L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.

PubMed

Koutalellis, Georgios; Stravodimos, Konstantinos; Avgeris, Margaritis; Mavridis, Konstantinos; Scorilas, Andreas; Lazaris, Andreas; Constantinides, Constantinos

2012-09-01

What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination-independent prognostic value of DDC expression for the prediction of disease-free survival (DFS) among patients with PCa (P = 0.036). Kaplan-Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P = 0.015). This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP. For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted. © 2012 BJU INTERNATIONAL.

DDC Systems for Searching for Near-Earth Asteroids

NASA Technical Reports Server (NTRS)

Harris, A.

1994-01-01

Large format CCD systems are superior to photographic systems in terms of quantum efficiency and that they yield digital output directly, which can be computer analyzed to detect moving objects and to obtain astrometric measurements.

Nonequilibrium Phase Transitions. Appendix A-F

DTIC Science & Technology

1988-09-20

Module allows the separation between the control unit and the power circuits . Communications with the hostcomputer occurs via RS 232 serial port. The...hre] - D905-10123.1 ’- 43 Appendix E K- Contents: Page: Glossary of Terms 1. Principle of Construction of the DDC 4 2Thermal Circuit Of the DDC 6...Appendix E % 0 . r. fell. * re. .*......... .... 2. Thermal Circuit of the DDC: The thermal behaviour of the DDC can be represented by a lumped element

The in vitro and in vivo evaluation of ddC as a topical antiviral for ocular adenovirus infections.

PubMed

Romanowski, Eric G; Yates, Kathleen A; Gordon, Y Jerold

2009-11-01

To evaluate the antiviral activity of 2', 3'-dideoxycytidine (ddC) in vitro against a panel of ocular adenovirus serotypes and in vivo in the ocular Ad5/NZW rabbit replication model. In vitro, the 50% inhibitory concentrations (IC(50)) of ddC and cidofovir were determined using standard plaque-reduction assays. In vivo, 40 rabbits were topically inoculated in both eyes with Ad5 after corneal scarification. On day 1, the rabbits were equally divided into four topical treatment groups: 3% ddC; 2% ddC; 0.5% cidofovir; and saline. ddC and saline eyes were treated four times daily for 7 days, and cidofovir-treated eyes were treated twice daily for 7 days. Eyes were cultured for virus a multiple times over 2 weeks. The in vitro IC(50) for ddC ranged from 0.18 to 1.85 microg/mL, whereas those for cidofovir ranged from 0.018 to 5.47 microg/mL. ddC was more potent than cidofovir for seven of nine serotypes. In vivo, 3% ddC, 2% ddC, and 0.5% cidofovir significantly reduced the number of Ad5-positive cultures per total (days 1-14), mean Ad5 ocular titer (days 1-5), and duration of shedding (among other outcome measures) compared with the saline control. The 3% and 2% ddC treatments were significantly more efficacious than the 0.5% cidofovir treatment in the parameters listed above. ddC demonstrated potent antiadenovirus activity in vitro and in vivo. Systemic safety studies after topical ocular administration are needed to evaluate ddC as a topical antiviral treatment for adenoviral ocular infections in the target population.

75 FR 72822 - Nationwide Categorical Waivers Under Section 1605 (Buy American) of the American Recovery and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... a temperature range of 15-55 degrees Fahrenheit and manual reset; (4) Programmable DDC controllers... manual reset; (4) Programmable DDC controllers for LON protocol, where an existing LON system exists that...

Effects of dynamic-demand-control appliances on the power grid frequency.

PubMed

Tchuisseu, E B Tchawou; Gomila, D; Brunner, D; Colet, P

2017-08-01

Power grid frequency control is a demanding task requiring expensive idle power plants to adapt the supply to the fluctuating demand. An alternative approach is controlling the demand side in such a way that certain appliances modify their operation to adapt to the power availability. This is especially important to achieve a high penetration of renewable energy sources. A number of methods to manage the demand side have been proposed. In this work we focus on dynamic demand control (DDC), where smart appliances can delay their switchings depending on the frequency of the system. We introduce a simple model to study the effects of DDC on the frequency of the power grid. The model includes the power plant equations, a stochastic model for the demand that reproduces, adjusting a single parameter, the statistical properties of frequency fluctuations measured experimentally, and a generic DDC protocol. We find that DDC can reduce small and medium-size fluctuations but it can also increase the probability of observing large frequency peaks due to the necessity of recovering pending task. We also conclude that a deployment of DDC around 30-40% already allows a significant reduction of the fluctuations while keeping the number of pending tasks low.

Effects of dynamic-demand-control appliances on the power grid frequency

NASA Astrophysics Data System (ADS)

Tchuisseu, E. B. Tchawou; Gomila, D.; Brunner, D.; Colet, P.

2017-08-01

Power grid frequency control is a demanding task requiring expensive idle power plants to adapt the supply to the fluctuating demand. An alternative approach is controlling the demand side in such a way that certain appliances modify their operation to adapt to the power availability. This is especially important to achieve a high penetration of renewable energy sources. A number of methods to manage the demand side have been proposed. In this work we focus on dynamic demand control (DDC), where smart appliances can delay their switchings depending on the frequency of the system. We introduce a simple model to study the effects of DDC on the frequency of the power grid. The model includes the power plant equations, a stochastic model for the demand that reproduces, adjusting a single parameter, the statistical properties of frequency fluctuations measured experimentally, and a generic DDC protocol. We find that DDC can reduce small and medium-size fluctuations but it can also increase the probability of observing large frequency peaks due to the necessity of recovering pending task. We also conclude that a deployment of DDC around 30-40% already allows a significant reduction of the fluctuations while keeping the number of pending tasks low.

Measured impacts of supermarket humidity level on defrost performance and refrigerating system energy use

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

Henderson, H.I.; Khattar, M.

This paper presents field-monitor data from two supermarkets where the impact of space humidity on refrigerating system energy use was evaluated. Direct digital control (DDC) systems were used at both stores to collect 15-minute monitored data. At Store A in Minneapolis, the DDC system was used to monitor system performance as well as to implement temperature-terminated control in place of time-terminated control on 16 refrigerated zones using hot gas defrost. At Store B in Indianapolis, the DDC system was used to quantify the performance trends for the single compressor rack system with electric defrost. The results at Store B showedmore » that refrigerating system energy use decreases by nearly 10 kWh/day for each 1% drop in space relative humidity, or about 0.4% of average annual system energy use. This value includes the impact of reduced latent loads, the reduction in direct energy use and imposed load from reduced electric defrost heater operation, and the smaller imposed load from reduced anti-sweat heater energy use. The measured reductions agree well with the impact predicted using the calculation methods developed by Howell (1933b) in ASHRAE Research Project 596. At Store A, the measured data show that implementing temperature-terminated defrost reduced refrigerating system energy use by nearly 70 kWh/day over the winter period when the average space humidity was 22% RH. The savings from temperature-terminated defrost increase by 4 kWh/day per each 1% drop in relative humidity. At both stores, the same type of mechanical controls were used to duty cycle the anti-sweat heaters based on store dew point. Anti-sweat heater electricity use was observed to decrease by 4.6 kWh/day at Store B and 3.4 kWh/day at Store A for each 1% drop in relative humidity. At Store A, a more aggressive control scheme was implemented with the DDC system that reduced anti-sweat heater energy use by 7.8 kWh/day per % RH. The more aggressive control approach was reported to properly control fogging and condensation on display case surfaces. The overall energy reduction factor at the two stores was 12 kWh/day per % RH at Store A and 15 kWh/day per % RH at Store B. With more aggressive anti-sweat heater control, reduction factors as high as 20 kWh/day per % RH appear to be possible.« less

A Dopa Decarboxylase Modulating the Immune Response of Scallop Chlamys farreri

PubMed Central

Zhou, Zhi; Yang, Jialong; Wang, Lingling; Zhang, Huan; Gao, Yang; Shi, Xiaowei; Wang, Mengqiang; Kong, Pengfei; Qiu, Limei; Song, Linsheng

2011-01-01

Background Dopa decarboxylase (DDC) is a pyridoxal 5-phosphate (PLP)-dependent enzyme that catalyzes the decarboxylation of L-Dopa to dopamine, and involved in complex neuroendocrine-immune regulatory network. The function for DDC in the immunomodulation remains unclear in invertebrate. Methodology The full-length cDNA encoding DDC (designated CfDDC) was cloned from mollusc scallop Chlamys farreri. It contained an open reading frame encoding a polypeptide of 560 amino acids. The CfDDC mRNA transcripts could be detected in all the tested tissues, including the immune tissues haemocytes and hepatopancreas. After scallops were treated with LPS stimulation, the mRNA expression level of CfDDC in haemocytes increased significantly (5.5-fold, P<0.05) at 3 h and reached the peak at 12 h (9.8-fold, P<0.05), and then recovered to the baseline level. The recombinant protein of CfDDC (rCfDDC) was expressed in Escherichia coli BL21 (DE3)-Transetta, and 1 mg rCfDDC could catalyze the production of 1.651±0.22 ng dopamine within 1 h in vitro. When the haemocytes were incubated with rCfDDC-coated agarose beads, the haemocyte encapsulation to the beads was increased significantly from 70% at 6 h to 93% at 24 h in vitro in comparison with that in the control (23% at 6 h to 25% at 24 h), and the increased haemocyte encapsulation was repressed by the addition of rCfDDC antibody (which is acquired via immunization 6-week old rats with rCfDDC). After the injection of DDC inhibitor methyldopa, the ROS level in haemocytes of scallops was decreased significantly to 0.41-fold (P<0.05) of blank group at 12 h and 0.47-fold (P<0.05) at 24 h, respectively. Conclusions These results collectively suggested that CfDDC, as a homologue of DDC in scallop, modulated the immune responses such as haemocytes encapsulation as well as the ROS level through its catalytic activity, functioning as an indispensable immunomodulating enzyme in the neuroendocrine-immune regulatory network of mollusc. PMID:21533240

Sharable Courseware Object Reference Model (SCORM), Version 1.0

DTIC Science & Technology

2000-07-01

or query tool may provide the top- level entries of a well-established classification (LOC, UDC, DDC , and so forth). SEL 9.2.2 Taxon This subcategory...YYYY/MM/DD. CMIFeedback Structured description of student response in an interaction. CMIDecimal Number which may have a decimal point. If not...Seconds shall contain 2 digits with an optional decimal point and additional digits. CMITimespan A length of time in hours, minutes, and seconds

Ductility dip cracking susceptibility of Inconel Filler Metal 52 and Inconel Alloy 690

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

Kikel, J.M.; Parker, D.M.

1998-06-01

Alloy 690 and Filler Metal 52 have become the materials of choice for commercial nuclear steam generator applications in recent years. Filler Metal 52 exhibits improved resistance to weld solidification and weld-metal liquation cracking as compared to other nickel-based filler metals. However, recently published work indicates that Filler Metal 52 is susceptible to ductility dip cracking (DDC) in highly restrained applications. Susceptibility to fusion zone DDC was evaluated using the transverse varestraint test method, while heat affected zone (HAZ) DDC susceptibility was evaluated using a newly developed spot-on-spot varestraint test method. Alloy 690 and Filler Metal 52 cracking susceptibility wasmore » compared to the DDC susceptibility of Alloy 600, Filler Metal 52, and Filler Metal 625. In addition, the effect of grain size and orientation on cracking susceptibility was also included in this study. Alloy 690, Filler Metal 82, Filler Metal 52, and Filler Metal 625 were found more susceptible to fusion zone DDC than Alloy 600. Filler Metal 52 and Alloy 690 were found more susceptible to HAZ DDC when compared to wrought Alloy 600, Filler Metal 82 and Filler Metal 625. Filler Metal 52 exhibited the greatest susceptibility to HAZ DDC of all the weld metals evaluated. The base materials were found much more resistant to HAZ DDC in the wrought condition than when autogenously welded. A smaller grain size was found to offer greater resistance to DDC. For weld metal where grain size is difficult to control, a change in grain orientation was found to improve resistance to DDC.« less

Multi-DSP and FPGA based Multi-channel Direct IF/RF Digital receiver for atmospheric radar

NASA Astrophysics Data System (ADS)

Yasodha, Polisetti; Jayaraman, Achuthan; Kamaraj, Pandian; Durga rao, Meka; Thriveni, A.

2016-07-01

Modern phased array radars depend highly on digital signal processing (DSP) to extract the echo signal information and to accomplish reliability along with programmability and flexibility. The advent of ASIC technology has made various digital signal processing steps to be realized in one DSP chip, which can be programmed as per the application and can handle high data rates, to be used in the radar receiver to process the received signal. Further, recent days field programmable gate array (FPGA) chips, which can be re-programmed, also present an opportunity to utilize them to process the radar signal. A multi-channel direct IF/RF digital receiver (MCDRx) is developed at NARL, taking the advantage of high speed ADCs and high performance DSP chips/FPGAs, to be used for atmospheric radars working in HF/VHF bands. Multiple channels facilitate the radar t be operated in multi-receiver modes and also to obtain the wind vector with improved time resolution, without switching the antenna beam. MCDRx has six channels, implemented on a custom built digital board, which is realized using six numbers of ADCs for simultaneous processing of the six input signals, Xilinx vertex5 FPGA and Spartan6 FPGA, and two ADSPTS201 DSP chips, each of which performs one phase of processing. MCDRx unit interfaces with the data storage/display computer via two gigabit ethernet (GbE) links. One of the six channels is used for Doppler beam swinging (DBS) mode and the other five channels are used for multi-receiver mode operations, dedicatedly. Each channel has (i) ADC block, to digitize RF/IF signal, (ii) DDC block for digital down conversion of the digitized signal, (iii) decoding block to decode the phase coded signal, and (iv) coherent integration block for integrating the data preserving phase intact. ADC block consists of Analog devices make AD9467 16-bit ADCs, to digitize the input signal at 80 MSPS. The output of ADC is centered around (80 MHz - input frequency). The digitized data is fed to DDC block, which down converts the data to base-band. The DDC block has NCO, mixer and two chains of Bessel filters (fifth order cascaded integration comb filter, two FIR filters, two half band filters and programmable FIR filters) for in-phase (I) and Quadrature phase (Q) channels. The NCO has 32 bits and is set to match the output frequency of ADC. Further, DDC down samples (decimation) the data and reduces the data rate to 16 MSPS. This data is further decimated and the data rate is reduced down to 4/2/1/0.5/0.25/0.125/0.0625 MSPS for baud lengths 0.25/0.5/1/2/4/8/16 μs respectively. The down sampled data is then fed to decoding block, which performs cross correlation to achieve pulse compression of the binary-phase coded data to obtain better range resolution with maximum possible height coverage. This step improves the signal power by a factor equal to the length of the code. Coherent integration block integrates the decoded data coherently for successive pulses, which improves the signal to noise ratio and reduces the data volume. DDC, decoding and coherent integration blocks are implemented in Xilinx vertex5 FPGA. Till this point, function of all six channels is same for DBS mode and multi-receiver modes. Data from vertex5 FPGA is transferred to PC via GbE-1 interface for multi-modes or to two Analog devices make ADSP-TS201 DSP chips (A and B), via link port for DBS mode. ADSP-TS201 chips perform the normalization, DC removal, windowing, FFT computation and spectral averaging on the data, which is transferred to storage/display PC via GbE-2 interface for real-time data display and data storing. Physical layer of GbE interface is implemented in an external chip (Marvel 88E1111) and MAC layer is implemented internal to vertex5 FPGA. The MCDRx has total 4 GB of DDR2 memory for data storage. Spartan6 FPGA is used for generating timing signals, required for basic operation of the radar and testing of the MCDRx.

Enhanced p53 gene transfer to human ovarian cancer cells using the cationic nonviral vector, DDC.

PubMed

Kim, Chong-Kook; Choi, Eun-Jeong; Choi, Sung-Hee; Park, Jeong-Sook; Haider, Khawaja Hasnain; Ahn, Woong Shick

2003-08-01

Previously we have formulated a new cationic liposome, DDC, composed of dioleoyltrimethylamino propane (DOTAP), 1,2-dioeoyl-3-phosphophatidylethanolamine (DOPE), and cholesterol (Chol), and it efficiently delivered plasmid DNA into ovarian cancer cells. Mutations in the p53 tumor suppressor gene are the most common molecular genetic abnormalities to be described in ovarian cancer. However, there has been so far no report of nonviral vector-mediated p53 gene deliveries in ovarian cancer. In this study, wild-type p53 DNA was transfected into the ovarian cancer cells, using the DDC as a nonviral vector and the expression and activity of p53 gene were evaluated both in vitro and in vivo. DDC liposomes were prepared by mixing DOTAP:DOPE:Chol in a 1:0.7:0.3 molar ratio using the extrusion method. Plasmid DNA (pp53-EGFP) and DDC complexes were transfected into ovarian carcinoma cells (OVCAR-3 cells) and gene expression was determined by reverse transcription-polymerase chain reaction and Western blot analysis. The cellular growth inhibition and apoptosis of DDC-mediated p53 transfection were assessed by trypan blue exclusion assay and annexin-V staining, respectively. The OVCAR-3 cells treated with DDC/pp53-EGFP complexes were inoculated into female balb/c nude mice and tumor growth was observed. The transfection of liposome-complexed p53 gene resulted in a high level of wild-type p53 mRNA and protein expressions in OVCAR-3 cells. In vitro cell growth assay showed growth inhibition of cancer cells transfected with DDC/pp53-EGFP complexes compared with the control cells. The reestablishment of wild-type p53 function in ovarian cancer cells restored the apoptotic pathway. Following the inoculation of DDC/pp53-EGFP complexes, the volumes of tumors in nude mice were significantly reduced more than 60% compared to the control group. The DDC-mediated p53 DNA delivery may have the potential for clinical application as nonviral vector-mediated ovarian cancer therapy due to its effective induction of apoptosis and tumor growth inhibition.

A DDC Bibliography on Computers in Information Sciences. Volume II. Information Sciences Series.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

The unclassified and unlimited bibliography compiles references dealing specifically with the role of computers in information sciences. The volume contains 239 annotated references grouped under three major headings: Artificial and Programming Languages, Computer Processing of Analog Data, and Computer Processing of Digital Data. The references…

Eight-Channel Digital Signal Processor and Universal Trigger Module

NASA Astrophysics Data System (ADS)

Skulski, Wojtek; Wolfs, Frank

2003-04-01

A 10-bit, 8-channel, 40 megasamples per second digital signal processor and waveform digitizer DDC-8 (nicknamed Universal Trigger Module) is presented. The digitizer features 8 analog inputs, 1 analog output for a reconstructed analog waveform, 16 NIM logic inputs, 8 NIM logic outputs, and a pool of 16 TTL logic lines which can be individually configured as either inputs or outputs. The first application of this device is to enhance the present trigger electronics for PHOBOS at RHIC. The status of the development and the first results are presented. Possible applications of the new device are discussed. Supported by the NSF grant PHY-0072204.

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages

PubMed Central

Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

2018-01-01

Objectives l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D2-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Methods Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7–13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T0AM and T1AM in vitro. Results Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T1AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Conclusions Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. PMID:29686031

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

PubMed

Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

2018-05-01

l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D 2 -dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T 0 AM and T 1 AM in vitro . Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T 1 AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. © 2018 The authors.

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent.

PubMed

Wehbe, Mohamed; Anantha, Malathi; Shi, Minghan; Leung, Ada Wai-Yin; Dragowska, Wieslawa H; Sanche, Léon; Bally, Marcel B

2017-01-01

Copper diethyldithiocarbamate (Cu(DDC) 2 ) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC) 2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC) 2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC) 2 formulation prepared through a method that involves synthesis of Cu(DDC) 2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC) 2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4-11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC) 2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC) 2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC) 2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC (0-∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC) 2 formulation was subsequently evaluated in the MV-4-11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC) 2 formulation in vivo.

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

PubMed Central

Wehbe, Mohamed; Anantha, Malathi; Shi, Minghan; Leung, Ada Wai-yin; Dragowska, Wieslawa H; Sanche, Léon; Bally, Marcel B

2017-01-01

Copper diethyldithiocarbamate (Cu(DDC)2) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC)2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC)2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC)2 formulation prepared through a method that involves synthesis of Cu(DDC)2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC)2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4–11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC)2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC)2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC)2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC(0−∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC)2 formulation was subsequently evaluated in the MV-4–11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC)2 formulation in vivo. PMID:28615941

Changes in IL12A methylation pattern in livers from mice fed DDC.

PubMed

Oliva, J; French, S W

2012-04-01

Mallory-Denk body (MDB) formation is a component of alcoholic and non alcoholic hepatitis. Proteins of the TLR pathway were shown to be involved in the formation of MDBs, in mice fed DDC. TLR genes are upregulated and SAMe supplementation prevents this up regulation and prevented the formation of MDBs. DNA of livers from control mice, from mice fed DDC 10weeks, refed 1week with DDC and with DDC+SAMe were extracted and used to study the methylation pattern of genes involves in the TLR pathway. A PCR array was used to analyze it. Using PCR arrays for the mouse TLR pathway,24 genes were found whose expression of IL12A was regulated by the methylation of its gene. DDC fed for 10weeks reduced the methylation of the IL12A gene expression. This expression was also reduced when DDC was refed. However, when SAMe was fed, the intermediate level methylation of IL12A was up regulated to the intermediate level and the methylation of the promoter decreased compared to DDC refeeding or DDC 10weeks. IL12A is known to induce the production of IFNg by NK and L(T). We showed in a previous publication that IFNg is one of the major cytokines involved in the induction of MDB formation. The low expression of IL12A associated with the intermediate methylation of its promoter could explain one step in the mechanism which leads to the formation of MDBs. Copyright © 2012 Elsevier Inc. All rights reserved.

Environmental Pollution: Noise Pollution - Sonic Boom

DTIC Science & Technology

1977-06-01

UNCLASSIFIED AD-A041 400 DDC/BIB-77/06 ENVIRONMENTAL POLLUTION NOISE POLLUTION SONIC BOOM A DDC BIBLIOGRAPHY DDC-TAS Cameron Station Alexandria, Va...rn7Sttio 658S-A041 400 4 TITLE xand r.VuhtlVlia) 2 TA i b- 1iblog ra ph y ENVIRONMENTAL POLLUTION : --. Apr-l IM59-Jul, 7NOISE POLLUTION -SONIC BOOM. 1,976...BIBLIOGRAPHY SEARCH CONTROL NO. /2OM09 AD- 769 970 20/1 1/3 DEFENSE UOCUMENTATION CENTER ALEXANDRIA VA ENVIRONMENTAL POLLUTION : NOISE POLLUTION

The USAF Stability and Control Digital DATCOM. Volume II. Implementation of Datcom Methods

DTIC Science & Technology

1979-04-01

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Ufmylation and FATylation Pathways are Down Regulated in Human Alcoholic and Non Alcoholic Steatohepatitis, and Mice Fed DDC, where Mallory-Denk Bodies (MDBs) Form

PubMed Central

Liu, H; Li, J; Tillman, B; French, BA; French, SW

2014-01-01

We previously reported the mechanisms involved in the formation of Mallory-Denk bodies (MDBs) in mice fed DDC. To further provide clinical evidence as to how ubiquitin-like protein (Ubls) modification, gene transcript expression in Ufmylation and FATylation were investigated in human archived formalin-fixed, paraffin-embedded (FFPE) liver biopsies and frozen liver sections from DDC re-fed mice were used. Real-time PCR analysis showed that all Ufmylation molecules (Ufm1, Uba5, Ufc1, Ufl1 and UfSPs) were significantly down regulated, both in DDC re-fed mice livers and patients’ livers where MDBs had formed, indicating that gene transcript changes were limited to MDB-forming livers where the protein quality control system was down regulated. FAT10 and subunits of the immunoproteasome (LMP2 and LMP7) were both up regulated as previously shown. An approximate 176- and 5-fold up regulation (respectively) of FAT10 were observed in the DDC re-fed mice liver and in the livers of human alcoholic hepatitis with MDBs present, implying that there was an important role played by this gene. The FAT10-specific E1 and E2 enzymes Uba6 and USE1, however, were found to be down regulated both in patients’ livers and in the liver of DDC re-fed mice. Interestedly, the down regulation of mRNA levels was proportionate to MDB abundance in the liver tissues. Our results show the first systematic demonstration of transcript regulation of Ufmylation and FATylation in the liver of patients who form MDBs, where protein quality control is down regulated. This was also shown in livers of DDC re-fed mice where MDBs had formed. PMID:24893112

Ufmylation and FATylation pathways are downregulated in human alcoholic and nonalcoholic steatohepatitis, and mice fed DDC, where Mallory-Denk bodies (MDBs) form.

PubMed

Liu, H; Li, J; Tillman, B; French, B A; French, S W

2014-08-01

We previously reported the mechanisms involved in the formation of Mallory-Denk bodies (MDBs) in mice fed DDC. To further provide clinical evidence as to how ubiquitin-like protein (Ubls) modification, gene transcript expression in Ufmylation and FATylation were investigated in human archived formalin-fixed, paraffin-embedded (FFPE) liver biopsies and frozen liver sections from DDC re-fed mice were used. Real-time PCR analysis showed that all Ufmylation molecules (Ufm1, Uba5, Ufc1, Ufl1 and UfSPs) were significantly downregulated, both in DDC re-fed mice livers and patients' livers where MDBs had formed, indicating that gene transcript changes were limited to MDB-forming livers where the protein quality control system was downregulated. FAT10 and subunits of the immunoproteasome (LMP2 and LMP7) were both upregulated as previously shown. An approximate 176- and 5-fold upregulation (respectively) of FAT10 was observed in the DDC re-fed mice liver and in the livers of human alcoholic hepatitis with MDBs present, implying that there was an important role played by this gene. The FAT10-specific E1 and E2 enzymes Uba6 and USE1, however, were found to be downregulated both in patients' livers and in the liver of DDC re-fed mice. Interestedly, the downregulation of mRNA levels was proportionate to MDB abundance in the liver tissues. Our results show the first systematic demonstration of transcript regulation of Ufmylation and FATylation in the liver of patients who form MDBs, where protein quality control is downregulated. This was also shown in the livers of DDC re-fed mice where MDBs had formed. Copyright © 2014 Elsevier Inc. All rights reserved.

Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC).

PubMed

Dalakas, M C; Semino-Mora, C; Leon-Monzon, M

2001-11-01

The 2'3'-dideoxycytidine (ddC), a nonazylated dideoxynucleoside analog used for the treatment of AIDS, causes a dose-dependent, painful, sensorimotor axonal peripheral neuropathy in up to 30% of the patients. To investigate the cause of the neuropathy, we performed morphological and molecular studies on nerve biopsy specimens from well-selected patients with ddC-neuropathy and from control subjects with disease, including patients with AIDS-related neuropathy never treated with ddC. Because ddC, in vitro, inhibits the replication of mitochondrial DNA (mtDNA), we counted the number of normal and abnormal mitochondria in a 0.04 mm(2) cross-sectional area of the nerves and quantified the copy numbers of mtDNA by competitive PCR in all specimens. A varying degree of axonal degeneration was present in all nerves. Abnormal mitochondria with enlarged size, excessive vacuolization, electron-dense concentric inclusions and degenerative myelin structures were prominent in the ddC-neuropathy and accounted for 55% +/- 2.5% of all counted mitochondria in the axon and Schwann cells, compared with 9% +/- 0.7% of the controls (p < 0.001). Significantly (p < 0.005) reduced copy numbers, with as high as 80% depletion, of the mtDNA was demonstrated in the nerves of the ddC-treated patients compared with the controls. We conclude that ddC induces a mitochondrial neuropathy with depletion of the nerve's mtDNA. The findings are consistent with the ability of ddC to selectively inhibit the gamma-DNA polymerase in neuronal cell lines. Toxicity to mitochondria of the peripheral nerve is a new cause of acquired neuropathy induced by exogenous toxins and may be the cause of neuropathy associated with the other neurotoxic antiretroviral drugs or toxic-metabolic conditions.

FAT10 knock out mice livers fail to develop Mallory-Denk bodies in the DDC mouse model.

PubMed

French, S W; French, B A; Oliva, J; Li, J; Bardag-Gorce, F; Tillman, B; Canaan, A

2012-12-01

Mallory-Denk bodies (MDBs) are aggresomes composed of undigested ubiqutinated short lived proteins which have accumulated because of a decrease in the rate of their degradation by the 26s proteasome. The decrease in the activity of the proteasome is due to a shift in the activity of the 26s proteasome to the immunoproteasome triggered by an increase in expression of the catalytic subunits of the immunoproteasome which replaces the catalytic subunits of the 26s proteasome. This switch in the type of proteasome in liver cells is triggered by the binding of IFNγ to the IFNγ sequence response element (ISRE) located on the FAT10 promoter. To determine if either FAT10 or IFNγ are essential for the formation of MDBs we fed both IFNγ and FAT10 knock out (KO) mice DDC added to the control diet for 10weeks in order to induce MDBs. Mice fed the control diet and Wild type mice fed the DDC or control diet were compared. MDBs were located by immunofluorescent double stains using antibodies to ubiquitin to stain MDBs and FAT10 to localize the increased expression of FAT10 in MDB forming hepatocytes. We found that MDB formation occurred in the IFNγ KO mice but not in the FAT10 KO mice. Western blots showed an increase in the ubiquitin smears and decreases β 5 (chymotrypsin-like 26S proteasome subunit) in the Wild type mice fed DDC but not in the FAT10 KO mice fed DDC. To conclude, we have demonstrated that FAT10 is essential to the induction of MDB formation in the DDC fed mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Anti-aliasing filter design on spaceborne digital receiver

NASA Astrophysics Data System (ADS)

Yu, Danru; Zhao, Chonghui

2009-12-01

In recent years, with the development of satellite observation technologies, more and more active remote sensing technologies are adopted in spaceborne system. The spaceborne precipitation radar will depend heavily on high performance digital processing to collect meaningful rain echo data. It will increase the complexity of the spaceborne system and need high-performance and reliable digital receiver. This paper analyzes the frequency aliasing in the intermediate frequency signal sampling of digital down conversion in spaceborne radar, and gives an effective digital filter. By analysis and calculation, we choose reasonable parameters of the half-band filters to suppress the frequency aliasing on DDC. Compared with traditional filter, the FPGA resources cost in our system are reduced by over 50%. This can effectively reduce the complexity in the spaceborne digital receiver and improve the reliability of system.

Use of Computers in Human Factors Engineering

DTIC Science & Technology

1974-11-01

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No association between polymorphisms in the DDC gene and paranoid schizophrenia in a northern Chinese population.

PubMed

Zhang, Boyu; Jia, Yanbin; Yuan, Yanbo; Yu, Xin; Xu, Qi; Shen, Yucun; Shen, Yan

2004-09-01

Several lines of evidence suggest that dysfunctions of neurotransmitters are associated with schizophrenia. DOPA decarboxylase (DDC) is an enzyme involved directly in the synthesis of dopamine and serotonin, and indirectly in the synthesis of noradrenaline. Therefore, the DDC gene can be considered a candidate gene for schizophrenia. We performed an association study between three single nucleotide polymorphisms in the DDC gene and paranoid schizophrenia. However, in our study no significant differences were found in the genotype distributions and allele frequencies between 80 paranoid schizophrenics and 108 controls for any of the polymorphisms. Neither did the haplotypes of the single nucleotide polymorphisms show any association with paranoid schizophrenia. Therefore, we conclude that the polymorphisms studied do not play a major role in paranoid schizophrenia pathogenesis in the population investigated.

The effects of ebselen on cisplatin and diethyldithiocarbamate (DDC) cytotoxicity in rat hippocampal astrocytes.

PubMed

Hardej, D; Trombetta, L D

2002-05-28

Ebselen is a seleno-organic compound with documented cytoprotective properties. Little work has been done, however, demonstrating ebselen's cytoprotective properties in neural cell lines. In order to examine the effects of this compound and its mechanism of action, astrocytes were exposed to two known neurotoxicants, cisplatin and diethyldithiocarbamate (DDC). Cells were pretreated with 30 microM ebselen and subsequently treated with either 150 microM DDC for 1 h or 250 and 500 microM cisplatin for 24 h. Results indicate significant increases in viability in cells pretreated with ebselen and exposed to cisplatin. Ebselen pretreatment did not significantly increase viability in cells exposed to DDC. Light and scanning electron microscopy studies confirm the viability studies. Gross morphological damage was seen in cells treated with cisplatin, however, cells pretreated with ebselen and then exposed to cisplatin, appeared similar to controls. No differences were noted in cells pretreated with ebselen and then exposed to DDC or cells treated with DDC alone. In order to examine the mechanism of protection of this compound, glutathione status was examined. Results show that ebselen does not significantly increase reduced or oxidized glutathione (GSH, GSSG). All cell groups treated with cisplatin showed an increase in GSH levels. Ebselen showed protection in glutathione depleted cells at the 250 microM cisplatin dose. DDC treatment showed no significant increase in either reduced or oxidized glutathione. We conclude that ebselen significantly protects against cisplatin, but not DDC toxicity. We further conclude that this protection is not related to changes in glutathione status in the rat hippocampal cell line as has been reported in other cell types.

Carbidopa abrogates L-dopa decarboxylase coactivation of the androgen receptor and delays prostate tumor progression.

PubMed

Wafa, Latif A; Cheng, Helen; Plaa, Nathan; Ghaidi, Fariba; Fukumoto, Takahiro; Fazli, Ladan; Gleave, Martin E; Cox, Michael E; Rennie, Paul S

2012-06-15

The androgen receptor (AR) plays a central role in prostate cancer progression to the castration-resistant (CR) lethal state. L-Dopa decarboxylase (DDC) is an AR coactivator that increases in expression with disease progression and is coexpressed with the receptor in prostate adenocarcinoma cells, where it may enhance AR activity. Here, we hypothesize that the DDC enzymatic inhibitor, carbidopa, can suppress DDC-coactivation of AR and retard prostate tumor growth. Treating LNCaP prostate cancer cells with carbidopa in transcriptional assays suppressed the enhanced AR transactivation seen with DDC overexpression and decreased prostate-specific antigen (PSA) mRNA levels. Carbidopa dose-dependently inhibited cell growth and decreased survival in LNCaP cell proliferation and apoptosis assays. The inhibitory effect of carbidopa on DDC-coactivation of AR and cell growth/survival was also observed in PC3 prostate cancer cells (stably expressing AR). In vivo studies demonstrated that serum PSA velocity and tumor growth rates elevated ∼2-fold in LNCaP xenografts, inducibly overexpressing DDC, were reverted to control levels with carbidopa administration. In castrated mice, treating LNCaP tumors, expressing endogenous DDC, with carbidopa delayed progression to the CR state from 6 to 10 weeks, while serum PSA and tumor growth decreased 4.3-fold and 5.4-fold, respectively. Our study is a first time demonstration that carbidopa can abrogate DDC-coactivation of AR in prostate cancer cells and tumors, decrease serum PSA, reduce tumor growth and delay CR progression. Since carbidopa is clinically approved, it may be readily used as a novel therapeutic strategy to suppress aberrant AR activity and delay prostate cancer progression. Copyright © 2011 UICC.

Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice

PubMed Central

Subramanian, Savitha; Han, Chang Yeop; Chiba, Tsuyoshi; McMillen, Timothy S.; Wang, Shari A.; Haw, Antonio; Kirk, Elizabeth A.; O’Brien, Kevin D.; Chait, Alan

2009-01-01

Objective Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease. Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor-deficient (LDLR-/-) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis. Methods and Results LDLR-/- mice were fed chow, high fat, high carbohydrate (diabetogenic) diet without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation and local inflammation were observed in intra-abdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group. Conclusions Obesity-induced macrophage accumulation in adipose tissue is exacerbated by dietary cholesterol. These local inflammatory changes in adipose tissue are associated with insulin resistance, systemic inflammation and increased atherosclerosis in this mouse model. PMID:18239153

Matrix metalloproteinase-1 induction by diethyldithiocarbamate is regulated via Akt and ERK/miR222/ETS-1 pathways in hepatic stellate cells.

PubMed

Liu, Tianhui; Wang, Ping; Cong, Min; Zhang, Dong; Liu, Lin; Li, Hongyi; Zhai, Qingling; Li, Zhuo; Jia, Jidong; You, Hong

2016-08-01

Matrix metalloproteinase-1 (MMP-1) plays an important role in fibrolysis by degrading excessively deposited collagen I and III. We previously demonstrated that diethyldithiocarbamate (DDC) up-regulates MMP-1 in hepatic stellate cells via the ERK1/2 and Akt signalling pathways. In the current study, we attempted to further explore the molecular mechanisms involved in the regulation of MMP-1. We treated a co-cultured system that included hepatocytes (C3A) and hepatic stellate cells (LX-2) with DDC. The data revealed that the transcriptional factor ETS-1, which is an important regulator of MMP-1, was up-regulated in LX-2 cells following DDC treatment. Furthermore, the up-regulation of MMP-1 by DDC has been abrogated through employing si-ETS-1 to block expression of ETS-1. We found that DDC significantly inhibited the expression of miR-222 in LX-2 cells. We transfected miR-222 mimic into LX-2 cells and then co-cultured the cells with C3A. The up-regulation of ETS-1 and MMP-1 in LX-2 cells treated with DDC were inhibited after miR-222 mimic transfection. These data indicate that DDC up-regulated MMP-1 in LX-2 cells through the miR-222/ETS-1 pathway. Finally, we treated the co-cultured system with an Akt inhibitor (T3830) and an ERK1/2 inhibitor (U0126). Both T3830 and U0126 blocked the suppression of miR-222 by DDC in LX-2. Collectively, these data indicate that DDC up-regulated MMP-1 in LX-2 cells through the Akt and ERK/miR-222/ETS-1 pathways. Our study provides experimental data that will aid the control of the process of fibrolysis in liver fibrosis prevention and treatment. © 2016 The Author(s).

Matrix metalloproteinase-1 induction by diethyldithiocarbamate is regulated via Akt and ERK/miR222/ETS-1 pathways in hepatic stellate cells

PubMed Central

Liu, Tianhui; Wang, Ping; Cong, Min; Zhang, Dong; Liu, Lin; Li, Hongyi; Zhai, Qingling; Li, Zhuo; Jia, Jidong; You, Hong

2016-01-01

Matrix metalloproteinase-1 (MMP-1) plays an important role in fibrolysis by degrading excessively deposited collagen I and III. We previously demonstrated that diethyldithiocarbamate (DDC) up-regulates MMP-1 in hepatic stellate cells via the ERK1/2 and Akt signalling pathways. In the current study, we attempted to further explore the molecular mechanisms involved in the regulation of MMP-1. We treated a co-cultured system that included hepatocytes (C3A) and hepatic stellate cells (LX-2) with DDC. The data revealed that the transcriptional factor ETS-1, which is an important regulator of MMP-1, was up-regulated in LX-2 cells following DDC treatment. Furthermore, the up-regulation of MMP-1 by DDC has been abrogated through employing si-ETS-1 to block expression of ETS-1. We found that DDC significantly inhibited the expression of miR-222 in LX-2 cells. We transfected miR-222 mimic into LX-2 cells and then co-cultured the cells with C3A. The up-regulation of ETS-1 and MMP-1 in LX-2 cells treated with DDC were inhibited after miR-222 mimic transfection. These data indicate that DDC up-regulated MMP-1 in LX-2 cells through the miR-222/ETS-1 pathway. Finally, we treated the co-cultured system with an Akt inhibitor (T3830) and an ERK1/2 inhibitor (U0126). Both T3830 and U0126 blocked the suppression of miR-222 by DDC in LX-2. Collectively, these data indicate that DDC up-regulated MMP-1 in LX-2 cells through the Akt and ERK/miR-222/ETS-1 pathways. Our study provides experimental data that will aid the control of the process of fibrolysis in liver fibrosis prevention and treatment. PMID:27412967

Role of DDC-4/sFRP-4, a secreted frizzled-related protein, at the onset of apoptosis in mammary involution.

PubMed

Lacher, M D; Siegenthaler, A; Jäger, R; Yan, Xi; Hett, S; Xuan, L; Saurer, S; Lareu, R R; Dharmarajan, A M; Friis, R

2003-05-01

Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3beta (GSK-3beta), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.

Modeling and experiments for the time-dependent diffusion coefficient during methane desorption from coal

NASA Astrophysics Data System (ADS)

Cheng-Wu, Li; Hong-Lai, Xue; Cheng, Guan; Wen-biao, Liu

2018-04-01

Statistical analysis shows that in the coal matrix, the diffusion coefficient for methane is time-varying, and its integral satisfies the formula μt κ /(1 + β κ ). Therefore, a so-called dynamic diffusion coefficient model (DDC model) is developed. To verify the suitability and accuracy of the DDC model, a series of gas diffusion experiments were conducted using coal particles of different sizes. The results show that the experimental data can be accurately described by the DDC and bidisperse models, but the fit to the DDC model is slightly better. For all coal samples, as time increases, the effective diffusion coefficient first shows a sudden drop, followed by a gradual decrease before stabilizing at longer times. The effective diffusion coefficient has a negative relationship with the size of the coal particle. Finally, the relationship between the constants of the DDC model and the effective diffusion coefficient is discussed. The constant α (μ/R 2 ) denotes the effective coefficient at the initial time, and the constants κ and β control the attenuation characteristic of the effective diffusion coefficient.

The Climate-G testbed: towards a large scale data sharing environment for climate change

NASA Astrophysics Data System (ADS)

Aloisio, G.; Fiore, S.; Denvil, S.; Petitdidier, M.; Fox, P.; Schwichtenberg, H.; Blower, J.; Barbera, R.

2009-04-01

The Climate-G testbed provides an experimental large scale data environment for climate change addressing challenging data and metadata management issues. The main scope of Climate-G is to allow scientists to carry out geographical and cross-institutional climate data discovery, access, visualization and sharing. Climate-G is a multidisciplinary collaboration involving both climate and computer scientists and it currently involves several partners such as: Centro Euro-Mediterraneo per i Cambiamenti Climatici (CMCC), Institut Pierre-Simon Laplace (IPSL), Fraunhofer Institut für Algorithmen und Wissenschaftliches Rechnen (SCAI), National Center for Atmospheric Research (NCAR), University of Reading, University of Catania and University of Salento. To perform distributed metadata search and discovery, we adopted a CMCC metadata solution (which provides a high level of scalability, transparency, fault tolerance and autonomy) leveraging both on P2P and grid technologies (GRelC Data Access and Integration Service). Moreover, data are available through OPeNDAP/THREDDS services, Live Access Server as well as the OGC compliant Web Map Service and they can be downloaded, visualized, accessed into the proposed environment through the Climate-G Data Distribution Centre (DDC), the web gateway to the Climate-G digital library. The DDC is a data-grid portal allowing users to easily, securely and transparently perform search/discovery, metadata management, data access, data visualization, etc. Godiva2 (integrated into the DDC) displays 2D maps (and animations) and also exports maps for display on the Google Earth virtual globe. Presently, Climate-G publishes (through the DDC) about 2TB of data related to the ENSEMBLES project (also including distributed replicas of data) as well as to the IPCC AR4. The main results of the proposed work are: wide data access/sharing environment for climate change; P2P/grid metadata approach; production-level Climate-G DDC; high quality tools for data visualization; metadata search/discovery across several countries/institutions; open environment for climate change data sharing.

[The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning].

PubMed

Liu, Jing; Wang, Qiu-ying; Wang, Bei; Xuan, Xiao-qiang; Chen, Qiong; Xu, Dong-wei; Cheng, Ning

2011-02-01

To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning. In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope. Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4 h or 30 h and tested on the 7th day after exposure, DDC group administrated at 30h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P < 0.05 or P < 0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone, DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels. The results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.

First-Principles Calculations for Chemical Reaction between Sodium Diethyldithiocarbamate and Transition-Metal (Cr) atom to Produce Cr(DDC)3 and Cr(DDC)2ODDC

NASA Astrophysics Data System (ADS)

Setiyanto, Henry; Muhida, Rifki; Kishi, Tomoya; Rempillo, Ofelia; Rahman, Mahmudur; Dipojono, Hermawan Kresno; Di\\ {n}o, Wilson Agerico; Matsumoto, Shigeno; Kasai, Hideaki

2006-10-01

We investigate the chemical reaction between a Cr transition-metal atom and sodium diethyldithiocarbamate (NaDDC), a complexing agent used to detect and extract Cr in human blood samples. Using density-functional-theory-based calculations, we determine their stable structures of Cr(DDC)2ODDC and Cr(DDC)3 complexes and obtain their dissociation energies. We found dissociation energies of -10.66 and -3.24 eV for Cr(DDC)2ODDC and Cr(DDC)3 complexes, respectively. Hence, on the basis of dissociation energies, we have verified that the reaction of NaDDC with Cr produces Cr(DDC)2ODDC as a major product.

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

PubMed

Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

2016-08-01

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

A Member of the p38 Mitogen-Activated Protein Kinase Family Is Responsible for Transcriptional Induction of Dopa decarboxylase in the Epidermis of Drosophila melanogaster during the Innate Immune Response▿ †

PubMed Central

Davis, Monica M.; Primrose, David A.; Hodgetts, Ross B.

2008-01-01

Drosophila innate immunity is controlled primarily by the activation of IMD (immune deficiency) or Toll signaling leading to the production of antimicrobial peptides (AMPs). IMD signaling also activates the JUN N-terminal kinase (JNK) cascade, which is responsible for immune induction of non-antimicrobial peptide immune gene transcription though the transcription factor AP-1. Transcription of the Dopa decarboxylase (Ddc) gene is induced in response to gram-negative and gram-positive septic injury, but not aseptic wounding. Transcription is induced throughout the epidermis and not specifically at the site of infection. Ddc transcripts are detectible within 2 h and remain high for several hours following infection with either gram-negative or gram-positive bacteria. Using Ddc-green fluorescent protein (GFP) reporter gene constructs, we show that a conserved consensus AP-1 binding site upstream of the Ddc transcription start site is required for induction. However, neither the Toll, IMD, nor JNK pathway is involved. Rather, Ddc transcription depends on a previously uncharacterized member of the p38 mitogen-activated protein kinase family, p38c. We propose that the involvement of DDC in a new pathway involved in Drosophila immunity increases the levels of dopamine, which is metabolized to produce reactive quinones that exert an antimicrobial effect on invading bacteria. PMID:18519585

Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet.

PubMed

Abiko, Yukie; Kojima, Takashi; Murata, Masaki; Tsujiwaki, Mitsuhiro; Takeuchi, Masaya; Sawada, Norimasa; Mori, Michio

2013-12-01

DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine)-fed mice are widely used as a model for cholestatic liver disease. We examined the expression of tight junction protein claudin subspecies by immunofluorescent histochemistry in small intestine and kidney tissues of mice fed a DDC diet for 12 weeks. In the small intestine, decreases in claudin-3, claudin-7 and claudin-15 were observed in villous epithelial cells corresponding to the severity of histological changes while leaving the abundance of these claudin subspecies unchanged in crypt cells. Nevertheless, the proliferative activity of intestinal crypt cells measured by immunohistochemistry for Ki-67 decreased in the mice fed the DDC diet compared with that of control mice. These results suggest the possibility that DDC feeding affects the barrier function of villous epithelial cells and thus inhibits the proliferative activity of crypt epithelial cells. On the other hand, in the kidney, remarkable changes were found in the subcellular localization of claudin subspecies in a segment-specific manner, although histological changes of renal epithelial cells were quite minimal. These results indicate that immunohistochemistry for claudin subspecies can serve as a useful tool for detecting minute functional alterations of intestinal and renal epithelial cells.

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo

PubMed Central

Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

2016-01-01

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [18F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment. PMID:26924680

Induction of the early-late Ddc gene during Drosophila metamorphosis by the ecdysone receptor.

PubMed

Chen, Li; Reece, Christian; O'Keefe, Sandra L; Hawryluk, Gregory W L; Engstrom, Monica M; Hodgetts, Ross B

2002-06-01

During Drosophila metamorphosis, the 'early-late' genes constitute a unique class regulated by the steroid hormone 20-hydroxyecdysone. Their induction is comprised of both a primary and a secondary response to ecdysone. Previous work has suggested that the epidermal expression of the dopa decarboxylase gene (Ddc) is likely that of a typical early-late gene. Accumulation of the Ddc transcript is rapidly initiated in the absence of protein synthesis, which implies that the ecdysone receptor plays a direct role in induction. However, full Ddc expression requires the participation of one of the transcription factors encoded by the Broad-Complex. In this paper, we characterize an ecdysone response element (EcRE) that contributes to the primary response. Using gel mobility shift assays and transgenic assays, we identified a single functional EcRE, located at position -97 to -83 bp relative to the transcription initiation site. This is the first report of an EcRE associated with an early-late gene in Drosophila. Competition experiments indicated that the affinity of the Ddc EcRE for the ecdysone receptor complex was at least four-fold less than that of the canonical EcRE of the hsp27 gene. Using in vitro mutagenesis, we determined that the reduced affinity of the EcRE resided at two positions where the nucleotides differed from those found in the canonical sequence. The ecdysone receptor, acting through this EcRE, releases Ddc from a silencing mechanism, whose cis-acting domain we have mapped to the 5'-upstream region between -2067 and -1427 bp. Deletion of this repressive element resulted in precocious expression of Ddc in both epidermis and imaginal discs. Thus, epidermal Ddc induction at pupariation is under the control of an extended genomic region that contains both positive and negative regulatory elements. Copyright 2002 Elsevier Science Ireland Ltd.

IF digitization receiver of wideband digital array radar test-bed

NASA Astrophysics Data System (ADS)

Li, Weixing; Zhang, Yue; Lin, Jianzhi; Chen, Zengping

2014-10-01

In this paper, an X-band, 8-element wideband digital array radar (DAR) test-bed is presented, which makes use of a novel digital backend coupled with highly-integrated, multi-channel intermediate frequency (IF) digital receiver. Radar returns are received by the broadband antenna and then down-converted to the IF of 0.6GHz-3.0GHz. Four band-pass filters are applied in the front-end to divide the IF returns into four frequency bands with the instantaneous bandwidth of 500MHz. Every four array elements utilize a digital receiver, which is focused in this paper. The digital receivers are designed in a compact and flexible manner to meet the demands of DAR system. Each receiver consists of a fourchannel ADC, a high-performance FPGA, four DDR3 chips and two optical transceivers. With the sampling rate of up to 1.2GHz each channel, the ADC is capable of directly sampling the IF returns of four array elements at 10bits. In addition to serving as FIFO and controller, the onboard FPGA is also utilized for the implementation of various real-time algorithms such as DDC and channel calibration. Data is converted to bit stream and transferred through two low overhead, high data rate and multi-channel optical transceivers. Key technologies such as channel calibration and wideband DOA are studied with the measured data which is obtained in the experiments to illustrate the functionality of the system.

Exploring the Acoustic Nonlinearity for Monitoring Complex Aerospace Structures

DTIC Science & Technology

2008-02-27

nonlinear elastic waves, embedded ultrasonics, nonlinear diagnostics, aerospace structures, structural joints. 16. SECURITY CLASSIFICATION OF: 17...sampling, 100 MHz bandwidth with noise and anti- aliasing filters, general-purpose alias-protected decimation for all sample rates and quad digital down...conversion ( DDC ) with up to 40 MHz IF bandwidth. Specified resolution of NI PXI 5142 is 14-bits with the noise floor approaching -85 dB. Such a

Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study.

PubMed

Turpin, Anthony; Paget-Bailly, Sophie; Ploquin, Anne; Hollebecque, Antoine; Peugniez, Charlotte; El-Hajbi, Farid; Bonnetain, Franck; Hebbar, Mohamed

2018-03-01

We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab. We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated. With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC. DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage.

PubMed

Deshpande, Ishan; Seeber, Andrew; Shimada, Kenji; Keusch, Jeremy J; Gut, Heinz; Gasser, Susan M

2017-10-19

Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited through the single-stranded (ss) DNA-binding replication protein A (RPA) to initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the absence of DNA damage is lethal. Therefore, it is important that damage-specific recruitment precedes kinase activation, which is achieved at least in part by Mec1-Ddc2 homodimerization. Here, we report a structural, biochemical, and functional characterization of the yeast Mec1-Ddc2-RPA assembly. High-resolution co-crystal structures of Ddc2-Rfa1 and Ddc2-Rfa1-t11 (K45E mutant) N termini and of the Ddc2 coiled-coil domain (CCD) provide insight into Mec1-Ddc2 homodimerization and damage-site targeting. Based on our structural and functional findings, we present a Mec1-Ddc2-RPA-ssDNA composite structural model. By way of validation, we show that RPA-dependent recruitment of Mec1-Ddc2 is crucial for maintaining its homodimeric state at ssDNA and that Ddc2's recruitment domain and CCD are important for Mec1-dependent survival of UV-light-induced DNA damage. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired bile acid handling and aggravated liver injury in mice expressing a hepatocyte-specific RXRα variant lacking the DNA-binding domain.

PubMed

Kosters, Astrid; Felix, Julio C; Desai, Moreshwar S; Karpen, Saul J

2014-02-01

Retinoid X Receptor α (RXRα) is the principal heterodimerization partner of class II Nuclear Receptors (NRs), and a major regulator of gene expression of numerous hepatic processes, including bile acid (BA) homeostasis through multiple partners. Specific contributions of hepatic RXRα domains in heterodimer function in response to either BA load or ductular cholestasis are not fully characterized. Wild-type (WT) mice and mice expressing a hepatocyte-specific RXRα lacking the DNA-Binding-Domain (hs-RxrαΔex4(-/-)), which retains partial ability to heterodimerize with its partners, were fed a 1% cholic acid (CA) diet for 5 days, a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 3 weeks, or control diet. Serum ALT (6.5-fold; p<0.05), AST (9.3-fold; p=0.06) and BA (2.8-fold; p<0.05) were increased in CA-fed hs-RxαΔex4(-/-) mice compared to CA-fed WT mice, but were equally induced between genotypes by DDC-feeding. CA-feeding elevated total (4.4-fold; p=0.06) and unconjugated (2.2-fold; p<0.02) bilirubin levels in hs-RxrαΔex4(-/-) mice compared to WT mice, but not in DDC-fed hs-RxrαΔex4(-/-) mice. Increased necrosis and inflammation was observed in CA-fed, but not in DDC-fed hs-RxrαΔex4(-/-) mice. Apoptotic markers DR5, CK8, CK18 RNA were increased in CA- and DDC-fed hs-RxrαΔex4(-/-) mice. Cleaved caspase 3, CK18 and p-JNK protein were elevated in CA-fed but not in DDC-fed hs-RxrαΔex4(-/-) mice. Induction of Ostβ and Cyp2b10 RNA was impaired in CA-fed and DDC-fed hs-RxrαΔex4(-/-) mice. Surprisingly, DDC-fed hs-RxrαΔex4(-/-) mice showed attenuated fibrosis compared to DDC-fed WT mice. These two models of cholestasis identify common and injury-specific roles for RXRα heterodimers and the functional relevance of an intact RXRα-DBD in the hepatocytic adaptive cholestatic response. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

An FPGA-based reconfigurable DDC algorithm

NASA Astrophysics Data System (ADS)

Juszczyk, B.; Kasprowicz, G.

2016-09-01

This paper describes implementation of reconfigurable digital down converter in an FPGA structure. System is designed to work with quadrature signals. One of the main criteria of the project was to provied wide range of reconfiguration in order to fulfill various application rage. Potential applications include: software defined radio receiver, passive noise radars and measurement data compression. This document contains general system overview, short description of hardware used in the project and gateware implementation.

l-DOPA Decarboxylase (DDC) Expression Status as a Novel Molecular Tumor Marker for Diagnostic and Prognostic Purposes in Laryngeal Cancer.

PubMed

Patsis, Christos; Glyka, Vasiliki; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

2012-08-01

l-DOPA decarboxylase (DDC) plays an essential role in the enzymatic synthesis of dopamine and alterations in its gene expression have been reported in several malignancies. Our objective was to analyze DDC messenger RNA (mRNA) and protein expression in laryngeal tissues and to evaluate the clinical implication of this molecule in laryngeal cancer. In this study, total RNA was isolated from 157 tissue samples surgically removed from 100 laryngeal cancer patients. A highly sensitive real-time polymerase chain reaction methodology based on SYBR Green I fluorescent dye was developed for the quantification of DDC mRNA levels. In addition, Western blot analysis was performed for the detection of DDC protein. DDC mRNA expression was revealed to be significantly downregulated in primary laryngeal cancer samples compared with their nonmalignant counterparts (P = .001). A significant negative association was also disclosed between DDC mRNA levels and TNM staging (P = .034). Univariate analysis showed that patients bearing DDC-positive tumors had a significantly decreased risk of death (hazard ratio = 0.23, P = .012) and local recurrence (hazard ratio = 0.32, P =.006), whereas DDC expression retained its favorable prognostic significance in the multivariate analysis. Kaplan-Meier curves further demonstrated that DDC-positive patients experienced longer overall and disease-free survival periods (P = .006 and P = .004, respectively). Moreover, DDC protein was detected in both neoplastic and noncancerous tissues. Therefore, our results suggest that DDC expression status could qualify as a promising biomarker for the future clinical management of laryngeal cancer patients.

l-DOPA Decarboxylase (DDC) Expression Status as a Novel Molecular Tumor Marker for Diagnostic and Prognostic Purposes in Laryngeal Cancer1

PubMed Central

Patsis, Christos; Glyka, Vasiliki; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

2012-01-01

l-DOPA decarboxylase (DDC) plays an essential role in the enzymatic synthesis of dopamine and alterations in its gene expression have been reported in several malignancies. Our objective was to analyze DDC messenger RNA (mRNA) and protein expression in laryngeal tissues and to evaluate the clinical implication of this molecule in laryngeal cancer. In this study, total RNA was isolated from 157 tissue samples surgically removed from 100 laryngeal cancer patients. A highly sensitive real-time polymerase chain reaction methodology based on SYBR Green I fluorescent dye was developed for the quantification of DDC mRNA levels. In addition, Western blot analysis was performed for the detection of DDC protein. DDC mRNA expression was revealed to be significantly downregulated in primary laryngeal cancer samples compared with their nonmalignant counterparts (P = .001). A significant negative association was also disclosed between DDC mRNA levels and TNM staging (P = .034). Univariate analysis showed that patients bearing DDC-positive tumors had a significantly decreased risk of death (hazard ratio = 0.23, P = .012) and local recurrence (hazard ratio = 0.32, P =.006), whereas DDC expression retained its favorable prognostic significance in the multivariate analysis. Kaplan-Meier curves further demonstrated that DDC-positive patients experienced longer overall and disease-free survival periods (P = .006 and P = .004, respectively). Moreover, DDC protein was detected in both neoplastic and noncancerous tissues. Therefore, our results suggest that DDC expression status could qualify as a promising biomarker for the future clinical management of laryngeal cancer patients. PMID:22937181

Aromatic L-Amino Acid Decarboxylase (AADC) Is Crucial for Brain Development and Motor Functions

PubMed Central

Shih, De-Fen; Hsiao, Chung-Der; Min, Ming-Yuan; Lai, Wen-Sung; Yang, Chianne-Wen; Lee, Wang-Tso; Lee, Shyh-Jye

2013-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children. PMID:23940784

L-Dopa decarboxylase expression profile in human cancer cells.

PubMed

Chalatsa, Ioanna; Nikolouzou, Eleftheria; Fragoulis, Emmanuel G; Vassilacopoulou, Dido

2011-02-01

L-Dopa decarboxylase (DDC) catalyses the decarboxylation of L-Dopa. It has been shown that the DDC gene undergoes alternative splicing within its 5'-untranslated region (UTR), in a tissue-specific manner, generating identical protein products. The employment of two alternative 5'UTRs is thought to be responsible for tissue-specific expression of the human DDC mRNA. In this study, we focused on the investigation of the nature of the mRNA expression in human cell lines of neural and non-neural origin. Our results show the expression of a neural-type DDC mRNA splice variant, lacking exon 3 in all cell lines studied. Co-expression of the full length non-neural DDC mRNA and the neural-type DDC splice variant lacking exon 3 was detected in all cell lines. The alternative DDC protein isoform, Alt-DDC, was detected in SH-SY5Y and HeLa cells. Our findings suggest that the human DDC gene undergoes complex processing, leading to the formation of multiple mRNA isoforms. The study of the significance of this phenomenon of multiple DDC mRNA isoforms could provide us with new information leading to the elucidation of the complex biological pathways that the human enzyme is involved in.

Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions.

PubMed

Shih, De-Fen; Hsiao, Chung-Der; Min, Ming-Yuan; Lai, Wen-Sung; Yang, Chianne-Wen; Lee, Wang-Tso; Lee, Shyh-Jye

2013-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.

CYP 2E1 mutant mice are resistant to DDC-induced enhancement of MPTP toxicity.

PubMed

Viaggi, C; Vaglini, F; Pardini, C; Sgadò, P; Caramelli, A; Corsini, G U

2007-01-01

In order to reach a deeper insight into the mechanism of diethyldithiocarbamate (DDC)-induced enhancement of MPTP toxicity in mice, we showed that CYP450 (2E1) inhibitors, such as diallyl sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective DA neuron degeneration in C57/bl mice. Furthermore we showed that CYP 2E1 is present in the brain and in the basal ganglia of mice (Vaglini et al., 2004). However, because DAS and PIC are not selective CYP 2E1 inhibitors and in order to provide direct evidence for CYP 2E1 involvement in the enhancement of MPTP toxicity, CYP 2E1 knockout mice (GONZ) and wild type animals (SVI) of the same genetic background were treated with MPTP or the combined DDC + MPTP treatment. In CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP toxicity, although enhancement of MPTP toxicity was regularly present in the SVI control animals. The immunohistochemical study confirms our results and suggests that CYP 2E1 may have a detoxifying role.

High performance 1553

NASA Astrophysics Data System (ADS)

Hegarty, Michael G.

2005-05-01

The U.S. Air Force is currently in the process of developing a revision to MIL-STD-1553 that will provide additional digital communication bandwidth beyond MIL-STD-1553B's 1 Megabit per second (Mbps) rate. The proposed revision to MIL-STD-1553 (referred to as MIL-STD-1553C) is targeting 200 Mbps as a baseline data rate. This paper explores the feasibility of the U.S. Air Force's proposed revision to MIL-STD-1553 based on studies conducted by Data Device Corporation (DDC). A combination of empirical and theoretical methods is used to determine if a MIL-STD-1553B network contains sufficient capacity to support the proposed 200 Mbps data rate. The results of DDC's analysis is that for some MIL-STD-1553 buses there is sufficient bandwidth to implement a broadband system in which legacy 1 Mbps 1553B waveforms could coexist with new 200 Mbps waveforms, thus providing an incremental high speed communication channel to existing MIL-STD-1553 buses.

An ocular drug delivery system containing zinc diethyldithiocarbamate and HPbetaCD inclusion complex--corneal permeability, anti-cataract effects and mechanism studies.

PubMed

Wang, Siling; Li, Dexin; Ito, Yoshimasa; Liu, Xia; Zhang, Jinghai; Wu, Chunfu

2004-10-01

Our purpose was to study the formulation and anti-cataract effects of aqueous eye drops containing a high concentration of zinc diethyldithiocarbamate (Zn-DDC). A possible mechanism of the anti-cataract effect of Zn-DDC was also studied. Zn-DDC and hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion complex (Zn-DDC/HPbetaCD) was studied using the saturation solution method and characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (IR). Suitable formulations for Zn-DDC eye drops were established by means of in-vitro trans-corneal penetration experiments. The anti-cataract effect of the selected formulation was demonstrated by the delay in lens opacity development in hereditary shumuya cataract rats (SCRs). Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to study the effect of diethyldithiocarbamate (DDC), a metabolite of Zn-DDC, on the transcription inducible nitric oxide synthase (iNOS) mRNA in human lens epithelial cells (HLEC). In the presence of 22% (w/v) HPbetaCD, the solubility of Zn-DDC in water (0.2 mM) was increased almost 850 fold (to 17 mM), by the formation of Zn-DDC/HPbetaCD. The stoichiometry of Zn-DDC inclusion was 1:1. The Zn-DDC/HPbetaCD stability constant, Ks (1:1) was estimated to be 3453 M(-1). The ophthalmic preparation containing 0.1% HPMC and 0.1% poloxamer 188 (P188) exhibited better permeability than the others in-vitro, and significantly delayed cataract formation in SCRs compared with non-treated SCRs. DDC inhibits the transcription of iNOS mRNA in HLEC. We concluded that this drug delivery system increases both the drug solubility in aqueous eye drops and the permeability of drug through the rabbit cornea, by the formation of a drug-cyclodextrin inclusion complex and the addition of polymers and penetration enhancers. The preparation effectively prevented the development of cataracts in SCRs. DDC, the metabolite of Zn-DDC, may be one of the factors in the prevention of cataract formation because it inhibits the transcription of iNOS mRNA.

Ada Compiler Validation Summary Report: Certificate Number: 940325S1. 11348 DDC-I, DACS Sun SPARC/Solaris to 80386 PM Bare Ada Cross Compiler System, Version 4.6.4 Sun SPARCclassic = Intel iSBC 386/116 (Bare Machine)

DTIC Science & Technology

1994-03-25

digits than SYSTEM.MAXDIGITS: C24113L..Y (14 tests) C35705L..Y (14 tests) C35706L..Y (14 tests) C35707L..Y (14 tests) 2-1 C35708L..Y (14 tests) C35802L...MACHINE CODETYPE : REGISTERTYPE MANTISSADOC : 31 A-2 MAX_- DIGITS : 15 MAX_-INT : 9223372036854775807 MAX_-INTPLUS_1 : 9223372036854775808 MIN_ INT...words. A libary task is formed when a task object is declared at the outermost level of a package. Library tasks ame created and activated during the

The DBBC environment for millimeter radioastronomy

NASA Astrophysics Data System (ADS)

Tuccari, Gino; Comoretto, Giovanni; Melis, Andrea; Buttaccio, Salvo

2012-09-01

The Digital Base Band Converter project developed in the last decade produced a general architecture and a class of boards, firmware and software, giving the possibility to build a general purpose back-end system for VLBI or single-dish observational activities. Such approach suggests the realization of a digital radio system, i.e. a receiver with conversion not realized with analogue techniques, maintaining only amplification stages in the analogue domain. This solution can be applied until a maximum around 16 GHz, the present limit for the instantaneous input band in the latest version of the DBBC project, while in the millimeter frequency range this maximum limit of 0.5-2 GHz of the previous versions allows the intermediate frequency to be processed in the digital domain. A description of the elements developed in the DBBC project is presented, with their use in different environments. The architecture is composed of a PC controlled mainframe, and of different modules that can be combined in a very flexible way in order to realize different instruments. The instrument can be expanded or retrofitted to meet increasing observational demands. Available modules include ADC converters, processing boards, physical interfaces (VSI and 10G Ethernet). Several applications have already been implemented and used in radioastronomic observations: a DDC (Direct Digital Conversion) for VLBI observations, a Polyphase Digital Filter Bank, and a Multiband Scansion Spectrometer. Other applications are currently studied for additional functionalities like a spectropolarimeter, a linear-to-circular polarization converter, a RFI-mitigation tool, and a phase-reference holographic tool-kit.

Installation of PMV Operation Program in DDC Controller and Air Conditioning Control Using PMV Directly as Set Point

NASA Astrophysics Data System (ADS)

Haramoto, Ken-Ichi

In general, air conditioning control in a building is operated mainly by indoor air temperature control. Although the operators of the machine in the building accepted a claim for indoor air temperature presented by the building inhabitants, the indoor conditions have been often too cool or warm. Therefore, in an attempt to create better thermal environments, the author paid attention to the PMV that is a thermal comfort index. And then, the possibility of air conditioning control using the PMV directly as the set point was verified by employing actual equipment in an air conditioning testing room and an office building. Prior to the execution of this control, the operation program of the PMV was installed in a DDC controller for the air conditioning control. And information from indoor sensors and so on was inputted to the controller, and the computed PMV was used as the feedback variable.

L-Dopa decarboxylase (DDC) constitutes an emerging biomarker in predicting patients' survival with stomach adenocarcinomas.

PubMed

Florou, Dimitra; Papadopoulos, Iordanis N; Fragoulis, Emmanuel G; Scorilas, Andreas

2013-02-01

Stomach adenocarcinoma represents a major health problem and is regarded as the second commonest cause of cancer-associated mortality, universally, since it is still difficult to be perceived at a curable stage. Several lines of evidence have pointed out that the expression of L-Dopa decarboxylase (DDC) gene and/or protein becomes distinctively modulated in several human neuroendocrine neoplasms as well as adenocarcinomas. In order to elucidate the clinical role of DDC on primary gastric adenocarcinomas, we determined qualitatively and quantitatively the mRNA levels of the gene with regular PCR and real-time PCR by using the comparative threshold cycle method, correspondingly, and detected the expression of DDC protein by immunoblotting in cancerous and normal stomach tissue specimens. A statistically significant association was disclosed between DDC expression and gastric intestinal histotype as well as tumor localization at the distal third part of the stomach (p = 0.025 and p = 0.029, respectively). Univariate and multivariate analyses highlighted the powerful prognostic importance of DDC in relation to disease-free survival and overall survival of gastric cancer patients. According to Kaplan-Meier curves, the relative risk of relapse was found to be decreased in DDC-positive (p = 0.031) patients who, also, exhibited higher overall survival rates (p = 0.016) than those with DDC-negative tumors. This work is the first to shed light on the potential clinical usefulness of DDC, as an efficient tumor biomarker in gastric cancer. The provided evidence underlines the propitious predictive value of DDC expression in the survival of stomach adenocarcinoma patients.

Economic evaluation of an oral rabies vaccination program for control of a domestic dog-coyote rabies epizootic: 1995-2006.

PubMed

Shwiff, Stephanie A; Kirkpatrick, Katy N; Sterner, Ray T

2008-12-01

To conduct a benefit-cost analysis of the results of the domestic dog and coyote (DDC) oral rabies vaccine (ORV) program in Texas from 1995 through 2006 by use of fiscal records and relevant public health data. Retrospective benefit-cost analysis. Procedures-Pertinent economic data were collected in 20 counties of south Texas affected by a DDC-variant rabies epizootic. The costs and benefits afforded by a DDC ORV program were then calculated. Costs were the total expenditures of the ORV program. Benefits were the savings associated with the number of potentially prevented human postexposure prophylaxis (PEP) treatments and animal rabies tests for the DDC-variant rabies virus in the epizootic area and an area of potential disease expansion. Total estimated benefits of the program approximately ranged from $89 million to $346 million, with total program costs of $26,358,221 for the study period. The estimated savings (ie, damages avoided) from extrapolated numbers of PEP treatments and animal rabies tests yielded benefit-cost ratios that ranged from 3.38 to 13.12 for various frequen-cies of PEP and animal testing. In Texas, the use of ORV stopped the northward spread and led to the progressive elimination of the DDC variant of rabies in coyotes (Canis latrans). The decision to implement an ORV program was cost-efficient, although many unknowns were involved in the original decision, and key economic variables were identified for consideration in future planning of ORV programs.

Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer.

PubMed

Avgeris, Margaritis; Koutalellis, Georgios; Fragoulis, Emmanuel G; Scorilas, Andreas

2008-10-01

L-Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (p<0.001). Logistic regression and ROC analysis have demonstrated that the DDC expression has significant discriminatory value between CaP and BPH (p<0.001). DDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p=0.022) as well as in advanced stage patients (p=0.032). Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.

Hemolysis of human red blood cells induced by the combination of diethyldithiocarbamate (DDC) and divalent metals: modulation by anaerobiosis, certain antioxidants and oxidants.

PubMed

Ginsburg, I; Sadovnic, M; Varani, J; Tirosh, O; Kohen, R

1999-08-01

The objective of the present communication is to describe the role played by combinations between diethydithiocarbamate (DDC) and divalent metals in hemolysis of human RBC. RBC which had been treated with DDC (10-50 microM) were moderately hemolyzed (about 50%) upon the addition of subtoxic amounts of Cu2+ (50 microM). However, a much stronger and a faster hemolysis occurred either if mixtures of RBC-DDC were immediately treated either by Co2+ (50 microM) or by a premixture of Cu2+ and Co2+ (Cu:Co) (50 microM). While Fe2+ and Ni2+, at 50 microM, initiated 30-50% hemolysis when combined with DDC (50 microM), on a molar basis, Cd2+ was at least 50 fold more efficient than any of the other metals in the initiation of hemolysis by DDC. On the other hand, neither Mn2+ nor Zn2+, had any hemolysis-initiating effects. Co2+ was the only metal which totally blocked hemolysis if added to DDC prior to the addition of the other metals. Hemolysis by mixtures of DDC + (Cu:Co) was strongly inhibited by anaerobiosis (flushing with nitrogen gas), by the reducing agents glutathione, N-acetyl cysteine, mercaptosuccinate, ascorbate, TEMPO, and alpha-tocopherol, by the PLA2 inhibitorbromophenacylbromide (BrPACBr), by tetracycline as well as by phosphatidyl choline, cholesterol and by trypan blue. However, TEMPO, BrPACBr and PC were the only agents which inhibited hemolysis induced by DDC: Cd2+ complexes. On the other hand, none of the classical scavengers of reactive oxygen species (ROS) employed e.g dimethylthiourea, catalase, histidine, mannitol, sodium benzoate, nor the metal chelators desferal and phenanthroline, had any appreciable inhibitory effects on hemolysis induced by DDC + (Cu:Co). DDC oxidized by H2O2 lost its capacity to act in concert either with Cu2+ or with Cd2+ to hemolyze RBC. While either heating RBC to temperatures greater than 37 degrees C or exposure of the cells to glucose-oxidase-generated peroxide diminished their susceptibility to hemolysis, exposure to the peroxyl radical from AAPH, enhanced hemolysis by DDC + (Cu:Co). The cyclovoltammetry patterns of DDC were drastically changed either by Cu2+, Co2+ or by Cd2+ suggesting a strong interaction of the metals with DDC. Also, while the absorbance spectrum of DDC at 280 nm was decreased by 50% either by Co2+, Cd2+ or by H2O2, a 90% reduction in absorbance occurred if DDC + H2O2 mixtures were treated either by Cu2+ or by Co2+, but not by Cd2+. Taken together, it is suggested that DDC-metal chelates can induce hemolysis by affecting the stability and the integrity of the RBC membrane, and possibly also of the cytoskeleton and the role played by reducing agents as inhibitors might be related to their ability to deplete oxygen which is also supported by the inhibitory effects of anaeobiosis.

Ada Compiler Validation Summary Report: Certificate Number: 940325S1. 11341 DDC-I, DACS Sun SPARC/SunOS to 80186 Bare Ada Cross Compiler System, Version 4.6.4 Sun SPARCstation IPX = Intel iSBC 186/100 (Bare Machine)

DTIC Science & Technology

1994-03-25

declarations requiring more digits than SYSTEM.MAXDIGITS: C24113L..Y (14 tests) C35705L..Y (14 tests) C35706L..Y (14 tests) C35707L..Y (14 tests) 2-1...before the DACS Run-Time System (RMs) libary normally searches for na-4ime routin;, in this way one can replace the standard DACS RTS routines with...SHORTINTEGER is range -128 .. 127; type INTEGER is range -32_768 .. 32_767; type LONGINTEGER is range -2147_483_648 .. 2_147_483_647; type FLOAT is digits 6

Dopa-decarboxylase gene polymorphisms affect the motor response to L-dopa in Parkinson's disease.

PubMed

Devos, David; Lejeune, Stéphanie; Cormier-Dequaire, Florence; Tahiri, Khadija; Charbonnier-Beaupel, Fanny; Rouaix, Nathalie; Duhamel, Alain; Sablonnière, Bernard; Bonnet, Anne-Marie; Bonnet, Cecilia; Zahr, Noel; Costentin, Jean; Vidailhet, Marie; Corvol, Jean-Christophe

2014-02-01

In Parkinson's disease (PD), the response to L-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from L-dopa is decarboxylation by aromatic L-amino acid decarboxylase (AAAD, encoded by the DDC gene). To determine the motor response to L-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC(T/C)) and rs3837091 AGAG del (DDC(AGAG/-))). Thirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to L-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUCΔUPDRS) in the 4 h following L-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of L-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study. When adjusted for the L-dopa dose, the AUCΔUPDRS was significantly lower in DDC(CC/CT) patients (n = 14) than in DDC(TT) patients (n = 19) and significantly lower in DDC(-/- or AGAG/-) patients (n = 8) than in DDC(AGAG/AGAG) patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for L-dopa and dopamine. The rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to L-dopa but do not significantly change peripheral pharmacokinetic parameters for L-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

The protective effects of ascorbic acid, cimetidine, and nifedipine on diethyldithiocarbamate-induced hepatic toxicity in albino rats.

PubMed

Gaafa, Khadiga Mohammed; Badawy, Mohammed M; Hamza, Alaaeldin A

2011-10-01

The aim of the present work was to clarify the involvement of free radicals, cytochrome P450 toxic metabolites, and deregulation of calcium homeostasis in the mechanism of diethyldithiocarbamate (DDC) hepatotoxicity. This was elucidated through the preadministration of ascorbic acid (a free radical scavenger), cimetidine (an inhibitor of cytochrome P450 enzymes), or nifedipine (a calcium-blocking agent) before DDC treatment to male albino rats. DDC was administered either as a single dose [800 mg/kg body weight (b.w.), subcutaneously, s.c.] or daily repeated doses for 30 days (400 mg/kg b.w., s.c.). Oxidative stress indicators [e.g., malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase enzyme (SOD)] showed that single or repeated DDC doses induce an increase in MDA level and a decrease in SOD activity in the liver, whereas it causes depletion in hepatic GSH after a single dose and an elevation in its value after repeated doses. Severe histopathological changes were also observed in the livers of rats treated with single or repeated DDC doses. Ascorbic acid, cimetidine, and nifedipine pretreatments were found to induce highly protective effects against the evinced DDC hepatotoxicity, manifesting that free radical, cytochrome P450, and calcium-dependent processes contribute to DDC liver toxicity. Finally, although multiple mechanisms may be involved in the hepatotoxic changes induced by DDC, calcium disarrangement and free radical formation play a more critical role than cytochrome P450 in metabolic events leading to toxic effects of DDC.

Bidirectional segmentation of prostate capsule from ultrasound volumes: an improved strategy

NASA Astrophysics Data System (ADS)

Wei, Liyang; Narayanan, Ramkrishnan; Kumar, Dinesh; Fenster, Aaron; Barqawi, Albaha; Werahera, Priya; Crawford, E. David; Suri, Jasjit S.

2008-03-01

Prostate volume is an indirect indicator for several prostate diseases. Volume estimation is a desired requirement during prostate biopsy, therapy and clinical follow up. Image segmentation is thus necessary. Previously, discrete dynamic contour (DDC) was implemented in orthogonal unidirectional on the slice-by-slice basis for prostate boundary estimation. This suffered from the glitch that it needed stopping criteria during the propagation of segmentation procedure from slice-to-slice. To overcome this glitch, axial DDC was implemented and this suffered from the fact that central axis never remains fixed and wobbles during propagation of segmentation from slice-to-slice. The effect of this was a multi-fold reconstructed surface. This paper presents a bidirectional DDC approach, thereby removing the two glitches. Our bidirectional DDC protocol was tested on a clinical dataset on 28 3-D ultrasound image volumes acquired using side fire Philips transrectal ultrasound. We demonstrate the orthogonal bidirectional DDC strategy achieved the most accurate volume estimation compared with previously published orthogonal unidirectional DDC and axial DDC methods. Compared to the ground truth, we show that the mean volume estimation errors were: 18.48%, 9.21% and 7.82% for unidirectional, axial and bidirectional DDC methods, respectively. The segmentation architecture is implemented in Visual C++ in Windows environment.

Duodenal duplication cyst (DDC) communicating with the pancreatobiliary duct--a rare cause of recurrent acute pancreatitis in adults.

PubMed

Bong, Jan Jin; Spalding, Duncan

2010-01-01

Duodenal duplication cysts (DDC) are rare congenital anomalies that usually present in infancy and childhood. Acute presentation in adults is even rarer. We report a case of a 34-year-old man who presented with recurrent acute pancreatitis and was found to have a cystic lesion in the second part of his duodenum. Further investigations revealed communication between the cystic lesion and the distal common bile duct. We describe the details of the operative approach taken to resect the DDC. We describe the differential diagnoses and the criteria for diagnosing DDC. Management options for DDC are discussed along with our recommendations.

[Research of expression of L-DOPA decarboxylase in laryngeal cancer].

PubMed

Lai, Shisheng; Wan, Zhili

2014-12-01

This study aimed to investigate the expression levels of L-DOPA decarboxylase (DDC) mRNA and protein in laryngeal cancer, and to determine the clinical significance of DDC in diagnosis and prognosis of laryngeal cancer. Total RNA was isolated from 106 tissue samples surgically removed from 53 laryngeal cancer patients. A quantitative real-time polymerase chain reaction (RT-PCR) methodology based on SYBR Green I fluorescent dye was developed for the quantification of mRNA levels. In addition, Western Blot analysis was performed to detect the expression level of DDC protein. DDC mRNA expression in both primary (P= 0. 000) and recurrent (P=0. 033) laryngeal cancer samples downregulated significantly compared with their nonmalignant counterparts. Moreover, expression of DDC mRNA was not associated with age and histologic grade, but the significantly decreased mRNA were correlated with early TMN stage (P=0. 021). Additionally, DDC protein was detected in both cancerous and noncancerous tissues. Expression levels of DDC may play a vital role in the progression of laryngeal cancer, which can be served as a promising biomarker for the future clinical management of laryngeal cancer patients.

Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

DTIC Science & Technology

2014-09-01

nucleoside reverse transcriptase inhibitor ddC as a small molecule inhibitor of HSATII reverse transcription. Initial data indicates there are anti...proliferative effects of ddC in cancer cell lines. We will evaluate ddC and anti-sense locked nucleic acids as methods for inhibiting this process and...of these hybrids, we tested the effect of the nucleoside analog RT inhibitor (NRTI) 2’,3’-dideoxycytidine ( ddC ) in COLO205 cells (Fig. 2e). Notably

Identification by Virtual Screening and In Vitro Testing of Human DOPA Decarboxylase Inhibitors

PubMed Central

Cellini, Barbara; Macchiarulo, Antonio; Giardina, Giorgio; Bossa, Francesco; Borri Voltattorni, Carla

2012-01-01

Dopa decarboxylase (DDC), a pyridoxal 5′-phosphate (PLP) enzyme responsible for the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease (PD). PD is a neurodegenerative disease mainly due to a progressive loss of dopamine-producing cells in the midbrain. Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide) is the most effective symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine (the in vivo hydrolysis product of benserazide) are both powerful irreversible DDC inhibitors, they are not selective because they irreversibly bind to free PLP and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of this study were (a) to use virtual screening to identify potential human DDC inhibitors and (b) to evaluate the reliability of our virtual-screening (VS) protocol by experimentally testing the “in vitro” activity of selected molecules. Starting from the crystal structure of the DDC-carbidopa complex, a new VS protocol, integrating pharmacophore searches and molecular docking, was developed. Analysis of 15 selected compounds, obtained by filtering the public ZINC database, yielded two molecules that bind to the active site of human DDC and behave as competitive inhibitors with Ki values ≥10 µM. By performing in silico similarity search on the latter compounds followed by a substructure search using the core of the most active compound we identified several competitive inhibitors of human DDC with Ki values in the low micromolar range, unable to bind free PLP, and predicted to not cross the blood-brain barrier. The most potent inhibitor with a Ki value of 500 nM represents a new lead compound, targeting human DDC, that may be the basis for lead optimization in the development of new DDC inhibitors. To our knowledge, a similar approach has not been reported yet in the field of DDC inhibitors discovery. PMID:22384042

Comparison of stretched-Exponential and monoexponential model diffusion-Weighted imaging in prostate cancer and normal tissues.

PubMed

Liu, Xiaohang; Zhou, Liangping; Peng, Weijun; Wang, He; Zhang, Yong

2015-10-01

To compare stretched-exponential and monoexponential model diffusion-weighted imaging (DWI) in prostate cancer and normal tissues. Twenty-seven patients with prostate cancer underwent DWI exam using b-values of 0, 500, 1000, and 2000 s/mm(2) . The distributed diffusion coefficients (DDC) and α values of prostate cancer and normal tissues were obtained with stretched-exponential model and apparent diffusion coefficient (ADC) values using monoexponential model. The ADC, DDC (both in 10(-3) mm(2)/s), and α values (range, 0-1) were compared among different prostate tissues. The ADC and DDC were also compared and correlated in each tissue, and the standardized differences between DDC and ADC were compared among different tissues. Data were obtained for 31 cancers, 36 normal peripheral zone (PZ) and 26 normal central gland (CG) tissues. The ADC (0.71 ± 0.12), DDC (0.60 ± 0.18), and α value (0.64 ± 0.05) of tumor were all significantly lower than those of the normal PZ (1.41 ± 0.22, 1.47 ± 0.20, and 0.85 ± 0.09) and CG (1.25 ± 0.14, 1.32 ± 0.13, and 0.82 ± 0.06) (all P < 0.05). ADC was significantly higher than DDC in cancer, but lower than DDC in the PZ and CG (all P < 0.05). The ADC and DDC were strongly correlated (R(2)  = 0.99, 0.98, 0.99, respectively, all P < 0.05) in all the tissue, and standardized difference between ADC and DDC of cancer was slight but significantly higher than that in normal tissue. The stretched-exponential model DWI provides more parameters for distinguishing prostate cancer and normal tissue and reveals slight differences between DDC and ADC values. © 2015 Wiley Periodicals, Inc.

The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism.

PubMed

Liu, Tianhui; Wang, Ping; Cong, Min; Xu, Youqing; Jia, Jidong; You, Hong

2013-06-05

DDC (diethyldithiocarbamate) could block collagen synthesis in HSC (hepatic stellate cells) through the inhibition of ROS (reactive oxygen species) derived from hepatocyte CYP2E1 (cytochrome P450 2E1). However, the effect of DDC on MMP-1 (matrix metalloproteinase-1), which is the main collagen degrading matrix metalloproteinase, has not been reported. In co-culture experiments, we found that DDC significantly enhanced MMP-1 expression in human HSC (LX-2) that were cultured with hepatocyte C3A cells either expressing or not expressing CYP2E1. The levels of both proenzyme and active MMP-1 enzyme were up-regulated in LX-2 cells, accompanied by elevated enzyme activity of MMP-1 and decreased collagen I, in both LX-2 cells and the culture medium. H2O2 treatment abrogated DDC-induced MMP-1 up-regulation and collagen I decrease, while catalase treatment slightly up-regulated MMP-1 expression. These data suggested that the decrease in ROS by DDC was partially responsible for the MMP-1 up-regulation. ERK1/2 (extracellular signal-regulated kinase 1/2), Akt (protein kinase B) and p38 were significantly activated by DDC. The ERK1/2 inhibitor (U0126) and Akt inhibitor (T3830) abrogated the DDC-induced MMP-1 up-regulation. In addition, a p38 inhibitor (SB203580) improved MMP-1 up-regulation through the stimulation of ERK1/2. Our data indicate that DDC significantly up-regulates the expression of MMP-1 in LX-2 cells which results in greater MMP-1 enzyme activity and decreased collagen I. The enhancement of MMP-1 expression by DDC was associated with H2O2 inhibition and coordinated regulation by the ERK1/2 and Akt pathways. These data provide some new insights into treatment strategies for hepatic fibrosis.

The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism

PubMed Central

Liu, Tianhui; Wang, Ping; Cong, Min; Xu, Youqing; Jia, Jidong; You, Hong

2013-01-01

DDC (diethyldithiocarbamate) could block collagen synthesis in HSC (hepatic stellate cells) through the inhibition of ROS (reactive oxygen species) derived from hepatocyte CYP2E1 (cytochrome P450 2E1). However, the effect of DDC on MMP-1 (matrix metalloproteinase-1), which is the main collagen degrading matrix metalloproteinase, has not been reported. In co-culture experiments, we found that DDC significantly enhanced MMP-1 expression in human HSC (LX-2) that were cultured with hepatocyte C3A cells either expressing or not expressing CYP2E1. The levels of both proenzyme and active MMP-1 enzyme were up-regulated in LX-2 cells, accompanied by elevated enzyme activity of MMP-1 and decreased collagen I, in both LX-2 cells and the culture medium. H2O2 treatment abrogated DDC-induced MMP-1 up-regulation and collagen I decrease, while catalase treatment slightly up-regulated MMP-1 expression. These data suggested that the decrease in ROS by DDC was partially responsible for the MMP-1 up-regulation. ERK1/2 (extracellular signal-regulated kinase 1/2), Akt (protein kinase B) and p38 were significantly activated by DDC. The ERK1/2 inhibitor (U0126) and Akt inhibitor (T3830) abrogated the DDC-induced MMP-1 up-regulation. In addition, a p38 inhibitor (SB203580) improved MMP-1 up-regulation through the stimulation of ERK1/2. Our data indicate that DDC significantly up-regulates the expression of MMP-1 in LX-2 cells which results in greater MMP-1 enzyme activity and decreased collagen I. The enhancement of MMP-1 expression by DDC was associated with H2O2 inhibition and coordinated regulation by the ERK1/2 and Akt pathways. These data provide some new insights into treatment strategies for hepatic fibrosis. PMID:23577625

Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors.

PubMed

Daidone, Frederick; Montioli, Riccardo; Paiardini, Alessandro; Cellini, Barbara; Macchiarulo, Antonio; Giardina, Giorgio; Bossa, Francesco; Borri Voltattorni, Carla

2012-01-01

Dopa decarboxylase (DDC), a pyridoxal 5'-phosphate (PLP) enzyme responsible for the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease (PD). PD is a neurodegenerative disease mainly due to a progressive loss of dopamine-producing cells in the midbrain. Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide) is the most effective symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine (the in vivo hydrolysis product of benserazide) are both powerful irreversible DDC inhibitors, they are not selective because they irreversibly bind to free PLP and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of this study were (a) to use virtual screening to identify potential human DDC inhibitors and (b) to evaluate the reliability of our virtual-screening (VS) protocol by experimentally testing the "in vitro" activity of selected molecules. Starting from the crystal structure of the DDC-carbidopa complex, a new VS protocol, integrating pharmacophore searches and molecular docking, was developed. Analysis of 15 selected compounds, obtained by filtering the public ZINC database, yielded two molecules that bind to the active site of human DDC and behave as competitive inhibitors with K(i) values ≥10 µM. By performing in silico similarity search on the latter compounds followed by a substructure search using the core of the most active compound we identified several competitive inhibitors of human DDC with K(i) values in the low micromolar range, unable to bind free PLP, and predicted to not cross the blood-brain barrier. The most potent inhibitor with a K(i) value of 500 nM represents a new lead compound, targeting human DDC, that may be the basis for lead optimization in the development of new DDC inhibitors. To our knowledge, a similar approach has not been reported yet in the field of DDC inhibitors discovery.

SU-E-T-503: IMRT Optimization Using Monte Carlo Dose Engine: The Effect of Statistical Uncertainty.

PubMed

Tian, Z; Jia, X; Graves, Y; Uribe-Sanchez, A; Jiang, S

2012-06-01

With the development of ultra-fast GPU-based Monte Carlo (MC) dose engine, it becomes clinically realistic to compute the dose-deposition coefficients (DDC) for IMRT optimization using MC simulation. However, it is still time-consuming if we want to compute DDC with small statistical uncertainty. This work studies the effects of the statistical error in DDC matrix on IMRT optimization. The MC-computed DDC matrices are simulated here by adding statistical uncertainties at a desired level to the ones generated with a finite-size pencil beam algorithm. A statistical uncertainty model for MC dose calculation is employed. We adopt a penalty-based quadratic optimization model and gradient descent method to optimize fluence map and then recalculate the corresponding actual dose distribution using the noise-free DDC matrix. The impacts of DDC noise are assessed in terms of the deviation of the resulted dose distributions. We have also used a stochastic perturbation theory to theoretically estimate the statistical errors of dose distributions on a simplified optimization model. A head-and-neck case is used to investigate the perturbation to IMRT plan due to MC's statistical uncertainty. The relative errors of the final dose distributions of the optimized IMRT are found to be much smaller than those in the DDC matrix, which is consistent with our theoretical estimation. When history number is decreased from 108 to 106, the dose-volume-histograms are still very similar to the error-free DVHs while the error in DDC is about 3.8%. The results illustrate that the statistical errors in the DDC matrix have a relatively small effect on IMRT optimization in dose domain. This indicates we can use relatively small number of histories to obtain the DDC matrix with MC simulation within a reasonable amount of time, without considerably compromising the accuracy of the optimized treatment plan. This work is supported by Varian Medical Systems through a Master Research Agreement. © 2012 American Association of Physicists in Medicine.

L-DOPA decarboxylase mRNA levels provide high diagnostic accuracy and discrimination between clear cell and non-clear cell subtypes in renal cell carcinoma.

PubMed

Papadopoulos, Emmanuel I; Petraki, Constantina; Gregorakis, Alkiviadis; Chra, Eleni; Fragoulis, Emmanuel G; Scorilas, Andreas

2015-06-01

Renal cell carcinoma (RCC) is the most frequent type of kidney cancer. RCC patients frequently present with arterial hypertension due to various causes, including intrarenal dopamine deficiency. L-DOPA decarboxylase (DDC) is the gene encoding the enzyme that catalyzes the biosynthesis of dopamine in humans. Several studies have shown that the expression levels of DDC are significantly deregulated in cancer. Thus, we herein sought to analyze the mRNA levels of DDC and evaluate their clinical significance in RCC. DDC levels were analyzed in 58 surgically resected RCC tumors and 44 adjacent non-cancerous renal tissue specimens via real-time PCR. Relative levels of DDC were estimated by applying the 2(-ΔΔC)T method, while their diagnostic accuracy and correlation with the clinicopathological features of RCC tumors were assessed by comprehensive statistical analysis. DDC mRNA levels were found to be dramatically downregulated (p<0.001) in RCC tumors, exhibiting remarkable diagnostic accuracy as assessed by ROC curve analysis (AUC: 0.910; p<0.001) and logistic regression (OR: 0.678; p=0.001). Likewise, DDC was found to be differentially expressed between clear cell RCC and the group of non-clear cell subtypes (p=0.001) consisted of papillary and chromophobe RCC specimens. Furthermore, a statistically significant inverse correlation was also observed when the mRNA levels of DDC were analyzed in relation to tumor grade (p=0.049). Our data showed that DDC constitutes a highly promising molecular marker for RCC, exhibiting remarkable diagnostic accuracy and potential to discriminate between clear cell and non-clear cell histological subtypes of RCC. Copyright © 2015. Published by Elsevier Inc.

Interaction of Ddc1 and RPA with single-stranded/double-stranded DNA junctions in yeast whole cell extracts: Proteolytic degradation of the large subunit of replication protein A in ddc1Δ strains.

PubMed

Sukhanova, Maria V; D'Herin, Claudine; Boiteux, Serge; Lavrik, Olga I

2014-10-01

To characterize proteins that interact with single-stranded/double-stranded (ss/ds) DNA junctions in whole cell free extracts of Saccharomyces cerevisiae, we used [(32)P]-labeled photoreactive partial DNA duplexes containing a 3'-ss/ds-junction (3'-junction) or a 5'-ss/ds-junction (5'-junction). Identification of labeled proteins was achieved by MALDI-TOF mass spectrometry peptide mass fingerprinting and genetic analysis. In wild-type extract, one of the components of the Ddc1-Rad17-Mec3 complex, Ddc1, was found to be preferentially photocrosslinked at a 3'-junction. On the other hand, RPAp70, the large subunit of the replication protein A (RPA), was the predominant crosslinking product at a 5'-junction. Interestingly, ddc1Δ extracts did not display photocrosslinking of RPAp70 at a 5'-junction. The results show that RPAp70 crosslinked to DNA with a 5'-junction is subject to limited proteolysis in ddc1Δ extracts, whereas it is stable in WT, rad17Δ, mec3Δ and mec1Δ extracts. The degradation of the RPAp70-DNA adduct in ddc1Δ extract is strongly reduced in the presence of the proteasome inhibitor MG 132. We also addressed the question of the stability of free RPA, using anti-RPA antibodies. The results show that RPAp70 is also subject to proteolysis without photocrosslinking to DNA upon incubation in ddc1Δ extract. The data point to a novel property of Ddc1, modulating the turnover of DNA binding proteins such as RPAp70 by the proteasome. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of indinavir used alone or in double or triple combination with AZT and ddC on human immune functions.

PubMed

Mattioli, Benedetta; Giordani, Luciana; Quaranta, Maria Giovanna; Viora, Marina

2004-03-19

Indinavir (IDV) is a potent and selective human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) widely used in antiretroviral therapy, but its effects on the immune system are relatively unknown. In this study we have investigated the in vitro effect of IDV on normal human peripheral blood mononuclear cells (PBMC). We used the drug alone or in double and triple combination with AZT and ddC to assess whether IDV interferes with the previously observed immunomodulatory effects induced by AZT and ddC. We found that proliferative response, induction of immunoglobulins (Ig) production and cytokine production was not modulated by IDV. More importantly, IDV used in double or triple combination with AZT and ddC, does not further strenghten the inhibition of proliferative response induced by AZT and is able to abrogate the inhibitory effect induced by ddC on proliferative response. Similarly, IDV/AZT, IDV/ddC and IDV/AZT/ddC combinations does not strenghten the modulation of TNF-alpha, IFN-gamma and IL-4 induced by AZT, ddC and AZT/ddC. On the other hand, IDV neutralizes the up-regulating effects of AZT on IL-2 production while the up-regulating effects of ddC on IL-2 production is not affected. These data suggest that IDV used in combination with AZT and ddC did not add any further immunotoxicity.

DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9.

PubMed

Ohouo, Patrice Y; Bastos de Oliveira, Francisco M; Liu, Yi; Ma, Chu Jian; Smolka, Marcus B

2013-01-03

In response to genotoxic stress, a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint (DDC) signalling pathway positively contributes to genome maintenance. Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest, cells must tightly regulate the activity of the kinases involved in this pathway. Despite their importance, the mechanisms for monitoring and modulating DDC signalling are not fully understood. Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae. On replication stress, cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53, whereas activation of the upstream DDC kinase Mec1 remains normal. An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A, two positive regulators of Rad9-dependent Rad53 activation. A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107. We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions. Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors.

Trapping Mode Dipolar DC Collisional Activation in the RF-Only Ion Guide of a Linear Ion Trap/Time-of-Flight Instrument for Gaseous Bio-Ion Declustering

PubMed Central

Webb, Ian K.; Gao, Yang; Londry, Frank A.; McLuckey, Scott A.

2013-01-01

The application of dipolar DC (DDC) to the RF-only ion guide (Q0) of a hybrid quadrupole/time-of-flight (QqTOF) mass spectrometer for collision-induced declustering of large bio-ions is described. As a broadband technique, ion trap DDC collision activation (CA) is employed to decluster ions simultaneously over a relatively broad mass-to-charge range. Declustering DDC CA can yield significantly narrower peaks relative to those observed in the absence of declustering methods, depending upon the extent of non-covalent adduction associated with the ions, and can also be used in conjunction with other methods, such as nozzle-skimmer collisional activation. The key experimental variables in the DDC experiment are the dipolar DC voltage (VDDC), VRF, and the time over which VDDC is applied. The VDDC/VRF ratio is key to the extent to which ion temperatures are elevated and also influences the upper mass-to-charge limit for ion storage. The VDDC/VRF ratio affects ion temperatures and upper m/z limit in opposing directions. That is, as the ratio increases, ion temperature increases whereas the upper m/z storage limit decreases. However, for a given VDDC/VRF ratio, the upper m/z storage limit can be increased by increasing VRF, at the expense of the lower m/z limit for ion storage. The key value of the approach is that it affords a relatively precise degree of control over ion temperatures as well as the time over which they are elevated to the higher temperature. The utility of the method is illustrated by the application of ion trap DDC CA in Q0 to oligonucleotide, protein, and multimeric protein complex analyte ions. PMID:24078247

From convection rolls to finger convection in double-diffusive turbulence

PubMed Central

Verzicco, Roberto; Lohse, Detlef

2016-01-01

Double-diffusive convection (DDC), which is the buoyancy-driven flow with fluid density depending on two scalar components, is ubiquitous in many natural and engineering environments. Of great interests are scalars' transfer rate and flow structures. Here we systematically investigate DDC flow between two horizontal plates, driven by an unstable salinity gradient and stabilized by a temperature gradient. Counterintuitively, when increasing the stabilizing temperature gradient, the salinity flux first increases, even though the velocity monotonically decreases, before it finally breaks down to the purely diffusive value. The enhanced salinity transport is traced back to a transition in the overall flow pattern, namely from large-scale convection rolls to well-organized vertically oriented salt fingers. We also show and explain that the unifying theory of thermal convection originally developed by Grossmann and Lohse for Rayleigh–Bénard convection can be directly applied to DDC flow for a wide range of control parameters (Lewis number and density ratio), including those which cover the common values relevant for ocean flows. PMID:26699474

A Cost Analysis of Forward Positioning Material in the Fifth Fleet Area of Responsibility

DTIC Science & Technology

2014-12-01

CTF combined task force CY calendar year DDC defense distribution center DDNB Defense Depot Navy Detachment, Bahrain DHL DHL Airways DLA...items from Bahrain to the requesting unit.  Defense Distribution Center ( DDC )– DDC is concerned with getting the requested national item

A Comparative Evaluation of the Thesaurus of Engineering and Scientific Terms and the DDC Retrieval and Indexing Terminology.

DTIC Science & Technology

1977-11-01

UNLIMITED!IBIR-4J1 * : . C)" A COMPARATIVE EVALUATION OF THE THESAURUS OF, SAENGINEERING AND SCIENTIFIC TERMS AND THE DDC RETRIEVAL AND INDEXING...f cce7,i on For TER1 AND THE DDC RETRIEVAL AND A--" o " INDEXING TERMINOLOGY NTIS - * ByD , 2 _jDitr" : i :/ _ _ . _Av: "jl r " 1 t v Codes...34 . (ii. ABSTRACT A comparative evaluation nas been undertaken or the DDC Retrieval and Indexing Terminology (DRIT) and the Thesaurus of Engineering and

Dehydrodiconiferyl alcohol suppresses monocyte adhesion to endothelial cells by attenuation of JNK signaling pathway.

PubMed

Tsuneyoshi, Tadamitsu; Kanamori, Yuta; Matsutomo, Toshiaki; Morihara, Naoaki

2015-09-25

Several clinical studies have shown that the intake of aged garlic extract improves endothelial dysfunction. Lignan compounds, (+)-(2S,3R)-dehydrodiconiferyl alcohol (DDC) and (-)-(2R,3S)-dihydrodehydrodiconiferyl alcohol (DDDC), have been isolated as antioxidants in aged garlic extract. There is evidence showing the importance of oxidative stress in endothelial dysfunction. In the present study, we examined whether DDC and DDDC enhance endothelial cell function in vitro. Cell adhesion assay was performed using THP-1 monocyte and human umbilical vein endothelial cells (HUVECs) which were activated by lipopolysaccharide (LPS) or advanced glycation end products (AGEs)-BSA. Cellular ELISA method was used for the evaluation of vascular cell adhesion molecule 1 (VCAM-1) expression on HUVECs. DDC and DDDC suppressed the adhesion of THP-1 to HUVECs which was activated by LPS or AGEs-BSA. DDC and DDDC also inhibited VCAM-1 expression induced by LPS or AGEs-BSA, but DDDC was less effective than DDC. In addition, the inhibitory effect of DDC on VCAM-1 expression involved suppressing JNK/c-Jun pathway rather than NF-κB pathway. DDC has an inhibitory effect on VCAM-1 expression via JNK pathway in endothelial cells and therefore may serve as a novel pharmacological agent to improve endothelial dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Biochemical identification of residues that discriminate between 3,4-dihydroxyphenylalanine decarboxylase and 3,4-dihydroxyphenylacetaldehyde synthase-mediated reactions.

PubMed

Liang, Jing; Han, Qian; Ding, Haizhen; Li, Jianyong

2017-12-01

In available insect genomes, there are several L-3,4-dihydroxyphenylalanine (L-dopa) decarboxylase (DDC)-like or aromatic amino acid decarboxylase (AAAD) sequences. This contrasts to those of mammals whose genomes contain only one DDC. Our previous experiments established that two DDC-like proteins from Drosophila actually mediate a complicated decarboxylation-oxidative deamination process of dopa in the presence of oxygen, leading to the formation of 3,4-dihydroxyphenylacetaldehyde (DHPA), CO 2 , NH 3, and H 2 O 2 . This contrasts to the typical DDC-catalyzed reaction, which produces CO 2 and dopamine. These DDC-like proteins were arbitrarily named DHPA synthases based on their critical role in insect soft cuticle formation. Establishment of reactions catalyzed by these AAAD-like proteins solved a puzzle that perplexed researchers for years, but to tell a true DHPA synthase from a DDC in the insect AAAD family remains problematic due to high sequence similarity. In this study, we performed extensive structural and biochemical comparisons between DHPA synthase and DDC. These comparisons identified several target residues potentially dictating DDC-catalyzed and DHPA synthase-catalyzed reactions, respectively. Comparison of DHPA synthase homology models with crystal structures of typical DDC proteins, particularly residues in the active sites, provided further insights for the roles these identified target residues play. Subsequent site-directed mutagenesis of the tentative target residues and activity evaluations of their corresponding mutants determined that active site His192 and Asn192 are essential signature residues for DDC- and DHPA synthase-catalyzed reactions, respectively. Oxygen is required in DHPA synthase-mediated process and this oxidizing agent is reduced to H 2 O 2 in the process. Biochemical assessment established that H 2 O 2 , formed in DHPA synthase-mediated process, can be reused as oxidizing agent and this active oxygen species is reduced to H 2 O; thereby avoiding oxidative stress by H 2 O 2 . Results of our structural and functional analyses provide a reasonable explanation of mechanisms involved in DHPA synthase-mediated reactions. Based on the key active site residue Asn192, identified in Drosophila DHPA synthase, we were able to distinguish all available insect DHPA synthases from DDC sequences primarily. Copyright © 2017. Published by Elsevier Ltd.

Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC.

PubMed

Toma, Claudio; Hervás, Amaia; Balmaña, Noemí; Salgado, Marta; Maristany, Marta; Vilella, Elisabet; Aguilera, Francisco; Orejuela, Carmen; Cuscó, Ivon; Gallastegui, Fátima; Pérez-Jurado, Luis Alberto; Caballero-Andaluz, Rafaela; Diego-Otero, Yolanda de; Guzmán-Alvarez, Guadalupe; Ramos-Quiroga, Josep Antoni; Ribasés, Marta; Bayés, Mònica; Cormand, Bru

2013-09-01

Neurotransmitter systems and neurotrophic factors can be considered strong candidates for autism spectrum disorder (ASD). The serotoninergic and dopaminergic systems are involved in neurotransmission, brain maturation and cortical organization, while neurotrophic factors (NTFs) participate in neurodevelopment, neuronal survival and synapses formation. We aimed to test the contribution of these candidate pathways to autism through a case-control association study of genes selected both for their role in central nervous system functions and for pathophysiological evidences. The study sample consisted of 326 unrelated autistic patients and 350 gender-matched controls from Spain. We genotyped 369 tagSNPs to perform a case-control association study of 37 candidate genes. A significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047). Haplotype-based analysis pinpointed a four-marker combination in this gene associated with the disorder (rs2329340C-rs2044859T-rs6592961A-rs11761683T, P = 4.988e-05). No significant results were obtained for the remaining genes after applying multiple testing corrections. However, the rs167771 marker in DRD3, associated with ASD in a previous study, displayed a nominal association in our analysis (P = 0.023). Our data suggest that common allelic variants in the DDC gene may be involved in autism susceptibility.

Implementation of dipolar direct current (DDC) collision-induced dissociation in storage and transmission modes on a quadrupole/time-of-flight tandem mass spectrometer.

PubMed

Webb, Ian K; Londry, Frank A; McLuckey, Scott A

2011-09-15

Means for effecting dipolar direct current collision-induced dissociation (DDC CID) on a quadrupole/time-of-flight in a mass spectrometer have been implemented for the broadband dissociation of a wide range of analyte ions. The DDC fragmentation method in electrodynamic storage and transmission devices provides a means for inducing fragmentation of ions over a large mass-to-charge range simultaneously. It can be effected within an ion storage step in a quadrupole collision cell that is operated as a linear ion trap or as ions are continuously transmitted through the collision cell. A DDC potential is applied across one pair of rods in the quadrupole collision cell of a QqTOF hybrid mass spectrometer to effect fragmentation. In this study, ions derived from a small drug molecule, a model peptide, a small protein, and an oligonucleotide were subjected to the DDC CID method in either an ion trapping or an ion transmission mode (or both). Several key experimental parameters that affect DDC CID results, such as time, voltage, low mass cutoff, and bath gas pressure, are illustrated with protonated leucine enkephalin. The DDC CID dissociation method gives a readily tunable, broadband tool for probing the primary structures of a wide range of analyte ions. The method provides an alternative to the narrow resonance conditions of conventional ion trap CID and it can access more extensive sequential fragmentation, depending upon conditions. The DDC CID approach constitutes a collision analog to infrared multiphoton dissociation (IRMPD). Copyright © 2011 John Wiley & Sons, Ltd.

Quantification and study of the L-DOPA decarboxylase expression in gastric adenocarcinoma cells treated with chemotherapeutic substances.

PubMed

Korbakis, Dimitrios; Fragoulis, Emmanuel G; Scorilas, Andreas

2013-03-01

3,4-Dihydroxy-L-phenylalanine decarboxylase (DDC) is an enzyme implicated in the biosynthetic pathways of the neurotransmitters dopamine and probably serotonin. DDC gene expression has been studied in numerous malignancies and the corresponding data have shown remarkable alterations in the mRNA and/or protein levels encoded by the gene. The aim of this study was to examine any modulations in the DDC mRNA levels in gastric cancer cells after their treatment with the chemotherapeutic agents 5-fluorouracil, leucovorin, irinotecan, etoposide, cisplatin, and taxol. The sensitivity of the AGS gastric adenocarcinoma cells to the antineoplastic drugs was evaluated using the MTT assay. Total RNA was extracted and reverse transcribed into cDNA. A highly sensitive quantitative real-time PCR methodology was developed for the quantification of DDC mRNA. GAPDH was used as a housekeeping gene. Relative quantification analysis was carried out using the comparative C T method ((Equation is included in full-text article.)). The treatment of AGS cells with several concentrations of various broadly used anticancer drugs resulted in significant modulations of the DDC mRNA levels compared with those in the untreated cells in a time-specific and drug-specific manner. Generally, DDC expression levels appeared to decrease after three time periods of exposure to the selected chemotherapeutic agents, suggesting a characteristic DDC mRNA expression profile that is possibly related to the mechanism of each drug. Our experimental data show that the DDC gene might serve as a new potential molecular biomarker predicting treatment response in gastric cancer cells.

Annual Historical Summary, Defense Documentation Center, 1 July 1968 to 30 June 1969.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

This summary describes the more significant activities and achievements of the Defense Documentation Center (DDC) including: DDC and the scientific and technical community. The DDC role in the Department of Defense Scientific and Technical Information Program continued to shift from the traditional concept of an archival repository and a…

Study on ductility dip cracking susceptibility in Filler Metal 82 during welding

NASA Astrophysics Data System (ADS)

Chen, Jing-Qing; Lu, Hao; Cui, Wei

2011-06-01

In this paper, Ductility Dip Cracking (DDC) susceptibility in Inconel600 companion Filler Metal 82 (FM82) under different stress states is investigated. Inconel600 is a Ni-Cr-Fe alloy with excellent resistance to general corrosion, localized corrosion, and stress corrosion, which has been widely used in nuclear power plants. However, the companion FM82 has been shown to be susceptible to DDC in welding process. To resolve the problem, this work is mainly focused on evaluating DDC susceptibility in FM82 in welding process. First of all, Strain to Fracture (STF) test is used to achieve the DDC criterion under simple stress state, and the formation mechanism of DDC was explained. Real welding is a process with complex stress state. Later, to get the DDC susceptibility under complex stress state, models about multi-pass welding were built up by means of finite element method. According to numerical simulation results, relationship of deformation and temperature history is achieved. Moreover, susceptible locations and moments could be determined associated with STF results. The simulation results fairly agree with welding experiment from another research.

Genetic background effects of keratin 8 and 18 in a DDC-induced hepatotoxicity and Mallory-Denk body formation mouse model.

PubMed

Haybaeck, Johannes; Stumptner, Cornelia; Thueringer, Andrea; Kolbe, Thomas; Magin, Thomas M; Hesse, Michael; Fickert, Peter; Tsybrovskyy, Oleksiy; Müller, Heimo; Trauner, Michael; Zatloukal, Kurt; Denk, Helmut

2012-06-01

Keratin 8 (K8) and keratin 18 (K18) form the major hepatocyte cytoskeleton. We investigated the impact of genetic loss of either K8 or K18 on liver homeostasis under toxic stress with the hypothesis that K8 and K18 exert different functions. krt8⁻/⁻ and krt18⁻/⁻ mice crossed into the same 129-ola genetic background were treated by acute and chronic administration of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC). In acutely DDC-intoxicated mice, macrovesicular steatosis was more pronounced in krt8⁻/⁻ and krt18⁻/⁻ compared with wild-type (wt) animals. Mallory-Denk bodies (MDBs) appeared in krt18⁻/⁻ mice already at an early stage of intoxication in contrast to krt8⁻/⁻ mice that did not display MDB formation when fed with DDC. Keratin-deficient mice displayed significantly lower numbers of apoptotic hepatocytes than wt animals. krt8⁻/⁻, krt18⁻/⁻ and control mice displayed comparable cell proliferation rates. Chronically DDC-intoxicated krt18⁻/⁻ and wt mice showed a similarly increased degree of steatohepatitis with hepatocyte ballooning and MDB formation. In krt8⁻/⁻ mice, steatosis was less, ballooning, and MDBs were absent. krt18⁻/⁻ mice developed MDBs whereas krt8⁻/⁻ mice on the same genetic background did not, highlighting the significance of different structural properties of keratins. They are independent of the genetic background as an intrinsic factor. By contrast, toxicity effects may depend on the genetic background. krt8⁻/⁻ and krt18⁻/⁻ mice on the same genetic background show similar sensitivity to DDC intoxication and almost resemble wt animals regarding survival, degree of porphyria, liver-to-body weight ratio, serum bilirubin and liver enzyme levels. This stands in contrast to previous work where krt8⁻/⁻ and krt18⁻/⁻ mice on different genetic backgrounds were investigated.

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro.

PubMed

Lu, Lin; Dong, Haixia; Liu, Guixiang; Yuan, Bin; Li, Yizhao; Liu, Huaxiang

2014-11-01

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro

PubMed Central

Lu, Lin; Dong, Haixia; Liu, Guixiang; Yuan, Bin; Li, Yizhao; Liu, Huaxiang

2014-01-01

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies. PMID:25489421

Crystal Structure and Substrate Specificity of Drosophila 3,4-Dihydroxyphenylalanine Decarboxylase

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

Han, Q.; Ding, H; Robinson, H

2010-01-01

3,4-Dihydroxyphenylalanine decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase, catalyzes the decarboxylation of a number of aromatic L-amino acids. Physiologically, DDC is responsible for the production of dopamine and serotonin through the decarboxylation of 3,4-dihydroxyphenylalanine and 5-hydroxytryptophan, respectively. In insects, both dopamine and serotonin serve as classical neurotransmitters, neuromodulators, or neurohormones, and dopamine is also involved in insect cuticle formation, eggshell hardening, and immune responses. In this study, we expressed a typical DDC enzyme from Drosophila melanogaster, critically analyzed its substrate specificity and biochemical properties, determined its crystal structure at 1.75 Angstrom resolution, and evaluated the roles residues T82more » and H192 play in substrate binding and enzyme catalysis through site-directed mutagenesis of the enzyme. Our results establish that this DDC functions exclusively on the production of dopamine and serotonin, with no activity to tyrosine or tryptophan and catalyzes the formation of serotonin more efficiently than dopamine. The crystal structure of Drosophila DDC and the site-directed mutagenesis study of the enzyme demonstrate that T82 is involved in substrate binding and that H192 is used not only for substrate interaction, but for cofactor binding of drDDC as well. Through comparative analysis, the results also provide insight into the structure-function relationship of other insect DDC-like proteins.« less

Protective effect of Nrf2-ARE activator isolated from green perilla leaves on dopaminergic neuronal loss in a Parkinson's disease model.

PubMed

Masaki, Yuta; Izumi, Yasuhiko; Matsumura, Atsuko; Akaike, Akinori; Kume, Toshiaki

2017-03-05

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN), and oxidative stress is thought to contribute to the pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which is a cellular defense system against oxidative stress, is a promising target for therapeutics aimed at reducing neuronal death in PD. Previously, we have isolated 2',3'-dihydroxy-4',6'-dimethoxychalcone (DDC) from green perilla leaves as an activator of the Nrf2-ARE pathway. The present study showed the protective effect of DDC on PD models in vivo and in vitro. In a 6-hydroxydopamine (6-OHDA)-induced hemiparkinson's disease mouse model, intracerebral administration of DDC suppressed the dopaminergic neuronal loss and behavioral dysfunction. DDC upregulated the expression of heme oxygenase-1 (HO-1), one of the ARE-driven antioxidant enzymes, in astrocytes and microglia of the SN. In primary mesencephalic cultures, treatment with DDC also increased the HO-1 expression in astrocytes and microglia. DDC showed a protective effect against 6-OHDA-induced dopaminergic neuronal death, and the effect was suppressed by an HO-1 inhibitor. These results suggest that DDC prevents dopaminergic neurons from oxidative stress by upregulation of glial expression of HO-1. Copyright © 2017 Elsevier B.V. All rights reserved.

Higher Dietary Cost Is Associated with Higher Diet Quality: A Cross-Sectional Study among Selected Malaysian Adults

PubMed Central

Pondor, Ibnteesam

2017-01-01

Food price is a determining factor of food choices; however its relationship with diet quality is unclear in Malaysia. This study aimed to examine socio-economic characteristics and daily dietary cost (DDC) in relation to diet quality in the state of Selangor, Malaysia. Dietary intake was assessed using a Food Frequency Questionnaire (FFQ) and diet quality was estimated using a Malaysian Healthy Eating Index (M-HEI). DDC in Malaysian Ringgit (RM) was calculated from dietary intake and national food prices. Linear regression models were fitted to determine associations between DDC and M-HEI scores and predictors of diet quality. The mean M-HEI score of respondents was 61.31 ± 10.88 and energy adjusted DDC was RM10.71/2000 kcal (USD 2.49). The highest quintile of adjusted DDC had higher M-HEI scores for all respondents (Q1: 57.14 ± 10.07 versus Q5: 63.26 ± 11.54, p = 0.001). There were also positive associations between DDC and M-HEI scores for fruits (p < 0.001) and vegetables (p = 0.017) for all respondents. Predictors of diet quality included carbohydrate (β = 0290; p < 0.001) and fat intakes (β = −0.242; p < 0.001) and energy adjusted DDC (β = 0.196; p < 0.001). Higher dietary cost is associated with healthy eating among Malaysian adults. PMID:28926947

Higher Dietary Cost Is Associated with Higher Diet Quality: A Cross-Sectional Study among Selected Malaysian Adults.

PubMed

Pondor, Ibnteesam; Gan, Wan Ying; Appannah, Geeta

2017-09-16

Food price is a determining factor of food choices; however its relationship with diet quality is unclear in Malaysia. This study aimed to examine socio-economic characteristics and daily dietary cost (DDC) in relation to diet quality in the state of Selangor, Malaysia. Dietary intake was assessed using a Food Frequency Questionnaire (FFQ) and diet quality was estimated using a Malaysian Healthy Eating Index (M-HEI). DDC in Malaysian Ringgit (RM) was calculated from dietary intake and national food prices. Linear regression models were fitted to determine associations between DDC and M-HEI scores and predictors of diet quality. The mean M-HEI score of respondents was 61.31 ± 10.88 and energy adjusted DDC was RM10.71/2000 kcal (USD 2.49). The highest quintile of adjusted DDC had higher M-HEI scores for all respondents (Q1: 57.14 ± 10.07 versus Q5: 63.26 ± 11.54, p = 0.001). There were also positive associations between DDC and M-HEI scores for fruits ( p < 0.001) and vegetables ( p = 0.017) for all respondents. Predictors of diet quality included carbohydrate (β = 0290; p < 0.001) and fat intakes (β = -0.242; p < 0.001) and energy adjusted DDC (β = 0.196; p < 0.001). Higher dietary cost is associated with healthy eating among Malaysian adults.

Adaptations of DDC in the Middle East. Occasional Papers Number 170.

ERIC Educational Resources Information Center

Momeni, Mahvash K.

This study analyzes the sociocultural factors that affect translations of the Dewey Decimal Classification system (DDC) from English into four other languages, i.e., Arabic, Farsi, Hindi, and Turkish. The study was performed in three stages: each entry in each translation was compared with the edition of DDC on which it was based; each class of…

CMIP6 Citation Services and the Data Services of the IPCC Data Distribution Centre for AR6

NASA Astrophysics Data System (ADS)

Stockhause, Martina; Lautenschlager, Michael

2017-04-01

As a result of the experiences from CMIP5 the two services contributed by DKRZ to the CMIP research infrastructure have been improved for CMIP6: the Citation Services and the Services of the IPCC Data Distribution Centre (DDC, http://ipcc-data.org). 1. Data Citation Services: Within CMIP5 it took a couple of years before the data was citable with their DataCite DOIs. The DataCite DOI registration by the WDC Climate at DKRZ (World Data Center Climate at the Climate Computing Center) requires data transfer and long-term archival at DKRZ according to DDC's quality standards. Based on a request from WGCM (Working Group on Climate Models) an additional early citation possibility for the evolving CMIP6 data was added to the citation service (http://cmip6cite.wdc-climate.de). 2. IPCC DDC Services: WDC Climate has been hosting the IPCC DDC's Reference Data Archive for the climate model output underlying the IPCC Assessment Reports (ARs) since the Second Assessment Report in 1995. One task of the DDC is the support of the IPCC Working Groups (WGs) and their authors. The WG support was not sufficient for AR5 resulting in WG I setting up and maintaining their own CMIP5 data repository hosting a data subset. The DDC will open DKRZ's CMIP data pool as an additional DDC service for the IPCC authors using a synergy with the interests of the national climate community. Within the PICO the Citation and the IPCC DDC services will be presented from a user's perspective. The connections to and integration into the infrastructure for CMIP6 (see https://www.earthsystemcog.org/projects/wip/) will be explained.

L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

PubMed Central

2012-01-01

Background Head and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. Methods 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt) method. Results DDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. Conclusion This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases. PMID:23083099

Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver

PubMed Central

Yamazaki, Yuichi; Moore, Rick; Negishi, Masahiko

2014-01-01

The liver is endowed with the ability to regenerate hepatocytes in response to injury. When this regeneration ability is impaired during liver injury, oval cells, which are considered to be postnatal hepatic progenitors, proliferate and differentiate into hepatocytes. Here we have demonstrated that 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) activates the nuclear receptor constitutive active/androstane receptor (CAR), resulting in proliferation of oval cells in mouse liver. Activation of CAR by DDC was shown by hepatic nuclear CAR accumulation and cytochrome P450 (CYP)2B10 mRNA induction after feeding a 0.1% DDC-containing diet to Car +/+ mice. After being fed the DDC diet, Car +/+, but not Car−/− mice, developed severe liver injury and an A6 antibody-stained ductular reaction in an area around the portal tract. Oval cell proliferation was confirmed by laser capture microdissection and real-time PCR; mRNAs for the two oval cell markers epithelial cell adhesion molecule and TROP2 were specifically induced in the periportal region of DDC diet-fed Car +/+, but not Car−/− mice. Although rates of both hepatocyte growth and death were initially enhanced only in DDC diet-fed Car +/+ mice, growth was attenuated when oval cells proliferated, whereas death continued unabated. DDC-induced liver injury, which differs from other CAR activators such as phenobarbital, occurred in the periportal region where cells developed hypertrophy, accumulated porphyrin crystals and inflammation developed, all in association with the proliferation of oval cells. Thus, CAR provides an excellent experimental model for further investigations into its roles in liver regeneration, as well as the development of diseases such as hepatocellular carcinoma. PMID:21826054

Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver.

PubMed

Yamazaki, Yuichi; Moore, Rick; Negishi, Masahiko

2011-11-01

The liver is endowed with the ability to regenerate hepatocytes in response to injury. When this regeneration ability is impaired during liver injury, oval cells, which are considered to be postnatal hepatic progenitors, proliferate and differentiate into hepatocytes. Here we have demonstrated that 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) activates the nuclear receptor constitutive active/androstane receptor (CAR), resulting in proliferation of oval cells in mouse liver. Activation of CAR by DDC was shown by hepatic nuclear CAR accumulation and cytochrome P450 (CYP)2B10 mRNA induction after feeding a 0.1% DDC-containing diet to Car(+/+) mice. After being fed the DDC diet, Car(+/+), but not Car(-/-) mice, developed severe liver injury and an A6 antibody-stained ductular reaction in an area around the portal tract. Oval cell proliferation was confirmed by laser capture microdissection and real-time PCR; mRNAs for the two oval cell markers epithelial cell adhesion molecule and TROP2 were specifically induced in the periportal region of DDC diet-fed Car(+/+), but not Car(-/-) mice. Although rates of both hepatocyte growth and death were initially enhanced only in DDC diet-fed Car(+/+) mice, growth was attenuated when oval cells proliferated, whereas death continued unabated. DDC-induced liver injury, which differs from other CAR activators such as phenobarbital, occurred in the periportal region where cells developed hypertrophy, accumulated porphyrin crystals and inflammation developed, all in association with the proliferation of oval cells. Thus, CAR provides an excellent experimental model for further investigations into its roles in liver regeneration, as well as the development of diseases such as hepatocellular carcinoma.

L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study.

PubMed

Geomela, Panagiota-Aikaterini; Kontos, Christos K; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

2012-10-20

Head and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients' prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt) method. DDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases.

Density Functional Study for Chemical Reaction between Cr and Fe with Sodium Diethyldithiocarbamate (NaDDC)

NASA Astrophysics Data System (ADS)

Setiyanto, Henry; Muhida, Rifki; Kishi, Tomoya; Rahman, Md. Mahmudur; Dipojono, Hermawan K.; Diño, Wilson A.; Matsumoto, Shigeno; Kasai, Hideaki

Analytical chemistry in the perspective of ab initio molecular orbital calculation is introduced by investigating the chemical reaction between transition metals Cr and Fe with sodium diethyldithiocarbamate (NaDDC), a complexing agent to detect and extract Cr in human blood sample. Using density functional theory—based calculations, we determine the stable structure of the Cr-DDC and Fe-DDC complexes and obtain its dissociation energies. We found dissociation energy values of -3.24 and -2.67 eV for Cr and Fe complexes, respectively; and hence the formation of the former complex is more favorable than the formation of the latter.

Metallurgical investigation into ductility dip cracking in nickel based alloys

NASA Astrophysics Data System (ADS)

Noecker, Fredrick F., II

A690 is a Ni-Cr-Fe alloy with excellent resistance to general corrosion, localized corrosion and stress corrosion cracking. However, the companion filler metal for A690, EN52, has been shown by several researchers to be susceptible to ductility dip cracking (DDC), which limits its widespread use in joining applications. The Gleeble hot ductility test was used to evaluate the DDC susceptibility of A600 and A690, along with their filler metals, EN82H and EN52, throughout the heating and cooling portions of a simulated weld reheat thermal cycle. Both macroscopic mechanical measures and microscopic measures of DDC were quantified and compared. Water quenching was conducted at select temperatures for subsequent microstructural characterization. Microstructural and microchemical characterization was carried out using scanning electron microscopy, transmission electron microscopy and analytical electron microscopy (AEM) techniques. The greatest resistance to DDC was observed in A600 and A690 during heating, where no DDC cracks formed even when the samples were fractured. Both A690 and EN52 were found to form an intermediate on-cooling dip in ductility and UTS, which corresponded to an increase in ductility dip crack length. The hot ductility and cracking resistance of EN82H remained high throughout the entire thermal cycle. DDC susceptibility in both EN52 and EN82H decreased when the thermal cycle was modified to promote coarsening/precipitation of intergranular carbides prior to straining. AEM analysis did not reveal any sulfur or phosphorous intergranular segregation in EN52 at 1600°F on-heating, on-cooling or after a 60 second hold. The ductility dip cracks were preferentially oriented at a 45° to the tensile axis and were of a wedge type appearance, both of which are characteristic of grain boundary sliding (GBS). Samples with microstructures that consisted of coarsened carbides and/or serrated grain boundaries, which are expected to decrease GBS, were found to be resistant to DDC. Based on the results of this work grain boundary sliding contributes to DDC, while sulfur and phosphorous embrittlement do not play a role in DDC of EN52 at the concentrations investigated. The dynamic precipitation of partially coherent intergranular M23C6 carbides at intermediate temperatures may exacerbate DDC in A690 and EN52, but requires further investigation.

Intronic variants in the dopa decarboxylase (DDC) gene are associated with smoking behavior in European-Americans and African-Americans.

PubMed

Yu, Yi; Panhuysen, Carolien; Kranzler, Henry R; Hesselbrock, Victor; Rounsaville, Bruce; Weiss, Roger; Brady, Kathleen; Farrer, Lindsay A; Gelernter, Joel

2006-07-15

We report here a study considering association of alleles and haplotypes at the DOPA decarboxylase (DDC) locus with the DSM-IV diagnosis of nicotine dependence (ND) or a quantitative measure for ND using the Fagerstrom Test for Nicotine Dependence (FTND). We genotyped 18 single nucleotide polymorphisms (SNPs) spanning a region of approximately 210 kb that includes DDC and the genes immediately flanking DDC in 1,590 individuals from 621 families of African-American (AA) or European-American (EA) ancestry. Evidence of association (family-based tests) was observed with several SNPs for both traits (0.0002

Alterations of mitochondrial DNA in CEM cells selected for resistance toward ddC toxicity.

PubMed

Bjerke, M; Franco, M; Johansson, M; Balzarini, J; Karlsson, A

2006-01-01

2 ',3 '-dideoxycytidine (ddC) is a nucleoside analog that has been shown to produce a delayed toxicity which may be due to the depletion of mitochondrial DNA (mtDNA). In order to gain further understanding of the events involved in mitochondrial toxicity, two different CEM cell lines were selected for resistance to the delayed ddC toxicity.

The Regulation of Non-Coding RNA Expression in the Liver of Mice Fed DDC

PubMed Central

Oliva, Joan; Bardag-Gorce, Fawzia; French, Barbara A; Li, Jun; French, Samuel W

2010-01-01

Mallory-Denk bodies (MDBs) are found in the liver of patients with alcoholic and chronic nonalcoholic liver disease, and hepatocellular carcinoma (HCC). Diethyl 1,4-dihydro-2,4,6,-trimethyl-3,5-pyridinedicarboxylate (DDC) is used as a model to induce the formation of MDBs in mouse liver. Previous studies in this laboratory showed that DDC induced epigenetic modifications in DNA and histones. The combination of these modifications changes the phenotype of the MDB forming hepatocytes, as indicated by the marker FAT10. These epigenetic modifications are partially prevented by adding to the diet S-adenosylmethionine (SAMe) or betaine, both methyl donors. The expression of three imprinted ncRNA genes was found to change in MDB forming hepatocytes, which is the subject of this report. NcRNA expression was quantitated by Real-Time PCR and RNA FISH in liver sections. Microarray analysis showed that the expression of three ncRNAs was regulated by DDC: up regulation of H19, antisense Igf2r (AIR), and down regulation of GTL2 (also called MEG3). S-adenosylmethionine (SAMe) feeding prevented these changes. Betaine, another methyl group donor, prevented only H19 and AIR up regulation induced by DDC, on microarrays. The results of the SAMe and betaine groups were confirmed by Real-Time PCR, except for AIR expression. After 1 month of drug withdrawal, the expression of the three ncRNAs tended toward control levels of expression. Liver tumors that developed also showed up regulation of H19 and AIR. The RNA FISH approach showed that the MDB forming cells’ phenotype changed the level of expression of AIR, H19 and GTL2, compared to the surrounding cells. Furthermore, over expression of H19 and AIR was demonstrated in tumors formed in mice withdrawn for 9 months. The disregulation of ncRNA in MDB forming liver cells has been observed for the first time in drug primed mice associated with liver preneoplastic foci and tumors. PMID:19362547

The regulation of non-coding RNA expression in the liver of mice fed DDC.

PubMed

Oliva, Joan; Bardag-Gorce, Fawzia; French, Barbara A; Li, Jun; French, Samuel W

2009-08-01

Mallory-Denk bodies (MDBs) are found in the liver of patients with alcoholic and chronic nonalcoholic liver disease, and hepatocellular carcinoma (HCC). Diethyl 1,4-dihydro-2,4,6,-trimethyl-3,5-pyridinedicarboxylate (DDC) is used as a model to induce the formation of MDBs in mouse liver. Previous studies in this laboratory showed that DDC induced epigenetic modifications in DNA and histones. The combination of these modifications changes the phenotype of the MDB forming hepatocytes, as indicated by the marker FAT10. These epigenetic modifications are partially prevented by adding to the diet S-adenosylmethionine (SAMe) or betaine, both methyl donors. The expression of three imprinted ncRNA genes was found to change in MDB forming hepatocytes, which is the subject of this report. NcRNA expression was quantitated by real-time PCR and RNA FISH in liver sections. Microarray analysis showed that the expression of three ncRNAs was regulated by DDC: up regulation of H19, antisense Igf2r (AIR), and down regulation of GTL2 (also called MEG3). S-adenosylmethionine (SAMe) feeding prevented these changes. Betaine, another methyl group donor, prevented only H19 and AIR up regulation induced by DDC, on microarrays. The results of the SAMe and betaine groups were confirmed by real-time PCR, except for AIR expression. After 1 month of drug withdrawal, the expression of the three ncRNAs tended toward control levels of expression. Liver tumors that developed also showed up regulation of H19 and AIR. The RNA FISH approach showed that the MDB forming cells' phenotype changed the level of expression of AIR, H19 and GTL2, compared to the surrounding cells. Furthermore, over expression of H19 and AIR was demonstrated in tumors formed in mice withdrawn for 9 months. The dysregulation of ncRNA in MDB forming liver cells has been observed for the first time in drug-primed mice associated with liver preneoplastic foci and tumors.

Cloning and characterization of the ddc homolog encoding L-2,4-diaminobutyrate decarboxylase in Enterobacter aerogenes.

PubMed

Yamamoto, S; Mutoh, N; Tsuzuki, D; Ikai, H; Nakao, H; Shinoda, S; Narimatsu, S; Miyoshi, S I

2000-05-01

L-2,4-diaminobutyrate decarboxylase (DABA DC) catalyzes the formation of 1,3-diaminopropane (DAP) from DABA. In the present study, the ddc gene encoding DABA DC from Enterobacter aerogenes ATCC 13048 was cloned and characterized. Determination of the nucleotide sequence revealed an open reading frame of 1470 bp encoding a 53659-Da protein of 490 amino acids, whose deduced NH2-terminal sequence was identical to that of purified DABA DC from E. aerogenes. The deduced amino acid sequence was highly similar to those of Acinetobacter baumannii and Haemophilus influenzae DABA DCs encoded by the ddc genes. The lysine-307 of the E. aerogenes DABA DC was identified as the pyridoxal 5'-phosphate binding residue by site-directed mutagenesis. Furthermore, PCR analysis revealed the distribution of E. aerogenes ddc homologs in some other species of Enterobacteriaceae. Such a relatively wide occurrence of the ddc homologs implies biological significance of DABA DC and its product DAP.

Information Hang-Ups; Problems Encountered by Users of the Technical Information Services Offered by DDC and CFSTI, with Recommendations for the Future.

ERIC Educational Resources Information Center

Committee of DDC Users in the Greater Washington, DC. Area, Washington, DC.

A change in policy of the Defense Documentation Center (DDC) with regard to supplying hard copy and/or microforms of reports caused problems to users of the DDC Technical Report Service. Discussions among users of the service, a questionnaire survey and committee reports summarized basic user concerns, provided selected statistics and a look at…

Lack of immunotoxicity of saquinavir (Ro 31-8959) used alone or in double or triple combination with AZT and ddC.

PubMed

Viora, M; Di Genova, G; Quaranta, M G; Boirivant, M; Camponeschi, B

1998-09-01

Saquinavir (Ro 31-8959; SQV) has been demonstrated to be a potent inhibitor of human immunodeficiency virus (HIV) proteinases and acts synergistically with dideoxynucleoside analogues. The aim of this study was to investigate the in vitro immunomodulatory effects of SQV on normal human peripheral blood mononuclear cells (PBMC) and on lamina propria mononuclear cells (LPMC). We used the drug either alone or in double and triple combination with AZT and ddC to assess whether SQV enhances the immunomodulatory effects induced by AZT and ddC that we previously observed. We demonstrated that SQV did not induce any modulation of the proliferative response either in PBMC or in LPMC. Similarly, NK cell-mediated cytotoxic activity and cytokine production were not modified by SQV. More importantly, SQV/AZT, SQV/ddC, and SQV/AZT/ddC combinations did not strengthen neither the inhibition of PBMC and LPMC proliferative response or the modulation of cytokine production induced by AZT, ddC, and AZT/ddC. On the other hand, the increased IL-2 production induced by AZT and ddC was not observed adding SQV to the dideoxynucleoside analogues. In conclusion, we demonstrated that SQV used in combination with AZT and ddC did not add any further immunotoxicity.

Novel fluorescence molecular imaging of chemotherapy-induced intestinal apoptosis

NASA Astrophysics Data System (ADS)

Levin, Galit; Shirvan, Anat; Grimberg, Hagit; Reshef, Ayelet; Yogev-Falach, Merav; Cohen, Avi; Ziv, Ilan

2009-09-01

Chemotherapy-induced enteropathy (CIE) is one of the most serious complications of anticancer therapy, and tools for its early detection and monitoring are highly needed. We report on a novel fluorescence method for detection of CIE, based on molecular imaging of the related apoptotic process. The method comprises systemic intravenous administration of the ApoSense fluorescent biomarker (N,N'-didansyl-L-cystine DDC) in vivo and subsequent fluorescence imaging of the intestinal mucosa. In the reported proof-of-concept studies, mice were treated with either taxol+cyclophosphamide or doxil. DDC was administered in vivo at various time points after drug administration, and tracer uptake by ileum tissue was subsequently evaluated by ex vivo fluorescent microscopy. Chemotherapy caused marked and selective uptake of DDC in ileal epithelial cells, in correlation with other hallmarks of apoptosis (i.e., DNA fragmentation and Annexin-V binding). Induction of DDC uptake occurred early after chemotherapy, and its temporal profile was parallel to that of the apoptotic process, as assessed histologically. DDC may therefore serve as a useful tool for detection of CIE. Future potential integration of this method with fluorescent endoscopic techniques, or development of radio-labeled derivatives of DDC for emission tomography, may advance early diagnosis and monitoring of this severe adverse effect of chemotherapy.

Identification of Histological Patterns in Clinically Affected and Unaffected Palm Regions in Dupuytren's Disease

PubMed Central

Alfonso-Rodríguez, Camilo-Andrés; Garzón, Ingrid; Garrido-Gómez, Juan; Oliveira, Ana-Celeste-Ximenes; Martín-Piedra, Miguel-Ángel; Scionti, Giuseppe; Carriel, Víctor; Hernández-Cortés, Pedro; Campos, Antonio; Alaminos, Miguel

2014-01-01

Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM) and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues—Dupuytren's diseased contracture cords (DDC), palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF), and normal forehand fascia (NFF). Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA), fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered. PMID:25379672

Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML.

PubMed

Liyanage, Sanduni U; Hurren, Rose; Voisin, Veronique; Bridon, Gaëlle; Wang, Xiaoming; Xu, ChangJiang; MacLean, Neil; Siriwardena, Thirushi P; Gronda, Marcela; Yehudai, Dana; Sriskanthadevan, Shrivani; Avizonis, Daina; Shamas-Din, Aisha; Minden, Mark D; Bader, Gary D; Laposa, Rebecca; Schimmer, Aaron D

2017-05-11

Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we used a nucleoside analog 2'3'-dideoxycytidine (ddC), which is phosphorylated to the activated antimetabolite, 2'3'-dideoxycytidine triphosphate by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase γ. ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitor cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML. © 2017 by The American Society of Hematology.

Identification of histological patterns in clinically affected and unaffected palm regions in dupuytren's disease.

PubMed

Alfonso-Rodríguez, Camilo-Andrés; Garzón, Ingrid; Garrido-Gómez, Juan; Oliveira, Ana-Celeste-Ximenes; Martín-Piedra, Miguel-Ángel; Scionti, Giuseppe; Carriel, Víctor; Hernández-Cortés, Pedro; Campos, Antonio; Alaminos, Miguel

2014-01-01

Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM) and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues-Dupuytren's diseased contracture cords (DDC), palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF), and normal forehand fascia (NFF). Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA), fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered.

Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML

PubMed Central

Liyanage, Sanduni U.; Hurren, Rose; Voisin, Veronique; Bridon, Gaëlle; Wang, Xiaoming; Xu, ChangJiang; MacLean, Neil; Siriwardena, Thirushi P.; Gronda, Marcela; Yehudai, Dana; Sriskanthadevan, Shrivani; Avizonis, Daina; Shamas-Din, Aisha; Minden, Mark D.; Bader, Gary D.; Laposa, Rebecca

2017-01-01

Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we used a nucleoside analog 2′3′-dideoxycytidine (ddC), which is phosphorylated to the activated antimetabolite, 2′3′-dideoxycytidine triphosphate by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase γ. ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitor cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML. PMID:28283480

Human L-DOPA decarboxylase mRNA is a target of miR-145: A prediction to validation workflow.

PubMed

Papadopoulos, Emmanuel I; Fragoulis, Emmanuel G; Scorilas, Andreas

2015-01-10

l-DOPA decarboxylase (DDC) is a multiply-regulated gene which encodes the enzyme that catalyzes the biosynthesis of dopamine in humans. MicroRNAs comprise a novel class of endogenously transcribed small RNAs that can post-transcriptionally regulate the expression of various genes. Given that the mechanism of microRNA target recognition remains elusive, several genes, including DDC, have not yet been identified as microRNA targets. Nevertheless, a number of specifically designed bioinformatic algorithms provide candidate miRNAs for almost every gene, but still their results exhibit moderate accuracy and should be experimentally validated. Motivated by the above, we herein sought to discover a microRNA that regulates DDC expression. By using the current algorithms according to bibliographic recommendations we found that miR-145 could be predicted with high specificity as a candidate regulatory microRNA for DDC expression. Thus, a validation experiment followed by firstly transfecting an appropriate cell culture system with a synthetic miR-145 sequence and sequentially assessing the mRNA and protein levels of DDC via real-time PCR and Western blotting, respectively. Our analysis revealed that miR-145 had no significant impact on protein levels of DDC but managed to dramatically downregulate its mRNA expression. Overall, the experimental and bioinformatic analysis conducted herein indicate that miR-145 has the ability to regulate DDC mRNA expression and potentially this occurs by recognizing its mRNA as a target. Copyright © 2014. Published by Elsevier B.V.

Oxidative stress and toxicity induced by the nucleoside reverse transcriptase inhibitor (NRTI)--2',3'-dideoxycytidine (ddC): relevance to HIV-dementia.

PubMed

Opii, Wycliffe O; Sultana, Rukhsana; Abdul, Hafiz Mohmmad; Ansari, Mubeen Ahmad; Nath, Avindra; Butterfield, D Allan

2007-03-01

Human immunodeficiency virus dementia (HIVD) is the most common form of dementia occurring among young adults. In HIVD, neuronal cell loss occurs in the absence of neuronal infection. With the advent of highly active anti-retroviral therapy (HAART), the incidence of HIVD has drastically reduced, though prevalence of milder forms of HIVD continues to rise. Though these agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. Here we examine the possible role of NRTIs, in particular 2',3'-dideoxycytidine (ddC), in the neuropathology of HIVD. Synaptosomes and isolated mitochondria treated and incubated for 6 h with CSF-achievable concentrations of ddC, i.e., 6-11 ng/ml, were found to show a significant increase in oxidative stress with 40 nM ddC as measured by protein carbonyls and 3-nitrotyrosine (3NT), effects that were not observed in the more tolerable NRTI, 3TC. Protection against protein oxidation induced by ddC was observed when brain mitochondria were isolated from gerbils 1 h after injection i.p. with the brain accessible antioxidant and glutathione mimetic, tricyclodecan-9-yl-xanthogenate (D609). In addition, there is a significant reduction in the levels of anti-apoptotic protein Bcl-2 and a significant increase in cytochrome c release and also a significant increase in the expression of pro-apoptotic protein caspase-3 after mitochondria were treated with 40 nM ddC. The results reported here show that ddC at 40 nM can induce oxidative stress, cause the release of cytochrome c, and in addition, reduce the levels of anti-apoptotic proteins, increase the levels of pro-apoptotic proteins, thereby increasing the possibility for induction of apoptosis. These findings are consistent with the notion of a possible role of the NRTIs, and in particular, ddC, in the mechanisms involved in HIVD.

Insulin-like growth factor-1 prevents dorsal root ganglion neuronal tyrosine kinase receptor expression alterations induced by dideoxycytidine in vitro.

PubMed

Liu, Huaxiang; Lu, Jing; He, Yong; Yuan, Bin; Li, Yizhao; Li, Xingfu

2014-03-01

Dideoxycytidine (zalcitabine, ddC) produces neurotoxic effects. It is particularly important to understand the toxic effects of ddC on different subpopulations of dorsal root ganglion (DRG) neurons which express distinct tyrosine kinase receptor (Trk) and to find therapeutic factors for prevention and therapy for ddC-induced peripheral sensory neuropathy. Insulin-like growth factor-1 (IGF-1) has been shown to have neurotrophic effects on DRG sensory neurons. However, little is known about the effects of ddC on distinct Trk (TrkA, TrkB, and TrkC) expression in DRG neurons and the neuroprotective effects of IGF-1 on ddC-induced neurotoxicity. Here, we have tested the extent to which the expression of TrkA, TrkB, and TrkC receptors in primary cultured DRG neurons is affected by ddC in the presence or absence of IGF-1. In this experiment, we found that exposure of 5, 25, and 50 μmol/L ddC caused a dose-dependent decrease of the mRNA, protein, and the proportion of TrkA-, TrkB-, and TrkC-expressing neurons. IGF-1 (20 nmol/L) could partially reverse the decrease of TrkA and TrkB, but not TrkC, expression with ddC exposure. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 μmol/L) blocked the effects of IGF-1. These results suggested that the subpopulations of DRG neurons which express distinct TrkA, TrkB, and TrkC receptors were affected by ddC exposure. IGF-1 might relieve the ddC-induced toxicity of TrkA- and TrkB-, but not TrkC-expressing DRG neurons. These data offer new clues for a better understanding of the association of ddC with distinct Trk receptor expression and provide new evidence of the potential therapeutic role of IGF-1 on ddC-induced neurotoxicity.

Zidovudine (AZT) versus AZT plus didanosine (ddI) versus AZT plus zalcitabine (ddC) in HIV infected adults.

PubMed

Darbyshire, J; Foulkes, M; Peto, R; Duncan, W; Babiker, A; Collins, R; Hughes, M; Peto, T; Walker, A

2000-01-01

Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC). To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival. Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events. Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009). The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.

A Subsystem Test Bed for Chinese Spectral Radioheliograph

NASA Astrophysics Data System (ADS)

Zhao, An; Yan, Yihua; Wang, Wei

2014-11-01

The Chinese Spectral Radioheliograph is a solar dedicated radio interferometric array that will produce high spatial resolution, high temporal resolution, and high spectral resolution images of the Sun simultaneously in decimetre and centimetre wave range. Digital processing of intermediate frequency signal is an important part in a radio telescope. This paper describes a flexible and high-speed digital down conversion system for the CSRH by applying complex mixing, parallel filtering, and extracting algorithms to process IF signal at the time of being designed and incorporates canonic-signed digit coding and bit-plane method to improve program efficiency. The DDC system is intended to be a subsystem test bed for simulation and testing for CSRH. Software algorithms for simulation and hardware language algorithms based on FPGA are written which use less hardware resources and at the same time achieve high performances such as processing high-speed data flow (1 GHz) with 10 MHz spectral resolution. An experiment with the test bed is illustrated by using geostationary satellite data observed on March 20, 2014. Due to the easy alterability of the algorithms on FPGA, the data can be recomputed with different digital signal processing algorithms for selecting optimum algorithm.

Intermediate temperature grain boundary embrittlement in nickel-base weld metals

NASA Astrophysics Data System (ADS)

Nissley, Nathan Eugene

The ductility-dip cracking (DDC) susceptibility of NiCrFe filler metals was evaluated using the strain-to-fracture (STF) GleebleRTM-based testing technique1. These high chromium Ni-base filler metals are frequently used in nuclear power plant applications for welding Ni-base Alloy 690 and included INCONELRTM Filler Metal 52 and 52M (FM-52 and FM-52M)2, and a number of FM-52M-type experimental alloys including two with additions of molybdenum and niobium. A wide range in DDC susceptibilities was observed in the tested alloys including significant variations in susceptibility with only small compositional changes. The interpretation of the STF results now includes both the threshold strain for cracking and the transition to "massive" cracking. While the threshold strain is still insightful and an indication of cracking susceptibility, materials which transition rapidly from the threshold strain to "massive" cracking are typically more susceptible to DDC. The spot pre-welds made on the STF samples, used to produce a repeatable microstructure were found to significantly affect the DDC resistance when the current downslope time was altered. Decreasing the downslope time resulted in a faster cooling rate, finer solidification substructure, fewer metastable intragranular precipitates, and a reduced DDC susceptibility. The downslope time has been found to be the most important STF testing variable evaluated to date. A significant decrease in DDC susceptibility was observed in the alloys with Mo and Nb additions. The threshold strain for cracking in the 2.5% Nb and 4% Mo NiCrFe alloy was approximately 10%, and demonstrated a DDC resistance of more than twice that observed in typical FM-82 alloys. This remarkable increase in DDC resistance was attributed to the skeletal precipitate morphology whose large surface area and dense distribution were highly effective at pinning grain boundaries and preventing crack initiation. The resulting wavy or tortuous grain boundaries act to mechanically lock the grains together and thereby reduce the cracking susceptibility. A general improvement in the DDC cracking resistance of FM-52M-type alloys was observed over FM-52, particularly at lower temperatures (750°C) in the DDC range. Compositional changes in the FM-52M experimental alloys resulted in a range of DDC susceptibilities, indicating the strong effect of minor changes in composition. Boron additions resulted in an increase in Cr-rich M23C6 intergranular carbides in the as-welded condition. Electron backscatter diffraction (EBSD) data showed increased intragranular deformation that was attributed to improved grain boundary strengthening as a result of the intergranular M23C6 formation prior to deformation. Elongated intergranular carbides were also found to be more effective in improving grain boundary strengthening when compared with more symmetrical carbides. (Abstract shortened by UMI.) 1GleebleRTM is a registered trademark of Dynamic Systems Inc. 2INCONELRTM is a registered trademark of Special Metals Company, a PCC company.

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

PubMed

De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development

PubMed Central

Wehbe, Mohamed; Anantha, Malathi; Backstrom, Ian; Leung, Ada; Chen, Kent; Malhotra, Armaan; Edwards, Katarina; Bally, Marcel B.

2016-01-01

The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)2), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)2 inside liposomes. DDC crosses the liposomal lipid bilayer, reacting with the entrapped copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. This method is successfully applied to other CDCs including the anti-parasitic drug clioquinol, the natural product quercetin and the novel targeted agent CX-5461. Our method provides a simple, transformative solution enabling, for the first time, the development of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients. PMID:27055237

Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development.

PubMed

Wehbe, Mohamed; Anantha, Malathi; Backstrom, Ian; Leung, Ada; Chen, Kent; Malhotra, Armaan; Edwards, Katarina; Bally, Marcel B

2016-01-01

The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)2), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)2 inside liposomes. DDC crosses the liposomal lipid bilayer, reacting with the entrapped copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. This method is successfully applied to other CDCs including the anti-parasitic drug clioquinol, the natural product quercetin and the novel targeted agent CX-5461. Our method provides a simple, transformative solution enabling, for the first time, the development of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients.

The Dimeric Architecture of Checkpoint Kinases Mec1ATR and Tel1ATM Reveal a Common Structural Organization.

PubMed

Sawicka, Marta; Wanrooij, Paulina H; Darbari, Vidya C; Tannous, Elias; Hailemariam, Sarem; Bose, Daniel; Makarova, Alena V; Burgers, Peter M; Zhang, Xiaodong

2016-06-24

The phosphatidylinositol 3-kinase-related protein kinases are key regulators controlling a wide range of cellular events. The yeast Tel1 and Mec1·Ddc2 complex (ATM and ATR-ATRIP in humans) play pivotal roles in DNA replication, DNA damage signaling, and repair. Here, we present the first structural insight for dimers of Mec1·Ddc2 and Tel1 using single-particle electron microscopy. Both kinases reveal a head to head dimer with one major dimeric interface through the N-terminal HEAT (named after Huntingtin, elongation factor 3, protein phosphatase 2A, and yeast kinase TOR1) repeat. Their dimeric interface is significantly distinct from the interface of mTOR complex 1 dimer, which oligomerizes through two spatially separate interfaces. We also observe different structural organizations of kinase domains of Mec1 and Tel1. The kinase domains in the Mec1·Ddc2 dimer are located in close proximity to each other. However, in the Tel1 dimer they are fully separated, providing potential access of substrates to this kinase, even in its dimeric form. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Pattern of cytokine receptors expressed by human dendritic cells migrated from dermal explants.

PubMed Central

Larregina, A T; Morelli, A E; Kolkowski, E; Sanjuan, N; Barboza, M E; Fainboim, L

1997-01-01

Different reasons account for the lack of information about the expression of cytokine receptors on human dendritic cells (DC): (a) DC are a trace population; (b) the proteolytic treatment used to isolate DC may alter enzyme-sensitive epitopes; and (c) low numbers of receptors per cell. In the present work the expression of cytokine receptors was analysed by flow cytometry on the population of dermal DC (DDC) that spontaneously migrate from short-term culture dermal explants. DDC obtained after dermal culture were CD1alow, CD1b+, CD1c+, human leucocyte antigen (HLA)-DR+, CD11chigh, CD11b+ and CD32+. The DC lineage was confirmed by ultrastructural analysis. DDC expressed interleukin (IL)-1R type 1 (monoclonal antibody (mAb) hIL-1R1-M1; and 6B5); IL-1R type 2 (mAb hIL-1R2-M22); IL-2R alpha chain (mAb anti-Tac; and hIL-2R-M1) and IL-2R gamma chain (mAb 3B5; and AG14C). DDC did not stain for IL-2R beta chain using four mAbs recognizing two different epitopes of IL-2R beta (mAb 2R-B; Mik-beta 1; and CF1; Mik-beta 3, respectively). DDC were also positive for the cytokine binding chains (alpha chains) of IL-3R (mAb 9F5); IL-4R (mAb hIL-4R-M57; and S456C9); and IL-7R (mAb hIL-7R-M20; and R3434). DDC showed low levels of IL-6R alpha chain (mAb B-F19; B-R6; and B-E23) and its signal transducer gp130 (mAb A2; and B1). DDC strongly expressed interferon-gamma receptor (IFN-gamma R) (mAb GIR-208) and were negative for IL-8R (mAb B-G20; and B-F25). All DDC were highly positive for granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain (mAb hGM-CSFR-M1; SC06; SC04, and 8G6) and to a lesser extent for the common beta chain of GM-CSFR, IL-3R and IL-5R (mAb 3D7). On the other hand, reactivity was not found for granulocyte colony-stimulating factor receptor (G-CSFR) (mAb hGCSFR-M1) nor macrophage colony-stimulating factor receptor (M-CSFR) (mAb 7-7A3-17) confirming the DC lineage of DDC. As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2). In summary, DDC express receptors for a broad panel of cytokines, even receptors for cytokines whose effects on DC are still unknown (i.e. IL-2R alpha gamma; IL-6R alpha/gp 130; IL-7R alpha gamma). Images Figure 1 PMID:9227332

TACS Central Control Facility.

DTIC Science & Technology

1981-02-12

PULSE RTC REAL TIME CLOCK -{> I . SIGNAL INVERSION UASC UNIVERSAL ASYNCHRONOUS SERIAL - ---- 4w SPECIAL INTERFACE CONTROLLER Fiq. 2-1. MAC hardware...34 Universal Asynchronous Serial Controller" (UASC) cards. The cards implement an RS-232 standard interface. All controllers are set to operate at a data...Bridwell and I. Richer, "A Preliminary Design of a TDMA System for FLEETSAT," Technical Note 1975-5, Lincoln Laboratory, M.I.T. (12 March 1975), DDC

Transition between Acute and Chronic Hepatotoxicity in Mice Is Associated with Impaired Energy Metabolism and Induction of Mitochondrial Heme Oxygenase-1

PubMed Central

Nikam, Aniket; Patankar, Jay V.; Lackner, Carolin; Schöck, Elisabeth; Kratky, Dagmar; Zatloukal, Kurt; Abuja, Peter M.

2013-01-01

The formation of protein inclusions is frequently associated with chronic metabolic diseases. In mice, short-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to hepatocellular damage indicated by elevated serum liver enzyme activities, whereas only minor morphological changes are observed. Conversely, chronic administration of DDC for several weeks results in severe morphological damage, characterized by hepatocellular ballooning, disruption of the intermediate filament cytoskeleton, and formation of Mallory-Denk bodies consisting predominantly of misfolded keratins, Sqstm1/p62, and heat shock proteins. To evaluate the mechanistic underpinnings for this dichotomy we dissected the time-course of DDC intoxication for up to 10 weeks. We determined body weight change, serum liver enzyme activities, morphologic alterations, induction of antioxidant response (heme oxygenase-1, HO-1), oxidative damage and ATP content in livers as well as respiration, oxidative damage and the presence and activity of HO-1 in endoplasmic reticulum and mitochondria (mtHO-1). Elevated serum liver enzyme activity and oxidative liver damage were already present at early intoxication stages without further subsequent increase. After 2 weeks of intoxication, mice had transiently lost 9% of their body weight, liver ATP-content was reduced to 58% of controls, succinate-driven respiration was uncoupled from ATP-production and antioxidant response was associated with the appearance of catalytically active mtHO-1. Oxidative damage was associated with both acute and chronic DDC toxicity whereas the onset of chronic intoxication was specifically associated with mitochondrial dysfunction which was maximal after 2 weeks of intoxication. At this transition stage, adaptive responses involving mtHO-1 were induced, indirectly leading to improved respiration and preventing further drop of ATP levels. Our observations clearly demonstrate principally different mechanisms for acute and chronic toxic damage. PMID:23762471

Disassortativity of random critical branching trees

NASA Astrophysics Data System (ADS)

Kim, J. S.; Kahng, B.; Kim, D.

2009-06-01

Random critical branching trees (CBTs) are generated by the multiplicative branching process, where the branching number is determined stochastically, independent of the degree of their ancestor. Here we show analytically that despite this stochastic independence, there exists the degree-degree correlation (DDC) in the CBT and it is disassortative. Moreover, the skeletons of fractal networks, the maximum spanning trees formed by the edge betweenness centrality, behave similarly to the CBT in the DDC. This analytic solution and observation support the argument that the fractal scaling in complex networks originates from the disassortativity in the DDC.

Quantitative differentiation of breast lesions at 3T diffusion-weighted imaging (DWI) using the ratio of distributed diffusion coefficient (DDC).

PubMed

Ertas, Gokhan; Onaygil, Can; Akin, Yasin; Kaya, Handan; Aribal, Erkin

2016-12-01

To investigate the accuracy of diffusion coefficients and diffusion coefficient ratios of breast lesions and of glandular breast tissue from mono- and stretched-exponential models for quantitative diagnosis in diffusion-weighted magnetic resonance imaging (MRI). We analyzed pathologically confirmed 170 lesions (85 benign and 85 malignant) imaged using a 3.0T MR scanner. Small regions of interest (ROIs) focusing on the highest signal intensity for lesions and also for glandular tissue of contralateral breast were obtained. Apparent diffusion coefficient (ADC) and distributed diffusion coefficient (DDC) were estimated by performing nonlinear fittings using mono- and stretched-exponential models, respectively. Coefficient ratios were calculated by dividing the lesion coefficient by the glandular tissue coefficient. A stretched exponential model provides significantly better fits then the monoexponential model (P < 0.001): 65% of the better fits for glandular tissue and 71% of the better fits for lesion. High correlation was found in diffusion coefficients (0.99-0.81 and coefficient ratios (0.94) between the models. The highest diagnostic accuracy was found by the DDC ratio (area under the curve [AUC] = 0.93) when compared with lesion DDC, ADC ratio, and lesion ADC (AUC = 0.91, 0.90, 0.90) but with no statistically significant difference (P > 0.05). At optimal thresholds, the DDC ratio achieves 93% sensitivity, 80% specificity, and 87% overall diagnostic accuracy, while ADC ratio leads to 89% sensitivity, 78% specificity, and 83% overall diagnostic accuracy. The stretched exponential model fits better with signal intensity measurements from both lesion and glandular tissue ROIs. Although the DDC ratio estimated by using the model shows a higher diagnostic accuracy than the ADC ratio, lesion DDC, and ADC, it is not statistically significant. J. Magn. Reson. Imaging 2016;44:1633-1641. © 2016 International Society for Magnetic Resonance in Medicine.

Decreased survival of prostate cancer cells in vitro by combined treatment of heat and an antioxidant inhibitor diethyldithiocarbamate (DDC).

PubMed

Moriyama-Gonda, Nobuko; Igawa, Mikio; Shiina, Hiroaki; Urakami, Shinji; Terashima, Masaharu

2003-11-01

The aim of this study was to examine a modulation of thermotolerance by treatment with combination of heat and the antioxidant inhibitor diethyldithiocarbamate (DDC) of the PC-3 prostate cancer cells. To determine thermotolerance, cells were heated once or twice. Two 1 h exposures at 43 degrees C, with a recovery period in between, revealed better survival/recovery of cells after the second exposure than after the first (fig. 1A + 1B). Additional experiments were performed, heating cells twice (fig. 1B + 1C). First, cells were heated at 43 degrees C for 1 h and, after various recovery times (intervals) at 37 degree C, subsequently reheated at 44 degrees C for 1 h. To ensure effective cell killing, efficiency of the combined treatments of 1 mM DDC and heating at 43 or 44 degrees C for 1 h was estimated by measuring cell survival, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and heat shock protein 70 (hsp 70) expression. To obtain a more effective method for subsequent heat exposure, cells were heated twice after a 24 h interval in the presence or absence of 1 mM DDC. ROS generation and SOD activity immediately increased correlating with duration of heating, but their levels gently decreased with time after discontinuation of heating. On the other hand, hsp 70 levels slowly increased, also correlating with duration of heating but continued to increase with time after discontinuation of heating for a certain period. DDC administration coupled with heating at 43 or 44 degrees C significantly decreased cell survival compared to heating alone (p < 0.05). Furthermore, significant decreases in numbers of viable cells were observed for cells after the first heat exposure when combined with DDC as compared to heat alone at 43 and 44 degrees C (p < 0.05). These findings suggest that heat combined with DDC could have potential benefits in the treatment of prostate cancer.

Delimiting regulatory sequences of the Drosophila melanogaster Ddc gene.

PubMed Central

Hirsh, J; Morgan, B A; Scholnick, S B

1986-01-01

We delimited sequences necessary for in vivo expression of the Drosophila melanogaster dopa decarboxylase gene Ddc. The expression of in vitro-altered genes was assayed following germ line integration via P-element vectors. Sequences between -209 and -24 were necessary for normally regulated expression, although genes lacking these sequences could be expressed at 10 to 50% of wild-type levels at specific developmental times. These genes showed components of normal developmental expression, which suggests that they retain some regulatory elements. All Ddc genes lacking the normal immediate 5'-flanking sequences were grossly deficient in larval central nervous system expression. Thus, this upstream region must contain at least one element necessary for this expression. A mutated Ddc gene without a normal TATA boxlike sequence used the normal RNA start points, indicating that this sequences is not required for start point specificity. Images PMID:3099170

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

PubMed

Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

2017-12-01

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

DOPA Decarboxylase Modulates Tau Toxicity.

PubMed

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies

PubMed Central

Syn, Wing-Kin; Lagaisse, Kimberly; van Hul, Noemi; Heindryckx, Femke; Sowa, Jan-Peter; Peeters, Liesbeth; Van Vlierberghe, Hans; Leclercq, Isabelle A.; Canbay, Ali

2016-01-01

Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes and macrophages, peribiliary extracellular matrix (ECM) deposition and ductular reaction (DR). This study aimed to elucidate the relevance of macrophages in the progression of chronic cholangiopathies through macrophage depletion in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group of mice received a single i.p. injection of Clodronate encapsulated liposomes (CLOLipo) at day 7 of a 14 day DDC treatment, while control animals were co-treated with PBSLipo instead. Mice were sacrificed after 7 or respectively 14 days of treatment for immunohistochemical assessment of macrophage recruitment (F4/80), ECM deposition (Sirius Red, Laminin) and DR (CK19). Macrophage depletion during a 14 day DDC treatment resulted in a significant inhibition of ECM deposition. Porto-lobular migration patterns of laminin-rich ECM and ductular structures were significantly attenuated and a progression of DR was effectively inhibited by macrophage depletion. CLOLipo co-treatment resulted in a confined DR to portal regions without amorphous cell clusters. This study suggests that therapeutic options selectively directed towards macrophages might represent a feasible treatment for chronic cholestatic liver diseases. PMID:27618307

Design and realization of the baseband processor in satellite navigation and positioning receiver

NASA Astrophysics Data System (ADS)

Zhang, Dawei; Hu, Xiulin; Li, Chen

2007-11-01

The content of this paper is focused on the Design and realization of the baseband processor in satellite navigation and positioning receiver. Baseband processor is the most important part of the satellite positioning receiver. The design covers baseband processor's main functions include multi-channel digital signal DDC, acquisition, code tracking, carrier tracking, demodulation, etc. The realization is based on an Altera's FPGA device, that makes the system can be improved and upgraded without modifying the hardware. It embodies the theory of software defined radio (SDR), and puts the theory of the spread spectrum into practice. This paper puts emphasis on the realization of baseband processor in FPGA. In the order of choosing chips, design entry, debugging and synthesis, the flow is presented detailedly. Additionally the paper detailed realization of Digital PLL in order to explain a method of reducing the consumption of FPGA. Finally, the paper presents the result of Synthesis. This design has been used in BD-1, BD-2 and GPS.

Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. The RV43 Study Group.

PubMed Central

Mayers, D L; Japour, A J; Arduino, J M; Hammer, S M; Reichman, R; Wagner, K F; Chung, R; Lane, J; Crumpacker, C S; McLeod, G X

1994-01-01

Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross-resistance to other similar dideoxynucleoside agents which contain a 3'-azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0-fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates. PMID:8192457

UVA radiation impairs phenotypic and functional maturation of human dermal dendritic cells.

PubMed

Furio, Laetitia; Berthier-Vergnes, Odile; Ducarre, Blandine; Schmitt, Daniel; Peguet-Navarro, Josette

2005-11-01

There is now strong evidence that the ultraviolet A (UVA) part of the solar spectrum contributes to the development of skin cancers. Its effect on the skin immune system, however, has not been fully investigated. Here, we analyzed the effects of UVA radiation on dermal dendritic cells (DDC), which, in addition, provided further characterization of these cells. Dermal sheets were obtained from normal human skin and irradiated, or not, with UVA at 2 or 12 J per cm2. After a 2 d incubation, the phenotype of emigrant cells was analyzed by double immunostaining and flow cytometry. Results showed that migratory DDC were best characterized by CD1c expression and that only few cells co-expressed the Langerhans cell marker Langerin. Whereas the DC extracted from the dermis displayed an immature phenotype, emigrant DDC showed increased expression of HLA-DR and acquired co-stimulation and maturation markers. We showed here that UVA significantly decreased the number of viable emigrant DDC, a process related to increased apoptosis. Furthermore, UVA irradiation impaired the phenotypic and functional maturation of migrating DDC into potent antigen-presenting cells, in a concentration-dependent manner. The results provide further evidence that UVA are immunosuppressive and suggest an additional mechanism by which solar radiation impairs immune response.

Energy determinants GAPDH and NDPK act as genetic modifiers for hepatocyte inclusion formation

PubMed Central

Weerasinghe, Sujith V.W.; Singla, Amika; Leonard, Jessica M.; Hanada, Shinichiro; Andrews, Philip C.; Lok, Anna S.; Omary, M. Bishr

2011-01-01

Genetic factors impact liver injury susceptibility and disease progression. Prominent histological features of some chronic human liver diseases are hepatocyte ballooning and Mallory-Denk bodies. In mice, these features are induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in a strain-dependent manner, with the C57BL and C3H strains showing high and low susceptibility, respectively. To identify modifiers of DDC-induced liver injury, we compared C57BL and C3H mice using proteomic, biochemical, and cell biological tools. DDC elevated reactive oxygen species (ROS) and oxidative stress enzymes preferentially in C57BL livers and isolated hepatocytes. C57BL livers and hepatocytes also manifested significant down-regulation, aggregation, and nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH knockdown depleted bioenergetic and antioxidant enzymes and elevated hepatocyte ROS, whereas GAPDH overexpression decreased hepatocyte ROS. On the other hand, C3H livers had higher expression and activity of the energy-generating nucleoside-diphosphate kinase (NDPK), and knockdown of hepatocyte NDPK augmented DDC-induced ROS formation. Consistent with these findings, cirrhotic, but not normal, human livers contained GAPDH aggregates and NDPK complexes. We propose that GAPDH and NDPK are genetic modifiers of murine DDC-induced liver injury and potentially human liver disease. PMID:22006949

BETAINE PREVENTS MALLORY-DENK BODY FORMATION IN DRUG-PRIMED MICE BY EPIGENETIC MECHANISMS

PubMed Central

Oliva, Joan; Bardag-Gorce, Fawzia; Li, Jun; French, Barbara A; Nguyen, Sheila K.; Lu, Shelly C.; French, Samuel W.

2012-01-01

Previous studies showed that S-Adenosylmethionine (SAMe) prevented MDB formation and the hypomethylation of histones induced by DDC feeding. These results suggest that formation of MDBs is an epigenetic phenomenon. To further test this theory, drug-primed mice were fed the methyl donor, betaine, together with DDC, which was refed for 7 days. Betaine significantly reduced MDB formation, decreased the liver/body weight ratio and decreased the number of FAT10 positive liver cells when they proliferate in response to DDC refeeding. Betaine also significantly prevented the decreased expression of BHMT, AHCY, MAT1a and GNMT and the increased expression of MTHFR, caused by DDC refeeding. S-Adenosylhomocysteine (SAH) levels were reduced by DDC refeeding and this was prevented by betaine. The results support the concept that betaine donates methyl groups, increasing methionine available in the cell. SAMe metabolism was reduced by the decrease in GNMT expression, which prevented the conversion of SAMe to SAH. As a consequence, betaine prevented MDB formation and FAT10 positive cell proliferation by blocking the epigenetic memory expressed by hepatocytes. The results further support the concept that MDB formation is the result of an epigenetic phenomenon, where a change in methionine metabolism causes global gene expression changes in hepatocytes. PMID:19073172

A new OTDR based on probe frequency multiplexing

NASA Astrophysics Data System (ADS)

Lu, Lidong; Liang, Yun; Li, Binglin; Guo, Jinghong; Zhang, Xuping

2013-12-01

Two signal multiplexing methods are proposed and experimentally demonstrated in optical time domain reflectometry (OTDR) for fault location of optical fiber transmission line to obtain high measurement efficiency. Probe signal multiplexing is individually obtained by phase modulation for generation of multi-frequency and time sequential frequency probe pulses. The backscattered Rayleigh light of the multiplexing probe signals is transferred to corresponding heterodyne intermediate frequency (IF) through heterodyning with the single frequency local oscillator (LO). Then the IFs are simultaneously acquired by use of a data acquisition card (DAQ) with sampling rate of 100Msps, and the obtained data are processed by digital band pass filtering (BPF), digital down conversion (DDC) and digital low pass filtering (BPF) procedure. For each probe frequency of the detected signals, the extraction of the time domain reflecting signal power is performed by parallel computing method. For a comprehensive performance comparison with conventional coherent OTDR on the probe frequency multiplexing methods, the potential for enhancement of dynamic range, spatial resolution and measurement time are analyzed and discussed. Experimental results show that by use of the probe frequency multiplexing method, the measurement efficiency of coherent OTDR can be enhanced by nearly 40 times.

The LUX experiment - trigger and data acquisition systems

NASA Astrophysics Data System (ADS)

Druszkiewicz, Eryk

2013-04-01

The Large Underground Xenon (LUX) detector is a two-phase xenon time projection chamber designed to detect interactions of dark matter particles with the xenon nuclei. Signals from the detector PMTs are processed by custom-built analog electronics which provide properly shaped signals for the trigger and data acquisition (DAQ) systems. During calibrations, both systems must be able to handle high rates and have large dynamic ranges; during dark matter searches, maximum sensitivity requires low thresholds. The trigger system uses eight-channel 64-MHz digitizers (DDC-8) connected to a Trigger Builder (TB). The FPGA cores on the digitizers perform real-time pulse identification (discriminating between S1 and S2-like signals) and event localization. The TB uses hit patterns, hit maps, and maximum response detection to make trigger decisions, which are reached within few microseconds after the occurrence of an event of interest. The DAQ system is comprised of commercial digitizers with customized firmware. Its real-time baseline suppression allows for a maximum event acquisition rate in excess of 1.5 kHz, which results in virtually no deadtime. The performance of the trigger and DAQ systems during the commissioning runs of LUX will be discussed.

Multiple model analysis with discriminatory data collection (MMA-DDC): A new method for improving measurement selection

NASA Astrophysics Data System (ADS)

Kikuchi, C.; Ferre, P. A.; Vrugt, J. A.

2011-12-01

Hydrologic models are developed, tested, and refined based on the ability of those models to explain available hydrologic data. The optimization of model performance based upon mismatch between model outputs and real world observations has been extensively studied. However, identification of plausible models is sensitive not only to the models themselves - including model structure and model parameters - but also to the location, timing, type, and number of observations used in model calibration. Therefore, careful selection of hydrologic observations has the potential to significantly improve the performance of hydrologic models. In this research, we seek to reduce prediction uncertainty through optimization of the data collection process. A new tool - multiple model analysis with discriminatory data collection (MMA-DDC) - was developed to address this challenge. In this approach, multiple hydrologic models are developed and treated as competing hypotheses. Potential new data are then evaluated on their ability to discriminate between competing hypotheses. MMA-DDC is well-suited for use in recursive mode, in which new observations are continuously used in the optimization of subsequent observations. This new approach was applied to a synthetic solute transport experiment, in which ranges of parameter values constitute the multiple hydrologic models, and model predictions are calculated using likelihood-weighted model averaging. MMA-DDC was used to determine the optimal location, timing, number, and type of new observations. From comparison with an exhaustive search of all possible observation sequences, we find that MMA-DDC consistently selects observations which lead to the highest reduction in model prediction uncertainty. We conclude that using MMA-DDC to evaluate potential observations may significantly improve the performance of hydrologic models while reducing the cost associated with collecting new data.

Syndromic intellectual disability: a new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant.

PubMed

Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F; Chaubey, Alka; Schwartz, Charles E; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco

2015-04-01

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. Copyright © 2015 Elsevier B.V. All rights reserved.

SU-E-T-395: Multi-GPU-Based VMAT Treatment Plan Optimization Using a Column-Generation Approach

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

Tian, Z; Shi, F; Jia, X

Purpose: GPU has been employed to speed up VMAT optimizations from hours to minutes. However, its limited memory capacity makes it difficult to handle cases with a huge dose-deposition-coefficient (DDC) matrix, e.g. those with a large target size, multiple arcs, small beam angle intervals and/or small beamlet size. We propose multi-GPU-based VMAT optimization to solve this memory issue to make GPU-based VMAT more practical for clinical use. Methods: Our column-generation-based method generates apertures sequentially by iteratively searching for an optimal feasible aperture (referred as pricing problem, PP) and optimizing aperture intensities (referred as master problem, MP). The PP requires accessmore » to the large DDC matrix, which is implemented on a multi-GPU system. Each GPU stores a DDC sub-matrix corresponding to one fraction of beam angles and is only responsible for calculation related to those angles. Broadcast and parallel reduction schemes are adopted for inter-GPU data transfer. MP is a relatively small-scale problem and is implemented on one GPU. One headand- neck cancer case was used for test. Three different strategies for VMAT optimization on single GPU were also implemented for comparison: (S1) truncating DDC matrix to ignore its small value entries for optimization; (S2) transferring DDC matrix part by part to GPU during optimizations whenever needed; (S3) moving DDC matrix related calculation onto CPU. Results: Our multi-GPU-based implementation reaches a good plan within 1 minute. Although S1 was 10 seconds faster than our method, the obtained plan quality is worse. Both S2 and S3 handle the full DDC matrix and hence yield the same plan as in our method. However, the computation time is longer, namely 4 minutes and 30 minutes, respectively. Conclusion: Our multi-GPU-based VMAT optimization can effectively solve the limited memory issue with good plan quality and high efficiency, making GPUbased ultra-fast VMAT planning practical for real clinical use.« less

A DDC Bibliography on On-Line Computer Systems, Volume I.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

This bibliography lists 162 unclassified - unlimited reports acquired by DDC, with their abstracts, grouped into five general subject areas: programing (computers), information retrieval, time sharing, graphics, and general applications. The topical arrangement is complemented by four indexes: corporate author/monitoring agency, personal author,…

Dewey Decimal Classification: A Quagmire.

ERIC Educational Resources Information Center

Gamaluddin, Ahmad Fouad

1980-01-01

A survey of 660 Pennsylvania school librarians indicates that, though there is limited professional interest in the Library of Congress Classification system, Dewey Decimal Classification (DDC) appears to be firmly entrenched. This article also discusses the relative merits of DDC, the need for a uniform system, librarianship preparation, and…

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

PubMed

Li, Zhaoyang; Easton, Rachael

2018-01-01

The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

PubMed Central

Easton, Rachael

2018-01-01

ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice.

PubMed

Kim, Kyung-Hyun; Sung, Hyun-Jung; Lee, Woo-Ram; An, Hyun-Jin; Kim, Jung-Yeon; Pak, Sok Cheon; Han, Sang-Mi; Park, Kwan-Kyu

2015-08-25

Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to mice is a well-established animal model to study cholangitis and biliary fibrosis. To investigate the effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing diet with or without melittin treatment for four weeks. Liver morphology, serum markers of liver injury, cholestasis markers for inflammation of liver, the degree of ductular reaction and the degree of liver fibrosis were compared between with or without melittin treatment DDC-fed mice. DDC feeding led to increased serum markers of hepatic injury, ductular reaction, induction of pro-inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment attenuated hepatic function markers, ductular reaction, the reactive phenotype of cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that melittin treatment can be protective against chronic cholestatic disease in DDC-fed mice. Further studies on the anti-inflammatory capacity of melittin are warranted for targeted therapy in cholangiopathy.

Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice

PubMed Central

Kim, Kyung-Hyun; Sung, Hyun-Jung; Lee, Woo-Ram; An, Hyun-Jin; Kim, Jung-Yeon; Pak, Sok Cheon; Han, Sang-Mi; Park, Kwan-Kyu

2015-01-01

Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to mice is a well-established animal model to study cholangitis and biliary fibrosis. To investigate the effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing diet with or without melittin treatment for four weeks. Liver morphology, serum markers of liver injury, cholestasis markers for inflammation of liver, the degree of ductular reaction and the degree of liver fibrosis were compared between with or without melittin treatment DDC-fed mice. DDC feeding led to increased serum markers of hepatic injury, ductular reaction, induction of pro-inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment attenuated hepatic function markers, ductular reaction, the reactive phenotype of cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that melittin treatment can be protective against chronic cholestatic disease in DDC-fed mice. Further studies on the anti-inflammatory capacity of melittin are warranted for targeted therapy in cholangiopathy. PMID:26308055

Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine.

PubMed Central

Fitzgibbon, J E; Howell, R M; Haberzettl, C A; Sperber, S J; Gocke, D J; Dubin, D T

1992-01-01

To investigate whether human immunodeficiency virus type 1 pol gene mutations are selected during prolonged 2',3'-dideoxycytidine (ddC) therapy, we used the polymerase chain reaction to amplify a portion of the reverse transcriptase segment of the pol gene from the peripheral blood mononuclear cell DNA of a patient with AIDS before and after an 80-week course of ddC therapy. The consensus sequence from the second sample contained a unique double mutation (ACT to GAT) in the codon for reverse transcriptase amino acid 69, causing substitution of aspartic acid (Asp) for the wild-type threonine (Thr). A mutation (ACA to ATA) also occurred in the codon for position 165, causing substitution of isoleucine (Ile) for Thr. The GAT (Asp) codon was introduced into the pol gene of a molecular clone of human immunodeficiency virus via site-directed mutagenesis. Following transfection, mutant and wild-type viruses were tested for susceptibility to ddC by a plaque reduction assay. The mutant virus was fivefold less susceptible to ddC than the wild type; cross-resistance to 3'-azido-3'-deoxythymidine or 2'3'-dideoxyinosine was not found. The Ile-165 mutation did not confer additional ddC resistance. The Asp-69 substitution may have contributed to the generation of resistant virus in this patient. Images PMID:1317143

Analysis of a Bibliographic Database Enhanced with a Library Classification.

ERIC Educational Resources Information Center

Drabenstott, Karen Markey; And Others

1990-01-01

Describes a project that examined the effects of incorporating subject terms from the Dewey Decimal Classification (DDC) into a bibliographic database. It is concluded that the incorporation of DDC and possibly other library classifications into online catalogs can enhance subject access and provide additional subject searching strategies. (11…

DDC Descriptor Frequencies.

ERIC Educational Resources Information Center

Klingbiel, Paul H.; Jacobs, Charles R.

This report summarizes the frequency of use of the 7144 descriptors used for indexing technical reports in the Defense Documentation Center (DDC) collection. The descriptors are arranged alphabetically in the first section and by frequency in the second section. The frequency data cover about 427,000 AD documents spanning the interval from March…

USP38, FREM3, SDC1, DDC, and LOC727982 Gene Polymorphisms and Differential Susceptibility to Severe Malaria in Tanzania.

PubMed

Manjurano, Alphaxard; Sepúlveda, Nuno; Nadjm, Behzad; Mtove, George; Wangai, Hannah; Maxwell, Caroline; Olomi, Raimos; Reyburn, Hugh; Drakeley, Christopher J; Riley, Eleanor M; Clark, Taane G

2015-10-01

Populations exposed to Plasmodium falciparum infection develop genetic mechanisms of protection against severe malarial disease. Despite decades of genetic epidemiological research, the sickle cell trait (HbAS) sickle cell polymorphism, ABO blood group, and other hemoglobinopathies remain the few major determinants in severe malaria to be replicated across different African populations and study designs. Within a case-control study in a region of high transmission in Tanzania (n = 983), we investigated the role of 40 new loci identified in recent genome-wide studies. In 32 loci passing quality control procedures, we found polymorphisms in USP38, FREM3, SDC1, DDC, and LOC727982 genes to be putatively associated with differential susceptibility to severe malaria. Established candidates explained 7.4% of variation in severe malaria risk (HbAS polymorphism, 6.3%; α-thalassemia, 0.3%; ABO group, 0.3%; and glucose-6-phosphate dehydrogenase deficiency, 0.5%) and the new polymorphisms, another 4.3%. The regions encompassing the loci identified are promising targets for the design of future treatment and control interventions. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Lack of Association Between Polymorphisms in Dopa Decarboxylase and Dopamine Receptor-1 Genes With Childhood Autism in Chinese Han Population.

PubMed

Yu, Hong; Liu, Jun; Yang, Aiping; Yang, Guohui; Yang, Wenjun; Lei, Heyue; Quan, Jianjun; Zhang, Zengyu

2016-04-01

Genetic factors play an important role in childhood autism. This study is to determine the association of single-nucleotide polymorphisms in dopa decarboxylase (DDC) and dopamine receptor-1 (DRD1) genes with childhood autism, in a Chinese Han population. A total of 211 autistic children and 250 age- and gender-matched healthy controls were recruited. The severity of disease was determined by Children Autism Rating Scale scores. TaqMan Probe by real-time polymerase chain reaction was used to determine genotypes and allele frequencies of single-nucleotide polymorphism rs6592961 in DDC and rs251937 in DRD1. Case-control and case-only studies were respectively performed, to determine the contribution of both single-nucleotide polymorphisms to the predisposition of disease and its severity. Our results showed that there was no significant association of the genotypes and allele frequencies of both single-nucleotide polymorphisms concerning childhood autism and its severity. More studies with larger samples are needed to corroborate their predicting roles. © The Author(s) 2015.

Dewey Decimal Classification for U. S. Conn: An Advantage?

ERIC Educational Resources Information Center

Marek, Kate

This paper examines the use of the Dewey Decimal Classification (DDC) system at the U. S. Conn Library at Wayne State College (WSC) in Nebraska. Several developments in the last 20 years which have eliminated the trend toward reclassification of academic library collections from DDC to the Library of Congress (LC) classification scheme are…

Machine-Aided Indexing of Technical Literature

ERIC Educational Resources Information Center

Klingbiel, Paul H.

1973-01-01

To index at the Defense Documentation Center (DDC), an automated system must choose single words or phrases rapidly and economically. Automation of DDC's indexing has been machine-aided from its inception. A machine-aided indexing system is described that indexes one million words of text per hour of CPU time. (22 references) (Author/SJ)

Government Acronyms and Alphabetic Designations Used in DDC.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

The compilation consists of a guide to acronyms and alphabetic designations used by the Department of Defense (DOD), federal government and foreign military organizations on documents to designate reports on research monitored by them and cataloged by the Defense Documentation Center (DDC). In all instances the acronyms are those actually used by…

TNF α is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

PubMed Central

Zheng, Xuexing; Ouyang, Handong; Liu, Shue; Mata, Marina; Fink, David J.; Hao, Shuanglin

2011-01-01

In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTI). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNFα in antiretroviral drug-induced neuropathic pain. We administered 2′,3′-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain. PMID:21741472

Effect of modeling factors on the dissolution-diffusion-convection process during CO2 geological storage in deep saline formations

NASA Astrophysics Data System (ADS)

Zhang, Wei

2013-06-01

It is well known that during CO2 geological storage, density-driven convective activity can significantly accelerate the dissolution of injected CO2 into water. This action could limit the escape of supercritical CO2 from the storage formation through vertical pathways such as fractures, faults and abandoned wells, consequently increasing permanence and security of storage. First, we investigated the effect of numerical perturbation caused by time and grid resolution and the convergence criteria on the dissolution-diffusion-convection (DDC) process. Then, using the model with appropriate spatial and temporal resolution, some uncertainty parameters investigated in our previous paper such as initial gas saturation and model boundaries, and other factors such as relative liquid permeability and porosity modification were used to examine their effects on the DDC process. Finally, we compared the effect of 2D and 3D models on the simulation of the DDC process. The above modeling results should contribute to clear understanding and accurate simulation of the DDC process, especially the onset of convective activity, and the CO2 dissolution rate during the convection-dominated stage.

Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes.

PubMed

Kot, Marta; Daniel, Władysława A

2009-01-01

The aim of the present study was to test the effect of diethyldithiocarbamate (DDC), which is regarded as a cytochrome P450 (CYP) CYP2A6 and CYP2E1 inhibitor, and ticlopidine, an efficient CYP2B6, CYP2C19 and CYP2D6 inhibitor, on the activity of human CYP1A2 and the metabolism of caffeine (1-N-, 3-N- and 7-N-demethylation, and C-8-hydroxylation). The experiment was carried out in vitro using human cDNA-expressed CYP1A2 (Supersomes) and human pooled liver microsomes. The effects of DDC and ticlopidine were compared to those of furafylline (a strong CYP1A2 inhibitor). A comparative in vitro study provides clear evidence that ticlopidine and DDC, applied at concentrations that inhibit the above-mentioned CYP isoforms, potently (as compared to furafylline) inhibit human CYP1A2 and caffeine metabolism, in particular 1-N- and 3-N-demethylation.

Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2',3'-dideoxycytidine.

PubMed Central

Medlin, H K; Zhu, Y Q; Remington, K M; Phillips, T R; North, T W

1996-01-01

We have selected and plaque purified a mutant of feline immunodeficiency virus (FIV) that is resistant to 2',3'-dideoxycytidine (ddC). This mutant was selected in cultured cells in the continuous presence of 25 microM ddC. The mutant, designated DCR-5c, was fourfold resistant to ddC, threefold resistant to 2',3'-dideoxyinosine, and more than fourfold resistant to phosphonoformic acid. DCR-5c displayed little or no resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine, 3'-azido-3'-deoxythymidine, or 9-(2-phosphonylmethoxyethyl) adenine. Reverse transcriptase purified from DCR-5c was less susceptible to inhibition by ddCTP, phosphonoformic acid, ddATP, or azido-dTTP than the wild-type FIV reverse transcriptase. Sequence analysis of DCR-5c revealed a single base change (G to C at nucleotide 2342) in the reverse transcriptase-encoding region of FIV. This mutation results in substitution of His for Asp at codon 3 of FIV reverse transcriptase. The role of this mutation in ddC resistance was confirmed by site-directed mutagenesis. PMID:8849258

SAMe prevents the induction of the immunoproteasome and preserves the 26S proteasome in the DDC-induced MDB mouse model.

PubMed

Bardag-Gorce, Fawzia; Oliva, Joan; Li, Jun; French, Barbara A; French, Samuel W

2010-06-01

Mallory-Denk bodies (MDBs) form in the liver of alcoholic patients. This occurs because of the accumulation and aggregation of ubiquitinated cytokeratins, which hypothetically is due to the ubiquitin-proteasome pathway's (UPP) failure to degrade the cytokeratins. The experimental model of MDB formation was used in which MDBs were induced by refeeding DDC to drug-primed mice. The gene expression and protein levels of LMP2, LMP7 and MECL-1, the catalytic subunits in the immunoproteasome, as well as FAT10, were increased in the liver cells forming MDBs but not in the intervening normal hepatocytes. Chymotrypsin-like activity of the UPP was decreased by DDC refeeding, indicating that a switch from the UPP to the immunoproteasome had occurred at the expense of the 26S proteasome. The failure of the UPP to digest cytokeratins would explain MDB aggregate formation. SAMe prevented the decrease in UPP activity, the increase in LMP2, LMP7, and MECL-1 protein levels and MDB formation induced by DDC. DDC refeeding also induced the TNFalpha and IFNgamma receptors. SAMe prevented the increase in the TNFalpha and IFNgamma receptors, supporting the idea that TNFalpha and IFNgamma were responsible for the up regulation of LMP2, LPM7, and FAT10. These results support the conclusion that MDBs form in FAT10 over-expressing hepatocytes where the up regulation of the immunoproteasome occurs at the expense of the 26S proteasome. Copyright 2010 Elsevier Inc. All rights reserved.

Comparative Analysis and Modeling of the Severity of Steatohepatitis in DDC-Treated Mouse Strains

PubMed Central

Pandey, Vikash; Sultan, Marc; Kashofer, Karl; Ralser, Meryem; Amstislavskiy, Vyacheslav; Starmann, Julia; Osprian, Ingrid; Grimm, Christina; Hache, Hendrik; Yaspo, Marie-Laure; Sültmann, Holger; Trauner, Michael; Denk, Helmut; Zatloukal, Kurt; Lehrach, Hans; Wierling, Christoph

2014-01-01

Background Non-alcoholic fatty liver disease (NAFLD) has a broad spectrum of disease states ranging from mild steatosis characterized by an abnormal retention of lipids within liver cells to steatohepatitis (NASH) showing fat accumulation, inflammation, ballooning and degradation of hepatocytes, and fibrosis. Ultimately, steatohepatitis can result in liver cirrhosis and hepatocellular carcinoma. Methodology and Results In this study we have analyzed three different mouse strains, A/J, C57BL/6J, and PWD/PhJ, that show different degrees of steatohepatitis when administered a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) containing diet. RNA-Seq gene expression analysis, protein analysis and metabolic profiling were applied to identify differentially expressed genes/proteins and perturbed metabolite levels of mouse liver samples upon DDC-treatment. Pathway analysis revealed alteration of arachidonic acid (AA) and S-adenosylmethionine (SAMe) metabolism upon other pathways. To understand metabolic changes of arachidonic acid metabolism in the light of disease expression profiles a kinetic model of this pathway was developed and optimized according to metabolite levels. Subsequently, the model was used to study in silico effects of potential drug targets for steatohepatitis. Conclusions We identified AA/eicosanoid metabolism as highly perturbed in DDC-induced mice using a combination of an experimental and in silico approach. Our analysis of the AA/eicosanoid metabolic pathway suggests that 5-hydroxyeicosatetraenoic acid (5-HETE), 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin D2 (PGD2) are perturbed in DDC mice. We further demonstrate that a dynamic model can be used for qualitative prediction of metabolic changes based on transcriptomics data in a disease-related context. Furthermore, SAMe metabolism was identified as being perturbed due to DDC treatment. Several genes as well as some metabolites of this module show differences between A/J and C57BL/6J on the one hand and PWD/PhJ on the other. PMID:25347188

SPONTANEOUS REPOPULATION OF β-CATENIN NULL LIVERS WITH β-CATENIN POSITIVE HEPATOCYTES AFTER CHRONIC MURINE LIVER INJURY

PubMed Central

Thompson, Michael D.; Wickline, Emily D.; Bowen, William B.; Lu, Amy; Singh, Sucha; Misse, Amalea; Monga, Satdarshan P. S.

2011-01-01

Prolonged exposure of mice to diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) results in hepatobiliary injury, atypical ductular proliferation, oval cell appearance and limited fibrosis. Previously, we reported that short-term ingestion of DDC diet by hepatocyte-specific β-catenin conditional knockout (KO) mice, led to fewer A6-positive oval cells than wild-type (WT) littermates. To examine the role of β-catenin in chronic hepatic injury and repair, we exposed WT and KO mice to DDC for 80 and 150 days. Paradoxically, long-term DDC exposure led to significantly more A6-positive cells indicating greater atypical ductular proliferation in KO, which coincided with increased fibrosis and cholestasis. Surprisingly, at 80 and 150 days in KO, we observed a significant amelioration of hepatocyte injury. This coincided with extensive repopulation of β-catenin null livers with β-catenin-positive hepatocytes at 150 days, which was preceded by appearance of β-catenin-positive hepatocyte clusters at 80 days and a few β-catenin-positive hepatocytes at earlier times. Intriguingly, occasional β-catenin-positive hepatocytes that were negative for progenitor markers were also observed at baseline in the KO livers suggesting spontaneous escape from cre-mediated recombination. These cells with hepatocyte morphology expressed mature hepatocyte markers but lacked markers of hepatic progenitors. The gradual repopulation of KO livers with β-catenin-positive hepatocytes occurred only following DDC injury and coincided with a progressive loss of hepatic cre-recombinase expression. A few β-catenin-positive cholangiocytes were observed albeit only after long-term DDC-exposure and trailed the appearance of β-catenin-positive hepatocytes. In conclusion, in a chronic liver injury model, β-catenin-positive hepatocytes exhibit growth and survival advantages and repopulate KO livers eventually limiting hepatic injury and dysfunction despite increased fibrosis and intrahepatic cholestasis. PMID:21721031

Comparative analysis and modeling of the severity of steatohepatitis in DDC-treated mouse strains.

PubMed

Pandey, Vikash; Sultan, Marc; Kashofer, Karl; Ralser, Meryem; Amstislavskiy, Vyacheslav; Starmann, Julia; Osprian, Ingrid; Grimm, Christina; Hache, Hendrik; Yaspo, Marie-Laure; Sültmann, Holger; Trauner, Michael; Denk, Helmut; Zatloukal, Kurt; Lehrach, Hans; Wierling, Christoph

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) has a broad spectrum of disease states ranging from mild steatosis characterized by an abnormal retention of lipids within liver cells to steatohepatitis (NASH) showing fat accumulation, inflammation, ballooning and degradation of hepatocytes, and fibrosis. Ultimately, steatohepatitis can result in liver cirrhosis and hepatocellular carcinoma. In this study we have analyzed three different mouse strains, A/J, C57BL/6J, and PWD/PhJ, that show different degrees of steatohepatitis when administered a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) containing diet. RNA-Seq gene expression analysis, protein analysis and metabolic profiling were applied to identify differentially expressed genes/proteins and perturbed metabolite levels of mouse liver samples upon DDC-treatment. Pathway analysis revealed alteration of arachidonic acid (AA) and S-adenosylmethionine (SAMe) metabolism upon other pathways. To understand metabolic changes of arachidonic acid metabolism in the light of disease expression profiles a kinetic model of this pathway was developed and optimized according to metabolite levels. Subsequently, the model was used to study in silico effects of potential drug targets for steatohepatitis. We identified AA/eicosanoid metabolism as highly perturbed in DDC-induced mice using a combination of an experimental and in silico approach. Our analysis of the AA/eicosanoid metabolic pathway suggests that 5-hydroxyeicosatetraenoic acid (5-HETE), 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin D2 (PGD2) are perturbed in DDC mice. We further demonstrate that a dynamic model can be used for qualitative prediction of metabolic changes based on transcriptomics data in a disease-related context. Furthermore, SAMe metabolism was identified as being perturbed due to DDC treatment. Several genes as well as some metabolites of this module show differences between A/J and C57BL/6J on the one hand and PWD/PhJ on the other.

Machine-Aided Indexing in Practice: An Encounter with Automatic Indexing of the Third Kind.

ERIC Educational Resources Information Center

Klingbiel, Paul H.

This three-part report includes a brief history of the Defense Documentation Center (DDC) with a description of the collections and their accessibility; categorization of automatic indexing into three kinds with a brief description of the DDC system of machine-aided indexing; and an indication of some operational experiences with the system.…

Use of the Dewey Decimal Classification in the United States and Canada.

ERIC Educational Resources Information Center

Comaromi, John P.

1978-01-01

A summary of use of DDC in U.S. and Canadian libraries shows that 85 percent of all libraries use DDC; of these, 75 percent use the most recent full or abridged edition. Divisions needing revision are listed and discussed. Librarians want continuous revision but they do not want numerical designation meanings changed. (Author/MBR)

Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells.

PubMed Central

Gao, W Y; Shirasaka, T; Johns, D G; Broder, S; Mitsuya, H

1993-01-01

The antiviral activity of azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddI) against HIV-1 was comparatively evaluated in PHA-stimulated PBM. The mean drug concentration which yielded 50% p24 Gag negative cultures were substantially different: 0.06, 0.2, and 6 microM for AZT, ddC, and ddI, respectively. We found that AZT was preferentially phosphorylated to its triphosphate (TP) form in PHA-PBM rather than unstimulated, resting PBM (R-PBM), producing 10- to 17-fold higher ratios of AZTTP/dTTP in PHA-PBM than in R-PBM. The phosphorylation of ddC and ddI to their TP forms was, however, much less efficient in PHA-PBM, resulting in approximately 5-fold and approximately 15-fold lower ratios of ddCTP/dCTP and ddATP/dATP, respectively, in PHA-PBM than in R-PBM. The comparative order of PHA-induced increase in cellular enzyme activities examined was: thymidine kinase > uridine kinase > deoxycytidine kinase > adenosine kinase > 5'-nucleotidase. We conclude that AZT, ddC, and ddI exert disproportionate antiviral effects depending on the activation state of the target cells, i.e., ddI and ddC exert antiviral activity more favorably in resting cells than in activated cells, while AZT preferentially protects activated cells against HIV infection. Considering that HIV-1 proviral DNA synthesis in resting lymphocytes is reportedly initiated at levels comparable with those of activated lymphocytes, the current data should have practical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy. PMID:8387546

A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

PubMed

Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

2004-04-29

Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

Histogram analysis of stretched-exponential and monoexponential diffusion-weighted imaging models for distinguishing low and intermediate/high gleason scores in prostate carcinoma.

PubMed

Liu, Wei; Liu, Xiao H; Tang, Wei; Gao, Hong B; Zhou, Bing N; Zhou, Liang P

2018-02-07

Noninvasive measures to evaluate the aggressiveness of prostate carcinoma (PCa) may benefit patients. To assess the value of stretched-exponential and monoexponential diffusion-weighted imaging (DWI) for predicting the aggressiveness of PCa. Retrospective study. Seventy-five patients with PCa. 3T DWI examinations were performed using b-values of 0, 500, 1000, and 2000 s/mm 2 . The research were based on entire-tumor histogram analysis and the reference standard was radical prostectomy. The correlation analysis was programmed with Spearman's rank-order analysis between the histogram variables and Gleason grade group (GG). Receiver operating characteristic (ROC) regression was used to analyze the ability of these histogram variables to differentiate low-grade (LG) from intermediate/high-grade (HG) PCa. The percentiles and mean of apparent diffusion coefficient (ADC) and distributed diffusion coefficient (DDC) were correlated with GG (ρ: 0.414-0.593), while there was no significant relation among α value, skewnesses, and kurtosises with GG (ρ:0.034-0.323). HG tumors (ADC:484 ± 136, 592 ± 139, 670 ± 144, 788 ± 146, 895 ± 141 mm 2 /s; DDC: 410 ± 142, 532 ± 172, 666 ± 193, 786 ± 196, 914 ± 181 mm 2 /s) had lower values in the 10 th , 25 th , 50 th , 75 th percentiles and means than LG tumors (ADC: 644 ± 779, 737 ± 84, 836 ± 83, 919 ± 82, 997 ± 107 mm 2 /s; DDC: 552 ± 82, 680 ± 94, 829 ± 112, 931 ± 106, 1045 ± 100 mm 2 /s). However, there was no difference between LG and HG tumors in α value (0.671 ± 0.041 vs. 0.633 ± 0.114), kurtosises (ADC 0.09 vs. 0.086; DDC -0.033 vs. -0.317), or skewnesses (ADC -0.036 vs. 0.073; DDC -0.063 vs. 0.136). The above statistics were P < 0.01. ADC10 with AUC = 0.840 and DDC10 with AUC = 0.799 were similar in discriminating between LG and HG PCa at P < 0.05. Histogram variables of DDC and ADC may predict the aggressiveness of PCa, while α value does not. The abilities of ADC10 and DDC10 to discriminate LG from HG tumors were similar, and both better than their respective means. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Safety and Efficacy of Endoscopic Therapy for Nonmalignant Duodenal Duplication Cysts: Case Report and Comprehensive Review of 28 Cases Reported in the Literature.

PubMed

Gjeorgjievski, Mihajlo; Manickam, Palaniappan; Ghaith, Gehad; Cappell, Mitchell S

2016-05-01

Analyze efficacy, safety of endoscopic therapy for duodenal duplication cysts (DDC) by comprehensively reviewing case reports.Tandem, independent, systematic, computerized, literature searches were performed via PubMed using medical subject headings or Keywords "cyst" and "duodenal" and "duplication"; or "cyst", and "endoscopy" or "endoscopic", and "therapy" or "decompression"; with reconciliation of generated references by two experts. Case report followed CARE guidelines.Literature review revealed 28 cases (mean = 1.3 ± 1.2 cases/report). Endoscopic therapy is increasingly reported recently (1984-1999: 3 cases, 2000-2015: 25 cases, P = 0.003, OR = 8.33, 95%-CI: 1.77-44.5). Fourteen (54%) of 26 patients were men (unknown-sex = 2). Mean age = 32.2 ± 18.3 years old. Procedure indications: acute pancreatitis-16, abdominal pain-8, jaundice-2, gastrointestinal (GI) obstruction-1, asymptomatic cyst-1. Mean maximal DDC dimension = 3.20 ± 1.53 cm (range, 1-6.5 cm). Endoscopic techniques included cyst puncture via needle knife papillotomy (NKP)/papillotome-18, snare resection of cyst-7, cystotome-2, and cyst needle aspiration/ligation-1. Endoscopic therapy was successful in all cases. Among 24 initially symptomatic patients, all remained asymptomatic post-therapy without relapses (mean follow-up = 36.5 ± 48.6 months, 3 others reported asymptomatic at follow-up of unknown duration; 1 initially asymptomatic patient remained asymptomatic 3 years post-therapy). Two complications occurred: mild intraprocedural duodenal bleeding related to NKP and treated locally endoscopically.A patient is reported who presented with vomiting, 15-kg-weight-loss, and profound dehydration for 1 month from extrinsic compression of duodenum by 14 × 6 cm DDC, underwent successful endosonographic cyst decompression with large fenestration of cyst and endoscopic aspiration of 1 L of fluid from cyst with rapid relief of symptoms. At endoscopy the DDC was intubated and visualized and random endoscopic mucosal biopsies were obtained to help exclude malignant or dysplastic DDC.Study limitations include retrospective literature review, potential reporting bias, limited patient number, variable follow-up.In conclusion, endoscopic therapy for DDC was efficacious in all 29 reported patients including current case, including patients presenting acutely with acute pancreatitis, or GI obstruction. Complications were rare and minor, suggesting that endoscopic therapy may be a useful alternative to surgery for nonmalignant DDC when performed by expert endoscopists.

A Classification Methodology and Retrieval Model to Support Software Reuse

DTIC Science & Technology

1988-01-01

Dewey Decimal Classification ( DDC 18), an enumerative scheme, occupies 40 pages [Buchanan 19791. Langridge [19731 states that the facets listed in the...sense of historical importance or wide spread use. The schemes are: Dewey Decimal Classification ( DDC ), Universal Decimal Classification (UDC...Classification Systems ..... ..... 2.3.3 Library Classification__- .52 23.3.1 Dewey Decimal Classification -53 2.33.2 Universal Decimal Classification 55 2333

Especially DDC. Users Look at the DoD Information Transfer Process

DTIC Science & Technology

1975-01-01

and new technologies when possible. Facsimile Transmission The need to transmit information accurately and quickly is a constant pressure in the field ...21 Generation and Management of DoD Information................ 23 Generation ofInformation ......................... 24 Management of...recommendations are made in the spirit that in every field of endeavor., improvements are always possible. The librarians using DDC services feel the Center is

Engineering Design Handbook. Development Guide for Reliability. Part 6. Mathematical Appendix and Glossary

DTIC Science & Technology

1976-01-08

Corps, nonmilitary Government agencies, contractors, private industry, individuals, universities , and others must purchase these Handbooks from...verified by an official Department of Army representative and processed from Defense Documentation Center ( DDC ), ATTN: DDC -TSR, Cameron Station...tell, by looking at a failed item, what classification of failure is involved. Some of the classifications are for mathematical conven- ience only

Altered regulation of miR-34a and miR-483-3p in alcoholic hepatitis and DDC fed mice.

PubMed

Liu, Hui; French, Barbara A; Li, Jun; Tillman, Brittany; French, Samuel W

2015-12-01

MicroRNAs are small noncoding RNAs that negatively regulate gene expression by binding to the untranslated regions of their target mRNAs. Deregulation of miRNAs is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of miR-34a and miR-483-3p by RNA sequencing (RNA-Seq) analyses. Real-time PCR further shows a 3- and 6-fold upregulation (respectively) of miR-34a in the AH livers and in the livers of DDC re-fed mice, while miR-483-3p was significantly downregulated in AH and DDC re-fed mice livers. This indicates that miR-34a and miR-483-3p may be crucial for liver MDB formation. P53 mRNA was found to be significantly downregulated both in the AH livers and in the livers of DDC re-fed mice, indicating that the upregulation of miR-34a is permitted by the decrease of p53 in AH since miR-34a is a main target of p53. Overexpression of miR-34a leads to an increase of p53 targets such as p27, which inhibits the cell cycle leading to cell cycle arrest. Importantly, BRCA1 is a target gene of miR-483-3p by RNA-Seq analyses and the downregulation of miR-483-3p may be the mechanism for liver MDB formation since the BRCA1 signal was markedly upregulated in AH livers. These results constitute a demonstration of the altered regulation of miR-34a and miR-483-3p in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by miR-34a and miR-483-3p in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

IL-8 signaling is up regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present

PubMed Central

Liu, Hui; French, Barbara A.; Nelson, Tyler J.; Li, Jun; Tillman, Brittany; French, Samuel W.

2015-01-01

Chemokines and their receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. The chemokine CXCL8, also known as interleukin-8 (IL-8), is a proinflammatory molecule that has functions within the tumor microenvironment. Deregulation of IL-8 signaling is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of IL-8 signaling by RNA sequencing (RNA-Seq) analyses. Real-time PCR analysis of CXCR2 further shows a 6-fold up regulation in AH livers and a 26-fold up regulation in the livers of DDC re-fed mice. IL-8 mRNA was also significantly up regulated in AH livers and DDC re-fed mice livers. This indicates that CXCR2 and IL-8 may be crucial for liver MDB formation. MDB containing balloon hepatocytes in AH livers had increased intensity of staining of the cytoplasm for both CXCR2 and IL-8. Over expression of IL-8 leads to an increase of the mitogen activated protein kinase (MAPK) cascade and exacerbates the inflammatory cycle. These observations constitute a demonstration of the altered regulation of IL-8 signaling in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by IL-8 signaling in AH. PMID:26260904

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine.

PubMed

Yi, Zhihua; Xie, Lihui; Zhou, Congfa; Yuan, Huilong; Ouyang, Shuai; Fang, Zhi; Zhao, Shanhong; Jia, Tianyu; Zou, Lifang; Wang, Shouyu; Xue, Yun; Wu, Bing; Gao, Yun; Li, Guilin; Liu, Shuangmei; Xu, Hong; Xu, Changshui; Zhang, Chunping; Liang, Shangdong

2018-03-01

The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y 12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y 12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y 12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca 2+ ] i activated by the P2Y 12 receptor agonist 2-(Methylthio) adenosine 5'-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y 12 receptor shRNA treatment inhibited 2-MeSADP-induced [Ca 2+ ] i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y 12 receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y 12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

ONCOGENIC DRIVER GENES AND THE INFLAMMATORY MICROENVIRONMENT DICTATE LIVER TUMOR PHENOTYPE

PubMed Central

Matter, Matthias S.; Marquardt, Jens U.; Andersen, Jesper B.; Quintavalle, Cristina; Korokhov, Nikolay; Stauffer, Jim K.; Kaji, Kosuke; Decaens, Thomas; Quagliata, Luca; Elloumi, Fathi; Hoang, Tanya; Molinolo, Alfredo; Conner, Elizabeth A.; Weber, Achim; Heikenwalder, Mathias; Factor, Valentina M.; Thorgeirsson, Snorri S.

2016-01-01

The majority of hepatocellular carcinoma (HCC) develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or non-alcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and β-catenin (CAT) followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl4). Also, the impact of DDC-induced chronic liver inflammation was compared between two liver tumor models using a combination of AKT-CAT or AKT-NRASG12V. Treatment with DDC and CCl4 significantly facilitated the adenoma-to-carcinoma conversion and accelerated the growth of AKT-CAT tumors. Furthermore, DDC treatment altered the morphology of AKT-CAT tumors and caused loss of lipid droplets. Transcriptome analysis of AKT-CAT tumors revealed that cellular growth and proliferation was mainly affected by chronic inflammation and caused upregulated of Cxcl16, Galectin-3 and Nedd9 among others. Integration with transcriptome profiles from human HCCs further demonstrated that AKT-CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT-NRASG12V tumors and primarily enhanced already existent tumor characteristics as supported by transcriptome analysis. However, it also reduced lipid droplets in AKT-NRASG12V tumors. Conclusion Our study suggests that liver tumor phenotype is defined by a combination of driving oncogenes but also the nature of chronic liver inflammation. PMID:26844528

Investigation on the Microstructure and Ductility-Dip Cracking Susceptibility of the Butt Weld Welded with ENiCrFe-7 Nickel-Base Alloy-Covered Electrodes

NASA Astrophysics Data System (ADS)

Qin, Renyao; Wang, Huang; He, Guo

2015-03-01

The weld metal of the ENiCrFe-7 nickel-based alloy-covered electrodes was investigated in terms of the microstructure, the grain boundary precipitation, and the ductility-dip cracking (DDC) susceptibility. Besides the dendritic gamma-Ni(Cr,Fe) phase, several types of precipitates dispersed on the austenitic matrix were observed, which were determined to be the Nb-rich MC-type carbides with "Chinese script" morphology and size of approximately 3 to 10 µm, the Mn-rich MO-type oxides with size of approximately 1 to 2 µm, and the spherical Al/Ti-rich oxides with size of less than 1 µm. The discontinuous Cr-rich M23C6-type carbides predominantly precipitate on the grain boundaries, which tend to coarsen during reheating but begin to dissolve above approximately 1273 K (1000 °C). The threshold strain for DDC at each temperature tested shows a certain degree of correlation with the grain boundary carbides. The DDC susceptibility increases sharply as the carbides coarsen in the temperature range of 973 K to 1223 K (700 °C to 950 °C). The growth and dissolution of the carbides during the welding heat cycles deteriorate the grain boundaries and increase the DDC susceptibility. The weld metal exhibits the minimum threshold strain of approximately 2.0 pct at 1323 K (1050 °C) and the DTR less than 873 K (600 °C), suggesting that the ENiCrFe-7—covered electrode has less DDC susceptibility than the ERNiCrFe-7 bare electrode but is comparable with the ERNiCrFe-7A.

Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC-induced cholestatic liver injury.

PubMed

Addante, Annalisa; Roncero, Cesáreo; Almalé, Laura; Lazcanoiturburu, Nerea; García-Álvaro, María; Fernández, Margarita; Sanz, Julián; Hammad, Seddik; Nwosu, Zeribe C; Lee, Se-Jin; Fabregat, Isabel; Dooley, Steven; Ten Dijke, Peter; Herrera, Blanca; Sánchez, Aránzazu

2018-05-11

Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. WT and BMP9KO mice were submitted to DDC diet. Livers were examined for liver injury, fibrosis, inflammation and oval cell expansion by serum biochemistry, histology, RT-qPCR and western blot. BMP9 signalling and effects in oval cells were studied in vitro using western blot and transcriptional assays, plus functional assays of DNA synthesis, cell viability and apoptosis. Crosslinking assays and short hairpin RNA approaches were used to identify the receptors mediating BMP9 effects. Deletion of BMP9 reduces liver damage and fibrosis, but enhances inflammation upon DDC feeding. Molecularly, absence of BMP9 results in overactivation of PI3K/AKT, ERK-MAPKs and c-Met signalling pathways, which together with an enhanced ductular reaction and oval cell expansion evidence an improved regenerative response and decreased damage in response to DDC feeding. Importantly, BMP9 directly targets oval cells, it activates SMAD1,5,8, decreases cell growth and promotes apoptosis, effects that are mediated by Activin Receptor-Like Kinase 2 (ALK2) type I receptor. We identify BMP9 as a negative regulator of oval cell expansion in cholestatic injury, its deletion enhancing liver regeneration. Likewise, our work further supports BMP9 as an attractive therapeutic target for chronic liver diseases. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression

PubMed Central

Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

2016-01-01

The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). DDC is metabolized mainly by cytochrome P450 (Cyp)3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC. PMID:26967735

IL-8 signaling is up-regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present.

PubMed

Liu, Hui; French, Barbara A; Nelson, Tyler J; Li, Jun; Tillman, Brittany; French, Samuel W

2015-10-01

Chemokines and their receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. The chemokine CXCL8, also known as interleukin-8 (IL-8), is a proinflammatory molecule that has functions within the tumor microenvironment. Deregulation of IL-8 signaling is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of IL-8 signaling by RNA sequencing (RNA-Seq) analyses. Real-time PCR analysis of CXCR2 further shows a 6-fold up-regulation in AH livers and a 26-fold up-regulation in the livers of DDC re-fed mice. IL-8 mRNA was also significantly up-regulated in AH livers and DDC re-fed mice livers. This indicates that CXCR2 and IL-8 may be crucial for liver MDB formation. MDB containing balloon hepatocytes in AH livers had increased intensity of staining of the cytoplasm for both CXCR2 and IL-8. Overexpression of IL-8 leads to an increase of the mitogen activated protein kinase (MAPK) cascade and exacerbates the inflammatory cycle. These observations constitute a demonstration of the altered regulation of IL-8 signaling in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by IL-8 signaling in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model

PubMed Central

Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

2016-01-01

The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet–fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of sublethal tubular cell injury. PMID:26752420

The distribution of the anti-HIV drug, 2'3'-dideoxycytidine (ddC), across the blood-brain and blood-cerebrospinal fluid barriers and the influence of organic anion transport inhibitors.

PubMed

Gibbs, J E; Thomas, S A

2002-02-01

The brain and CSF distribution of the HIV reverse transcriptase inhibitor, 2'3'-dideoxycytidine (ddC), was investigated by the in situ brain perfusion and isolated incubated choroid plexus methods in the guinea pig. Multiple-time brain perfusions indicated that the distribution of [3H]ddC to the brain and CSF was low and the unidirectional rate constant (K(in)) for the brain uptake of this nucleoside analogue (0.52 +/- 0.10 microL/min/g) was not significantly different to that for the vascular marker, [14C]mannitol (0.44 +/- 0.09 microL/min/g). The influence of unlabelled ddC, six organic anion transport inhibitors and 3'-azido 3'-deoxythymidine (AZT) on the CNS uptake of [3H]ddC was examined in situ and in vitro. ddC, probenecid and 2,4-dichlorophenoxyacetic acid altered the distribution of [3H]ddC into the brain and choroid plexuses, indicating that the limited distribution of [3H]ddC was a result of an organic anion efflux transporter, in addition to the low lipophilicity of this drug (octanol-saline partition coefficient, 0.047 +/- 0.001). The CNS distribution was also sensitive to p-aminohippurate and deltorphin II, but not digoxin, suggesting the involvement of organic anion transporters (OAT1/OAT3-like) and organic anion transporting polypeptides (OATP1/OATPA-like). AZT did not effect the accumulation of [3H]ddC, indicating that when these nucleoside analogues are used in anti-HIV combination therapy, the CNS distribution of ddC is unchanged.

Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population.

PubMed

Al-Absi, Boshra; Razif, Muhammad F M; Noor, Suzita M; Saif-Ali, Riyadh; Aqlan, Mohammed; Salem, Sameer D; Ahmed, Radwan H; Muniandy, Sekaran

2017-10-01

Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent. Seven single-nucleotide polymorphisms (SNPs) in IKZF1, three SNPs in DDC, two SNPs in CDKN2A, two SNPs in CEBPE, and three SNPs in LMO1 were genotyped in 289 Yemeni children (136 cases and 153 controls), using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Logistic regression analyses were used to estimate ALL risk, and the strength of association was expressed as odds ratios with 95% confidence intervals. We found that the IKZF1 SNP rs10235796 C allele (p = 0.002), the IKZF1 rs6964969 A>G polymorphism (p = 0.048, GG vs. AA), the CDKN2A rs3731246 G>C polymorphism (p = 0.047, GC+CC vs. GG), and the CDKN2A SNP rs3731246 C allele (p = 0.007) were significantly associated with ALL in Yemenis of Arab-Asian descent. In addition, a borderline association was found between IKZF1 rs4132601 T>G variant and ALL risk. No associations were found between the IKZF1 SNPs (rs11978267; rs7789635), DDC SNPs (rs3779084; rs880028; rs7809758), CDKN2A SNP (rs3731217), the CEBPE SNPs (rs2239633; rs12434881) and LMO1 SNPs (rs442264; rs3794012; rs4237770) with ALL in Yemeni children. The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.

Control of the yeast telomeric senescence survival pathways of recombination by the Mec1 and Mec3 DNA damage sensors and RPA

PubMed Central

Grandin, Nathalie; Charbonneau, Michel

2007-01-01

Saccharomyces cerevisiae telomerase-negative cells undergo homologous recombination on subtelomeric or TG1–3 telomeric sequences, thus allowing Type I or Type II post-senescence survival, respectively. Here, we find that the DNA damage sensors, Mec1, Mec3 and Rad24 control Type II recombination, while the Rad9 adaptor protein and the Rad53 and Chk1 effector kinases have no effect on survivor type selection. Therefore, the Mec1 and Mec3 checkpoint complexes control telomeric recombination independently of their roles in generating and amplifying the Mec1-Rad53-Chk1 kinase cascade. rfa1-t11 mutant cells, bearing a mutation in Replication Protein A (RPA) conferring a defect in recruiting Mec1-Ddc2, were also deficient in both types of telomeric recombination. Importantly, expression of an Rfa1-t11-Ddc2 hybrid fusion protein restored checkpoint-dependent arrest, but did not rescue defective telomeric recombination. Therefore, the Rfa1-t11-associated defect in telomeric recombination is not solely due to its failure to recruit Mec1. We have also isolated novel alleles of RFA1 that were deficient in Type I but not in Type II recombination and proficient in checkpoint control. Therefore, the checkpoint and recombination functions of RPA can be genetically separated, as can the RPA-mediated control of the two types of telomeric recombination. PMID:17202155

Applications for Micrographics in Large Scale Information Systems of the Future. Volume I: Part I. Summary. Part II. Five-Year Plan for DDC Micrographic Development Actions.

ERIC Educational Resources Information Center

Information Dynamics Corp., Reading, MA.

A study intended to provide the Defense Documentation Center (DDC) with a five-year plan for the development of improved and new microfiche products, services, and production capabilities is summarized in this report. In addition, the major findings, conclusions, and recommendations developed during the study are noted. The results of the research…

Dewey Decimal Classification Online Project: Evaluation of a Library Schedule and Index Integrated into the Subject Searching Capabilities of an Online Catalog. Final Report.

ERIC Educational Resources Information Center

Markey, Karen; Demeyer, Anh N.

In this research project, subject terms from the Dewey Decimal Classification (DDC) Schedules and Relative Index were incorporated into an online catalog as searcher's tools for subject access, browsing, and display. Four features of the DDC were employed to help searchers browse for and match their own subject terms with the online catalog's…

Nucleotide variation at the dopa decarboxylase (Ddc) gene in natural populations of Drosophila melanogaster.

PubMed

Tatarenkov, Andrey; Ayala, Francisco J

2007-08-01

We studied nucleotide sequence variation at the gene coding for dopa decarboxylase (Ddc) in seven populations of Drosophila melanogaster. Strength and pattern of linkage disequilibrium are somewhat distinct in the extensively sampled Spanish and Raleigh populations. In the Spanish population, a few sites are in strong positive association, whereas a large number of sites in the Raleigh population are associated nonrandomly but the association is not strong. Linkage disequilibrium analysis shows presence of two groups of haplotypes in the populations, each of which is fairly diverged, suggesting epistasis or inversion polymorphism. There is evidence of two forms of natural selection acting on Ddc. The McDonald-Kreitman test indicates a deficit of fixed amino acid differences between D. melanogaster and D. simulans, which may be due to negative selection. An excess of derived alleles at high frequency, significant according to the H-test, is consistent with the effect of hitchhiking. The hitchhiking may have been caused by directional selection downstream of the locus studied, as suggested by a gradual decrease of the polymorphism-to-divergence ratio. Altogether, the Ddc locus exhibits a complicated pattern of variation apparently due to several evolutionary forces. Such a complex pattern may be a result of an unusually high density of functionally important genes.

Mutation-adapted U1 snRNA corrects a splicing error of the dopa decarboxylase gene.

PubMed

Lee, Ni-Chung; Lee, Yu-May; Chen, Pin-Wen; Byrne, Barry J; Hwu, Wuh-Liang

2016-12-01

Aromatic l-amino acid decarboxylase (AADC) deficiency is an inborn error of monoamine neurotransmitter synthesis, which results in dopamine, serotonin, epinephrine and norepinephrine deficiencies. The DDC gene founder mutation IVS6 + 4A > T is highly prevalent in Chinese patients with AADC deficiency. In this study, we designed several U1 snRNA vectors to adapt U1 snRNA binding sequences of the mutated DDC gene. We found that only the modified U1 snRNA (IVS-AAA) that completely matched both the intronic and exonic U1 binding sequences of the mutated DDC gene could correct splicing errors of either the mutated human DDC minigene or the mouse artificial splicing construct in vitro. We further injected an adeno-associated viral (AAV) vector to express IVS-AAA in the brain of a knock-in mouse model. This treatment was well tolerated and improved both the survival and brain dopamine and serotonin levels of mice with AADC deficiency. Therefore, mutation-adapted U1 snRNA gene therapy can be a promising method to treat genetic diseases caused by splicing errors, but the efficiency of such a treatment still needs improvements. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Three Specialized Innovations for FAST Wideband Receiver

NASA Astrophysics Data System (ADS)

Zhang, Xia; Yu, Xinying; Duan, Ran; Hao, Jie; Li, Di

2015-08-01

The National Astronomical Observatories of the Chinese Academy of Sciences (NAOC) will soon finish the largest antenna in the world. Known as FAST, the Five-hundred-meter Aperture Spherical Radio Telescope will be the most sensitive single-dish radio telescope in the low frequency radio bands between 70 MHz and 3 GHz.To take advantage of its giant aperture, all relevant cutting-edge technology should be applied to FAST to ensure that it achieves the best possible overall performance. The wideband receiver that is currently under development can not only be directly applied to FAST, but also used for other Chinese radio telescopes, such as the Shanghai 65-meter telescope and the Xinjiang 110-meter telescope, to ensure that these telescopes are among the best in the world. Recently, rapid development related to this wideband receiver has been underway. In this paper, we will introduce three key aspects of the FAST wideband receiver project. First is the use of a high-performance analog-to-digital converter (ADC). With the cooperation of Hao Jie’s team from the Institute of Automation of the Chinese Academy of Sciences(CASIA), we have developed 3-Gsps,12-bit ADCs, which have not been used previously in astronomy, and we expect to realize the 3-GHz bandwidth in a single step by covering the entire bandwidth via interleaving or a complex fast Fourier transform (FFT).Second is the front-end analog signal integrated circuit board. We wish to achieve a series of amplification, attenuation, and mixing filtering operations on a single small board, thereby achieving digital control of the bandpass behavior both flexibly and highly-efficiently. This design will not only greatly reduce the required cost and power but will also make the best use of the digital-system’s flexibility. Third is optimization of the FFT: the existing FFT is not very efficient; therefore, we will optimize the FFT for large-scale operation. For this purpose, we intend to cascade two FFTs. Another possibility is to combine digital down conversion (DDC) with the FFT to achieve a flexible FFT.

Enhancement of radiosensitizing effect of the nitroimidazole derivative RK28 on the proliferation of MethA tumor cells in combined use with diethyldithiocarbamate

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

Mashiba, Harukazu; Matsunaga, Keiko; Hata, Kazuo

1991-01-01

The radiosensitizing effect of the nitroimidazole derivative RK28 and diethyldithiocarbamate (DDC), which is an inhibitor of superoxide dismutase activity, was examined in vitro by using Meth A tumor cells. The radiosensitizing effect of 0.5 mM RK28 was observed in both of 10 Gy and 15 Gy irradiated groups. The addition of 5 {times} 10{sup {minus}7} M DDC also enhanced the radiation-induced proliferation inhibition. Marked enhancement of the anti-proliferative effect was observed in combined use of 0.2 mM or 0.5 mM RK28 with 2 {times} 10 M or 5 {times} 10{sup {minus}7} M DDC. These results suggest that enhanced oxygen effectmore » could be expected through combined use of the ionizing irradiation with both of these agents.« less

Semi-automated segmentation of the prostate gland boundary in ultrasound images using a machine learning approach

NASA Astrophysics Data System (ADS)

Diaz, Kristians; Castaneda, Benjamin

2008-03-01

This paper presents a semi-automated algorithm for prostate boundary segmentation from three-dimensional (3D) ultrasound (US) images. The US volume is sampled into 72 slices which go through the center of the prostate gland and are separated at a uniform angular spacing of 2.5 degrees. The approach requires the user to select four points from slices (at 0, 45, 90 and 135 degrees) which are used to initialize a discrete dynamic contour (DDC) algorithm. 4 Support Vector Machines (SVMs) are trained over the output of the DDC and classify the rest of the slices. The output of the SVMs is refined using binary morphological operations and DDC to produce the final result. The algorithm was tested on seven ex vivo 3D US images of prostate glands embedded in an agar mold. Results show good agreement with manual segmentation.

Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions.

PubMed

Skuta, G; Fischer, G M; Janaky, T; Kele, Z; Szabo, P; Tozser, J; Sumegi, B

1999-12-15

The short-term cardiac side effects of 2',3'-dideoxycytidine (ddC, zalcitabine) were studied in rats in order to understand the biochemical events contributing to the development of ddC-induced cardiomyopathy. In developing animals, ddC treatment provoked a surprisingly rapid appearance of cardiac malfunctions characterized by prolonged RR, PR, and QT intervals and J point depression. The energy metabolism in the heart was compromised, characterized by a decreased creatine phosphate/creatine ratio (from 2.05 normal value to 0.75) and a decreased free ATP/ADP ratio (from 332 normal value to 121). The activity of respiratory complexes (NADH: cytochrome c oxidoreductase and cytochrome oxidase) also decreased significantly. Southern blot and polymerase chain reaction analysis did not show deletions or a decrease in the quantity of mitochondrial DNA (mtDNA) deriving from ddC-treated rat hearts, indicating that under our experimental conditions, ddC-induced heart abnormalities were not the direct consequence of mtDNA-related damage. The ddC treatment of rats significantly increased the formation of reactive oxygen species (ROS) in heart and skeletal muscle as determined by the oxidation of non-fluorescent dihydrorhodamine123 to fluorescent rhodamine123 and the oxidation of cellular proteins determined from protein carbonyl content. An activation of the nuclear poly-(ADP-ribose) polymerase (EC 2.4.2.30) and an increase in the mono-ADP-ribosylation of glucose-regulated protein and desmin were observed in the cardiac tissue from ddC-treated animals. A decrease in the quantity of heat shock protein (HSP)70s was also detected, while the level of HSP25 and HSP60 remained unchanged. Surprisingly, ddC treatment induced a skeletal muscle-specific decrease in the quantity of three proteins, one of which was identified by N-terminal sequencing as myoglobin, and another by tandem mass spectrometer sequencing as triosephosphate isomerase (EC 5.3.1.1). These data show that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling through poly- and mono-ADP-ribosylation reactions and depression of HSP70 levels, whose processes represent a new mtDNA independent mechanism for ddC-induced cell damage.

Maintenance of Genome Stability and Breast Cancer: Molecular Analysis of DNA Damage-Activated Kinases

DTIC Science & Technology

2008-03-01

Breast Cancer: Molecular Analysis of DNA Damage-Activated Kinases PRINCIPAL INVESTIGATOR: Daniel Mordes...Maintenance of Genome Stability and Breast Cancer: Molecular Analysis of DNA Damage-Activated Kinases 5b. GRANT NUMBER W81XWH-06-1-0352 5c...shown that this domain of Dpb11 stimulates the kinase activity of wild-type Mec1-Ddc2 yet did not simulate Mec1-ddc2-top. Thus, we have demonstrated

A Bibliography on Non-Gaussian Signal Processing: 1971-1980.

DTIC Science & Technology

1980-08-20

Narrowband Acoustic Signals in Noise," DDC Report AD-A069 829, May 1979. 9. Evans, James, Kersten , Paul, Kurz, Ludwik, "Robustized Recursive Esti...Kazakos, D., and Papantoni-Kazakos, P., "Nonparanietric Methods in Communication Systems," Marcel Dekker, Inc., New York, 1977. 17. Kersten , P., Kurz...ARRAY PFOCESSING 1. Adams , S.L.; Doubek, J.W., "Frequency Coherence and Time Cbherence in Random Multipath Channels", DDC Peport, PD-A047 456, August

Characterization of Dendritic Cells Subpopulations in Skin and Afferent Lymph in the Swine Model

PubMed Central

Marquet, Florian; Bonneau, Michel; Pascale, Florentina; Urien, Celine; Kang, Chantal; Schwartz-Cornil, Isabelle; Bertho, Nicolas

2011-01-01

Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC) and dermal DC (DDC) that could be divided in 3 subsets according to their phenotypes: (1) the CD163neg/CD172aneg, (2) the CD163highCD172apos and (3) the CD163lowCD172apos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163negCD172low DDC share properties with the CD8+ T cell response-inducing murine skin CD103pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC. PMID:21298011

Airlift Cargo Hub Port Hold Times: Controlling Variations in Defense Supply Chain Delivery

DTIC Science & Technology

2010-06-01

AIR UNIVERSITY AIR FORCE INSTITUTE OF TECHNOLOGY Wright-Patterson Air Force Base, Ohio APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED...Department of Operational Sciences Graduate School of Engineering and Management Air Force Institute of Technology Air University Air...process for a seamless flow of cargo onto the aircraft segment (AMC and DDC , 24 Sep 08). Figure 6 AMC Velocity Efforts (Anderson D. , 2009) While

From convection rolls to finger convection in double-diffusive turbulence

NASA Astrophysics Data System (ADS)

Yang, Yantao; Verzicco, Roberto; Lohse, Detlef

2015-11-01

The double diffusive convection (DDC), where the fluid density depends on two scalar components with very different molecular diffusivities, is frequently encountered in oceanography, astrophysics, and electrochemistry. In this talk we report a systematic study of vertically bounded DDC for various control parameters. The flow is driven by an unstable salinity difference between two plates and stabilized by a temperature difference. As the relative strength of temperature difference becomes stronger, the flow transits from a state with large-scale convection rolls, which is similar to the Rayleigh-Bénard (RB) flow, to a state with well-organised salt fingers. When the temperature difference increases further, the flow breaks down to a purely conductive state. During this transit the velocity decreases monotonically. Counterintuitively, the salinity transfer can be enhanced when a stabilising temperature field is applied to the system. This happens when convection rolls are replaced by salt fingers. In addition, we show that the Grossmann-Lohse theory originally developed for RB flow can be directly applied to the current problem and accurately predicts the salinity transfer rate for a wide range of control parameters. Supported by Stichting FOM and the National Computing Facilities (NCF), both sponsored by NWO. The simulations were conducted on the Dutch supercomputer Cartesius at SURFsara.

Multi-model Analysis of Diffusion-weighted Imaging of Normal Testes at 3.0 T: Preliminary Findings.

PubMed

Min, Xiangde; Feng, Zhaoyan; Wang, Liang; Cai, Jie; Li, Basen; Ke, Zan; Zhang, Peipei; You, Huijuan; Yan, Xu

2018-04-01

This study aimed to establish diffusion quantitative parameters (apparent diffusion coefficient [ADC], DDC, α, D app , and K app ) in normal testes at 3.0 T. Sixty-four healthy volunteers in two age groups (A: 10-39 years; B: ≥ 40 years) underwent diffusion-weighted imaging scanning at 3.0 T. ADC 1000 , ADC 2000 , ADC 3000 , DDC, α, D app , and K app were calculated using the mono-exponential, stretched-exponential, and kurtosis models. The correlations between parameters and the age were analyzed. The parameters were compared between the age groups and between the right and the left testes. The average ADC 1000 , ADC 2000 , ADC 3000 , DDC, α, D app , and K app values did not significantly differ between the right and the left testes (P > .05 for all). The following significant correlations were found: positive correlations between age and testicular ADC 1000 , ADC 2000 , ADC 3000 , DDC, and D app (r = 0.516, 0.518, 0.518, 0.521, and 0.516, respectively; P < .01 for all) and negative correlations between age and testicular α and K app (r = -0.363, -0.427, respectively; P < .01 for both). Compared to group B, in group A, ADC 1000 , ADC 2000 , ADC 3000 , DDC, and D app were significantly lower (P < .05 for all), but α and K app were significantly higher (P < .05 for both). Our study demonstrated the applicability of the testicular mono-exponential, stretched-exponential, and kurtosis models. Our results can help establish a baseline for the normal testicular parameters in these diffusion models. The contralateral normal testis can serve as a suitable reference for evaluating the abnormalities of the other side. The effect of age on these parameters requires further attention. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Liver fibrosis: stretched exponential model outperforms mono-exponential and bi-exponential models of diffusion-weighted MRI.

PubMed

Seo, Nieun; Chung, Yong Eun; Park, Yung Nyun; Kim, Eunju; Hwang, Jinwoo; Kim, Myeong-Jin

2018-07-01

To compare the ability of diffusion-weighted imaging (DWI) parameters acquired from three different models for the diagnosis of hepatic fibrosis (HF). Ninety-five patients underwent DWI using nine b values at 3 T magnetic resonance. The hepatic apparent diffusion coefficient (ADC) from a mono-exponential model, the true diffusion coefficient (D t ), pseudo-diffusion coefficient (D p ) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched exponential model were compared with the pathological HF stage. For the stretched exponential model, parameters were also obtained using a dataset of six b values (DDC # , α # ). The diagnostic performances of the parameters for HF staging were evaluated with Obuchowski measures and receiver operating characteristics (ROC) analysis. The measurement variability of DWI parameters was evaluated using the coefficient of variation (CoV). Diagnostic accuracy for HF staging was highest for DDC # (Obuchowski measures, 0.770 ± 0.03), and it was significantly higher than that of ADC (0.597 ± 0.05, p < 0.001), D t (0.575 ± 0.05, p < 0.001) and f (0.669 ± 0.04, p = 0.035). The parameters from stretched exponential DWI and D p showed higher areas under the ROC curve (AUCs) for determining significant fibrosis (≥F2) and cirrhosis (F = 4) than other parameters. However, D p showed significantly higher measurement variability (CoV, 74.6%) than DDC # (16.1%, p < 0.001) and α # (15.1%, p < 0.001). Stretched exponential DWI is a promising method for HF staging with good diagnostic performance and fewer b-value acquisitions, allowing shorter acquisition time. • Stretched exponential DWI provides a precise and accurate model for HF staging. • Stretched exponential DWI parameters are more reliable than D p from bi-exponential DWI model • Acquisition of six b values is sufficient to obtain accurate DDC and α.

Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence.

PubMed

Ma, Jennie Z; Beuten, Joke; Payne, Thomas J; Dupont, Randolph T; Elston, Robert C; Li, Ming D

2005-06-15

DOPA decarboxylase (DDC; also known as L-amino acid decarboxylase; AADC) is involved in the synthesis of dopamine, norepinephrine and serotonin. Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND). Further, this gene is located within the 7p11 region that showed a 'suggestive linkage' to ND in our previous genome-wide scan in the Framingham Heart Study population. In the present study, we tested eight single nucleotide polymorphisms (SNPs) within DDC for association with ND, which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstrom test for ND (FTND) score, in a total of 2037 smokers and non-smokers from 602 nuclear families of African- or European-American (AA or EA, respectively) ancestry. Association analysis for individual SNPs using the PBAT-GEE program indicated that SNP rs921451 was significantly associated with two of the three adjusted ND measures in the EA sample (P=0.01-0.04). Haplotype-based association analysis revealed a protective T-G-T-G haplotype for rs921451-rs3735273-rs1451371-rs2060762 in the AA sample, which was significantly associated with all three adjusted ND measures after correction for multiple testing (min Z=-2.78, P=0.006 for HSI). In contrast, we found a high-risk T-G-T-G haplotype for a different SNP combination in the EA sample, rs921451-rs3735273-rs1451371-rs3757472, which showed a significant association after Bonferroni correction with the SQ and FTND score (max Z=2.73, P=0.005 for FTND). In summary, our findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.

Intravoxel water diffusion heterogeneity MR imaging of nasopharyngeal carcinoma using stretched exponential diffusion model.

PubMed

Lai, Vincent; Lee, Victor Ho Fun; Lam, Ka On; Sze, Henry Chun Kin; Chan, Queenie; Khong, Pek Lan

2015-06-01

To determine the utility of stretched exponential diffusion model in characterisation of the water diffusion heterogeneity in different tumour stages of nasopharyngeal carcinoma (NPC). Fifty patients with newly diagnosed NPC were prospectively recruited. Diffusion-weighted MR imaging was performed using five b values (0-2,500 s/mm(2)). Respective stretched exponential parameters (DDC, distributed diffusion coefficient; and alpha (α), water heterogeneity) were calculated. Patients were stratified into low and high tumour stage groups based on the American Joint Committee on Cancer (AJCC) staging for determination of the predictive powers of DDC and α using t test and ROC curve analyses. The mean ± standard deviation values were DDC = 0.692 ± 0.199 (×10(-3) mm(2)/s) for low stage group vs 0.794 ± 0.253 (×10(-3) mm(2)/s) for high stage group; α = 0.792 ± 0.145 for low stage group vs 0.698 ± 0.155 for high stage group. α was significantly lower in the high stage group while DDC was negatively correlated. DDC and α were both reliable independent predictors (p < 0.001), with α being more powerful. Optimal cut-off values were (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) DDC = 0.692 × 10(-3) mm(2)/s (94.4 %, 64.3 %, 2.64, 0.09), α = 0.720 (72.2 %, 100 %, -, 0.28). The heterogeneity index α is robust and can potentially help in staging and grading prediction in NPC. • Stretched exponential diffusion models can help in tissue characterisation in nasopharyngeal carcinoma • α and distributed diffusion coefficient (DDC) are negatively correlated • α is a robust heterogeneity index marker • α can potentially help in staging and grading prediction.

Motivation and self-efficacy in the context of moderated drinking: global self-report and ecological momentary assessment.

PubMed

Kuerbis, Alexis; Armeli, Stephen; Muench, Frederick; Morgenstern, Jon

2013-12-01

Despite ample research demonstrating the role of motivation and self-efficacy in predicting drinking in the context of abstinence, little research explicitly explores their role in the context of moderation, and none have utilized daily diary methods. The purpose of this study was to (a) explore the concordance between global self-report and daily diary composite measures of motivation and self-efficacy and (b) compare the ability of each in predicting drinking outcomes in the context of a study of brief AUD treatments focused on controlled drinking. Problem drinkers (N = 89) were assessed, provided feedback about their drinking, and randomly assigned to one of three conditions: two brief AUD treatments or a third group asked to change on their own. Global self-report (GSR) measures were administered at baseline and Week 8 (end of treatment). Daily diary composites (DDC) were created from data collected via an Interactive Voice Recording system during the week prior to baseline and the week prior to Week 8. Findings revealed some concordance between GSR and DDC at both baseline and Week 8, indicating the two methods capture some of the same construct; however, their respective relationships to drinking differed. DDC for both baseline and Week 8 significantly predicted Week 8 drinking outcomes, whereas only change in GSR significantly predicted drinking outcomes. Findings suggest that motivation and self-efficacy are important to moderated drinking, and that both GSR and daily diary methods are useful in understanding mechanisms of change in the context of moderation. Daily diary methods may provide significant advantages. Limitations and arenas for future research are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed.

PubMed

Hitchins, Megan P; Bentley, Louise; Monk, David; Beechey, Colin; Peters, Jo; Kelsey, Gavin; Ishino, Fumitoshi; Preece, Michael A; Stanier, Philip; Moore, Gudrun E

2002-12-01

Maternal duplication of human 7p11.2-p13 has been associated with Silver-Russell syndrome (SRS) in two familial cases. GRB10 is the only imprinted gene identified within this region to date. GRB10 demonstrates an intricate tissue- and isoform-specific imprinting profile in humans, with paternal expression in fetal brain and maternal expression of one isoform in skeletal muscle. The mouse homolog is maternally transcribed. The GRB10 protein is a potent growth inhibitor and represents a candidate for SRS, which is characterized by pre- and postnatal growth retardation and a spectrum of additional dysmorphic features. Since imprinted genes tend to be grouped in clusters, we investigated the imprinting status of the dopa-decarboxylase gene (DDC) and the Cordon-bleu gene (COBL) which flank GRB10 within the 7p11.2-p13 SRS duplicated region. Although both genes were found to replicate asynchronously, suggestive of imprinting, SNP expression analyses showed that neither gene was imprinted in multiple human fetal tissues. The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region on proximal Chr 11, were also biallelically expressed in mice with uniparental maternal or paternal inheritance of this region. With the intent of using mouse Grb10 as an imprinted control, biallelic expression was consistently observed in fetal, postnatal, and adult brain of these mice, in contrast to the maternal-specific transcription previously demonstrated in brain in inter-specific F1 progeny. This may be a further example of over-expression of maternally derived transcripts in inter-specific mouse crosses. GRB10 remains the only imprinted gene identified within 7p11.2-p13.

PKC-mediated HuD-GAP43 pathway activation in a mouse model of antiretroviral painful neuropathy.

PubMed

Sanna, M D; Quattrone, A; Ghelardini, C; Galeotti, N

2014-03-01

Patients treated with nucleoside reverse transcriptase inhibitors (NRTIs) develop painful neuropathies that lead to discontinuation of antiretroviral therapy thus limiting viral suppression strategies. The mechanisms by which NRTIs contribute to the development of neuropathy are not known. In order to elucidate the mechanisms underlying this drug-induced neuropathy, we have characterized cellular events in the central nervous system following antiretroviral treatment. Systemic administration of the antiretroviral agent, 2',3'-dideoxycytidine (ddC) considerably increased the expression and phosphorylation of protein kinase C (PKC) γ and ɛ, enzymes highly involved in pain processes, within periaqueductal grey matter (PAG), and, to a lesser extent, within thalamus and prefrontal cortex. These events appeared in coincidence with thermal and mechanical allodynia, but PKC blockade did not prevent the antiretroviral-induced pain hypersensitivity, ruling out a major involvement of PKC in the ddC-induced nociceptive behaviour. An increased expression of GAP43, a marker of neuroregeneration, and decreased levels of ATF3, a marker of neuroregeneration, were detected in all brain areas. ddC treatment also increased the expression of HuD, a RNA-binding protein target of PKC known to stabilize GAP43 mRNA. Pharmacological blockade of PKC prevented HuD and GAP43 overexpression. Silencing of both PKCγ and HuD reduced GAP43 levels in control mice and prevented the ddC-induced GAP43 enhanced expression. Present findings illustrate the presence of a supraspinal PKC-mediated HuD-GAP43 pathway activated by ddC. Based on our results, we speculate that antiretroviral drugs may recruit the HuD-GAP43 pathway, potentially contributing to a response to the antiretroviral neuronal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Directional filtering for block recovery using wavelet features

NASA Astrophysics Data System (ADS)

Hyun, Seung H.; Eom, Il K.; Kim, Yoo S.

2005-07-01

When images compressed with block-based compression techniques are transmitted over a noisy channel, unexpected block losses occur. Conventional methods that do not consider edge directions can cause blocked blurring artifacts. In this paper, we present a post-processing-based block recovery scheme using Haar wavelet features. The adaptive selection of neighboring blocks is performed based on the energy of wavelet subbands (EWS) and difference between DC values (DDC). The lost blocks are recovered by linear interpolation in the spatial domain using selected blocks. The method using only EWS performs well for horizontal and vertical edges, but not as well for diagonal edges. Conversely, only using DDC performs well for diagonal edges with the exception of line- or roof-type edge profiles. Therefore, we combine EWS and DDC for better results. The proposed directional recovery method is effective for the strong edge because exploit the varying neighboring blocks adaptively according to the edges and the directional information in the image. The proposed method outperforms the previous methods that used only fixed blocks.

Stress regime in the Philippine Sea slab beneath Kanto, Japan

NASA Astrophysics Data System (ADS)

Nakajima, Junichi; Hasegawa, Akira; Hirose, Fuyuki

2011-08-01

We determine the focal mechanisms of earthquakes within the Philippine Sea slab beneath the Tokyo metropolitan area, and perform stress tensor inversions to investigate the detailed stress field within the slab. The results show a characteristic spatial variation in earthquake-generating stress. Slab stress in northeastern part of the PHS slab is characterized by down-dip tension (DDT), except for the uppermost tip of the seismic portion of the slab where down-dip compression (DDC) stress is dominant. We interpret that DDT is caused by the net slab pull and DDC is attributable to local resistance to subduction at the tip of the slab. In southwestern part of the PHS slab, σ1 and σ3 are generally rotated oblique to the dip of the slab, suggesting that earthquakes occur under stress conditions of neither DDC nor DDT. The rotations in σ1 and σ3 may be related to stress accumulation by the slip deficit along the asperity of the 1923 Kanto earthquake (M7.9).

Modeling and characterization of as-welded microstructure of solid solution strengthened Ni-Cr-Fe alloys resistant to ductility-dip cracking Part II: Microstructure characterization

NASA Astrophysics Data System (ADS)

Unfried-Silgado, Jimy; Ramirez, Antonio J.

2014-03-01

In part II of this work is evaluated the as-welded microstructure of Ni-Cr-Fe alloys, which were selected and modeled in part I. Detailed characterization of primary and secondary precipitates, subgrain and grain structures, partitioning, and grain boundary morphology were developed. Microstructural characterization was carried out using optical microscopy, SEM, TEM, EBSD, and XEDS techniques. These results were analyzed and compared to modeling results displaying a good agreement. The Hf additions produced the highest waviness of grain boundaries, which were related to distribution of Hf-rich carbonitrides. Experimental evidences about Mo distribution into crystal lattice have provided information about its possible role in ductility-dip cracking (DDC). Characterization results of studied alloys were analyzed and linked to their DDC resistance data aiming to establish relationships between as-welded microstructure and hot deformation performance. Wavy grain boundaries, primary carbides distribution, and strengthened crystal lattice are metallurgical characteristics related to high DDC resistance.

The DOPA decarboxylase (DDC) gene is associated with alerting attention.

PubMed

Zhu, Bi; Chen, Chuansheng; Moyzis, Robert K; Dong, Qi; Chen, Chunhui; He, Qinghua; Li, Jin; Li, Jun; Lei, Xuemei; Lin, Chongde

2013-06-03

DOPA decarboxylase (DDC) is involved in the synthesis of dopamine, norepinephrine and serotonin. It has been suggested that genes involved in the dopamine, norepinephrine, and cholinergic systems play an essential role in the efficiency of human attention networks. Attention refers to the cognitive process of obtaining and maintaining the alert state, orienting to sensory events, and regulating the conflicts of thoughts and behavior. The present study tested seven single nucleotide polymorphisms (SNPs) within the DDC gene for association with attention, which was assessed by the Attention Network Test to detect three networks of attention, including alerting, orienting, and executive attention, in a healthy Han Chinese sample (N=451). Association analysis for individual SNPs indicated that four of the seven SNPs (rs3887825, rs7786398, rs10499695, and rs6969081) were significantly associated with alerting attention. Haplotype-based association analysis revealed that alerting was associated with the haplotype G-A-T for SNPs rs7786398-rs10499695-rs6969081. These associations remained significant after correcting for multiple testing by max(T) permutation. No association was found for orienting and executive attention. This study provides the first evidence for the involvement of the DDC gene in alerting attention. A better understanding of the genetic basis of distinct attention networks would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped alerting attention as well as its related prevalent neuropsychiatric disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Quantum phase transitions in the S=(1)/(2) distorted diamond chain

NASA Astrophysics Data System (ADS)

Li, Yan-Chao; Li, Shu-Shen

2008-11-01

By means of the second derivative of the ground-state and first-excited energy, the quantum phase transitions (QPTs) for the distorted diamond chain (DDC) with ferromagnetic and antiferromagnetic frustrated interactions and the trimerized case are investigated, respectively. Our results show the plentiful quantum phases owing to the spin interaction competitions in the model. Meanwhile, by using the transfer-matrix renormalization-group technique, we study the two-site thermal entanglement of the DDC model in the thermodynamic limit for a further understanding of the QPTs.

Inducing mutations through γ-irradiation in seeds of Mucuna pruriens for developing high L-DOPA-yielding genotypes.

PubMed

Singh, Susheel Kumar; Yadav, Deepti; Lal, Raj Kishori; Gupta, Madan M; Dhawan, Sunita Singh

2017-04-01

To develop elite genotypes in Mucuna pruriens (L.) DC with high L-DOPA (L-3, 4 dihydroxyphenylalanine) yields, with non-itching characteristics and better adaptability by applying γ-irradiation. Molecular and chemical analysis was performed for screening based on specific characteristics desired for developing suitable genotypes. Developed, mutant populations were analyzed for L-DOPA % in seeds through TLC (thin layer chromatography), and the results obtained were validated with the HPLC (High performance liquid chromatography). The DNA (Deoxyribonucleic acid) was isolated from the leaf at the initial stage and used for DNA polymorphism. RNA (Ribonucleic acid) was isolated from the leaf during maturity and used for expression analysis. The selected mutant T-I-7 showed 5.7% L-DOPA content compared to 3.18% of parent CIM-Ajar. The total polymorphism obtained was 57% with the molecular marker analysis. The gene expression analysis showed higher fold change expression of the dopadecarboxylase gene (DDC) in control compared to selected mutants (T-I-7, T-II-23, T-IV-9, T-VI-1). DNA polymorphism was used for the screening of mutants for efficient screening at an early stage. TLC was found suitable for the large-scale comparative chemical analysis of L-DOPA. The expression profile of DDC clearly demonstrated the higher yields of L-DOPA in selected mutants developed by γ-irradiation in the seeds of the control.

Breast lesion characterization using whole-lesion histogram analysis with stretched-exponential diffusion model.

PubMed

Liu, Chunling; Wang, Kun; Li, Xiaodan; Zhang, Jine; Ding, Jie; Spuhler, Karl; Duong, Timothy; Liang, Changhong; Huang, Chuan

2018-06-01

Diffusion-weighted imaging (DWI) has been studied in breast imaging and can provide more information about diffusion, perfusion and other physiological interests than standard pulse sequences. The stretched-exponential model has previously been shown to be more reliable than conventional DWI techniques, but different diagnostic sensitivities were found from study to study. This work investigated the characteristics of whole-lesion histogram parameters derived from the stretched-exponential diffusion model for benign and malignant breast lesions, compared them with conventional apparent diffusion coefficient (ADC), and further determined which histogram metrics can be best used to differentiate malignant from benign lesions. This was a prospective study. Seventy females were included in the study. Multi-b value DWI was performed on a 1.5T scanner. Histogram parameters of whole lesions for distributed diffusion coefficient (DDC), heterogeneity index (α), and ADC were calculated by two radiologists and compared among benign lesions, ductal carcinoma in situ (DCIS), and invasive carcinoma confirmed by pathology. Nonparametric tests were performed for comparisons among invasive carcinoma, DCIS, and benign lesions. Comparisons of receiver operating characteristic (ROC) curves were performed to show the ability to discriminate malignant from benign lesions. The majority of histogram parameters (mean/min/max, skewness/kurtosis, 10-90 th percentile values) from DDC, α, and ADC were significantly different among invasive carcinoma, DCIS, and benign lesions. DDC 10% (area under curve [AUC] = 0.931), ADC 10% (AUC = 0.893), and α mean (AUC = 0.787) were found to be the best metrics in differentiating benign from malignant tumors among all histogram parameters derived from ADC and α, respectively. The combination of DDC 10% and α mean , using logistic regression, yielded the highest sensitivity (90.2%) and specificity (95.5%). DDC 10% and α mean derived from the stretched-exponential model provides more information and better diagnostic performance in differentiating malignancy from benign lesions than ADC parameters derived from a monoexponential model. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1701-1710. © 2017 International Society for Magnetic Resonance in Medicine.

Demountable damped cavity for HOM-damping in ILC superconducting accelerating cavities

NASA Astrophysics Data System (ADS)

Konomi, T.; Yasuda, F.; Furuta, F.; Saito, K.

2014-01-01

We have designed a new higher-order-mode (HOM) damper called a demountable damped cavity (DDC) as part of the R&D efforts for the superconducting cavity of the International Linear Collider (ILC). The DDC has two design concepts. The first is an axially symmetrical layout to obtain high damping efficiency. The DDC has a coaxial structure along the beam axis to realize strong coupling with HOMs. HOMs are damped by an RF absorber at the end of the coaxial waveguide and the accelerating mode is reflected by a choke filter mounted at the entrance of the coaxial waveguide. The second design concept is a demountable structure to facilitate cleaning, in order to suppress the Q-slope problem in a high field. A single-cell cavity with the DDC was fabricated to test four performance parameters. The first was frequency matching between the accelerating cavity and the choke filter. Since the bandwidth of the resonance frequency in a superconducting cavity is very narrow, there is a possibility that the accelerating field will leak to the RF absorber because of thermal shrinkage. The design bandwidth of the choke filter is 25 kHz. It was demonstrated that frequency matching adjusted at room temperature could be successfully maintained at 2 K. The second parameter was the performance of the demountable structure. At the joint, the magnetic field is 1/6 of the maximum field in the accelerating cavity. Ultimately, the accelerating field reached 19 MV/m and Q0 was 1.5×1010 with a knife-edge shape. The third parameter was field emission and multipacting. Although the choke structure has numerous parallel surfaces that are susceptible to the multipacting problem, it was found that neither field emission nor multipacting presented problems in both an experiment and simulation. The final parameter was the Q values of the HOM. The RF absorber adopted in the system is a Ni-Zn ferrite type. The RF absorber shape was designed based on the measurement data of permittivity and permeability at 77 K. The Q values of the HOM in the DDC are 10-100 times lower than those of a TESLA-type HOM coupler.

Fibroblast Growth Factor signaling regulates the expansion of A6-expressing hepatocytes in association with AKT-dependent β-catenin activation

PubMed Central

Utley, Sarah; James, David; Mavila, Nirmala; Nguyen, Marie V.; Vendryes, Christopher; Salisbury, S. Michael; Phan, Jennifer; Wang, Kasper S.

2014-01-01

Background & Aims Fibroblast Growth Factors (FGFs) promote the proliferation and survival of hepatic progenitor cells (HPCs) via AKT-dependent β-catenin activation. Moreover, the emergence of hepatocytes expressing the HPC marker A6 during 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury is mediated partly by FGF and β-catenin signaling. Herein, we investigate the role of FGF signaling and AKT-mediated β-catenin activation in acute DDC liver injury. Methods Transgenic mice were fed DDC chow for 14 days concurrent with either Fgf10 over-expression or inhibition of FGF signaling via expression of soluble dominant-negative FGF Receptor (R)-2IIIb. Results After 14 days of DDC treatment, there was an increase in periportal cells expressing FGFR1, FGFR2, and AKT-activated phospho-Serine 552 (pSer552) β-CATENIN in association with up-regulation of genes encoding FGFR2IIIb ligands, Fgf7, Fgf10, and Fgf22. In response to Fgf10 over-expression, there was an increase in the number of pSer552-β-CATENIN(positive)+ive periportal cells as well as cells co-positive for A6 and hepatocyte marker, Hepatocyte Nuclear Factor-4α (HNF4α). A similar expansion of A6+ive cells was observed after Fgf10 over-expression with regular chow and after partial hepatectomy during ethanol toxicity. Inhibition of FGF signaling increased the periportal A6+iveHNF4α+ive cell population while reducing centrolobular A6+ive HNF4α+ive cells. AKT inhibition with Wortmannin attenuated FGF10-mediated A6+iveHNF4α+ive cell expansion. In vitro analyses using FGF10 treated HepG2 cells demonstrated AKT-mediated β-CATENIN activation but not enhanced cell migration. Conclusion During acute DDC treatment, FGF signaling promotes the expansion of A6-expressing liver cells partly via AKT-dependent activation of β-CATENIN expansion of A6+ive periportal cells and possibly by reprogramming of centrolobular hepatocytes. PMID:24365171

Nonlinear interface between the piezoelectric harvesting structure and the modulating circuit of an energy harvester with a real storage battery.

PubMed

Hu, Yuantai; Xue, Huan; Hu, Ting; Hu, Hongping

2008-01-01

This paper studies the performance of an energy harvester with a piezoelectric bimorph (PB) and a real electrochemical battery (ECB), both are connected as an integrated system through a rectified dc-dc converter (DDC). A vibrating PB can scavenge energy from the operating environment by the electromechanical coupling. A DDC can effectively match the optimal output voltage of the harvesting structure to the battery voltage. To raise the output power density of PB, a synchronized switch harvesting inductor (SSHI) is used in parallel with the harvesting structure to reverse the voltage through charge transfer between the output electrodes at the transition moments from closed-to open-circuit. Voltage reversal results in earlier arrival of rectifier conduction because the output voltage phases of any two adjacent closed-circuit states are just opposite each other. In principle, a PB is with a smaller, flexural stiffness under closed-circuit condition than under open-circuit condition. Thus, the PB subjected to longer closed-circuit condition will be easier to be accelerated. A larger flexural velocity makes the PB to deflect with larger amplitude, which implies that more mechanical energy will be converted into an electric one. Nonlinear interface between the vibrating PB and the modulating circuit is analyzed in detail, and the effects of SSHI and DDC on the charging efficiency of the storage battery are researched numerically. It was found that the introduction of a DDC in the modulating circuit and an SSHI in the harvesting structure can raise the charging efficiency by several times.

Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a

PubMed Central

Wu, Hsuan-Hui; Chen, Meng-Chun; Liu, Wen-Huan; Wu, Wu-Hsiung; Chang, Peter Mu-Hsin; Huang, Chi-Ying F.; Tsou, Ann-Ping; Shiao, Ming-Shi

2017-01-01

The liver is a vital organ involving in various major metabolic functions in human body. MicroRNA-122 (miR-122) plays an important role in the regulation of liver metabolism, but its intrinsic physiological functions require further clarification. This study integrated the genome-scale metabolic model of hepatocytes and mouse experimental data with germline deletion of Mir122a (Mir122a–/–) to infer Warburg-like effects. Elevated expression of MiR-122a target genes in Mir122a–/–mice, especially those encoding for metabolic enzymes, was applied to analyze the flux distributions of the genome-scale metabolic model in normal and deficient states. By definition of the similarity ratio, we compared the flux fold change of the genome-scale metabolic model computational results and metabolomic profiling data measured through a liquid-chromatography with mass spectrometer, respectively, for hepatocytes of 2-month-old mice in normal and deficient states. The Ddc gene demonstrated the highest similarity ratio of 95% to the biological hypothesis of the Warburg effect, and similarity of 75% to the experimental observation. We also used 2, 6, and 11 months of mir-122 knockout mice liver cell to examined the expression pattern of DDC in the knockout mice livers to show upregulated profiles of DDC from the data. Furthermore, through a bioinformatics (LINCS program) prediction, BTK inhibitors and withaferin A could downregulate DDC expression, suggesting that such drugs could potentially alter the early events of metabolomics of liver cancer cells. PMID:28686599

Emergencies planning and response: Coupling an exposure model with different atmospheric dispersion models

NASA Astrophysics Data System (ADS)

Sanchez, E. Y.; Colman Lerner, J. E.; Porta, A.; Jacovkis, P. M.

2013-11-01

Information on spatial and time dependent concentration patterns of hazardous substances, as well as on the potential effects on population, is necessary to assist in chemical emergency planning and response. To that end, some models predict transport and dispersion of hazardous substances, and others estimate potential effects upon exposed population. Taken together, both groups constitute a powerful tool to estimate vulnerable regions and to evaluate environmental impact upon affected populations. The development of methodologies and models with direct application to the context in which we live allows us to draft a more clear representation of the risk scenario and, hence, to obtain the adequate tools for an optimal response. By means of the recently developed DDC (Damage Differential Coupling) exposure model, it was possible to optimize, from both the qualitative and the quantitative points of view, the estimation of the population affected by a toxic cloud, because the DDC model has a very good capacity to couple with different atmospheric dispersion models able to provide data over time. In this way, DDC analyzes the different concentration profiles (output from the transport model) associating them with some reference concentration to identify risk zones. In this work we present a disaster scenario in Chicago (USA), by coupling DDC with two transport models of different complexity, showing the close relationship between a representative result and the run time of the models. In the same way, it becomes evident that knowing the time evolution of the toxic cloud and of the affected regions significantly improves the probability of taking the correct decisions on planning and response facing the emergency.

S-Adenosylmethionine Prevents Mallory Denk Body Formation in Drug-Primed Mice by Inhibiting the Epigenetic Memory

PubMed Central

Li, Jun; Bardag-Gorce, Fawzia; Dedes, Jennifer; French, Barbara Alan; Amidi, Fataneh; Oliva, Joan; French, Samuel William

2010-01-01

In previous studies, microarray analysis of livers from mice fed diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridine decarboxylate (DDC) for 10 weeks followed by 1 month of drug withdrawal (drug-primed mice) and then 7 days of drug refeeding showed an increase in the expression of numerous genes referred to here as the molecular cellular memory. This memory predisposes the liver to Mallory Denk body formation in response to drug refeeding. In the current study, drug-primed mice were refed DDC with or without a daily dose of S-adenosylmethionine (SAMe; 4 g/kg of body weight). The livers were studied for evidence of oxidative stress and changes in gene expression with microarray analysis. SAMe prevented Mallory Denk body formation in vivo. The molecular cellular memory induced by DDC refeeding lasted for 4 months after drug withdrawal and was not manifest when SAMe was added to the diet in the in vivo experiment. Liver cells from drug-primed mice spontaneously formed Mallory Denk bodies in primary tissue cultures. SAMe prevented Mallory Denk bodies when it was added to the culture medium. Conclusion SAMe treatment prevented Mallory Denk body formation in vivo and in vitro by preventing the expression of a molecular cellular memory induced by prior DDC feeding. No evidence for the involvement of oxidative stress in induction of the memory was found. The molecular memory included the up-regulation of the expression of genes associated with the development of liver cell preneoplasia. PMID:18098314

Effect of disease progression on liver apparent diffusion coefficient and T2 values in a murine model of hepatic fibrosis at 11.7 Tesla MRI.

PubMed

Anderson, Stephan W; Jara, Hernan; Ozonoff, Al; O'Brien, Michael; Hamilton, James A; Soto, Jorge A

2012-01-01

To evaluate the effects of hepatic fibrosis on ADC and T(2) values of ex vivo murine liver specimens imaged using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male, C57BL/6 mice were divided into control (n = 2) and experimental groups (n = 15), the latter fed a 3, 5-dicarbethoxy-1, 4-dihydrocollidine (DDC) supplemented diet, inducing hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7T MRI scanner. Spin-echo pulsed field gradient and multi-echo spin-echo acquisitions were used to generate parametric ADC and T(2) maps, respectively. Degrees of fibrosis were determined by the evaluation of a pathologist as well as digital image analysis. Scatterplot graphs comparing ADC and T(2) to degrees of fibrosis were generated and correlation coefficients were calculated. Strong correlation was found between degrees of hepatic fibrosis and ADC with higher degrees of fibrosis associated with lower hepatic ADC values. Moderate correlation between hepatic fibrosis and T(2) values was seen with higher degrees of fibrosis associated with lower T(2) values. Inverse relationships between degrees of fibrosis and both ADC and T(2) are seen, highlighting the utility of these parameters in the ongoing development of an MRI methodology to quantify hepatic fibrosis. Copyright © 2011 Wiley Periodicals, Inc.

Classification Management. Journal. Volume X - 1974. Papers from the National Seminar (10th), 16-17-18 July 1974

DTIC Science & Technology

1974-01-01

bigi share oft the credit coming to film , because converted yet,* but it’s being atdopted and pot we senit him raw people ovter there. Hvi’ sat them...belongs in DDC we’d like you to confirm i,: in writing to us. When DDC receives documents, those documents are microfiched. That is, we put them on film ...you have a long reel of film and perhaps only of classified material in the hands of industry. certain things within that were declassified or It says

Low Emissions Aftertreatment and Diesel Emissions Reduction

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

None

2005-05-27

Detroit Diesel Corporation (DDC) has successfully completed a five-year Low Emissions Aftertreatment and Diesel Emissions Reduction (LEADER) program under a DOE project entitled: ''Research and Development for Compression-Ignition Direct-Injection Engines (CIDI) and Aftertreatment Sub-Systems''. The objectives of the LEADER Program were to: Demonstrate technologies that will achieve future federal Tier 2 emissions targets; and Demonstrate production-viable technical targets for engine out emissions, efficiency, power density, noise, durability, production cost, aftertreatment volume and weight. These objectives were successfully met during the course of the LEADER program The most noteworthy achievements in this program are listed below: (1) Demonstrated Tier 2 Binmore » 3 emissions target over the FTP75 cycle on a PNGV-mule Neon passenger car, utilizing a CSF + SCR system These aggressive emissions were obtained with no ammonia (NH{sub 3}) slip and a combined fuel economy of 63 miles per gallon, integrating FTP75 and highway fuel economy transient cycle test results. Demonstrated feasibility to achieve Tier 2 Bin 8 emissions levels without active NOx aftertreatment. (2) Demonstrated Tier 2 Bin 3 emissions target over the FTP75 cycle on a light-duty truck utilizing a CSF + SCR system, synergizing efforts with the DOE-DDC DELTA program. This aggressive reduction in tailpipe out emissions was achieved with no ammonia slip and a 41% fuel economy improvement, compared to the equivalent gasoline engine-equipped vehicle. (3) Demonstrated Tier 2 near-Bin 9 emissions compliance on a light-duty truck, without active NOx aftertreatment devices, in synergy with the DOE-DDC DELTA program. (4) Developed and applied advanced combustion technologies such as ''CLEAN Combustion{copyright}'', which yields simultaneous reduction in engine out NOx and PM emissions while also improving engine and aftertreatment integration by providing favorable exhaust species and temperature characteristics. These favorable emissions characteristics were obtained while maintaining performance and fuel economy. These aggressive emissions and performance results were achieved by applying a robust systems technology development methodology. This systems approach benefits substantially from an integrated experimental and analytical approach to technology development, which is one of DDCs core competencies Also, DDC is uniquely positioned to undertake such a systems technology development approach, given its vertically integrated commercial structure within the DaimlerChrysler organization. State-of-the-art analytical tools were developed targeting specific LEADER program objectives and were applied to guide system enhancements and to provide testing directions, resulting in a shortened and efficient development cycle. Application examples include ammonia/NO{sub x} distribution improvement and urea injection controls development, and were key contributors to significantly reduce engine out as well as tailpipe out emissions. Successful cooperation between DDC and Engelhard Corporation, the major subcontractor for the LEADER program and provider of state-of-the-art technologies on various catalysts, was another contributing factor to ensure that both passenger car and LD truck applications achieved Tier 2 Bin 3 emissions levels. Significant technical challenges, which highlight barriers of commercialization of diesel technology for passenger cars and LD truck applications, are presented at the end of this report.« less

Model-free adaptive speed control on travelling wave ultrasonic motor

NASA Astrophysics Data System (ADS)

Di, Sisi; Li, Huafeng

2018-01-01

This paper introduced a new data-driven control (DDC) method for the speed control of ultrasonic motor (USM). The model-free adaptive control (MFAC) strategy was presented in terms of its principles, algorithms, and parameter selection. To verify the efficiency of the proposed method, a speed-frequency-time model, which contained all the measurable nonlinearity and uncertainties based on experimental data was established for simulation to mimic the USM operation system. Furthermore, the model was identified using particle swarm optimization (PSO) method. Then, the control of the simulated system using MFAC was evaluated under different expectations in terms of overshoot, rise time and steady-state error. Finally, the MFAC results were compared with that of proportion iteration differentiation (PID) to demonstrate its advantages in controlling general random system.

Comparison between types I and II epithelial ovarian cancer using histogram analysis of monoexponential, biexponential, and stretched-exponential diffusion models.

PubMed

Wang, Feng; Wang, Yuxiang; Zhou, Yan; Liu, Congrong; Xie, Lizhi; Zhou, Zhenyu; Liang, Dong; Shen, Yang; Yao, Zhihang; Liu, Jianyu

2017-12-01

To evaluate the utility of histogram analysis of monoexponential, biexponential, and stretched-exponential models to a dualistic model of epithelial ovarian cancer (EOC). Fifty-two patients with histopathologically proven EOC underwent preoperative magnetic resonance imaging (MRI) (including diffusion-weighted imaging [DWI] with 11 b-values) using a 3.0T system and were divided into two groups: types I and II. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), distributed diffusion coefficient (DDC), and intravoxel water diffusion heterogeneity (α) histograms were obtained based on solid components of the entire tumor. The following metrics of each histogram were compared between two types: 1) mean; 2) median; 3) 10th percentile and 90th percentile. Conventional MRI morphological features were also recorded. Significant morphological features for predicting EOC type were maximum diameter (P = 0.007), texture of lesion (P = 0.001), and peritoneal implants (P = 0.001). For ADC, D, f, DDC, and α, all metrics were significantly lower in type II than type I (P < 0.05). Mean, median, 10th, and 90th percentile of D* were not significantly different (P = 0.336, 0.154, 0.779, and 0.203, respectively). Most histogram metrics of ADC, D, and DDC had significantly higher area under the receiver operating characteristic curve values than those of f and α (P < 0.05) CONCLUSION: It is feasible to grade EOC by morphological features and three models with histogram analysis. ADC, D, and DDC have better performance than f and α; f and α may provide additional information. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1797-1809. © 2017 International Society for Magnetic Resonance in Medicine.

Characterization of double diffusive convection step and heat budget in the deep Arctic Ocean

NASA Astrophysics Data System (ADS)

Zhou, S.; Lu, Y.

2013-12-01

In this paper, we explore the hydrographic structure and heat budget in deep Canada Basin using data measured with McLane-Moored-Profilers (MMPs), bottom-pressure-recorders (BPRs), and conductivity-temperature-depth (CTD) profilers. From the bottom upward, a homogenous bottom layer and its overlaying double diffusive convection (DDC) steps are well identified at Mooring A (75oN, 150oW). We find that the deep water is in weak diapycnal mixing because the effective diffusivity of the bottom layer is ~1.8×10-5 m 2s-1 while that of the other steps is ~10-6 m 2s-1. The vertical heat flux through DDC steps is evaluated with different methods. We find that the heat flux (0.1-11 mWm-2) is much smaller than geothermal heating (~50 mWm-2), which suggests that the stack of DDC steps acts as a thermal barrier in the deep basin. Moreover, the temporal distributions of temperature and salinity differences across the interface are exponential, while those of heat flux and effective diffusivity are found to be approximately log-normal. Both are the result of strong intermittency. Between 2003 and 2011, temperature fluctuation close to the sea floor distributed asymmetrically and skewed towards positive values, which provides direct indication that geothermal heating is transferred into ocean. Both BPR and CTD data suggest that geothermal heating, not the warming of upper ocean, is the dominant mechanism responsible for the warming of deep water. As the DDC steps prevent the vertical heat transfer, geothermal heating will be unlikely to have significant effect on the middle and upper oceans.

Sry HMG Box Protein 9-positive (Sox9+) Epithelial Cell Adhesion Molecule-negative (EpCAM−) Biphenotypic Cells Derived from Hepatocytes Are Involved in Mouse Liver Regeneration*

PubMed Central

Tanimizu, Naoki; Nishikawa, Yuji; Ichinohe, Norihisa; Akiyama, Haruhiko; Mitaka, Toshihiro

2014-01-01

It has been shown that mature hepatocytes compensate tissue damages not only by proliferation and/or hypertrophy but also by conversion into cholangiocyte-like cells. We found that Sry HMG box protein 9-positive (Sox9+) epithelial cell adhesion molecule-negative (EpCAM−) hepatocyte nuclear factor 4α-positive (HNF4α+) biphenotypic cells showing hepatocytic morphology appeared near EpCAM+ ductular structures in the livers of mice fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing diet. When Mx1-Cre:ROSA mice, which were injected with poly(I:C) to label mature hepatocytes, were fed with the DDC diet, we found LacZ+Sox9+ cells near ductular structures. Although Sox9+EpCAM− cells adjacent to expanding ducts likely further converted into ductular cells, the incidence was rare. To know the cellular characteristics of Sox9+EpCAM− cells, we isolated them as GFP+EpCAM− cells from DDC-injured livers of Sox9-EGFP mice. Sox9+EpCAM− cells proliferated and could differentiate to functional hepatocytes in vitro. In addition, Sox9+EpCAM− cells formed cysts with a small central lumen in collagen gels containing Matrigel® without expressing EpCAM. These results suggest that Sox9+EpCAM− cells maintaining biphenotypic status can establish cholangiocyte-type polarity. Interestingly, we found that some of the Sox9+ cells surrounded luminal spaces in DDC-injured liver while they expressed HNF4α. Taken together, we consider that in addition to converting to cholangiocyte-like cells, Sox9+EpCAM− cells provide luminal space near expanded ductular structures to prevent deterioration of the injuries and potentially supply new hepatocytes to repair damaged tissues. PMID:24482234

Characterization of double diffusive convection steps and heat budget in the deep Arctic Ocean

NASA Astrophysics Data System (ADS)

Zhou, Sheng-Qi; Lu, Yuan-Zheng

2013-12-01

In this paper, we explore the hydrographic structure and heat budget in the deep Canada Basin by using data measured with McLane-Moored-Profilers (MMP), bottom pressure recorders (BPR), and conductivity-temperature-depth (CTD) profilers. Upward from the bottom, a homogeneous bottom layer and its overlaying double diffusive convection (DDC) steps are well identified at Mooring A (75°N,150°W). We find that the deep water is in weak diapycnal mixing because the effective diffusivity of the bottom layer is ˜1.8 × 10-5 m2s-1, while that of the other steps is ˜10-6 m2s-1. The vertical heat flux through the DDC steps is evaluated by using different methods. We find that the heat flux (0.1-11 mWm -2) is much smaller than geothermal heating (˜50 mWm -2). This suggests that the stack of DDC steps acts as a thermal barrier in the deep basin. Moreover, the temporal distributions of temperature and salinity differences across the interface are exponential, whereas those of heat flux and effective diffusivity are found to be approximately lognormal. Both are the result of strong intermittency. Between 2003 and 2011, temperature fluctuations close to the sea floor were distributed asymmetrically and skewed toward positive values, which provide a direct observation that geothermal heating was transferred into the ocean. Both BPR and CTD data suggest that geothermal heating and not the warming of the upper ocean is the dominant mechanism responsible for the warming of deep water. As the DDC steps prevent vertical heat transfer, geothermal heating is unlikely to have a significant effect on the middle and upper Arctic Ocean.

Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy.

PubMed

Jemail, Leila; Miyao, Masashi; Kotani, Hirokazu; Kawai, Chihiro; Minami, Hirozo; Abiru, Hitoshi; Tamaki, Keiji

2018-04-23

Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.

In vivo reflectance-mode confocal microscopy assessments: impact of overweight on human skin microcirculation and histomorphology

NASA Astrophysics Data System (ADS)

Altintas, Ahmet A.; Aust, Matthias C.; Krämer, Robert; Vogt, Peter M.; Altintas, Mehmet A.

2016-03-01

Reflectance-mode confocal microscopy (RCM) enables in vivo assessment of the human skin. Impact of overweight on both human skin microcirculation and histomorphology has not been investigated in vivo. The purpose of this study is to evaluate both microcirculation and histomorphology in vivo in overweight. In 10 normotensive overweight nondiabetic individuals (OW-group, BMI 29.1±2.7 kg/m2) and 10 age- and sex-matched healthy lean controls (CO-group, BMI 20.4±1.9 kg/m2) the following parameters were evaluated using RCM: dermal blood cell flow (DBCF), density of dermal capillaries (DDC), epidermal thickness (ET), and epidermal cell size (ECS). DBCF was counted at 63.11±4.14 cells/min in OW-group and at 51.06±3.84 cells/min in CO-group (P<0.05). DDC was reduced in OW-group (4.91±0.39 capillaries/mm2) compared to the controls (6.02±0.64 capillaries/mm2, P<0.05). Histometric evaluation of ET reveals thickening in OW-group compared to the CO-group (54.79±4.25 μm versus 44.03±3.11 μm, P<0.05). ECS differed significantly (P<0.05) in OW-group (821.3±42.02 μm2) compared to the controls (772.6±34.79 μm2). Inverse correlation of dermal capillary density and overweight point to reduced total tissue perfusion while positive related blood cell flow reveals vasodilatation. Increase of both ET and cell size indicates remodeling of cutaneous histomorphology, maybe as an early stage of adiposity-related skin condition.

Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway.

PubMed

Nakada, Daisuke; Hirano, Yukinori; Sugimoto, Katsunori

2004-11-01

The large protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate DNA damage checkpoint pathways. In budding yeast, ATM and ATR homologs are encoded by TEL1 and MEC1, respectively. The Mre11 complex consists of two highly related proteins, Mre11 and Rad50, and a third protein, Xrs2 in budding yeast or Nbs1 in mammals. The Mre11 complex controls the ATM/Tel1 signaling pathway in response to double-strand break (DSB) induction. We show here that the Mre11 complex functions together with exonuclease 1 (Exo1) in activation of the Mec1 signaling pathway after DNA damage and replication block. Mec1 controls the checkpoint responses following UV irradiation as well as DSB induction. Correspondingly, the Mre11 complex and Exo1 play an overlapping role in activation of DSB- and UV-induced checkpoints. The Mre11 complex and Exo1 collaborate in producing long single-stranded DNA (ssDNA) tails at DSB ends and promote Mec1 association with the DSBs. The Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway. However, Ddc1 association with DSBs does not require the function of the Mre11 complex and Exo1. Mec1 controls checkpoint responses to stalled DNA replication as well. Accordingly, the Mre11 complex and Exo1 contribute to activation of the replication checkpoint pathway. Our results provide a model in which the Mre11 complex and Exo1 cooperate in generating long ssDNA tracts and thereby facilitate Mec1 association with sites of DNA damage or replication block.

Design of Sounding Rocket Payloads

DTIC Science & Technology

1976-06-01

AUOHtSS Northeastern University Electromcs Researcn Laboratory Boston, Massachusetts 02115 II. CONTROLLING OFFICE NAMr »NOAOORtSS Air Force...D I JAN 71 1473 EDITION Or I NOV (S IS OBSOLETE Unclassified j-’K. SECURITY CLASSIFICATION OF THIS RAGE (»»>«<iO«IA KnltioJ) i yj7...ACC:SSION (or IfTIS \\\\ ’l PJ;’ ’.’, DDC D.i r UNAHNri::cr3 JUSTKi^lTUN & p^lflreu’lü.’ ■.•;,!5--Mry f/^s . fist. K ,,, ■ ,;, , aiAiT

’Exact’ Two-Sided Confidence Intervals on Nonnegative Linear Combinations of Variances.

DTIC Science & Technology

1980-07-01

Colorado State University ( 042_402) II. CONTrOLLING OFFICE NAME AND ADDRESS It. REPORT OAT Office of Naval Rsearch -// 1 Jul MjW80 Statistics and...MONNEGATIVE LINEAR COMBINATIONS OF VARIANCES by Franklin A. Graybill Colorado State University and Chih-Ming Wang SPSS Inc. 1. Introduction In a paper to soon...1 + a2’ called the Nodf Led Lace Sample (HLS) confidence interval, is in 2. Aoce-3Ion For DDC TAO u*.- *- -. n c edI Ju.-’I if iction_, i !~BV . . I

Dipolar DC Collisional Activation in a "Stretched" 3-D Ion Trap: The Effect of Higher Order Fields on rf-Heating

NASA Astrophysics Data System (ADS)

Prentice, Boone M.; McLuckey, Scott A.

2012-04-01

Applying dipolar DC (DDC) to the end-cap electrodes of a 3-D ion trap operated with a bath gas at roughly 1 mTorr gives rise to `rf-heating' and can result in collision-induced dissociation (CID). This approach to ion trap CID differs from the conventional single-frequency resonance excitation approach in that it does not rely on tuning a supplementary frequency to coincide with the fundamental secular frequeny of the precursor ion of interest. Simulations using the program ITSIM 5.0 indicate that application of DDC physically displaces ions solely in the axial (inter end-cap) dimension whereupon ion acceleration occurs via power absorption from the drive rf. Experimental data shows that the degree of rf-heating in a stretched 3-D ion trap is not dependent solely on the ratio of the dipolar DC voltage/radio frequency (rf) amplitude, as a model based on a pure quadrupole field suggests. Rather, ion temperatures are shown to increase as the absolute values of the dipolar DC and rf amplitude both decrease. Simulations indicate that the presence of higher order multi-pole fields underlies this unexpected behavior. These findings have important implications for the use of DDC as a broad-band activation approach in multi-pole traps.

Skin-Resident T Cells Drive Dermal Dendritic Cell Migration in Response to Tissue Self-Antigen.

PubMed

Ali, Niwa; Zirak, Bahar; Truong, Hong-An; Maurano, Megan M; Gratz, Iris K; Abbas, Abul K; Rosenblum, Michael D

2018-05-01

Migratory dendritic cell (DC) subsets deliver tissue Ags to draining lymph nodes (DLNs) to either initiate or inhibit T cell-mediated immune responses. The signals mediating DC migration in response to tissue self-antigen are largely unknown. Using a mouse model of inducible skin-specific self-antigen expression, we demonstrate that CD103 + dermal DCs (DDCs) rapidly migrate from skin to skin DLN (SDLNs) within the first 48 h after Ag expression. This window of time was characterized by the preferential activation of tissue-resident Ag-specific effector T cells (Teffs), with no concurrent activation of Ag-specific Teffs in SDLNs. Using genetic deletion and adoptive transfer approaches, we show that activation of skin-resident Teffs is required to drive CD103 + DDC migration in response to tissue self-antigen and this Batf3-dependent DC population is necessary to mount a fulminant autoimmune response in skin. Conversely, activation of Ag-specific Teffs in SDLNs played no role in DDC migration. Our studies reveal a crucial role for skin-resident T cell-derived signals, originating at the site of self-antigen expression, to drive DDC migration during the elicitation phase of an autoimmune response. Copyright © 2018 by The American Association of Immunologists, Inc.

Olfactory cytochrome P-450. Studies with suicide substrates of the haemoprotein.

PubMed Central

Reed, C J; Lock, E A; De Matteis, F

1988-01-01

1. The olfactory epithelium of male hamsters has been found to be extremely active in the cumene hydroperoxide-supported oxidation of tetramethylphenylenediamine, and this peroxidase activity has been shown to be cytochrome P-450-dependent. 2. The interaction of a series of suicide substrates of cytochrome P-450 with the hepatic and olfactory mono-oxygenase systems has been assessed by determination of peroxidase, 7-ethoxycoumarin O-de-ethylase (ECOD) and 7-ethoxyresorufin O-de-ethylase (EROD) activities after treatment in vivo with these compounds. Chloramphenicol, OOS-trimethylphosphorothiolate and two dihydropyridines [DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) and 4-ethyl DDC (3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine)] all caused similar percentage inhibitions of hepatic and olfactory activities, but the absolute amounts of enzymic activity lost were considerably greater in the latter tissue. In contrast, halothane had little effect upon hepatic cytochrome P-450-dependent reactions, whereas it severely inhibited those of the olfactory epithelium. 3. The time course of loss and recovery of hepatic and olfactory peroxidase, ECOD and EROD activities after a single dose of 4-ethyl DDC was studied. The rates of loss of activity observed were very similar, irrespective of tissue or reaction examined. In the olfactory epithelium, all three activities recovered concurrently and at a rate similar to that of the hepatic peroxidase activity. In contrast, the hepatic de-ethylation of 7-ethoxycoumarin and 7-ethoxy-resorufin recovered significantly more rapidly. 4. It is suggested that this behaviour is due to 4-ethyl DDC acting not only as a suicidal inhibitor but also as an inducer of certain forms of cytochrome P-450 in the liver; in the olfactory epithelium, however, inactivation, but not induction, occurs. Classical inducing agents were reported to have no effect upon olfactory cytochrome P-450, and in the present study neither phenobarbitone nor beta-naphthoflavone treatment had any effect upon olfactory cytochrome P-450-dependent reactions, although it induced those of the liver. PMID:3263118

Le don après un décès d'origine cardiocirculatoire au Canada

PubMed Central

Shemie, Sam D.; Baker, Andrew J.; Knoll, Greg; Wall, William; Rocker, Graeme; Howes, Daniel; Davidson, Janet; Pagliarello, Joe; Chambers-Evans, Jane; Cockfield, Sandra; Farrell, Catherine; Glannon, Walter; Gourlay, William; Grant, David; Langevin, Stéphan; Wheelock, Brian; Young, Kimberly; Dossetor, John

2006-01-01

Résumé Ces recommandations sont le fruit d'un processus multidisciplinaire national ayant duré un an et visant à déterminer si et comment l'on pourrait procéder au don d'organes après un décès d'origine cardiocirculatoire («don après le décès cardiocirculatoire», ou DDC) au Canada. Le forum national organisé en février 2005 a permis aux participants de discuter et d'élaborer des recommandations sur les principes, interventions et pratiques se rapportant au DDC. Les aspects éthiques et juridiques ont été abordés dans les discussions. À la fin du Forum, la majorité des participants ont été favorables à l'implantation de programmes de DDC au Canada. Les participants du Forum ont également convenu qu'il fallait formuler et prôner des valeurs fondamentales pour orienter l'élaboration de programmes et de protocoles basés sur le cadre médical, éthique et juridique établi lors de cette réunion. Même si la possibilité d'un don d'organes et de tissus doit faire partie intégrante des soins de fin de vie, il faut insister sur le fait que le devoir de diligence envers les patients mourants et leurs familles doit demeurer la priorité des équipes soignantes. La complexité et les répercussions profondes du décès sont reconnues et doivent être respectées, de même que les différences personnelles, ethnoculturelles et religieuses face à la mort et au don d'organes. Les décisions d'arrêter le traitement de maintien des fonctions vitales, la prise en charge des derniers moments de la vie et le diagnostic de décès selon des critères cardiocirculatoires doivent être distincts et indépendants des processus de don et transplantation. Ce rapport contient des recommandations destinées aux gestionnaires de program, aux autorités sanitaires régionales et aux instances appelés à élaborer les protocoles de DDC. Les programmes doivent être conçus en fonction des éléments suivants : direction et planification locales, éducation et engagement des intervenants, mécanismes d'assurance de la sécurité et de la qualité et information du public. Il est recommandé de commencer par un program de DDC contrôlé à l'unité de soins intensifs où, après une décision par consentement mutuel de cesser le traitement de maintien des fonctions vitales, la mort est attendue, mais n'est pas survenue, ce qui rend possible des discussions non précipitées sur le consentement. Un don non contrôlé, en cas de décès après un arrêt cardiaque non prévu, doit être envisagé seulement une fois que le program de DDC contrôlé a été établi. Bien qu'il soit recommandé de restreindre le programme initial au don de reins, le don d'autres organes peut aussi être envisagé selon l'expertise régionale en matière de transplantation. Les répercussions d'un DDC, y compris les interventions pratiquées avant et après le décès, sur la famille du donneur, la disponibilité des organes, la fonction du greffon et la survie du receveur doivent être documentées de façon méthodique et examinées.

Connective tissue growth factor and integrin αvβ6: a new pair of regulators critical for ductular reaction and biliary fibrosis in mice.

PubMed

Pi, Liya; Robinson, Paulette M; Jorgensen, Marda; Oh, Seh-Hoon; Brown, Alicia R; Weinreb, Paul H; Trinh, Thu Le; Yianni, Protopapadakis; Liu, Chen; Leask, Andrew; Violette, Shelia M; Scott, Edward W; Schultz, Gregory S; Petersen, Bryon E

2015-02-01

Connective tissue growth factor (CTGF) is a matricellular protein that mediates cell-matrix interaction through various subtypes of integrin receptors. This study investigated the role of CTGF and integrin αvβ6 in hepatic progenitor/oval cell activation, which often occurs in the form of ductular reactions (DRs) when hepatocyte proliferation is inhibited during severe liver injury. CTGF and integrin αvβ6 proteins were highly expressed in DRs of human cirrhotic livers and cholangiocarcinoma. Confocal microscopy analysis of livers from Ctgf promoter-driven green fluorescent protein reporter mice suggested that oval cells and cholangiocytes were the main sources of CTGF and integrin αvβ6 during liver injury induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Deletion of exon 4 of the Ctgf gene using tamoxifen-inducible Cre-loxP system down-regulated integrin αvβ6 in DDC-damaged livers of knockout mice. Ctgf deficiency or inhibition of integrin αvβ6, by administrating the neutralizing antibody, 6.3G9 (10 mg/kg body weight), caused low levels of epithelial cell adhesion molecule and cytokeratin 19 gene messenger RNAs. Also, there were smaller oval cell areas, fewer proliferating ductular epithelial cells, and lower cholestasis serum markers within 2 weeks after DDC treatment. Associated fibrosis was attenuated, as indicated by reduced expression of fibrosis-related genes, smaller areas of alpha-smooth muscle actin staining, and low collagen production based on hydroxyproline content and Sirius Red staining. Finally, integrin αvβ6 could bind to CTGF mediating oval cell adhesion to CTGF and fibronection substrata and promoting transforming growth factor (TGF)-β1 activation in vitro. CTGF and integrin αvβ6 regulate oval cell activation and fibrosis, probably through interacting with their common matrix and signal partners, fibronectin and TGF-β1. CTGF and integrin αvβ6 are potential therapeutic targets to control DRs and fibrosis in related liver disease. © 2014 by the American Association for the Study of Liver Diseases.

DELTA-DIESEL ENGINE LIGHT TRUCK APPLICATION Contract DE-FC05-97OR22606 Final Report

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

Hakim, Nabil Balnaves, Mike

2003-05-27

DELTA Diesel Engine Light Truck Application End of Contract Report DE-FC05-97-OR22606 EXECUTIVE SUMMARY This report is the final technical report of the Diesel Engine Light Truck Application (DELTA) program under contract DE-FC05-97-OR22606. During the course of this contract, Detroit Diesel Corporation analyzed, designed, tooled, developed and applied the ''Proof of Concept'' (Generation 0) 4.0L V-6 DELTA engine and designed the successor ''Production Technology Demonstration'' (Generation 1) 4.0L V-6 DELTA engine. The objectives of DELTA Program contract DE-FC05-97-OR22606 were to: Demonstrate production-viable diesel engine technologies, specifically intended for the North American LDT and SUV markets; Demonstrate emissions compliance with significant fuelmore » economy advantages. With a clean sheet design, DDC produced the DELTA engine concept promising the following attributes: 30-50% improved fuel economy; Low cost; Good durability and reliability; Acceptable noise, vibration and harshness (NVH); State-of-the-art features; Even firing, 4 valves per cylinder; High pressure common rail fuel system; Electronically controlled; Turbocharged, intercooled, cooled EGR; Extremely low emissions via CLEAN Combustion{copyright} technology. To demonstrate the engine technology in the SUV market, DDC repowered a 1999 Dodge Durango with the DELTA Generation 0 engine. Fuel economy improvements were approximately 50% better than the gasoline engine replaced in the vehicle.« less

Inhibition of Atg6 and Pi3K59F autophagy genes in neurons decreases lifespan and locomotor ability in Drosophila melanogaster.

PubMed

M'Angale, P G; Staveley, B E

2016-10-24

Autophagy is a cellular mechanism implicated in the pathology of Parkinson's disease. The proteins Atg6 (Beclin 1) and Pi3K59F are involved in autophagosome formation, a key step in the initiation of autophagy. We first used the GMR-Gal4 driver to determine the effect of reducing the expression of the genes encoding these proteins on the developing Drosophila melanogaster eye. Subsequently, we inhibited their expression in D. melanogaster neurons under the direction of a Dopa decarboxylase (Ddc) transgene, and examined the effects on longevity and motor function. Decreased longevity coupled with an age-dependent loss of climbing ability was observed. In addition, we investigated the roles of these genes in the well-studied α-synuclein-induced Drosophila model of Parkinson's disease. In this context, lowered expression of Atg6 or Pi3K59F in Ddc-Gal4-expressing neurons results in decreased longevity and associated age-dependent loss of locomotor ability. Inhibition of Atg6 or Pi3K59F together with overexpression of the sole pro-survival Bcl-2 Drosophila homolog Buffy in Ddc-Gal4-expressing neurons resulted in further decrease in the survival and climbing ability of Atg6-RNAi flies, whereas these measures were ameliorated in Pi3K59F-RNAi flies.

Microstructure and Ductility-Dip Cracking Susceptibility of Circumferential Multipass Dissimilar Weld Between 20MND5 and Z2CND18-12NS with Ni-Base Filler Metal 52

NASA Astrophysics Data System (ADS)

Qin, Renyao; Duan, Zhaoling; He, Guo

2013-10-01

The large circumferential multipass dissimilar weld between 20MND5 steel and Z2CND18-12NS stainless steel welded with FM52 filler material was investigated in terms of the diluted composition, the grain boundary precipitation, and the ductility-dip cracking (DDC) susceptibility of the weld. The diluted composition of the weld is composed of 37 to 47 pct Ni, 21 to 24 pct Cr, and 28 to 40 pct Fe, which are inhomogeneous along the depth and over the width of the deep weld. The carbon content has a distribution in the region of the surface weld from a high level (~0.20 pct) in the zone near 20MND5 steel to a normal level (~0.03 pct) in the zone near Z2CND18-12NS stainless steel. The carbon distribution is corresponding to the grain boundary carbides. The minimum threshold strains for DDC occur in the temperature range of 1223 K to 1323 K (950 °C to 1050 °C), which are 0.5, 0.35, and 0.4 pct for the root weld, middle region, and the surface weld, respectively. The dissimilar weld has the largest susceptibility to the DDC compared to the filler metal 52 and the Inconel 690.

Molecular Dynamic Studies of Particle Wake Potentials in Plasmas

NASA Astrophysics Data System (ADS)

Ellis, Ian; Graziani, Frank; Glosli, James; Strozzi, David; Surh, Michael; Richards, David; Decyk, Viktor; Mori, Warren

2010-11-01

Fast Ignition studies require a detailed understanding of electron scattering, stopping, and energy deposition in plasmas with variable values for the number of particles within a Debye sphere. Presently there is disagreement in the literature concerning the proper description of these processes. Developing and validating proper descriptions requires studying the processes using first-principle electrostatic simulations and possibly including magnetic fields. We are using the particle-particle particle-mesh (P^3M) code ddcMD to perform these simulations. As a starting point in our study, we examined the wake of a particle passing through a plasma. In this poster, we compare the wake observed in 3D ddcMD simulations with that predicted by Vlasov theory and those observed in the electrostatic PIC code BEPS where the cell size was reduced to .03λD.

Earthquakes and strain in subhorizontal slabs

NASA Astrophysics Data System (ADS)

Brudzinski, Michael R.; Chen, Wang-Ping

2005-08-01

Using an extensive database of fault plane solutions and precise locations of hypocenters, we show that the classic patterns of downdip extension (DDE) or downdip compression (DDC) in subduction zones deteriorate when the dip of the slab is less than about 20°. This result is depth-independent, demonstrated by both intermediate-focus (depths from 70 to 300 km) and deep-focus (depths greater than 300 km) earthquakes. The absence of pattern in seismic strain in subhorizontal slabs also occurs locally over scales of about 10 km, as evident from a detailed analysis of a large (Mw 7.1) earthquake sequence beneath Fiji. Following the paradigm that a uniform strain of DDE/DDC results from sinking of the cold, dense slab as it encounters resistance from the highly viscous mantle at depth, breakdown of DDE/DDC in subhorizontal slabs reflects waning negative buoyancy ("slab pull") in the downdip direction. Our results place a constraint on the magnitude of slab pull that is required to dominate over localized sources of stress and to align seismic strain release in dipping slabs. Under the condition of a vanishing slab pull, eliminating the only obvious source of regional stress, the abundance of earthquakes in subhorizontal slabs indicates that a locally variable source of stress is both necessary and sufficient to sustain the accumulation of elastic strain required to generate intermediate- and deep-focus seismicity. Evidence is growing that the process of seismogenesis under high pressures, including localized sources of stress, is tied to the presence of petrologic anomalies.

Members of the Cyr61/CTGF/NOV Protein Family: Emerging Players in Hepatic Progenitor Cell Activation and Intrahepatic Cholangiocarcinoma

PubMed Central

Jorgensen, Marda; Song, Joanna; Zhou, Junmei; Liu, Chen

2016-01-01

Hepatic stem/progenitor cells (HPC) reside quiescently in normal biliary trees and are activated in the form of ductular reactions during severe liver damage when the replicative ability of hepatocytes is inhibited. HPC niches are full of profibrotic stimuli favoring scarring and hepatocarcinogenesis. The Cyr61/CTGF/NOV (CCN) protein family consists of six members, CCN1/CYR61, CCN2/CTGF, CCN3/NOV, CCN4/WISP1, CCN5/WISP2, and CCN6/WISP3, which function as extracellular signaling modulators to mediate cell-matrix interaction during angiogenesis, wound healing, fibrosis, and tumorigenesis. This study investigated expression patterns of CCN proteins in HPC and cholangiocarcinoma (CCA). Mouse HPC were induced by the biliary toxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Differential expression patterns of CCN proteins were found in HPC from DDC damaged mice and in human CCA tumors. In addition, we utilized reporter mice that carried Ccn2/Ctgf promoter driven GFP and detected strong Ccn2/Ctgf expression in epithelial cell adhesion molecule (EpCAM)+ HPC under normal conditions and in DDC-induced liver damage. Abundant CCN2/CTGF protein was also found in cytokeratin 19 (CK19)+ human HPC that were surrounded by α-smooth muscle actin (α-SMA)+ myofibroblast cells in intrahepatic CCA tumors. These results suggest that CCN proteins, particularly CCN2/CTGF, function in HPC activation and CCA development. PMID:27829832

76 FR 43990 - Procurement List; Proposed Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

... Polished Nickel Finish NSN: AF430--Nameplate, Class B, USAF, Cloth, Dark Navy Blue with Silver/Gray Thread... Distribution. In 2010, the Defense Distribution Center (DDC) was renamed DLA Distribution. A process was also...

Studies of particle wake potentials in plasmas

NASA Astrophysics Data System (ADS)

Ellis, Ian N.; Graziani, Frank R.; Glosli, James N.; Strozzi, David J.; Surh, Michael P.; Richards, David F.; Decyk, Viktor K.; Mori, Warren B.

2011-09-01

A detailed understanding of electron stopping and scattering in plasmas with variable values for the number of particles within a Debye sphere is still not at hand. Presently, there is some disagreement in the literature concerning the proper description of these processes. Theoretical models assume electrostatic (Coulomb force) interactions between particles and neglect magnetic effects. Developing and validating proper descriptions requires studying the processes using first-principle plasma simulations. We are using the particle-particle particle-mesh (PPPM) code ddcMD and the particle-in-cell (PIC) code BEPS to perform these simulations. As a starting point in our study, we examine the wake of a particle passing through a plasma in 3D electrostatic simulations performed with ddcMD and BEPS. In this paper, we compare the wakes observed in these simulations with each other and predictions from collisionless kinetic theory. The relevance of the work to Fast Ignition is discussed.

Modality-based organization of ascending somatosensory axons in the direct dorsal column pathway.

PubMed

Niu, Jingwen; Ding, Long; Li, Jian J; Kim, Hyukmin; Liu, Jiakun; Li, Haipeng; Moberly, Andrew; Badea, Tudor C; Duncan, Ian D; Son, Young-Jin; Scherer, Steven S; Luo, Wenqin

2013-11-06

The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the "somatotopic map" model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial-lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough "somatotopic map" was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway.

A review of pitfalls and progress in chelation treatment of metal poisonings.

PubMed

Andersen, Ole; Aaseth, Jan

2016-12-01

Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

p62/Sequestosome-1 Is Indispensable for Maturation and Stabilization of Mallory-Denk Bodies

PubMed Central

Lahiri, Pooja; Schmidt, Volker; Smole, Claudia; Kufferath, Iris; Denk, Helmut; Strnad, Pavel; Rülicke, Thomas; Fröhlich, Leopold F.; Zatloukal, Kurt

2016-01-01

Mallory-Denk bodies (MDBs) are hepatocytic protein aggregates found in steatohepatitis and several other chronic liver diseases as well as hepatocellular carcinoma. MDBs are mainly composed of phosphorylated keratins and stress protein p62/Sequestosome-1 (p62), which is a common component of cytoplasmic aggregates in a variety of protein aggregation diseases. In contrast to the well-established role of keratins, the role of p62 in MDB pathogenesis is still elusive. We have generated total and hepatocyte-specific p62 knockout mice, fed them with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to induce MDBs and allowed the mice to recover from DDC intoxication on a standard diet to investigate the role of p62 in MDB formation and elimination. In the absence of p62, smaller, granular and less distinct MDBs appeared, which failed to mature to larger and compact inclusions. Moreover, p62 deficiency impaired the binding of other proteins such as NBR1 and Hsp25 to MDBs and altered the cellular defense mechanism by downregulation of Nrf2 target genes. Upon recovery from DDC intoxication on a standard diet, there was an enhanced reduction of p62-deficient MDBs, which was accompanied by a pronounced decrease in ubiquitinated proteins. Our data provide strong evidence that keratin aggregation is the initial step in MDB formation in steatohepatitis-related mouse models. Interaction of p62 with keratin aggregates then leads to maturation i.e., enlargement and stabilization of the MDBs as well as recruitment of other MDB-associated proteins. PMID:27526095

Constraints on the explosion mechanism and progenitors of Type Ia supernovae

NASA Astrophysics Data System (ADS)

Dessart, Luc; Blondin, Stéphane; Hillier, D. John; Khokhlov, Alexei

2014-06-01

Observations of SN 2011fe at early times reveal an evolution analogous to a fireball model of constant colour. In contrast, our unmixed delayed detonations of Chandrasekhar-mass white dwarfs (DDC series) exhibit a faster brightening concomitant with a shift in colour to the blue. In this paper, we study the origin of these discrepancies. We find that strong chemical mixing largely resolves the photometric mismatch at early times, but it leads to an enhanced line broadening that contrasts, for example, with the markedly narrow Si II 6355 Å line of SN 2011fe. We also explore an alternative configuration with pulsational-delayed detonations (PDDEL model series). Because of the pulsation, PDDEL models retain more unburnt carbon, have little mass at high velocity, and have a much hotter outer ejecta after the explosion. The pulsation does not influence the inner ejecta, so PDDEL and DDC models exhibit similar radiative properties beyond maximum. However, at early times, PDDEL models show bluer optical colours and a higher luminosity, even for weak mixing. Their early-time radiation is derived primarily from the initial shock-deposited energy in the outer ejecta rather than radioactive-decay heating. Furthermore, PDDEL models show short-lived C II lines, reminiscent of SN 2013dy. They typically exhibit lines that are weaker, narrower, and of near-constant width, reminiscent of SN 2011fe. In addition to multidimensional effects, varying configurations for such `pulsations' offer a source of spectral diversity amongst Type Ia supernovae (SNe Ia). PDDEL and DDC models also provide one explanation for low- and high-velocity-gradient SNe Ia.

CMCC Data Distribution Centre

NASA Astrophysics Data System (ADS)

Aloisio, Giovanni; Fiore, Sandro; Negro, A.

2010-05-01

The CMCC Data Distribution Centre (DDC) is the primary entry point (web gateway) to the CMCC. It is a Data Grid Portal providing a ubiquitous and pervasive way to ease data publishing, climate metadata search, datasets discovery, metadata annotation, data access, data aggregation, sub-setting, etc. The grid portal security model includes the use of HTTPS protocol for secure communication with the client (based on X509v3 certificates that must be loaded into the browser) and secure cookies to establish and maintain user sessions. The CMCC DDC is now in a pre-production phase and it is currently used only by internal users (CMCC researchers and climate scientists). The most important component already available in the CMCC DDC is the Search Engine which allows users to perform, through web interfaces, distributed search and discovery activities by introducing one or more of the following search criteria: horizontal extent (which can be specified by interacting with a geographic map), vertical extent, temporal extent, keywords, topics, creation date, etc. By means of this page the user submits the first step of the query process on the metadata DB, then, she can choose one or more datasets retrieving and displaying the complete XML metadata description (from the browser). This way, the second step of the query process is carried out by accessing to a specific XML document of the metadata DB. Finally, through the web interface, the user can access to and download (partially or totally) the data stored on the storage device accessing to OPeNDAP servers and to other available grid storage interfaces. Requests concerning datasets stored in deep storage will be served asynchronously.

A Technique for Machine-Aided Indexing

ERIC Educational Resources Information Center

Klingbiel, Paul H.

1973-01-01

The technique for machine-aided indexing developed at the Defense Documentation Center (DDC) is illustrated on a randomly chosen abstract. Additional text is provided in coded form so that the reader can more fully explore this technique. (2 references) (Author)

Mechanical allodynia induced by nucleoside reverse transcriptase inhibitor is suppressed by p55TNFSR mediated by herpes simplex virus vector through the SDF1α/CXCR4 system in rats.

PubMed

Huang, Wan; Zheng, Wenwen; Ouyang, Handong; Yi, Hyun; Liu, Shue; Zeng, Weian; Levitt, Roy C; Candiotti, Keith A; Lubarsky, David A; Hao, Shuanglin

2014-03-01

In the human immunodeficiency virus (HIV)-associated sensory neuropathy, neuropathic pain associated with the use of nucleoside reverse transcriptase inhibitors (NRTIs) in patients with HIV/acquired immunodeficiency syndrome is clinically common. While evidence demonstrates that neuropathic pain is influenced by neuroinflammatory events that include the proinflammatory molecules, tumor necrosis factor-α (TNF-α), stromal cell-derived factor 1-α (SDF1-α), and C-X-C chemokine receptor type 4 (CXCR4), the detailed mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In this study, we investigated the role of these proinflammatory molecules in the dorsal root ganglion (DRG) and the spinal dorsal horn in NRTIs-mediated neuropathic pain state. Neuropathic pain was induced by intraperitoneal administration of 2',3'-dideoxycytidine (ddC, one of the NRTIs). Mechanical threshold was tested using von Frey filament fibers. Nonreplicating herpes simplex virus (HSV) vectors expressing p55 TNF soluble receptor (p55TNFSR) were inoculated into hindpaw of rats. The expression of TNF-α, SDF1-α, and CXCR4 in both the lumbar spinal cord and the L4/5 DRG was examined using Western blots. Intrathecal CXCR4 antagonist was administered. The present study demonstrated that (1) systemic ddC induced upregulation of TNF-α, SDF1-α, and CXCR4 in both the lumbar spinal cord and the L4/5 DRG; (2) p55TNFSR mediated by a nonreplicating HSV vector reversed mechanical allodynia induced by systemic ddC; (3) intrathecal administration of the CXCR4 antagonist AMD3100 increased mechanical threshold; and (4) HSV vector expressing p55TNFSR reversed upregulation of TNF-α, SDF1-α, and CXCR4 induced by ddC in the lumbar spinal dorsal horn and the DRG. Our studies demonstrate that TNF-α through the SDF1/CXCR4 system is involved in the NRTIs-related neuropathic pain state and that blocking the signaling of these proinflammatory molecules is able to reduce NRTIs-related neuropathic pain. These results provide a novel mechanism-based approach (gene therapy) to treating HIV-associated neuropathic pain.

A loss of Pdxk model of Parkinson disease in Drosophila can be suppressed by Buffy.

PubMed

M'Angale, P Githure; Staveley, Brian E

2017-06-12

The identification of a DNA variant in pyridoxal kinase (Pdxk) associated with increased risk to Parkinson disease (PD) gene led us to study the inhibition of this gene in the Dopa decarboxylase (Ddc)-expressing neurons of the well-studied model organism Drosophila melanogaster. The multitude of biological functions attributable to the vitamers catalysed by this kinase reveal an overabundance of possible links to PD, that include dopamine synthesis, antioxidant activity and mitochondrial function. Drosophila possesses a single homologue of Pdxk and we used RNA interference to inhibit the activity of this kinase in the Ddc-Gal4-expressing neurons. We further investigated any association between this enhanced disease risk gene with the established PD model induced by expression of α-synuclein in the same neurons. We relied on the pro-survival functions of Buffy, an anti-apoptotic Bcl-2 homologue, to rescue the Pdxk-induced phenotypes. To drive the expression of Pdxk RNA interference in DA neurons of Drosophila, we used Ddc-Gal4 which drives expression in both dopaminergic and serotonergic neurons, to result in decreased longevity and compromised climbing ability, phenotypes that are strongly associated with Drosophila models of PD. The inhibition of Pdxk in the α-synuclein-induced Drosophila model of PD did not alter longevity and climbing ability of these flies. It has been previously shown that deficiency in vitamers lead to mitochondrial dysfunction and neuronal decay, therefore, co-expression of Pdxk-RNAi with the sole pro-survival Bcl-2 homologue Buffy in the Ddc-Gal4-expressing neurons, resulted in increased survival and a restored climbing ability. In a similar manner, when we inhibited Pdxk in the developing eye using GMR-Gal4, we found that there was a decrease in the number of ommatidia and the disruption of the ommatidial array was more pronounced. When Pdxk was inhibited with the α-synuclein-induced developmental eye defects, the eye phenotypes were unaltered. Interestingly co-expression with Buffy restored ommatidia number and decreased the severity of disruption of the ommatidial array. Though Pdxk is not a confirmed Parkinson disease gene, the inhibition of this kinase recapitulated the PD-like symptoms of decreased lifespan and loss of locomotor function, possibly producing a new model of PD.

ATLAS tile calorimeter cesium calibration control and analysis software

NASA Astrophysics Data System (ADS)

Solovyanov, O.; Solodkov, A.; Starchenko, E.; Karyukhin, A.; Isaev, A.; Shalanda, N.

2008-07-01

An online control system to calibrate and monitor ATLAS Barrel hadronic calorimeter (TileCal) with a movable radioactive source, driven by liquid flow, is described. To read out and control the system an online software has been developed, using ATLAS TDAQ components like DVS (Diagnostic and Verification System) to verify the hardware before running, IS (Information Server) for data and status exchange between networked computers, and other components like DDC (DCS to DAQ Connection), to connect to PVSS-based slow control systems of Tile Calorimeter, high voltage and low voltage. A system of scripting facilities, based on Python language, is used to handle all the calibration and monitoring processes from hardware perspective to final data storage, including various abnormal situations. A QT based graphical user interface to display the status of the calibration system during the cesium source scan is described. The software for analysis of the detector response, using online data, is discussed. Performance of the system and first experience from the ATLAS pit are presented.

76 FR 18231 - Federal Property Suitable as Facilities To Assist the Homeless

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

...-101 and 15-115 Olympic Nat'l Park Lake Crescent WA 98362 Landholding Agency: Interior Property Number... National Coalition for the Homeless v. Veterans Administration, No. 88-2503-OG (D.D.C.). Properties...-based paint [[Page 18232

DORS: DDC Online Retrieval System.

ERIC Educational Resources Information Center

Liu, Songqiao; Svenonius, Elaine

1991-01-01

Describes the Dewey Online Retrieval System (DORS), which was developed at the University of California, Los Angeles (UCLA), to experiment with classification-based search strategies in online catalogs. Classification structures in automated information retrieval are discussed; and specifications for a classification retrieval interface are…

Face gender categorization and hemispheric asymmetries: Contrasting evidence from connected and disconnected brains.

PubMed

Prete, Giulia; Fabri, Mara; Foschi, Nicoletta; Tommasi, Luca

2016-12-17

We investigated hemispheric asymmetries in categorization of face gender by means of a divided visual field paradigm, in which female and male faces were presented unilaterally for 150ms each. A group of 60 healthy participants (30 males) and a male split-brain patient (D.D.C.) were asked to categorize the gender of the stimuli. Healthy participants categorized male faces presented in the right visual field (RVF) better and faster than when presented in the left visual field (LVF), and female faces presented in the LVF than in the RVF, independently of the participants' sex. Surprisingly, the recognition rates of D.D.C. were at chance levels - and significantly lower than those of the healthy participants - for both female and male faces presented in the RVF, as well as for female faces presented in the LVF. His performance was higher than expected by chance - and did not differ from controls - only for male faces presented in the LVF. The residual right-hemispheric ability of the split-brain patient in categorizing male faces reveals an own-gender bias lateralized in the right hemisphere, in line with the rightward own-identity and own-age bias previously shown in split-brain patients. The gender-contingent hemispheric dominance found in healthy participants confirms the previously shown right-hemispheric superiority in recognizing female faces, and also reveals a left-hemispheric superiority in recognizing male faces, adding an important evidence of hemispheric imbalance in the field of face and gender perception. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease.

PubMed

Kraemmer, Julia; Smith, Kara; Weintraub, Daniel; Guillemot, Vincent; Nalls, Mike A; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Singleton, Andrew B; Corvol, Jean-Christophe

2016-10-01

Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson's disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD. Data from de novo patients with PD, drug-naïve and free of ICD behaviour at baseline, were obtained from the Parkinson's Progression Markers Initiative cohort. Incident ICD behaviour was defined as positive score on the Questionnaire for Impulsive-Compulsive Disorders in PD. ICD heritability was estimated by restricted maximum likelihood analysis on whole exome sequencing data. 13 candidate variants were selected from the DRD2, DRD3, DAT1, COMT, DDC, GRIN2B, ADRA2C, SERT, TPH2, HTR2A, OPRK1 and OPRM1 genes. ICD prediction was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Among 276 patients with PD included in the analysis, 86% started DRT, 40% were on dopamine agonists (DA), 19% reported incident ICD behaviour during follow-up. We found heritability of this symptom to be 57%. Adding genotypes from the 13 candidate variants significantly increased ICD predictability (AUC=76%, 95% CI (70% to 83%)) compared to prediction based on clinical variables only (AUC=65%, 95% CI (58% to 73%), p=0.002). The clinical-genetic prediction model reached highest accuracy in patients initiating DA therapy (AUC=87%, 95% CI (80% to 93%)). OPRK1, HTR2A and DDC genotypes were the strongest genetic predictive factors. Our results show that adding a candidate genetic panel increases ICD predictability, suggesting potential for developing clinical-genetic models to identify patients with PD at increased risk of ICD development and guide DRT management. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Team Training and Evaluation Strategies: A State-of-Art Review.

ERIC Educational Resources Information Center

Wagner, H.; And Others

Educational Resources Information Center (ERIC), the Defense Documentation Center (DDC), National Technical Information Service (NTIS), Psychological Abstracts, HumRRO Library, and industrial training publications were surveyed to analyze instructional and evaluative techniques relevant to team training. Research studies and team training…

Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures.

PubMed

Stray, Kirsten M; Park, Yeojin; Babusis, Darius; Callebaut, Christian; Cihlar, Tomas; Ray, Adrian S; Perron, Michel

2017-04-01

HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes. First, activated or resting peripheral blood mononuclear cells (PBMCs), as well as MT-2 and Jurkat T-cell lines, were continuously treated with ddC for 10 days to establish their susceptibility to mtDNA depletion. PBMCs had low sensitivity to NRTI-mediated mtDNA depletion in vitro. In contrast, ddC treatment of rapidly dividing MT-2 and Jurkat cells resulted in a dose-dependent decrease in mtDNA. Therefore, these two T-cell lines were selected for evaluating TAF and TDF treatment effects. MT-2 and Jurkat cells were pulse-treated with TAF or TDF every 24 h for 10 days to mimic pharmacologically relevant drug exposures. Pulse treatment of cells with 3.3 μM TAF or 1.1 μM TDF for 10 days resulted in 2- to 7-fold greater steady-state intracellular TFV-diphosphate (TFV-DP) levels than those observed clinically in TAF- or TDF-treated patients. At these concentrations, no significant TAF- (106.7% and 84.1% of control; p = 0.77 and 0.12 for MT-2 and Jurkat, respectively) or TDF- (100.6% and 91.0% of control; p = 0.91 and 0.37, respectively) associated reduction in mtDNA content was observed compared with untreated control cells. This study demonstrates that, despite delivering higher intracellular levels of TFV-DP than TDF, TAF does not inhibit mtDNA synthesis in vitro at concentrations exceeding the clinically relevant intracellular drug exposures. Thus, TAF has a low potential for mitochondrial toxicity in T-cells of HIV-infected patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Campus-Based, Community-Based, and Philanthropic Contributions to Predoctoral Pediatric Dental Clinical Education: Two Years of Experiences at One Dental College.

PubMed

Spiritoso, Stephen; Gross, Erin; Bean, Canise Y; Casamassimo, Paul S; Levings, Kevin; Lloyd, Patrick

2015-08-01

The aim of this study was to investigate the contribution of a tiered predoctoral pediatric dentistry clinical education model to competency achievement by dental students over a two-year clinical education. Retrospective data were obtained for academic years 2012-13 and 2013-14 from three sources: a campus-based, dental school-housed clinic; division-directed clinics in community-based pediatric and special needs clinics (DDC); and clinics affiliated with the dental college's community-based dental education (CBDE) program, the OHIO Project (OP). A fourth dataset was obtained for the same two-year period from a biannual clinic event held at the college in conjunction with Give Kids a Smile Day (GKAS). Procedures considered essential to the care of children were sorted by 12 dental codes from all services for patients 18 years of age and younger. The dental school clinic provided 11,060 procedures; the DDC, 28,462; the OP, 17,863; and GKAS, 2,028. The two-year total was 59,433 procedures. Numbers of diagnostic and preventive procedures were 19,441, restorative procedures were 13,958, and pulp and surgical procedures were 7,392. Site contribution ranged from 52.2 to 144.9 procedures per attending student, with the DDC yielding the highest per student average for each year (126.4 and 144.9) and the dental school clinic the lowest (52.2 and 53.1). This study found that a combination of school-based, community-based, and philanthropic pediatric dental experiences offered a large number of essential pediatric dentistry experiences for predoctoral dental students, with CBDE opportunities offering the largest contribution.

Prostate segmentation by feature enhancement using domain knowledge and adaptive region based operations

NASA Astrophysics Data System (ADS)

Nanayakkara, Nuwan D.; Samarabandu, Jagath; Fenster, Aaron

2006-04-01

Estimation of prostate location and volume is essential in determining a dose plan for ultrasound-guided brachytherapy, a common prostate cancer treatment. However, manual segmentation is difficult, time consuming and prone to variability. In this paper, we present a semi-automatic discrete dynamic contour (DDC) model based image segmentation algorithm, which effectively combines a multi-resolution model refinement procedure together with the domain knowledge of the image class. The segmentation begins on a low-resolution image by defining a closed DDC model by the user. This contour model is then deformed progressively towards higher resolution images. We use a combination of a domain knowledge based fuzzy inference system (FIS) and a set of adaptive region based operators to enhance the edges of interest and to govern the model refinement using a DDC model. The automatic vertex relocation process, embedded into the algorithm, relocates deviated contour points back onto the actual prostate boundary, eliminating the need of user interaction after initialization. The accuracy of the prostate boundary produced by the proposed algorithm was evaluated by comparing it with a manually outlined contour by an expert observer. We used this algorithm to segment the prostate boundary in 114 2D transrectal ultrasound (TRUS) images of six patients scheduled for brachytherapy. The mean distance between the contours produced by the proposed algorithm and the manual outlines was 2.70 ± 0.51 pixels (0.54 ± 0.10 mm). We also showed that the algorithm is insensitive to variations of the initial model and parameter values, thus increasing the accuracy and reproducibility of the resulting boundaries in the presence of noise and artefacts.

Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

PubMed Central

Martin, H.L.; Alsaady, I.; Howell, G.; Prandovszky, E.; Peers, C.; Robinson, P.; McConkey, G.A.

2015-01-01

Infection by the neurotropic agent Toxoplasma gondii alters rodent behavior and can result in neuropsychiatric symptoms in humans. Little is understood regarding the effects of infection on host neural processes but alterations to dopaminergic neurotransmission are implicated. We have previously reported elevated levels of dopamine (DA) in infected dopaminergic cells however the involvement of the host enzymes and fate of the produced DA were not defined. In order to clarify the effects of infection on host DA biosynthetic enzymes and DA packaging we examined enzyme levels and activity and DA accumulation and release in T. gondii-infected neurosecretory cells. Although the levels of the host tyrosine hydroxylase (TH) and DOPA decarboxylase and AADC (DDC) did not change significantly in infected cultures, DDC was found within the parasitophorous vacuole (PV), the vacuolar compartment where the parasites reside, as well as in the host cytosol in infected dopaminergic cells. Strikingly, DDC was found within the intracellular parasite cysts in infected brain tissue. This finding could provide some explanation for observations of DA within tissue cysts in infected brain as a parasite-encoded enzyme with TH activity was also localized within tissue cysts. In contrast, cellular DA packaging appeared unchanged in single-cell microamperometry experiments and only a fraction of the increased DA was accessible to high potassium-induced release. This study provides some understanding of how this parasite produces elevated DA within dopaminergic cells without the toxic ramifications of free cytosolic DA. The mechanism for synthesis and packaging of DA by T. gondii-infected dopaminergic cells may have important implications for the effects of chronic T. gondii infection on humans and animals. PMID:26297895

Habenula Circuit Development: Past, Present, and Future

PubMed Central

Beretta, Carlo A.; Dross, Nicolas; Guiterrez-Triana, Jose A.; Ryu, Soojin; Carl, Matthias

2012-01-01

The habenular neural circuit is attracting increasing attention from researchers in fields as diverse as neuroscience, medicine, behavior, development, and evolution. Recent studies have revealed that this part of the limbic system in the dorsal diencephalon is involved in reward, addiction, and other behaviors and its impairment is associated with various neurological conditions and diseases. Since the initial description of the dorsal diencephalic conduction system (DDC) with the habenulae in its center at the end of the nineteenth century, increasingly sophisticated techniques have resolved much of its anatomy and have shown that these pathways relay information from different parts of the forebrain to the tegmentum, midbrain, and hindbrain. The first part of this review gives a brief historical overview on how the improving experimental approaches have allowed the stepwise uncovering much of the architecture of the habenula circuit as we know it today. Our brain distributes tasks differentially between left and right and it has become a paradigm that this functional lateralization is a universal feature of vertebrates. Moreover, task dependent differential brain activities have been linked to anatomical differences across the left–right axis in humans. A good way to further explore this fundamental issue will be to study the functional consequences of subtle changes in neural network formation, which requires that we fully understand DDC system development. As the habenular circuit is evolutionarily highly conserved, researchers have the option to perform such difficult experiments in more experimentally amenable vertebrate systems. Indeed, research in the last decade has shown that the zebrafish is well suited for the study of DDC system development and the phenomenon of functional lateralization. We will critically discuss the advantages of the zebrafish model, available techniques, and others that are needed to fully understand habenular circuit development. PMID:22536170

Habenula circuit development: past, present, and future.

PubMed

Beretta, Carlo A; Dross, Nicolas; Guiterrez-Triana, Jose A; Ryu, Soojin; Carl, Matthias

2012-01-01

The habenular neural circuit is attracting increasing attention from researchers in fields as diverse as neuroscience, medicine, behavior, development, and evolution. Recent studies have revealed that this part of the limbic system in the dorsal diencephalon is involved in reward, addiction, and other behaviors and its impairment is associated with various neurological conditions and diseases. Since the initial description of the dorsal diencephalic conduction system (DDC) with the habenulae in its center at the end of the nineteenth century, increasingly sophisticated techniques have resolved much of its anatomy and have shown that these pathways relay information from different parts of the forebrain to the tegmentum, midbrain, and hindbrain. The first part of this review gives a brief historical overview on how the improving experimental approaches have allowed the stepwise uncovering much of the architecture of the habenula circuit as we know it today. Our brain distributes tasks differentially between left and right and it has become a paradigm that this functional lateralization is a universal feature of vertebrates. Moreover, task dependent differential brain activities have been linked to anatomical differences across the left-right axis in humans. A good way to further explore this fundamental issue will be to study the functional consequences of subtle changes in neural network formation, which requires that we fully understand DDC system development. As the habenular circuit is evolutionarily highly conserved, researchers have the option to perform such difficult experiments in more experimentally amenable vertebrate systems. Indeed, research in the last decade has shown that the zebrafish is well suited for the study of DDC system development and the phenomenon of functional lateralization. We will critically discuss the advantages of the zebrafish model, available techniques, and others that are needed to fully understand habenular circuit development.

Methods and initial findings from the Durham Diabetes Coalition: Integrating geospatial health technology and community interventions to reduce death and disability.

PubMed

Spratt, Susan E; Batch, Bryan C; Davis, Lisa P; Dunham, Ashley A; Easterling, Michele; Feinglos, Mark N; Granger, Bradi B; Harris, Gayle; Lyn, Michelle J; Maxson, Pamela J; Shah, Bimal R; Strauss, Benjamin; Thomas, Tainayah; Califf, Robert M; Miranda, Marie Lynn

2015-03-01

The Durham Diabetes Coalition (DDC) was established in response to escalating rates of disability and death related to type 2 diabetes mellitus, particularly among racial/ethnic minorities and persons of low socioeconomic status in Durham County, North Carolina. We describe a community-based demonstration project, informed by a geographic health information system (GHIS), that aims to improve health and healthcare delivery for Durham County residents with diabetes. A prospective, population-based study is assessing a community intervention that leverages a GHIS to inform community-based diabetes care programs. The GHIS integrates clinical, social, and environmental data to identify, stratify by risk, and assist selection of interventions at the individual, neighborhood, and population levels. The DDC is using a multifaceted approach facilitated by GHIS to identify the specific risk profiles of patients and neighborhoods across Durham County. A total of 22,982 patients with diabetes in Durham County were identified using a computable phenotype. These patients tended to be older, female, African American, and not covered by private health insurance, compared with the 166,041 persons without diabetes. Predictive models inform decision-making to facilitate care and track outcomes. Interventions include: 1) neighborhood interventions to improve the context of care; 2) intensive team-based care for persons in the top decile of risk for death or hospitalization within the coming year; 3) low-intensity telephone coaching to improve adherence to evidence-based treatments; 4) county-wide communication strategies; and 5) systematic quality improvement in clinical care. To improve health outcomes and reduce costs associated with type 2 diabetes, the DDC is matching resources with the specific needs of individuals and communities based on their risk characteristics.

Drug–drug conditioning between citalopram and haloperidol or olanzapine in a conditioned avoidance response model: implications for polypharmacy in schizophrenia

PubMed Central

Sparkman, Nathan L.; Li, Ming

2016-01-01

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. Following acquisition of the avoidance response, rats were then randomly assigned to receive vehicle, citalopram (10.0 mg/kg, intraperitoneally), haloperidol (0.05 mg/kg, subcutaneously), olanzapine (1.0 mg/kg, subcutaneously), combined haloperidol with citalopram, or combined olanzapine with citalopram treatment for seven avoidance test sessions. In comparison with antipsychotic treatment alone, combined treatment with citalopram potentiated the antiavoidance effect of olanzapine or haloperidol (to a lesser extent) during the seven drug-test sessions. In addition, repeated pairing of citalopram with haloperidol or olanzapine caused citalopram to show a newly acquired avoidance-disruptive effect. This effect was context specific because citalopram paired with haloperidol or olanzapine outside the avoidance testing context (i.e. home cages) did not show such an effect. These findings indicate that concurrent antidepressant and antipsychotic treatments may engender a DDC process that follows the general Pavlovian associative conditioning principles. They also indicate that adjunctive citalopram treatment may enhance the antipsychotic efficacy of haloperidol and olanzapine in the treatment of schizophrenia. PMID:22903071

Assessment of tumor response to oxygen challenge using quantitative diffusion MRI in an animal model.

PubMed

Zhang, Zhongwei; Yuan, Qing; Zhou, Heling; Zhao, Dawen; Li, Li; Gerberich, Jenifer L; Mason, Ralph P

2015-11-01

To assess tumor response to oxygen challenge using quantitative diffusion magnetic resonance imaging (MRI). A well-characterized Dunning R3327-AT1 rat prostate cancer line was implanted subcutaneously in the right thigh of male Copenhagen rats (n = 8). Diffusion-weighted images (DWI) with multiple b values (0, 25, 50, 100, 150, 200, 300, 500, 1000, 1500 s/mm(2) ) in three orthogonal directions were obtained using a multishot FSE-based Stejskal-Tanner DWI sequence (FSE-DWI) at 4.7T, while rats breathed medical air (21% oxygen) and with 100% oxygen challenge. Stretched-exponential and intravoxel incoherent motion (IVIM) models were used to calculate and compare quantitative diffusion parameters: diffusion heterogeneity index (α), intravoxel distribution of diffusion coefficients (DDC), tissue diffusivity (Dt), pseudo-diffusivity (Dp), and perfusion fraction (f) on a voxel-by-voxel basis. A significant increase of α (73.9 ± 4.7% in air vs. 78.1 ± 4.5% in oxygen, P = 0.0198) and a significant decrease of f (13.4 ± 3.7% in air vs. 10.4 ± 2.7% in oxygen, P = 0.0201) were observed to accompany oxygen challenge. Correlations between f and α during both air and oxygen breathing were found; the correlation coefficients (r) were -0.90 and -0.96, respectively. Positive correlations between Dt and DDC with oxygen breathing (r = 0.95, P = 0.0003), f and DDC with air breathing were also observed (r = 0.95, P = 0.0004). Quantitative diffusion MRI demonstrated changes in tumor perfusion in response to oxygen challenge. © 2015 Wiley Periodicals, Inc.

Differential Patterning of Genes Involved in Serotonin Metabolism and Transport in Extra-embryonic Tissues of the Mouse

PubMed Central

Wu, Hsiao-Huei; Choi, Sera; Levitt, Pat

2016-01-01

Introduction Serotonin (5-HT) is an important neuromodulator, but recently has been shown to be involved in neurodevelopment. Although previous studies have demonstrated that the placenta is a major source of forebrain 5-HT during early forebrain development, the processes of how 5-HT production, metabolism, and transport from placenta to fetus are regulated are unknown. As an initial step in determining the mechanisms involved, we investigated the expression patterns of genes critical for 5-HT system function in mouse extraembryonic tissues. Methods Mid- through late gestation expression of 5-HT system-related enzymes, Tph1, Ddc, Maoa, and 5-HT transporters, Sert/Slc6a4, Oct3/Slc22a3, Vmat2/Slc18a2, and 5-HT in placenta and yolk sac were examined, with cell type-specific resolution, using multiplex fluorescent in situ hybridization to co-localize transcripts and immunocytochemistry to co-localize the corresponding proteins and neurotransmitter. Results Tph1 and Ddc are found in the syncytiotrophoblast I (SynT-I) and sinusoidal trophoblast giant cells (S-TGC), whereas Maoa is expressed in SynT-I, syncytiotrophoblast II (SynT-II) and S-TGC. Oct3 expression is observed in the SynT-II only, while Vmat2 is mainly expressed in S-TGC. Surprisingly, there were comparatively high expression of Tph1, Ddc, and Maoa in the yolk sac visceral endoderm. Discussion In addition to trophoblast cells, visceral endoderm cells in the yolk sac may contribute to fetal 5-HT production. The findings raise the possibility of a more complex regulation of 5-HT access to the fetus through the differential roles of trophoblasts that surround maternal and fetal blood space and of yolk sac endoderm prior to normal degeneration. PMID:27238716

Evaluating Multi-Input/Multi-Output Digital Control Systems

NASA Technical Reports Server (NTRS)

Pototzky, Anthony S.; Wieseman, Carol D.; Hoadley, Sherwood T.; Mukhopadhyay, Vivek

1994-01-01

Controller-performance-evaluation (CPE) methodology for multi-input/multi-output (MIMO) digital control systems developed. Procedures identify potentially destabilizing controllers and confirm satisfactory performance of stabilizing ones. Methodology generic and used in many types of multi-loop digital-controller applications, including digital flight-control systems, digitally controlled spacecraft structures, and actively controlled wind-tunnel models. Also applicable to other complex, highly dynamic digital controllers, such as those in high-performance robot systems.

Interhemispheric balance patterns detected by selective phonemic dichotic laterality measures in four clinical subtypes of reading-disabled children.

PubMed

Morton, L L

1994-08-01

Identifying disabilities in word-attack, word-recognition, or reading comprehension, allowed for four categories of reading disability: (1) reading comprehension only (RC), (2) word-attack plus comprehension (WA+RC), (3) word-attack, word-recognition, and comprehension (WA+WR+RC), and (4) word-attack but not comprehension (WA-RC). Along with age-matched controls (AMC) and developmental-delay controls (DDC), the disabled were tested on a directed-attention dichotic task using consonant-vowel combinations. Laterality results for each place of articulation (i.e., bilabial, alveolar, and velar) selectively attested to greater left hemisphere involvement or engagement for the RC group and greater right hemisphere involvement or engagement for the WA+RC group. Performance of the other two disabled groups was consistent with less efficient right hemisphere involvement or callosal transfer. Implications for theory, research, and remediation are discussed.

Thesaurus of DDC Descriptors

DTIC Science & Technology

1966-06-01

BIRDS BLASTOMYCES BLATTIDAE BOVINES CANDIDA CANNABIS CARNIVORA CATS CEPHALOPODA CEREALS CETACEA CHICKENS CHILDREN CHIMPANZEES CHLORELLA...POLIOMYELITIS VIRUS POX VIRUSES PROTEUS PROTEUS VULGAR1S PROTOZOA PSEUOOMONADACEAE PSEUUOMONADALES PSEUDOMONAS PSEUDOMONAS AEROGINOSA RABIES VIRUS...ISLANUS MARYLAND MASSACHUSETTS MASSACHUSETTS BAY MEDITERRANEAN SEA MEDITERRANEAN SEA ISLANDS MELANESIA MEXICO MEXICO GULF MICHIGAN MICRONESIA

Crisis in Cataloging Revisited: The Year's Work in Subject Analysis, 1990.

ERIC Educational Resources Information Center

Young, James Bradford

1991-01-01

Reviews the 1990 literature that concerns subject analysis. Issues addressed include subject cataloging, including Library of Congress Subject Headings (LCSH); classification, including Dewey Decimal Classification (DDC), Library of Congress Classification, and classification in online systems; subject access, including the online use of…

DDC19: An Indictment.

ERIC Educational Resources Information Center

Berman, Sanford

1980-01-01

Criticizes the 19th edition of "Dewey Decimal Classification" for violating traditional classification goals for library materials and ignoring the desires of libraries and other users. A total reform is proposed to eliminate Phoenix schedules and to accept only those relocations approved by an editorial board of users. (RAA)

11 CFR 100.57 - Funds received in response to solicitations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 100.57 is vacated. See Final Order, EMILY's List v. FEC, No. 05-0049 (D.D.C. Nov. 30, 2009). [69 FR....S.C. 431) Definition of Contribution (2 U.S.C. 431(8)) § 100.57 Funds received in response to...

Salinity transfer in double diffusive convection bounded by two parallel plates

NASA Astrophysics Data System (ADS)

Yang, Yantao; van der Poel, Erwin P.; Ostilla-Monico, Rodolfo; Sun, Chao; Verzicco, Roberto; Grossmann, Siegfried; Lohse, Detlef

2014-11-01

The double diffusive convection (DDC) is the convection flow with the fluid density affected by two different components. In this study we numerically investigate DDC between two parallel plates with no-slip boundary conditions. The top plate has higher salinity and temperature than the lower one. Thus the flow is driven by the salinity difference and stabilised by the temperature difference. Our simulations are compared with the experiments by Hage and Tilgner (Phys. Fluids 22, 076603 (2010)) for several sets of parameters. Reasonable agreement is achieved for the salinity flux and its dependence on the salinity Rayleigh number. For all parameters considered, salt fingers emerge and extend through the entire domain height. The thermal Rayleigh number shows minor influence on the salinity flux although it does affect the Reynolds number. We apply the Grossmann-Lohse theory for Rayleigh-Bénard flow to the current problem without introducing any new coefficients. The theory successfully predicts the salinity flux with respect to the scaling for both the numerical and experimental results.

Studies of Particle Wake Potentials in Plasmas

NASA Astrophysics Data System (ADS)

Ellis, Ian; Graziani, Frank; Glosli, James; Strozzi, David; Surh, Michael; Richards, David; Decyk, Viktor; Mori, Warren

2011-10-01

Fast Ignition studies require a detailed understanding of electron scattering, stopping, and energy deposition in plasmas with variable values for the number of particles within a Debye sphere. Presently there is disagreement in the literature concerning the proper description of these processes. Developing and validating proper descriptions requires studying the processes using first-principle electrostatic simulations and possibly including magnetic fields. We are using the particle-particle particle-mesh (PPPM) code ddcMD and the particle-in-cell (PIC) code BEPS to perform these simulations. As a starting point in our study, we examine the wake of a particle passing through a plasma in 3D electrostatic simulations performed with ddcMD and with BEPS using various cell sizes. In this poster, we compare the wakes we observe in these simulations with each other and predictions from Vlasov theory. Prepared by LLNL under Contract DE-AC52-07NA27344 and by UCLA under Grant DE-FG52-09NA29552.

Nurses negotiating professional-familial care boundaries: striving for balance within double duty caregiving.

PubMed

Ward-Griffin, Catherine; Brown, Judith Belle; St-Amant, Oona; Sutherland, Nisha; Martin-Matthews, Anne; Keefe, Janice; Kerr, Mickey

2015-02-01

The purpose of this sequential, two-phase mixed-methods study was to examine the health of male and female nurses who provided care to older relatives (i.e., double duty caregivers). We explored the experiences of 32 double duty caregivers, which led to the development of an emergent grounded theory, Negotiating Professional-Familial Care Boundaries with two broad dialectical processes: professionalizing familial care and striving for balance. This article examines striving for balance, which is the process that responds to familial care expectations in the midst of available resources and reflects the health experiences of double duty caregivers. Two subprocesses of striving for balance, reaping the benefits and taking a toll, are presented in three composite vignettes, each representing specific double duty caregiving (DDC) prototypes (making it work, working to manage, living on the edge). This emergent theory extends current thinking of family caregiving that will inform the development and refinement of practices and policies relevant to DDC. © The Author(s) 2014.

Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break.

PubMed

Anderson, Carol M; Korkin, Dmitry; Smith, Dana L; Makovets, Svetlana; Seidel, Jeffrey J; Sali, Andrej; Blackburn, Elizabeth H

2008-04-01

The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.

Structural characterization of a new lipid/DNA complex showing a selective transfection efficiency in ovarian cancer cells

NASA Astrophysics Data System (ADS)

Caracciolo, G.; Pozzi, D.; Caminiti, R.; Congiu Castellano, A.

2003-04-01

We investigated, for the first time, by using Energy Dispersive X-ray Diffraction, the structure of a new ternary cationic liposome formulated with dioleoyl trimethylammonium propane (DOTAP), 1,2-dioleoyl-3-phosphatidylethanolamine (DOPE) and cholesterol (Chol) (DDC) which has been recently found to have a selective high gene transfer ability in ovarian cancer cells. Our structural results provide a further experimental support to the widely accepted statement that there is not a simple and direct correlation between structure and transfection efficiency and that the factors controlling cationic lipid/DNA (CL-DNA) complexes-mediated gene transfer depend not only on the formulations of the cationic liposomes and their thermodynamic phase, but also significantly on the cell properties.

Unregulated emissions from compressed natural gas (CNG) transit buses configured with and without oxidation catalyst.

PubMed

Okamoto, Robert A; Kado, Norman Y; Kuzmicky, Paul A; Ayala, Alberto; Kobayashi, Reiko

2006-01-01

The unregulated emissions from two in-use heavy-duty transit buses fueled by compressed natural gas (CNG) and equipped with oxidation catalyst (OxiCat) control were evaluated. We tested emissions from a transit bus powered by a 2001 Cummins Westport C Gas Plus 8.3-L engine (CWest), which meets the California Air Resources Board's (CARB) 2002 optional NOx standard (2.0 g/bhp-hr). In California, this engine is certified only with an OxiCat, so our study did not include emissions testing without it. We also tested a 2000 New Flyer 40-passenger low-floor bus powered by a Detroit Diesel series 50G engine (DDCs50G) that is currently certified in California without an OxiCat. The original equipment manufacturer (OEM) offers a "low-emission" package for this bus that includes an OxiCat for transit bus applications, thus, this configuration was also tested in this study. Previously, we reported that formaldehyde and other volatile organic emissions detected in the exhaust of the DDCs50G bus equipped with an OxiCat were significantly reduced relative to the same DDCs50G bus without OxiCat. In this paper, we examine othertoxic unregulated emissions of significance. The specific mutagenic activity of emission sample extracts was examined using the microsuspension assay. The total mutagenic activity of emissions (activity per mile) from the OxiCat-equipped DDC bus was generally lower than that from the DDC bus without the OxiCat. The CWest bus emission samples had mutagenic activity that was comparable to that of the OxiCat-equipped DDC bus. In general, polycyclic aromatic hydrocarbon (PAH) emissions were lower forthe OxiCat-equipped buses, with greater reductions observed for the volatile and semivolatile PAH emissions. Elemental carbon (EC) was detected in the exhaust from the all three bus configurations, and we found that the total carbon (TC) composition of particulate matter (PM) emissions was primarily organic carbon (OC). The amount of carbon emissions far exceeded the PM-associated inorganic element emissions, which were detected in all exhaust samples, at comparatively small emission rates. In summary, based on these results and those referenced from our group, the use of OxiCat for the new CWest engine and as a retrofit option for the DDCs50G engine generally results in the reduction of tailpipe toxic emissions. However, the conclusions of this study do not take into account OxiCat durability, deterioration, lubricant consumption, or vehicle maintenance, and these parameters merit further study.

Teaching Information Retrieval Using Telediscussion Techniques.

ERIC Educational Resources Information Center

Heiliger, Edward M.

This paper concerns an experiment in teaching a graduate seminar on Information Retrieval using telediscussion techniques. Outstanding persons from Project INTREX, MEDLARS, Chemical Abstracts, the University of Georgia, the SUNY biomedical Network, AEC, NASA, and DDC gave hour-long telelectures. A Conference Telephone Set was used with success.…

Automatic Selective Documentation Services.

ERIC Educational Resources Information Center

George, Ray L.

User needs studies often present figures indicating that documentation services systems which rely on the mails are inherently incapable of effectively supporting more than half of all research and development tasks. In addition to investigating faster ways of transmitting information, DDC has also been developing and testing systems based on…

MARC Coding of DDC for Subject Retrieval.

ERIC Educational Resources Information Center

Wajenberg, Arnold S.

1983-01-01

Recommends an expansion of MARC codes for decimal class numbers to enhance automated subject retrieval. Five values for a second indicator and two new subfields are suggested for encoding hierarchical relationships among decimal class numbers. Additional subfields are suggested to enhance retrieval through analysis of synthesized numbers in…

Antihyperalgesic Activities of Endocannabinoids in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.

PubMed

Munawar, Neha; Oriowo, Mabayoje A; Masocha, Willias

2017-01-01

Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are the cornerstone of the antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). However, their use is sometimes limited by the development of a painful sensory neuropathy, which does not respond well to drugs. Smoked cannabis has been reported in clinical trials to have efficacy in relieving painful HIV-associated sensory neuropathy. Objectives: The aim of this study was to evaluate whether the expression of endocannabinoid system molecules is altered during NRTI-induced painful neuropathy, and also whether endocannabinoids can attenuate NRTI-induced painful neuropathy. Methods: BALB/c mice were treated with 25 mg/kg of 2',3'-dideoxycytidine (ddC, zalcitabine), a NRTI, to induce thermal hyperalgesia. The expression of endocannabinoid system molecules was evaluated by real time polymerase chain reaction in the brain, spinal cord and paw skin at 6 days post ddC administration, a time point when mice had developed thermal hyperalgesia. The effects of the endocannabinoids, N -arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG), the cannabinoid type 1 (CB1) receptor antagonist AM 251, CB2 receptor antagonist AM 630, and G protein-coupled receptor 55 (GPR55) antagonists ML193 and CID 16020046 on ddC-induced thermal hyperalgesia were evaluated using the hot plate test. Results: ddC treatment resulted in thermal hyperalgesia and increased transcripts of the synthesizing enzyme Plcβ1 and decreased Daglβ in the paw skins, but not Napepld , and Daglα compared to vehicle treatment. Transcripts of the inactivating enzymes Faah and Mgll were downregulated in the brain and/or paw skin but not in the spinal cord of ddC-treated mice. Both AEA and 2-AG had antihyperalgesic effects in mice with ddC-induced thermal hyperalgesia, but had no effect in ddC-naïve mice. The antihyperalgesic activity of AEA was antagonized by AM251 and AM630, whereas the activity of 2-AG was antagonized by AM251, ML193 and CID 16020046, but not by AM630. Conclusion: These data show that ddC induces thermal hyperalgesia, which is associated with dysregulation of the mRNA expression of some endocannabinoid system molecules. The endocannabinoids AEA and 2-AG have antihyperalgesic activity, which is dependent on cannabinoid receptor and GPR55 activation. Thus, agonists of cannabinoid receptors and GPR55 could be useful therapeutic agents for the management of NRTI-induced painful sensory neuropathy.

Antihyperalgesic Activities of Endocannabinoids in a Mouse Model of Antiretroviral-Induced Neuropathic Pain

PubMed Central

Munawar, Neha; Oriowo, Mabayoje A.; Masocha, Willias

2017-01-01

Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are the cornerstone of the antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). However, their use is sometimes limited by the development of a painful sensory neuropathy, which does not respond well to drugs. Smoked cannabis has been reported in clinical trials to have efficacy in relieving painful HIV-associated sensory neuropathy. Objectives: The aim of this study was to evaluate whether the expression of endocannabinoid system molecules is altered during NRTI-induced painful neuropathy, and also whether endocannabinoids can attenuate NRTI-induced painful neuropathy. Methods: BALB/c mice were treated with 25 mg/kg of 2′,3′-dideoxycytidine (ddC, zalcitabine), a NRTI, to induce thermal hyperalgesia. The expression of endocannabinoid system molecules was evaluated by real time polymerase chain reaction in the brain, spinal cord and paw skin at 6 days post ddC administration, a time point when mice had developed thermal hyperalgesia. The effects of the endocannabinoids, N-arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG), the cannabinoid type 1 (CB1) receptor antagonist AM 251, CB2 receptor antagonist AM 630, and G protein-coupled receptor 55 (GPR55) antagonists ML193 and CID 16020046 on ddC-induced thermal hyperalgesia were evaluated using the hot plate test. Results: ddC treatment resulted in thermal hyperalgesia and increased transcripts of the synthesizing enzyme Plcβ1 and decreased Daglβ in the paw skins, but not Napepld, and Daglα compared to vehicle treatment. Transcripts of the inactivating enzymes Faah and Mgll were downregulated in the brain and/or paw skin but not in the spinal cord of ddC-treated mice. Both AEA and 2-AG had antihyperalgesic effects in mice with ddC-induced thermal hyperalgesia, but had no effect in ddC-naïve mice. The antihyperalgesic activity of AEA was antagonized by AM251 and AM630, whereas the activity of 2-AG was antagonized by AM251, ML193 and CID 16020046, but not by AM630. Conclusion: These data show that ddC induces thermal hyperalgesia, which is associated with dysregulation of the mRNA expression of some endocannabinoid system molecules. The endocannabinoids AEA and 2-AG have antihyperalgesic activity, which is dependent on cannabinoid receptor and GPR55 activation. Thus, agonists of cannabinoid receptors and GPR55 could be useful therapeutic agents for the management of NRTI-induced painful sensory neuropathy. PMID:28373843

Digital redesign of anti-wind-up controller for cascaded analog system.

PubMed

Chen, Y S; Tsai, J S H; Shieh, L S; Moussighi, M M

2003-01-01

The cascaded conventional anti-wind-up (CAW) design method for integral controller is discussed. Then, the prediction-based digital redesign methodology is utilized to find the new pulse amplitude modulated (PAM) digital controller for effective digital control of the analog plant with input saturation constraint. The desired digital controller is determined from existing or pre-designed CAW analog controller. The proposed method provides a novel methodology for indirect digital design of a continuous-time unity output-feedback system with a cascaded analog controller as in the case of PID controllers for industrial control processes with the presence of actuator saturations. It enables us to implement an existing or pre-designed cascaded CAW analog controller via a digital controller effectively.

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB.

PubMed

Ribasés, M; Ramos-Quiroga, J A; Hervás, A; Bosch, R; Bielsa, A; Gastaminza, X; Artigas, J; Rodriguez-Ben, S; Estivill, X; Casas, M; Cormand, B; Bayés, M

2009-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. Genetic, biochemical and pharmacological studies support the idea that the serotonin system participates in the etiology of ADHD. Based on these data, we aimed to analyze single nucleotide polymorphisms across 19 genes involved in the serotoninergic neurotransmission in a clinical sample of 451 ADHD patients (188 adults and 263 children) and 400 controls using a population-based association study. Several significant associations were found after correcting for multiple testing: (1) the DDC gene was strongly associated with both adulthood (P=0.00053; odds ratio (OR)=2.17) and childhood ADHD (P=0.0017; OR=1.90); (2) the MAOB gene was found specifically associated in the adult ADHD sample (P=0.0029; OR=1.90) and (3) the 5HT2A gene showed evidence of association only with the combined ADHD subtype both in adults (P=0.0036; OR=1.63) and children (P=0.0084; OR=1.49). Our data support the contribution of the serotoninergic system in the genetic predisposition to ADHD, identifying common childhood and adulthood ADHD susceptibility factors, associations that are specific to ADHD subtypes and one variant potentially involved in the continuity of the disorder throughout lifespan.

Absence of a Universal Mechanism of Mitochondrial Toxicity by Nucleoside Analogs▿

PubMed Central

Lund, Kaleb C.; Peterson, LaRae L.; Wallace, Kendall B.

2007-01-01

Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 μM; 2.7 and 13.4 μg/ml), didanosine (ddI) (10 and 50 μM; 2.4 and 11.8 μg/ml), and zalcitabine (ddC) (1 and 5 μM; 0.21 and 1.1 μg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. Ethidium bromide (EtBr) (0.5 μg/ml; 1.3 μM) was used as a positive control. AZT treatment resulted in metabolic disruption (increased lactate and superoxide) and increased cell mortality with decreased proliferation, while mtDNA remained unchanged or increased (HepG2 cells; 50 μM AZT). ddC caused pronounced mtDNA depletion in HepG2 cells but not in H9c2 cells and increased mortality in HepG2 cells, but no significant metabolic disruption in either cell type. ddI caused a moderate depletion of mtDNA in both cell types but showed no other effects. EtBr exposure resulted in metabolic disruption, increased cell mortality with decreased cell proliferation, and mtDNA depletion in both cell types. We conclude that nucleoside analogs display unique toxicities within and between culture models, and therefore, care should be taken when generalizing about the mechanisms of nucleoside reverse transcriptase inhibitor toxicity. Additionally, mtDNA abundance does not necessarily correlate with metabolic disruption, especially in cell culture; careful discernment is recommended in this regard. PMID:17470651

Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs.

PubMed

Lund, Kaleb C; Peterson, LaRae L; Wallace, Kendall B

2007-07-01

Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 microM; 2.7 and 13.4 microg/ml), didanosine (ddI) (10 and 50 microM; 2.4 and 11.8 microg/ml), and zalcitabine (ddC) (1 and 5 microM; 0.21 and 1.1 microg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. Ethidium bromide (EtBr) (0.5 microg/ml; 1.3 microM) was used as a positive control. AZT treatment resulted in metabolic disruption (increased lactate and superoxide) and increased cell mortality with decreased proliferation, while mtDNA remained unchanged or increased (HepG2 cells; 50 microM AZT). ddC caused pronounced mtDNA depletion in HepG2 cells but not in H9c2 cells and increased mortality in HepG2 cells, but no significant metabolic disruption in either cell type. ddI caused a moderate depletion of mtDNA in both cell types but showed no other effects. EtBr exposure resulted in metabolic disruption, increased cell mortality with decreased cell proliferation, and mtDNA depletion in both cell types. We conclude that nucleoside analogs display unique toxicities within and between culture models, and therefore, care should be taken when generalizing about the mechanisms of nucleoside reverse transcriptase inhibitor toxicity. Additionally, mtDNA abundance does not necessarily correlate with metabolic disruption, especially in cell culture; careful discernment is recommended in this regard.

Molecular detection of establishment and geographical distribution of Brazilian isolates of Neozygites tanajoae, a fungus pathogenic to cassava green mite, in Benin (West Africa)

PubMed Central

Hanna, Rachid; von Tiedemann, Andreas

2010-01-01

Diagnostic PCR with two specific primer pairs (NEOSSU and 8DDC) were used to monitor the establishment and geographical distribution of Brazilian isolates of Neozygites tanajoae Delalibera, Hajek and Humber (Entomophthorales: Neozygitaceae) released in Benin for the biological control of the cassava green mite, Mononychellus tanajoa (Bondar) (Acari: Tetranychidae). A total of 141 cassava fields were visited and samples of M. tanajoa suspected to be infected by N. tanajoae were collected in 60 fields distributed between the coastal Southern Forest Mosaic (SFM) and the Northern Guinea Savanna (NGS) zones of Benin, West Africa. Analysis of DNA samples of dead mites using the species specific NEOSSU primers revealed the presence of N. tanajoae in 46 fields. The second country specific pair of primers 8DDC revealed the presence of Brazilian isolates of N. tanajoae in 36 fields, representing 78.3% of fields positive for N. tanajoae. Brazilian isolates occurred from SFM to NGS zones in Benin, however, they were concentrated in fields located within former release zones (e.g. Department of Ouémé in the South and Borgou in the North). In contrast, the indigenous African isolates of N. tanajoae were evenly distributed in the sub-humid and humid savannah zones of the country. The mean infection rate of M. tanajoa with indigenous isolates of N. tanajoae was relatively low (5.3%) compared to Brazilian isolates (28%), indicating a higher biocontrol potential of the latter. This first post-release monitoring using PCR techniques showed that the Brazilian strains of N. tanajoae is well established in Benin and spread effectively in this area. PMID:20838883

A resolution to authorize document production in United States v. Douglas D. Hampton (D.D.C.).

THOMAS, 112th Congress

Sen. Reid, Harry [D-NV

2011-04-07

Senate - 04/07/2011 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

Dewey: How to Make It Work for You

ERIC Educational Resources Information Center

Panzer, Michael

2013-01-01

As knowledge brokers, librarians are living in interesting times for themselves and libraries. It causes them to wonder sometimes if the traditional tools like the Dewey Decimal Classification (DDC) system can cope with the onslaught of information. The categories provided do not always seem adequate for the knowledge-discovery habits of…

Naval Training Device Center Index of Technical Reports.

ERIC Educational Resources Information Center

Walker, Lemuel E.

Published Naval Training Device Center technical reports and some technical notes (those available through the Defense Documentation Center-DDC) which have resulted from basic research, exploratory development, and advanced development type projects are listed. The reports are indexed by technical note number, by title, and by contractor code. The…

A DDC Bibliography on Microfiche, Microfilm and Related Equipment, Volume 1.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

This bibliography contains abstracts of 40 unclassified-unlimited reports on microfiche, microfilm and related equipment acquired by the Defense Documentation Center since 1953. Citations are topically arranged in AD sequence, ascending order. The following computer produced indexes are provided: subject, corporate author, personal author,…

THE ROLE OF SEARCHING SERVICES IN AN ACQUISITIONS PROGRAM.

ERIC Educational Resources Information Center

LUECK, ANTOINETTE L.; AND OTHERS

A USER PRESENTS HIS POINT OF VIEW ON LITERATURE SEARCHING THROUGH THE MAJOR SEARCHING SERVICES IN THE OVERALL PROGRAM OF ACQUISITIONS FOR THE ENGINEERING STAFF OF THE AIR FORCE AERO PROPULSION LABORATORY. THESE MAJOR SEARCHING SERVICES INCLUDE THE DEFENSE DOCUMENTATION CENTER (DDC), THE NATIONAL AERONAUTICS AND SPACE ADMINISTRATION (NASA), THE…

Success Prediction: A DDC Bibliography. December 1949--December 1971.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

This document contains bibliographic information, descriptive terms, and abstracts for 145 technical reports on the general subject of success prediction. The bibliography includes reports on development of individuals during military training, peer evaluation, biographical inventory, and the validity of tests which may be used as predictors of…

A DDC Bibliography on Optical or Graphic Information Processing (Information Sciences Series). Volume I.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

This unclassified-unlimited bibliography contains 183 references, with abstracts, dealing specifically with optical or graphic information processing. Citations are grouped under three headings: display devices and theory, character recognition, and pattern recognition. Within each group, they are arranged in accession number (AD-number) sequence.…

Library Classification 2020

ERIC Educational Resources Information Center

Harris, Christopher

2013-01-01

In this article the author explores how a new library classification system might be designed using some aspects of the Dewey Decimal Classification (DDC) and ideas from other systems to create something that works for school libraries in the year 2020. By examining what works well with the Dewey Decimal System, what features should be carried…

Characteristics of the Class of 1982

DTIC Science & Technology

1978-08-01

classification systems have you used? A. Dewey Decimal System. B. Library of Congress System. C. Both. D. Neither. 93. Have you consulted periodical...I y 4󈨒-019 UNITED V STATES, -- I ~j~1MILITARY I ~ ACADEMY WEST POINT, NEW YORK ~ J~x~ A ’ CHARACTERISTICS OF -THE CLASS OF 1982 ID DDC

Doppler Spectra of Bistatic Reverberation from the Sea Surface.

DTIC Science & Technology

1979-05-08

GOVT ACCESSIN NO RECIPIENTS8 CATALOG NUMBER S. TtE ... wuw~tP RED DOPPLER .&PECTRA OF JISTATIC REVERBEATION( 9; t - .e:. TROM THE SEA SURFACE...National Resear-h Council, Committee Undersea Warfare 1 Woods Hole Oceanographic Institution 1 NORDA Code 110, 200, 300, 500, 600 5 DDC, Alexandria 12

Seasonal postembryonic maturation of the diurnal rhythm of serotonin in the chicken pineal gland.

PubMed

Piesiewicz, Aneta; Kedzierska, Urszula; Turkowska, Elzbieta; Adamska, Iwona; Majewski, Pawel M

2015-02-01

Previously, we have demonstrated the postembryonic development of chicken (Gallus gallus domesticus L.) pineal gland functions expressed as changes in melatonin (MEL) biosynthesis. Pineal concentrations of MEL and its precursor serotonin (5-HT) were shown to increase between the 2nd and 16th day of life. We also found that levels of the mRNAs encoding the enzymes participating in the final two steps of MEL biosynthesis from 5-HT: arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as their enzymatic activities, were raised during postembryonic development. Moreover, the manner of these changes was season-of-hatch dependent, even in animals kept under constant laboratory conditions (L:D 12:12). The most pronounced changes were seen in the concentrations of 5-HT and MEL, as well as in Aanat mRNA level and its enzymatic activity. The high daily variability in 5-HT content suggested that season- and age-dependent changes in the activity of the chicken pineal gland might rely on the availability of 5-HT, i.e. it may be limited by changes in pineal tryptophan (TRP) and/or 5-hydroxytryptophan (5-HTP) levels as well as by the activity of tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC): two enzymes participating in the conversion of TRP to 5-HT. The present study was undertaken with the following objectives: (1) to examine whether the pineal concentration of the 5-HT precursors TRP and 5-HTP exhibit age- and season-related changes; (2) to look for season-related differences in the transcription of the Tph1 and Ddc genes encoding enzymes TPH and AADC; (3) to identify the step(s) in postembryonic development in which these season-related variations in pineal gland function are most pronounced. Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held in L:D 16:8 conditions were kept from the day of hatch in L:D 12:12 conditions. At the age of 2 or 9 days, animals were sacrificed every 2 or 4 h over a 24-h period and their pineal glands were isolated under dim red light and processed for the measurement of (i) the pineal content of TRP, 5-HTP and 5-HT, and (ii) the level of Tph1 and Ddc mRNAs. Circadian rhythmicity of all the measured parameters was evaluated by the cosinor method. The pineal levels of TRP and 5-HT as well as the Tph1 and Ddc transcripts changed during postembryonic development in a season-related way. Whereas, the 5-HTP concentration did not vary between animals from both age groups, regardless of the season. Circadian rhythmicity of all the measured parameters was dependent on both the age and the season of hatch, and was greatest in older animals in the summer. These findings indicated that the efficiency of season-related MEL biosynthesis, reported previously, is limited by 5-HT availability and this limitation depends on the transcription of both the Tph1 and Ddc genes. Moreover, Ddc mRNA level in 9-d-old birds changed rhythmically, even though this gene is generally considered to be arrhythmic.

Multi-GPU implementation of a VMAT treatment plan optimization algorithm.

PubMed

Tian, Zhen; Peng, Fei; Folkerts, Michael; Tan, Jun; Jia, Xun; Jiang, Steve B

2015-06-01

Volumetric modulated arc therapy (VMAT) optimization is a computationally challenging problem due to its large data size, high degrees of freedom, and many hardware constraints. High-performance graphics processing units (GPUs) have been used to speed up the computations. However, GPU's relatively small memory size cannot handle cases with a large dose-deposition coefficient (DDC) matrix in cases of, e.g., those with a large target size, multiple targets, multiple arcs, and/or small beamlet size. The main purpose of this paper is to report an implementation of a column-generation-based VMAT algorithm, previously developed in the authors' group, on a multi-GPU platform to solve the memory limitation problem. While the column-generation-based VMAT algorithm has been previously developed, the GPU implementation details have not been reported. Hence, another purpose is to present detailed techniques employed for GPU implementation. The authors also would like to utilize this particular problem as an example problem to study the feasibility of using a multi-GPU platform to solve large-scale problems in medical physics. The column-generation approach generates VMAT apertures sequentially by solving a pricing problem (PP) and a master problem (MP) iteratively. In the authors' method, the sparse DDC matrix is first stored on a CPU in coordinate list format (COO). On the GPU side, this matrix is split into four submatrices according to beam angles, which are stored on four GPUs in compressed sparse row format. Computation of beamlet price, the first step in PP, is accomplished using multi-GPUs. A fast inter-GPU data transfer scheme is accomplished using peer-to-peer access. The remaining steps of PP and MP problems are implemented on CPU or a single GPU due to their modest problem scale and computational loads. Barzilai and Borwein algorithm with a subspace step scheme is adopted here to solve the MP problem. A head and neck (H&N) cancer case is then used to validate the authors' method. The authors also compare their multi-GPU implementation with three different single GPU implementation strategies, i.e., truncating DDC matrix (S1), repeatedly transferring DDC matrix between CPU and GPU (S2), and porting computations involving DDC matrix to CPU (S3), in terms of both plan quality and computational efficiency. Two more H&N patient cases and three prostate cases are used to demonstrate the advantages of the authors' method. The authors' multi-GPU implementation can finish the optimization process within ∼ 1 min for the H&N patient case. S1 leads to an inferior plan quality although its total time was 10 s shorter than the multi-GPU implementation due to the reduced matrix size. S2 and S3 yield the same plan quality as the multi-GPU implementation but take ∼4 and ∼6 min, respectively. High computational efficiency was consistently achieved for the other five patient cases tested, with VMAT plans of clinically acceptable quality obtained within 23-46 s. Conversely, to obtain clinically comparable or acceptable plans for all six of these VMAT cases that the authors have tested in this paper, the optimization time needed in a commercial TPS system on CPU was found to be in an order of several minutes. The results demonstrate that the multi-GPU implementation of the authors' column-generation-based VMAT optimization can handle the large-scale VMAT optimization problem efficiently without sacrificing plan quality. The authors' study may serve as an example to shed some light on other large-scale medical physics problems that require multi-GPU techniques.

Low-to-Medium Power Single Chip Digital Controlled DC-DC Regulator for Point-of-Load Applications

NASA Technical Reports Server (NTRS)

Adell, Philippe C. (Inventor); Bakkaloglu, Bertan (Inventor); Vermeire, Bert (Inventor); Liu, Tao (Inventor)

2015-01-01

A DC-DC converter for generating a DC output voltage includes: a digitally controlled pulse width modulator (DPWM) for controlling a switching power stage to supply a varying voltage to an inductor; and a digital voltage feedback circuit for controlling the DPWM in accordance with a feedback voltage corresponding to the DC output voltage, the digital voltage feedback circuit including: a first voltage controlled oscillator for converting the feedback voltage into a first frequency signal and to supply the first frequency signal to a first frequency discriminator; a second voltage controlled oscillator for converting a reference voltage into a second frequency signal and to supply the second frequency signal to a second frequency discriminator; a digital comparator for comparing digital outputs of the first and second frequency discriminators and for outputting a digital feedback signal; and a controller for controlling the DPWM in accordance with the digital feedback signal.

A DDC Bibliography on Computers in Information Sciences. Volume I. Information Sciences Series.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

The unclassified and unlimited bibliography compiles references dealing specifically with the role of computers in information sciences. The volume contains 249 annotated references grouped under two major headings: Time Shared, On-Line, and Real Time Systems, and Computer Components. The references are arranged in accesion number (AD-number)…

78 FR 43221 - Federal Property Suitable as Facilities To Assist the Homeless

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... speech-impaired (202) 708-2565 (these telephone numbers are not toll-free), or call the toll-free Title V... the Homeless v. Veterans Administration, No. 88-2503-OG (D.D.C.). Properties reviewed are listed in... Assistant Secretary for Special Needs. TITLE V, FEDERAL SURPLUS PROPERTY PROGRAM FEDERAL REGISTER REPORT FOR...

Machine-Aided Indexing. Technical Progress Report for Period January 1967-June 1969.

ERIC Educational Resources Information Center

Klingbiel, Paul H.

Working toward the goal of an automatic indexing system which is truly competitive with human indexing in cost, time and comprehensiveness the Machine-Aided Indexing (MAI) process was developed at the Defense Documentation Center (DDC). This indexing process uses linguistic techniques but does not require complete syntactic analysis of sentences…

Dewey or Don't We?

ERIC Educational Resources Information Center

Pendergrass, Devona J.

2013-01-01

"Dewey or don't we?" is the question that hundreds, if not thousands, of school librarians across the country are currently asking themselves. Do they throw out what is old but trusted for new organizational systems, or do they continue using the Dewey Decimal Classification (DDC) system and make changes and adjustments to the…

Automated SDI Services. (Selective Dissemination of Information).

ERIC Educational Resources Information Center

Altmann, Berthold

An automated SDI service based on tapes supplied by DDC, Science Abstracts, and Engineering Index is evaluated as a component element of the entire HDL information system. Current studies for improving the efficiency are briefly described,--in particular, the establishment of a parameter reference service that should shorten the lead-time for the…

RSCREEN and OPGEN: Two Problem Structuring Decision Aids Which Employ Decision Templates

DTIC Science & Technology

1980-10-01

example, a hierarchical taxonomy could be provided to the user (something like a Dewey Decimal System for models), either as a complete directory or as...Attention: DDC -TC Cameron Station Alexandria, Virginia 22314 DCASMA Baltimore Office 1 copy Attention: Mrs. Betty L. Drisk-11 300 East Joppa Road Towson

Comparing Three Patterns of Strengths and Weaknesses Models for the Identification of Specific Learning Disabilities

ERIC Educational Resources Information Center

Miller, Daniel C.; Maricle, Denise E.; Jones, Alicia M.

2016-01-01

Processing Strengths and Weaknesses (PSW) models have been proposed as a method for identifying specific learning disabilities. Three PSW models were examined for their ability to predict expert identified specific learning disabilities cases. The Dual Discrepancy/Consistency Model (DD/C; Flanagan, Ortiz, & Alfonso, 2013) as operationalized by…

29 CFR 452.80 - Bona fide candidates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... nominated in order to be a bona fide candidate entitled to exercise the rights mentioned in §§ 452.67 and... able to take advantage of the distribution rights even before the convention meets and thus attempt to.... United Mine Workers, 71 LRRM 2606, 60 L.C. 10,204 (D.D.C. 1969). ...

Molecular and functional analyses of amino acid decarboxylases involved in cuticle tanning in Tribolium castaneum

USDA-ARS?s Scientific Manuscript database

Aspartate 1-decarboxylase (ADC) and dopa decarboxylase (DDC) provide b–alanine and dopamine used in insect cuticle tanning. Beta-alanine is conjugated with dopamine to yield N-b-alanyldopamine (NBAD), a substrate for the phenoloxidase laccase that catalyzes the synthesis of cuticle protein cross-li...

Second-generation detector work in Israel

NASA Astrophysics Data System (ADS)

Rosenfeld, David

2001-10-01

A tremendous developmental effort in the field of infrared detectors during the last decade in Israel has resulted in a variety of InSb and HgCdTe infrared detectors. Additional and significant R&D effort associated with other IR components, have also been done in Israel, in order to integrate the detectors into advanced Detector-Dewar-Cooler assemblies (DDCs). This R&D effort included notable activities in the field of materials, signal processors, dewars and cryocoolers. These activities are presented together with the status of infrared detector work in Israel. Several two-dimensional InSb staring detectors and DDCs are demonstrated. This includes two versions of the classical 256 X 256 detectors and DDCs, improved 640 X 480 InSb detectors and DDC, and a 2000- element detector with high TDI level. SADA II type HgCdTe detectors are also presented. Considerations regarding the course of future detector work are also described. The classical DDC requirement list which traditionally included demands for high D*, low NETD and high resolution is widened to include cost related issues such as higher reliability, lower maintenance, smaller volume, lower power consumption and higher operation temperature.

Double-diffusive layers in the Adriatic Sea

NASA Astrophysics Data System (ADS)

Carniel, Sandro; Sclavo, Mauro; Kantha, Lakshmi; Prandke, Hartmut

2008-01-01

A microstructure profiler was deployed to make turbulence measurements in the upper layers of the southern Adriatic Sea in the Mediterranean during the Naval Research Laboratory (NRL) DART06A (Dynamics of the Adriatic in Real Time) winter cruise in March 2006. Measurements in the Po river plume along the Italian coast near the Gargano promontory displayed classic double-diffusive layers and staircase structures resulting from the relatively colder and fresher wintertime Po river outflow water masses overlying warmer and more saline water masses from the Adriatic Sea. We report here on the water mass and turbulence structure measurements made both in the double-diffusive interfaces and the adjoining mixed layers in the water columns undergoing double-diffusive convection (DDC). This dataset augments the relatively sparse observations available hitherto on the diffusive layer type of DDC. Measured turbulence diffusivities are consistent with those from earlier theoretical and experimental formulations, suggesting that the wintertime Po river plume is a convenient and easily accessible place to study double diffusive convective processes of importance to mixing in the interior of many regions of the global oceans.

A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from feline immunodeficiency virus confers resistance to oxathiolane nucleosides.

PubMed Central

Smith, R A; Remington, K M; Lloyd, R M; Schinazi, R F; North, T W

1997-01-01

Variants of feline immunodeficiency virus (FIV) that possess a unique methionine-to-threonine mutation within the YMDD motif of reverse transcriptase (RT) were selected by culturing virus in the presence of inhibitory concentrations of (-)-beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC]. The mutants were resistant to (-)-FTC and (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) and additionally exhibited low-level resistance to 2',3'-dideoxycytidine (ddC). DNA sequence analysis of the RT-encoding region of the pol gene amplified from resistant viruses consistently identified a Met-to-Thr mutation in the YMDD motif. Purified RT from the mutants was also resistant to the 5'-triphosphate forms of 3TC, (-)-FTC, and ddC. Site-directed mutants of FIV were engineered which contain either the novel Met-to-Thr mutation or the Met-to-Val mutation seen in oxathiolane nucleoside-resistant HIV-1. Both site-directed mutants displayed resistance to 3TC, thus confirming the role of these mutations in the resistance of FIV to beta-L-3'-thianucleosides. PMID:9032372

Comparison of digital controllers used in magnetic suspension and balance systems

NASA Technical Reports Server (NTRS)

Kilgore, William A.

1990-01-01

Dynamic systems that were once controlled by analog circuits are now controlled by digital computers. Presented is a comparison of the digital controllers presently used with magnetic suspension and balance systems. The overall responses of the systems are compared using a computer simulation of the magnetic suspension and balance system and the digital controllers. The comparisons include responses to both simulated force and position inputs. A preferred digital controller is determined from the simulated responses.

Application of digital control techniques for satellite medium power DC-DC converters

NASA Astrophysics Data System (ADS)

Skup, Konrad R.; Grudzinski, Pawel; Nowosielski, Witold; Orleanski, Piotr; Wawrzaszek, Roman

2010-09-01

The objective of this paper is to present a work concerning a digital control loop system for satellite medium power DC-DC converters that is done in Space Research Centre. The whole control process of a described power converter bases on a high speed digital signal processing. The paper presents a development of a FPGA digital controller for voltage mode stabilization that was implemented using VHDL. The described controllers are a classical digital PID controller and a bang-bang controller. The used converter for testing is a simple model of 5-20 W, 200 kHz buck power converter. A high resolution digital PWM approach is presented. Additionally a simple and effective solution of filtering of an analog-to-digital converter output is presented.

Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine.

PubMed Central

Gu, Z; Gao, Q; Li, X; Parniak, M A; Wainberg, M A

1992-01-01

We have used the technique of in vitro selection to generate variants of human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxyinosine (ddI) and cross-resistant to 2',3'-dideoxycytidine (ddC). The complete reverse transcriptase (RT)-coding regions, plus portions of flanking sequences, of viruses possessing a ddI-resistant phenotype were cloned and sequenced by polymerase chain reaction (PCR)-based methods. We observed that several of these viruses possessed mutations at amino acid sites 184 (Met-->Val; ATG-->GTG) and 294 (Pro-->Ser; CCA-->TCA). These mutations were introduced in the pol gene of infectious, cloned HXB2-D DNA by site-directed mutagenesis. Viral replication assays confirmed the importance of site 184 with regard to resistance to ddI. The recombinant viruses thus generated displayed more than fivefold-greater resistance to ddI than parental HXB2-D did. Moreover, more than fivefold-greater resistance to ddC was also documented; however, the recombinant viruses continued to be inhibited by zidovudine (AZT). No resistance to ddI, ddC, or AZT was introduced by inclusion of mutation site 294 in the pol gene of HXB2-D. PCR analysis performed on viral samples obtained from patients receiving long-term ddI therapy confirmed the presence of mutation site 184 in five of seven cases tested. In three of these five positive cases, the wild-type codon was also detected, indicating that mixtures of viral quasispecies were apparently present. Viruses possessing a ddI resistance phenotype were isolated from both subjects whose viruses contained only the mutated rather than wild-type codon at position 184 as well as from a third individual, whose viruses appeared to be mostly of the mutated variety. Images PMID:1279198

Thermohaline Staircases in the Amundsen Basin: possible disruption by shear and mixing.

NASA Astrophysics Data System (ADS)

Guthrie, J.; Fer, I.; Morison, J.

2016-02-01

As part of the 2013 and 2014 Field Seasons of the North Pole Environmental Observatory in the Amundsen Basin of the Arctic Ocean, two temperature microstructure experiments were performed. A Rockland Scientific Microrider with FP07 fast response thermistors was attached to a Conductivity-Temperature-Depth unit (SBE 19+ in 2013, SBE 911 in 2014). From a heated hut, the instrument package was lowered through a 30" hole in the sea ice at a speed of 25 cm s-1 with a motorized winch. The 2013 data set was characterized by an extensive thermohaline staircase, indicative of the diffusive convective type of double diffusion (DDC), from 150-250 m depths. The staircase was absent in the upper part of that depth range in 2014, even though an analysis of density ratio, Rρ, still shows high susceptibility to DDC. In the depth range of interest, survey averaged Rρ = 3 in 2013 and Rρ = 3.3 in 2014, indicating that hydrographic differences might not be the cause of staircase disappearance. We propose that increased upper ocean shear and turbulent mixing, possibly associated with strong wind events, caused disruption of the staircase in 2014. Average thermal diffusivity, KT, between 70 - 120 m is elevated in 2014, 7 x 10-6 m2s-1, compared to 2013, 2 x 10-6 m2s-1. Also, finescale shear variance between 70-200 m calculated from eXpendable Current Profilers in 2014 is nearly 3 times as high when compared to 2013. Despite increased turbulence over the staircase region in 2014, heat fluxes are remarkably consistent between the surveys. Even though they have been previously reported and the basin has favorable stratification, DDC staircases are less prevalent in the Amundsen Basin when compared to the Canada Basin. Possible reasons behind the lack of an omnipresent thermohaline staircase in the Amundsen Basin will be discussed.

DJ-1 deficiency attenuates expansion of liver progenitor cells through modulating the inflammatory and fibrogenic niches

PubMed Central

Chen, L; Luo, M; Sun, X; Qin, J; Yu, C; Wen, Y; Zhang, Q; Gu, J; Xia, Q; Kong, X

2016-01-01

Our previous study suggested that DJ-1 has a critical role in initiating an inflammatory response, but its role in the liver progenitor cell (LPC) expansion, a process highly dependent on the inflammatory niche, remains elusive. The objective of this study is to determine the role of DJ-1 in LPC expansion. The correlation of DJ-1 expression with LPC markers was examined in the liver of patients with hepatitis B or hepatitis C virus (HBV and HCV, respectively) infection, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), nonalcoholic fatty liver disease (NAFLD), cirrhosis or hepatocellular carcinoma (HCC), respectively. The role of DJ-1 in LPC expansion and the formation of LPC-associated fibrosis and inflammation was examined in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced liver injury murine model. We also determined the ability of hepatic stellate cells (HSCs) in recruiting macrophages in DJ-1 knockout (KO) mice. The expression levels of DJ-1 were upregulated in the liver of HBV, HCV, PBC and PSC patients and DDC-fed mice. Additionally, DJ-1 expression was positively correlated with LPC proliferation in patients with liver injury and mice with DDC exposure. DJ-1 has no direct effect on LPC proliferation. Reduced activation of HSCs and collagen deposition were observed in DJ-1 KO mice. Furthermore, infiltrated CD11b+Gr-1low macrophages and pro-inflammatory factors (IL-6, TNF-α) were attenuated in DJ-1 KO mice. Mechanistically, we found that HSCs isolated from DJ-1 KO mice had decreased secretion of macrophage-mobilizing chemokines, such as CCL2 and CX3CL1, resulting in impaired macrophage infiltration. DJ-1 positively correlates with LPC expansion during liver injury. DJ-1 deficiency negatively regulates LPC proliferation by impairing the formation of LPC-associated fibrosis and inflammatory niches. PMID:27277679

The relationship between rs3779084 in the dopa decarboxylase (DDC) gene and alcohol consumption is mediated by drinking motives in regular smokers.

PubMed

Kristjansson, Sean D; Agrawal, Arpana; Lessov-Schlaggar, Christina N; Madden, Pamela A F; Cooper, M Lynne; Bucholz, Kathleen K; Sher, Kenneth J; Lynskey, Michael T; Heath, Andrew C

2012-01-01

Motivational models of alcohol use propose that the motivation to consume alcohol is the final common pathway to its use. Both alcohol consumption and drinking motives are influenced by latent genetic factors that partially overlap. This study investigated whether drinking motives mediate the associations between alcohol consumption and 2 single-nucleotide polymorphisms (SNPs) from genes involved in serotonin (TPH2; rs1386496) and dopamine synthesis (DDC; rs3779084). Based on earlier work showing that enhancement and coping motives were heritable in regular smokers but not in nonregular smokers, we hypothesized these motives would mediate the relationships between alcohol consumption and these SNPs in regular smokers. Drinking motives data were available from 830 young adult female twins (n = 344 regular smokers and n = 486 never/nonregular smokers). We used confirmatory factor analyses to model enhancement, coping, and alcohol consumption factors and to conduct mediation analyses in the regular smoker and never/nonregular smoker groups. Our hypothesis was partially supported. The relationship between alcohol consumption and rs1386496 was not mediated by drinking motives in either group. However, in the regular smokers, the relationship between alcohol consumption and rs3779084 was mediated by enhancement and coping motives. Carriers of the rs3779084 minor allele who were regular smokers reported more motivation to consume alcohol. Given this pattern of results was absent in the never/nonregular smokers, our results are consistent with a gene × smoking status interaction. In regular smokers, variability at the locus marked by rs3779084 in the DDC gene appears to index biologically based individual differences in the motivation to consume alcohol to attain or improve a positive affective state or to relieve a negative one. These results could be because of increased sensitivity to the reinforcing effects of alcohol among minor allele carriers who smoke, which might be due to structural or functional differences in mesorticolimic dopamine "reward" circuitry. Copyright © 2011 by the Research Society on Alcoholism.

Superoxide dismutase (SOD) in boar spermatozoa: purification, biochemical properties and changes in activity during semen storage (16°C) in different extenders.

PubMed

Orzołek, Aleksandra; Wysocki, Paweł; Strzeżek, Jerzy; Kordan, Władysław

2013-03-01

The antioxidant system in semen is composed of enzymes, low-molecular weight antioxidants and seminal plasma proteins. Loss of enzymatic activity of superoxide dismutase (SOD) during semen preservation may cause insufficient antioxidant defense of boar spermatozoa. The aim of this study was to isolate and characterize SOD molecular forms from spermatozoa and to describe changes in SOD activity in boar sperm during preservation at 16°C. Sperm extracts were prepared from fresh or diluted semen and used for SOD purification or activity measurement. Ion-exchange chromatography and gel filtration was used to purify SOD molecular forms. BTS, Dilu Cell, M III and Vitasem were used as diluents for 5-day storage of semen at +16°C. The molecular form of SOD released from spermatozoa after cold shock and homogenization had a molecular weight of approximately 67kDa. The activity of the SOD form was the highest at pH 10 within the temperature range between 20 and 45°C. The enzymatic activity of form released after cold shock was inhibited by H2O2 and diethyldithiocarbamate (DDC; by 65 and 40%, respectively). The SOD form released by homogenization was inhibited by H2O2 and DDC (40%). The molecular form released after urea treatment was a 30kDa protein with maximum activity at 20°C and pH 10. Enzymatic activity of this form was inhibited by H2O2 by 35%, DDC by 80% and 2-mercaptoethanol by 15%. The antigenic determinants of SOD isolated from boar seminal plasma and spermatozoa were similar to each other. Susceptibility of spermatozoa to cold shock increased during storage, but the differences between extenders were statistically non-significant. Copyright © 2013 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A proposal of the diagnosis-dynamic characteristic (DDC) model describing the relation between search time and confidence levels for a dichotomous judgment, and its application to ROC curve generation

NASA Astrophysics Data System (ADS)

Matsumoto, Toru; Fukuda, Nobuo; Furukawa, Akira; Suwa, Koji; Wada, Shinichi; Matsumoto, Mitsuomi; Sone, Shusuke

2006-03-01

When physicians inspect an image, they make up a certain degree of confidence that the image are abnormal; p(t), or normal; n(t)[n(t)=1-p(t)]. After infinite time of the inspection, they reach the equilibrium levels of the confidence of p*=p(∞) and n*=n(∞). There are psychological conflicts between the decisions of normal and abnormal. We assume that the decision of "normal" is distracted by the decision of "abnormal" by a factor of k(1 + ap), and in an inverse direction by a factor of k(1 + bn), where k ( > 0) is a parameter that relates with image quality and skill of the physicians, and a and b are unknown constants. After the infinite time of inspection, the conflict reaches the equilibrium, which satisfies the equation, k(1 + ap*)n* = k(1 + bn*)p*. Here we define a parameter C, which is 2p*/[p*(1 - p*)]. After the infinite time of inspection, the conflict reaches the equilibrium, which satisfies t that changes in the confidence level with the time (dp/dt) is proportional to [k(1+ap)n - k(1+bn)p], i.e. k[-cp2 + (c - 2)p + 1]. Solving the differential equation, we derived the equation; t(p) and p(t) depending with the parameters; k, c, S. S (0-1) is the value arbitrary selected and related with probability of "abnormal" before the image inspection (S = p(0)). Image reading studies were executed for CT images. ROC curves were generated both by the traditional 4-step score-based method and by the confidence level; p estimated from the equation t(p) of the DDC model using observed judgment time. It was concluded that ROC curves could be generated by measuring time for dichotomous judgment without the subjective scores of diagnostic confidence and applying the DDC model.

Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic mice.

PubMed

Shan, Lin; Aster, Jon C; Sklar, Jeffrey; Sunday, Mary E

2007-02-01

The notch gene family encodes transmembrane receptors that regulate cell differentiation by interacting with surface ligands on adjacent cells. Previously, we demonstrated that tumor necrosis factor-alpha (TNF) induces neuroendocrine (NE) cell differentiation in H82, but not H526, undifferentiated small cell lung carcinoma lines. We now test the hypothesis that TNF mediates NE cell differentiation in part by altering Notch gene expression. First, using RT-PCR, we determined that TNF treatment of H82, but not H526, transiently decreases notch-1 mRNA in parallel with induction of gene expression for the NE-specific marker DOPA decarboxylase (DDC). Second, we treated H82 and H526 with notch-1 antisense vs. sense oligodeoxynucleotides. Using quantitative RT-PCR and Western analyses we demonstrate that DDC mRNA and protein are increased in H82 by notch-1 antisense, whereas notch-1 mRNA and activated Notch-1 protein are decreased. mRNA for Hes1, a transcription factor downstream from activated Notch, is also decreased by Notch-1 antisense in H82 but not H526. After 7 days of Notch-1 antisense treatment, neural cell adhesion molecule (NCAM) immunoreactivity is induced in H82 but not H526. Third, we generated transgenic mice bearing notch-1 driven by the neural/NE-specific calcitonin promoter, which express activated Notch-1 in developing lung epithelium. Newborn NotchCal mouse lungs have high levels of hes1 mRNA, reflecting increased activated Notch, compared with wild-type. NotchCal lungs have decreased CGRP-positive NE cells, decreased protein gene product 9.5 (PGP9.5)-positive NE cells, and decreased gastrin-releasing peptide (GRP), CGRP, and DDC mRNA levels compared with normal littermates. Cumulatively, these observations provide further support for a role for Notch-1 signaling in regulating pulmonary NE cell differentiation.

47 CFR 73.9001 - Redistribution control of digital television broadcasts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Redistribution control of digital television... RADIO SERVICES RADIO BROADCAST SERVICES Digital Broadcast Television Redistribution Control § 73.9001 Redistribution control of digital television broadcasts. Licensees of TV broadcast stations may utilize the...

Variation in embryonic mortality and maternal transcript expression among Atlantic cod (Gadus morhua) broodstock: a functional genomics study.

PubMed

Rise, Matthew L; Nash, Gordon W; Hall, Jennifer R; Booman, Marije; Hori, Tiago S; Trippel, Edward A; Gamperl, A Kurt

2014-12-01

Early life stage mortality is an important issue for Atlantic cod aquaculture, yet the impact of the cod maternal (egg) transcriptome on egg quality and mortality during embryonic development is poorly understood. In the present work, we studied embryonic mortality and maternal transcript expression using eggs from 15 females. Total mortality at 7days post-fertilization (7 dpf, segmentation stage) was used as an indice of egg quality. A 20,000 probe (20K) microarray experiment compared the 7hours post-fertilization (7 hpf, ~2-cell stage) egg transcriptome of the two lowest quality females (>90% mortality at 7 dpf) to that of the highest quality female (~16% mortality at 7 dpf). Forty-three microarray probes were consistently differentially expressed in both low versus high quality egg comparisons (25 higher expressed in low quality eggs, and 18 higher expressed in high quality eggs). The microarray experiment also identified many immune-relevant genes [e.g. interferon (IFN) pathway genes ifngr1 and ifrd1)] that were highly expressed in eggs of all 3 females regardless of quality. Twelve of the 43 candidate egg quality-associated genes, and ifngr1, ifrd1 and irf7, were included in a qPCR study with 7 hpf eggs from all 15 females. Then, the genes that were confirmed by qPCR to be greater than 2-fold differentially expressed between 7 hpf eggs from the lowest and highest quality females (dcbld1, ddc, and acy3 more highly expressed in the 2 lowest quality females; kpna7 and hacd1 more highly expressed in the highest quality female), and the 3 IFN pathway genes, were included in a second qPCR study with unfertilized eggs. While some maternal transcripts included in these qPCR studies were associated with extremes in egg quality, there was little correlation between egg quality and gene expression when all females were considered. Both dcbld1 and ddc showed greater than 100-fold differences in transcript expression between females and were potentially influenced by family. The Atlantic cod ddc (dopa decarboxylase) complete cDNA was characterized, and has a 1461bp open reading frame encoding a 486 amino acid protein that contains all eight residues of the conserved pyridoxal 5'-phosphate binding site including the catalytic lysine. This study provides valuable new information and resources related to the Atlantic cod egg transcriptome. Some of these microarray-identified, qPCR-confirmed, Atlantic cod egg transcripts (e.g. ddc, kpna7) play important roles during embryonic development of other vertebrate species, and may have similar functions in Atlantic cod. Copyright © 2014. Published by Elsevier B.V.

75 FR 30077 - Advisory Committee On Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee On Digital I&C...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-28

... Subcommittee On Digital I&C Systems The ACRS Subcommittee on Digital Instrumentation and Control (DI&C) Systems... the area of Digital Instrumentation and Control (DI&C) Probabilistic Risk Assessment (PRA). Topics... software reliability methods (QSRMs), NUREG/CR--6997, ``Modeling a Digital Feedwater Control System Using...

Digital control of the Kuiper Airborne Observatory telescope

NASA Technical Reports Server (NTRS)

Mccormack, Ann C.; Snyder, Philip K.

1989-01-01

The feasibility of using a digital controller to stabilize a telescope mounted in an airplane is investigated. The telescope is a 30 in. infrared telescope mounted aboard a NASA C-141 aircraft known as the Kuiper Airborne Observatory. Current efforts to refurbish the 14-year-old compensation system have led to considering a digital controller. A typical digital controller is modeled and added into the telescope system model. This model is simulated on a computer to generate the Bode plots and time responses which determine system stability and performance parameters. Important aspects of digital control system hardware are discussed. A summary of the findings shows that a digital control system would result in satisfactory telescope performance.

Digital Signal Processing and Control for the Study of Gene Networks

NASA Astrophysics Data System (ADS)

Shin, Yong-Jun

2016-04-01

Thanks to the digital revolution, digital signal processing and control has been widely used in many areas of science and engineering today. It provides practical and powerful tools to model, simulate, analyze, design, measure, and control complex and dynamic systems such as robots and aircrafts. Gene networks are also complex dynamic systems which can be studied via digital signal processing and control. Unlike conventional computational methods, this approach is capable of not only modeling but also controlling gene networks since the experimental environment is mostly digital today. The overall aim of this article is to introduce digital signal processing and control as a useful tool for the study of gene networks.

Digital Signal Processing and Control for the Study of Gene Networks.

PubMed

Shin, Yong-Jun

2016-04-22

Thanks to the digital revolution, digital signal processing and control has been widely used in many areas of science and engineering today. It provides practical and powerful tools to model, simulate, analyze, design, measure, and control complex and dynamic systems such as robots and aircrafts. Gene networks are also complex dynamic systems which can be studied via digital signal processing and control. Unlike conventional computational methods, this approach is capable of not only modeling but also controlling gene networks since the experimental environment is mostly digital today. The overall aim of this article is to introduce digital signal processing and control as a useful tool for the study of gene networks.

Digital Signal Processing and Control for the Study of Gene Networks

PubMed Central

Shin, Yong-Jun

2016-01-01

Thanks to the digital revolution, digital signal processing and control has been widely used in many areas of science and engineering today. It provides practical and powerful tools to model, simulate, analyze, design, measure, and control complex and dynamic systems such as robots and aircrafts. Gene networks are also complex dynamic systems which can be studied via digital signal processing and control. Unlike conventional computational methods, this approach is capable of not only modeling but also controlling gene networks since the experimental environment is mostly digital today. The overall aim of this article is to introduce digital signal processing and control as a useful tool for the study of gene networks. PMID:27102828

Defense Documentation Center Referral Data Bank Directory.

ERIC Educational Resources Information Center

Cox, Alice L.

This revised directory of the information sources in the DDC Referral Data Bank (previously issued in October 1970 as AD-712 800 and in July 1971 as AD-724 700) consists of a compilation of computer printouts, each of which gives for a single activity detailed descriptive information on the mission, scope and services provided. Arrangement is by…

Exploiting LCSH, LCC, and DDC To Retrieve Networked Resources: Issues and Challenges.

ERIC Educational Resources Information Center

Chan, Lois Mai

This paper examines how the nature of the World Wide Web and characteristics of networked resources affect subject access and analyzes the requirements of effective indexing and retrieval tools. The current and potential uses of existing tools and possible courses of future development are explored in the context of recent research. The first…

A DDC Bibliography on Cost/Benefits of Technical Information Services and Technology Transfer.

ERIC Educational Resources Information Center

Defense Documentation Center, Alexandria, VA.

This bibliography is a compilation of literature existing in both the government and public sectors and concerning Cost/Benefits of Technical information Services and Technology Transfer. Not only was the cost-benefit to the user reflected, but consideration was given to the initial cost of information collections, the cost of processing the…

An Evaluation of On-Line Information Retrieval System Techniques.

ERIC Educational Resources Information Center

Wolfe, Theodore

This report presents a review and evaluation of three remote access on-line information retrieval systems and some ideas on what the capabilities of an ideal on-line information retrieval system should be. The three systems reviewed are the DDC Remote On-Line Retrieval System, the National Aeronautics and Space Administration RECON System, and the…

Statistical Analysis of the Association Between Subject Headings and Their Corresponding Class Notations in Science and Technology Monographs.

ERIC Educational Resources Information Center

Khosh-khui, Abolghasem

This study investigates the degree of relationship between scientific and technical subject headings and their corresponding class notations in the Dewey Decimal (DDC) and Library of Congress Classification (LCC) systems. The degree of association between a subject heading and its corresponding class of notation or notations is measured by…

A Challenge to Change: Necessary Changes in the Library Classification System for the Chicago Public Schools.

ERIC Educational Resources Information Center

Williams, Florence M.

This report addresses the feasibility of changing the classification of library materials in the Chicago Public School libraries from the Dewey Decimal classification system (DDC) to the Library of Congress system (LC), thus patterning the city school libraries after the Chicago Public Library and strengthening the existing close relationship…

Annual Report on Electronics Research at the University of Texas at Austin.

DTIC Science & Technology

1984-05-15

Beall, E.J. Powers, Roger D. Bengtson and K. Nelin, "Edge Turbulence in TEXT and PRETEXT." Ch.P. Ritz , S.J. Levinson, E.J. Powers, and Roger D...DC 20234 314 Phillips Hall Ithaca, MY 1480 Ori. ay.Harris Office of the Dean Dr. Carlton Walter School of Engineering ElectroScionce Laboratory San

11 CFR 106.6 - Allocation of expenses between federal and non-federal activities by separate segregated funds...

Code of Federal Regulations, 2011 CFR

2011-01-01

... Final Order, EMILY's List v. FEC, No. 05-0049 (D.D.C. Nov. 30, 2009). [55 FR 26071, June 26, 1990, as... instructions direct the separate segregated fund's or nonconnected committee's employee or volunteer to refer... instructions direct the separate segregated fund's or nonconnected committee's employee or volunteer to refer...

77 FR 40221 - Endangered and Threatened Wildlife and Plants; Listing the Scarlet Macaw

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

..., Case No. 10 CV 00357 D.D.C.). On July 21, 2010, a settlement agreement was approved by the Court (CV-10... cases, it is sufficient to submit comments through the Federal eRulemaking Portal, described above in..., Ecuador, Peru, Venezuela, Suriname, Guyana, French Guiana, and Bolivia and Brazil as far south as Santa...

Comparison of flight results with digital simulation for a digital electronic engine control in an F-15 airplane

NASA Technical Reports Server (NTRS)

Myers, L. P.; Burcham, F. W., Jr.

1983-01-01

Substantial benefits of a full authority digital electronic engine control on an air breathing engine were demonstrated repeatedly in simulation studies, ground engine tests, and engine altitude test facilities. A digital engine electronic control system showed improvements in efficiency, performance, and operation. An additional benefit of full authority digital controls is the capability of detecting and correcting failures and providing engine health diagnostics.

Sea-level evaluation of digitally implemented turbojet engine control functions

NASA Technical Reports Server (NTRS)

Arpasi, D. J.; Cwynar, D. S.; Wallhagen, R. E.

1972-01-01

The standard hydromechanical control system of a turbojet engine was replaced with a digital control system that implemented the same control laws. A detailed discussion of the digital control system in use with the engine is presented. The engine was operated in a sea-level test stand. The effects of control update interval are defined, and a method for extending this interval by using digital compensation is discussed.

Army/NASA small turboshaft engine digital controls research program

NASA Technical Reports Server (NTRS)

Sellers, J. F.; Baez, A. N.

1981-01-01

The emphasis of a program to conduct digital controls research for small turboshaft engines is on engine test evaluation of advanced control logic using a flexible microprocessor based digital control system designed specifically for research on advanced control logic. Control software is stored in programmable memory. New control algorithms may be stored in a floppy disk and loaded directly into memory. This feature facilitates comparative evaluation of different advanced control modes. The central processor in the digital control is an Intel 8086 16 bit microprocessor. Control software is programmed in assembly language. Software checkout is accomplished prior to engine test by connecting the digital control to a real time hybrid computer simulation of the engine. The engine currently installed in the facility has a hydromechanical control modified to allow electrohydraulic fuel metering and VG actuation by the digital control. Simulation results are presented which show that the modern control reduces the transient rotor speed droop caused by unanticipated load changes such as cyclic pitch or wind gust transients.

Highly integrated digital electronic control: Digital flight control, aircraft model identification, and adaptive engine control

NASA Technical Reports Server (NTRS)

Baer-Riedhart, Jennifer L.; Landy, Robert J.

1987-01-01

The highly integrated digital electronic control (HIDEC) program at NASA Ames Research Center, Dryden Flight Research Facility is a multiphase flight research program to quantify the benefits of promising integrated control systems. McDonnell Aircraft Company is the prime contractor, with United Technologies Pratt and Whitney Aircraft, and Lear Siegler Incorporated as major subcontractors. The NASA F-15A testbed aircraft was modified by the HIDEC program by installing a digital electronic flight control system (DEFCS) and replacing the standard F100 (Arab 3) engines with F100 engine model derivative (EMD) engines equipped with digital electronic engine controls (DEEC), and integrating the DEEC's and DEFCS. The modified aircraft provides the capability for testing many integrated control modes involving the flight controls, engine controls, and inlet controls. This paper focuses on the first two phases of the HIDEC program, which are the digital flight control system/aircraft model identification (DEFCS/AMI) phase and the adaptive engine control system (ADECS) phase.

Fabrication and test of digital output interface devices for gas turbine electronic controls

NASA Technical Reports Server (NTRS)

Newirth, D. M.; Koenig, E. W.

1978-01-01

A program was conducted to develop an innovative digital output interface device, a digital effector with optical feedback of the fuel metering valve position, for future electronic controls for gas turbine engines. A digital effector (on-off solenoids driven directly by on-off signals from a digital electronic controller) with optical position feedback was fabricated, coupled with the fuel metering valve, and tested under simulated engine operating conditions. The testing indicated that a digital effector with optical position feedback is a suitable candidate, with proper development for future digital electronic gas turbine controls. The testing also identified several problem areas which would have to be overcome in a final production configuration.

47 CFR 76.1909 - Redistribution control of unencrypted digital terrestrial broadcast content.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Redistribution control of unencrypted digital... Redistribution control of unencrypted digital terrestrial broadcast content. (a) For the purposes of this section, the terms unencrypted digital terrestrial broadcast content, EIT, PMT, broadcast flag, covered...

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

Li, B; Yu, H; Jara, H

Purpose: To compare enhanced Laws texture derived from parametric proton density (PD) maps to other MRI-based surrogate markers (T2, PD, ADC) in assessing degrees of liver fibrosis in a murine model of hepatic fibrosis using 11.7T scanner. Methods: This animal study was IACUC approved. Fourteen mice were divided into control (n=1) and experimental (n=13). The latter were fed a DDC-supplemented diet to induce hepatic fibrosis. Liver specimens were imaged using an 11.7T scanner; the parametric PD, T2, and ADC maps were generated from spin-echo pulsed field gradient and multi-echo spin-echo acquisitions. Enhanced Laws texture analysis was applied to the PDmore » maps: first, hepatic blood vessels and liver margins were segmented/removed using an automated dual-clustering algorithm; secondly, an optimal thresholding algorithm was applied to reduce the partial volume artifact; next, mean and stdev were corrected to minimize grayscale variation across images; finally, Laws texture was extracted. Degrees of fibrosis was assessed by an experienced pathologist and digital image analysis (%Area Fibrosis). Scatterplots comparing enhanced Laws texture, T2, PD, and ADC values to degrees of fibrosis were generated and correlation coefficients were calculated. Unenhanced Laws texture was also compared to assess the effectiveness of the proposed enhancements. Results: Hepatic fibrosis and the enhanced Laws texture were strongly correlated with higher %Area Fibrosis associated with higher Laws texture (r=0.89). Only a moderate correlation was detected between %Area Fibrosis and unenhanced Laws texture (r=0.70). Strong correlation also existed between ADC and %Area Fibrosis (r=0.86). Moderate correlations were seen between %Area Fibrosis and PD (r=0.65) and T2 (r=0.66). Conclusions: Higher degrees of hepatic fibrosis are associated with increased Laws texture. The proposed enhancements improve the accuracy of Laws texture. Enhanced Laws texture features are more accurate than PD and T2 in assessing fibrosis, and can potentially serve as an accurate surrogate marker for hepatic fibrosis.« less

Demonstration of Standard HVAC Single-Loop Digital Control Systems

DTIC Science & Technology

1993-01-01

AD-A265 372 T N FEAP-TR-FE-93/05 REPORT January 1993 FACILITIES ENGINEERING APPLICATIONS PROGRAM Demonstration of Standard HVAC Single-Loop Digital...AND DATES COVERED January 1993 Final 4. TITLE AND SUBTITLE [5. FUNDING NUMBERS Demonstration of Standard HVAC Single-Loop Digital Control Systems FEAP...conditioning ( HVAC ) control systems provide guidance on designing and specifying standard HVAC control systems that use single-loop digital controllers

Digital flight control research

NASA Technical Reports Server (NTRS)

Potter, J. E.; Stern, R. G.; Smith, T. B.; Sinha, P.

1974-01-01

The results of studies which were undertaken to contribute to the design of digital flight control systems, particularly for transport aircraft are presented. In addition to the overall design considerations for a digital flight control system, the following topics are discussed in detail: (1) aircraft attitude reference system design, (2) the digital computer configuration, (3) the design of a typical digital autopilot for transport aircraft, and (4) a hybrid flight simulator.

Digital-computer normal shock position and restart control of a Mach 2.5 axisymmetric mixed-compression inlet

NASA Technical Reports Server (NTRS)

Neiner, G. H.; Cole, G. L.; Arpasi, D. J.

1972-01-01

Digital computer control of a mixed-compression inlet is discussed. The inlet was terminated with a choked orifice at the compressor face station to dynamically simulate a turbojet engine. Inlet diffuser exit airflow disturbances were used. A digital version of a previously tested analog control system was used for both normal shock and restart control. Digital computer algorithms were derived using z-transform and finite difference methods. Using a sample rate of 1000 samples per second, the digital normal shock and restart controls essentially duplicated the inlet analog computer control results. At a sample rate of 100 samples per second, the control system performed adequately but was less stable.

Is It Truly a Matter of "Dewey or Don't We"?

ERIC Educational Resources Information Center

Kaplan, Allison G.

2013-01-01

To some, discussing the demise of the Dewey Decimal Classification (DDC) system is tantamount to blasphemy, while to others it is a discussion long overdue (no pun intended). The author was asked, as an educator of librarians, to present her thoughts on the issue. Her conclusions are based not on thorough scientifically sound research, but rather…

Development of the Defense Documentation Center Remote On-Line Retrieval System - Past, Present and Future.

ERIC Educational Resources Information Center

Bennertz, Richard K.

The document highlights in nontechnical language the development of the Defense Documentation Center (DDC) Remote On-Line Retrieval System from its inception in 1967 to what is planned. It describes in detail the current operating system, equipment configuration and associated costs, user training and system evaluation and may be of value to other…

Microfiche/Telex Oriented Document Services Center Established in Sylvania Library Through Cooperative Test Program with Defense Documentation Center.

ERIC Educational Resources Information Center

Little, Dean K.

In a cooperative program with Defense Documentation Center Headquarters, Sylvania arranged for procurement of 70,000 unclassified-unlimited documents without DDC Form I cards and 30,000 unclassified-limited and classified documents with Form I's. This was done in order to overcome effects of an in-house documents inventory/selective destruction…

Patterns in Stable Isotope Values of Nitrogen and Carbon in Particulate Matter from the Northwest Atlantic Continental Shelf, from the Gulf of Maine to Cape Hatteras

EPA Science Inventory

Stable isotope measurements of nitrogen and carbon (15N, 13ddC) are often used to characterize estuarine, nearshore, and open ocean ecosystems. Reliable information about the spatial distribution of base-level stable isotope values, often represented by primary producers, is crit...

Nutritional Relationships in Schistosomiasis.

DTIC Science & Technology

1978-07-01

to presence of ou~bain, phlorizin, phloretin . 1lexose mediated accumulation is Na coupled. Accession For NTIS GREA&I DDC TAB Unannounced...mediat,!d system is apparently Na + dependent and sensitive to presence of ouabain, phlorizin, phloretin . Hexose mediated accumulation is Na+ coupled. i...decreased Na+, ouabain, phiorizin phloretin and other sugars. Studies with Na22 suggest that the accumulation of 2-deoxyglucose and Na+ were coupled

75 FR 27580 - Notice of Lodging of Consent Decree Under the Clean Air Act

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... given that on May 10, 2010, a proposed Consent Decree (``Decree'') in United States v. The Pep Boys... (``CAA'') against The Pep Boys--Manny, Moe & Jack, and Baja, Inc., for violations of the mobile source.... The Pep Boys--Manny, Moe & Jack, and Baja, Inc., Civil Action No. 10-cv-00745, (D.D.C.), D.J. Ref. 90...

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation.

PubMed

Chu, Chung-Ching; Ali, Niwa; Karagiannis, Panagiotis; Di Meglio, Paola; Skowera, Ania; Napolitano, Luca; Barinaga, Guillermo; Grys, Katarzyna; Sharif-Paghaleh, Ehsan; Karagiannis, Sophia N; Peakman, Mark; Lombardi, Giovanna; Nestle, Frank O

2012-05-07

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation

PubMed Central

Chu, Chung-Ching; Ali, Niwa; Karagiannis, Panagiotis; Di Meglio, Paola; Skowera, Ania; Napolitano, Luca; Barinaga, Guillermo; Grys, Katarzyna; Sharif-Paghaleh, Ehsan; Karagiannis, Sophia N.; Peakman, Mark; Lombardi, Giovanna

2012-01-01

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141+ DDCs). CD141+ DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D3 (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141+ DDCs from human blood DCs. These CD141+ DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141+ DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141+ DDC-like cells have potential clinical use for their capacity to induce immune tolerance. PMID:22547651

The Genetic and Molecular Organization of the Dopa Decarboxylase Gene Cluster of Drosophila Melanogaster

PubMed Central

Stathakis, D. G.; Pentz, E. S.; Freeman, M. E.; Kullman, J.; Hankins, G. R.; Pearlson, N. J.; Wright, TRF.

1995-01-01

We report the complete molecular organization of the Dopa decarboxylase gene cluster. Mutagenesis screens recovered 77 new Df(2L)TW130 recessive lethal mutations. These new alleles combined with 263 previously isolated mutations in the cluster to define 18 essential genes. In addition, seven new deficiencies were isolated and characterized. Deficiency mapping, restriction fragment length polymorphism (RFLP) analysis and P-element-mediated germline transformation experiments determined the gene order for all 18 loci. Genomic and cDNA restriction endonuclease mapping, Northern blot analysis and DNA sequencing provided information on exact gene location, mRNA size and transcriptional direction for most of these loci. In addition, this analysis identified two transcription units that had not previously been identified by extensive mutagenesis screening. Most of the loci are contained within two dense subclusters. We discuss the effectiveness of mutagens and strategies used in our screens, the variable mutability of loci within the genome of Drosophila melanogaster, the cytological and molecular organization of the Ddc gene cluster, the validity of the one band-one gene hypothesis and a possible purpose for the clustering of genes in the Ddc region. PMID:8647399

Detection of submicron-sized raft-like domains in membranes by small-angle neutron scattering

NASA Astrophysics Data System (ADS)

Pencer, J.; Mills, T.; Anghel, V.; Krueger, S.; Epand, R. M.; Katsaras, J.

2005-12-01

Using coarse grained models of heterogeneous vesicles we demonstrate the potential for small-angle neutron scattering (SANS) to detect and distinguish between two different categories of lateral segregation: 1) unilamellar vesicles (ULV) containing a single domain and 2) the formation of several small domains or “clusters” (~10 nm in radius) on a ULV. Exploiting the unique sensitivity of neutron scattering to differences between hydrogen and deuterium, we show that the liquid ordered (lo) DPPC-rich phase can be selectively labeled using chain deuterated dipalymitoyl phosphatidylcholine (dDPPC), which greatly facilitates the use of SANS to detect membrane domains. SANS experiments are then performed in order to detect and characterize, on nanometer length scales, lateral heterogeneities, or so-called “rafts”, in ~30 nm radius low polydispersity ULV made up of ternary mixtures of phospholipids and cholesterol. For 1:1:1 DOPC:DPPC:cholesterol (DDC) ULV we find evidence for the formation of lateral heterogeneities on cooling below 30 °C. These heterogeneities do not appear when DOPC is replaced by SOPC. Fits to the experimental data using coarse grained models show that, at room temperature, DDC ULV each exhibit approximately 30 domains with average radii of ~10 nm.

TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs

PubMed Central

Huang, Shar-yin N.; Murai, Junko; Dalla Rosa, Ilaria; Dexheimer, Thomas S.; Naumova, Alena; Gmeiner, William H.; Pommier, Yves

2013-01-01

Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not well understood how cells repair the DNA damage induced by these drugs. Here, we reveal the importance of tyrosyl–DNA phosphodiesterase 1 (TDP1) in the repair of nuclear and mitochondrial DNA damage induced by CTNAs. On investigating the effects of four CTNAs—acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT) and zalcitabine (ddC)—we show that TDP1 is capable of removing the covalently linked corresponding CTNAs from DNA 3′-ends. We also show that Tdp1−/− cells are hypersensitive and accumulate more DNA damage when treated with ACV and Ara-C, implicating TDP1 in repairing CTNA-induced DNA damage. As AZT and ddC are known to cause mitochondrial dysfunction, we examined whether TDP1 repairs the mitochondrial DNA damage they induced. We find that AZT and ddC treatment leads to greater depletion of mitochondrial DNA in Tdp1−/− cells. Thus, TDP1 seems to be critical for repairing nuclear and mitochondrial DNA damage caused by CTNAs. PMID:23775789

Digital control analysis and design of a field-sensed magnetic suspension system.

PubMed

Li, Jen-Hsing; Chiou, Juing-Shian

2015-03-13

Magnetic suspension systems are mechatronic systems and crucial in several engineering applications, such as the levitation of high-speed trains, frictionless bearings, and wind tunnels. Magnetic suspension systems are nonlinear and unstable systems; therefore, they are suitable educational benchmarks for testing various modeling and control methods. This paper presents the digital modeling and control of magnetic suspension systems. First, the magnetic suspension system is stabilized using a digital proportional-derivative controller. Subsequently, the digital model is identified using recursive algorithms. Finally, a digital mixed linear quadratic regulator (LQR)/H∞ control is adopted to stabilize the magnetic suspension system robustly. Simulation examples and a real-world example are provided to demonstrate the practicality of the study results. In this study, a digital magnetic suspension system model was developed and reviewed. In addition, equivalent state and output feedback controls for magnetic suspension systems were developed. Using this method, the controller design for magnetic suspension systems was simplified, which is the novel contribution of this study. In addition, this paper proposes a complete digital controller design procedure for magnetic suspension systems.

Multi-GPU implementation of a VMAT treatment plan optimization algorithm

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

Tian, Zhen, E-mail: Zhen.Tian@UTSouthwestern.edu, E-mail: Xun.Jia@UTSouthwestern.edu, E-mail: Steve.Jiang@UTSouthwestern.edu; Folkerts, Michael; Tan, Jun

Purpose: Volumetric modulated arc therapy (VMAT) optimization is a computationally challenging problem due to its large data size, high degrees of freedom, and many hardware constraints. High-performance graphics processing units (GPUs) have been used to speed up the computations. However, GPU’s relatively small memory size cannot handle cases with a large dose-deposition coefficient (DDC) matrix in cases of, e.g., those with a large target size, multiple targets, multiple arcs, and/or small beamlet size. The main purpose of this paper is to report an implementation of a column-generation-based VMAT algorithm, previously developed in the authors’ group, on a multi-GPU platform tomore » solve the memory limitation problem. While the column-generation-based VMAT algorithm has been previously developed, the GPU implementation details have not been reported. Hence, another purpose is to present detailed techniques employed for GPU implementation. The authors also would like to utilize this particular problem as an example problem to study the feasibility of using a multi-GPU platform to solve large-scale problems in medical physics. Methods: The column-generation approach generates VMAT apertures sequentially by solving a pricing problem (PP) and a master problem (MP) iteratively. In the authors’ method, the sparse DDC matrix is first stored on a CPU in coordinate list format (COO). On the GPU side, this matrix is split into four submatrices according to beam angles, which are stored on four GPUs in compressed sparse row format. Computation of beamlet price, the first step in PP, is accomplished using multi-GPUs. A fast inter-GPU data transfer scheme is accomplished using peer-to-peer access. The remaining steps of PP and MP problems are implemented on CPU or a single GPU due to their modest problem scale and computational loads. Barzilai and Borwein algorithm with a subspace step scheme is adopted here to solve the MP problem. A head and neck (H and N) cancer case is then used to validate the authors’ method. The authors also compare their multi-GPU implementation with three different single GPU implementation strategies, i.e., truncating DDC matrix (S1), repeatedly transferring DDC matrix between CPU and GPU (S2), and porting computations involving DDC matrix to CPU (S3), in terms of both plan quality and computational efficiency. Two more H and N patient cases and three prostate cases are used to demonstrate the advantages of the authors’ method. Results: The authors’ multi-GPU implementation can finish the optimization process within ∼1 min for the H and N patient case. S1 leads to an inferior plan quality although its total time was 10 s shorter than the multi-GPU implementation due to the reduced matrix size. S2 and S3 yield the same plan quality as the multi-GPU implementation but take ∼4 and ∼6 min, respectively. High computational efficiency was consistently achieved for the other five patient cases tested, with VMAT plans of clinically acceptable quality obtained within 23–46 s. Conversely, to obtain clinically comparable or acceptable plans for all six of these VMAT cases that the authors have tested in this paper, the optimization time needed in a commercial TPS system on CPU was found to be in an order of several minutes. Conclusions: The results demonstrate that the multi-GPU implementation of the authors’ column-generation-based VMAT optimization can handle the large-scale VMAT optimization problem efficiently without sacrificing plan quality. The authors’ study may serve as an example to shed some light on other large-scale medical physics problems that require multi-GPU techniques.« less

Computer aided design of digital controller for radial active magnetic bearings

NASA Technical Reports Server (NTRS)

Cai, Zhong; Shen, Zupei; Zhang, Zuming; Zhao, Hongbin

1992-01-01

A five degree of freedom Active Magnetic Bearing (AMB) system is developed which is controlled by digital controllers. The model of the radial AMB system is linearized and the state equation is derived. Based on the state variables feedback theory, digital controllers are designed. The performance of the controllers are evaluated according to experimental results. The Computer Aided Design (CAD) method is used to design controllers for magnetic bearings. The controllers are implemented with a digital signal processing (DSP) system. The control algorithms are realized with real-time programs. It is very easy to change the controller by changing or modifying the programs. In order to identify the dynamic parameters of the controlled magnetic system, a special experiment was carried out. Also, the online Recursive Least Squares (RLS) parameter identification method is studied. It can be realized with the digital controllers. Online parameter identification is essential for the realization of an adaptive controller.

Development and testing of controller performance evaluation methodology for multi-input/multi-output digital control systems

NASA Technical Reports Server (NTRS)

Pototzky, Anthony; Wieseman, Carol; Hoadley, Sherwood Tiffany; Mukhopadhyay, Vivek

1991-01-01

Described here is the development and implementation of on-line, near real time controller performance evaluation (CPE) methods capability. Briefly discussed are the structure of data flow, the signal processing methods used to process the data, and the software developed to generate the transfer functions. This methodology is generic in nature and can be used in any type of multi-input/multi-output (MIMO) digital controller application, including digital flight control systems, digitally controlled spacecraft structures, and actively controlled wind tunnel models. Results of applying the CPE methodology to evaluate (in near real time) MIMO digital flutter suppression systems being tested on the Rockwell Active Flexible Wing (AFW) wind tunnel model are presented to demonstrate the CPE capability.

Emergency Flight Control Using Computer-Controlled Thrust

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Fullerton, C. Gordon; Stewart, James F.; Gilyard, Glenn B.; Conley, Joseph A.

1995-01-01

Propulsion Controlled Aircraft (PCA) systems are digital electronic control systems undergoing development to provide limited maneuvering ability through variations of individual engine thrusts in multiple-engine airplanes. Provide landing capability when control surfaces inoperable. Incorporated on existing and future airplanes that include digital engine controls, digital flight controls, and digital data buses, adding no weight for additional hardware to airplane. Possible to handle total failure of hydraulic system, depending on how surfaces respond to loss of hydraulic pressure, and broken control cables or linkages. Future airplanes incorporate data from Global Positioning System for guidance to any suitable emergency runway in world.

IL30 (IL27p28) attenuates liver fibrosis through inducing NKG2D-Rae1 interaction between NKT and activated hepatic stellate cells

PubMed Central

Mitra, Abhisek; Satelli, Arun; Yan, Jun; Xueqing, Xia; Gagea, Mihai; Hunter, Christopher A.; Mishra, Lopa; Li, Shulin

2014-01-01

Chronic hepatic diseases such as cirrhosis, hepatocellular carcinoma and virus mediated immunopathogenic infections are affecting billions of people worldwide. These diseases commonly initiate with fibrosis. Owing to the various side effects of anti-fibrotic therapy and the difficulty of diagnosing asymptomatic patients, suitable medication remains a major concern. To overcome this drawback, the use of cytokine-based sustained therapy might be a suitable alternative with minimal side effects. Here, we studied the therapeutic efficacy and potential mechanisms of IL30 as anti-fibrosis therapy in murine liver fibrosis models. Carbon tetrachloride (CCl4) mixed with corn oil at a ratio 1:3 was injected intraperitoneally (IP) 1µl/gm body weight twice per week for 1 month or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) 0.1% (wt/wt) Purnima 5015 Chow was fed for 3 weeks to induce liver fibrosis. Either control vector (pCtr) or pIL30 was injected hydrodynamically once per week. A significant decrease in collagen deposition and reduced expression of α-smooth muscle Actin (αSMA) protein indicated that IL30–based gene therapy dramatically reduced bridging fibrosis that was induced by CCl4 or DDC. Immunophenotyping and knockout studies showed that IL30 recruits NKT cells to the liver to decrease activated hepatic stellate cells (HSCs) significantly and ameliorate liver fibrosis. Both flow cytometric and antibody mediated neutralization studies showed NKT cells alleviate liver fibrosis in an NKG2D dependent manner. Furthermore, chronic treatment with CCl4 showed inducible surface expression of the NKG2D ligand Rae1 on activated HSCs as compared to quiescent ones. Taken together, our results show that highly target specific liver NKT cells selectively remove activated HSCs via an NKG2D-Rae1 interaction to ameliorate liver fibrosis after IL30 treatment. PMID:25351459

Medical devices; radiology devices; reclassification of full-field digital mammography system. Final rule.

PubMed

2010-11-05

The Food and Drug Administration (FDA) is announcing the reclassification of the full-field digital mammography (FFDM) system from class III (premarket approval) to class II (special controls). The device type is intended to produce planar digital x-ray images of the entire breast; this generic type of device may include digital mammography acquisition software, full-field digital image receptor, acquisition workstation, automatic exposure control, image processing and reconstruction programs, patient and equipment supports, component parts, and accessories. The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Full-Field Digital Mammography System." FDA is reclassifying the device into class II (special controls) because general controls along with special controls will provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document that will serve as the special control for this device.

Implementation of Adaptive Digital Controllers on Programmable Logic Devices

NASA Technical Reports Server (NTRS)

Gwaltney, David A.; King, Kenneth D.; Smith, Keary J.; Monenegro, Justino (Technical Monitor)

2002-01-01

Much has been made of the capabilities of FPGA's (Field Programmable Gate Arrays) in the hardware implementation of fast digital signal processing. Such capability also makes an FPGA a suitable platform for the digital implementation of closed loop controllers. Other researchers have implemented a variety of closed-loop digital controllers on FPGA's. Some of these controllers include the widely used proportional-integral-derivative (PID) controller, state space controllers, neural network and fuzzy logic based controllers. There are myriad advantages to utilizing an FPGA for discrete-time control functions which include the capability for reconfiguration when SRAM-based FPGA's are employed, fast parallel implementation of multiple control loops and implementations that can meet space level radiation tolerance requirements in a compact form-factor. Generally, a software implementation on a DSP (Digital Signal Processor) or microcontroller is used to implement digital controllers. At Marshall Space Flight Center, the Control Electronics Group has been studying adaptive discrete-time control of motor driven actuator systems using digital signal processor (DSP) devices. While small form factor, commercial DSP devices are now available with event capture, data conversion, pulse width modulated (PWM) outputs and communication peripherals, these devices are not currently available in designs and packages which meet space level radiation requirements. In general, very few DSP devices are produced that are designed to meet any level of radiation tolerance or hardness. The goal of this effort is to create a fully digital, flight ready controller design that utilizes an FPGA for implementation of signal conditioning for control feedback signals, generation of commands to the controlled system, and hardware insertion of adaptive control algorithm approaches. An alternative is required for compact implementation of such functionality to withstand the harsh environment encountered on spacecraft. Radiation tolerant FPGA's are a feasible option for reaching this goal.

Digital PI-PD controller design for arbitrary order systems: Dominant pole placement approach.

PubMed

Dincel, Emre; Söylemez, Mehmet Turan

2018-05-02

In this paper, a digital PI-PD controller design method is proposed for arbitrary order systems with or without time-delay to achieve desired transient response in the closed-loop via dominant pole placement approach. The digital PI-PD controller design problem is solved by converting the original problem to the digital PID controller design problem. Firstly, parametrization of the digital PID controllers which assign dominant poles to desired location is done. After that the subset of digital PID controller parameters in which the remaining poles are located away from the dominant pole pair is found via Chebyshev polynomials. The obtained PID controller parameters are then transformed into the PI-PD controller parameters by considering the closed-loop controller zero and the design is completed. Success of the proposed design method is firstly demonstrated on an example transfer function and compared with the well-known PID controller methods from the literature through simulations. After that the design method is implemented on the fan and plate laboratory system in a real environment. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Impacts of Urbanization on Precipitation and Storms: Physical Insights and Vulnerabilities

Treesearch

J. M. Shepherd

2013-01-01

On January 19, 2011, an unusual weather event occurred. The National Weather Service Web site (http://www.crh.noaa. gov/news/display_cmsstory.php?wfo¼ddc&storyid¼62980& source¼0) described the event in the following way: “the atmosphere was cold and moist with low clouds and fog preceding the formation of the snow.

Dewey Redux: Virtual Dewey Resources Deliver Trusted, Familiar 21st-Century Information

ERIC Educational Resources Information Center

Adamich, Tom

2013-01-01

Where do school librarians go to find out the latest on how the Dewey Decimal Classification (DDC) system is being used (and will be used) in the 21st-century virtual-knowledge world? The answer is two great websites containing: (1) the most current information on both Dewey and linked data at ; (2) Dewey here-and-now…

Applications for Micrographics in Large Scale Information Systems of the Future. Volume II: Part III. A Review of Micrographics State-of-the-Art.

ERIC Educational Resources Information Center

Information Dynamics Corp., Reading, MA.

A five-year development program plan was drawn up for the Defense Documentation Center (DDC). This report presents in summary form the results of various surveys and reviews performed in selected areas of micrographics to support the efforts of the program's planners. Exhibits of supporting documentation are presented, together with a discussion…

Dewey Decimal Classification Online Project: Interim Reports to the Council on Library Resources, April 1984, September 1984, and February 1985.

ERIC Educational Resources Information Center

Markey, Karen; Demeyer, Anh N.

This research project focuses on the implementation and testing of the Dewey Decimal Classification (DDC) system as an online searcher's tool for subject access, browsing, and display in an online catalog. The research project comprises 12 activities. The three interim reports in this document cover the first seven of these activities: (1) obtain…

DDC 10 Year Requirements and Planning Study. Interagency Survey Report

DTIC Science & Technology

1975-12-12

RDT&E Management Information Services Traditional bibliographic information storage and retrieval techniques are insufficienL for satisfaction of...a private source. 3.3 Economics and Marketing ERDA’s tradition of absorbing costs for information 1rocessing shows no indication of changing...Libraries. Its products, in addition to traditional library services, include three prime data bases: 0 MEDLINE - journal citations and subject

Radio Frequency Simulation System (RFSS) Capabilities Summary

DTIC Science & Technology

1977-04-01

rooms to facilitate data transfer 1977 Addition of radome boresight positioner. 1977 Target array real-time display. 1977 Two additional targets, two ECK ...tabLes on the Datacraft. 28 The RFSS ECK capability is extremely diverse. Either denial or deceptive jamming techniques can be simulated with prerent...DDC-TCA 2 Development Activity Cameron Station Fort Leavenworth, Kansas 66027 Alexandria, Virginia 22314 Commander Commander US Army Frankford

Crustal and Upper Mantle Velocity and Q Structures of Mainland China

DTIC Science & Technology

1979-11-01

CLASIFICATION OFTHIS PAGE(117..t- [).(t ntred) with identical source-receiver geometry. The generalized surface wave inversion technique was applied...in the recent past. A particularly unusual crustal and upper mantle structure is found underlying the Tibet Dlateau. AOceSIon For DDC TAB Ubazmnounced...the AIR FORCE OFFICE OF SCIENTIFIC RESEARCH by the GEOPHYSICAL LABORATORY UNIVERSITY OF SOUTHERN CALIFORNIA Contractor: University of Southern

OTH Radar Surveillance at WARF During the LRAPP Church Opal Exercise

DTIC Science & Technology

1976-11-01

UNCLASSIFIED AD NUMBER ADC010483 CLASSIFICATION CHANGES TO: unclassified FROM: secret LIMITATION CHANGES TO: Approved for public release... DDC SRI STANFORD RESEARCH INSTITUTE Menlo Park, California 94025 U.S.A.D SECRET UNCLASSIFIED The views and conclusions contained in this document are...3 SRI 6-4696 DECLASSIFIED ON 31 December 2005 SECRET (This page is UNCLASSIFIED) . ... ..... .. SECRET SECURITY CLASSIFICATION OF THIS PAGE (When

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy.

PubMed

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C; Lomax, Antony J; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6[Formula: see text] layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with [Formula: see text]5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy

NASA Astrophysics Data System (ADS)

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C.; Lomax, Antony J.; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6× layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with > 5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Electrically-Assisted Turbocharger Development for Performance and Emissions

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

Bailey, Milton

2000-08-20

Turbocharger transient lag inherently imposes a tradeoff between a robust engine response to transient load shifts and exhaust emissions. By itself, a well matched turbocharger for an engine has limited flexibility in improving this transient response. Electrically-assisted turbocharging has been seen as an attractive option to improve response and lower transient emissions. This paper presents the results of a multi-year joint CRADA between DDC and ORNL. Virtual lab diesel simulation models characterized the performance improvement potential of an electrically assisted turbocharger technology. Operating requirements to reduce transient duration between load shift time by up to 50% were determined. A turbomachinemore » has been conceptualized with an integrated motor-generator, providing transient burst boost plus energy recovery capability. Numerous electric motor designs were considered, and a prototype motor was developed, fabricated, and is undergoing tests. Power controls have been designed and fabricated.« less

Versioned distributed arrays for resilience in scientific applications: Global view resilience

DOE PAGES

Chien, A.; Balaji, P.; Beckman, P.; ...

2015-06-01

Exascale studies project reliability challenges for future high-performance computing (HPC) systems. We propose the Global View Resilience (GVR) system, a library that enables applications to add resilience in a portable, application-controlled fashion using versioned distributed arrays. We describe GVR’s interfaces to distributed arrays, versioning, and cross-layer error recovery. Using several large applications (OpenMC, the preconditioned conjugate gradient solver PCG, ddcMD, and Chombo), we evaluate the programmer effort to add resilience. The required changes are small (<2% LOC), localized, and machine-independent, requiring no software architecture changes. We also measure the overhead of adding GVR versioning and show that generally overheads <2%more » are achieved. We conclude that GVR’s interfaces and implementation are flexible and portable and create a gentle-slope path to tolerate growing error rates in future systems.« less

Spectroscopic analysis and control

DOEpatents

Tate; , James D.; Reed, Christopher J.; Domke, Christopher H.; Le, Linh; Seasholtz, Mary Beth; Weber, Andy; Lipp, Charles

2017-04-18

Apparatus for spectroscopic analysis which includes a tunable diode laser spectrometer having a digital output signal and a digital computer for receiving the digital output signal from the spectrometer, the digital computer programmed to process the digital output signal using a multivariate regression algorithm. In addition, a spectroscopic method of analysis using such apparatus. Finally, a method for controlling an ethylene cracker hydrogenator.

Floating-point system quantization errors in digital control systems

NASA Technical Reports Server (NTRS)

Phillips, C. L.; Vallely, D. P.

1978-01-01

This paper considers digital controllers (filters) operating in floating-point arithmetic in either open-loop or closed-loop systems. A quantization error analysis technique is developed, and is implemented by a digital computer program that is based on a digital simulation of the system. The program can be integrated into existing digital simulations of a system.

A spaceborne receiver for measuring electromagnetic field intensity

NASA Technical Reports Server (NTRS)

Reich, B. W.; Van Dusen, M. R.; Habib, E. J.

1973-01-01

Description of a very accurately controlled receiver for monitoring the electromagnetic radiations in both existing and projected space communication bands. Based on analysis of the existing and projected space communication bands, 108 to 174 MHz, 240 to 478 MHz, and 1535 to 1665 MHz were covered. The receiver achieves accurate control via a digitally tuned synthesizer and a wide range of digital control including frequency band coverage and gain control selection. Digital memory was provided to store 16 separate digital command instructions which can be programmed via a command data link. The receiver provides for transmission to the ground of both a predetection signal and signals in digital format, which in turn, were provided by sampling and analog-to-digital conversions.

An optimization-based approach for facility energy management with uncertainties, and, Power portfolio optimization in deregulated electricity markets with risk management

NASA Astrophysics Data System (ADS)

Xu, Jun

Topic 1. An Optimization-Based Approach for Facility Energy Management with Uncertainties. Effective energy management for facilities is becoming increasingly important in view of the rising energy costs, the government mandate on the reduction of energy consumption, and the human comfort requirements. This part of dissertation presents a daily energy management formulation and the corresponding solution methodology for HVAC systems. The problem is to minimize the energy and demand costs through the control of HVAC units while satisfying human comfort, system dynamics, load limit constraints, and other requirements. The problem is difficult in view of the fact that the system is nonlinear, time-varying, building-dependent, and uncertain; and that the direct control of a large number of HVAC components is difficult. In this work, HVAC setpoints are the control variables developed on top of a Direct Digital Control (DDC) system. A method that combines Lagrangian relaxation, neural networks, stochastic dynamic programming, and heuristics is developed to predict the system dynamics and uncontrollable load, and to optimize the setpoints. Numerical testing and prototype implementation results show that our method can effectively reduce total costs, manage uncertainties, and shed the load, is computationally efficient. Furthermore, it is significantly better than existing methods. Topic 2. Power Portfolio Optimization in Deregulated Electricity Markets with Risk Management. In a deregulated electric power system, multiple markets of different time scales exist with various power supply instruments. A load serving entity (LSE) has multiple choices from these instruments to meet its load obligations. In view of the large amount of power involved, the complex market structure, risks in such volatile markets, stringent constraints to be satisfied, and the long time horizon, a power portfolio optimization problem is of critical importance but difficulty for an LSE to serve the load, maximize its profit, and manage risks. In this topic, a mid-term power portfolio optimization problem with risk management is presented. Key instruments are considered, risk terms based on semi-variances of spot market transactions are introduced, and penalties on load obligation violations are added to the objective function to improve algorithm convergence and constraint satisfaction. To overcome the inseparability of the resulting problem, a surrogate optimization framework is developed enabling a decomposition and coordination approach. Numerical testing results show that our method effectively provides decisions for various instruments to maximize profit, manage risks, and is computationally efficient.

Bax-inhibitor-1 knockdown phenotypes are suppressed by Buffy and exacerbate degeneration in a Drosophila model of Parkinson disease

PubMed Central

2017-01-01

Background Bax inhibitor-1 (BI-1) is an evolutionarily conserved cytoprotective transmembrane protein that acts as a suppressor of Bax-induced apoptosis by regulation of endoplasmic reticulum stress-induced cell death. We knocked down BI-1 in the sensitive dopa decarboxylase (Ddc) expressing neurons of Drosophila melanogaster to investigate its neuroprotective functions. We additionally sought to rescue the BI-1-induced phenotypes by co-expression with the pro-survival Buffy and determined the effect of BI-1 knockdown on the neurodegenerative α-synuclein-induced Parkinson disease (PD) model. Methods We used organismal assays to assess longevity of the flies to determine the effect of the altered expression of BI-1 in the Ddc-Gal4-expressing neurons by employing two RNAi transgenic fly lines. We measured the locomotor ability of these RNAi lines by computing the climbing indices of the climbing ability and compared them to a control line that expresses the lacZ transgene. Finally, we performed biometric analysis of the developing eye, where we counted the number of ommatidia and calculated the area of ommatidial disruption. Results The knockdown of BI-1 in these neurons was achieved under the direction of the Ddc-Gal4 transgene and resulted in shortened lifespan and precocious loss of locomotor ability. The co-expression of Buffy, the Drosophila anti-apoptotic Bcl-2 homologue, with BI-1-RNAi resulted in suppression of the reduced lifespan and impaired climbing ability. Expression of human α-synuclein in Drosophila dopaminergic neurons results in neuronal degeneration, accompanied by the age-dependent loss in climbing ability. We exploited this neurotoxic system to investigate possible BI-1 neuroprotective function. The co-expression of α-synuclein with BI-1-RNAi results in a slight decrease in lifespan coupled with an impairment in climbing ability. In supportive experiments, we employed the neuron-rich Drosophila compound eye to investigate subtle phenotypes that result from altered gene expression. The knockdown of BI-1 in the Drosophila developing eye under the direction of the GMR-Gal4 transgene results in reduced ommatidia number and increased disruption of the ommatidial array. Similarly, the co-expression of BI-1-RNAi with Buffy results in the suppression of the eye phenotypes. The expression of α-synuclein along with the knockdown of BI-1 resulted in reduction of ommatidia number and more disruption of the ommatidial array. Conclusion Knockdown of BI-1 in the dopaminergic neurons of Drosophila results in a shortened lifespan and premature loss in climbing ability, phenotypes that appear to be strongly associated with models of PD in Drosophila, and which are suppressed upon overexpression of Buffy and worsened by co-expression with α-synuclein. This suggests that BI-1 is neuroprotective and its knockdown can be counteracted by the overexpression of the pro-survival Bcl-2 homologue. PMID:28243526

47 CFR 97.221 - Automatically controlled digital station.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Automatically controlled digital station. 97.221 Section 97.221 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Special Operations § 97.221 Automatically controlled digital...

Test and control computer user's guide for a digital beam former test system

NASA Technical Reports Server (NTRS)

Alexovich, Robert E.; Mallasch, Paul G.

1992-01-01

A Digital Beam Former Test System was developed to determine the effects of noise, interferers and distortions, and digital implementations of beam forming as applied to the Tracking and Data Relay Satellite 2 (TDRS 2) architectures. The investigation of digital beam forming with application to TDRS 2 architectures, as described in TDRS 2 advanced concept design studies, was conducted by the NASA/Lewis Research Center for NASA/Goddard Space Flight Center. A Test and Control Computer (TCC) was used as the main controlling element of the digital Beam Former Test System. The Test and Control Computer User's Guide for a Digital Beam Former Test System provides an organized description of the Digital Beam Former Test System commands. It is written for users who wish to conduct tests of the Digital Beam forming Test processor using the TCC. The document describes the function, use, and syntax of the TCC commands available to the user while summarizing and demonstrating the use of the commands wtihin DOS batch files.

User guide for the digital control system of the NASA/Langley Research Center's 13-inch Magnetic Suspension and Balance System

NASA Technical Reports Server (NTRS)

Britcher, Colin P.

1987-01-01

The technical background to the development of the digital control system of the NASA/Langley Research Center's 13 inch Magnetic Supension and Balance Systen (MSBS) is reviewed. The implementation of traditional MSBS control algorithms in digital form is examined. Extensive details of the 13-inch MSBS digital controller and related hardware are given, together with the introductory instructions for systems operators. Full listings of software are included in the Appendices.

Quantum Cascade Laser Tuning by Digital Micromirror Array-controlled External Cavity

DTIC Science & Technology

2014-01-01

P. Vujkovic-Cvijin, B. Gregor, A. C. Samuels, E. S. Roese, Quantum cascade laser tuning by digital micromirror array-controlled external cavity...REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Quantum cascade laser tuning by digital micromirror array-controlled...dimensional digital micromirror array (DMA) is described. The laser is tuned by modulating the reflectivity of DMA micromirror pixels under computer

Integrated Real-Time Control and Imaging System for Microbiorobotics and Nanobiostructures

DTIC Science & Technology

2016-01-11

kit with a control board and ALP 4.1 basic controller suite. The digital micromirror device is the highest resolution 16:9 aspect ratio system. This...in Figure 1, consisted of the following: (1) digital micromirror device (DMD) and controller, (2) an inverted epifluorescence microscope with a flat...accompanying control board and ALP 4.1 basic controller suite. The digital micromirror device is currently the highest commercially available

Digital phase-locked-loop speed sensor for accuracy improvement in analog speed controls. [feedback control and integrated circuits

NASA Technical Reports Server (NTRS)

Birchenough, A. G.

1975-01-01

A digital speed control that can be combined with a proportional analog controller is described. The stability and transient response of the analog controller were retained and combined with the long-term accuracy of a crystal-controlled integral controller. A relatively simple circuit was developed by using phase-locked-loop techniques and total error storage. The integral digital controller will maintain speed control accuracy equal to that of the crystal reference oscillator.

HIMAC RF system with a digital synthesizer

NASA Astrophysics Data System (ADS)

Kanazawa, M.; Sato, K.; Itano, A.; Sudou, M.; Noda, K.; Takada, E.; Kumada, M.; Yamazaki, C.; Yamagishi, T.; Morii, Y.; Toyoda, E.; Tsuzuki, N.; Yagi, T.

2000-04-01

An RF acceleration system, in which digital control with a direct digital synthesizer (DDS) is applied, has been developed for the Heavy Ion Medical Accelerator in Chiba (HIMAC) synchrotron. This digital system allows us to obtain stable operation of the acceleration system over a wide frequency range from 1.04 to 7.9 MHz. In this paper the designed digital RF control system and its performance are described.

Propulsion control experience used in the Highly Integrated Digital Electronic Control (HIDEC) program

NASA Technical Reports Server (NTRS)

Myers, L. P.; Burcham, F. W., Jr.

1984-01-01

The highly integrated digital electronic control (HIDEC) program will integrate the propulsion and flight control systems on an F-15 airplane at NASA Ames Research Center's Dryden Flight Research Facility. Ames-Dryden has conducted several propulsion control programs that have contributed to the HIDEC program. The digital electronic engine control (DEEC) flight evaluation investigated the performance and operability of the F100 engine equipped with a full-authority digital electronic control system. Investigations of nozzle instability, fault detection and accommodation, and augmentor transient capability provided important information for the HIDEC program. The F100 engine model derivative (EMD) was also flown in the F-15 airplane, and airplane performance was significantly improved. A throttle response problem was found and solved with a software fix to the control logic. For the HIDEC program, the F100 EMD engines equipped with DEEC controls will be integrated with the digital flight control system. The control modes to be implemented are an integrated flightpath management mode and an integrated adaptive engine control system mode. The engine control experience that will be used in the HIDEC program is discussed.

Field Programmable Gate Array for Implementation of Redundant Advanced Digital Feedback Control

NASA Technical Reports Server (NTRS)

King, K. D.

2003-01-01

The goal of this effort was to develop a digital motor controller using field programmable gate arrays (FPGAs). This is a more rugged approach than a conventional microprocessor digital controller. FPGAs typically have higher radiation (rad) tolerance than both the microprocessor and memory required for a conventional digital controller. Furthermore, FPGAs can typically operate at higher speeds. (While speed is usually not an issue for motor controllers, it can be for other system controllers.) Other than motor power, only a 3.3-V digital power supply was used in the controller; no analog bias supplies were used. Since most of the circuit was implemented in the FPGA, no additional parts were needed other than the power transistors to drive the motor. The benefits that FPGAs provide over conventional designs-lower power and fewer parts-allow for smaller packaging and reduced weight and cost.

Fast and robust control of nanopositioning systems: Performance limits enabled by field programmable analog arrays.

PubMed

Baranwal, Mayank; Gorugantu, Ram S; Salapaka, Srinivasa M

2015-08-01

This paper aims at control design and its implementation for robust high-bandwidth precision (nanoscale) positioning systems. Even though modern model-based control theoretic designs for robust broadband high-resolution positioning have enabled orders of magnitude improvement in performance over existing model independent designs, their scope is severely limited by the inefficacies of digital implementation of the control designs. High-order control laws that result from model-based designs typically have to be approximated with reduced-order systems to facilitate digital implementation. Digital systems, even those that have very high sampling frequencies, provide low effective control bandwidth when implementing high-order systems. In this context, field programmable analog arrays (FPAAs) provide a good alternative to the use of digital-logic based processors since they enable very high implementation speeds, moreover with cheaper resources. The superior flexibility of digital systems in terms of the implementable mathematical and logical functions does not give significant edge over FPAAs when implementing linear dynamic control laws. In this paper, we pose the control design objectives for positioning systems in different configurations as optimal control problems and demonstrate significant improvements in performance when the resulting control laws are applied using FPAAs as opposed to their digital counterparts. An improvement of over 200% in positioning bandwidth is achieved over an earlier digital signal processor (DSP) based implementation for the same system and same control design, even when for the DSP-based system, the sampling frequency is about 100 times the desired positioning bandwidth.

Design and development progress of a LLRF control system for a 500 MHz superconducting cavity

NASA Astrophysics Data System (ADS)

Lee, Y. S.; Kim, H. W.; Song, H. S.; Lee, J. H.; Park, K. H.; Yu, I. H.; Chai, J. S.

2012-07-01

The LLRF (low-level radio-frequency) control system which regulates the amplitude and the phase of the accelerating voltage inside a RF cavity is essential to ensure the stable operation of charged particle accelerators. Recent advances in digital signal processors and data acquisition systems have allowed the LLRF control system to be implemented in digitally and have made it possible to meet the higher demands associated with the performance of LLRF control systems, such as stability, accuracy, etc. For this reason, many accelerator laboratories have completed or are completing the developments of digital LLRF control systems. The digital LLRF control system has advantages related with flexibility and fast reconfiguration. This paper describes the design of the FPGA (field programmable gate array) based LLRF control system and the status of development for this system. The proposed LLRF control system includes an analog front-end, a digital board (ADC (analog to digital converter), DAC (digital to analog converter), FPGA, etc.) and a RF & clock generation system. The control algorithms will be implemented by using the VHDL (VHSIC (very high speed integrated circuits) hardware description language), and the EPICS (experiment physics and industrial control system) will be ported to the host computer for the communication. In addition, the purpose of this system is to control a 500 MHz RF cavity, so the system will be applied to the superconducting cavity to be installed in the PLS storage ring, and its performance will be tested.

Stability of Fiber Optic Networked Decentralized Distributed Engine Control Under Time Delays

DTIC Science & Technology

2009-08-01

Nomenclature FADEC = Full Authority Digital Engine Control D2FADEC = Decentralized Distributed Full Authority Digital Engine Control DEC...Corporation (IFOS), bm@ifos.com. I American Institute of Aeronautics and Astronautics 2 II. Distributed Engine Control Systems FADEC Based on...of Full Authority Digital Engine Control ( FADEC ) are distributed at the component level. Each sensor/actuator is to be replaced by a smart sensor

Electrical Subsystems Flight Test Handbook

DTIC Science & Technology

1984-01-01

distribution of this handbook to the public at large, or by DDC to the National Technical Information Service (NTIS). At NTIS, it will be available to...Abnormal Mode 58 Emergency Mode 61 Instrumentation 62 Test Information Sheets 62 Integration with Flight Test Program 62 DATA MEASUREMENT, ANALYS IS...AND EVALUATION 65 REFERENCES 73 -APPENDIX A - EXAMPLE OF TEST INFORMATION SHEET 75 APPENDIX B - EXAMPLE OF TEST PLAN SAFETY REVIEW 85 APPENDIX C

Correlating the Classes of Books Taken Out Of and Books Used Within an Open-Stack Library. Research Report.

ERIC Educational Resources Information Center

Domas, Ralph E.

The purpose of this study was to determine if a correlation existed between the classes of books checked out of the San Antonio College Library and the classes of books used in the Library. Data for out-of-library and in-library use were collected during February, 1978, and arranged by Dewey Decimal Classification (DDC) tens. By using the Pearson…

Weapons Effects in Cities. Volume 2. Appendices

DTIC Science & Technology

1974-12-01

reenforced 1st Division’s defense of the compound, its manpower decimated by the roadblock fight which had also cost it 12 AFCs destroyed. On coming...CONFIDENTIAL). 159. Calfee, Dewey , E. Limited Range Test of the M-16 Rifle with Eight Types of Rifle and Hand Grenades. (AD458570), Eglin Air...30 September 1954. 165. Defense Documentation Center. Propellant Flashes. A DDC Biblio- graphy (U). (AD516700), Alexandria, Virginia: Defense

TRADOC Library and Information Network (TRALINET)

DTIC Science & Technology

1979-03-01

by the Library of Congress, Dewey materials that have beer photographically reduced Decimal , or any other classification scheme adopted in size for...sites at Forts Hood, TX; Gordon, GA; Monroe, VA; Knox, KY, and Leavenworth, KS. DTIC, formally Defense Documentation Center ( DDC ), serves as the primary...locally expanded subject schedules, whether schedules aic for Dewey , Library of Congress, etc., particularly in the are& of Military Arts and Sciences. 1 4

Vancomycin-Resistance Enterococci Infections in the Department of the Defense: Annual Report 2013

DTIC Science & Technology

2014-08-01

str.r.:lioos, S€’ £l "r:’hi fl!’:: lil<i~lin ,:l ddc ~o.r-c.;s, !]:l:ho:>r rr:, aY. nflinttlirir~ :he !::f;, ·nod c ol ’ HO: Io ~:·rnhlir’U ;;· ;d ro...16. Morris JG, et al. Enterococci resistant to multiple antimicrobial agents, including vancomycin: establishment of endemicity in a university

78 FR 35663 - Endangered and Threatened Wildlife and Plants; Removing the Gray Wolf (Canis lupus) From the List...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

.... Kempthorne, 579 F. Supp. 2d 7 (D.D.C. 2008)) and, in one case, a settlement agreement (Humane Society of the... INFORMATION CONTACT by July 29, 2013. ADDRESSES: You may submit comments by one of the following methods: (1.... You may submit your comments and materials by one of the methods listed in ADDRESSES. We will not...

75 FR 13223 - Funds Received in Response to Solicitations; Allocation of Expenses by Separate Segregated Funds...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

... Appeals for the District of Columbia Circuit in EMILY's List v. FEC, 581 F.3d 1 (DC Cir. 2009). On... of the United States Constitution. See EMILY's List v. FEC, 581 F.3d 1 (DC Cir. 2009). The court also... vacated. See Final Order, EMILY's List v. FEC, No. 05-0049 (D.D.C. Nov. 30, 2009). The Commission...

Active flutter suppression using optical output feedback digital controllers

NASA Technical Reports Server (NTRS)

1982-01-01

A method for synthesizing digital active flutter suppression controllers using the concept of optimal output feedback is presented. A convergent algorithm is employed to determine constrained control law parameters that minimize an infinite time discrete quadratic performance index. Low order compensator dynamics are included in the control law and the compensator parameters are computed along with the output feedback gain as part of the optimization process. An input noise adjustment procedure is used to improve the stability margins of the digital active flutter controller. Sample rate variation, prefilter pole variation, control structure variation and gain scheduling are discussed. A digital control law which accommodates computation delay can stabilize the wing with reasonable rms performance and adequate stability margins.

Contextualizing neuro-collaborations: reflections on a transdisciplinary fMRI lie detection experiment

PubMed Central

Littlefield, Melissa M.; Fitzgerald, Des; Knudsen, Kasper; Tonks, James; Dietz, Martin J.

2014-01-01

Recent neuroscience initiatives (including the E.U.’s Human Brain Project and the U.S.’s BRAIN Initiative) have reinvigorated discussions about the possibilities for transdisciplinary collaboration between the neurosciences, the social sciences, and the humanities. As STS scholars have argued for decades, however, such inter- and transdisciplinary collaborations are potentially fraught with tensions between researchers. This essay build on such claims by arguing that the tensions of transdisciplinary research also exist within researchers’ own experiences of working between disciplines - a phenomenon that we call “disciplinary double consciousness” (DDC). Building on previous work that has characterized similar spaces (and especially on the Critical Neuroscience literature), we argue that “neuro-collaborations” inevitably engage researchers in DDC - a phenomenon that allows us to explore the useful dissonance that researchers can experience when working between a “home” discipline and a secondary discipline. Our case study is a five-year research project in functional magnetic resonance imaging (fMRI) lie detection involving a transdisciplinary research team made up of social scientists, a neuroscientist, and a humanist. In addition to theorizing neuro-collaborations from the inside-out, this essay presents practical suggestions for developing transdisciplinary infrastructures that could support future neuro-collaborations. PMID:24744713

Influences of Cr/Ni equivalent ratios of filler wires on pitting corrosion and ductility-dip cracking of AISI 316L weld metals

NASA Astrophysics Data System (ADS)

Kim, Y. H.; Kim, D. G.; Sung, J. H.; Kim, I. S.; Ko, D. E.; Kang, N. H.; Hong, H. U.; Park, J. H.; Lee, H. W.

2011-02-01

To study the pitting corrosion of AISI 316L weld metals according to the chromium/nickel equivalent ratio (Creq/Nieq ratio), three filler wires were newly designed for the flux-cored arc welding process. The weld metal with delta-ferrite at less than 3 vol.%, was observed for ductility-dip cracking (DDC) in the reheated region after multi-pass welding. The tensile strength and yield strength increased with increasing Creq/Nieq ratio. The result of anodic polarization tests in a 0.1 M NaCl solution at the room temperature (25) for 45 min, revealed that the base metal and weld metals have a similar corrosion potential of -0.34 VSCE. The weld metal with the highest content of Cr had the highest pitting potential (0.39 VSCE) and the passivation range (0.64 VSCE) was higher than the base metal (0.21 VSCE and 0.46 VSCE, respectively). Adding 0.001 M Na2S to the 0.1M NaCl solution, the corrosion occurred more severely by H2S. The corrosion potentials of the base metal and three weld metals decreased to -1.0 VSCE. DDC caused the decrease of the pitting potential by inducing a locally intense corrosion attack around the crack openings.

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

PubMed Central

Capilla, Amalia; Karachentsev, Dmitry; Patterson, Rachel A.; Hermann, Anita; Juarez, Michelle T.; McGinnis, William

2017-01-01

The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal–ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci. PMID:28289197

Effect of various electrokinetic treatment regimes on solids surface properties and thermal behavior of oil sediments.

PubMed

Kariminezhad, Esmaeel; Elektorowicz, Maria

2018-04-10

The electrokinetic process has shown its ability to separate the different material phases. However, not much is known about the effect of the electric fields on the surface properties of solids in the oil sediments and their behavior under different electrical regimes. In this study, the effect of four different types of electrical current on the surface properties of oil sediments was investigated, namely constant direct current (CDC), pulsed direct current (PDC), incremental direct current (IDC) and decremental direct current (DDC). X-ray photoelectron spectroscopy (XPS) analyses showed a decrease in the concentration of carbon from 99% in centrifuged samples to 63% on the surface of the solids in the PDC-treated oil sediment. Wettability alteration and contact angle studies showed an enhance in hydrophilicity of the solids following electrokinetic treatment. A significant change in carbon and oxygen-containing functionalities at the surface solids of the DDC-treated sediment was also observed. Thermogravimetric analyses (TGA) confirmed the ability of electrokinetic treatment in separating the phases by shifting the thermogram profiles towards lower temperatures. The findings showed that the electrokinetic process exerts its effect by altering the surface properties of the sediment solids and destabilizing water-in-oil emulsions to facilitate phase separation of this complex waste. Copyright © 2018 Elsevier B.V. All rights reserved.

FAT10 IS AN EPIGENETIC MARKER FOR LIVER PRENEOPLASIA IN A DRUG-PRIMED MOUSE MODEL OF TUMORIGENESIS

PubMed Central

Oliva, Joan; Bardag-Gorce, Fawzia; French, Barbara A; Li, Jun; McPhaul, Laron; Amidi, Fataneh; Dedes, Jeniffer; Habibi, Amir; Nguyen, Sheila; French, Samuel W

2010-01-01

There is clinical evidence that chronic liver diseases in which MDBs (Mallory Denk Bodies) form progress to hepatocellular carcinoma. The present study provides evidence that links MDB formation induced by chronic drug injury, with preneoplasia and later to the formation of tumors, which develop long after drug withdrawal. Evidence indicated that this link was due to an epigenetic cellular memory induced by chronic drug ingestion. Microarray analysis showed that the expressions of many markers of preneoplasia (UBD, Alpha Fetoprotein, KLF6 and Glutathione-S-Transferase mu2) were increased together when the drug DDC was refed. These changes were suppressed by S-adenosylmethionine feeding, indicating that the drug was affecting DNA and histones methylation in an epigenetic manner. The link between MDB formation and neoplasia formation was likely due to the over expression of UBD (also called FAT10), which is up regulated in 90% of human hepatocellular carcinomas. Immunohistochemical staining of drug primed mouse livers showed that FAT10 positive liver cells persisted up to 4 months after drug withdrawal and they were still found in the livers of mice, 14 months after drug withdrawal. The refeeding of DDC increased the percent of FAT10 hepatocytes. PMID:18280469

Analysis of the ductility dip cracking in the nickel-base alloy 617mod

NASA Astrophysics Data System (ADS)

Eilers, A.; Nellesen, J.; Zielke, R.; Tillmann, W.

2017-03-01

While testing steam leading power plant components made of the nickel-base alloy A617mod at elevated temperatures (700 °C), ductility dip cracking (DDC) was observed in welding seams and their surroundings. In order to clarify the mechanism of crack formation, investigations were carried out on welded specimens made of A617mod. Interrupted tensile tests were performed on tensile specimens taken from the area of the welding seam. To simulate the conditions, the tensile tests were conducted at a temperature of 700 °C and with a low strain rate. Local strain fields at grain boundaries and inside single grains were determined at different deformation states by means of two-dimensional digital image correlation (DIC). Besides the strain fields, local hardnesses (nanoindentation), energy dispersive X-Ray spectroscopy (EDX), and electron backscatter diffraction (EBSD) measurements were performed. Besides information concerning the grain orientation, the EBSD measurement provides information on the coincidence site lattice (CSL) at grain boundaries as well as the Schmid factor of single grains. All results of the analysis methods mentioned above were correlated and compared to each other and related to the crack formation. Among other things, correlations between strain fields and Schmid factors were determined. The investigations show that the following influences affect the crack formation: orientation of the grain boundaries to the direction of the loading, the orientation of the grains to each other (CSL), and grain boundary sliding.

Research in digital adaptive flight controllers

NASA Technical Reports Server (NTRS)

Kaufman, H.

1976-01-01

A design study of adaptive control logic suitable for implementation in modern airborne digital flight computers was conducted. Both explicit controllers which directly utilize parameter identification and implicit controllers which do not require identification were considered. Extensive analytical and simulation efforts resulted in the recommendation of two explicit digital adaptive flight controllers. Interface weighted least squares estimation procedures with control logic were developed using either optimal regulator theory or with control logic based upon single stage performance indices.

A monitor for the laboratory evaluation of control integrity in digital control systems operating in harsh electromagnetic environments

NASA Technical Reports Server (NTRS)

Belcastro, Celeste M.; Fischl, Robert; Kam, Moshe

1992-01-01

This paper presents a strategy for dynamically monitoring digital controllers in the laboratory for susceptibility to electromagnetic disturbances that compromise control integrity. The integrity of digital control systems operating in harsh electromagnetic environments can be compromised by upsets caused by induced transient electrical signals. Digital system upset is a functional error mode that involves no component damage, can occur simultaneously in all channels of a redundant control computer, and is software dependent. The motivation for this work is the need to develop tools and techniques that can be used in the laboratory to validate and/or certify critical aircraft controllers operating in electromagnetically adverse environments that result from lightning, high-intensity radiated fields (HIRF), and nuclear electromagnetic pulses (NEMP). The detection strategy presented in this paper provides dynamic monitoring of a given control computer for degraded functional integrity resulting from redundancy management errors, control calculation errors, and control correctness/effectiveness errors. In particular, this paper discusses the use of Kalman filtering, data fusion, and statistical decision theory in monitoring a given digital controller for control calculation errors.

Implementation of Adaptive Digital Controllers on Programmable Logic Devices

NASA Technical Reports Server (NTRS)

Gwaltney, David A.; King, Kenneth D.; Smith, Keary J.; Montenegro, Justino (Technical Monitor)

2002-01-01

Much has been made of the capabilities of Field Programmable Gate Arrays (FPGA's) in the hardware implementation of fast digital signal processing functions. Such capability also makes an FPGA a suitable platform for the digital implementation of closed loop controllers. Other researchers have implemented a variety of closed-loop digital controllers on FPGA's. Some of these controllers include the widely used Proportional-Integral-Derivative (PID) controller, state space controllers, neural network and fuzzy logic based controllers. There are myriad advantages to utilizing an FPGA for discrete-time control functions which include the capability for reconfiguration when SRAM- based FPGA's are employed, fast parallel implementation of multiple control loops and implementations that can meet space level radiation tolerance requirements in a compact form-factor. Generally, a software implementation on a Digital Signal Processor (DSP) device or microcontroller is used to implement digital controllers. At Marshall Space Flight Center, the Control Electronics Group has been studying adaptive discrete-time control of motor driven actuator systems using DSP devices. While small form factor, commercial DSP devices are now available with event capture, data conversion, Pulse Width Modulated (PWM) outputs and communication peripherals, these devices are not currently available in designs and packages which meet space level radiation requirements. In general, very few DSP devices are produced that are designed to meet any level of radiation tolerance or hardness. An alternative is required for compact implementation of such functionality to withstand the harsh environment encountered on spacemap. The goal of this effort is to create a fully digital, flight ready controller design that utilizes an FPGA for implementation of signal conditioning for control feedback signals, generation of commands to the controlled system, and hardware insertion of adaptive-control algorithm approaches. Radiation tolerant FPGA's are a feasible option for reaching this goal.

Development and implementation of an automated quantitative film digitizer quality control program

NASA Astrophysics Data System (ADS)

Fetterly, Kenneth A.; Avula, Ramesh T. V.; Hangiandreou, Nicholas J.

1999-05-01

A semi-automated, quantitative film digitizer quality control program that is based on the computer analysis of the image data from a single digitized test film was developed. This program includes measurements of the geometric accuracy, optical density performance, signal to noise ratio, and presampled modulation transfer function. The variability of the measurements was less than plus or minus 5%. Measurements were made on a group of two clinical and two laboratory laser film digitizers during a trial period of approximately four months. Quality control limits were established based on clinical necessity, vendor specifications and digitizer performance. During the trial period, one of the digitizers failed the performance requirements and was corrected by calibration.

Floating-point system quantization errors in digital control systems

NASA Technical Reports Server (NTRS)

Phillips, C. L.

1973-01-01

The results are reported of research into the effects on system operation of signal quantization in a digital control system. The investigation considered digital controllers (filters) operating in floating-point arithmetic in either open-loop or closed-loop systems. An error analysis technique is developed, and is implemented by a digital computer program that is based on a digital simulation of the system. As an output the program gives the programing form required for minimum system quantization errors (either maximum of rms errors), and the maximum and rms errors that appear in the system output for a given bit configuration. The program can be integrated into existing digital simulations of a system.

YF-12 cooperative airframe/propulsion control system program, volume 1

NASA Technical Reports Server (NTRS)

Anderson, D. L.; Connolly, G. F.; Mauro, F. M.; Reukauf, P. J.; Marks, R. (Editor)

1980-01-01

Several YF-12C airplane analog control systems were converted to a digital system. Included were the air data computer, autopilot, inlet control system, and autothrottle systems. This conversion was performed to allow assessment of digital technology applications to supersonic cruise aircraft. The digital system was composed of a digital computer and specialized interface unit. A large scale mathematical simulation of the airplane was used for integration testing and software checkout.

Bandwidth controller for phase-locked-loop

NASA Technical Reports Server (NTRS)

Brockman, Milton H. (Inventor)

1992-01-01

A phase locked loop utilizing digital techniques to control the closed loop bandwidth of the RF carrier phase locked loop in a receiver provides high sensitivity and a wide dynamic range for signal reception. After analog to digital conversion, a digital phase locked loop bandwidth controller provides phase error detection with automatic RF carrier closed loop tracking bandwidth control to accommodate several modes of transmission.

Development of a High Chromium Ni-Base Filler Metal Resistant to Ductility Dip Cracking and Solidification Cracking

NASA Astrophysics Data System (ADS)

Hope, Adam T.

Many nuclear reactor components previously constructed with Ni-based alloys containing 20 wt% Cr have been found to be susceptible to stress corrosion cracking. The nuclear power industry now uses high chromium (˜30wt%) Ni-based filler metals to mitigate stress corrosion cracking. Current alloys are plagued with weldability issues, either solidification cracking or ductility dip cracking (DDC). Solidification cracking is related to solidification temperature range and the DDC is related to the fraction eutectic present in the microstructure. It was determined that an optimal alloy should have a solidification temperature range less than 150°C and at least 2% volume fraction eutectic. Due to the nature of the Nb rich eutectic that forms, it is difficult to avoid both cracking types simultaneously. Through computational modeling, alternative eutectic forming elements, Hf and Ta, have been identified as replacements for Nb in such alloys. Compositions have been optimized through a combination of computational and experimental techniques combined with a design of experiment methodology. Small buttons were melted using commercially pure materials in a copper hearth to obtain the desired compositions. These buttons were then subjected to a gas tungsten arc spot weld. A type C thermocouple was used to acquire the cooling history during the solidification process. The cooling curves were processed using Single Sensor Differential Thermal Analysis to determine the solidification temperature range, and indicator of solidification cracking susceptibility. Metallography was performed to determine the fraction eutectic present, an indicator of DDC resistance. The optimal level of Hf to resist cracking was found to be 0.25 wt%. The optimal level of Ta was found to be 4 wt%. gamma/MC type eutectics were found to form first in all Nb, Ta, and Hf-bearing compositions. Depending on Fe and Cr content, gamma/Laves eutectic was sometimes found in Nb and Ta-bearing compositions, while Hf-bearing compositions had gamma/Ni7Hf2 as the final eutectic to solidify. This study found that the extra Cr in the current generation alloys promotes the gamma/Laves phase eutectic, which expands the solidification temperature range and promotes solidification cracking. Both Ta-bearing and Hf-bearing eutectics were found to solidify at higher temperatures than Nb-bearing eutectics, leading to narrower solidification temperature ranges. Weldability testing on the optimized Ta-bearing compositions revealed good resistance to both DDC and solidification cracking. Unexpectedly, the optimized Hf-bearing compositions were quite susceptible to solidification cracking. This led to an investigation on the possible wetting effect of eutectics on solidification cracking susceptibly, and a theory on how wetting affects the solidification crack susceptibility and the volume fraction of eutectic needed for crack healing has been proposed. Alloys with eutectics that easily wet the grain boundaries have increased solidification crack susceptibility at low volume fraction eutectics, but as the fraction eutectic is increased, experience crack healing at relatively lower fraction eutectics than alloys with eutectics that don't wet as easily. Hf rich eutectics were found to wet grain boundaries significantly more than Nb rich eutectics. Additions of Mo were also found to increase the wetting of eutectics in Nb-bearing alloys.

Digitally controlled distributed phase shifter

DOEpatents

Hietala, V.M.; Kravitz, S.H.; Vawter, G.A.

1993-08-17

A digitally controlled distributed phase shifter is comprised of N phase shifters. Digital control is achieved by using N binary length-weighted electrodes located on the top surface of a waveguide. A control terminal is attached to each electrode thereby allowing the application of a control signal. The control signal is either one or two discrete bias voltages. The application of the discrete bias voltages changes the modal index of a portion of the waveguide that corresponds to a length of the electrode to which the bias voltage is applied, thereby causing the phase to change through the underlying portion of the waveguide. The digitally controlled distributed phase shift network has a total phase shift comprised of the sum of the individual phase shifters.

Digitally controlled distributed phase shifter

DOEpatents

Hietala, Vincent M.; Kravitz, Stanley H.; Vawter, Gregory A.

1993-01-01

A digitally controlled distributed phase shifter is comprised of N phase shifters. Digital control is achieved by using N binary length-weighted electrodes located on the top surface of a waveguide. A control terminal is attached to each electrode thereby allowing the application of a control signal. The control signal is either one or two discrete bias voltages. The application of the discrete bias voltages changes the modal index of a portion of the waveguide that corresponds to a length of the electrode to which the bias voltage is applied, thereby causing the phase to change through the underlying portion of the waveguide. The digitally controlled distributed phase shift network has a total phase shift comprised of the sum of the individual phase shifters.

A Nonlinear Digital Control Solution for a DC/DC Power Converter

NASA Technical Reports Server (NTRS)

Zhu, Minshao

2002-01-01

A digital Nonlinear Proportional-Integral-Derivative (NPID) control algorithm was proposed to control a 1-kW, PWM, DC/DC, switching power converter. The NPID methodology is introduced and a practical hardware control solution is obtained. The design of the controller was completed using Matlab (trademark) Simulink, while the hardware-in-the-loop testing was performed using both the dSPACE (trademark) rapid prototyping system, and a stand-alone Texas Instruments (trademark) Digital Signal Processor (DSP)-based system. The final Nonlinear digital control algorithm was implemented and tested using the ED408043-1 Westinghouse DC-DC switching power converter. The NPID test results are discussed and compared to the results of a standard Proportional-Integral (PI) controller.

Flight test of a full authority Digital Electronic Engine Control system in an F-15 aircraft

NASA Technical Reports Server (NTRS)

Barrett, W. J.; Rembold, J. P.; Burcham, F. W.; Myers, L.

1981-01-01

The Digital Electronic Engine Control (DEEC) system considered is a relatively low cost digital full authority control system containing selectively redundant components and fault detection logic with capability for accommodating faults to various levels of operational capability. The DEEC digital control system is built around a 16-bit, 1.2 microsecond cycle time, CMOS microprocessor, microcomputer system with approximately 14 K of available memory. Attention is given to the control mode, component bench testing, closed loop bench testing, a failure mode and effects analysis, sea-level engine testing, simulated altitude engine testing, flight testing, the data system, cockpit, and real time display.

Digital control of wind tunnel magnetic suspension and balance systems

NASA Technical Reports Server (NTRS)

Britcher, Colin P.; Goodyer, Michael J.; Eskins, Jonathan; Parker, David; Halford, Robert J.

1987-01-01

Digital controllers are being developed for wind tunnel magnetic suspension and balance systems, which in turn permit wind tunnel testing of aircraft models free from support interference. Hardware and software features of two existing digital control systems are reviewed. Some aspects of model position sensing and system calibration are also discussed.

COSPAS/SARSAT 406-MHz emergency beacon digital controller

NASA Technical Reports Server (NTRS)

Ivancic, William D.

1988-01-01

The digital control portion of a low-cost 406-MHz COSPAS/SARSAT emergency beacon has been designed and breadboarded at the NASA Lewis Research Center. This report discusses the requirements and design tradeoffs of the digital controller and describes the hardware and software design, which is available only to United States citizens and companies.

77 FR 43405 - Final Standard Review Plan, Branch Technical Position 7-19 on Guidance for Evaluation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

... Digital Computer-Based Instrumentation and Control Systems.'' This BTP is to be cited as the acceptance criteria for Diversity and Defense-in-Depth in Digital Computer-Based Instrumentation and Control Systems... Evaluation of Diversity and Defense-in-Depth in Digital Computer-Based Instrumentation and Control Systems...

What can formal methods offer to digital flight control systems design

NASA Technical Reports Server (NTRS)

Good, Donald I.

1990-01-01

Formal methods research begins to produce methods which will enable mathematic modeling of the physical behavior of digital hardware and software systems. The development of these methods directly supports the NASA mission of increasing the scope and effectiveness of flight system modeling capabilities. The conventional, continuous mathematics that is used extensively in modeling flight systems is not adequate for accurate modeling of digital systems. Therefore, the current practice of digital flight control system design has not had the benefits of extensive mathematical modeling which are common in other parts of flight system engineering. Formal methods research shows that by using discrete mathematics, very accurate modeling of digital systems is possible. These discrete modeling methods will bring the traditional benefits of modeling to digital hardware and hardware design. Sound reasoning about accurate mathematical models of flight control systems can be an important part of reducing risk of unsafe flight control.

A digital control system for high level acoustic noise generation

NASA Technical Reports Server (NTRS)

Lee, John P.; Bosco, Jerry H.

1986-01-01

As part of the modernization of the Acoustic Test Facility at Lockheed Missiles and Space Company, Sunnyvale, a digital acoustic control system was designed and built. The requirements imposed by Lockheed on the control system and the degree to which those requirements were met are discussed. Acceptance test results as well as some of the features of the digital control system not found in traditional manual control systems are discussed.

Digital flight control actuation system study

NASA Technical Reports Server (NTRS)

Rossing, R.; Hupp, R.

1974-01-01

Flight control actuators and feedback sensors suitable for use in a redundant digital flight control system were examined. The most appropriate design approach for an advanced digital flight control actuation system for development and use in a fly-by-wire system was selected. The concept which was selected consisted of a PM torque motor direct drive. The selected system is compatible with concurrent and independent development efforts on the computer system and the control law mechanizations.

Precision digital control systems

NASA Astrophysics Data System (ADS)

Vyskub, V. G.; Rozov, B. S.; Savelev, V. I.

This book is concerned with the characteristics of digital control systems of great accuracy. A classification of such systems is considered along with aspects of stabilization, programmable control applications, digital tracking systems and servomechanisms, and precision systems for the control of a scanning laser beam. Other topics explored are related to systems of proportional control, linear devices and methods for increasing precision, approaches for further decreasing the response time in the case of high-speed operation, possibilities for the implementation of a logical control law, and methods for the study of precision digital control systems. A description is presented of precision automatic control systems which make use of electronic computers, taking into account the existing possibilities for an employment of computers in automatic control systems, approaches and studies required for including a computer in such control systems, and an analysis of the structure of automatic control systems with computers. Attention is also given to functional blocks in the considered systems.

Digital control of diode laser for atmospheric spectroscopy

NASA Technical Reports Server (NTRS)

Menzies, R. T.; Rutledge, C. W. (Inventor)

1985-01-01

A system is described for remote absorption spectroscopy of trace species using a diode laser tunable over a useful spectral region of 50 to 200 cm(-1) by control of diode laser temperature over range from 15 K to 100 K, and tunable over a smaller region of typically 0.1 to 10 cm(-1) by control of the diode laser current over a range from 0 to 2 amps. Diode laser temperature and current set points are transmitted to the instrument in digital form and stored in memory for retrieval under control of a microprocessor during measurements. The laser diode current is determined by a digital to analog converter through a field effect transistor for a high degree of ambient temperature stability, while the laser diode temperature is determined by set points entered into a digital to analog converter under control of the microprocessor. Temperature of the laser diode is sensed by a sensor diode to provide negative feedback to the temperature control circuit that responds to the temperature control digital to analog converter.

Digitally controlled analog proportional-integral-derivative (PID) controller for high-speed scanning probe microscopy

NASA Astrophysics Data System (ADS)

Dukic, Maja; Todorov, Vencislav; Andany, Santiago; Nievergelt, Adrian P.; Yang, Chen; Hosseini, Nahid; Fantner, Georg E.

2017-12-01

Nearly all scanning probe microscopes (SPMs) contain a feedback controller, which is used to move the scanner in the direction of the z-axis in order to maintain a constant setpoint based on the tip-sample interaction. The most frequently used feedback controller in SPMs is the proportional-integral (PI) controller. The bandwidth of the PI controller presents one of the speed limiting factors in high-speed SPMs, where higher bandwidths enable faster scanning speeds and higher imaging resolution. Most SPM systems use digital signal processor-based PI feedback controllers, which require analog-to-digital and digital-to-analog converters. These converters introduce additional feedback delays which limit the achievable imaging speed and resolution. In this paper, we present a digitally controlled analog proportional-integral-derivative (PID) controller. The controller implementation allows tunability of the PID gains over a large amplification and frequency range, while also providing precise control of the system and reproducibility of the gain parameters. By using the analog PID controller, we were able to perform successful atomic force microscopy imaging of a standard silicon calibration grating at line rates up to several kHz.

Digitally controlled analog proportional-integral-derivative (PID) controller for high-speed scanning probe microscopy.

PubMed

Dukic, Maja; Todorov, Vencislav; Andany, Santiago; Nievergelt, Adrian P; Yang, Chen; Hosseini, Nahid; Fantner, Georg E

2017-12-01

Nearly all scanning probe microscopes (SPMs) contain a feedback controller, which is used to move the scanner in the direction of the z-axis in order to maintain a constant setpoint based on the tip-sample interaction. The most frequently used feedback controller in SPMs is the proportional-integral (PI) controller. The bandwidth of the PI controller presents one of the speed limiting factors in high-speed SPMs, where higher bandwidths enable faster scanning speeds and higher imaging resolution. Most SPM systems use digital signal processor-based PI feedback controllers, which require analog-to-digital and digital-to-analog converters. These converters introduce additional feedback delays which limit the achievable imaging speed and resolution. In this paper, we present a digitally controlled analog proportional-integral-derivative (PID) controller. The controller implementation allows tunability of the PID gains over a large amplification and frequency range, while also providing precise control of the system and reproducibility of the gain parameters. By using the analog PID controller, we were able to perform successful atomic force microscopy imaging of a standard silicon calibration grating at line rates up to several kHz.

Digital robust control law synthesis using constrained optimization

NASA Technical Reports Server (NTRS)

Mukhopadhyay, Vivekananda

1989-01-01

Development of digital robust control laws for active control of high performance flexible aircraft and large space structures is a research area of significant practical importance. The flexible system is typically modeled by a large order state space system of equations in order to accurately represent the dynamics. The active control law must satisy multiple conflicting design requirements and maintain certain stability margins, yet should be simple enough to be implementable on an onboard digital computer. Described here is an application of a generic digital control law synthesis procedure for such a system, using optimal control theory and constrained optimization technique. A linear quadratic Gaussian type cost function is minimized by updating the free parameters of the digital control law, while trying to satisfy a set of constraints on the design loads, responses and stability margins. Analytical expressions for the gradients of the cost function and the constraints with respect to the control law design variables are used to facilitate rapid numerical convergence. These gradients can be used for sensitivity study and may be integrated into a simultaneous structure and control optimization scheme.

The Soviet Decision to Invade Czechoslovakia

DTIC Science & Technology

1975-09-01

inuary 1976 DDC - ’■’ rv > Canoron Station O T "> 1 ." Mexancria The caveat appearing on the title pi c.r. ol: Center for hib- avanced^earch...Soviets viewed the political developments in Czechoslovakia in 1968 with alarm bordering on paranoia, conditioned by the "dagger" phobia and by...published its Action Program entitled "The Czechoslovak Road to Socialism ," a program described by a Western authority as "a remarkable

Classification Schedules as Subject Enhancement in Online Catalogs. A Review of a Conference Sponsored by Forest Press, the OCLC Online Computer Library Center, and the Council on Library Resources.

ERIC Educational Resources Information Center

Mandel, Carol A.

This paper presents a synthesis of the ideas and issues developed at a conference convened to review the results of the Dewey Decimal Classification Online Project and explore the potential for future use of the Dewey Decimal Classification (DDC) and Library of Congress Classification (LCC) schedules in online library catalogs. Conference…

Nonlinear Interactions between Laser Radiation and Spin-Aligned Carriers in Semiconductors.

DTIC Science & Technology

1980-11-25

Massachusetts 02154 AIR FORCE OFFICEK OF SCIWMTIFIC RESWACHi (AISC) NOTICE OF TRJAZSMITTAL TO DDC This techniical raouti has been reviewed an I approved...f’or PuAli release JAN A.FR 190-12 (7b). Distribution is wilimited. &. D. BLOSA Technical Inorwatiom Oftlee UNCLASSIFIED SECURITY CLASSIFICATION OF...well. The material of choice D I 1473 UNCLASSIFIED.6- SECURITY CLASSIFICATION OF THIS PAGE (mien Deta Entered) UNCLASSIFIED SECURITY CLASSIFICATION OF

Simulation of an Air Cushion Vehicle

DTIC Science & Technology

1977-03-01

Massachusetts 02139 ! DDC Niov 219T March 1977 Final Report for Period January 1975 - December 1976 DOD DISTRIBUTION STATEMENT Approved for public...or in ,art is permitted for any purpose of the United States Government. II II JI UNCLASSI FIED SECURITY CLASSIFICATiON OF TIlS PAGE flWhen Dato...overflow Floating point fault Decimal arithmetic fault Watch Dog timer runout 186 NAVTRAEQUIPCEN 75-C-0057- 1 PROGRAM ENi\\TRY Initial Program - LOAD Inhibit

Projectile Measurements and Instrumentation Laboratory Mass Property Measurements

DTIC Science & Technology

1974-09-01

STATEMENT (ol III* abalrael anlarad In Block 20, II dlllaranl Irom Rmpotl) 11. SUPPLEMENTARY NOTES Available in DDC . 1». KEY WORDS fConllnu* on...FORM I JAN 73 1473 EDITION OF I NOV SB IS OBSOLETE UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE (Whmn Dmlm Enlmrmd) ■auHHaUi^L^u^. ^^-..-^-i... CLASSIFICATION Of THIS PAQE(Whm> Dmlm Knltrmd) Item 19 (Continued): Top Loading Balance Center of Gravity Balance Moment of Inertia Instrument

Designed cell consortia as fragrance-programmable analog-to-digital converters.

PubMed

Müller, Marius; Ausländer, Simon; Spinnler, Andrea; Ausländer, David; Sikorski, Julian; Folcher, Marc; Fussenegger, Martin

2017-03-01

Synthetic biology advances the rational engineering of mammalian cells to achieve cell-based therapy goals. Synthetic gene networks have nearly reached the complexity of digital electronic circuits and enable single cells to perform programmable arithmetic calculations or to provide dynamic remote control of transgenes through electromagnetic waves. We designed a synthetic multilayered gaseous-fragrance-programmable analog-to-digital converter (ADC) allowing for remote control of digital gene expression with 2-bit AND-, OR- and NOR-gate logic in synchronized cell consortia. The ADC consists of multiple sampling-and-quantization modules sensing analog gaseous fragrance inputs; a gas-to-liquid transducer converting fragrance intensity into diffusible cell-to-cell signaling compounds; a digitization unit with a genetic amplifier circuit to improve the signal-to-noise ratio; and recombinase-based digital expression switches enabling 2-bit processing of logic gates. Synthetic ADCs that can remotely control cellular activities with digital precision may enable the development of novel biosensors and may provide bioelectronic interfaces synchronizing analog metabolic pathways with digital electronics.

Dynamical beam manipulation based on 2-bit digitally-controlled coding metasurface.

PubMed

Huang, Cheng; Sun, Bo; Pan, Wenbo; Cui, Jianhua; Wu, Xiaoyu; Luo, Xiangang

2017-02-08

Recently, a concept of digital metamaterials has been proposed to manipulate field distribution through proper spatial mixtures of digital metamaterial bits. Here, we present a design of 2-bit digitally-controlled coding metasurface that can effectively modulate the scattered electromagnetic wave and realize different far-field beams. Each meta-atom of this metasurface integrates two pin diodes, and by tuning their operating states, the metasurface has four phase responses of 0, π/2, π, and 3π/2, corresponding to four basic digital elements "00", "01", "10", and "11", respectively. By designing the coding sequence of the above digital element array, the reflected beam can be arbitrarily controlled. The proposed 2-bit digital metasurface has been demonstrated to possess capability of achieving beam deflection, multi-beam and beam diffusion, and the dynamical switching of these different scattering patterns is completed by a programmable electric source.

Dynamical beam manipulation based on 2-bit digitally-controlled coding metasurface

PubMed Central

Huang, Cheng; Sun, Bo; Pan, Wenbo; Cui, Jianhua; Wu, Xiaoyu; Luo, Xiangang

2017-01-01

Recently, a concept of digital metamaterials has been proposed to manipulate field distribution through proper spatial mixtures of digital metamaterial bits. Here, we present a design of 2-bit digitally-controlled coding metasurface that can effectively modulate the scattered electromagnetic wave and realize different far-field beams. Each meta-atom of this metasurface integrates two pin diodes, and by tuning their operating states, the metasurface has four phase responses of 0, π/2, π, and 3π/2, corresponding to four basic digital elements “00”, “01”, “10”, and “11”, respectively. By designing the coding sequence of the above digital element array, the reflected beam can be arbitrarily controlled. The proposed 2-bit digital metasurface has been demonstrated to possess capability of achieving beam deflection, multi-beam and beam diffusion, and the dynamical switching of these different scattering patterns is completed by a programmable electric source. PMID:28176870

Automation of extrusion of porous cable products based on a digital controller

NASA Astrophysics Data System (ADS)

Chostkovskii, B. K.; Mitroshin, V. N.

2017-07-01

This paper presents a new approach to designing an automated system for monitoring and controlling the process of applying porous insulation material on a conductive cable core, which is based on using structurally and parametrically optimized digital controllers of an arbitrary order instead of calculating typical PID controllers using known methods. The digital controller is clocked by signals from the clock length sensor of a measuring wheel, instead of a timer signal, and this provides the robust properties of the system with respect to the changing insulation speed. Digital controller parameters are tuned to provide the operating parameters of the manufactured cable using a simulation model of stochastic extrusion and are minimized by moving a regular simplex in the parameter space of the tuned controller.

F-15 digital electronic engine control system description

NASA Technical Reports Server (NTRS)

Myers, L. P.

1984-01-01

A digital electronic engine control (DEEC) was developed for use on the F100-PW-100 turbofan engine. This control system has full authority control, capable of moving all the controlled variables over their full ranges. The digital computational electronics and fault detection and accomodation logic maintains safe engine operation. A hydromechanical backup control (BUC) is an integral part of the fuel metering unit and provides gas generator control at a reduced performance level in the event of an electronics failure. The DEEC's features, hardware, and major logic diagrams are described.

Apollo guidance, navigation and control: Guidance system operations plan for manned CM earth orbital and lunar missions using Program COLOSSUS 3. Section 3: Digital autopilots (revision 14)

NASA Technical Reports Server (NTRS)

1972-01-01

Digital autopilots for the manned command module earth orbital and lunar missions using program COLOSSUS 3 are discussed. Subjects presented are: (1) reaction control system digital autopilot, (2) thrust vector control autopilot, (3) entry autopilot and mission control programs, (4) takeover of Saturn steering, and (5) coasting flight attitude maneuver routine.

Anticipatory planning and control of grasp positions and forces for dexterous two-digit manipulation.

PubMed

Fu, Qiushi; Zhang, Wei; Santello, Marco

2010-07-07

Dexterous object manipulation requires anticipatory control of digit positions and forces. Despite extensive studies on sensorimotor learning of digit forces, how humans learn to coordinate digit positions and forces has never been addressed. Furthermore, the functional role of anticipatory modulation of digit placement to object properties remains to be investigated. We addressed these questions by asking human subjects (12 females, 12 males) to grasp and lift an inverted T-shaped object using precision grip at constrained or self-chosen locations. The task requirement was to minimize object roll during lift. When digit position was not constrained, subjects could have implemented many equally valid digit position-force coordination patterns. However, choice of digit placement might also have resulted in large trial-to-trial variability of digit position, hence challenging the extent to which the CNS could have relied on sensorimotor memories for anticipatory control of digit forces. We hypothesized that subjects would modulate digit placement for optimal force distribution and digit forces as a function of variable digit positions. All subjects learned to minimize object roll within the first three trials, and the unconstrained device was associated with significantly smaller grip forces but larger variability of digit positions. Importantly, however, digit load force modulation compensated for position variability, thus ensuring consistent object roll minimization on each trial. This indicates that subjects learned object manipulation by integrating sensorimotor memories with sensory feedback about digit positions. These results are discussed in the context of motor equivalence and sensorimotor integration of grasp kinematics and kinetics.

Arc-An OAI Service Provider for Digital Library Federation; Kepler-An OAI Data/Service Provider for the Individual; Information Objects and Rights Management: A Mediation-Based Approach to DRM Interoperability; Automated Name Authority Control and Enhanced Searching in the Levy Collection; Renardus Project Developments and the Wider Digital Library Context.

ERIC Educational Resources Information Center

Liu, Xiaoming; Maly, Kurt; Zubair, Mohammad; Nelson, Michael L.; Erickson, John S.; DiLauro, Tim; Choudhury, G. Sayeed; Patton, Mark; Warner, James W.; Brown, Elizabeth W.; Heery, Rachel; Carpenter, Leona; Day, Michael

2001-01-01

Includes five articles that discuss the OAI (Open Archive Initiative), an interface between data providers and service providers; information objects and digital rights management interoperability; digitizing library collections, including automated name authority control, metadata, and text searching engines; and building digital library services…

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

Hatley, Darrel D.; Underhill, Ronald M.

Document describes an onsite workshop and building retuning training conducted in Guam in August 2010. Document reports on issues identified during an audit of several buildings and recommendations to save energy throughout the site. During the workshop, it became apparent that as site personnel maintain the facilities at Guam, the following retuning efforts and strategies should be prioritized: (1) Controlling the mechanical systems operational hours and zone temperature set points appeared to present the best opportunities for savings; (2) Zone temperature set points in some buildings are excessively low, especially at night, when the zone temperatures are so cold thatmore » they approached the dewpoint; and (3) Manually-set outside air dampers are providing excessive outside air, especially for spaces that are unoccupied. Two of the larger schools, one on the Naval Base and one on Anderson AFB, are in need of a significant recommissioning effort. These facilities are relatively new, with direct digital controls (DDC) but are significantly out of balance. The pressure in one school is extremely negative, which is pulling humid air through the facility each time a door is opened. The draft can be felt several feet down the halls. The pressure in the other school is extremely positive relative to the outside, and you can stand 20-feet outside and still feel cool drafts of air exiting the building. It is recommended that humidity sensors be installed in all new projects and retrofitted into exist facilities. In this humid climate, control of humidity is very important. There are significant periods of time when the mechanical systems in many buildings can be unloaded and dehumidification is not required. The use of CO{sub 2} sensors should also be considered in representative areas. CO{sub 2} sensors determine whether spaces are occupied so that fresh air is only brought into the space when needed. By reducing the amount of outside air brought into the space, the humidity load is also substantially reduced. CO{sub 2} and humidity sensors, combined with outside air sensors, can be used to predict whether conditions are amenable to mold growth and to automatically adjust systems to help prevent mold without using extra energy. The goal of this training is to give the building operators the knowledge needed to make positive changes in the operation of building systems. As class participants apply this knowledge, building systems will run more efficiently, occupant comfort should improve, while saving energy and reducing greenhouse gas emissions.« less

Quiet Clean Short-haul Experimental Engine (QCSEE) over-the-wing control system design report

NASA Technical Reports Server (NTRS)

1977-01-01

A control system incorporating a digital electronic control was designed for the over-the-wing engine. The digital electronic control serves as the primary controlling element for engine fuel flow and core compressor stator position. It also includes data monitoring capability, a unique failure indication and corrective action feature, and optional provisions for operating with a new type of servovalve designed to operate in response to a digital-type signal and to fail with its output device hydraulically locked into position.

Report on Disclosure Issues Related to the Use of Copy Control and Digital Rights Management Technologies. OECD Digital Economy Papers, No. 115

ERIC Educational Resources Information Center

OECD Publishing (NJ1), 2006

2006-01-01

This report analyses the disclosure issues raised by technically-imposed restrictions on the use of digital content. It focuses on the application of copy control and digital rights management technologies in three areas: copy-protected CDs; online music, and DVD regional coding. In each of these areas, the report examines the kinds of…

Implementation of Adaptive Digital Controllers on Programmable Logic Devices

NASA Technical Reports Server (NTRS)

Gwaltney, David A.; King, Kenneth D.; Smith, Keary J.; Ormsby, John (Technical Monitor)

2002-01-01

Much has been made of the capabilities of FPGA's (Field Programmable Gate Arrays) in the hardware implementation of fast digital signal processing (DSP) functions. Such capability also makes and FPGA a suitable platform for the digital implementation of closed loop controllers. There are myriad advantages to utilizing an FPGA for discrete-time control functions which include the capability for reconfiguration when SRAM- based FPGA's are employed, fast parallel implementation of multiple control loops and implementations that can meet space level radiation tolerance in a compact form-factor. Other researchers have presented the notion that a second order digital filter with proportional-integral-derivative (PID) control functionality can be implemented in an FPGA. At Marshall Space Flight Center, the Control Electronics Group has been studying adaptive discrete-time control of motor driven actuator systems using digital signal processor (DSF) devices. Our goal is to create a fully digital, flight ready controller design that utilizes an FPGA for implementation of signal conditioning for control feedback signals, generation of commands to the controlled system, and hardware insertion of adaptive control algorithm approaches. While small form factor, commercial DSP devices are now available with event capture, data conversion, pulse width modulated outputs and communication peripherals, these devices are not currently available in designs and packages which meet space level radiation requirements. Meeting our goals requires alternative compact implementation of such functionality to withstand the harsh environment encountered on spacecraft. Radiation tolerant FPGA's are a feasible option for reaching these goals.

Controlled-Root Approach To Digital Phase-Locked Loops

NASA Technical Reports Server (NTRS)

Stephens, Scott A.; Thomas, J. Brooks

1995-01-01

Performance tailored more flexibly and directly to satisfy design requirements. Controlled-root approach improved method for analysis and design of digital phase-locked loops (DPLLs). Developed rigorously from first principles for fully digital loops, making DPLL theory and design simpler and more straightforward (particularly for third- or fourth-order DPLL) and controlling performance more accurately in case of high gain.

AVIRIS onboard data handling and control

NASA Technical Reports Server (NTRS)

Steinkraus, Ronald E.; Hickok, Roger W.

1987-01-01

The timing and flow of detector and ancillary data for the Airborne Visible/Infrared imaging spectrometer (AVIRIS) are controlled within the instrument by its digital electronics assembly. In addition to providing detector and signal chain timing, the digital electronics receives, formats, and rate-buffers digitized science data; collects and formats ancillary (calibration and engineering) data; and merges both into a single tape record. Overall AVIRIS data handling is effected by a combination of dedicated digital electronics to control instrument timing, image data flow, and data rate buffering and a microcomputer programmed to handle real-time control of instrument mechanisms and the coordinated preparation of ancillary data.

Development and testing of methodology for evaluating the performance of multi-input/multi-output digital control systems

NASA Technical Reports Server (NTRS)

Polotzky, Anthony S.; Wieseman, Carol; Hoadley, Sherwood Tiffany; Mukhopadhyay, Vivek

1990-01-01

The development of a controller performance evaluation (CPE) methodology for multiinput/multioutput digital control systems is described. The equations used to obtain the open-loop plant, controller transfer matrices, and return-difference matrices are given. Results of applying the CPE methodology to evaluate MIMO digital flutter suppression systems being tested on an active flexible wing wind-tunnel model are presented to demonstrate the CPE capability.

Migration of Older to New Digital Control Systems in Nuclear Power Plant Main Control Rooms

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

Kovesdi, Casey Robert; Joe, Jeffrey Clark

The United States (U.S.) Department of Energy (DOE) Office of Nuclear Energy (NE) has the primary mission to advance nuclear power by resolving socio-technical issues through research and development (R&D). One DOE-NE activity supporting this mission is the Light Water Reactor Sustainability (LWRS) program. LWRS has the overall objective to sustain the operation of existing commercial nuclear power plants (NPPs) through conducting R&D across multiple “pathways,” or R&D focus areas. The Advanced Instrumentation, Information, and Control (II&C) Systems Technologies pathway conducts targeted R&D to address aging and reliability concerns with the legacy instrumentation and control (I&C) and related information systemsmore » in operating U.S. NPPs. This work involves (1) ensuring that legacy analog II&C systems are not life-limiting issues for the LWR fleet, and (2) implementing digital II&C technology in a manner that enables broad innovation and business improvement in the NPP operating model. Under the LWRS Advanced II&C pathway, Human Factors experts at Idaho National Laboratory (INL) have been conducting R&D in support of NPP main control room (MCR) modernization activities. Work in prior years has focused on migrating analog I&C systems to new digital I&C systems (). In fiscal year 2016 (FY16), one new focus area for this research is migrating older digital I&C systems to new and advanced digital I&C systems. This report summarizes a plan for conducting a digital-to-digital migration of a legacy digital I&C system to a new digital I&C system in support of control room modernization activities.« less

Analytical design of a parasitic-loading digital speed controller for a 400-hertz turbine driven alternator

NASA Technical Reports Server (NTRS)

Ingle, B. D.; Ryan, J. P.

1972-01-01

A design for a solid-state parasitic speed controller using digital logic was analyzed. Parasitic speed controllers are used in space power electrical generating systems to control the speed of turbine-driven alternators within specified limits. The analysis included the performance characteristics of the speed controller and the generation of timing functions. The speed controller using digital logic applies step loads to the alternator. The step loads conduct for a full half wave starting at either zero or 180 electrical degrees.

47 CFR 76.1909 - Redistribution control of unencrypted digital terrestrial broadcast content.

Code of Federal Regulations, 2011 CFR

2011-10-01

... content. Where a multichannel video programming distributor retransmits unencrypted digital terrestrial... 47 Telecommunication 4 2011-10-01 2011-10-01 false Redistribution control of unencrypted digital... (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Encoding Rules § 76.1909...

Follow-on Simulator Comparative Evaluation.

DTIC Science & Technology

1979-05-01

FOLLOW- ON SIMULATOR CC1~1PARATIVE EVALUAT ION Final Report May 1979 Prepared by...Aircrew Training Devices (USAFrAWC/Th), Eglin AFJ3, Florida, was responsible for the planning and conduct of the follow- on simulator comparative...DDC TAB lJfl~ 2~~OU!1CC d Jn ~~ t i f i c at i on ____________ - I A~z r f l r U L Code ~ Aiall and /or Dist spucial f l u V A

Vandenberg AFB, Lompoc, California. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1979-08-07

this report to the puolic at large, or by DDC to the National Technical Information Service (NTIS). This tecnnical report has been reviewed and is...occurrences of various atmopheric phenomena. These data are obtained from all recorded information on the reporting forms and combined into a daily...notations an awiinb ie ad ftatin s itory for further Information om reporting pvaetiess of individual statame.t 2. hxtrew values - derived from daily

Enrollments. Educational Programs Operated by Department of Health and Social Services, Department of Corrections, Department of Services for Children, Youth and Their Families: 1990. Document No. 95-01/90/10/11. R & E No. 91-10.

ERIC Educational Resources Information Center

Delaware State Dept. of Public Instruction, Dover.

The September 30, 1990 enrollments are reported for educational programs administered by three agencies of the Delaware State Government: the Department of Health and Social Services (DHSS); Department of Corrections (DDC); and Department of Services for Children, Youth, and Their Families (DSCYF). Data concerning 474 students in this report…

Description of the MHS Health Level 7 Anatomic Pathology for Public Health Surveillance

DTIC Science & Technology

2014-06-01

t ’ "’ frX ’I!’Vi""">inq ir str.r.:lioos, S€’ £l "r:’hi fl!’:: li l<i ~lin,:l ddc ~o.r-c.;s, !] :l:ho:>r rr:, aY. nflinttlirir~ :he !::f;, ·nod c ol...including average age, gender distribution, physical fitness, and health status. Further, this population has universal access to medical care, which

Human Engineering Aspects of a Deep Dive Facility.

DTIC Science & Technology

1977-03-01

Whit" Sectin " DDC Buff S ection r UNANNO¶!’CV D r , JUSTI’ IC .", ,",ON ........ .. . . . . . . . . ............................... DYIlSIRIDtI !fla...would consist mainly of coffee, tea, hot chocolate, or soup and cookies , crackers or other dried food that can be kept without refrigeration. It is...should be used in the Living Chamber. Age..-.. . • :YLi 13 The final recommended decor is based on the use of three basic shades: cream (Munsell 5Y 9/1

Private Security Contractors in Iraq and Afghanistan: Legal Issues

DTIC Science & Technology

2010-01-07

involving Blackwater Worldwide private security guards on contract with the State Department, who reportedly opened fire in the crowded traffic circle in the...Background and Analysis, by Moshe Schwartz. 2 See James Risen and Mark Mazzetti, Blackwater Guards Tied to Secret C.I.A. Raids, NY TIMES, December 10...0360 (RMU), slip op. (D.D.C, .Dec. 31, 2009). 6 See Iraq: U.S. Blackwater Case Dismissal “Unacceptable,” REUTERS, Jan. 1, 2010. 7 See Iraq to

A Design Study for Quick Strike Reconnaissance/Reconnaissance Reporting Facility

DTIC Science & Technology

1976-06-01

Engineer: Ronald B. Haynes (IRRO) Copies available in DDC . ’*■ KEY WORDS (Conllnut on ranfM »id* (/ n*c»«ary and Idmnllly by block number... CLASSIFICATION OF THIS PAGE (("),.„ D.I, Bm.rvd) 40 60% mmmmm tu ’~mmmmmmmm~~-’ rfÜk UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGEfWun...include the following: Systems time and date Operators name Project/mission identification Classification Organisation. (3) Station Release

Detectability of Cold Rocket Plumes.

DTIC Science & Technology

1979-10-11

blackbody temperature measurements (after Fetterman et al., Ref.9). 41 DIRECTION 118-8-1457i01 OF MAXIMUM Z RADIATION 1*I y CORERRELECOR. QU--MASRE...34 Aspen Int. Conf. on Fourier Spectroscopy, (1970), p. 19, DDC AD-724 100. 9. H. R. Fetterman , P. E. Tannenwald, B. J. Clifton, C. D. Parker, W. D...A. Blumberg, H. R. Fetterman , D. D. Peck, and P. F. Goldsmith, "Tunable Submillimeter Sources Applied to the Excited State Rotational Spectro- scopy

Comparison of non-Gaussian and Gaussian diffusion models of diffusion weighted imaging of rectal cancer at 3.0 T MRI.

PubMed

Zhang, Guangwen; Wang, Shuangshuang; Wen, Didi; Zhang, Jing; Wei, Xiaocheng; Ma, Wanling; Zhao, Weiwei; Wang, Mian; Wu, Guosheng; Zhang, Jinsong

2016-12-09

Water molecular diffusion in vivo tissue is much more complicated. We aimed to compare non-Gaussian diffusion models of diffusion-weighted imaging (DWI) including intra-voxel incoherent motion (IVIM), stretched-exponential model (SEM) and Gaussian diffusion model at 3.0 T MRI in patients with rectal cancer, and to determine the optimal model for investigating the water diffusion properties and characterization of rectal carcinoma. Fifty-nine consecutive patients with pathologically confirmed rectal adenocarcinoma underwent DWI with 16 b-values at a 3.0 T MRI system. DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models (IVIM-mono, IVIM-bi and SEM) on primary tumor and adjacent normal rectal tissue. Parameters of standard apparent diffusion coefficient (ADC), slow- and fast-ADC, fraction of fast ADC (f), α value and distributed diffusion coefficient (DDC) were generated and compared between the tumor and normal tissues. The SEM exhibited the best fitting results of actual DWI signal in rectal cancer and the normal rectal wall (R 2  = 0.998, 0.999 respectively). The DDC achieved relatively high area under the curve (AUC = 0.980) in differentiating tumor from normal rectal wall. Non-Gaussian diffusion models could assess tissue properties more accurately than the ADC derived Gaussian diffusion model. SEM may be used as a potential optimal model for characterization of rectal cancer.

Synthesis of dopamine in E. coli using plasmid-based expression system and its marked effect on host growth profiles.

PubMed

Das, Arunangshu; Verma, Anita; Mukherjee, Krishna J

2017-09-14

L-Dopa and dopamine are important pathway intermediates toward the synthesis of catecholamine such as epinephrine and norepinephrine from amino acid L-tyrosine. Dopamine, secreted from dopaminergic nerve cells, serves as an important neurotransmitter. We report the synthesis of dopamine by extending the aromatic amino acid pathway of Escherichia coli DH5α by the expression of 4-hydroxyphenylacetate-3-hydrolase (HpaBC) from E. coli and an engineered dopa decarboxylase (DDC) from pig kidney cell. The activity of HpaBC and DDC require 200 µM iron supplementation and 50 µM vitamin B6, respectively as additives to the growth media. The maximum concentration of L-dopa and dopamine obtained from the broth was around 26 and 27 mg/L after 24 hr of separate shake flask studies. We observed that in the presence of dopamine synthesized in vivo host growth was remarkably enhanced. These observations lead us to an interesting finding about the role of these catecholamines on bacterial growth. It is clear that synthesis of dopamine in vivo actually promotes growth much efficiently as compared to when dopamine is added to the system from outside. From HPLC and GC-MS data it was further observed that L-dopa was stable within the observable time of experiments whereas dopamine actually was subjected to degradation via oxidation and host consumption.

The formation of thermohaline staircases for large salt concentration differences in double diffusive convection

NASA Astrophysics Data System (ADS)

Yang, Yantao; Verzicco, Roberto; Lohse, Detlef

2016-11-01

In the upper layers of the tropical and subtropical ocean, step-like mean profiles for both temperature and salinity are often observed, a phenomenon referred to as thermohaline staircase. It consists of alternatively stacked mixing layers, and finger layers with sharp gradients in both mean temperature and salinity. It is believed that thermohaline staircases are caused by double diffusive convection (DDC), i.e. the convection flow with fluid density affected by two different scalars. Here we conducted direct numerical simulations of DDC bounded by two parallel plates and aimed to realise the multi-layer state similar to the oceanic thermohaline staircase. We applied an unstable salinity difference and a stable temperature difference across the two plates. We gradually increased the salinity Rayleigh number RaS , i.e. the strength of salinity difference, and fixed the relative strength of temperature difference. When RaS is high enough the flow undergoes a transition from a single finger layer to a triple layer state, where one mixing layer emerges between two finger layers. Such triple layer state is stable up to the turbulent diffusive time scale. The finger-layer height is larger for higher RaS . The dependences of the scalar fluxes on RaS were also investigated. Supported by Dutch FOM Foundation and NWO rpogramme MCEC; Computing resources from SURFSara and PRACE project 2015133124.

Access control based on attribute certificates for medical intranet applications.

PubMed

Mavridis, I; Georgiadis, C; Pangalos, G; Khair, M

2001-01-01

Clinical information systems frequently use intranet and Internet technologies. However these technologies have emphasized sharing and not security, despite the sensitive and private nature of much health information. Digital certificates (electronic documents which recognize an entity or its attributes) can be used to control access in clinical intranet applications. To outline the need for access control in distributed clinical database systems, to describe the use of digital certificates and security policies, and to propose the architecture for a system using digital certificates, cryptography and security policy to control access to clinical intranet applications. We have previously developed a security policy, DIMEDAC (Distributed Medical Database Access Control), which is compatible with emerging public key and privilege management infrastructure. In our implementation approach we propose the use of digital certificates, to be used in conjunction with DIMEDAC. Our proposed access control system consists of two phases: the ways users gain their security credentials; and how these credentials are used to access medical data. Three types of digital certificates are used: identity certificates for authentication; attribute certificates for authorization; and access-rule certificates for propagation of access control policy. Once a user is identified and authenticated, subsequent access decisions are based on a combination of identity and attribute certificates, with access-rule certificates providing the policy framework. Access control in clinical intranet applications can be successfully and securely managed through the use of digital certificates and the DIMEDAC security policy.

The research of laser marking control technology

NASA Astrophysics Data System (ADS)

Zhang, Qiue; Zhang, Rong

2009-08-01

In the area of Laser marking, the general control method is insert control card to computer's mother board, it can not support hot swap, it is difficult to assemble or it. Moreover, the one marking system must to equip one computer. In the system marking, the computer can not to do the other things except to transmit marking digital information. Otherwise it can affect marking precision. Based on traditional control methods existed some problems, introduced marking graphic editing and digital processing by the computer finish, high-speed digital signal processor (DSP) control marking the whole process. The laser marking controller is mainly contain DSP2812, digital memorizer, DAC (digital analog converting) transform unit circuit, USB interface control circuit, man-machine interface circuit, and other logic control circuit. Download the marking information which is processed by computer to U disk, DSP read the information by USB interface on time, then processing it, adopt the DSP inter timer control the marking time sequence, output the scanner control signal by D/A parts. Apply the technology can realize marking offline, thereby reduce the product cost, increase the product efficiency. The system have good effect in actual unit markings, the marking speed is more quickly than PCI control card to 20 percent. It has application value in practicality.