up to day 4 postnatally, after which it declines until weaning; thereafter, it increases steadily to reach high adult values that may contribute to the high rates of turnover of cytosolic triacylglycerol (TAG). By contrast, latent DGAT activity increases continuously during the suckling period but falls sharply upon weaning onto chow but not onto a high-fat diet. Rates of TAG secretion by hepatocytes are higher than in the adult during the first 7 days after birth, and are largely dependent on the mobilization of the abundant intrahepatocyte TAG as a source of acyl moieties. When the hepatic steatosis is cleared (after day 7) the TAG secretion rate declines by 80% to reach adult values. Quantification of the content of mRNA for the DGAT1 and DGAT2 genes does not show correlation with either of the DGAT activities. We conclude that post-translational modification may play an important role in the overt and latent distribution of DGAT activity in the liver microsomal membrane.

Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 vs. D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

Science.gov (United States)

Li, Jing Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

2018-04-23

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally sub-threshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II (CaMKII-α) or extracellular-signal-related-kinase 1-2 (ERK 1/2), following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Significance Statement: Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

International Nuclear Information System (INIS)

Fu, Meili; Wan, Fuqiang; Li, Zhengling; Zhang, Fenghua

2016-01-01

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Fu, Meili, E-mail: fumeilidrlinyi@tom.com [Department of Infectious Disease, Linyi People' s Hospital, Linyi 276000 (China); Wan, Fuqiang [Department of Head and Neck Surgery, Linyi Tumor Hospital, Linyi 276000 (China); Li, Zhengling [Department of Nursing, Tengzhou Central People' s Hospital, Tengzhou 277500 (China); Zhang, Fenghua [Department of Operating Room, Linyi People' s Hospital, Linyi 276000 (China)

2016-03-04

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

4D scattering amplitudes and asymptotic symmetries from 2D CFT

Science.gov (United States)

Cheung, Clifford; de la Fuente, Anton; Sundrum, Raman

2017-01-01

We reformulate the scattering amplitudes of 4D flat space gauge theory and gravity in the language of a 2D CFT on the celestial sphere. The resulting CFT structure exhibits an OPE constructed from 4D collinear singularities, as well as infinite-dimensional Kac-Moody and Virasoro algebras encoding the asymptotic symmetries of 4D flat space. We derive these results by recasting 4D dynamics in terms of a convenient foliation of flat space into 3D Euclidean AdS and Lorentzian dS geometries. Tree-level scattering amplitudes take the form of Witten diagrams for a continuum of (A)dS modes, which are in turn equivalent to CFT correlators via the (A)dS/CFT dictionary. The Ward identities for the 2D conserved currents are dual to 4D soft theorems, while the bulk-boundary propagators of massless (A)dS modes are superpositions of the leading and subleading Weinberg soft factors of gauge theory and gravity. In general, the massless (A)dS modes are 3D Chern-Simons gauge fields describing the soft, single helicity sectors of 4D gauge theory and gravity. Consistent with the topological nature of Chern-Simons theory, Aharonov-Bohm effects record the "tracks" of hard particles in the soft radiation, leading to a simple characterization of gauge and gravitational memories. Soft particle exchanges between hard processes define the Kac-Moody level and Virasoro central charge, which are thereby related to the 4D gauge coupling and gravitational strength in units of an infrared cutoff. Finally, we discuss a toy model for black hole horizons via a restriction to the Rindler region.

Room-temperature synthesis of nanoporous 1D microrods of graphitic carbon nitride (g-C3N4) with highly enhanced photocatalytic activity and stability.

Science.gov (United States)

Pawar, Rajendra C; Kang, Suhee; Park, Jung Hyun; Kim, Jong-Ho; Ahn, Sunghoon; Lee, Caroline S

2016-08-08

A one-dimensional (1D) nanostructure having a porous network is an exceptional photocatalytic material to generate hydrogen (H2) and decontaminate wastewater using solar energy. In this report, we synthesized nanoporous 1D microrods of graphitic carbon nitride (g-C3N4) via a facile and template-free chemical approach at room temperature. The use of concentrated acids induced etching and lift-off because of strong oxidation and protonation. Compared with the bulk g-C3N4, the porous 1D microrod structure showed five times higher photocatalytic degradation performance toward methylene blue dye (MB) under visible light irradiation. The photocatalytic H2 evolution of the 1D nanostructure (34 μmol g(-1)) was almost 26 times higher than that of the bulk g-C3N4 structure (1.26 μmol g(-1)). Additionally, the photocurrent stability of this nanoporous 1D morphology over 24 h indicated remarkable photocorrosion resistance. The improved photocatalytic activities were attributed to prolonged carrier lifetime because of its quantum confinement effect, effective separation and transport of charge carriers, and increased number of active sites from interconnected nanopores throughout the microrods. The present 1D nanostructure would be highly suited for photocatalytic water purification as well as water splitting devices. Finally, this facile and room temperature strategy to fabricate the nanostructures is very cost-effective.

Long-term 4D Geoelectrical Imaging of Moisture Dynamics in an Active Landslide

Science.gov (United States)

Uhlemann, S.; Chambers, J. E.; Wilkinson, P. B.; Maurer, H.; Meldrum, P.; Gunn, D.; Smith, A.; Dijkstra, T.

2016-12-01

Landslides are a major natural hazard, endangering communities and infrastructure worldwide. Mitigating landslide risk relies on understanding causes and triggering processes, which are often linked to moisture dynamics in slopes causing material softening and elevated pore water pressures. Geoelectrical monitoring is frequently applied to study landslide hydrology. However, its sensitivity to sensor movements has been a challenge for long-term studies on actively failing slopes. Although 2D data acquisition has previously been favoured, it provides limited resolution and relatively poor representation of important 3D landslide structures. We present a novel methodology to incorporate electrode movements into a time-lapse 3D inversion workflow, resulting in a virtually artefact-free time-series of resistivity models. Using temperature correction and laboratory hydro-geophysical relationships, resistivity models are translated into models of moisture content. The data span more than three years, enabling imaging of processes pre- and post landslide reactivation. In the two years before reactivation, the models showed surficial wetting and drying, drainage pathways, and deeper groundwater dynamics. During reactivation, exceptionally high moisture contents were imaged throughout the slope, which was confirmed by independent measurements. Preferential flow was imaged that stabilized parts of the landslide by diverting moisture, and thus dissipating pore pressures, from the slip surface. The results highlight that moisture levels obtained from resistivity monitoring may provide a better activity threshold than rainfall intensity. Based on this work, pro-active remediation measures could be designed and effective early-warning systems implemented. Eventually, resistivity monitoring that can account for moving electrodes may provide a new means for pro-active mitigation of landslide risk, especially for communities and critical infrastructure.

Degradation of 2,4-D in soils by Fe₃O₄ nanoparticles combined with stimulating indigenous microbes.

Science.gov (United States)

Fang, Guodong; Si, Youbin; Tian, Chao; Zhang, Gangya; Zhou, Dongmei

2012-03-01

Degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) in soils by Fe₃O₄ nanoparticles combined with soil indigenous microbes was investigated, and the effects of Fe₃O₄ nanoparticles on soil microbial populations and enzyme activities were also studied. The soils contaminated with 2,4-D were treated with Fe₃O₄ nanoparticles. The microbial populations and enzyme activities were analyzed by dilution plate method and chemical assay, respectively, and the concentration of 2,4-D in soil was determined by high-performance liquid chromatography (HPLC). The results indicated that Fe₃O₄ nanoparticles combined with soil indigenous microbes led to a higher degradation efficiency of 2,4-D than the treatments with Fe₃O₄ nanoparticles or indigenous microbes alone. The degradation of 2,4-D in soils followed the pseudo first-order kinetic. The half-lives of 2,4-D degradation (DT₅₀) of the combined treatments were 0.9, 1.9 and 3.1 days in a Red soil, Vertisol and Alfisol, respectively, which implied that the DT₅₀ of the combination treatments were significantly shorter than that of the treatments Fe₃O₄ nanoparticles or indigenous microbes alone. The effects of Fe₃O₄ nanoparticles on soil microbial populations and enzyme activities were also investigated and compared with the α-Fe₂O₃ nanoparticles. The results suggested that the α-Fe₂O₃ nanoparticles had only comparatively small effects on degradation of 2,4-D in soils, while the Fe₃O₄ nanoparticles not only degraded 2,4-D in soils but also increased the soil microbial populations and enzyme activities; the maximum increase in enzyme activities were 67.8% (amylase), 53.8% (acid phosphatase), 26.5% (catalase) and 38.0% (urease), compared with the untreated soil. Moreover, the introduction of Fe₃O₄ nanoparticles at the different dosage resulted in a variable degradation efficiency of 2,4-D in soil. The method of combining Fe₃O₄ nanoparticles with indigenous soil microbes may

Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase.

Directory of Open Access Journals (Sweden)

Kara R Barber

2017-02-01

Full Text Available Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated.

Resonance quadripolaire nucleaire dans les halogenures d'actinides, ThBr 4, ThCl 4 ET UCl 4. II. Polymorphisme et transition de phase du premier ordre dans ThBr 4. Resonance du Brome dans UBr 4.

Science.gov (United States)

Gourdji, M.; Péneau, A.; Genet, M.; Guibé, L.

1983-12-01

La poursuite de recherches antérieures a permis de caractériser la résonance quadripolaire du brome dans la phase α de ThBr 4 et d'étudier la variation, en fonction de la température, entre 63 et 295 K, de la fréquence de résonance, ν Q(T), correspondante. Une première analyse des conditions expérimentales du passage de la transition α↔β à 426 C a été faite. La résonance du brome dans UBr 4 a également été observée et l'étude en fonction de la température des fréquences de résonance (il y a deux résonances distinctes pour chacun des deux isotopes du brome dans ce composé) a révélé un comportement inattendu en ce sens que les pentes dν Q/dT des courbes ν Q(T) correspondant aux deux résonances sont de signe contraire.

Synthesis of 4-Triazolylamino- and 4-Benzothiazolylamino-3-nitro-2H-[1]-Benzopyran-2-ones and their Antimicrobial Activity

Directory of Open Access Journals (Sweden)

Ramiz Hoti

2014-10-01

Full Text Available Novel substituted benzopyran-2-one derivatives were synthesized by catalytic condensation reactions under reflux conditions. 4-(1,2,4-Triazolyl-3-amino-3-nitro-2H-[1]-benzopyran-2-ones 4(a-b were synthesized by condensation of 4-chloro-3-nitro-2H-[1]-benzopyran-2-one (2 and corresponding 3-aminotriazoles 3(a-b. 4-(4’-methoxy-2-benzothiazolylamino-3-nitro-2H-[1]-benzopyran-2-one (4c, 4-(6’-nitro-2-benzothiazolylamino-3-nitro-2H-[1]-benzopyiran-2-one (4d and 4-(6’-fluoro-2-benzothiazolylamino-3-nitro-2H-[1]-benzopyran-2-one (4e were synthesized by condensation of 4-chloro-3-nitro-2H-[1]-benzopyran-2-one (2 and corresponding 2-aminobenzothiazole 3(c-e under reflux reaction conditions. Further, alkali hydrolysis of 4(a-e afforded the 2-hydroxy-ω-nitroacetophenone (5. Antimicrobial activity of products 4(a-e against S. aurous, E. coli and Klebsiella were investigated measuring of inhibition zones around the discs which are marked with DMF, concentration 2 mg/mL, 4 mg/mL and 6 mg/mL solutions. Compounds 4c, 4e and 4d were more active against S. aureus. Emphatic activity against E. coli exhibited compounds 4b and 4e, whereas 4c and 4d were more active against Klebsiella.

Bio indices for 2,4-D sensitivity between two plant species: Azolla pinnata R.Br. and Vernonia cinerea L. with their cellular responses.

Science.gov (United States)

De, Arnab Kumar; Dey, Narottam; Adak, Malay Kumar

2016-07-01

In the present experiment a pteridophytic species Azolla and an angiospermic species Vernonia were evaluated on the basis of cellular reactivity for herbicidal action through ongoing concentrations. Initially, both the species recorded a significant activity of IAA-oxidase as mark of IAA metabolism with herbicidal sensitivity. Still, Vernonia species were more affected on 2,4-D mediated auxin catabolism. The loss of auxin concentrations on the tissues by 2,4-D reaction was also reflected on growth parameters including relative growth rate and chlorophyll biosynthesis. In a dose dependent manner Vernonia plants were more affected with loss of chlorophyll content and decline in relative growth rate. On the other hand, both those parameters were adjusted significantly with 2,4-D accumulation in Azolla . The stability of cellular metabolism was documented by significant down regulation of protein and lipid peroxidation with concomitant moderation to superoxide and hydrogen peroxide accumulation. The later two were more vulnerable to damage in the Vernonia plant with profuse accumulation of protein and lipid peroxidation products. Similarly, tissue specific reaction to superoxide and hydrogen peroxide accumulation were distinctly demarcated in two species significantly. As a whole, the cellular responses and metabolite distribution to 2,4-D sensitization are the features to describe bio-indices for aquatic fern species Azolla with comparison to angiospermic species Vernonia .

Topological wave functions and the 4D-5D lift

OpenAIRE

Gao, Peng; Pioline, Boris

2008-01-01

We revisit the holomorphic anomaly equations satisfied by the topological string amplitude from the perspective of the 4D-5D lift, in the context of ''magic'' N=2 supergravity theories. In particular, we interpret the Gopakumar-Vafa relation between 5D black hole degeneracies and the topological string amplitude as the result of a canonical transformation from 4D to 5D charges. Moreover we use the known Bekenstein-Hawking entropy of 5D black holes to constrain the asymptotic behavior of the t...

Instant Cinema 4D starter

CERN Document Server

Kaminar, Aaron

2013-01-01

Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks.This book is written in a friendly, practical style with lots of screenshots and help that will ensure you grow in confidence chapter by chapter.This book is recommended for artists that have experience in other 3D software packages, and who want to learn Cinema 4D. That being said, dedicated readers without experience in other 3D software should not be discouraged from reading this book to learn the basics of Cinema 4D as their first 3D package.

D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking.

Science.gov (United States)

Helms, C M; Gubner, N R; Wilhelm, C J; Mitchell, S H; Grandy, D K

2008-09-01

Alleles of the human dopamine D(4) receptor (D(4)R) gene (DRD4.7) have repeatedly been found to correlate with novelty seeking, substance abuse, pathological gambling, and attention-deficit hyperactivity disorder (ADHD). If these various psychopathologies are a result of attenuated D(4)R-mediated signaling, mice lacking D(4)Rs (D(4)KO) should be more impulsive than wild-type (WT) mice and exhibit more novelty seeking. However, in our study, D(4)KO and WT mice showed similar levels of impulsivity as measured by delay discounting performance and response inhibition on a Go/No-go test, suggesting that D(4)R-mediated signaling may not affect impulsivity. D(4)KO mice were more active than WT mice in the first 5 min of a novel open field test, suggesting greater novelty seeking. For both genotypes, more impulsive mice habituated less in the novel open field. These data suggest that the absence of D(4)Rs is not sufficient to cause psychopathologies associated with heightened impulsivity and novelty seeking.

Theoretical level energies and transition data for 4p64d4, 4p64d34f and 4p54d5 configurations of W34+ ion

Science.gov (United States)

Karpuškienė, R.; Bogdanovich, P.; Kisielius, R.

2017-05-01

The ab initio quasirelativistic approach developed specifically for the calculation of spectral parameters of highly charged ions was used to derive transition data for the tungsten ion W34+. The configuration interaction method was applied to include electron correlation effects. The relativistic effects were taken into account in the Breit-Pauli approximation. The level energies, radiative lifetimes τ, Landé g-factors are determined for the ground configuration 4p64d4 and two excited configurations 4p64d34f and 4p54d5. The radiative transition wavelengths λ and emission transition probabilities A for the electric dipole, electric quadrupole, electric octupole, magnetic dipole, and magnetic quadrupole transitions among the levels of these configurations are produced.

4d N=1 from 6d (1,0)

Energy Technology Data Exchange (ETDEWEB)

Razamat, Shlomo S. [Physics Department, Technion,Haifa, 32000 (Israel); Vafa, Cumrun [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States); Zafrir, Gabi [Physics Department, Technion,Haifa, 32000 (Israel); Kavli IPMU (WPI), UTIAS, the University of Tokyo,Kashiwa, Chiba 277-8583 (Japan)

2017-04-11

We study the geometry of 4d N=1 SCFT’s arising from compactification of 6d (1,0) SCFT’s on a Riemann surface. We show that the conformal manifold of the resulting theory is characterized, in addition to moduli of complex structure of the Riemann surface, by the choice of a connection for a vector bundle on the surface arising from flavor symmetries in 6d. We exemplify this by considering the case of 4d N=1 SCFT’s arising from M5 branes probing ℤ{sub k} singularity compactified on a Riemann surface. In particular, we study in detail the four dimensional theories arising in the case of two M5 branes on ℤ{sub 2} singularity. We compute the conformal anomalies and indices of such theories in 4d and find that they are consistent with expectations based on anomaly and the moduli structure derived from the 6 dimensional perspective.

Chemically different non-thermal plasmas target distinct cell death pathways

Czech Academy of Sciences Publication Activity Database

Lunov, O.; Zablotskyy, V.; Chrupina, O.; Lunova, M.; Jirsa, M.; Dejneka, A.; Kubinová, Šárka

2017-01-01

Roč. 7, apr (2017), s. 600 ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : chemically different * non-thermal plasmas * target distinct cell death pathways Subject RIV: FP - Other Medical Disciplines OBOR OECD: Biophysics Impact factor: 4.259, year: 2016

Fully digital 1-D, 2-D and 3-D multiscroll chaos as hardware pseudo random number generators

KAUST Repository

Mansingka, Abhinav S.

2012-10-07

This paper introduces the first fully digital implementation of 1-D, 2-D and 3-D multiscroll chaos using the sawtooth nonlinearity in a 3rd order ODE with the Euler approximation. Systems indicate chaotic behaviour through phase space boundedness and positive Lyapunov exponent. Low-significance bits form a PRNG and pass all tests in the NIST SP. 800-22 suite without post-processing. Real-time control of the number of scrolls allows distinct output streams with 2-D and 3-D multiscroll chaos enabling greater controllability. The proposed PRNGs are experimentally verified on a Xilinx Virtex 4 FPGA with logic utilization less than 1.25%, throughput up to 5.25 Gbits/s and up to 512 distinct output streams with low cross-correlation.

Oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics: Immunofluorescent localization in the mouse hypothalamus.

Science.gov (United States)

Anderson, Brian M; Jacobson, Lauren; Novakovic, Zachary M; Grasso, Patricia

2017-06-01

This study describes the localization of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics, in the hypothalamus of Swiss Webster and C57BL/6J wild-type mice, leptin-deficient ob/ob mice, and leptin-resistant diet-induced obese (DIO) mice. The mice were given [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in 0.3% dodecyl maltoside by oral gavage. Once peak serum concentrations were reached, the mice received a lethal dose of pentobarbital and were subjected to intracardiac perfusion fixation. The brains were excised, post-fixed in paraformaldehyde, and cryo-protected in sucrose. Free-floating frozen coronal sections were cut at 25-µm and processed for imaging by immunofluorescence microscopy. In all four strains of mice, dense staining was concentrated in the area of the median eminence, at the base and/or along the inner wall of the third ventricle, and in the brain parenchyma at the level of the arcuate nucleus. These results indicate that [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 cross the blood-brain barrier and concentrate in an area of the hypothalamus known to regulate energy balance and glucose homeostasis. Most noteworthy is the localization of [D-Leu-4]-OB3 immunoreactivity within the hypothalamus of DIO mice via a conduit that is closed to leptin in this rodent model, and in most cases of human obesity. Together with our previous studies describing the effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on energy balance, glucose regulation, and signal transduction pathway activation, these findings are consistent with a central mechanism of action for these synthetic peptide leptin mimetics, and suggest their potential usefulness in the management of leptin-resistant obesity and type 2 diabetes in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of mitochondrial and nucleolar RNase MRP reveals identical RNA components with distinct enzymatic activities and protein components.

Science.gov (United States)

Lu, Qiaosheng; Wierzbicki, Sara; Krasilnikov, Andrey S; Schmitt, Mark E

2010-03-01

RNase MRP is a ribonucleoprotein endoribonuclease found in three cellular locations where distinct substrates are processed: the mitochondria, the nucleolus, and the cytoplasm. Cytoplasmic RNase MRP is the nucleolar enzyme that is transiently relocalized during mitosis. Nucleolar RNase MRP (NuMRP) was purified to homogeneity, and we extensively purified the mitochondrial RNase MRP (MtMRP) to a single RNA component identical to the NuMRP RNA. Although the protein components of the NuMRP were identified by mass spectrometry successfully, none of the known NuMRP proteins were found in the MtMRP preparation. Only trace amounts of the core NuMRP protein, Pop4, were detected in MtMRP by Western blot. In vitro activity of the two enzymes was compared. MtMRP cleaved only mitochondrial ORI5 substrate, while NuMRP cleaved all three substrates. However, the NuMRP enzyme cleaved the ORI5 substrate at sites different than the MtMRP enzyme. In addition, enzymatic differences in preferred ionic strength confirm these enzymes as distinct entities. Magnesium was found to be essential to both enzymes. We tested a number of reported inhibitors including puromycin, pentamidine, lithium, and pAp. Puromycin inhibition suggested that it binds directly to the MRP RNA, reaffirming the role of the RNA component in catalysis. In conclusion, our study confirms that the NuMRP and MtMRP enzymes are distinct entities with differing activities and protein components but a common RNA subunit, suggesting that the RNA must be playing a crucial role in catalytic activity.

Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake

Directory of Open Access Journals (Sweden)

Xianglong eZhu

2016-04-01

Full Text Available While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The NAc is one brain region that has received attention for its role in the regulation of energy balance; its D1 and D2 receptor containing neurons have distinct functions in regulating reward behavior and require further examination. The goal of the present study is to investigate how activation and inhibition of D1 and D2 neurons in the NAc influences behaviors related to energy intake and expenditure. Specific manipulation of D1 vs D2 neurons was done in both low expenditure and high expenditure (wheel running conditions to assess behavioral effects in these different states. Direct control of neural activity was achieved using a DREADD (Designer Receptors Exclusively Activated by Designer Drugs strategy. Activation of NAc D1 neurons increased food intake, wheel running and locomotor activity. In contrast, activation of D2 neurons in the NAc reduced running and locomotion while D2 neuron inhibition had opposite effects. These results highlight the importance of considering both intake and expenditure in the analysis of D1 and D2 neuronal manipulations. Moreover, the behavioral outcomes from D1 NAc neuronal manipulations depend upon the activity state of the animals (wheel running vs non-running. The data support and complement the hypothesis of specific NAc dopamine pathways facilitating energy expenditure and suggest a potential strategy for human weight control.

Adsorption of 2,4-dichlorophenoxyacetic acid and 4-chloro-2-metylphenoxyacetic acid onto activated carbons derived from various lignocellulosic materials.

Science.gov (United States)

Doczekalska, Beata; Kuśmierek, Krzysztof; Świątkowski, Andrzej; Bartkowiak, Monika

2018-05-04

Adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-metylphenoxyacetic acid (MCPA) from aqueous solution onto activated carbons derived from various lignocellulosic materials including willow, miscanthus, flax, and hemp shives was investigated. The adsorption kinetic data were analyzed using two kinetic models: the pseudo-first order and pseudo-second order equations. The adsorption kinetics of both herbicides was better represented by the pseudo-second order model. The adsorption isotherms of 2,4-D and MCPA on the activated carbons were analyzed using the Freundlich and Langmuir isotherm models. The equilibrium data followed the Langmuir isotherm. The effect of pH on the adsorption was also studied. The results showed that the activated carbons prepared from the lignocellulosic materials are efficient adsorbents for the removal of 2,4-D and MCPA from aqueous solutions.

Phosphorylation and nuclear accumulation are distinct events contributing to the activation of p53

International Nuclear Information System (INIS)

O'Hagan, Heather M.; Ljungman, Mats

2004-01-01

It has been recently shown that ionizing radiation (IR) and the mRNA synthesis inhibitor 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) act in synergy to induce p53-mediated transactivation of reporter plasmids in human cells [Oncogene 19 (2000) 3829]. We have extended these studies and show that ionizing radiation and DRB also act in synergy to induce ATM-mediated phosphorylation of the ser15 site of p53 and enhance the expression of endogenous p21 protein. Examination of the localization of p53 revealed that while DRB did not induce phosphorylation of the ser15 site of p53 but efficiently accumulated p53 in the nucleus, ionizing radiation induced phosphorylation of the ser15 site of p53 without prolonged nuclear accumulation. Importantly, the combination of DRB and IR resulted in a strong accumulation of phosphorylated p53 in the nucleus that was more persistent then p53 accumulation after IR alone. Furthermore, the nuclear export inhibitor leptomycin B showed a similar synergy with IR as did DRB regarding ser15 phosphorylation of p53 and p21 induction. These results suggest that the synergistic activation of the p53 response by the combination treatment is due to the activation of two distinct pathways where DRB causes the prolonged nuclear accumulation of p53 while ionizing radiation activates p53 by ATM-mediated phosphorylation

D1/D5 systems in N=4 string theories

International Nuclear Information System (INIS)

Gava, Edi; Hammou, Amine B.; Morales, Jose F.; Narain, Kumar S.

2001-01-01

We propose CFT descriptions of the D1/D5 system in a class of freely acting Z 2 orbifolds/orientifolds of type IIB theory, with sixteen unbroken supercharges. The CFTs describing D1/D5 systems involve N=(4,4) or N=(4,0) sigma models on (R 3 xS 1 xT 4 x(T 4 ) N /S N )/Z 2 , where the action of Z 2 is diagonal and its precise nature depends on the model. We also discuss D1(D5)-brane states carrying non-trivial Kaluza-Klein charges, which correspond to excitations of two-dimensional CFTs of the type (R 3 xS 1 xT 4 ) N /S N xZ 2 N . The resulting multiplicities for two-charge bound states are shown to agree with the predictions of U-duality. We raise a puzzle concerning the multiplicities of three-charge systems, which is generically present in all vacuum configurations with sixteen unbroken supercharges studied so far, including the more familiar type IIB on K3 case: the constraints put on BPS counting formulae by U-duality are apparently in contradiction with any CFT interpretation. We argue that the presence of RR backgrounds appearing in the symmetric product CFT may provide a resolution of this puzzle. Finally, we show that the whole tower of D-instanton corrections to certain 'BPS saturated couplings' in the low energy effective actions match with the corresponding one-loop threshold corrections on the dual fundamental string side

Dopamine receptor D3 expressed on CD4+ T cells favors neurodegeneration of dopaminergic neurons during Parkinson's disease.

Science.gov (United States)

González, Hugo; Contreras, Francisco; Prado, Carolina; Elgueta, Daniela; Franz, Dafne; Bernales, Sebastián; Pacheco, Rodrigo

2013-05-15

Emerging evidence has demonstrated that CD4(+) T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and in animal models of PD. SN-infiltrated CD4(+) T cells bearing inflammatory phenotypes promote microglial activation and strongly contribute to neurodegeneration of dopaminergic neurons. Importantly, altered expression of dopamine receptor D3 (D3R) in PBLs from PD patients has been correlated with disease severity. Moreover, pharmacological evidence has suggested that D3R is involved in IFN-γ production by human CD4(+) T cells. In this study, we examined the role of D3R expressed on CD4(+) T cells in neurodegeneration of dopaminergic neurons in the SN using a mouse model of PD. Our results show that D3R-deficient mice are strongly protected against loss of dopaminergic neurons and microglial activation during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Notably, D3R-deficient mice become susceptible to MPTP-induced neurodegeneration and microglial activation upon transfer of wild-type (WT) CD4(+) T cells. Furthermore, RAG1 knockout mice, which are devoid of T cells and are resistant to MPTP-induced neurodegeneration, become susceptible to MPTP-induced loss of dopaminergic neurons when reconstituted with WT CD4(+) T cells but not when transferred with D3R-deficient CD4(+) T cells. In agreement, experiments analyzing activation and differentiation of CD4(+) T cells revealed that D3R favors both T cell activation and acquisition of the Th1 inflammatory phenotype. These findings indicate that D3R expressed on CD4(+) T cells plays a fundamental role in the physiopathology of MPTP-induced PD in a mouse model.

Experimental and theoretical investigation on photocatalytic activities of 1D Ag/Ag2WO4 nanostructures

Science.gov (United States)

Liu, Danqing; Huang, Weicheng; Li, Long; Liu, Lu; Sun, Xiaojun; Liu, Bo; Yang, Bin; Guo, Chongshen

2017-09-01

Ag2WO4 is a significant photocatalyst that responds to UV light irradiation only, which greatly hinders it for further practical application for solar light. To address this problem, herein, 1D plasmonic Ag/Ag2WO4 photocatalysts have been fabricated by a successive process including hydrothermal synthesis to obtain Ag2WO4 followed by an additional in situ chemical-reduction process for Ag decoration. Then, the structural features, optical properties, and electronic structures of Ag2WO4 and Ag/Ag2WO4 nanowires were systematically investigated via a combination of theoretical calculations and experimental evidence. The plasmon-enhanced Ag/Ag2WO4 nanowires exhibited higher visible-light-driven photocatalytic activity, which performed a desired photodestruction ratio of 91.2% on methylene blue within 60 min and good stability in five cycles. The Ag decoration greatly facilitates visible-light harvesting and thus promotes photogenerated radical oxidation to dye, which is evidenced by the higher hydroxyl radical level of Ag/Ag2WO4 detected in the ESR test during the photocatalytic process. The theoretical calculation based on density functional theory indicates that Ag nanoparticles formed on the surface of Ag2WO4 could narrow the band gap of Ag2WO4. In addition, the surface plasmon resonance absorption effect and fast charge transfer effect in the metal-semiconductor system contribute to the photocatalytic performance of Ag/Ag2WO4.

Selective and interactive effects of D2 receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

Science.gov (United States)

Isherwood, Sarah N; Robbins, Trevor W; Nicholson, Janet R; Dalley, Jeffrey W; Pekcec, Anton

2017-09-01

Metabotropic glutamate receptor 4 (mGluR4) and dopamine D 2 receptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and D 2 receptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-((E)-styryl)-pyrimidin-2-ylamine (Cpd11), both alone and in combination with the D 2 receptor antagonist eticlopride, on two distinct forms of impulsivity. Rats were trained on the five-choice serial reaction time task (5-CSRTT) of sustained visual attention and segregated according to low, mid, and high levels of motor impulsivity (LI, MI and HI, respectively), with unscreened rats used as an additional control group. A separate group of rats was trained on a delay discounting task (DDT) to assess choice impulsivity. Systemic administration of Cpd11 dose-dependently increased motor impulsivity and impaired attentional accuracy on the 5-CSRTT in all groups tested. Eticlopride selectively attenuated the increase in impulsivity induced by Cpd11, but not the accompanying attentional impairment, at doses that had no significant effect on behavioural performance when administered alone. Cpd11 also decreased choice impulsivity on the DDT (i.e. increased preference for the large, delayed reward) and decreased locomotor activity. These findings demonstrate that mGluR4s, in conjunction with D 2 receptors, affect motor- and choice-based measures of impulsivity, and therefore may be novel targets to modulate impulsive behaviour associated with a number of neuropsychiatric syndromes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Digit Ratio (2D:4D and Gender Inequalities Across Nations

Directory of Open Access Journals (Sweden)

John T. Manning

2014-10-01

Full Text Available Gender inequality varies across nations, where such inequality is defined as the disproportionate representation of one sex over the other in desirable social, economic, and biological roles (typically male over female. Thus in Norway, 40% of parliamentarians are women, in the USA 17%, and in Saudi Arabia 0%. Some of this variation is associated with economic prosperity but there is evidence that this cause and effect can go in either direction. Here we show that within a population the average ratio of index (2D to ring (4D finger lengths (2D:4D—a proxy measure of the relative degree to which offspring is exposed in utero to testosterone versus estrogen—is correlated with measures of gender inequality between nations. We compared male and female 2D:4D ratios to female parliamentary representation, labor force participation, female education level, maternal mortality rates, and juvenile pregnancy rates per nation in a sample of 29 countries. We found those nations who showed higher than expected female fetal exposure to testosterone (low 2D:4D and lower than expected male exposure to fetal testosterone (high 2D:4D had higher rates of female parliamentary representation, and higher female labor force participation. In short, the more similar the two sexes were in 2D:4D, the more equal were the two sexes in parliamentary and labor force participation. The other variables were not as strongly correlated. We suggest that higher than expected fetal testosterone in females and lower fetal testosterone in males may lead to high female representation in the national labor force and in parliament.

Facts and Misconceptions about 2D:4D, Social and Risk Preferences

Science.gov (United States)

Alonso, Judit; Di Paolo, Roberto; Ponti, Giovanni; Sartarelli, Marcello

2018-01-01

We study how the ratio between the length of the second and fourth digit (2D:4D) correlates with choices in social and risk preferences elicitation tasks by building a large dataset from five experimental projects with more than 800 subjects. Our results confirm the recent literature that downplays the link between 2D:4D and many domains of economic interest, such as social and risk preferences. As for the former, we find that social preferences are significantly lower when 2D:4D is above the median value only for subjects with low cognitive ability. As for the latter, we find that a high 2D:4D is not correlated with the frequency of subjects' risky choices. PMID:29487510

Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells.

Science.gov (United States)

Kim, Hyun-Jung; Park, Young In; Dong, Mi-Sook

2005-11-01

2,4-Dichlorophenoxyacetic acid (2,4-D) and its metabolite 2,4-dichlorophenol (DCP) are used extensively in agriculture as herbicides, and are suspected of potential endocrine disruptor activity. In a previous study, we showed that these compounds exhibited synergistic androgenic effects by co-treatment with testosterone in the Hershberger assay. To elucidate the mechanisms of the synergistic effects of these compounds on the androgenicity of testosterone, the androgenic action of 2,4-D and DCP was characterized using a mammalian detection system in prostate cancer cell lines. In in vitro assay systems, while 2,4-D or DCP alone did not show androgenic activity, 2,4-D or DCP with 5alpha-dihydroxytestosterone (DHT) exhibited synergistic androgenic activities. Co-treatment of 10 nM 2,4-D or DCP with 10 nM DHT was shown to stimulate the cell proliferation by 1.6-fold, compared to 10 nM DHT alone. In addition, in transient transfection assays, androgen-induced transactivation was also increased to a maximum of 32-fold or 1.28-fold by co-treatment of 2,4-D or DCP with DHT, respectively. However, 2,4-D and DCP exerted no effects on either mRNA or protein levels of AR. In a competitive AR binding assay, 2,4-D and DCP inhibited androgen binding to AR, up to 50% at concentrations of approximately 0.5 microM for both compounds. The nuclear translocation of green fluorescent protein-AR fusion protein in the presence of DHT was promoted as the result of the addition of 2,4-D and DCP. Collectively, these results that 2,4-D and DCP enhanced DHT-induced AR transcriptional activity might be attributable, at least in part, to the promotion of AR nuclear translocation.

2D:4D digit ratio predicts delay of gratification in preschoolers.

Directory of Open Access Journals (Sweden)

Sergio Da Silva

Full Text Available We replicate the Stanford marshmallow experiment with a sample of 141 preschoolers and find a correlation between lack of self-control and 2D:4D digit ratio. Children with low 2D:4D digit ratio are less likely to delay gratification. Low 2D:4D digit ratio may indicate high fetal testosterone. If this hypothesis is true, our finding means high fetal testosterone children are less likely to delay gratification.

Cloning and functional characterization of IRAK4 in large yellow croaker (Larimichthys crocea) that associates with MyD88 but impairs NF-κB activation.

Science.gov (United States)

Zou, Peng Fei; Huang, Xue Na; Yao, Cui Luan; Sun, Qing Xue; Li, Ying; Zhu, Qian; Yu, Zhen Xing; Fan, Ze Jun

2017-04-01

As crucial signaling transducer in Toll-like receptor (TLR) and interleukin (IL)-1 receptor (IL-1R) signaling pathway, IL-1R-associated kinase 4 (IRAK4) mediates downstream signaling cascades and plays important roles in innate and adaptive immune responses. In the present study, an IRAK4 orthologue was characterized from large yellow croaker (Larimichthys crocea), named Lc-IRAK4, with a conservative N-terminal death domain and a C-terminal protein kinase domain. The genome of Lc-IRAK4 is structured into eleven exons and ten introns. Expression analysis indicated that Lc-IRAK4 was widely expressed in tested tissues, with the highest level in liver and weakest in muscle. Additionally, in the spleen, liver tissues and blood, it could be induced by poly I:C and LPS stimulation, but not be induced by Vibrio parahemolyticus infection. Fluorescence microscopy assays revealed that Lc-IRAK4 localized in the cytoplasm in HEK 293T cells. It was also determined that Lc-IRAK4 could interact with MyD88, whereas MyD88-mediated NF-κB activation was significantly impaired when co-transfected the two in HEK 293T cells. These findings collectively indicated that although Lc-IRAK4 was evolutionarily conserved in vertebrates, the exact function especially the signaling transduction mediated by IRAK4 in fish immune response was different from that in mammals, which impaired MyD88-mediated NF-κB activation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Leisure activities, apolipoprotein E e4 status, and the risk of dementia.

Science.gov (United States)

Yang, Sheng-Ying; Weng, Pei-Hsuan; Chen, Jen-Hau; Chiou, Jeng-Min; Lew-Ting, Chih-Yin; Chen, Ta-Fu; Sun, Yu; Wen, Li-Li; Yip, Ping-Keung; Chu, Yi-Min; Chen, Yen-Ching

2015-12-01

Leisure activities have been associated with a decreased risk of dementia. However, to date, no study has explored how apolipoprotein E (ApoE) e4 status or vascular risk factors modified the association between leisure activities and dementia risks. This case-control study recruited patients (age ≥ 60 years) with Alzheimer's disease (AD; n = 292) and vascular dementia (VaD; n = 144) and healthy controls (n = 506) from three teaching hospitals in Taiwan between 2007 and 2010. Information on patient's leisure activities were obtained through a questionnaire. Conditional logistic regression models were used to assess the association of leisure activities and ApoE e4 status with the risk of dementia. High-frequency physical activity was associated with a decreased risk of AD [adjusted odds ratio (AOR) = 0.45], and the results become more evident among ApoE e4 carriers with AD (AOR = 0.30) and VaD (AOR = 0.26). Similar findings were observed for cognitive (AOR = 0.42) and social activities (AOR = 0.55) for AD. High-frequency physical, cognitive, and social activities were associated with a decreased risk of VaD (AOR = 0.29-0.60). Physical and social activities significantly interacted with each other on the risk of VaD (pinteraction = 0.04). Physical activity consistently protects against AD and VaD. Significant interactions were identified across different types of leisure activities in lowering dementia risk. Copyright © 2014. Published by Elsevier B.V.

Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

Directory of Open Access Journals (Sweden)

Angela Cassese

Full Text Available Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15 causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1. Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4 restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15 by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

CINEMA 4D The Artist's Project Sourcebook

CERN Document Server

McQuilkin, Kent

2011-01-01

Cinema 4D is a fully integrated 3D modeling, animation, and rendering package used extensively in the film, television, science, architecture, engineering and other industries. Generally ranked as the 3rd most widely-used 3Dapplication Cinema 4D is widely praised for its stability, speed and ease of use. Recent film and broadcast productions that have used Cinema 4D include Open Season, Monster House, Superman Returns, Polar Express, Monday Night Football. This third edition of Cinema 4D is updated to address the latest release of the application as well as its critically acclaimed MoGr

The neural cell adhesion molecule L1 is distinct from the N-CAM related group of surface antigens BSP-2 and D2

DEFF Research Database (Denmark)

Faissner, A; Kruse, J; Goridis, C

1984-01-01

The neural cell adhesion molecule L1 and the group of N-CAM related molecules, BSP-2 and D2 antigen, are immunochemically distinct molecular species. The two groups of surface molecules are also functionally distinct entities, since inhibition of Ca2+-independent adhesion among early post-natal m...

Activated sludge model No. 2d, ASM2d

DEFF Research Database (Denmark)

Henze, M.

1999-01-01

The Activated Sludge Model No. 2d (ASM2d) presents a model for biological phosphorus removal with simultaneous nitrification-denitrification in activated sludge systems. ASM2d is based on ASM2 and is expanded to include the denitrifying activity of the phosphorus accumulating organisms (PAOs......). This extension of ASM2 allows for improved modeling of the processes, especially with respect to the dynamics of nitrate and phosphate. (C) 1999 IAWQ Published by Elsevier Science Ltd. All rights reserved....

Synthesis, anti-microbial activity, cytotoxicity of some novel substituted (5-(3-(1H-benzo[d]imidazol-2-yl)-4-hydroxybenzyl)benzofuran-2-yl)(phenyl)methanone analogs.

Science.gov (United States)

Shankar, Bhookya; Jalapathi, Pochampally; Saikrishna, Balabadra; Perugu, Shaym; Manga, Vijjulatha

2018-01-09

There is a dire need for the discovery and development of new antimicrobial agents after several experiments for a better resistance of microorganisms towards antimicrobial agents become a serious health problem for a few years in the past. As benzimidazole possess various types of biological activities, it has been synthesized, in the present study, a new series of (5-(3-(1H-benzo[d]imidazol-2-yl)-4-hydroxybenzyl)benzofuran-2-yl)(phenyl)methanone analogs by using the condensation and screened for its in vitro antimicrobial activity and cytotoxicity. The synthesized (5-(3-(1H-benzo[d]imidazol-2-yl)-4-hydroxybenzyl) benzofuran-2-yl)(phenyl)methanone analogs were confirmed by IR, 1 H and 13 C-NMR, MS spectra and HRMS spectral data. The synthesized compounds were evaluated for their in vitro antimicrobial potential against Gram-positive (Bacillus subtilis, Bacillus megaterium, Staph aureus and Streptococcus pyogenes), Gram-negative (Escherichia coli, Proteus vulgaris, Proteus mirabilis and Enterobacter aerogenes) bacterial and fungal (Aspergillus niger, Candida albicans, Fusarium oxysporum, Fusarium solani) strains by disc diffusion method and the minimum inhibitory concentration (MIC) in which it has been recorded in microgram per milliliter in comparison to the reference drugs, ciprofloxacin (antibacterial) and nystatin (antifungal). Further, the cytotoxicity (IC 50 value) has also been assessed on human cervical (HeLa), Supt1 cancer cell lines by using MTT assay. The following screened compounds (4d), (4f), (4g), (4k), (4l), (4o) and (4u) were found to be the best active against all the tested bacterial and fungal strains among all the demonstrated compounds of biological study. The MIC determination was also carried out against bacteria and fungi, the compounds (4f) and (4u) are found to be exhibited excellent potent against bacteria and fungi respectively. The compounds (4f) and (4u) were shown non-toxic in nature after screened for cytotoxicity against the

From 3D to 4D printing: approaches and typical applications

International Nuclear Information System (INIS)

Zhou, Ye; Huang, Wei Min; Kang Shu Feng; Wu, Xue Lian; Lu, Hai Bao; Fu, Jun; Cui, Haipo

2015-01-01

With the additional dimension, 4D printing is emerging as a novel technique to enable configuration switching in 3D printed items. In this paper, four major approaches, namely self-assembly of elements, deformation mismatch, bi-stability, and the Shape memory effect (SME), are identified as the generic approaches to achieve 4D printing. The main features of these approaches are briefly discussed. Utilizing these approaches either individually or in a combined manner, the potential of 4D printing to reshape product design is demonstrated by a few example applications.

From 3D to 4D printing: approaches and typical applications

Energy Technology Data Exchange (ETDEWEB)

Zhou, Ye; Huang, Wei Min [Nanyang Technological University, Singapore (Singapore); Kang Shu Feng [Shenzhen Woer Heat-Shrinkable Material Co. Ltd, Shenzhen (China); Wu, Xue Lian [Jiangsu University, Zhenjiang (China); Lu, Hai Bao [Harbin Institute of Technology, Harbin (China); Fu, Jun [Chinese Academy of Sciences, Ningbo (China); Cui, Haipo [University of Shanghai for Science and Technology, Shanghai (China)

2015-10-15

With the additional dimension, 4D printing is emerging as a novel technique to enable configuration switching in 3D printed items. In this paper, four major approaches, namely self-assembly of elements, deformation mismatch, bi-stability, and the Shape memory effect (SME), are identified as the generic approaches to achieve 4D printing. The main features of these approaches are briefly discussed. Utilizing these approaches either individually or in a combined manner, the potential of 4D printing to reshape product design is demonstrated by a few example applications.

Thermally activated 3D to 2D structural transformation of [Ni2(en)2(H2O)6(pyr)]·4H2O flexible coordination polymer

International Nuclear Information System (INIS)

Begović, Nebojša N.; Blagojević, Vladimir A.; Ostojić, Sanja B.; Radulović, Aleksandra M.; Poleti, Dejan; Minić, Dragica M.

2015-01-01

Thermally activated 3D to 2D structural transformation of the binuclear [Ni 2 (en) 2 (H 2 O) 6 (pyr)]·4H 2 O complex was investigated using a combination of theoretical and experimental methods. Step-wise thermal degradation (dehydration followed by release of ethylene diamine) results in two layered flexible coordination polymer structures. Dehydration process around 365 K results in a conjugated 2D structure with weak interlayer connectivity. It was shown to be a reversible 3D to 2D framework transformation by a guest molecule, and rehydration of the dehydration product occurs at room temperature in saturated water vapor. Rehydrated complex exhibits lower dehydration temperature, due to decreased average crystalline size, with higher surface area resulting in easier release and diffusion of water during dehydration. Thermal degradation of dehydration around 570 K, results in loss of ethylene diamine, producing a related 2D layered polymer structure, without interconnectivity between individual polymer layers. - Highlights: • Reversible 3D to 2D framework topochemical transformation on dehydration around 365 K. • Resulting polymer exhibits 2D layered structure with weak interlayer connectivity. • Dehydration is fully reversible in saturated water vapor at room temperature. • Further degradation around 570 K yields 2D polymer without interlayer connectivity. • 2D polymer exhibits conjugated electronic system

Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

Science.gov (United States)

Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming

2016-07-01

Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis, Antifungal and Antitumor Activity of Novel (Z-5-Hetarylmethylidene-1,3-thiazol-4-ones and (Z-5-Ethylidene-1,3-thiazol-4-ones

Directory of Open Access Journals (Sweden)

Susana A. Zacchino

2013-05-01

Full Text Available New hetaryl- and alkylidenerhodanine derivatives 3a–d, 3e, and 4a–d were prepared from heterocyclic aldehydes 1a–d or acetaldehyde 1e. The treatment of several rhodanine derivatives 3a–d and 3e with piperidine or morpholine in THF under reflux, afforded (Z-5-(hetarylmethylidene-2-(piperidin-1-ylthiazol-4(5H-ones and 2-morpholinothiazol-4(5H-ones 5a–d, 6a–d, and (Z-5-ethylidene-2-morpholinothiazol-4(5H-one (5e, respectively, in good yields. Structures of all compounds were determined by IR, 1D and 2D NMR and mass spectrometry. Several of these compounds were screened by the U.S. National Cancer Institute (NCI to assess their antitumor activity against 60 different human tumor cell lines. Compound 3c showed high activity against HOP-92 (Non-Small Cell Lung Cancer, which was the most sensitive cell line, with GI50 = 0.62 μM and LC50 > 100 μM from the in vitro assays. In vitro antifungal activity of these compounds was also determined against 10 fungal strains. Compound 3e showed activity against all fungal strains tested, but showed high activity against Saccharomyces cerevisiae (MIC 3.9 μg/mL.

Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4

Directory of Open Access Journals (Sweden)

Tobias Zöller

2018-03-01

Full Text Available Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB and six ULBP molecules (ULBP1–6, there are a total of eight human NKG2D ligands (NKG2DL. Since the discovery of the NKG2D–NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions. Here, we critically review the current state of knowledge on the poorly studied human NKG2DL ULBP4. Summarizing available facts and previous studies, we picture ULBP4 as a peculiar ULBP family member distinct from other ULBP family members by various aspects. In addition, we provide novel experimental evidence suggesting that cellular processing gives rise to mature ULBP4 glycoproteins different to previous reports. Finally, we report on the proteolytic release of soluble ULBP4 and discuss these results in the light of known mechanisms for generation of soluble NKG2DL.

No Evidence for a Relationship Between Hair Testosterone Concentrations and 2D:4D Ratio or Risk Taking

Directory of Open Access Journals (Sweden)

Richard Ronay

2018-03-01

Full Text Available Using a recently developed alternative assay procedure to measure hormone levels from hair samples, we examined the relationships between testosterone, cortisol, 2D:4D ratio, overconfidence and risk taking. A total of 162 (53 male participants provided a 3 cm sample of hair, a scanned image of their right and left hands from which we determined 2D:4D ratios, and completed measures of overconfidence and behavioral risk taking. While our sample size for males was less than ideal, our results revealed no evidence for a relationship between hair testosterone concentrations, 2D:4D ratios and risk taking. No relationships with overconfidence emerged. Partially consistent with the Dual Hormone Hypothesis, we did find evidence for the interacting effect of testosterone and cortisol on risk taking but only in men. Hair testosterone concentrations were positively related to risk taking when levels of hair cortisol concentrations were low, in men. Our results lend support to the suggestion that endogenous testosterone and 2D:4D ratio are unrelated and might then exert diverging activating vs. organizing effects on behavior. Comparing our results to those reported in the existing literature we speculate that behavioral correlates of testosterone such as direct effects on risk taking may be more sensitive to state-based fluctuations than baseline levels of testosterone.

Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

Science.gov (United States)

Lorefice, S.; Becerra, L. O.

2017-01-01

Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Low 2D:4D values are associated with video game addiction.

Science.gov (United States)

Kornhuber, Johannes; Zenses, Eva-Maria; Lenz, Bernd; Stoessel, Christina; Bouna-Pyrrou, Polyxeni; Rehbein, Florian; Kliem, Sören; Mößle, Thomas

2013-01-01

Androgen-dependent signaling regulates the growth of the fingers on the human hand during embryogenesis. A higher androgen load results in lower 2D:4D (second digit to fourth digit) ratio values. Prenatal androgen exposure also impacts brain development. 2D:4D values are usually lower in males and are viewed as a proxy of male brain organization. Here, we quantified video gaming behavior in young males. We found lower mean 2D:4D values in subjects who were classified according to the CSAS-II as having at-risk/addicted behavior (n = 27) compared with individuals with unproblematic video gaming behavior (n = 27). Thus, prenatal androgen exposure and a hyper-male brain organization, as represented by low 2D:4D values, are associated with problematic video gaming behavior. These results may be used to improve the diagnosis, prediction, and prevention of video game addiction.

Low 2D:4D values are associated with video game addiction.

Directory of Open Access Journals (Sweden)

Johannes Kornhuber

Full Text Available Androgen-dependent signaling regulates the growth of the fingers on the human hand during embryogenesis. A higher androgen load results in lower 2D:4D (second digit to fourth digit ratio values. Prenatal androgen exposure also impacts brain development. 2D:4D values are usually lower in males and are viewed as a proxy of male brain organization. Here, we quantified video gaming behavior in young males. We found lower mean 2D:4D values in subjects who were classified according to the CSAS-II as having at-risk/addicted behavior (n = 27 compared with individuals with unproblematic video gaming behavior (n = 27. Thus, prenatal androgen exposure and a hyper-male brain organization, as represented by low 2D:4D values, are associated with problematic video gaming behavior. These results may be used to improve the diagnosis, prediction, and prevention of video game addiction.

4D Bioprinting for Biomedical Applications.

Science.gov (United States)

Gao, Bin; Yang, Qingzhen; Zhao, Xin; Jin, Guorui; Ma, Yufei; Xu, Feng

2016-09-01

3D bioprinting has been developed to effectively and rapidly pattern living cells and biomaterials, aiming to create complex bioconstructs. However, placing biocompatible materials or cells into direct contact via bioprinting is necessary but insufficient for creating these constructs. Therefore, '4D bioprinting' has emerged recently, where 'time' is integrated with 3D bioprinting as the fourth dimension, and the printed objects can change their shapes or functionalities when an external stimulus is imposed or when cell fusion or postprinting self-assembly occurs. In this review, we highlight recent developments in 4D bioprinting technology. Additionally, we review the uses of 4D bioprinting in tissue engineering and drug delivery. Finally, we discuss the major roadblocks to this approach, together with possible solutions, to provide future perspectives on this technology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Finger length ratio (2D:4D) in adults with gender identity disorder.

Science.gov (United States)

Kraemer, Bernd; Noll, Thomas; Delsignore, Aba; Milos, Gabriella; Schnyder, Ulrich; Hepp, Urs

2009-06-01

From early childhood, gender identity and the 2nd to 4th finger length ratio (2D:4D) are discriminative characteristics between sexes. Both the human brain and 2D:4D may be influenced by prenatal testosterone levels. This calls for an examination of 2D:4D in patients with gender identity disorder (GID) to study the possible influence of prenatal testosterone on gender identity. Until now, the only study carried out on this issue suggests lower prenatal testosterone levels in right-handed male-to-female GID patients (MtF). We compared 2D:4D of 56 GID patients (39 MtF; 17 female-to-male GID patients, FtM) with data from a control sample of 176 men and 190 women. Bivariate group comparisons showed that right hand 2D:4D in MtF was significantly higher (feminized) than in male controls, but similar to female controls. The comparison of 2D:4D ratios of biological women revealed significantly higher (feminized) values for right hands of right handed FtM. Analysis of variance confirmed significant effects for sex and for gender identity on 2D:4D ratios but not for sexual orientation or for the interaction among variables. Our results indirectly point to the possibility of a weak influence of reduced prenatal testosterone as an etiological factor in the multifactorially influenced development of MtF GID. The development of FtM GID seems even more unlikely to be notably influenced by prenatal testosterone.

Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

Directory of Open Access Journals (Sweden)

Hua Bai

Full Text Available Mutations of the insulin/IGF signaling (IIS pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1. Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP. Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

Relationships of Smiling and Flirtation to Aggression and 2D:4D, a Prenatal Androgen Index

Directory of Open Access Journals (Sweden)

Leslie Burton

2011-01-01

Full Text Available Smiling has been reported to be a signal of submission/lower status, or a sign of cooperation. In the present study, use of smiling and flirtation to “make people receptive to my ideas” was conceptualized as mild aggression, since it is mildly manipulative of the perception of others as to one's internal emotional status. For 91 participants (55 female, 36 male, use of smiling and flirtation to make others receptive to one's ideas were associated with relational aggression and a more male-typical (smaller right 2D:4D finger length ratio. The only significant relationship in the male sample alone was the relationship between smiling and relational aggression. In the female sample alone, use of smiling and flirtation to “make people receptive to my ideas” was associated with a more male-typical 2D:4D finger length ratio pattern, and there was a trend for flirtation to be associated with greater physical aggression. Both 2D:4D and physical aggression have been associated with higher prenatal androgen level. It is concluded that deliberate smiling and flirtation are mild forms of relational aggression, and are related to prenatal androgenic activity in a manner similar to physical aggression. These findings are discussed in terms of the different evolutionary strategies of men and women to control their social environments.

Different bacteriocin activities of Streptococcus mutans reflect distinct phylogenetic lineages

DEFF Research Database (Denmark)

Balakrishnan, M; Simmonds, RS; Kilian, Mogens

2002-01-01

Bacteriocins produced by mutans streptococci are known as mutacins. In this study 16 broadly active mutacin-producing Streptococcus mutans strains from New Zealand, North America and Europe were classified into four groups (A-D) on the basis of differences in their activity in deferred antagonism...... described by Caufield and co-workers. One of the New Zealand isolates of group A (S. mutans strain N) appeared to produce inhibitory activity similar to that of the group I prototype strain UA140. Four other New Zealand isolates of group B (S. mutans strains M19, M34, B34 and D14) had mutacin II......-like activity. The group B mutacin producers differed from the group A mutacin producers in their additional activity against Staph. aureus 46. Seven S. mutans strains (M46, B46, B57, M12, M28, B28 and 13M) were distinguished from the group A and group B mutacin producers in that they inhibited E. faecium TE1...

SP-D impedes transfer of HIV-1 from multi-layered vaginal epithelium with a distinct gene signature

Directory of Open Access Journals (Sweden)

Hrishikesh Pandit

2017-12-01

Full Text Available Surfactant Protein (SP D is a member of the collectin family of soluble pattern recognition receptors. We have previously shown that a recombinant fragment of SP-D (rhSP-D inhibits gp120-CD4 interaction and HIV-1 entry in target cells. To potentiate its prophylactic use as a vaginal microbicide, we determined ex vivo efficacy using organotypic human vaginal-ectocervical epithelia (VEC-100 that closely resemble the native tissues of origin. VEC-100, stratified human vaginal-ectocervical tissues grown on membrane inserts were treated with rhSP-D followed by a challenge with HIV-1 to assess the transfer of HIV-1 through the VEC-100 tissues to PBMCs in the basal submucosal compartment. Treated VEC tissues were subjected to mRNA Illumina microarray analysis. Levels of transcripts encoding for immune mediators, adhesion and tight junction proteins were also evaluated. Effect of rhSP-D on viability, NFκB activation, cytokine secretion and bacterial colonization of cervical vaginal epithelial cells was determined. rhSP-D significantly inhibited HIV-1 transfer from the multi-layered epithelial tissues to the basal PBMCs as compared to HIV-1 alone. Global gene expression profile of HIV-1 challenged VEC-100 tissues revealed differential regulation of genes and pathways majorly involved in inflammation, cell survival and transcription factors. Levels of Guanylate-binding proteins (GBPs and interferon-inducible proteins were significantly upregulated suggesting an interferon host defense response. rhSP-D showed an inhibition in the levels of GBPs and rescued the cell adhesion molecules such as Claudin 2, 3, 4, 5 and Occludin, known to be down regulated by HIV-1 in primary vaginal cells. Importantly, rhSP-D conditioned VEC tissue supernatants did not enhance susceptibility of target cells to HIV-1. rhSP-D treated vaginal epithelial cells did not show any significant alteration in viability, NFκB activation and levels of immune mediators like IL-1RA, Elafin

3D and 4D Seismic Technics Today

Directory of Open Access Journals (Sweden)

Marcin Marian

2004-09-01

Full Text Available Years ago, exploration was done through surface observations and „divining rods“ – now, it is done by satellites, microprocessors, remote sensing, and supercomputers. In the 1970´ s, the exploration success rate was 14 percent, today, it is nearly 29 percent. Not so long ago, three – dimension (3D seismic diagnostic techniques helped recover 25-50 percent of the oil in place – now, 4D seismic helps recover up to 70 percent of the oil in place. 3D and 4D seismic and earth imaging systems also help in understanding the subsurface flow of other fluids, such as groundwater and pollutants.Seismic surveys – a technique in which sound waves are bounced off underground rock struktures to reveal possible oil and gas bearing formation – are now standard fare for the modern petroleum industry. But today’s seismic methods are best at locating „structural traps“ where faults or folds in the underground rock have created zones where oil can become trapped.

Anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose isolated from leaves of Mangifera indica.

Science.gov (United States)

Viswanatha, G L; Mohan, C G; Shylaja, H; Yuvaraj, H C; Sunil, V

2013-07-01

The present study was aimed to evaluate the anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) isolated from methanolic leaf extracts of Mangifera indica in mice. Anticonvulsant activity of PGG was evaluated against pentylenetetrazole (PTZ)-induced and maximal electroshock (MES)-induced convulsions in mice. Additionally, locomotor activity and GABA levels in the brain were estimated to explore the possible CNS-depressant activity and mechanism behind the anticonvulsant activity, respectively. In these studies, PGG (2.5, 5, and 10 mg/kg, intraperitoneal (i.p.)) showed significant and dose-dependent inhibition of PTZ and MES-induced convulsions. Furthermore, PGG administration showed significant decrease in the locomotor activity as an indication of its CNS-depressant property; also, PGG has significantly increased the GABA levels in the cerebellum and whole brain other than the cerebellum. In conclusion, PGG isolated from M. indica showed potent anticonvulsant activity, and possible mechanism may be due to enhanced GABA levels in the brain.

Structure-activity relationships for flavone interactions with amyloid β reveal a novel anti-aggregatory and neuroprotective effect of 2',3',4'-trihydroxyflavone (2-D08).

Science.gov (United States)

Marsh, Dylan T; Das, Sukanya; Ridell, Jessica; Smid, Scott D

2017-07-15

Naturally-occurring flavonoids have well documented anti-aggregatory and neuroprotective properties against the hallmark toxic protein in Alzheimer's disease, amyloid β (Aβ). However the extensive diversity of flavonoids has limited the insight into the precise structure-activity relationships that confer such bioactive properties against the Aβ protein. In the present study we have characterised the Aβ binding properties, anti-aggregatory and neuroprotective effects of a discreet set of flavones, including the recently described novel protein sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Quercetin, transilitin, jaceosidin, nobiletin and 2-D08 were incubated with human Aβ 1-42 for 48h in vitro and effects on Aβ fibrillisation kinetics and morphology measured using Thioflavin T (ThT) and electron microscopy respectively, in addition to effects on neuronal PC12 cell viability. Of the flavones studied, only quercetin, transilitin and 2-D08 significantly inhibited Aβ 1-42 aggregation and toxicity in PC12 cells. Of those, 2-D08 was the most effective inhibitor. The strong anti-amyloid activity of 2-D08 indicates that extensive hydroxylation in the B ring is the most important determinant of activity against β amyloid within the flavone scaffold. The lack of efficacy of jaceosidin and nobiletin indicate that extension of B ring hydroxylation with methoxyl groups result in an incremental loss of anti-fibrillar and neuroprotective activity, highlighting the constraint to vicinal hydroxyl groups in the B ring for effective inhibition of aggregation. These findings reveal further structural insights into anti-amyloid bioactivity of flavonoids in addition to a novel and efficacious anti-aggregatory and neuroprotective effect of the semi-synthetic flavone and sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Such modified flavones may facilitate drug development targeting multiple pathways in neurodegenerative disease. Crown Copyright © 2017

Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

Science.gov (United States)

Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

2018-02-22

Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

4d quantum geometry from 3d supersymmetric gauge theory and holomorphic block

International Nuclear Information System (INIS)

Han, Muxin

2016-01-01

A class of 3d N=2 supersymmetric gauge theories are constructed and shown to encode the simplicial geometries in 4-dimensions. The gauge theories are defined by applying the Dimofte-Gaiotto-Gukov construction http://dx.doi.org/10.1007/s00220-013-1863-2 in 3d-3d correspondence to certain graph complement 3-manifolds. Given a gauge theory in this class, the massive supersymmetric vacua of the theory contain the classical geometries on a 4d simplicial complex. The corresponding 4d simplicial geometries are locally constant curvature (either dS or AdS), in the sense that they are made by gluing geometrical 4-simplices of the same constant curvature. When the simplicial complex is sufficiently refined, the simplicial geometries can approximate all possible smooth geometries on 4-manifold. At the quantum level, we propose that a class of holomorphic blocks defined in http://dx.doi.org/10.1007/JHEP12(2014)177 from the 3d N=2 gauge theories are wave functions of quantum 4d simplicial geometries. In the semiclassical limit, the asymptotic behavior of holomorphic block reproduces the classical action of 4d Einstein-Hilbert gravity in the simplicial context.

D$^{6}$ℛ$^{4}$ amplitudes in various dimensions

CERN Document Server

Pioline, Boris

2015-01-01

Four-graviton couplings in the low energy effective action of type II string vacua compactified on tori are strongly constrained by supersymmetry and U-duality. While the $R^4$ and $D^4 R^4$ couplings are known exactly in terms of Langlands-Eisenstein series of the U-duality group, the $D^6 R^4$ couplings are not nearly as well understood. Exploiting the coincidence of the U-duality group in $D=6$ with the T-duality group in $D=5$, we propose an exact formula for the $D^6 R^4$ couplings in type II string theory compactified on $T^4$, in terms of a genus-two modular integral plus a suitable Eisenstein series. The same modular integral computes the two-loop correction to $D^6 R^4$ in 5 dimensions, but here provides the non-perturbative completion of the known perturbative terms in $D=6$. This proposal hinges on a systematic re-analysis of the weak coupling and large radius of the $D^6 R^4$ in all dimensions $D\\geq 3$, which fills in some gaps and resolves some inconsistencies in earlier studies.

25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression.

Directory of Open Access Journals (Sweden)

Zaki K Hassan-Smith

Full Text Available Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia, but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH2D3, but not inactive 25-hydroxyvitamin D3 (25OHD3, correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02, velocity (Vmax, rho = 0.40, p = 0.02 and jump height (rho = 0.36, p = 0.04. Lean mass correlated positively with 1α,25(OH2D3 (rho = 0.47, p = 0.02, in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH2D3 had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively. Serum 25OHD3 and 24,25(OH2D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH2D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH2D3 has limited effects on muscle gene

4D ultrasound and 3D MRI registration of beating heart

International Nuclear Information System (INIS)

Herlambang, N.; Matsumiya, K.; Masamune, K.; Dohi, T.; Liao, H.; Tsukihara, H.; Takamoto, S.

2007-01-01

To realize intra-cardiac surgery without cardio-pulmonary bypass, a medical imaging technique with both high image quality and data acquisition rate that is fast enough to follow heart beat movements is required. In this research, we proposed a method that utilized the image quality of MRI and the speed of ultrasound. We developed a 4D image reconstruction method using image registration of 3D MRI and 4D ultrasound images. The registration method consists of rigid registration between 3D MRI and 3D ultrasound with the same heart beat phase, and non-rigid registration between 3D ultrasound images from different heart beat phases. Non-rigid registration was performed with B-spline based registration using variable spring model. In phantom experiment using balloon phantom, registration accuracy was less than 2 mm for total heart volume variation range of 10%. We applied our registration method on 3D MRI and 4D ultrasound images of a volunteer's beating heart data and confirmed through visual observation that heart beat pattern was well reproduced. (orig.)

4D printing of a self-morphing polymer driven by a swellable guest medium.

Science.gov (United States)

Su, Jheng-Wun; Tao, Xiang; Deng, Heng; Zhang, Cheng; Jiang, Shan; Lin, Yuyi; Lin, Jian

2018-01-31

There is a significant need of advanced materials that can be fabricated into functional devices with defined three-dimensional (3D) structures for application in tissue engineering, flexible electronics, and soft robotics. This need motivates an emerging four-dimensional (4D) printing technology, by which printed 3D structures consisting of active materials can transform their configurations over time in response to stimuli. Despite the ubiquity of active materials in performing self-morphing processes, their potential for 4D printing has not been fully explored to date. In this study, we demonstrate 4D printing of a commercial polymer, SU-8, which has not been reported to date in this field. The working principle is based on a self-morphing process of the printed SU-8 structures through spatial control of the swelling medium inside the polymer matrix by a modified process. To understand the self-morphing behavior, fundamental studies on the effect of the geometries including contours and filling patterns were carried out. A soft electronic device as an actuator was demonstrated to realize an application of this programmable polymer using the 3D printing technology. These studies provide a new paradigm for application of SU-8 in 4D printing, paving a new route to the exploration of more potential candidates by this demonstrated strategy.

The 4D Nucleome: Genome Compartmentalization in an Evolutionary Context.

Science.gov (United States)

Cremer, T; Cremer, M; Cremer, C

2018-04-01

4D nucleome research aims to understand the impact of nuclear organization in space and time on nuclear functions, such as gene expression patterns, chromatin replication, and the maintenance of genome integrity. In this review we describe evidence that the origin of 4D genome compartmentalization can be traced back to the prokaryotic world. In cell nuclei of animals and plants chromosomes occupy distinct territories, built up from ~1 Mb chromatin domains, which in turn are composed of smaller chromatin subdomains and also form larger chromatin domain clusters. Microscopic evidence for this higher order chromatin landscape was strengthened by chromosome conformation capture studies, in particular Hi-C. This approach demonstrated ~1 Mb sized, topologically associating domains in mammalian cell nuclei separated by boundaries. Mutations, which destroy boundaries, can result in developmental disorders and cancer. Nucleosomes appeared first as tetramers in the Archaea kingdom and later evolved to octamers built up each from two H2A, two H2B, two H3, and two H4 proteins. Notably, nucleosomes were lost during the evolution of the Dinoflagellata phylum. Dinoflagellate chromosomes remain condensed during the entire cell cycle, but their chromosome architecture differs radically from the architecture of other eukaryotes. In summary, the conservation of fundamental features of higher order chromatin arrangements throughout the evolution of metazoan animals suggests the existence of conserved, but still unknown mechanism(s) controlling this architecture. Notwithstanding this conservation, a comparison of metazoans and protists also demonstrates species-specific structural and functional features of nuclear organization.

TCTEX1D4, a novel protein phosphatase 1 interactor: connecting the phosphatase to the microtubule network

Science.gov (United States)

Korrodi-Gregório, Luís; Vieira, Sandra I.; Esteves, Sara L. C.; Silva, Joana V.; Freitas, Maria João; Brauns, Ann-Kristin; Luers, Georg; Abrantes, Joana; Esteves, Pedro J.; da Cruz e Silva, Odete A. B.; Fardilha, Margarida; da Cruz e Silva, Edgar F.

2013-01-01

Summary Reversible phosphorylation plays an important role as a mechanism of intracellular control in eukaryotes. PPP1, a major eukaryotic Ser/Thr-protein phosphatase, acquires its specificity by interacting with different protein regulators, also known as PPP1 interacting proteins (PIPs). In the present work we characterized a physiologically relevant PIP in testis. Using a yeast two-hybrid screen with a human testis cDNA library, we identified a novel PIP of PPP1CC2 isoform, the T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) that has recently been described as a Tctex1 dynein light chain family member. The overlay assays confirm that TCTEX1D4 interacts with the different spliced isoforms of PPP1CC. Also, the binding domain occurs in the N-terminus, where a consensus PPP1 binding motif (PPP1BM) RVSF is present. The distribution of TCTEX1D4 in testis suggests its involvement in distinct functions, such as TGFβ signaling at the blood–testis barrier and acrosome cap formation. Immunofluorescence in human ejaculated sperm shows that TCTEX1D4 is present in the flagellum and in the acrosome region of the head. Moreover, TCTEX1D4 and PPP1 co-localize in the microtubule organizing center (MTOC) and microtubules in cell cultures. Importantly, the TCTEX1D4 PPP1BM seems to be relevant for complex formation, for PPP1 retention in the MTOC and movement along microtubules. These novel results open new avenues to possible roles of this dynein, together with PPP1. In essence TCTEX1D4/PPP1C complex appears to be involved in microtubule dynamics, sperm motility, acrosome reaction and in the regulation of the blood–testis barrier. PMID:23789093

Assessment of the 2D:4D ratio in aggression-related injuries in children attending a paediatric emergency department.

Science.gov (United States)

O'Briain, D E; Dawson, P H; Kelly, J C; Connolly, P

2017-05-01

The 2D:4D ratio is a sexually dimorphic trait. A lower ratio is correlated with sporting prowess, successful financial trading, risk taking behaviour, aggression, and aggression-related injuries, such as the fifth metacarpal fractures. We aimed to assess if the ratio correlates to skeletally immature patient aggression. Radiology reports were searched for the terms "5th metacarpal" or "boxer". Of 537 X-rays, 142 had fractures. The mechanism of injury was recorded in 102 patients, differentiating aggressive and non-aggressive injury groups. Bone age and chronological age were recorded. A clear male preponderance for aggression was identified with only 60% of non-aggressive injuries occurring in males compared to 95% in the aggression group (p aggression injuries were older chronologically (14.6 vs 12.7, p Aggression injuries occur at an older age and are more common in males. In the female cohort, there was a distinct difference in digit ratio.

1996 Activity report; Rapport d`activite 1996

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

The 1996 activity report of the Direction for Waste Management of the CEA, is presented. Its activities have been developed in the framework of the general CEA cleaning plan, and include the management of wastes generated before 1992 in R and D CEA facilities, the disposal of spent fuels generated by research reactors (Orphee and Siloe) or prototype reactors (EL4 at Brennilis), and the dismantling and cleaning of obsolete facilities such as the plutonium radiochemistry building at Fontenay-aux-Roses and the pilot workshop at Marcoule

Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

Directory of Open Access Journals (Sweden)

Mengwen Qi

2018-02-01

Full Text Available Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4 is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047 and GlyR (strychnine, indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC (BIM II or D-sphingosine or calcium/calmodulin-dependent protein kinase II (CaMKII (KN-62 or KN-93 antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv. injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

Anti-trypanosomal activity of 1,2,3,4,6-penta-O-galloyl-? -D-glucose isolated from Plectranthus barbatus Andrews (Lamiaceae)

Energy Technology Data Exchange (ETDEWEB)

Santos, Roberta T. dos; Hiramoto, Liliane L.; Lago, Joao Henrique G.; Sartorelli, Patricia [Universidade Federal de Sao Paulo (UNIFESP), Diadema, SP (Brazil). Inst. de Ciencias Ambientais, Quimicas e Farmaceuticas; Tempone, Andre G.; Pinto, Erika G. [Instituto Adolfo Lutz, Sao Paulo, SP (Brazil). Dept. de Parasitologia; Lorenzi, Harri, E-mail: psartorelli@unifesp.br [Instituto Plantarum de Estudos da Flora, Nova Odessa, SP (Brazil)

2012-07-01

MeOH extract from the leaves of Plectranthus barbatus Andrews (Lamiaceae), showed in vitro anti-trypanosomal activity. The bioassay-guided fractionation resulted in the isolation of a gallic acid derivative, identified as 1,2,3,4,6-penta-O-galloyl-{beta}-D-glucose (PGG), after thorough NMR and MS spectral analysis. Finally, this compound was tested against trypomastigote forms of T. cruzi and displayed an EC{sub 50} value of 67 {mu}M, at least 6.6-fold more effective than the standard drug benznidazole. This is the first occurrence of PGG in the Plectranthus genus and the first anti-parasitic activity described for PGG in the literature (author)

Synthesis, antimicrobial and cytotoxic activities of 5-benzylidene-2-[(pyridine-4-ylmethylenehydrazono]-thiazolidin-4-one and 2-[(pyridine-4-ylmethylene hydrazono]-thiazolidin-4-one derivatives

Directory of Open Access Journals (Sweden)

Danniel Delmondes Feitoza

2012-01-01

Full Text Available A new series of 5-benzylidene-2-[(pyridine-4-ylmethylenehydrazono]-thiazolidin-4-ones 4a-l have been synthesized. These compounds were designed by a molecular hybridization approach. 2-[(Pyridine-4-ylmethylenehydrazono]-thiazolidin-4-ones 3a-d were also obtained and used as intermediates to give the target compounds. The in vitro antimicrobial and cytotoxic activities were evaluated for both series. The intermediate 3b showed considerable antibiotic activity against B. subtilis and C. albicans. In the cytotoxic activity compounds 3b (IC50= 4.25 ± 0.36 µg/mL and 4l (IC50= 1.38 ± 0.04 µg/mL were effective for inhibition of human erythromyeloblastoid leukemia (K-562 and human lung carcinoma (NCI-H292 cell lines, respectively.

D6R4 amplitudes in various dimensions

International Nuclear Information System (INIS)

Pioline, Boris

2015-01-01

Four-graviton couplings in the low energy effective action of type II string vacua compactified on tori are strongly constrained by supersymmetry and U-duality. While the R 4 and D 4 R 4 couplings are known exactly in terms of Langlands-Eisenstein series of the U-duality group, the D 6 R 4 couplings are not nearly as well understood. Exploiting the coincidence of the U-duality group in D=6 with the T-duality group in D=5, we propose an exact formula for the D 6 R 4 couplings in type II string theory compactified on T 4 , in terms of a genus-two modular integral plus a suitable Eisenstein series. The same modular integral computes the two-loop correction to D 6 R 4 in 5 dimensions, but here provides the non-perturbative completion of the known perturbative terms in D=6. This proposal hinges on a systematic re-analysis of the weak coupling and large radius of the D 6 R 4 in all dimensions D≥3, which fills in some gaps and resolves some inconsistencies in earlier studies.

Synthesis and biological evaluation of new pyrazolo[3,4-d]pyrimidine derivatives

Directory of Open Access Journals (Sweden)

Asma Agrebi

2014-05-01

Full Text Available Several new pyrazolopyrimidine compounds were achieved from aminocyanopyarazole 1. The starting material 1 was initially coupled with orthoester at refluxed with various primary amines, ammonia, hydrazines and hydroxylamine to furnish a series of pyrazolo[3,4-d]pyrimidines. The reaction of imidate 2a-b with hydrazide derivatives led to the formation of pyrazolo[3,4-d][1,2,4]triazolo[4,3-c]pyrimidines. Some of the synthesized compounds 3a and 4c were evaluated for their anti-inflammatory, antipyretic and nociceptive activities. We start by studing the toxicity of these two molecules by measuring the corresponding DL50. The DL50 of 3a and 4c are estimated to 1333.2mg / kg and 1593.5mg / kg respectively. Pharmacological evaluation showed that compounds 3a and 4c at doses (5.5-22.2 mg / Kg, i.p exhibited anti-inflammatory activities compared to Ibuprofen (150 mg / Kg, i.p, used as a refer ence drug. Further, our study showed that the injection of derived pyrazolopyrimidines on hyperthermic animal leads to a decrease in temperature after 1 hours of treatment compared to paracetamol used as reference. In addition, the injection of derived pyrazolopyrimidines at different doses contains a potent nociceptive activity. This effect is dose-dependent compared to aspirin.

The combination of maltose-binding protein and BCG-induced Th1 activation is involved in TLR2/9-mediated upregulation of MyD88-TRAF6 and TLR4-mediated downregulation of TRIF-TRAF3.

Science.gov (United States)

Liu, Guomu; Zhai, Xiaoyu; Zhou, Hongyue; Yang, Xiaoyu; Zhang, Nannan; Tai, Guixiang; Ni, Weihua

2018-03-01

Our previous study demonstrated that maltose-binding protein (MBP) activated Th1 through the TLR2-mediated MyD88-dependent pathway and the TLR4-mediated TRIF-dependent pathway. The combination of MBP and BCG synergistically induced Th1 activation, and the TLR2/9-mediated MyD88-dependent pathway is involved in this process. To further explore this mechanism, we stimulated purified mouse CD4 + T cells with MBP and BCG in vitro. The results demonstrated that MBP combined with BCG synergistically increased IFN-γ production and TLR2/4/9 expression, suggesting the involvement of TLR2/4/9 in the combination-induced Th1 activation. Next, TLRs 2/4/9 were blocked to analyze the effects of TLRs on Th1 activation. The results demonstrated that MBP induced a low level of Th1 activation by upregulating TLR2-mediated MyD88-TRAF6 and TLR4-mediated TRIF-TRAF3 expression, whereas MBP combined with BCG induced synergistic Th1 activation, which was not only triggered by strong upregulation of TLR2/9-mediated MyD88-TRAF6 expression but also by shifting TLR4-mediated TRIF-TRAF3 into the TRIF-TRAF6 pathway. Moreover, we observed that a TLR4 antibody upregulated MyD88 expression and a TLR9 inhibitor downregulated TRIF expression, indicating that there was cross-talk between TLRs 2/4/9 in MBP combined with BCG-induced Th1 activation. Our findings may expand the knowledge regarding TLR cross-talk involved in regulating the Th1 response. Copyright © 2018 Elsevier Inc. All rights reserved.

Distinct Neural Activity Associated with Focused-Attention Meditation and Loving-Kindness Meditation

Science.gov (United States)

Lee, Tatia M. C.; Leung, Mei-Kei; Hou, Wai-Kai; Tang, Joey C. Y.; Yin, Jing; So, Kwok-Fai; Lee, Chack-Fan; Chan, Chetwyn C. H.

2012-01-01

This study examined the dissociable neural effects of ānāpānasati (focused-attention meditation, FAM) and mettā (loving-kindness meditation, LKM) on BOLD signals during cognitive (continuous performance test, CPT) and affective (emotion-processing task, EPT, in which participants viewed affective pictures) processing. Twenty-two male Chinese expert meditators (11 FAM experts, 11 LKM experts) and 22 male Chinese novice meditators (11 FAM novices, 11 LKM novices) had their brain activity monitored by a 3T MRI scanner while performing the cognitive and affective tasks in both meditation and baseline states. We examined the interaction between state (meditation vs. baseline) and expertise (expert vs. novice) separately during LKM and FAM, using a conjunction approach to reveal common regions sensitive to the expert meditative state. Additionally, exclusive masking techniques revealed distinct interactions between state and group during LKM and FAM. Specifically, we demonstrated that the practice of FAM was associated with expertise-related behavioral improvements and neural activation differences in attention task performance. However, the effect of state LKM meditation did not carry over to attention task performance. On the other hand, both FAM and LKM practice appeared to affect the neural responses to affective pictures. For viewing sad faces, the regions activated for FAM practitioners were consistent with attention-related processing; whereas responses of LKM experts to sad pictures were more in line with differentiating emotional contagion from compassion/emotional regulation processes. Our findings provide the first report of distinct neural activity associated with forms of meditation during sustained attention and emotion processing. PMID:22905090

How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

Science.gov (United States)

Sholder, Gabriel; Creech, Amanda; Loechler, Edward L

2015-11-01

To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal

Analysis of the 4d7 (4f + 6p) and 4p54d9 configurations of Sn VII, Sb VIII and Te IX

International Nuclear Information System (INIS)

Azarov, V.I.; Joshi, Y.N.; Churilov, S.S.; Ryabtsev, A.N.

1994-01-01

The spectra of tin, antimony and tellerium were photographed in the 120-200 A region on 10.7 m and 3 m grazing incidence spectrographs using a triggered spark source. The 4d 8 -4d 7 (4f + 6p) + 4p 5 4d 9 transitions of Sn VII, Sb VIII and Te IX were investigated. In the Sn VII spectrum 109 new lines were classified in the 152-192 A region and 34 new levels were established, in the Sb VIII spectrum 78 new lines were classified in the 138-158 A region and 21 new levels were established, and in the Te IX 76 new lines were classified in the 121-139 A region and 21 new levels were established. Strong configuration interaction among the 4d 7 (np + mf), and 4p 5 4d 9 (n = 5, 6; m = 4, 5) configurations was observed. Least-squares-fitting (LSF) parametric calculations involving configuration interaction were carried out to interpret the observed spectra. (orig.)

Correlation of neural activity with behavioral kinematics reveals distinct sensory encoding and evidence accumulation processes during active tactile sensing.

Science.gov (United States)

Delis, Ioannis; Dmochowski, Jacek P; Sajda, Paul; Wang, Qi

2018-03-23

Many real-world decisions rely on active sensing, a dynamic process for directing our sensors (e.g. eyes or fingers) across a stimulus to maximize information gain. Though ecologically pervasive, limited work has focused on identifying neural correlates of the active sensing process. In tactile perception, we often make decisions about an object/surface by actively exploring its shape/texture. Here we investigate the neural correlates of active tactile decision-making by simultaneously measuring electroencephalography (EEG) and finger kinematics while subjects interrogated a haptic surface to make perceptual judgments. Since sensorimotor behavior underlies decision formation in active sensing tasks, we hypothesized that the neural correlates of decision-related processes would be detectable by relating active sensing to neural activity. Novel brain-behavior correlation analysis revealed that three distinct EEG components, localizing to right-lateralized occipital cortex (LOC), middle frontal gyrus (MFG), and supplementary motor area (SMA), respectively, were coupled with active sensing as their activity significantly correlated with finger kinematics. To probe the functional role of these components, we fit their single-trial-couplings to decision-making performance using a hierarchical-drift-diffusion-model (HDDM), revealing that the LOC modulated the encoding of the tactile stimulus whereas the MFG predicted the rate of information integration towards a choice. Interestingly, the MFG disappeared from components uncovered from control subjects performing active sensing but not required to make perceptual decisions. By uncovering the neural correlates of distinct stimulus encoding and evidence accumulation processes, this study delineated, for the first time, the functional role of cortical areas in active tactile decision-making. Copyright © 2018 Elsevier Inc. All rights reserved.

Application of PQR Theory for control of a 3-phase 4-wire 4-legs shunt active power filter in the aß?-axes using 3D-SVM technique

Directory of Open Access Journals (Sweden)

Ali CHEBABHI

2015-05-01

Full Text Available This article discusses and compares two control strategies applied to a 3-phase 4-wire 4-leg shunt active power filter. These two control strategies, including the cross-vector theory called CV theory and the direct method called PQR theory, are based on the instantaneous control of active and reactive power. On one hand, it is shown that, in some cases, cross-vector theory requires elimination of the zero sequence currents in a 3-phase 4-wire 4-leg shunt active power filter, which needs a power storage element, and on the other hand pretreatment system voltage is necessary to obtain compensated sinusoidal current and a degree of freedom. By relying on the cross-vector theory, the PQR theory is used to extract and remove harmonic currents components. In this control technique, there are two internal current control loops and an external voltage control loop, these control loops have been realized by PI controllers when applied 3D-SVM of switching technique. We choose as criteria for comparison the transient and the Total Harmonic Distortion in the line current. A series of simulations in MATLAB/ Simulink environment have been presented and discussed to show the performance of the two control strategies.

Hyperfine fields at some 4d, 5d and 4f impurities in ferromagnetic GdZn and GdCd

International Nuclear Information System (INIS)

Kasamatsu, Y.; Kojima, K.; Hihara, T.

1995-01-01

Hyperfine (hf) fields at 4d (Y, Nb, Rh, Pd), 5d (Lu, Ta, Ir) and 4f (La, Nd, Sm, Eu) impurities in ferromagnetic GdZn and GdCd have been measured by NMR at 4.2 K. The local moment contributions to the hf field suggest that the impurity moments at the beginning and end of the d series are parallel and antiparallel to Gd moments, respectively. The hf results for 4f impurities are also discussed. ((orig.))

Semaphorin 4D induces vaginal epithelial cell apoptosis to control mouse postnatal vaginal tissue remodeling

Science.gov (United States)

ITO, TAKUJI; BAI, TAO; TANAKA, TETSUJI; YOSHIDA, KENJI; UEYAMA, TAKASHI; MIYAJIMA, MASAYASU; NEGISHI, TAKAYUKI; KAWASAKI, TAKAHIKO; TAKAMATSU, HYOTA; KIKUTANI, HITOSHI; KUMANOGOH, ATSUSHI; YUKAWA, KAZUNORI

2015-01-01

The opening of the mouse vaginal cavity to the skin is a postnatal tissue remodeling process that occurs at approximately five weeks of age for the completion of female genital tract maturation at puberty. The tissue remodeling process is primarily composed of a hormonally triggered apoptotic process predominantly occurring in the epithelium of the distal section of the vaginal cavity. However, the detailed mechanism underlying the apoptotic induction remains to be elucidated. In the present study, it was observed that the majority of BALB/c mice lacking the class 4 semaphorin, semaphorin 4D (Sema4D), developed imperforate vagina and hydrometrocolpos resulting in a perpetually unopened vaginal cavity regardless of a normal estrogen level comparable with that in wild-type (WT) mice. Administration of β-estradiol to infant Sema4D-deficient (Sema4D−/−) mice did not induce precocious vaginal opening, which was observed in WT mice subjected to the same β-estradiol administration, excluding the possibility that the closed vaginal phenotype was due to insufficient estrogen secretion at the time of vaginal opening. In order to assess the role of Sema4D in the postnatal vaginal tissue remodeling process, the expression of Sema4D and its receptor, plexin-B1, was examined as well as the level of apoptosis in the vaginal epithelia of five-week-old WT and Sema4D−/− mice. Immunohistochemical analyses confirmed the localization of Sema4D and plexin-B1 in the mouse vaginal epithelia. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry detecting activated caspase-3 revealed significantly fewer apoptotic cells in situ in the vaginal mucosa of five-week-old Sema4D−/− mice compared with WT mice. The addition of recombinant Sema4D to Sema4D−/− vaginal epithelial cells in culture significantly enhanced apoptosis of the vaginal epithelial cells, demonstrating the apoptosis-inducing activity of Sema4D. The experimental reduction of

The 4p5rd10 and 4d86p configurations of Te VIII

International Nuclear Information System (INIS)

Churilov, S.S.; Rossijskaya Akademiya Nauk, Troitsk; Joshi, Y.N.; Kildiyarova, R.R.

1998-01-01

The spectrum of tellurium was photographed in the 100-500 A region on a variety of grazing incidence spectrographs using a triggered spark source. The analysis of the lines in the 117-216 A region has lead to establishing 42 out of 45 levels of the 4d 8 6p configuration of Te VIII. Four levels of the 4d 8 4f configuration were confirmed and their level values revised, and an additional 4d 8 4f level was established. The 4p 5 4d 10 levels reported earlier were found to be erroneous and new values have been found for them. Eighty seven (87) new lines have been classified in the (4d 9 + 4d 8 5s)-(4d 8 4f + 4p 5 4d 10 + 4d 8 6p) transition array. Hartree-Fock with relativistic corrections (HFR) and parametric least-squares-fitted (lSF) calculations were carried out to interpret the present analysis adequately. (orig.)

Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis.

Science.gov (United States)

Lagishetty, Venu; Misharin, Alexander V; Liu, Nancy Q; Lisse, Thomas S; Chun, Rene F; Ouyang, Yi; McLachlan, Sandra M; Adams, John S; Hewison, Martin

2010-06-01

Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis. Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D(3) (2.5 +/- 0.1 vs. 24.4 +/- 1.8 ng/ml) and active 1,25-dihydroxyvitamin D(3) (28.8 +/- 3.1 vs. 45.6 +/- 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 +/- 0.85 vs. 1.57 +/- 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria. Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans.

Synthesis of Substituted Thieno[2,3-d]pyrimidin-4-ones and Their Testing for Evaluation of Cytotoxic Activity on Mammalian Cell Models

Directory of Open Access Journals (Sweden)

Kh. A. Bozorov

2013-01-01

Full Text Available From 2-amino-3-ethoxycarbonyl-4,5-dimethyl-, -polymethylenethiophenes (1-4 were synthesized 2,3-disubstituted thieno[2,3-d]dihydropyrrolo-, tetrahydropyrido-, and tetrahydroazepino[1,2-a]pyrimidin-4-ones (5-16 for pharmacological investigations. The 12 compounds (5-16 were individually evaluated for their antiproliferative activities on mammalian cancer cell models. All tested compounds showed weak affection on human cervix adenocarcinoma cells (HeLa whereas some of the tested compounds exhibited more consistent inhibition of cell growth on murine myeloma cells (P3X. In both cases some compounds enhanced cell proliferation.

Combretastatin A-4 based thiophene derivatives as antitumor agent: Development of structure activity correlation model using 3D-QSAR, pharmacophore and docking studies

Directory of Open Access Journals (Sweden)

Vijay K. Patel

2017-12-01

Full Text Available The structure and ligand based synergistic approach is being applied to design ligands more correctly. The present report discloses the combination of structure and ligand based tactics i.e., molecular docking, energetic based pharmacophore, pharmacophore and atom based 3D-QSAR modeling for the analysis of thiophene derivatives as anticancer agent. The main purpose of using structure and ligand based synergistic approach is to ascertain a correlation between structure and its biological activity. Thiophene derivatives have been found to possess cytotoxic activity in several cancer cell lines and its mechanism of action basically involves the binding to the colchicine site on β-tubulin. The structure based approach (molecular docking was performed on a series of thiophene derivatives. All the structures were docked to colchicine binding site of β tubulin for examining the binding affinity of compounds for antitumor activity. The pharmacophore and atom based 3D-QSAR modeling was accomplished on a series of thiophene (32 compounds analogues. Five-point common pharmacophore hypotheses (AAAAR.38 were selected for alignment of all compounds. The atom based 3D-QSAR models were developed by selection of 23 compounds as training set and 9 compounds as test set, demonstrated good partial least squares statistical results. The generated common pharmacophore hypothesis and 3D-QSAR models were validated further externally by measuring the activity of database compounds and assessing it with actual activity. The common pharmacophore hypothesis AAAAR.38 resulted in a 3D-QSAR model with excellent PLSs data for factor two characterized by the best predication coefficient Q2 (cross validated r2 (0.7213, regression R2 (0.8311, SD (0.3672, F (49.2, P (1.89E-08, RMSE (0.3864, Stability (0.8702, Pearson-r (0.8722. The results of these molecular modeling studies i.e., molecular docking, energetic based pharmacophore, pharmacophore and atom based 3D-QSAR modeling

Noval 1-substituted-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazole derivatives: Synthesis and pharmacological activity

Directory of Open Access Journals (Sweden)

Sabir Hussain

2015-05-01

Full Text Available Several-1-carbothioamide-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 2a–d, 1-(pyridine-4-ylcarbonyl-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 3a–d, 1-(5-chloro-6-fluoro-1,3-benzothiazole-2-ylthiocarbamoyl-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 4a–d and 1-[(1,2,4-triazole-4-yl carbothioamide]-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 5a–d were synthesized. The structures of the newly synthesized compounds were supported by IR, 1H NMR and mass spectral data. These compounds were investigated for their, anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, antibacterial and antifungal activities. Some of the synthesized compounds showed potent anti-inflammatory activity along with minimal ulcerogenic effect and lipid peroxidation, compared to ibuprofen and flurbiprofen. Some of the tested compounds also showed moderate antimicrobial activity against tested bacterial and fungal strains.

Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells.

Directory of Open Access Journals (Sweden)

Helle Jensen

Full Text Available NKG2D is a stimulatory receptor expressed by natural killer (NK cells, CD8(+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4(+ T-cells, however recently a subset of NKG2D(+ CD4(+ T-cells has been found, which is specific for human cytomegalovirus (HCMV. This particular subset of HCMV-specific NKG2D(+ CD4(+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D(+ CD4(+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4(+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA to investigate the gene expression profile of NKG2D(+ CD4(+ T-cells, generated from HCMV-primed CD4(+ T-cells. We show that the HCMV-primed NKG2D(+ CD4(+ T-cells possess a higher differentiated phenotype than the NKG2D(- CD4(+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4(+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4(+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4(+ T-cells, whereas it is produced de novo in resting CD4(+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D(+ CD4(+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

Elevated levels of the complement activation product C4d in bronchial fluids for the diagnosis of lung cancer.

Directory of Open Access Journals (Sweden)

Daniel Ajona

Full Text Available Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort. The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls and the HUVR cohort (60 cases and 98 controls. A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort. Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71-0.94 and 0.67 (95%CI = 0.58-0.76 for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts. Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56-0.83. In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease.

Exploring the relation between 4D and 5D BPS solutions

Energy Technology Data Exchange (ETDEWEB)

Behrndt, Klaus [Arnold-Sommerfeld-Center for Theoretical Physics, Department fuer Physik, Ludwig-Maximilians-Universitaet Muenchen, Theresienstrasse 37, 80333 Munich (Germany)]. E-mail: behrndt@theorie.physik.uni-muenchen.de; Lopes Cardoso, Gabriel [Arnold-Sommerfeld-Center for Theoretical Physics, Department fuer Physik, Ludwig-Maximilians-Universitaet Muenchen, Theresienstrasse 37, 80333 Munich (Germany)]. E-mail: gcardoso@theorie.physik.uni-muenchen.de; Mahapatra, Swapna [Physics Department, Utkal University, Bhubaneswar 751 004 (India)]. E-mail: swapna@iopb.res.in

2006-01-02

Based on recent proposals linking four and five-dimensional BPS solutions, we discuss the explicit dictionary between general stationary 4D and 5D supersymmetric solutions in N=2 supergravity theories with cubic prepotentials. All these solutions are completely determined in terms of the same set of harmonic functions and the same set of attractor equations. As an example, we discuss black holes and black rings in Godel-Taub-NUT spacetime. Then we consider corrections to the 4D solutions associated with more general prepotentials and comment on analogous corrections on the 5D side.

Laser spectroscopy of the 4s4p(3) P-2-4s3d(1) D-2 transition on magnetically trapped calcium atoms

NARCIS (Netherlands)

Dammalapati, U.; Norris, I.; Burrows, C.; Riis, E.

2011-01-01

Laser excitation of the 4s4p(3) P-2-4s3d(1) D-2 transition in atomic calcium has been observed and the wavelength determined to 1530.5298(6) nm. The metastable 4s4p(3) P-2 atoms were magnetically trapped in the quadrupole magnetic field of a magneto-optical trap. This state represents the only

New derivatives of 3,4-dihydroisoquinoline-3-carboxylic acid with free-radical scavenging, D-amino acid oxidase, acetylcholinesterase and butyrylcholinesterase inhibitory activity.

Science.gov (United States)

Solecka, Jolanta; Guśpiel, Adam; Postek, Magdalena; Ziemska, Joanna; Kawęcki, Robert; Lęczycka, Katarzyna; Osior, Agnieszka; Pietrzak, Bartłomiej; Pypowski, Krzysztof; Wyrzykowska, Agata

2014-09-30

A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS·+), superoxide anion radical (O2·-) and nitric oxide radical (·NO) assays. We also studied d-amino acid oxidase (DAAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Almost each of newly synthesised compounds exhibited radical scavenging capabilities. Moreover, several compounds showed moderate inhibitory activities against DAAO, AChE and BuChE. Compounds with significant free-radical scavenging activity may be potential candidates for therapeutics used in oxidative-stress-related diseases.

Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

Science.gov (United States)

Swinny, Jerome D.; O'Farrell, Eimear; Bingham, Brian C.; Piel, David A.; Valentino, Rita J.; Beck, Sheryl G.

2010-01-01

Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morphology. Rat pups were separated from the dam for 15 min/d (HMS-15) or 180 min/d (HMS-180) from post-natal days 2–14. Others were either undisturbed (HMS-0) or were vendor-purchased controls. LC characteristics were compared at age 22–35 d using whole-cell recordings in vitro. Cells were filled with biocytin for morphological analysis. LC neurons of HMS-180 rats were tonically activated compared to HMS-15 and control rats, with firing rates that were 2-fold higher than these groups. Corticotrophin-releasing factor (CRF) application did not further activate LC neurons of HMS-180 rats but increased LC firing rate in HMS-0 and control rats. LC neurons of HMS-15 rats were resistant to excitation by CRF. Maternal separation also affected LC dendritic morphology. LC dendrites of HMS-15 rats exhibited less branching and decreased total dendritic length, an effect that could decrease the probability of contacting limbic afferents that terminate in the pericoerulear region. This effect may provide a structural basis for an attenuated magnitude of emotional arousal. Together, these results demonstrate long-term consequences of early life events on the LC–norepinephrine system that may shape adult behaviour. PMID:19653930

Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

Directory of Open Access Journals (Sweden)

Yunjiu Cheng

Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

Regulation and Gene Expression Profiling of NKG2D Positive Human Cytomegalovirus-Primed CD4+ T-Cells

Science.gov (United States)

Jensen, Helle; Folkersen, Lasse; Skov, Søren

2012-01-01

NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D– CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression. PMID:22870231

Synthesis, antimicrobial and cytotoxic activities of 5-benzylidene-2-[(pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-one and 2-[(pyridine-4-ylmethylene) hydrazono]-thiazolidin-4-one derivatives

Energy Technology Data Exchange (ETDEWEB)

Feitoza, Danniel Delmondes; Alves, Antonio Jose; Lima, Jose Gildo de, E-mail: jgildolima@gmail.com [Departamento de Ciencias Farmaceuticas, Universidade Federal de Pernambuco, Recife - PE (Brazil); Araujo, Janete Magali; Aguiar, Jaciana Santos; Rodrigues, Maria do Desterro; Silva, Teresinha Goncalves; Nascimento, Silene Carneiro do; Goes, Alexandre Jose da Silva [Departamento de Antibioticos, Universidade Federal de Pernambuco, Recife - PE (Brazil)

2012-07-01

A new series of 5-benzylidene-2-[(pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 4a-l have been synthesized. These compounds were designed by a molecular hybridization approach. 2-[(Pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 3a-d were also obtained and used as intermediates to give the target compounds. The in vitro antimicrobial and cytotoxic activities were evaluated for both series. The intermediate 3b showed considerable antibiotic activity against B. subtilis and C. albicans. In the cytotoxic activity compounds 3b (IC{sub 50} = 4.25 +- 0.36 {mu}g/mL) and 4l (IC{sub 50} = 1.38 +- 0.04 {mu}g/mL) were effective for inhibition of human erythromyeloblastoid leukemia (K-562) and human lung carcinoma (NCI-H292) cell lines, respectively. (author)

Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats.

Science.gov (United States)

Sanna, Fabrizio; Contini, Andrea; Melis, Maria Rosaria; Argiolas, Antonio

2015-10-01

Dopamine influences the anticipatory and consummatory phases of sexual behavior, by acting on receptors of the D2 family (D2, D3 and D4) and in particular of the D2 subtype, although evidence for a role of D4 receptors in erectile function and copulatory behavior is also available. In order to clarify such a role of D4 receptors, the effect of selective D4 receptor agonists and antagonists on copulatory behavior of sexually potent male rats in classic copulation tests with a receptive female, was compared with that of apomorphine and haloperidol, a classic dopamine receptor agonist and antagonist, respectively. PD-168,077 (0.05-0.2mg/kg) and ABT-724 (0.01-0.04mg/kg), two selective D4 receptor agonists, given subcutaneously, improved dose-dependently copulatory behavior as shown by the decrease of mount frequency and post ejaculatory interval induced by PD-168,077, and of mount frequency, ejaculation latency, post ejaculatory and inter intromission intervals induced by ABT-724, and by the increase of ejaculation frequency and copulatory efficacy induced by both drugs. Conversely, L-745,870 (1-5mg/kg), a selective D4 receptor antagonist, given intraperitoneally, impaired dose-dependently copulatory behavior, as shown by the increase in intromission and ejaculation latencies, mount frequency, post ejaculatory interval and the decrease in ejaculation frequency and copulatory efficacy induced by this drug. L-745,870 (5mg/kg) administered before PD-168,077 (0.2mg/kg) or ABT-724 (0.04mg/kg), also abolished completely the facilitatory effects of both PD-168,077 and ABT-724 on sexual behavior. These results confirm the involvement of D4 receptors in specific aspects of male rat copulatory behavior that overlap only partially with those influenced by apomorphine and haloperidol. Copyright © 2015 Elsevier Inc. All rights reserved.

4D-QSAR: Perspectives in Drug Design

Directory of Open Access Journals (Sweden)

Carolina H. Andrade

2010-05-01

Full Text Available Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design.

Synthesis of 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone as a candidate anticancer against cervical (WiDr), colon (HeLa), and breast (T47d) cancer cell lines in vitro

Science.gov (United States)

Matsjeh, Sabirin; Swasono, Respati Tri; Anwar, Chairil; Solikhah, Eti Nurwening; Lestari, Endang

2017-03-01

The compound 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone have been synthesized through Claisen-Schmidt reaction from 2-hydroxyacetophenone and 2,4-dihydroxyacetophenone with 4-hydroxy-3-methoxy benzaldehida (vanillin) in aqueous KOH 40% and KSF montmorillonite as catalyst in methanol. All these products were characterized by FT-IR, TLC Scanner, GC-MS, MS-Direct, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical, colon, and breast cancer cells (Hela, WiDr, and T47D cell lines) using MTT assay in vitro. Dose series given test solution concentration on Hela, WiDr, and T47D cells started from 6,25; 25; 50 and 100 µg/mL with incubation treatment for 24 hours. The result of study showed that the 2',4-dihydroxy-3-methoxychalcone as bright yellow crystal with the melting point of 114-115 °C and the yield of 13.77% and the 2',4',4-trihydroxy-3-methoxychalcone as bright yellow crystals with the melting point of 195-197 °C and the yield of 6%. Other 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone also exhibited cytotoxic activity against the cancer cell lines, with the 2',4',4-trihydroxy-3-methoxychalcone showed greater activities than the 2',4-dihydroxy-3-methoxychalcone in WiDr cell lines. The 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone exhibited strong anticancer activities with IC50 value below 20 µg/mL. The activity of 2',4',4-trihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 8.53 and 2.66 µg/mL respectively, than T47D cell lines with IC50 value 24.61 µg/mL. The test results cytotoxic of 2',4-dihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 12.80, 19.57 µg/mL than T47D cell lines with IC50 value of 20.73 µg/mL. IC50 value indicated that 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3

Locomotor activity: A distinctive index in morphine self-administration in rats.

Science.gov (United States)

Zhang, Jian-Jun; Kong, Qingyao

2017-01-01

Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration.

Locomotor activity: A distinctive index in morphine self-administration in rats

Science.gov (United States)

Kong, Qingyao

2017-01-01

Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration. PMID:28380023

Human decidual macrophages and NK cells differentially express Toll-like receptors and display distinct cytokine profiles upon TLR stimulation.

Directory of Open Access Journals (Sweden)

Marion eDuriez

2014-07-01

Full Text Available Maternofetal pathogen transmission is partially controlled at the level of the maternal uterine mucosa at the fetal implantation site (the decidua basalis, where maternal and fetal cells are in close contact. Toll-like receptors (TLRs may play an important role in initiating rapid immune responses against pathogens in the decidua basalis, however the tolerant microenvironment should be preserved in order to allow fetal development. Here we investigated the expression and functionality of TLRs expressed by decidual macrophages (dMs and NK cells (dNKs, the major decidual immune cell populations.We report for the first time that both human dMs and dNK cells express mRNAs encoding TLRs 1-9, albeit with a higher expression level in dMs. TLR2, TLR3 and TLR4 protein expression checked by flow cytometry was positive for both dMs and dNK cells. In vitro treatment of primary dMs and dNK cells with specific TLR2, TLR3, TLR4, TLR7/8 and TLR9 agonists enhanced their secretion of pro- and anti-inflammatory cytokines, as well as cytokines and chemokines involved in immune cell crosstalk. Only dNK cells released IFN-γ, whereas only dMs released IL-1β, IL-10 and IL-12. TLR9 activation of dMs resulted in a distinct pattern of cytokine expression compared to the other TLRs. The cytokine profiles expressed by dMs and dNK cells upon TLR activation are compatible with maintenance of the fetotolerant immune environment during initiation of immune responses to pathogens at the maternofetal interface.

2D CFT blocks for the 4D class Sk theories

International Nuclear Information System (INIS)

Mitev, Vladimir; Pomoni, Elli

2017-03-01

This is the first in a series of papers on the search for the 2D CFT description of a large class of 4D N=1 gauge theories. Here, we identify the 2D CFT symmetry algebra and its representations, namely the conformal blocks of the Virasoro/W-algebra, that underlie the 2D theory and reproduce the Seiberg-Witten curves of the N=1 gauge theories. We find that the blocks corresponding to the SU(N) S k gauge theories involve fields in certain non-unitary representations of the W kN algebra. These conformal blocks give a prediction for the instanton partition functions of the 4D N=1 SCFTs of class S k .

Lithocholic acid controls adaptive immune responses by inhibition of Th1 activation through the Vitamin D receptor.

Science.gov (United States)

Pols, Thijs W H; Puchner, Teresa; Korkmaz, H Inci; Vos, Mariska; Soeters, Maarten R; de Vries, Carlie J M

2017-01-01

Bile acids are established signaling molecules next to their role in the intestinal emulsification and uptake of lipids. We here aimed to identify a potential interaction between bile acids and CD4+ Th cells, which are central in adaptive immune responses. We screened distinct bile acid species for their potency to affect T cell function. Primary human and mouse CD4+ Th cells as well as Jurkat T cells were used to gain insight into the mechanism underlying these effects. We found that unconjugated lithocholic acid (LCA) impedes Th1 activation as measured by i) decreased production of the Th1 cytokines IFNγ and TNFαα, ii) decreased expression of the Th1 genes T-box protein expressed in T cells (T-bet), Stat-1 and Stat4, and iii) decreased STAT1α/β phosphorylation. Importantly, we observed that LCA impairs Th1 activation at physiological relevant concentrations. Profiling of MAPK signaling pathways in Jurkat T cells uncovered an inhibition of ERK-1/2 phosphorylation upon LCA exposure, which could provide an explanation for the impaired Th1 activation. LCA induces these effects via Vitamin D receptor (VDR) signaling since VDR RNA silencing abrogated these effects. These data reveal for the first time that LCA controls adaptive immunity via inhibition of Th1 activation. Many factors influence LCA levels, including bile acid-based drugs and gut microbiota. Our data may suggest that these factors also impact on adaptive immunity via a yet unrecognized LCA-Th cell axis.

Ventilation measured on clinical 4D-CBCT

DEFF Research Database (Denmark)

Rørdam Jensen, Kasper; Brink, Carsten; Hansen, Olfred

2017-01-01

as a gold standard the current study investigates if image improvements increase the accuracy of 4D-CBCT measured ventilation. MATERIAL AND METHODS: The study consists of 4D-CBCT and 4D-CT scans of 20 non-small-cell lung cancer patients. Raw CBCT projections were subjected to a standard or an improved...... and the SART reconstruction increased the accuracy of CBCT ventilation and this result can be a stepping stone to extract dynamic changes in respiration pattern of patients during radiotherapy....

Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

Science.gov (United States)

Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa

2018-01-01

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461

The D4Z4 macrosatellite repeat acts as a CTCF and A-type lamins-dependent insulator in facio-scapulo-humeral dystrophy.

Directory of Open Access Journals (Sweden)

Alexandre Ottaviani

2009-02-01

Full Text Available Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD, which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the FSHD-associated gene(s through position effect mechanisms. We investigated this hypothesis by creating a large collection of constructs carrying 1 to >11 D4Z4 repeats integrated into the human genome, either at random sites or proximal to a telomere, mimicking thereby the organization of the 4q35 locus. We show that D4Z4 acts as an insulator that interferes with enhancer-promoter communication and protects transgenes from position effect. This last property depends on both CTCF and A-type Lamins. We further demonstrate that both anti-silencing activity of D4Z4 and CTCF binding are lost upon multimerization of the repeat in cells from FSHD patients compared to control myoblasts from healthy individuals, suggesting that FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats. We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients.

Leukotriene E4 induces airflow obstruction and mast cell activation through the cysteinyl leukotriene type 1 receptor.

Science.gov (United States)

Lazarinis, Nikolaos; Bood, Johan; Gomez, Cristina; Kolmert, Johan; Lantz, Ann-Sofie; Gyllfors, Pär; Davis, Andy; Wheelock, Craig E; Dahlén, Sven-Erik; Dahlén, Barbro

2018-03-05

Leukotriene (LT) E 4 is the final active metabolite among the cysteinyl leukotrienes (CysLTs). Animal studies have identified a distinct LTE 4 receptor, suggesting that current cysteinyl leukotriene type 1 (CysLT 1 ) receptor antagonists can provide incomplete inhibition of CysLT responses. We tested this hypothesis by assessing the influence of the CysLT 1 antagonist montelukast on responses induced by means of inhalation of LTE 4 in asthmatic patients. Fourteen patients with mild intermittent asthma and 2 patients with aspirin-exacerbated respiratory disease received 20 mg of montelukast twice daily and placebo for 5 to 7 days in a randomized, double-blind, crossover study (NCT01841164). The PD 20 value was determined at the end of each treatment period based on an increasing dose challenge. Measurements included lipid mediators in urine and sputum cells 4 hours after LTE 4 challenge. Montelukast completely blocked LTE 4 -induced bronchoconstriction. Despite tolerating an at least 10 times higher dose of LTE 4 after montelukast, there was no difference in the percentage of eosinophils in sputum. Urinary excretion of all major lipid mediators increased after LTE 4 inhalation. Montelukast blocked release of the mast cell product prostaglandin (PG) D 2 , as well as release of PGF 2α and thromboxane (Tx) A 2 , but not increased excretion of PGE 2 and its metabolites or isoprostanes. LTE 4 induces airflow obstruction and mast cell activation through the CysLT 1 receptor. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Semaphorin 4D induces vaginal epithelial cell apoptosis to control mouse postnatal vaginal tissue remodeling.

Science.gov (United States)

Ito, Takuji; Bai, Tao; Tanaka, Tetsuji; Yoshida, Kenji; Ueyama, Takashi; Miyajima, Masayasu; Negishi, Takayuki; Kawasaki, Takahiko; Takamatsu, Hyota; Kikutani, Hitoshi; Kumanogoh, Atsushi; Yukawa, Kazunori

2015-02-01

The opening of the mouse vaginal cavity to the skin is a postnatal tissue remodeling process that occurs at approximately five weeks of age for the completion of female genital tract maturation at puberty. The tissue remodeling process is primarily composed of a hormonally triggered apoptotic process predominantly occurring in the epithelium of the distal section of the vaginal cavity. However, the detailed mechanism underlying the apoptotic induction remains to be elucidated. In the present study, it was observed that the majority of BALB/c mice lacking the class 4 semaphorin, semaphorin 4D (Sema4D), developed imperforate vagina and hydrometrocolpos resulting in a perpetually unopened vaginal cavity regardless of a normal estrogen level comparable with that in wild‑type (WT) mice. Administration of β‑estradiol to infant Sema4D‑deficient (Sema4D‑/‑) mice did not induce precocious vaginal opening, which was observed in WT mice subjected to the same β‑estradiol administration, excluding the possibility that the closed vaginal phenotype was due to insufficient estrogen secretion at the time of vaginal opening. In order to assess the role of Sema4D in the postnatal vaginal tissue remodeling process, the expression of Sema4D and its receptor, plexin‑B1, was examined as well as the level of apoptosis in the vaginal epithelia of five‑week‑old WT and Sema4D‑/‑ mice. Immunohistochemical analyses confirmed the localization of Sema4D and plexin‑B1 in the mouse vaginal epithelia. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry detecting activated caspase‑3 revealed significantly fewer apoptotic cells in situ in the vaginal mucosa of five‑week‑old Sema4D‑/‑ mice compared with WT mice. The addition of recombinant Sema4D to Sema4D‑/‑ vaginal epithelial cells in culture significantly enhanced apoptosis of the vaginal epithelial cells, demonstrating the apoptosis‑inducing activity of Sema4D. The

1,25-(OH)2-vitamin D3 prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4−/− model

International Nuclear Information System (INIS)

Reiter, Florian P.; Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena; Makeschin, Marie-Christine; Mayr, Doris; Rust, Christian; Trauner, Michael; Denk, Gerald U.

2015-01-01

Background/Purpose of the study: Vitamin D 3 -deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D 3 -administration has thus been proposed as a therapeutic approach. Vitamin D 3 has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH) 2 -vitamin D 3 inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen ® -assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4 −/− (Abcb4 −/− )-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4 −/− -mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4 −/− -mice, administration of calcitriol ameliorates inflammatory liver-damage but has no effect on biliary fibrosis after 4 weeks

Distinct developmental defense activations in barley embryos identified by transcriptome profiling

DEFF Research Database (Denmark)

Nielsen, ME; Lok, F; Nielsen, Henrik Bjørn

2006-01-01

analyses of > 22,000 genes, which together with measurements of jasmonic acid and salicylic acid during embryo development provide new information on the initiation in the developing barley embryo of at least two distinct types of developmental defense activation (DDA). Early DDA is characterized by the up......-regulation of several PR genes is notable. Throughout barley embryo development, there are no indications of an increased biosynthesis of either jasmonic acid or salicylic acid. Collectively, the results help explain how the proposed DDA enables protection of the developing barley embryo and grain for purposes...

Opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation

International Nuclear Information System (INIS)

Jin Xun; Kim, Jong-Gun; Oh, Myung-Joo; Oh, Ho-Yeon; Sohn, Young-Woo; Pian, Xumin; Yin, Jin Long; Beck, Samuel; Lee, Namkyung; Son, Jeesoo; Kim, Hyunggee; Yan Changguo; Wang Jihui; Choi, Yun-Jaie; Whang, Kwang Youn

2007-01-01

The basic helix-loop-helix myogenic regulatory factors play critical roles in skeletal myogenesis. Among the myogenic regulatory factors (MRFs), MRF4 shows a biphasic expression pattern during the formation of myotomes, although its function remains unclear. In this study, we used BEF (spontaneously immortalized bovine embryonic fibroblast that shows myogenic differentiation by overexpression of MyoD) and C2C12 cells to investigate the function of MRF4. Ectopic expressions of MRF4 did not stimulate myogenic differentiation in the BEF and C2C12 cells, but did show a marked increase of cell proliferation, upregulation of cyclin E, and downregulation of p21 WAF1 . Furthermore, MRF4 was found to induce degradation of the MyoD protein, which acts as a transcriptional activator for p21 WAF1 , and thus indicates that MRF4 accelerates cell proliferation by suppressing MyoD-dependent p21 WAF1 expression. However, forced expression of MyoD in the MRF4-overexpressing cells inhibited cell proliferation and partially induced myogenic differentiation, which suggests that MyoD is a potential negative intercessor of MRF4 in the regulation of the cell cycle. Taken together, these results indicate that MRF4 and MyoD play competitive roles in myogenesis by stimulating cell proliferation and differentiation, respectively

Multi-shape active composites by 3D printing of digital shape memory polymers.

Science.gov (United States)

Wu, Jiangtao; Yuan, Chao; Ding, Zhen; Isakov, Michael; Mao, Yiqi; Wang, Tiejun; Dunn, Martin L; Qi, H Jerry

2016-04-13

Recent research using 3D printing to create active structures has added an exciting new dimension to 3D printing technology. After being printed, these active, often composite, materials can change their shape over time; this has been termed as 4D printing. In this paper, we demonstrate the design and manufacture of active composites that can take multiple shapes, depending on the environmental temperature. This is achieved by 3D printing layered composite structures with multiple families of shape memory polymer (SMP) fibers - digital SMPs - with different glass transition temperatures (Tg) to control the transformation of the structure. After a simple single-step thermomechanical programming process, the fiber families can be sequentially activated to bend when the temperature is increased. By tuning the volume fraction of the fibers, bending deformation can be controlled. We develop a theoretical model to predict the deformation behavior for better understanding the phenomena and aiding the design. We also design and print several flat 2D structures that can be programmed to fold and open themselves when subjected to heat. With the advantages of an easy fabrication process and the controllable multi-shape memory effect, the printed SMP composites have a great potential in 4D printing applications.

Multi-shape active composites by 3D printing of digital shape memory polymers

Science.gov (United States)

Wu, Jiangtao; Yuan, Chao; Ding, Zhen; Isakov, Michael; Mao, Yiqi; Wang, Tiejun; Dunn, Martin L.; Qi, H. Jerry

2016-04-01

Recent research using 3D printing to create active structures has added an exciting new dimension to 3D printing technology. After being printed, these active, often composite, materials can change their shape over time; this has been termed as 4D printing. In this paper, we demonstrate the design and manufacture of active composites that can take multiple shapes, depending on the environmental temperature. This is achieved by 3D printing layered composite structures with multiple families of shape memory polymer (SMP) fibers - digital SMPs - with different glass transition temperatures (Tg) to control the transformation of the structure. After a simple single-step thermomechanical programming process, the fiber families can be sequentially activated to bend when the temperature is increased. By tuning the volume fraction of the fibers, bending deformation can be controlled. We develop a theoretical model to predict the deformation behavior for better understanding the phenomena and aiding the design. We also design and print several flat 2D structures that can be programmed to fold and open themselves when subjected to heat. With the advantages of an easy fabrication process and the controllable multi-shape memory effect, the printed SMP composites have a great potential in 4D printing applications.

Nanostructured Co3O4 grown on nickel foam: An efficient and readily recyclable 3D catalyst for heterogeneous peroxymonosulfate activation.

Science.gov (United States)

Yuan, Ruixia; Hu, Lin; Yu, Peng; Wang, Huaiyuan; Wang, Zhaohui; Fang, Jingyun

2018-05-01

Cobalt-based heterogeneous catalyst has been recognized as one of most efficient activators for peroxymonosulfate (PMS) decomposition, but usually suffers from the poor stability and difficulty to recover and reuse. Here easily recyclable cobalt oxide (Co 3 O 4 ) nanowires and nanoflowers grown on nickel foam (NF) are fabricated by a hydrothermal and calcination method. The prepared 3D Co 3 O 4 /NF catalyst is characterized and applied as a heterogeneous catalyst for PMS activation to generate sulfate radicals for decomposition of Acid Orange 7 (AO7). The results show that the AO7 degradation rate increases with cobalt loading and PMS dosage, but decreases with the increase of solution pH. The Co 3 O 4 /NF catalyst using 2 mM Co(NO 3 ) 2 ·6H 2 O as cobalt source exhibits highest activity, and almost complete decolorization could be achieved within 30 min. The diverse effects of coexisting anions (SO 4 2- , HCO 3 - , NO 3 - and Cl - ) on AO7 degradation are observed and explained. After 10 consecutive runs, excellent catalytic reactivity of the catalyst remains while the level of leached cobalt during the catalyst usage is much lower than the maximum allowable concentration in drinking and natural water. More importantly, the macroscopic Co 3 O 4 /NF catalyst shows advantage of easy recycling after application compared to traditional catalysts. It is believed that the as-prepared Co 3 O 4 /NF is promising to be an effective and green heterogeneous catalyst for PMS activation to degrade organic pollutants for environmental application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physical activity, sedentary behavior, and vitamin D metabolites.

Science.gov (United States)

Hibler, Elizabeth A; Sardo Molmenti, Christine L; Dai, Qi; Kohler, Lindsay N; Warren Anderson, Shaneda; Jurutka, Peter W; Jacobs, Elizabeth T

2016-02-01

Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (β (95% CI): 3.10 (1.51-6.35)) versus men (β (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

19 CFR 4.7d - Container status messages.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Container status messages. 4.7d Section 4.7d... TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.7d Container status messages. (a) Container status messages required. In addition to the advance filing requirements pursuant...

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

Science.gov (United States)

Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, pbrain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Four-dimensional MAP-RBI-EM image reconstruction method with a 4D motion prior for 4D gated myocardial perfusion SPECT

Energy Technology Data Exchange (ETDEWEB)

Lee, Taek-Soo; Tsui, Benjamin M.W. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Radiology; Gullberg, Grant T. [Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

2011-07-01

We evaluated and proposed here a 4D maximum a posteriori rescaled-block iterative (MAP-RBI)-EM image reconstruction method with a motion prior to improve the accuracy of 4D gated myocardial perfusion (GMP) SPECT images. We hypothesized that a 4D motion prior which resembles the global motion of the true 4D motion of the heart will improve the accuracy of the reconstructed images with regional myocardial motion defect. Normal heart model in the 4D XCAT (eXtended CArdiac-Torso) phantom is used as the prior in the 4D MAP-RBI-EM algorithm where a Gaussian-shaped distribution is used as the derivative of potential function (DPF) that determines the smoothing strength and range of the prior in the algorithm. The mean and width of the DPF equal to the expected difference between the reconstructed image and the motion prior, and smoothing range, respectively. To evaluate the algorithm, we used simulated projection data from a typical clinical {sup 99m}Tc Sestamibi GMP SPECT study using the 4D XCAT phantom. The noise-free projection data were generated using an analytical projector that included the effects of attenuation, collimator-detector response and scatter (ADS) and Poisson noise was added to generated noisy projection data. The projection datasets were reconstructed using the modified 4D MAP-RBI-EM with various iterations, prior weights, and sigma values as well as with ADS correction. The results showed that the 4D reconstructed image estimates looked more like the motion prior with sharper edges as the weight of prior increased. It also demonstrated that edge preservation of the myocardium in the GMP SPECT images could be controlled by a proper motion prior. The Gaussian-shaped DPF allowed stronger and weaker smoothing force for smaller and larger difference of neighboring voxel values, respectively, depending on its parameter values. We concluded the 4D MAP-RBI-EM algorithm with the general motion prior can be used to provide 4D GMP SPECT images with improved

Discovery of 2-(4-Substituted-piperidin/piperazine-1-yl-N-(5-cyclopropyl-1H-pyrazol-3-yl-quinazoline-2,4-diamines as PAK4 Inhibitors with Potent A549 Cell Proliferation, Migration, and Invasion Inhibition Activity

Directory of Open Access Journals (Sweden)

Tianxiao Wu

2018-02-01

Full Text Available A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4 inhibitors. All compounds showed significant inhibitory activity against PAK4 (half-maximal inhibitory concentration IC50 < 1 μM. Among them, compounds 8d and 9c demonstrated the most potent inhibitory activity against PAK4 (IC50 = 0.060 μM and 0.068 μM, respectively. Furthermore, we observed that compounds 8d and 9c displayed potent antiproliferative activity against the A549 cell line and inhibited cell cycle distribution, migration, and invasion of this cell line. In addition, molecular docking analysis was performed to predict the possible binding mode of compound 8d. This series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity.

D=2 and D=4 realization of κ-conformal algebra

International Nuclear Information System (INIS)

Klimek, M.

1996-01-01

The generators of κ-conformal transformations leaving the κ-deformed d'Alembert equation invariant are described. The algebraic structure of the conformal extension of the off-shell spin zero realization of κ-Poincare algebra is discussed for D=4. The D=2 off-shell realization of κ-conformal algebra for an arbitrary spin and its commutation relations were studied. 14 refs

Real-Time and High-Resolution 3D Face Measurement via a Smart Active Optical Sensor.

Science.gov (United States)

You, Yong; Shen, Yang; Zhang, Guocai; Xing, Xiuwen

2017-03-31

The 3D measuring range and accuracy in traditional active optical sensing, such as Fourier transform profilometry, are influenced by the zero frequency of the captured patterns. The phase-shifting technique is commonly applied to remove the zero component. However, this phase-shifting method must capture several fringe patterns with phase difference, thereby influencing the real-time performance. This study introduces a smart active optical sensor, in which a composite pattern is utilized. The composite pattern efficiently combines several phase-shifting fringes and carrier frequencies. The method can remove zero frequency by using only one pattern. Model face reconstruction and human face measurement were employed to study the validity and feasibility of this method. Results show no distinct decrease in the precision of the novel method unlike the traditional phase-shifting method. The texture mapping technique was utilized to reconstruct a nature-appearance 3D digital face.

4D Dynamic Required Navigation Performance Final Report

Science.gov (United States)

Finkelsztein, Daniel M.; Sturdy, James L.; Alaverdi, Omeed; Hochwarth, Joachim K.

2011-01-01

New advanced four dimensional trajectory (4DT) procedures under consideration for the Next Generation Air Transportation System (NextGen) require an aircraft to precisely navigate relative to a moving reference such as another aircraft. Examples are Self-Separation for enroute operations and Interval Management for in-trail and merging operations. The current construct of Required Navigation Performance (RNP), defined for fixed-reference-frame navigation, is not sufficiently specified to be applicable to defining performance levels of such air-to-air procedures. An extension of RNP to air-to-air navigation would enable these advanced procedures to be implemented with a specified level of performance. The objective of this research effort was to propose new 4D Dynamic RNP constructs that account for the dynamic spatial and temporal nature of Interval Management and Self-Separation, develop mathematical models of the Dynamic RNP constructs, "Required Self-Separation Performance" and "Required Interval Management Performance," and to analyze the performance characteristics of these air-to-air procedures using the newly developed models. This final report summarizes the activities led by Raytheon, in collaboration with GE Aviation and SAIC, and presents the results from this research effort to expand the RNP concept to a dynamic 4D frame of reference.

Direct 4D printing via active composite materials

Science.gov (United States)

Ding, Zhen; Yuan, Chao; Peng, Xirui; Wang, Tiejun; Qi, H. Jerry; Dunn, Martin L.

2017-01-01

We describe an approach to print composite polymers in high-resolution three-dimensional (3D) architectures that can be rapidly transformed to a new permanent configuration directly by heating. The permanent shape of a component results from the programmed time evolution of the printed shape upon heating via the design of the architecture and process parameters of a composite consisting of a glassy shape memory polymer and an elastomer that is programmed with a built-in compressive strain during photopolymerization. Upon heating, the shape memory polymer softens, releases the constraint on the strained elastomer, and allows the object to transform into a new permanent shape, which can then be reprogrammed into multiple subsequent shapes. Our key advance, the markedly simplified creation of high-resolution complex 3D reprogrammable structures, promises to enable myriad applications across domains, including medical technology, aerospace, and consumer products, and even suggests a new paradigm in product design, where components are simultaneously designed to inhabit multiple configurations during service. PMID:28439560

Direct 4D printing via active composite materials.

Science.gov (United States)

Ding, Zhen; Yuan, Chao; Peng, Xirui; Wang, Tiejun; Qi, H Jerry; Dunn, Martin L

2017-04-01

We describe an approach to print composite polymers in high-resolution three-dimensional (3D) architectures that can be rapidly transformed to a new permanent configuration directly by heating. The permanent shape of a component results from the programmed time evolution of the printed shape upon heating via the design of the architecture and process parameters of a composite consisting of a glassy shape memory polymer and an elastomer that is programmed with a built-in compressive strain during photopolymerization. Upon heating, the shape memory polymer softens, releases the constraint on the strained elastomer, and allows the object to transform into a new permanent shape, which can then be reprogrammed into multiple subsequent shapes. Our key advance, the markedly simplified creation of high-resolution complex 3D reprogrammable structures, promises to enable myriad applications across domains, including medical technology, aerospace, and consumer products, and even suggests a new paradigm in product design, where components are simultaneously designed to inhabit multiple configurations during service.