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Sample records for pseudoanalog true-time-delay ttd

  1. Chirped-pulse programming of optical coherent transient true-time delays.

    Science.gov (United States)

    Merkel, K D; Babbitt, W R

    1998-04-01

    Programming an optical coherent transient true-time delay device with two frequency-chirped pulses provides a novel means of performing broadband (> >GHz) true-time delay with a wide dynamic range of delays with fine temporal resolution. We have demonstrated true-time delays exceeding 2micros with sub-100-ps resolution. Chirped-pulse programming has the advantages over the previously proposed brief pulse programming [Opt. Lett. 21 1102 (1996)] of reduced instantaneous power requirements and the ability to control the true-time delay by frequency shifting the programming pulses.

  2. Compact optically-fed microwave true-time delay using liquid crystal photonic bandgap fiber device

    DEFF Research Database (Denmark)

    Wei, Lei; Xue, Weiqi; Chen, Yaohui

    2009-01-01

    Electrically tunable liquid crystal photonic bandgap fiber device based optically-fed microwave true-time delay is demonstrated. A maximum ~60° phase shift and an averaged ~7.2ps true time delay are obtained over the modulation frequency range 1GHz-19GHz.......Electrically tunable liquid crystal photonic bandgap fiber device based optically-fed microwave true-time delay is demonstrated. A maximum ~60° phase shift and an averaged ~7.2ps true time delay are obtained over the modulation frequency range 1GHz-19GHz....

  3. Integrated High-Speed Digital Optical True-Time-Delay Modules for Synthetic Aperture Radars Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Crystal Research, Inc. proposes an integrated high-speed digital optical true-time-delay module for advanced synthetic aperture radars. The unique feature of this...

  4. Three Dimensionally Interconnected Silicon Nanomembranes for Optical Phased Array (OPA) and Optical True Time Delay (TTD) Applications

    Science.gov (United States)

    2012-06-01

    Electronics 16(1), 61-69 (2010). [4-21] A. Brown, G. O’Neill, and S. Blackstone , Proc. SPIE 4174, 406-415 (2000). [4-22] F. Laermer and A. Urban...baking. The insets show the top view of SU-8 waveguides before and after baking. The insets on the right shows the screen shots of the power meter...devices such as hybrid silicon modulators1-3, optical switches4, on-chip environmental sensors for underground water pollution detection5, and gas

  5. Slow light in a semiconductor waveguide for true-time delay applications in microwave photonics

    DEFF Research Database (Denmark)

    Öhman, Filip; Yvind, Kresten; Mørk, Jesper

    2007-01-01

    We have investigated the slowand fast light properties of a semiconductor waveguide device employing concatenated gain and absorber sections. This letter presents the experimental results as well as theoretical modeling. A large phase shift of 110 and a true-time delay of more than 150 ps...

  6. True-time delay by slow light in a semiconductor waveguide with alternating amplifying and absorbing sections

    DEFF Research Database (Denmark)

    Öhman, Filip; Mørk, Jesper

    2006-01-01

    Modeling of slow light in a semiconductor waveguide with alternating gain and absorption sections demonstrate an increase in time delay by concatenating segments. A true-time delay is predicted over a large bandwidth at high frequency.......Modeling of slow light in a semiconductor waveguide with alternating gain and absorption sections demonstrate an increase in time delay by concatenating segments. A true-time delay is predicted over a large bandwidth at high frequency....

  7. Optically fed microwave true-time delay based on a compact liquid-crystal hotonic-bandgap-fiber device

    DEFF Research Database (Denmark)

    Wei, Lei; Xue, Weiqi; Chen, Yaohui

    2009-01-01

    An electrically tunable liquid-crystal, photonic-bandgap-fiber-device-based, optically fed microwave true-time delay is demonstrated with the response time in the millisecond range. A maximum electrically controlled phase shift of around 70° at 15GHz and an averaged 12.9ps true time delay over...... the whole modulation frequency range of 1-15GHz are obtained....

  8. True-time-delay photonic beamformer for an L-band phased array radar

    Science.gov (United States)

    Zmuda, Henry; Toughlian, Edward N.; Payson, Paul M.; Malowicki, John E.

    1995-10-01

    The problem of obtaining a true-time-delay photonic beamformer has recently been a topic of great interest. Many interesting and novel approaches to this problem have been studied. This paper examines the design, construction, and testing of a dynamic optical processor for the control of a 20-element phased array antenna operating at L-band (1.2-1.4 GHz). The approach taken here has several distinct advantages. The actual optical control is accomplished with a class of spatial light modulator known as a segmented mirror device (SMD). This allows for the possibility of controlling an extremely large number (tens of thousands) of antenna elements using integrated circuit technology. The SMD technology is driven by the HDTV and laser printer markets so ultimate cost reduction as well as technological improvements are expected. Optical splitting is efficiently accomplished using a diffractive optical element. This again has the potential for use in antenna array systems with a large number of radiating elements. The actual time delay is achieved using a single acousto-optic device for all the array elements. Acousto-optic device technologies offer sufficient delay as needed for a time steered array. The topological configuration is an optical heterodyne system, hence high, potentially millimeter wave center frequencies are possible by mixing two lasers of slightly differing frequencies. Finally, the entire system is spatially integrated into a 3D glass substrate. The integrated system provides the ruggedness needed in most applications and essentially eliminates the drift problems associated with free space optical systems. Though the system is presently being configured as a beamformer, it has the ability to operate as a general photonic signal processing element in an adaptive (reconfigurable) transversal frequency filter configuration. Such systems are widely applicable in jammer/noise canceling systems, broadband ISDN, and for spread spectrum secure communications

  9. True-time delay line with separate carrier tuning using dual-parallel MZM and stimulated Brillouin scattering-induced slow light.

    Science.gov (United States)

    Li, Wei; Zhu, Ning Hua; Wang, Li Xian; Wang, Jia Sheng; Liu, Jian Guo; Liu, Yu; Qi, Xiao Qiong; Xie, Liang; Chen, Wei; Wang, Xin; Han, Wei

    2011-06-20

    We experimentally demonstrate a novel tunable true-time delay line with separate carrier tuning using dual-parallel Mach-Zehnder modulator and stimulated Brillouin scattering-induced slow light. The phase of the optical carrier can be continuously and precisely controlled by simply adjusting the dc bias of the dual-parallel Mach-Zehnder modulator. In addition, both the slow light and single-sideband modulation can be simultaneously achieved in the stimulated Brillouin scattering process with three types of configuration. Finally, the true-time delay technique is clearly verified by a two-tap incoherent microwave photonic filter as the free spectral range of the filter is changed.

  10. PENDAMPINGAN MINUM TABLET TAMBAH DARAH (TTD DAPAT MENINGKATKAN KEPATUHAN KONSUMSI TTD PADA IBU HAMIL ANEMIA

    Directory of Open Access Journals (Sweden)

    Aditianti Aditianti

    2015-12-01

    Full Text Available ABSTRACTAnemia contributed 20 persen the death of pregnancy. Low consumption of iron is one of the cause of anemia prevalences among pregnant women. Iron intake can be gained from iron tablet. However the iron tabletconsumption still very low. The purpose of this study was to obtain the role of family and posyandu kadre support to the compliance of iron tablet consumption among anemic pregnant women and its relation tohaemoglobin levels of anemic pregnant women. The research design was quasi experimental Anemic pregnant women as a sample respondens were divided into two groups, 29 in the intervention group and 32 in thecontrol group. The study was conducted at Cibungbulang and Pamijahan sub district, Bogor. Compliance measurements using MMAS - 8 (Morisky Medication Adherence Scale - 8 questionnaires. Compliance of irontablet consumption categorized by low, middle and high. The intervention was counseling about anemia and how important iron tablet consumption among pregnant women to their family (husband/parents/in-laws/otherclose relatives or posyandu cadre whose lived in the same house or as their neighbour. Data analysis was performed using Chi - square and different t-test. The results showed that the anemic pregnant women withsupport from their family and posyandu cadre improve their compliance of iron tablet (p< 0,05.Keywords: anemia, iron tablet, family and posyandu cadre support, complianceABSTRAKAnemia memberikan kontribusi hingga 20 persen terhadap semua kematian pada kehamilan. Salah satu penyebab tingginya prevalensi anemia adalah rendahnya asupan zat besi. Salah satu sumber asupan zat besi berasal dari tablet tambah darah (TTD, namun kepatuhan mengonsumsinya masih sangat rendah. Tujuan penelitian ini adalah mendapatkan pengaruh peran pendamping terhadap kepatuhan konsumsi TTD dan hubungannya dengan kadar hemoglobin (Hb ibu hamil anemia. Desain penelitian adalah kuasi eksperimen. Responden adalah ibu hamil anemia, yang dibagi menjadi

  11. Accuracy of travel time distribution (TTD) models as affected by TTD complexity, observation errors, and model and tracer selection

    Science.gov (United States)

    Green, Christopher T.; Zhang, Yong; Jurgens, Bryant C.; Starn, J. Jeffrey; Landon, Matthew K.

    2014-01-01

    Analytical models of the travel time distribution (TTD) from a source area to a sample location are often used to estimate groundwater ages and solute concentration trends. The accuracies of these models are not well known for geologically complex aquifers. In this study, synthetic datasets were used to quantify the accuracy of four analytical TTD models as affected by TTD complexity, observation errors, model selection, and tracer selection. Synthetic TTDs and tracer data were generated from existing numerical models with complex hydrofacies distributions for one public-supply well and 14 monitoring wells in the Central Valley, California. Analytical TTD models were calibrated to synthetic tracer data, and prediction errors were determined for estimates of TTDs and conservative tracer (NO3−) concentrations. Analytical models included a new, scale-dependent dispersivity model (SDM) for two-dimensional transport from the watertable to a well, and three other established analytical models. The relative influence of the error sources (TTD complexity, observation error, model selection, and tracer selection) depended on the type of prediction. Geological complexity gave rise to complex TTDs in monitoring wells that strongly affected errors of the estimated TTDs. However, prediction errors for NO3− and median age depended more on tracer concentration errors. The SDM tended to give the most accurate estimates of the vertical velocity and other predictions, although TTD model selection had minor effects overall. Adding tracers improved predictions if the new tracers had different input histories. Studies using TTD models should focus on the factors that most strongly affect the desired predictions.

  12. [Comment on “Doctorate time rising sharply: How long should it take” by William Glen] Defining TTD

    Science.gov (United States)

    Jedlovec, Gary J.

    In response to the Forum article “Doctorate Time Rising Sharply: How long should it take?” by William Glen (March 27, 1990), I contend that Glen (and the authors of a book he cites) may be overlooking a possible explanation for the rise in time to doctorate (TTD). Is the time one spends working in his/her field between degrees considered and tabulated? It might be that after obtaining a bachelors or masters degree, the student seeks employment for a number of years before returning to school.Using myself as an example, after graduating with a masters degree in 1981 (bachelors in 1979), I worked as a research associate for NASA before returning to school in 1984. I completed my doctorate degree in 1987, making my actual time in school between the bachelors and doctorate degrees only 5 years. The TTD as defined in Forum would yield 8 years. I know of many others who have proceeded in getting a doctorate degree in a similar fashion. My TTD of 8 years in no way reflects institutional factors as suggested in the article.

  13. [Inspirations from natural products based drug research and development for Chinese medicine research--analysis of natural products recoded in TTD].

    Science.gov (United States)

    Chen, Xiu-Ping; Lu, Jin-Jian; Guo, Jia-Jie; Bao, Jiao-Lin; Xu, Wen-Shan; Ding, Qian; Wang, Yi-Tao

    2012-11-01

    Natural product is an important source of new drug research and development (R&D). Traditional Chinese medicine (TCM) innovation is the key step for its modernization and internationalization. However, due to the complexity of TCM, there are many difficulties and confusions in this process. Target-based drug discovery is the mainstream model and method of R&D. TTD, short for therapeutic target database, is developed by National University of Singapore. Besides a large amount of information on drug targets, the database also contains considerable information related to natural products. This paper briefly introduces the TTD, analyzes the natural products derived drugs/compounds recorded in TTD, which we think might provide some inspiration for the innovation of TCM.

  14. Functional and molecular genetic analyses of nine newly identified XPD-deficient patients reveal a novel mutation resulting in TTD as well as in XP/CS complex phenotypes

    NARCIS (Netherlands)

    Schaefer, Annika; Gratchev, Alexei; Seebode, Christina; Hofmann, Lars; Schubert, Steffen; Laspe, Petra; Apel, Antje; Ohlenbusch, Andreas; Tzvetkov, Mladen; Weishaupt, Carsten; Oji, Vinzenz; Schoen, Michael P.; Emmert, Steffen

    The xeroderma pigmentosum (XP) group D protein is involved in nucleotide excision repair (NER) as well as in basal transcription. Determined by the type of XPD mutation, six different clinical entities have been distinguished: XP, XP with neurological symptoms, trichothiodystrophy (TTD), XP/TTD

  15. A Review on the Development of Rotman Lens Antenna

    Directory of Open Access Journals (Sweden)

    Shruti Vashist

    2014-01-01

    Full Text Available Rotman lenses are the beguiling devices used by the beamforming networks (BFNs. These lenses are generally used in the radar surveillance systems to see targets in multiple directions due to its multibeam capability without physically moving the antenna system. Now a days these lenses are being integrated into many radars and electronic warfare systems around the world. The antenna should be capable of producing multiple beams which can be steered without changing the orientation of the antenna. Microwave lenses are the one who support low-phase error, wideband, and wide-angle scanning. They are the true time delay (TTD devices producing frequency independent beam steering. The emerging printed lenses in recent years have facilitated the advancement of designing high performance but low-profile, light-weight, and small-size and networks (BFNs. This paper will review and analyze various design concepts used over the years to improve the scanning capability of the lens developed by various researchers.

  16. Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.

    Directory of Open Access Journals (Sweden)

    Eduardo Díaz-Rubio

    Full Text Available In the MACRO study, patients with metastatic colorectal cancer (mCRC were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS, overall survival (OS and response rates.KRAS data (tumour KRAS status and type of mutation were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1% in the MACRO study. Wild-type (WT KRAS tumours were found in 219 patients (56% and mutant (MT KRAS in 175 patients (44%. Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77. The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96. Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5% with WT KRAS tumours and 76 patients (43.4% with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64.This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

  17. Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

    Science.gov (United States)

    Díaz-Rubio, Eduardo; Gómez-España, Auxiliadora; Massutí, Bartomeu; Sastre, Javier; Reboredo, Margarita; Manzano, José Luis; Rivera, Fernando; Safont, MªJosé; Montagut, Clara; González, Encarnación; Benavides, Manuel; Marcuello, Eugenio; Cervantes, Andrés; Martínez de Prado, Purificación; Fernández-Martos, Carlos; Arrivi, Antonio; Bando, Inmaculada; Aranda, E.; Gómez, A.; Massutí, B.; Yuste, A.; Rubio, E. Díaz; Sastre, J.; Valladares, M.; Abad, A.; Rivera, F.; Safont, MªJosé; Gallén, M.; González, E.; Benavides, M.; Marcuello, E.; Tobeña, M.; Cervantes, A.; Martínez de Prado, P.; Fernández-Martos, C.; Arrivi, A.; López-Ladrón, A.; Lacasta, A.; Llanos, M.; Remón, J.; Anton, A.; Vicent, J. Mª.; Gala´n, A.; Dueñas, R.; Tabernero, J. Mª.; Manzano, H.; Gómez, Mª. J.; Alfaro, J.; Losa, F.; Escudero, P.; García, T.; García López, J. L.; de Paredes, Mª L. García; Velasco, A.; Almenar, D.; Vera, R.; García Puche, J. L.; Carrato, A.; Lescure, A. Rodriguez; Jiménez, E.; Alberola, V.; García-Foncillas, J.; Constenla, M.; Ruiz, A.; Bueso, P.; Cabrera, E.; del Río,, L.; Ponce, J.; Oltra, A.; Checa, T.; Etxeberría, A.; Alonso, C.

    2012-01-01

    Background In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12–1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23–1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18–2.64). Conclusions/Significance This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses. PMID:23174912

  18. Applications of Slow Light in Telecommunications

    National Research Council Canada - National Science Library

    Boyd, Robert W; Gauthier, Daniel J; Gaeta, Alexander L

    2006-01-01

    .... Now, optical scientists are turning their attention toward developing useful applications of slow light, including controllable optical delay lines, optical buffers and true time delay methods...

  19. Herstellung eines federelastischen Spangutes geringer Dichte als Matrix für Schüttdämmstoffe, für plattenförmige Dämmstoffe und leichte Spanplatten

    Science.gov (United States)

    Tröger, Johannes; Groß, Lucia

    Klimaschutz und die ständig steigenden Energiekosten erfordern eine kontinuierliche Verbesserung der Dämmstoffe. Eine Alternative zur relativ kostenaufwändigen Wärmedämmung durch Platten bzw. Matten auf Basis von mineralischen Stoffen, ist der Einsatz von schütt-bzw. einblasbaren Dämmstoffpartikeln. Späne aus Holz und andere Dämmstoffe aus nachwachsenden Rohstoffen waren schon vor dem ersten Weltkrieg die gebräuchlichsten Dämmstoffe überhaupt. Seit etwa fünfzehn Jahren werden u.a. für den Holzhausbau im zunehmenden Maße auch Fräs-, Säge und Hobelspäne für Wärmedämmzwecke eingesetzt [1], [2], [3]. Hervorzuheben ist der ökologische Aspekt dieser Dämmstoffe durch die Bindung von CO2 und den sinkenden Heizenergiebedarf. Die bisherige Philosophie bei der Gewinnung von Dämmstoffspänen beruhte darauf, anfallendes Spangut stofflich weiter zu nutzen. Die Recyclingspäne sollten dabei sowohl die Setzungssicherheit als auch eine möglichst gute Wärmedämmung gewährleisten.

  20. Examining temptation to drink from an existential perspective: Associations among temptation, purpose in life, and drinking outcomes.

    Science.gov (United States)

    Roos, Corey R; Kirouac, Megan; Pearson, Matthew R; Fink, Brandi C; Witkiewitz, Katie

    2015-09-01

    Temptation to drink (TTD), defined as the degree to which one feels compelled to drink in the presence of internal or external alcohol-related cues, has been shown to predict alcohol-treatment outcomes among individuals with alcohol-use disorders (AUDs). Research examining TTD from an existential perspective is lacking and little is known about how existential issues such as purpose in life (PIL) relate to TTD, which is surprising given the role of existential issues in many treatments and mutual help approaches for AUDs. In the current study, we examined the longitudinal associations in a sample of 1726 among TTD, PIL, and drinking outcomes using data from Project MATCH (1997, 1998). Parallel process latent growth curve analyses indicated that PIL and TTD were significantly associated across time, such that higher initial levels of PIL and increases in PIL over time were associated with lower initial levels of TTD and decreases in TTD over time. Higher initial levels of TTD, lower initial levels of PIL, increases in TTD, and decreases in PIL were significantly associated with greater intensity and frequency of drinking and greater drinking-related consequences at the 15-month follow-up. Accordingly, TTD and PIL may be important constructs for clinicians to consider throughout the course of treatment. Future studies should examine if and how various kinds of treatments for AUDs are associated with increases in PIL, and whether these increases are related to decreased TTD and reduced drinking. (c) 2015 APA, all rights reserved).

  1. On-chip, CMOS-compatible, hardware-compressive integrated photonic beamformer based on WDM

    NARCIS (Netherlands)

    Burla, M.; Zhuang, L.; Marpaung, D.A.I.; Khan, M.R.H.; Leinse, Arne; Beeker, Willem; Hoekman, M.; Heideman, Rene; Roeloffzen, C.G.H.

    2013-01-01

    We propose and experimentally demonstrate a novel, hardware-compressive architecture for broadband and continuously tunable integrated optical true-time-delay beamformers. The architecture is based on on-chip wavelength division multiplexing (WDM) that, in conjunction with the frequency-periodic

  2. Multiwavelength optical beam forming network with ring resonator-based binary-tree architecture for broadband phased array antenna systems

    NARCIS (Netherlands)

    Burla, M.; Khan, M.R.H.; Zhuang, L.; Roeloffzen, C.G.H.

    2008-01-01

    Integrated optical beam forming networks (OBFNs) offer many advantages for phased array applications. ORR-based true-time-delay units can be cascaded in a binary tree topology and tuned for continuously-adjustable broadband time delay. Nonetheless, with large number of antenna elements, the OBFN may

  3. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Weeda, G.; Donker, I.; Vermeulen, W. [Erasmus Univ., Rotterdam (Netherlands)] [and others

    1997-02-01

    Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual development, and ichthyosis. Photosensitivity has been reported in {approximately}50% of the cases, but no skin cancer is associated with TTD. Virtually all photosensitive TTD patients have a deficiency in the nucleotide excision repair (NER) of UV-induced DNA damage that is indistinguishable from that of xeroderma pigmentosum (XP) complementation group D (XP-D) patients. DNA repair defects in XP-D are associated with two additional, quite different diseases; XP, a sun-sensitive and cancer-prone repair disorder, and Cockayne syndrome (CS), a photosensitive condition characterized by physical and mental retardation and wizened facial appearance. One photosensitive TTD case constitutes a new repair-deficient complementation group, TTD-A. Remarkably, both TTD-A and XP-D defects are associated with subunits of TFIIH, a basal transcription factor with a second function in DNA repair. Thus, mutations in TFIIH components may, on top of a repair defect, also cause transcriptional insufficiency, which may explain part of the non-XP clinical features of TTD. To date, three patients with the remarkable conjunction of XP and CS but not TM have been assigned to XP complementation group B (XP-B). Here we present the characterization of the NER defect in two mild TTD patients (TTD6VI and TTD4VI) and confirm the assignment to X-PB. The causative mutation was found to be a single base substitution resulting in a missense mutation (T119P) in a region of the XPB protein. These findings define a third TTD complementation group, extend the clinical heterogeneity associated with XP-B, stress the exclusive relationship between TTD and mutations in subunits of repair/transcription factor TFIIH, and strongly support the concept of {open_quotes}transcription syndromes.{close_quotes} 46 refs., 6 figs., 2 tabs.

  4. I-123 hydroxyiodobenzyl propanediamine (HIPDM) cerebral blood flow imaging demonstrating transtentorial diaschisis

    Energy Technology Data Exchange (ETDEWEB)

    Shih, W.J.; Dekosky, S.T.; Coupal, J.J.; Simmons, G.; Pulmano, C.; Kung, H.F.; Ryo, U.Y.; Clark, D.B. (Veterans Affairs Medical Center, Lexington, KY (USA))

    1990-09-01

    To assess the clinical significance of transtentorial diaschisis (TTD) as demonstrated by I-123 HIPDM brain imaging, SPECT and/or planar images of 35 patients with stroke, 26 patients with Alzheimer's disease (AD), 2 patients with Creutzfeldt-Jakob disease (CJD), and 1 patient with a schizoaffective disorder were analyzed. TTD was observed in 21 of the 35 patients with strokes. In 13 stroke patients, TTD was associated with large infarcts in the middle cerebral artery (MCA) territory; in the remaining 8 stroke patients, TTD was associated with internal capsule and/or basal ganglia infarcts. TTD was not associated with small occipital or parietal infarcts. Despite cortical perfusion decrements, TTD was not seen in the AD patients, the CJD patients, or the patient with schizoaffective disorder. It is concluded that (1) TTD frequently occurs following cerebral infarct of the MCA territory (60% of the patients in this sample); (2) absence of TTD in the presence of a large cerebral perfusion abnormality may represent neuronal dysfunction of the cerebral cortex; and (3) the presence of TTD without a significant cortical perfusion abnormality may indicate basal ganglia and/or internal capsule infarct.

  5. Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice.

    Science.gov (United States)

    Diderich, Karin E M; Nicolaije, Claudia; Priemel, Matthias; Waarsing, Jan H; Day, Judd S; Brandt, Renata M C; Schilling, Arndt F; Botter, Sander M; Weinans, Harrie; van der Horst, Gijsbertus T J; Hoeijmakers, Jan H J; van Leeuwen, Johannes P T M

    2012-08-01

    Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype. Here, we show that female TTD mice exhibit accelerated bone aging from 39 weeks onwards as well as lack of periosteal apposition leading to reduced bone strength. Before 39 weeks have passed, bones of wild-type and TTD mice are identical excluding a developmental defect. Albeit that bone formation is decreased, osteoblasts in TTD mice retain bone-forming capacity as in vivo PTH treatment leads to increased cortical thickness. In vitro bone marrow cell cultures showed that TTD osteoprogenitors retain the capacity to differentiate into osteoblasts. However, after 13 weeks of age TTD females show decreased bone nodule formation. No increase in bone resorption or the number of osteoclasts was detected. In conclusion, TTD mice show premature bone aging, which is preceded by a decrease in mesenchymal stem cells/osteoprogenitors and a change in systemic factors, identifying DNA damage and repair as key determinants for bone fragility by influencing osteogenesis and bone metabolism.

  6. Translucent tissue defect in potato (Solanum tuberosum L.) tubers is associated with oxidative stress accompanying an accelerated aging phenotype.

    Science.gov (United States)

    Zommick, Daniel H; Kumar, G N Mohan; Knowles, Lisa O; Knowles, N Richard

    2013-12-01

    Translucent tissue defect (TTD) is an undesirable postharvest disorder of potato tubers characterized by the development of random pockets of semi-transparent tissue containing high concentrations of reducing sugars. Translucent areas turn dark during frying due to the Maillard reaction. The newly released cultivar, Premier Russet, is highly resistant to low temperature sweetening, but susceptible to TTD. Symptoms appeared as early as 170 days after harvest and worsened with time in storage (4-9 °C, 95 % RH). In addition to higher concentrations of glucose, fructose and sucrose, TTD resulted in lower dry matter, higher specific activities of starch phosphorylase and glc-6-phosphate dehydrogenase, higher protease activity, loss of protein, and increased concentrations of free amino acids (esp. asparagine and glutamine). The mechanism of TTD is unknown; however, the disorder has similarities with the irreversible senescent sweetening that occurs in tubers during long-term storage, where much of the decline in quality is a consequence of progressive increases in oxidative stress with advancing age. The respiration rate of non-TTD 'Premier Russet' tubers was inherently higher (ca. 40 %) than that of 'Russet Burbank' tubers (a non-TTD cultivar). Moreover, translucent tissue from 'Premier Russet' tubers had a 1.9-fold higher respiration rate than the average of non-translucent tissue and tissue from non-TTD tubers. Peroxidation of membrane lipids during TTD development resulted in increased levels of malondialdehyde and likely contributed to a measurable increase in membrane permeability. Superoxide dismutase and catalase activities and the ratio of oxidized to total glutathione were substantially higher in translucent tissue. TTD tubers also contained twofold less ascorbate than non-TTD tubers. TTD appears to be a consequence of oxidative stress associated with accelerated aging of 'Premier Russet' tubers.

  7. The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor.

    NARCIS (Netherlands)

    G. Weeda (Geert); M. Rossignol; R.A. Fraser; G.S. Winkler (Sebastiaan); W. Vermeulen (Wim); L.J. van 't Veer (Laura); L. Ma (Libin); J.H.J. Hoeijmakers (Jan); J-M. Egly (Jean-Marc)

    1997-01-01

    textabstractMutations in the basal transcription initiation/DNA repair factor TFIIH are responsible for three human disorders: xeroderma pigmentosum (XP), cockayne syndrome (CS) and trichothiodystrophy (TTD). The non-repair features of CS and TTD are thought to be due to a partial inactivation of

  8. Evaluation of a tertiary teledermatology service between peripheral and academic dermatologists in the Netherlands

    NARCIS (Netherlands)

    van der Heijden, Job P.; de Keizer, Nicolette F.; Witkamp, Leonard; Spuls, Phyllis I.

    2014-01-01

    Tertiary teledermatology (TTD)-secondary-care to tertiary-care teleconsultation-is applied rarely compared with the frequently applied secondary teledermatology (primary to secondary care). The objective of this study was to determine the effect of TTD on referrals from peripheral dermatologists to

  9. Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice

    NARCIS (Netherlands)

    K.E.M. Diderich (Karin); C. Nicolaije (Claudia); M. Priemel (Matthias); J.H. Waarsing (Jan); J.S. Day (Judd); R.M.C. Brandt (Renata); A.F. Schilling (Arndt); S.M. Botter (Sander); H.H. Weinans (Harrie); G.T.J. van der Horst (Gijsbertus); J.H.J. Hoeijmakers (Jan); J.P.T.M. van Leeuwen (Hans)

    2012-01-01

    textabstractTrichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many

  10. Slow and fast light effects and their applications to microwave photonics using semiconductor optical amplifiers

    DEFF Research Database (Denmark)

    Sales, Salvador; Xue, Weiqi; Mørk, Jesper

    2010-01-01

    We provide a comprehensive review of the application of slow and fast light (SFL) techniques to the field of microwave photonics. Basic principles leading to the implementation of phase shifting and true time delay operations which are instrumental in this field are first considered. We then focu....... Finally, the main results obtained for several microwave photonic applications such as filtering, arbitrary waveform generation and optoelectronic scillators (OEOs)are reviewed, and other directions for future research in the field are discussed.......We provide a comprehensive review of the application of slow and fast light (SFL) techniques to the field of microwave photonics. Basic principles leading to the implementation of phase shifting and true time delay operations which are instrumental in this field are first considered. We then focus...

  11. Impact of response shift on time to deterioration in quality of life scores in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Zeinab Hamidou

    Full Text Available BACKGROUND: This prospective multicenter study aimed to study the impact of the recalibration component of response-shift (RS on time to deterioration (TTD in health related quality of life (QoL scores in breast cancer (BC patients and the influence of baseline QoL expectations on TTD. METHODS: The EORTC-QLQ-C30 and BR-23 questionnaires were used to assess the QoL in a prospective multicenter study at inclusion (T0, at the end of the first hospitalization (T1 and, three (T2 and 6 months after the first hospitalization (T3. Recalibration was investigated by the then-test method. QoL expectancy was assessed at diagnosis. Deterioration was defined as a 5-point decrease in QoL scores, considered a minimal clinically important difference (MCID. TTD was estimated using the Kaplan-Meier method. Cox regression analyses were used to identify factors influencing TTD. RESULTS: From February 2006 to February 2008, 381 women were included. Recalibration of breast cancer patients' internal standards in the assessment of their QoL had an impact on TTD. Median TTD were significantly shorter when recalibration was not taken into account than when recalibration was taken into account for global health, role-functioning, social-functioning, body-image and side effects of systemic therapy. Cox multivariate analyses showed that for body image, when recalibration was taken into account, radiotherapy was associated with a shorter TTD (HR: 0.60[0.38-0.94], whereas, no significant impact of surgery type on TTD was observed. For global health, cognitive and social functioning dimensions, patients expecting a deterioration in their QoL at baseline had a significantly shorter TTD. CONCLUSIONS: Our results showed that RS and baseline QoL expectations were associated with time to deterioration in breast cancer patients.

  12. An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria.

    NARCIS (Netherlands)

    Andressoo, Jaan-Olle; Mitchell, James R; Wit, Jan de; Hoogstraten, Deborah; Volker, Marcel; Toussaint, Wendy; Speksnijder, Ewoud; Beems, Rudolf B; Steeg, Harry van; Jans, Judith; Zeeuw, Chris I de; Jaspers, Nicolaas G J; Raams, Anja; Lehmann, Alan R; Vermeulen, Wim; Hoeijmakers, Jan H J; Horst, Gijsbertus T J van der

    2006-01-01

    Inborn defects in nucleotide excision DNA repair (NER) can paradoxically result in elevated cancer incidence (xeroderma pigmentosum [XP]) or segmental progeria without cancer predisposition (Cockayne syndrome [CS] and trichothiodystrophy [TTD]). We report generation of a knockin mouse model for the

  13. Oxidative and energy metabolism as potential clues for clinical heterogeneity in nucleotide excision repair disorders.

    Science.gov (United States)

    Hosseini, Mohsen; Ezzedine, Khaled; Taieb, Alain; Rezvani, Hamid R

    2015-02-01

    Nucleotide excision repair (NER) is an important DNA repair pathway involved in the removal of a wide array of DNA lesions. The absence or dysfunction of NER results in the following distinct disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS), cerebro-oculo-facio-skeletal (COFS) syndrome, UV-sensitive syndrome (UVSS), trichothiodystrophy (TTD), or combined syndromes including XP/CS, XP/TTD, CS/TTD, and COFS/TTD. In addition to their well-characterized role in the NER signaling pathway, NER factors also seem to be important in biological processes that are not directly associated with DNA damage responses, including mitochondrial function and redox homeostasis. The potential causative role of these factors in the large clinical spectrum seen in NER diseases is discussed in this review.

  14. IVHS Institutional Issues And Case Studies: Help/Cresent Case Study

    Science.gov (United States)

    1994-04-01

    This operational test case study is one of six performed in response to a Volpe National Transportation Systems Center technical task directive (TTD) to Science Applications International Corporation (SAIC) entitled, "IVHS Institutional Issues and Ca...

  15. IVHS institutional issues and case studies : Travtek case study

    Science.gov (United States)

    1994-04-01

    This operational test case study is one of six performed in response to a Volpe : National Transportation Systems Center technical task directive (TTD) to : Science Applications International Corporation (SAIC) entitled, IVHS : Institutional Issue...

  16. IVHS institutional issues and case studies : ADVANCE case study

    Science.gov (United States)

    1994-04-01

    This operational test case study is one of six performed in response to a Volpe : National Transportation Systems Center technical task directive (TTD) to : Science Applications International Corporation (SAIC) entitled, IVHS : Institutional Issue...

  17. Time to Detection with BacT/Alert FA Plus Compared to BacT/Alert FA Blood Culture Media.

    Science.gov (United States)

    Nutman, A; Fisher Even-Tsur, S; Shapiro, G; Braun, T; Schwartz, D; Carmeli, Y

    2016-09-01

    Rapid identification of the causative pathogen in patients with bacteremia allows adjustment of antibiotic therapy and improves patient outcomes. We compared in vitro and real-life time to detection (TTD) of two blood culture media, BacT/Alert FA (FA) and BacT/Alert FA Plus (FA Plus), for the nine most common species of bacterial pathogens recovered from blood samples. Experimental data from simulated cultures was compared with microbiology records of TTD for both culture media with growth of the species of interest in clinical blood cultures. In the experimental conditions, median TTD was 3.8 hours (23.9 %) shorter using FA Plus media. The magnitude of reduction differed between species. Similarly, in real life data, FA Plus had shorter TTD than FA media; however, the difference between culture media was smaller, and median TTD was only 1 hour (8.5 %) less. We found shorter TTD with BacT/Alert FA Plus culture media, both experimentally and in real-life conditions and unrelated to antibiotic neutralization, highlighting the importance of appropriate blood culture media selection.

  18. Time-to-Detection Comparison for a Novel Blood Culture System Using Simulated Blood Cultures: DLTM versus BacT/ALERTTM and BACTECTM.

    Science.gov (United States)

    Demiray, Tayfur; Koroglu, Mehmet; Altindis, Mustafa

    2016-09-01

    Automated blood culture systems are routinely used in microbiology laboratories to isolate bacteria and fungi causing bloodstream infections. A novel automated blood culture system, DL-Bt112TM (DL) was compared with the BACTEC 9050TM (BCT) and BacT/Alert 3DTM (B3D) systems for time-to-detection (TTD) using 10 different clinical bacteria that commonly cause bloodstream infections. Simulated blood cultures were used to compare the three automated blood culture systems. Blood drawn from healthy donors was inoculated with known concentrations of 10 different species of commonly isolated bacteria and analysed using the automated systems. TTD values for the three systems were recorded and analysed. Significant differences in the TTD were observed among the three systems. The DL system exhibited the longest detection time of all the systems (p significance difference was observed between the BCT and the B3D systems when overall TTD values were evaluated; however, the BCT system yielded significantly better results than did the B3D system for the Gram-positive bacteria. TTD values were longer for the DL system than for the two commonly used blood culture systems when tested on simulated blood cultures. Thus, clinical laboratories considering the DL system should take its long TTD into consideration.

  19. Performance of Web-based image distribution: client-oriented measurements

    Energy Technology Data Exchange (ETDEWEB)

    Bergh, B. [Department of Information and Communication Technology, Klinikum der Johann Wolfgang Goethe Universitaet, Theodor-Stern-Kai 7, 60590, Frankfurt am Main (Germany); Dezernat 7 DICT, Klinikum der Johann Wolfgang Goethe Universitaet, Theodor-Stern-Kai 7, 60590, Frankfurt am Main (Germany); Pietsch, M.; Schlaefke, A. [Department of Information and Communication Technology, Klinikum der Johann Wolfgang Goethe Universitaet, Theodor-Stern-Kai 7, 60590, Frankfurt am Main (Germany); Vogl, T.J. [Institute of Diagnostic and Interventional Radiology, Klinikum der Johann Wolfgang Goethe Universitaet, Theodor-Stern-Kai 7, 60590, Frankfurt am Main (Germany)

    2003-09-01

    The aim of this study was to define a clinically suitable personal computer (PC) configuration for Web-based image distribution and to assess the influence of different hard- and software configurations on the performance. Through specially developed software the time-to-display (TTD) for various PC configurations was measured. Different processor speeds, random access memory (RAM), screen resolutions, graphic adapters, network speeds, operating systems and examination types (computed radiography, CT, MRI) were evaluated, providing more than half a million measurements. Processor speed was the most relevant factor for the TTD; doubling the speed halved the TTD. Under processor speeds of 350 MHz, TTD mostly remained above 5 s for 1 CR or 16 CT images. Here Windows NT with lossy compression were superior. Processor speeds of 350 MHz and over delivered TTD <5 s. In this case Windows 2000 and lossless compression were preferable. Screen resolutions above 1280 x 1024 pixels increased the TTD mainly for CR images. The RAM amount, network speed and graphic adapter did not have a significant influence. The minimum threshold for clinical routine is any standard off-the-shelf PC better than Pentium II 350 MHz, 128 MB RAM; hence, high-end PC hardware is not required. (orig.)

  20. SAR processing with stepped chirps and phased array antennas.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2006-09-01

    Wideband radar signals are problematic for phased array antennas. Wideband radar signals can be generated from series or groups of narrow-band signals centered at different frequencies. An equivalent wideband LFM chirp can be assembled from lesser-bandwidth chirp segments in the data processing. The chirp segments can be transmitted as separate narrow-band pulses, each with their own steering phase operation. This overcomes the problematic dilemma of steering wideband chirps with phase shifters alone, that is, without true time-delay elements.

  1. Design of chirped fiber gratings for optical beamforming networks

    Science.gov (United States)

    Ye, Ying-Bo; Shi, Pei-Ming; Huang, Shan-Guo; Zhou, Jing

    2011-11-01

    The properties of the linear chirped fiber grating (CFG) which is used in the true time delay unit of the optical beamforming networks (OBFNs) are studied intensively through theoretical analyses and numerical calculations. It is concluded that the dispersion of the CFG is equal to 1/(3 Gc), where G is the chirp coefficient of CFG and c is the light speed. Based on this relationship, a simplified designing process of a CFG which satisfies the requirements of the OBFN is given. The simulation results are coincident with the theoretical conclusions.

  2. Performance of Web-based image distribution: client-oriented measurements.

    Science.gov (United States)

    Bergh, B; Pietsch, M; Schlaefke, A; Vogl, T J

    2003-09-01

    The aim of this study was to define a clinically suitable personal computer (PC) configuration for Web-based image distribution and to assess the influence of different hard- and software configurations on the performance. Through specially developed software the time-to-display (TTD) for various PC configurations was measured. Different processor speeds, random access memory (RAM), screen resolutions, graphic adapters, network speeds, operating systems and examination types (computed radiography, CT, MRI) were evaluated, providing more than half a million measurements. Processor speed was the most relevant factor for the TTD; doubling the speed halved the TTD. Under processor speeds of 350 MHz, TTD mostly remained above 5 s for 1 CR or 16 CT images. Here Windows NT with lossy compression were superior. Processor speeds of 350 MHz and over delivered TTD images. The RAM amount, network speed and graphic adapter did not have a significant influence. The minimum threshold for clinical routine is any standard off-the-shelf PC better than Pentium II 350 MHz, 128 MB RAM; hence, high-end PC hardware is not required.

  3. Implementation of the new VIRTUO blood culture system: evaluation and comparison to the 3D system using simulated blood cultures.

    Science.gov (United States)

    Miller, Nathalie; Brassinne, Laetitia; Allemeersch, Daniel

    2017-06-05

    To evaluate the performances of the newly approved BacT/ALERT VIRTUO blood culture system for the recovery of bloodstream pathogens and compare it to the BacT/ALERT 3D system. Simulated blood cultures of eight clinically relevant microorganisms were used: Bacteroides fragilis (ATCC 25285), Escherichia coli (ATCC 25922), Haemophilus influenzae (ATCC 49247), Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 29213), Streptococcus pneumoniae (ATCC 49619) and Candida krusei (ATCC 6258). Criteria for comparison were culture positivity and time to detection (TTD). The effects of delayed entry on recovery and TTD were also evaluated. The VIRTUO exhibited around 3 h faster detection time compared to the 3D system. (p < 0.01) for aerobic and facultative microorganisms. The difference in TTD was greatest for the B. fragilis, with a median difference of 46.67 h. The anaerobic bottle of the VIRTUO (FN Plus) did not support the growth of obligate aerobes, whereas the 3D did so. Delayed entry (studied with an E. Coli isolate) had no effect on the recovery rate but proportionally reduced TTD. The VIRTUO performed better than the 3D in terms of TTD and hands-on-time. FN Plus vial appears to be more efficient than the SN bottle in the recovery of anaerobes.

  4. Investigation of the detoxification mechanism of formaldehyde-treated tetanus toxin

    DEFF Research Database (Denmark)

    Thaysen-Andersen, Morten; Jørgensen, Sys Borcher; Wilhelmsen, Ellen Sloth

    2007-01-01

     The tetanus vaccine is based on the extremely potent tetanus neurotoxin (TeNT), which is converted by treatment with formaldehyde and lysine into the non-toxic, but still immunogenic tetanus toxoid (TTd). This formaldehyde-induced detoxification, which to a large extend determines the quality...... and formaldehyde in the detoxification process and (ii) characterisation of the chemically detoxified TTd. (i) We examined a number of TTd components that was produced by varying the concentrations of formaldehyde and lysine during the inactivation. Toxicity tests showed that the detoxification failed when...... the lysine or formaldehyde concentration was formaldehyde-dependent and, furthermore, revealed that inter-chain cross-linking was not the only requirement for the inactivation...

  5. Comparative Molecular Dynamics Studies of Human DNA Polymerase η

    Science.gov (United States)

    2015-01-01

    High-energy ultraviolet radiation damages DNA through the formation of cyclobutane pyrimidine dimers, which stall replication. When the lesion is a thymine–thymine dimer (TTD), human DNA polymerase η (Pol η) assists in resuming the replication process by inserting nucleotides opposite the damaged site. We performed extensive molecular dynamics (MD) simulations to investigate the structural and dynamical effects of four different Pol η complexes with or without a TTD and with either dATP or dGTP as the incoming base. No major differences in the overall structures and equilibrium dynamics were detected among the four systems, suggesting that the specificity of this enzyme is due predominantly to differences in local interactions in the binding regions. Analysis of the hydrogen-bonding interactions between the enzyme and the DNA and dNTP provided molecular-level insights. Specifically, the TTD was observed to engage in more hydrogen-bonding interactions with the enzyme than its undamaged counterpart of two normal thymines. The resulting greater rigidity and specific orientation of the TTD are consistent with the experimental observation of higher processivity and overall efficiency at TTD sites than at analogous sites with two normal thymines. The similarities between the systems containing dATP and dGTP are consistent with the experimental observation of relatively low fidelity with respect to the incoming base. Moreover, Q38 and R61, two strictly conserved amino acids across the Pol η family, were found to exhibit persistent hydrogen-bonding interactions with the TTD and cation-π interactions with the free base, respectively. Thus, these simulations provide molecular level insights into the basis for the selectivity and efficiency of this enzyme, as well as the roles of the two most strictly conserved residues. PMID:26562587

  6. Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation

    DEFF Research Database (Denmark)

    Kralund, Henrik H; Ousager, Lilian; Jaspers, Nicolaas G

    2013-01-01

    Xeroderma Pigmentosum (XP), Trichothiodystrophy (TTD) and Cockayne Syndrome (CS) are rare, recessive disorders caused by mutational defects in the Nucleotide Excision Repair (NER) pathway and/or disruption of basic cellular DNA transcription. To date, a multitude of mutations in the XPD/ERCC2 gene...... outcome from many of these mutations. We demonstrate a patient, believed to represent an overlap between XP and TTD/CS. In addition to other organ dysfunctions, the young man presented with Photosensitivity, Ichthyosis, Brittle hair, Impaired physical and mental development, Decreased fertility and Short...

  7. Disease: H00403 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available orrelated with mutations in specific XP genes (XPA, ERCC3, ERCC2 and ERCC5). Some patients of XP- A develop neurolog...ith mutations in the ERCC6 gene. CS is caused by mutations in ERCC8/CSA, ERCC6/CSB. CS is predominantly a developmental and neurolog...) PMID:18339586 (TTD and CS) Brooks PJ, Cheng TF, Cooper L Do all of the neurolog...rological abnormalities or skin tumors. TTD is a premature aging syndrome, with the... UV-sensitive syndrome (UVS) which is characterized by photosensitivity and mild freckling but without neu

  8. Data-Driven Assessment of the Association of Polymorphisms in 5-Fluorouracil Metabolism Genes with Outcome in Adjuvant Treatment of Colorectal Cancer

    DEFF Research Database (Denmark)

    Sarac, Sinan B.; Rasmussen, Christian H.; Afzal, Shoaib

    2012-01-01

    (the MDR-1 group) of dihydropyrimidine dehydrogenase and thymidylate synthase polymorphisms is associated with increased and clinically significant difference for cure and survival rates, TTD and probably also for TTR, which are seen as the most important endpoints. An inferior profile was observed...

  9. XERODERMA PIGMENTOSUM, TRICHOTHIODYSTROPHY AND COCKAYNE SYNDROME: A COMPLEX GENOTYPE-PHENOTYPE RELATIONSHIP

    Science.gov (United States)

    Kraemer, Kenneth H.; Patronas, Nicholas J.; Schiffmann, Raphael; Brooks, Brian P.; Tamura, Deborah; DiGiovanna, John J.

    2008-01-01

    Patients with the rare genetic disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS) have defects in DNA nucleotide excision repair (NER). The NER pathway involves at least 28 genes. Three NER genes are also part of the basal transcription factor, TFIIH. Mutations in 11 NER genes have been associated with clinical diseases with at least 8 overlapping phenotypes. The clinical features of these patients have some similarities and but also have marked differences. NER is involved in protection against sunlight induced DNA damage. While XP patients have 1000-fold increase in susceptibility to skin cancer, TTD and CS patients have normal skin cancer risk. Several of the genes involved in NER also affect somatic growth and development. Some patients have short stature and immature sexual development. TTD patients have sulfur deficient brittle hair. Progressive sensorineural deafness is an early feature of XP and CS. Many of these clinical diseases are associated with developmental delay and progressive neurological degeneration. The main neuropathology of XP is a primary neuronal degeneration. In contrast, CS and TTD patients have reduced myelination of the brain. These complex neurological abnormalities are not related to sunlight exposure but may be caused by developmental defects as well as faulty repair of DNA damage to neuronal cells induced by oxidative metabolism or other endogenous processes. PMID:17276014

  10. Comparison of 'time to detection' values between BacT/ALERT VIRTUO and BacT/ALERT 3D instruments for clinical blood culture samples.

    Science.gov (United States)

    Congestrì, Francesco; Pedna, Maria Federica; Fantini, Michela; Samuelli, Michela; Schiavone, Pasqua; Torri, Arianna; Bertini, Stefania; Sambri, Vittorio

    2017-09-01

    The early detection of bacteraemia and fungemia is of paramount importance to guide antimicrobial therapy in septic patients. In this study the 'time to detection' (TTD) value for the new blood culture system BacT/ALERT VIRTUO (VIRTUO) was evaluated in 1462 positive clinical bottles and compared with the TTD for 1601 positive clinical bottles incubated in the BacT/ALERT 3D system (BTA-3D). The most representative microorganisms isolated from bottles incubated in both blood culture systems were divided into eight categories (in order of frequency): coagulase-negative staphylococci (CoNS), Escherichia coli, Enterobacteriaceae (other than E. coli), Staphylococcus aureus, Enterococcus spp, viridans group streptococci, Pseudomonas aeruginosa, and Candida spp. The comparison of TTD values for the two blood culture systems strongly indicated that growth of the first five groups listed above was detected earlier with VIRTUO than with BTA-3D (p culture system can reduce the TTD for more than 75% of isolated microorganisms. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Functional architecture of the Reb1-Ter complex of Schizosaccharomyces pombe.

    Science.gov (United States)

    Jaiswal, Rahul; Choudhury, Malay; Zaman, Shamsu; Singh, Samarendra; Santosh, Vishaka; Bastia, Deepak; Escalante, Carlos R

    2016-04-19

    Reb1 ofSchizosaccharomyces pomberepresents a family of multifunctional proteins that bind to specific terminator sites (Ter) and cause polar termination of transcription catalyzed by RNA polymerase I (pol I) and arrest of replication forks approaching the Ter sites from the opposite direction. However, it remains to be investigated whether the same mechanism causes arrest of both DNA transactions. Here, we present the structure of Reb1 as a complex with a Ter site at a resolution of 2.7 Å. Structure-guided molecular genetic analyses revealed that it has distinct and well-defined DNA binding and transcription termination (TTD) domains. The region of the protein involved in replication termination is distinct from the TTD. Mechanistically, the data support the conclusion that transcription termination is not caused by just high affinity Reb1-Ter protein-DNA interactions. Rather, protein-protein interactions between the TTD with the Rpa12 subunit of RNA pol I seem to be an integral part of the mechanism. This conclusion is further supported by the observation that double mutations in TTD that abolished its interaction with Rpa12 also greatly reduced transcription termination thereby revealing a conduit for functional communications between RNA pol I and the terminator protein.

  12. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy.

    NARCIS (Netherlands)

    G. Weeda (Geert); E. Eveno; I. Donker (Ingrid); W. Vermeulen (Wim); O. Chevalier-Lagente (Odile); A. Taieb; A. Stary; J.H.J. Hoeijmakers (Jan); M. Mezzina; A. Sarasin

    1997-01-01

    textabstractTrichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual development, and ichthyosis. Photosensitivity has been reported in approximately 50% of the cases, but no skin cancer is

  13. Using a Video Game to Teach Supply Chain and Logistics Management

    Science.gov (United States)

    Liu, Chiung-Lin

    2017-01-01

    This study used OpenTTD, a video game that supports in-depth experiential learning, to evaluate undergraduate students' opinions regarding supply chain and logistics management learning. The 101 undergraduate participants were assigned to either an experimental group or a control group. From the post-test questionnaires, the analytical results…

  14. 75 FR 2122 - Additional Guidance Regarding Application of Current Procedures for Testing Energy Consumption of...

    Science.gov (United States)

    2010-01-14

    ... models with bottom-mounted freezers and TTD ice service, which are designed to permit ice to be produced... Refrigerator-Freezers With Automatic Ice Makers AGENCY: Office of the General Counsel, U.S. Department of... ensure the consistent application of DOE's current test procedure to refrigerator-freezers with French...

  15. Consequences of mixing assumptions for time-variable travel time distributions

    NARCIS (Netherlands)

    Velde, van der Y.; Heidbüchel, I.; Lyon, S.W.; Nyberg, L.; Rodhe, A.; Bishop, K.; Troch, P.A.

    2015-01-01

    The current generation of catchment travel time distribution (TTD) research, integrating nearly three decades of work since publication of Water's Journey from Rain to Stream, seeks to represent the full distribution in catchment travel times and its temporal variability. Here, we compare

  16. Integrated response and transit time distributions of watersheds by combining hydrograph separation and long-term transit time modeling

    Directory of Open Access Journals (Sweden)

    M. C. Roa-García

    2010-08-01

    Full Text Available We present a new modeling approach analyzing and predicting the Transit Time Distribution (TTD and the Response Time Distribution (RTD from hourly to annual time scales as two distinct hydrological processes. The model integrates Isotope Hydrograph Separation (IHS and the Instantaneous Unit Hydrograph (IUH approach as a tool to provide a more realistic description of transit and response time of water in catchments. Individual event simulations and parameterizations were combined with long-term baseflow simulation and parameterizations; this provides a comprehensive picture of the catchment response for a long time span for the hydraulic and isotopic processes. The proposed method was tested in three Andean headwater catchments to compare the effects of land use on hydrological response and solute transport. Results show that the characteristics of events and antecedent conditions have a significant influence on TTD and RTD, but in general the RTD of the grassland dominated catchment is concentrated in the shorter time spans and has a higher cumulative TTD, while the forest dominated catchment has a relatively higher response distribution and lower cumulative TTD. The catchment where wetlands concentrate shows a flashier response, but wetlands also appear to prolong transit time.

  17. Heterogeneity of T-Tubules in Pig Hearts.

    Science.gov (United States)

    Gadeberg, Hanne C; Bond, Richard C; Kong, Cherrie H T; Chanoit, Guillaume P; Ascione, Raimondo; Cannell, Mark B; James, Andrew F

    2016-01-01

    T-tubules are invaginations of the sarcolemma that play a key role in excitation-contraction coupling in mammalian cardiac myocytes. Although t-tubules were generally considered to be effectively absent in atrial myocytes, recent studies on atrial cells from larger mammals suggest that t-tubules may be more numerous than previously supposed. However, the degree of heterogeneity between cardiomyocytes in the extent of the t-tubule network remains unclear. The aim of the present study was to investigate the t-tubule network of pig atrial myocytes in comparison with ventricular tissue. Cardiac tissue was obtained from young female Landrace White pigs (45-75 kg, 5-6 months old). Cardiomyocytes were isolated by arterial perfusion with a collagenase-containing solution. Ca2+ transients were examined in field-stimulated isolated cells loaded with fluo-4-AM. Membranes of isolated cells were visualized using di-8-ANEPPS. T-tubules were visualized in fixed-frozen tissue sections stained with Alexa-Fluor 488-conjugated WGA. Binary images were obtained by application of a threshold and t-tubule density (TTD) calculated. A distance mapping approach was used to calculate half-distance to nearest t-tubule (HDTT). The spatio-temporal properties of the Ca2+ transient appeared to be consistent with the absence of functional t-tubules in isolated atrial myocytes. However, t-tubules could be identified in a sub-population of atrial cells in frozen sections. While all ventricular myocytes had TTD >3% (mean TTD = 6.94±0.395%, n = 24), this was true of just 5/22 atrial cells. Mean atrial TTD (2.35±0.457%, n = 22) was lower than ventricular TTD (P3% (1.65±0.06 μm, n = 5, Ppig cardiomyocytes in the extent of t-tubule network, which correlated with cell size.

  18. Nano-optomechanical transducer

    Science.gov (United States)

    Rakich, Peter T; El-Kady, Ihab F; Olsson, Roy H; Su, Mehmet Fatih; Reinke, Charles; Camacho, Ryan; Wang, Zheng; Davids, Paul

    2013-12-03

    A nano-optomechanical transducer provides ultrabroadband coherent optomechanical transduction based on Mach-wave emission that uses enhanced photon-phonon coupling efficiencies by low impedance effective phononic medium, both electrostriction and radiation pressure to boost and tailor optomechanical forces, and highly dispersive electromagnetic modes that amplify both electrostriction and radiation pressure. The optomechanical transducer provides a large operating bandwidth and high efficiency while simultaneously having a small size and minimal power consumption, enabling a host of transformative phonon and signal processing capabilities. These capabilities include optomechanical transduction via pulsed phonon emission and up-conversion, broadband stimulated phonon emission and amplification, picosecond pulsed phonon lasers, broadband phononic modulators, and ultrahigh bandwidth true time delay and signal processing technologies.

  19. Silicon-based tunable optical delay lines and switches for next generation optical telecommunications

    Science.gov (United States)

    Zhou, Linjie; Xie, Jingya; Lu, Liangjun; Li, Zuxiang; Chen, Jianping

    2015-02-01

    We report our recent progress on reconfigurable optical true time delay lines (RTTDL) and optical switches. The RTTDL is composed of 8 stages of MZIs connected by 7 waveguide pairs with an incremental length difference. Variable optical attenuators are inserted in the delay waveguides to suppress crosstalk caused by the residual signals from noise paths. Transmission of a 25 Gbps PRBS signal confirms the signal fidelity after a maximum of 1.27 ns delay. The optical switch is based on a Benes architecture with Mach-Zehnder interferometers (MZI) as the switching elements. Both p-i-n diodes and silicon resistive micro-heaters are integrated in the MZI arms for electrical tuning and phase correction, respectively. The measured on-chip insertion loss of the 4×4 switch is optical signal verifies its switching functionality.

  20. Frequency Invariant Beam Steering for Short-Pulse Systems with a Rotman Lens

    Directory of Open Access Journals (Sweden)

    Andreas Lambrecht

    2010-01-01

    Full Text Available A promising approach for beam steering of high-voltage transient signals for HPEM-systems (High Power Electro Magnetic is presented. The inherent capability of the Rotman lens to provide true time delays is used to develop a prototype beam steering device for an antielectronics HPEM system in the frequency range from 350 MHz to 5 GHz. Results of analytical calculations, simulations, and measurements from a hardware prototype are presented. The detailed mechanical setup of the Rotman lens is presented. Additionally the output pulses are investigated when inputting a Gaussian-like transient signal. Then time domain measures of quality (full width at half maximum, ringing, delay spread, maximum of transfer function are investigated for these output transients, and the simulation and measurement results are compared. A concluding analysis of the realizable time domain array pattern shows the radiated pulse form.

  1. Time Delay Estimation Algoritms for Echo Cancellation

    Directory of Open Access Journals (Sweden)

    Boris Simak

    2011-01-01

    Full Text Available The following case study describes how to eliminate echo in a VoIP network using delay estimation algorithms. It is known that echo with long transmission delays becomes more noticeable to users. Thus, time delay estimation, as a part of echo cancellation, is an important topic during transmission of voice signals over packetswitching telecommunication systems. An echo delay problem associated with IP-based transport networks is discussed in the following text. The paper introduces the comparative study of time delay estimation algorithm, used for estimation of the true time delay between two speech signals. Experimental results of MATLab simulations that describe the performance of several methods based on cross-correlation, normalized crosscorrelation and generalized cross-correlation are also presented in the paper.

  2. Deconstructing anti-harm-reduction metaphors; mortality risk from falls and other traumatic injuries compared to smokeless tobacco use

    Directory of Open Access Journals (Sweden)

    Bergen Paul

    2006-04-01

    Full Text Available Abstract Anti-harm-reduction advocates sometimes resort to pseudo-analogies to ridicule harm reduction. Those opposed to the use of smokeless tobacco as an alternative to smoking sometimes suggest that the substitution would be like jumping from a 3 story building rather than 10 story, or like shooting yourself in the foot rather than the head. These metaphors are grossly inappropriate for several reasons, notably including the fact that they are misleading about the actual risk levels. Based on the available literature on mortality from falls, we estimate that smoking presents a mortality risk similar to a fall of about 4 stories, while mortality risk from smokeless tobacco is no worse than that from an almost certainly non-fatal fall from less than 2 stories. Other metaphors are similarly misleading. These metaphors, like other false and misleading anti-harm-reduction statements are inherently unethical attempts to prevent people from learning accurate health information. Moreover, they implicitly provide bad advice about health behavior priorities and are intended to persuade people to stick with a behavior that is more dangerous than an available alternative. Finally, the metaphors exhibit a flippant tone that seems inappropriate for a serious discussion of health science.

  3. Water transit time distributions as indicators of nitrate transport systematics in different agriculturally used catchments

    Science.gov (United States)

    Osenbrück, K.; Dilbat, M.; Knöller, K.

    2009-04-01

    The transit time distribution (TTD) of water is a fundamental parameter in hydrogeology, revealing information about the distribution of flow pathways and the origin of water in a catchment. Hence, the TTD of groundwater or of water discharging from a catchment may be used as an indicator to assess the transport of solutes like nitrate in groundwater wells or streams of agriculturally used catchments. Here we present hydrochemical and isotopic data from 4 subcatchments of the Weisse Elster basin, Germany, which range from the small to the meso scale. Catchment TTDs have been modeled using measured time series of the stable (18O and 2H) and radioactive (tritium) isotopes of water (sampled weekly to bi-weekly). In case of groundwater wells additional environmental tracers (tritiogenic 3He, CFCs) were used to further constrain the groundwater TTD. Mean residence times for baseflow range from 3 to 10 years (exponential and dispersion model) and most probably are mainly controlled by the geological characteristics of the subcatchments. However, all investigated catchments showed a positive relationship between nitrate and stream discharge indicating that a major part of the nitrate load is released during and after storm runoff. TTDs based on stream samples during baseflow as well as stormflow conditions show substantially lower mean residence times of less than 1 to about 4 months. However, the calculation of a reliable TTD on the event time scale is limited by the ‘steady state' assumption required for the modeling of the TTD with lumped parameter models. If the temporal variation of nitrate input into the subsurface is known, the TTD calculated from environmental tracers and isotopes can be used to estimate the development of nitrate concentrations in water and hence to evaluate management options and measures. This has been done in a small groundwater catchment used for drinking water purposes. The derived TTDs with high mean residence times of >30a suggest, that

  4. Hereditary Disorders with Defective Repair of UV-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Shinichi Moriwaki

    2013-01-01

    Full Text Available Nucleotide excision repair (NER is an essential system for correcting ultraviolet (UV–-induced DNA damage. Lesions remaining in DNA due to reduced capacity of NER may result in cellular death, premature aging, mutagenesis and carcinogenesis of the skin. So, NER is an important protection against these changes. There are three representative genodermatoses resulting from genetic defects in NER: xeroderma pigmentosum (XP, Cockayne syndrome (CS, and trichothiodystrophy (TTD. In Japan, CS is similarly rare but XP is more common and TTD is less common compared to Western countries. In 1998, we established the system for the diagnosis of these disorders and we have been performing DNA repair and genetic analysis for more than 400 samples since then. At present, there is no cure for any human genetic disorder. Early diagnosis and symptomatic treatment of neurological, ocular and dermatological abnormalities should contribute to prolonging life and elevating QOL in patients.

  5. The Sensorium: A Multimodal Neurofeedback Environment

    Directory of Open Access Journals (Sweden)

    Thilo Hinterberger

    2011-01-01

    Full Text Available The Sensorium is a neurofeedback environment that allows people to experience signals from their nonperceptible body processes visually and auditorily. Various (neuro-physiological rhythms and frequencies are projected simultaneously as soundscapes and “lightscapes” into the environment. A wireless physiological amplifier device sends signals such as EEG and ECG to a computer for real-time processing using the modified brain-computer interface software “Thought Translation Device” (TTD. The TTD performs signal filtering, parametric orchestral sonification, and light control. In a pilot study, 20 participants have been exposed to their ongoing brain and heart signals while sitting inside the Sensorium, a small room equipped with a speaker and lighting system. Almost all of them reported an increase in contentment, relaxation, happiness, and inner harmony. They also reported a widening in their body consciousness. In future, therapeutic paradigms will be developed and the treatment effects on people with psychosomatic diseases will be evaluated.

  6. COBAS® TaqMan® MTB, smear positivity grade and MGIT culture; correlation analyses of three methods for bacillary quantification.

    Science.gov (United States)

    Chikamatsu, Kinuyo; Aono, Akio; Kato, Tomoko; Takaki, Akiko; Yamada, Hiroyuki; Sasaki, Yuka; Izumi, Kiyohiko; Yi, Lina; Mitarai, Satoshi

    2016-01-01

    We investigated the correlation between the cycle threshold (Ct) value of the COBAS(®) TaqMan(®) MTB (TaqMan MTB), the mycobacterial smear positivity grade, and the time to detection (TTD) in the Mycobacteria Growth Indicator Tube (MGIT) for quantification of Mycobacterium tuberculosis (MTB). For 57 sputum samples, significant correlations were observed between the Ct value, the smear positivity grade, and the MGIT TTD (Spearman's rank correlation coefficient: r(s) = -0.940, P MTB bacilli calculated by the Ct value (r(s) = 0.930, P MTB, which is based on a real-time PCR system, for diagnostic samples. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Time to health-related quality of life score deterioration as a modality of longitudinal analysis for health-related quality of life studies in oncology: do we need RECIST for quality of life to achieve standardization?

    Science.gov (United States)

    Anota, Amélie; Hamidou, Zeinab; Paget-Bailly, Sophie; Chibaudel, Benoist; Bascoul-Mollevi, Caroline; Auquier, Pascal; Westeel, Virginie; Fiteni, Frederic; Borg, Christophe; Bonnetain, Franck

    2015-01-01

    Longitudinal analysis of health-related quality of life (HRQoL) remains unstandardized and compromises comparison of results between trials. In oncology, despite available statistical approaches, results are poorly used to change standards of care, mainly due to lack of standardization and the ability to propose clinical meaningful results. In this context, the time to deterioration (TTD) has been proposed as a modality of longitudinal HRQoL analysis for cancer patients. As for tumor response and progression, we propose to develop RECIST criteria for HRQoL. Several definitions of TTD are investigated in this paper. We applied this approach in early breast cancer and metastatic pancreatic cancer with a 5-point minimal clinically important difference. In breast cancer, TTD was defined as compared to the baseline score or to the best previous score. In pancreatic cancer (arm 1: gemcitabine with FOLFIRI.3, arm 2: gemcitabine alone), the time until definitive deterioration (TUDD) was investigated with or without death as event. In the breast cancer study, 381 women were included. The median TTD was influenced by the choice of the reference score. In pancreatic cancer study, 98 patients were enrolled. Patients in Arm 1 presented longer TUDD than those in Arm 2 for most of HRQoL scores. Results of TUDD were slightly different according to the definition of deterioration applied. Currently, the international ARCAD group supports the idea of developing RECIST for HRQoL in pancreatic and colorectal cancer with liver metastasis, with a view to using HRQoL as a co-primary endpoint along with a tumor parameter.

  8. Demonstration Applications of ARAMS for Aquatic and Terrestrial Ecological Risk Assessment

    Science.gov (United States)

    2006-01-01

    Description classes of Amphibia, Aves, and Mammalia. At the time of this study, TTD did not have data for Reptilia . Therefore, if this option is selected...species, 13 effect classes , and 126 endpoints. Most papers involving mix- tures of contaminants were excluded from the database because effects could not...are supplied in a Microsoft Access 2000 database that is searchable by genus, family, order, class , general data groupings (e.g., all soil benchmark

  9. Manual MGIT™ system for the detection of Mycobacterium tuberculosis: insights from a high TB burden setting.

    Science.gov (United States)

    Quispe, R; Valle, G A; Huapaya, J A; Novoa, I; Giraldo, J; Caceres, T; Gotuzzo, E; Zamudio, C; Seas, C

    2016-05-01

    To evaluate the diagnostic performance of manual MGIT™ (MMGIT) compared to the gold standard, Löwenstein-Jensen (LJ), in the diagnosis of pulmonary tuberculosis (TB) in a high-burden setting. Individuals with suspected TB enrolled in parallel diagnostic trials during 2007-2011 were included. Two samples were obtained from each patient and inoculated into MMGIT and LJ medium. Diagnostic tests were performed, and the incremental yield of a second test and time to detection (TTD) were calculated. Analyses were performed per patient and per sample. Gold standard was based on LJ culture. In the per patient and per sample analysis, we evaluated 1436 patients and 4142 samples. The sensitivity and specificity for smear and MMGIT per sample were respectively 89.9%/92.2% and 97.1%/98.9%. Contamination was observed in 1.4% of samples on MMGIT. The mean TTD (days) was 11.8 for MMGIT and 22.9 for LJ. The sensitivity and specificity for smear and MMGIT per patient were respectively 89.9% and 92.2% and 97.1% and 98.3%. A second MMGIT culture had an incremental yield of 1.6%. MMGIT has high sensitivity and specificity, regardless of smear result, with a 50% reduction in TTD compared to LJ. These features make MMGIT an acceptable TB diagnostic method for use in resource-limited settings.

  10. TTDA: big impact of a small protein.

    Science.gov (United States)

    Theil, Arjan F; Hoeijmakers, Jan H J; Vermeulen, Wim

    2014-11-15

    Nucleotide excision repair (NER) is a highly versatile DNA repair process which is able to remove a broad spectrum of structurally unrelated DNA helix-destabilizing lesions. The multi-subunit transcription/repair factor IIH (TFIIH) is an important decision maker in NER, by opening the DNA double helix after the initial damage recognition and subsequently verifying the lesion. Inherited mutations in TFIIH subunits are associated with NER-deficiency and a perplexing clinical heterogeneity, ranging from cancer-prone Xeroderma Pigmentosum to the progeroid diseases Cockayne Syndrome and Trichothiodystrophy (TTD). Three different TFIIH coding genes are implicated in TTD: XPD, XPB and TTDA. The latter gene encodes for a small (71 amino-acid) subunit and appeared important for the stabilization of the entire TFIIH complex. Based on analyzing TTD group A patient derived cells it was initially thought that TTDA has only a NER-stimulating role. In this review we summarize recent data showing that full disruption of TTDA expression in a knock-out mouse-model completely inactivates NER. Surprisingly, next to being essential for NER, TTDA appeared to be required also for embryonic development, indicative for the big impact this small protein has on basal biological processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Tribotronic Tuning Diode for Active Analog Signal Modulation.

    Science.gov (United States)

    Zhou, Tao; Yang, Zhi Wei; Pang, Yaokun; Xu, Liang; Zhang, Chi; Wang, Zhong Lin

    2017-01-24

    Realizing active interaction with external environment/stimuli is a great challenge for current electronics. In this paper, a tribotronic tuning diode (TTD) is proposed by coupling a variable capacitance diode and a triboelectric nanogenerator in free-standing sliding mode. When the friction layer is sliding on the device surface for electrification, a reverse bias voltage is created and applied to the diode for tuning the junction capacitance. When the sliding distance increases from 0 to 25 mm, the capacitance of the TTD decreases from about 39 to 8 pF. The proposed TTD has been integrated into analog circuits and exhibited excellent performances in frequency modulation, phase shift, and filtering by sliding a finger. This work has demonstrated tunable diode and active analog signal modulation by tribotronics, which has great potential to replace ordinary variable capacitance diodes in various practical applications such as signal processing, electronic tuning circuits, precise tuning circuits, active sensor networks, electronic communications, remote controls, flexible electronics, etc.

  12. Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition

    Science.gov (United States)

    Fang, Jian; Cheng, Jingdong; Wang, Jiaolong; Zhang, Qiao; Liu, Mengjie; Gong, Rui; Wang, Ping; Zhang, Xiaodan; Feng, Yangyang; Lan, Wenxian; Gong, Zhou; Tang, Chun; Wong, Jiemin; Yang, Huirong; Cao, Chunyang; Xu, Yanhui

    2016-04-01

    UHRF1 is an important epigenetic regulator for maintenance DNA methylation. UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown. Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition. Hm-DNA impairs the intramolecular interactions and promotes H3K9me3 recognition by TTD-PHD. The Spacer also facilitates UHRF1-DNMT1 interaction and enhances hm-DNA-binding affinity of the SRA. When TTD-PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin. Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1.

  13. Numerical modeling of cracking pattern's influence on the dynamic response of thickened tailings disposals: a periodic approach

    Science.gov (United States)

    Ferrer, Gabriel; Sáez, Esteban; Ledezma, Christian

    2018-01-01

    Copper production is an essential component of the Chilean economy. During the extraction process of copper, large quantities of waste materials (tailings) are produced, which are typically stored in large tailing ponds. Thickened Tailings Disposal (TTD) is an alternative to conventional tailings ponds. In TTD, a considerable amount of water is extracted from the tailings before their deposition. Once a thickened tailings layer is deposited, it loses water and it shrinks, forming a relatively regular structure of tailings blocks with vertical cracks in between, which are then filled up with "fresh" tailings once the new upper layer is deposited. The dynamic response of a representative column of this complex structure made out of tailings blocks with softer material in between was analyzed using a periodic half-space finite element model. The tailings' behavior was modeled using an elasto-plastic multi-yielding constitutive model, and Chilean earthquake records were used for the seismic analyses. Special attention was given to the liquefaction potential evaluation of TTD.

  14. Use of conductimetry to rapidly determine relative stress sensitivity in Salmonella isolates.

    Science.gov (United States)

    Sherry, A E; Patterson, M F; Madden, R H

    2009-02-01

    To compare conventional plate counting and indirect conductimetry as techniques for ranking the resistance of Salmonella spp. to processing stressors. Forty Salmonella isolates were subjected to three separate stressors used in food processing; irradiation, heat and high hydrostatic pressure (HHP). Total viable counts (TVC) using conventional plate counts and time to detection (TTD) using indirect conductimetry were determined. A significant negative correlation between TVC and TTD was seen with irradiation (P conductimetry can rapidly determine a ranking of isolate sensitivity to irradiation and heat. However, for HHP, the results indicated that conventional plate counting alone cannot be used to determine sensitivity. The resistance of micro-organisms to processing systems must be ranked to allow the selection of appropriate isolates for process validation. TTD measurements allow rapid screening of salmonellas to rank isolates for resistance to irradiation and heat stress. However, following HHP, the TVC of survivors is independent of the time required for growth to a set cell density and therefore it cannot be used as the sole measure of relative stress resistance.

  15. Comparison of Tunable Diode Laser Absorption Spectroscopy and Isothermal Micro-calorimetry for Non-invasive Detection of Microbial Growth in Media Fills.

    Science.gov (United States)

    Brueckner, David; Roesti, David; Zuber, Ulrich Georg; Schmidt, Rainer; Kraehenbuehl, Stefan; Bonkat, Gernot; Braissant, Olivier

    2016-06-10

    Two methods were investigated for non-invasive microbial growth-detection in intact glass vials as possible techniques for automated inspection of media-filled units. Tunable diode laser absorption spectroscopy (TDLAS) was used to determine microbially induced changes in O2 and CO2 concentrations within the vial headspaces. Isothermal microcalorimetry (IMC) allowed the detection of metabolic heat production. Bacillus subtilis and Streptococcus salivarius were chosen as test organisms. Parameters as robustness, sensitivity, comparability and time to detection (TtD) were evaluated to assess method adequacy. Both methods robustly detected growth of the tested microorganisms within less than 76 hours using an initial inoculum of <10CFU. TDLA turned out to be less sensitive than TDLA and IMC, as some false negative results were observed. Compared to the visual media-fill examination of spiked samples, the investigated techniques were slightly slower regarding TtD. Although IMC showed shorter TtD than TDLAS the latter is proposed for automating the media-fill inspection, as larger throughput can be achieved. For routine use either TDLA or a combination of TDLA and TDLA should be considered. IMC may be helpful for replacing the sterility assessment of commercial drug products before release.

  16. An Allosteric Interaction Links USP7 to Deubiquitination and Chromatin Targeting of UHRF1

    Directory of Open Access Journals (Sweden)

    Zhi-Min Zhang

    2015-09-01

    Full Text Available The protein stability and chromatin functions of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1 are regulated in a cell-cycle-dependent manner. We report a structural characterization of the complex between UHRF1 and the deubiquitinase USP7. The first two UBL domains of USP7 bind to the polybasic region (PBR of UHRF1, and this interaction is required for the USP7-mediated deubiquitination of UHRF1. Importantly, we find that the USP7-binding site of the UHRF1 PBR overlaps with the region engaging in an intramolecular interaction with the N-terminal tandem Tudor domain (TTD. We show that the USP7-UHRF1 interaction perturbs the TTD-PBR interaction of UHRF1, thereby shifting the conformation of UHRF1 from a TTD-“occluded” state to a state open for multivalent histone binding. Consistently, introduction of a USP7-interaction-defective mutation to UHRF1 significantly reduces its chromatin association. Together, these results link USP7 interaction to the dynamic deubiquitination and chromatin association of UHRF1.

  17. Upload capacity and time-to-display of an image Web system during simultaneous up- and download processes.

    Science.gov (United States)

    Bergh, B; Pietsch, M; Schlaefke, A; Garcia, I; Vogl, T J

    2004-03-01

    The aim of this study was to assess the up- and download performance of an image Web system (IWS) during simultaneous up- and download procedures. Following preparatory tests, the upload capacity (UC) with and without simultaneous download and the time-to-display (TTD) with and without simultaneous upload were determined for different image, server and compression types, and with up to 16 concurrent clients. The UC varied between 1.7-5.5 Gigabyte per hour (GB/h) and was slightly influenced by a simultaneous download; however, the TTDs were substantially prolonged during an upload and only below 5 s with up to four to six concurrent clients. The choice of image and server type had a strong impact on UC and TTD. Lossy primary compression proved slightly superior. An effective UC of approximately 4.0 GB/h or 96 Gigabyte per day (GB/day) can be achieved, which appears suitable even for large institutions. Because of its substantial influence on UC and TTD during simultaneous up- and download, the server hardware should be equipped with two processors and 1 GB RAM. Lossy primary compression may be used with slight performance benefits when full-resolution images are not required. The upload is a time-demanding process, and it is possible that during peak hours the waiting times are unacceptable for clinicians.

  18. Baseline predictors of sputum culture conversion in pulmonary tuberculosis: importance of cavities, smoking, time to detection and W-Beijing genotype.

    Directory of Open Access Journals (Sweden)

    Marianne E Visser

    Full Text Available Time to detection (TTD on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes.To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis.Between May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960. Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable.113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities. On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR = 1.11, 95% CI 1.02; 1.2, lung cavities (aHR = 0.13, 95% CI 0.02; 0.95, ever smoking (aHR = 0.32, 95% CI 0.1; 1.02 and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07. On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype.We found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture

  19. Intermodulation and harmonic distortion in slow light Microwave Photonic phase shifters based on Coherent Population Oscillations in SOAs.

    Science.gov (United States)

    Gasulla, Ivana; Sancho, Juan; Capmany, José; Lloret, Juan; Sales, Salvador

    2010-12-06

    We theoretically and experimentally evaluate the propagation, generation and amplification of signal, harmonic and intermodulation distortion terms inside a Semiconductor Optical Amplifier (SOA) under Coherent Population Oscillation (CPO) regime. For that purpose, we present a general optical field model, valid for any arbitrarily-spaced radiofrequency tones, which is necessary to correctly describe the operation of CPO based slow light Microwave Photonic phase shifters which comprise an electrooptic modulator and a SOA followed by an optical filter and supplements another recently published for true time delay operation based on the propagation of optical intensities. The phase shifter performance has been evaluated in terms of the nonlinear distortion up to 3rd order, for a modulating signal constituted of two tones, in function of the electrooptic modulator input RF power and the SOA input optical power, obtaining a very good agreement between theoretical and experimental results. A complete theoretical spectral analysis is also presented which shows that under small signal operation conditions, the 3rd order intermodulation products at 2Ω1 + Ω2 and 2Ω2 + Ω1 experience a power dip/phase transition characteristic of the fundamental tones phase shifting operation.

  20. NASA Tech Briefs, October 2004

    Science.gov (United States)

    2004-01-01

    Topics include: Relative-Motion Sensors and Actuators for Two Optical Tables; Improved Position Sensor for Feedback Control of Levitation; Compact Tactile Sensors for Robot Fingers; Improved Ion-Channel Biosensors; Suspended-Patch Antenna With Inverted, EM-Coupled Feed; System Would Predictively Preempt Traffic Lights for Emergency Vehicles; Optical Position Encoders for High or Low Temperatures; Inter-Valence-Subband/Conduction-Band-Transport IR Detectors; Additional Drive Circuitry for Piezoelectric Screw Motors; Software for Use with Optoelectronic Measuring Tool; Coordinating Shared Activities; Software Reduces Radio-Interference Effects in Radar Data; Using Iron to Treat Chlorohydrocarbon-Contaminated Soil; Thermally Insulating, Kinematic Tensioned-Fiber Suspension; Back Actuators for Segmented Mirrors and Other Applications; Mechanism for Self-Reacted Friction Stir Welding; Lightweight Exoskeletons with Controllable Actuators; Miniature Robotic Submarine for Exploring Harsh Environments; Electron-Spin Filters Based on the Rashba Effect; Diffusion-Cooled Tantalum Hot-Electron Bolometer Mixers; Tunable Optical True-Time Delay Devices Would Exploit EIT; Fast Query-Optimized Kernel-Machine Classification; Indentured Parts List Maintenance and Part Assembly Capture Tool - IMPACT; An Architecture for Controlling Multiple Robots; Progress in Fabrication of Rocket Combustion Chambers by VPS; CHEM-Based Self-Deploying Spacecraft Radar Antennas; Scalable Multiprocessor for High-Speed Computing in Space; and Simple Systems for Detecting Spacecraft Meteoroid Punctures.

  1. The Modeling of Time-Varying Stream Water Age Distributions: Preliminary Investigations with Non-Conservative Solutes

    Science.gov (United States)

    Wilusz, D. C.; Harman, C. J.; Ball, W. P.

    2014-12-01

    Modeling the dynamics of chemical transport from the landscape to streams is necessary for water quality management. Previous work has shown that estimates of the distribution of water age in streams, the transit time distribution (TTD), can improve prediction of the concentration of conservative tracers (i.e., ones that "follow the water") based on upstream watershed inputs. A major challenge however has been accounting for climate and transport variability when estimating TDDs at the catchment scale. In this regard, Harman (2014, in review) proposed the Omega modeling framework capable of using watershed hydraulic fluxes to approximate the time-varying TTD. The approach was previously applied to the Plynlimon research watershed in Wales to simulate stream concentration dynamics of a conservative tracer (chloride) including 1/f attenuation of the power spectra density. In this study we explore the extent to which TTDs estimated by the Omega model vary with the concentration of non-conservative tracers (i.e., ones whose concentrations are also affected by transformations and interactions with other phases). First we test the hypothesis that the TTD calibrated in Plynlimon can explain a large part of the variation in non-conservative stream water constituents associated with storm flow (acidity, Al, DOC, Fe) and base flow (Ca, Si). While controlling for discharge, we show a correlation between the percentage of water of different ages and constituent concentration. Second, we test the hypothesis that TTDs help explain variation in stream nitrate concentration, which is of particular interest for pollution control but can be highly non-conservative. We compare simulation runs from Plynlimon and the agricultural Choptank watershed in Maryland, USA. Following a top-down approach, we estimate nitrate concentration as if it were a conservative tracer and examine the structure of residuals at different temporal resolutions. Finally, we consider model modifications to

  2. Effect of blood volume in standard anaerobic blood culture bottles of the BacT/ALERT 3D system used for the detection of pathogens and time to detection.

    Directory of Open Access Journals (Sweden)

    Seong Chun Kim

    Full Text Available Blood volume may profoundly affect the isolation of microorganisms in blood cultures. The effect of blood volume in standard anaerobic bottles of the BacT/ALERT 3D system was investigated.Adult patients who visited the emergency department and referred for blood culture (n = 824 were enrolled from June to September 2013. Two sets of blood cultures were obtained from each patient. One set consisted of 5 mL that was collected in a standard aerobic bottle (SA5, 5 mL that was collected in a standard anaerobic bottle (SN5, and 10 mL that was collected in a standard anaerobic bottle (SN10. The growth of clinically significant pathogens and the time to detection (TTD were compared between the SN5 and SN10 samples.Increasing the volume of blood collected from 5 to 10 mL yielded a 14.7% improvement in the isolation of microorganisms. There was a statistically significant difference in the isolation of pathogens (14 vs. 30, P = 0.023 between the SN5 and SN10 samples. Gram-positive microorganisms were detected earlier in the SN10 samples than the SN5 samples (P = 0.052. The mean TTD of all pathogens was 13.5 h for the SN5 samples and 12.9 h for the SN10 samples (P = 0.099.Increased blood volume in the SN bottle yielded a significantly higher pathogen detection rate. However, there was no difference in the frequency of earlier detection or TTD between the SN5 and SN10 samples.

  3. Transient thermal dissipation method for xylem sap flow measurement: implementation with a single probe.

    Science.gov (United States)

    Do, F C; Isarangkool Na Ayutthaya, S; Rocheteau, A

    2011-04-01

    Comparisons of tree water relations between treatments, species and sites are facilitated by the use of simple and low-cost measurements of xylem sap flow rates. The transient thermal dissipation (TTD) method is a variant of the constant thermal dissipation (CTD) method of Granier. It has the advantages of limiting thermal interference and of saving electrical energy. Here, our concern was to test a new step towards simplicity and low cost: the applicability of the TTD method with a single probe, i.e., without a reference sensor, following a cycle of 10 min heating and 10 min cooling, and using the same thermal index and multi-species calibration previously assessed with a dual probe. First, the responses of the dual and single probes were compared in an artificial hydraulic column of sawdust in the laboratory over a complete range of flux densities, from 0.3 to 4.0 l dm⁻² h⁻¹. Second, diurnal kinetics were compared in a young tree with rapid changes in the sapwood reference temperature of up to 5 °C h⁻¹ for 5 consecutive days. With a relatively stable reference temperature, laboratory results showed that a single probe yielded the same temperature signal and thermal index as a dual probe for the full range of sap flux densities. Within the tree, the cooled temperature of the heated probe, linearly interpolated, proved to be an accurate indicator of the change in the reference temperature over time. Logically, the temperature signals and estimates of sap flux density with the single probe did not differ from the dual-sensor measurements when the cooled temperature was interpolated. Additionally, the responses of the thermal index, yielded in the hydraulic experiment with the sawdust column, fell within the variability of the multi-species calibration. This result supports the previous assessment of a non-species-specific calibration for the TTD method with diffuse porous media. In conclusion, our results showed that the TTD method can be directly applied

  4. SNIFFER: a System that Understands Bugs.

    Science.gov (United States)

    1981-06-01

    further inbrmation. If the bug the sniffer knows about is present, it proditces a detailed error report. This jcporr includes a high level sutmmary of...he ILisp Machine was chosen h,’c,tte it has the high speed and Lirgc rtinco l ic keuired hN Snilffer. The programs Sibl1ttd to tihe S.,ilml eiCl 1,0...are only two ways to compare objects. One can ask if’ they are eq. mecaning that they ha~e the same name or address 0% hich is equivalent to asking if

  5. Evaluation of the Flying Qualities Requirements of MIL-F-8785B (ASG) using the C-5A Airplane

    Science.gov (United States)

    1975-03-20

    ft. . * CA1&.;J’.7 TAKEOIF KT 4firi 5~ttdW v C dPOAC( Q-%) 111 V 1S 0.000 ft .11 2.0 , Aproach Spe j ta H LmI) a N.) r--AI f v 10.OOaft. .1 2.0 56 C...35 70 Cor.mpor i son For the C-5A airplane, this requirement translates into the following: Maximum Wheel Minimum Wheel Level Categor Force force A

  6. Comparative effectiveness of early-line nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer: a US community-based real-world analysis

    Directory of Open Access Journals (Sweden)

    Mahtani RL

    2018-02-01

    Full Text Available Reshma L Mahtani,1 Monika Parisi,2 Stefan Glück,3 Quanhong Ni,2 Siyeon Park,4 Corey Pelletier,2 Claudio Faria,2 Fadi Braiteh5,6 1Division of Hematology/Oncology, University of Miami, Miami, FL, 2Health Economics and Outcomes Research, Celgene Corporation, Summit, NJ, 3Global Medical Affairs, Celgene Corporation, Summit, NJ, 4School of Pharmacy, The Ohio State University, Columbus, OH, 5Department of Hematology/Oncology, University of Nevada School of Medicine, Las Vegas, NV, 6Department of Hematology/Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA.Methods: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014. The clinical efficacy objectives were time to treatment discontinuation (TTD and time to next treatment (TTNT. Subgroup analyses were performed in patients with 2 types of metastatic breast cancer as follows: 1 hormone receptor-positive and human epidermal growth factor receptor 2 negative, and 2 triple-negative disease. Results: This analysis included 925 patients. Patients receiving nab-paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8 months, P<0.0001 and TTNT (median 6.0 vs. 4.2 months, P<0.0001; similar outcomes were observed for patients with hormone receptor-positive/human epidermal growth factor receptor 2 negative disease. Compared with paclitaxel, nab-paclitaxel was associated with significantly longer TTD in patients with triple

  7. The performance of 4 different supplements and 5 blood culture bottles types in detection of bacteria and Candida spp. in simulated sterile body fluid cultures.

    Science.gov (United States)

    Nylén, Therese; Saeedi, Baharak; Borg, Camilla; Ullberg, Måns; Özenci, Volkan

    2013-09-01

    The purpose of this investigation was to evaluate the performance of 4 supplements: horse blood, fastidious organisms supplement (FOS), haemin isovitalex albumine (HIA), and brain heart infusion-haemin isovitalex albumine (BHI-HIA) and 5 blood culture bottles: Bactec Mycosis IC/F, Plus Aerobic/F, Peds Plus/F from the Bactec 9240 system, and BacT/Alert FA and BacT/Alert PF from the BacT/Alert 3D system, in detection of bacteria and Candida spp. in simulated sterile body fluids other than blood models. In total, 8 reference strains (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Candida albicans, and Candida parapsilosis) and 11 clinical bacteria and yeast isolates (6 isolates from cerebrospinal fluid and 5 isolates from blood) were included in this study. Horse blood, FOS, and HIA were significantly better than no supplements (P culture bottles with horse blood had shorter time to detection (TTD) compared to bottles with FOS and HIA (P culture bottles with Candida spp. signaled positive even in the absence of supplements. Bactec Mycosis IC/F had significantly shorter TTD compared to Bactec Peds Plus/F, Bactec Plus Aerobic/F, BacT/Alert FA, and BacT/Alert PF bottles in detection of Candida spp. (P culture bottles that were analyzed in the study. © 2013.

  8. A Drosophila XPD model links cell cycle coordination with neuro-development and suggests links to cancer

    Directory of Open Access Journals (Sweden)

    Karin Stettler

    2015-01-01

    Full Text Available XPD functions in transcription, DNA repair and in cell cycle control. Mutations in human XPD (also known as ERCC2 mainly cause three clinical phenotypes: xeroderma pigmentosum (XP, Cockayne syndrome (XP/CS and trichothiodystrophy (TTD, and only XP patients have a high predisposition to developing cancer. Hence, we developed a fly model to obtain novel insights into the defects caused by individual hypomorphic alleles identified in human XP-D patients. This model revealed that the mutations that displayed the greatest in vivo UV sensitivity in Drosophila did not correlate with those that led to tumor formation in humans. Immunoprecipitations followed by targeted quantitative MS/MS analysis showed how different xpd mutations affected the formation or stability of different transcription factor IIH (TFIIH subcomplexes. The XP mutants most clearly linked to high cancer risk, Xpd R683W and R601L, showed a reduced interaction with the core TFIIH and also an abnormal interaction with the Cdk-activating kinase (CAK complex. Interestingly, these two XP alleles additionally displayed high levels of chromatin loss and free centrosomes during the rapid nuclear division phase of the Drosophila embryo. Finally, the xpd mutations showing defects in the coordination of cell cycle timing during the Drosophila embryonic divisions correlated with those human mutations that cause the neurodevelopmental abnormalities and developmental growth defects observed in XP/CS and TTD patients.

  9. Mechanisms and biological impact of DNA repair pathways for UV and {gamma}-ray-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Hoeijmakers, J.H.J. [MGC, Department of Cell Biology et Genetics, Erasmus Universtiy, Rotterdam (Netherlands)

    1997-03-01

    Nature has equipped all living systems with an intricate network of DNA repair pathways, to cope with damage induced by genotoxic agents (such as UV light, {gamma}-rays and numerous chemicals). These pathways ensure genome stability and prevent carcinogenesis. Examples of multi-step damage repair processes are: nucleotide excision repair (NER, for removal of a wide variety of lesions, including UV) and recombination repair (for elimination of the very genotoxic radiation-induced double strand breaks). The NER pathway is understood in great detail and is associated with three human syndromes characterized by marked sun sensitivity: xeroderma pigmentosum (XP), cockayne syndrome (CS) and tricho-thio-dystrophy (TTD), XP patients show an over 1000 x increased risk of skin cancer, in contrast to CS and TTD. At least 25 proteins re involved some are also implicated in other cellular processes, explaining puzzling features associated with defects in these genes. NER-deficient mouse mutants have been generated, that permit evaluation of the biological impact of this process. Recombination repair is much less understood. However, recently a number of genes has been cloned based on sequence homology with yeast genes and mouse mutants are being generated. These will be invaluable to investigate e.g. radioresistance and radiation-induced tumorigenesis and for radiotherapy. (author)

  10. XPD Helicase Structures And Activities: Insights Into the Cancer And Aging Phenotypes From XPD Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Fan, L.; Fuss, J.O.; Cheng, Q.J.; Arvai, A.S.; Hammel, M.; Roberts, V.A.; Cooper, P.K.; Tainer, J.A.

    2009-05-18

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  11. Genetics of human sensitivity to ultraviolet radiation

    Science.gov (United States)

    Cleaver, James E.

    1994-07-01

    the major human health effects of solar and artificial UV light occur from the UVB and UVC wavelength ranges and involve a variety of short-term and long-term deleterious changes to the skin and eyes. the more important initial damage to cellular macromolecules involves dimerization of adjacent pyrimidines in DNA to produce cyclobutane pyrimidine dimes, (6-4) pyrimidine- pyrimidone, and (6-4) dewar photoproducts. these photoproducts can be repaired by a genetically regulated enzyme system (nucleotide excision repair) which removes oligonucleotides 29-30 nucleotides long that contain the photoproducts, and synthesizes replacement patches. At least a dozen gene products are involved in the process of recognizing photoproducts in DNA, altering local DNA helicity and cleaving the polynucleotide chain at defined positions either side of a photoproduct. Hereditary mutations in many of these genes are recognized in the human genetic disorders xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Several of the gene products have other functions involving the regulation of gene transcription which accounts for the complex clinical presentation of repair deficient diseases that involve sensitivity of the skin and eyes to UV light, increased solar carcinogenesis (in XP), demyelination, and ganglial calcification (in CS), hair abnormalities (in TTD), and developmental and neurological abnormalities

  12. Time to career: Science and engineering education to career trajectories

    Science.gov (United States)

    Choi, Angie Nim

    Two waves of data from the 2006 and 2008 Survey of Earned Doctorates and Survey of Doctorate Recipients were used in this study to investigate time to doctorate (TTD) and time to career (TTC) for science and engineering PhDs. Three-way factorial ANOVAs were conducted, and TTD results indicated main effects for gender, US citizenship, and Biglan classification, and interaction effects for gender and US citizenship. US citizen PhDs progressed to their career approximately one mean year faster than foreign PhDs. For TTC, PhDs who held postdocs progressed to their careers in 14 and 15 years for females and males respectively compared to 19 years for those without postdoctoral appointments. PhDs working in academe also had shorter TTC rates than those working in industry or government settings. TTC rates were lowest for PhDs from engineering fields and highest for those from health sciences. A multiple linear regression based upon the 2006 data was also used to determine the best predictors of TTC based upon individual, academic, and employer characteristics, and the model was cross-validated with an independent sample from the 2008 data. The regression solution was significant, F (20, 11000) = 97.06, p effect size (R2 = .14), and the cross-validated model had a slightly higher effect (R2 = .28).

  13. Sobre la teoría impura del derecho

    Directory of Open Access Journals (Sweden)

    Danilo Rojas Betancourt

    2006-01-01

    Full Text Available La reseña hecha al libro del profesor Diego López, la Teoría impura del derecho, muestra algunos aspectos que debilitan la novedosa e importante tesis allí sostenida sobre la transformación de la teoría jurídica en Latinoamérica. En especial, señala que la particular apreciación de López sobre algunos tópicos kelsenianos deja demasiado expuesta la demostración que respecto de Kelsen proporciona como ejemplo de transformación teórica en Colombia. El reparo central radica en que la construcción hecha por López de lo que se denominaría regla de tanteo de la Teoría Transnacional del Derecho, TTD, toma como base una versión formalizada y no crítica de esta. Al hacerlo, López cae en la misma trampa que pretende mostrar como característica de la transformación local y que, conforme a la lectura estándar de cierta TTD, debe señalarse como incorrecta.

  14. XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Tainer, John; Fan, Li; Fuss, Jill O.; Cheng, Quen J.; Arvai, Andrew S.; Hammel, Michal; Roberts, Victoria A.; Cooper, Priscilla K.; Tainer, John A.

    2008-06-02

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  15. Factors Associated with Missed Detection of Mycobacterium tuberculosis by Automated BACTEC MGIT 960 System

    Directory of Open Access Journals (Sweden)

    Yu Pang

    2016-01-01

    Full Text Available Despite the demonstration of excellent performance, mycobacterial growth in BACTEC MGIT 960 can go undetected. The aim of this study was to investigate the prevalence of “false-negative” culture sample in Beijing and the potential factors associated with the detection failures by MGIT 960. Of the 577 sputum samples tested, 141 (24.4% were culture-positive for mycobacteria, of which 133 (94.3% were automatically determined by MGIT 960 system and 8 (5.7% were positive for visual growth (false negative by MGIT. Statistical analysis showed that positive grade of specimen had no influence on the false-negative rate by MGIT 960 system (χ2=2.207, P=0.820. In addition, the mean time to detection (TTD was 241.4 (range: 224–261 hours for false-negative group and 186.8 (range: 173–199 hours for positive group. The difference in TTD between false-negative and positive groups was statistically significant (P<0.01. In conclusion, our data demonstrate that the automatic MGIT missed a small portion of bacteriological mycobacterial patients. In addition, the poor growth rate rather than the low grade of AFB smear is associated with the detection failure by MGIT. Our findings highlight the notion that manual inspection for all instrument-negative MGIT tubes will bring about considerable benefit to patients and clinicians.

  16. Classification of ankle joint movements based on surface electromyography signals for rehabilitation robot applications.

    Science.gov (United States)

    Al-Quraishi, Maged S; Ishak, Asnor J; Ahmad, Siti A; Hasan, Mohd K; Al-Qurishi, Muhammad; Ghapanchizadeh, Hossein; Alamri, Atif

    2017-05-01

    Electromyography (EMG)-based control is the core of prostheses, orthoses, and other rehabilitation devices in recent research. Nonetheless, EMG is difficult to use as a control signal given the complex nature of the signal. To overcome this problem, the researchers employed a pattern recognition technique. EMG pattern recognition mainly involves four stages: signal detection, preprocessing feature extraction, dimensionality reduction, and classification. In particular, the success of any pattern recognition technique depends on the feature extraction stage. In this study, a modified time-domain features set and logarithmic transferred time-domain features (LTD) were evaluated and compared with other traditional time-domain features set (TTD). Three classifiers were employed to assess the two feature sets, namely linear discriminant analysis (LDA), k nearest neighborhood, and Naïve Bayes. Results indicated the superiority of the new time-domain feature set LTD, on conventional time-domain features TTD with the average classification accuracy of 97.23 %. In addition, the LDA classifier outperformed the other two classifiers considered in this study.

  17. Crash testing difference-smoothing algorithm on a large sample of simulated light curves from TDC1

    Science.gov (United States)

    Rathna Kumar, S.

    2017-09-01

    In this work, we propose refinements to the difference-smoothing algorithm for the measurement of time delay from the light curves of the images of a gravitationally lensed quasar. The refinements mainly consist of a more pragmatic approach to choose the smoothing time-scale free parameter, generation of more realistic synthetic light curves for the estimation of time delay uncertainty and using a plot of normalized χ2 computed over a wide range of trial time delay values to assess the reliability of a measured time delay and also for identifying instances of catastrophic failure. We rigorously tested the difference-smoothing algorithm on a large sample of more than thousand pairs of simulated light curves having known true time delays between them from the two most difficult 'rungs' - rung3 and rung4 - of the first edition of Strong Lens Time Delay Challenge (TDC1) and found an inherent tendency of the algorithm to measure the magnitude of time delay to be higher than the true value of time delay. However, we find that this systematic bias is eliminated by applying a correction to each measured time delay according to the magnitude and sign of the systematic error inferred by applying the time delay estimator on synthetic light curves simulating the measured time delay. Following these refinements, the TDC performance metrics for the difference-smoothing algorithm are found to be competitive with those of the best performing submissions of TDC1 for both the tested 'rungs'. The MATLAB codes used in this work and the detailed results are made publicly available.

  18. Performance of GCC- and AMDF-Based Time-Delay Estimation in Practical Reverberant Environments

    Directory of Open Access Journals (Sweden)

    Benesty Jacob

    2005-01-01

    Full Text Available Recently, there has been an increased interest in the use of the time-delay estimation (TDE technique to locate and track acoustic sources in a reverberant environment. Typically, the delay estimate is obtained through identifying the extremum of the generalized cross-correlation (GCC function or the average magnitude difference function (AMDF. These estimators are well studied and their statistical performance is well understood for single-path propagation situations. However, fewer efforts have been reported to show their performance behavior in real reverberation conditions. This paper reexamines the GCC- and AMDF-based TDE techniques in real room reverberant and noisy environments. Our contribution is threefold. First, we propose a weighted cross-correlation (WCC estimator in which the GCC function is weighted by the reciprocal of AMDF. This new method can sharpen the peak of the GCC function, which corresponds to the true time delay and thus leads to a better estimation performance as compared to the conventional GCC estimator. Second, we propose a modified version of the AMDF (MAMDF estimator in which the delay is determined by jointly considering the AMDF and the average magnitude sum function (AMSF. Third, we compare the performance of the GCC, AMDF, WCC, and MAMDF estimators in real reverberant and noisy environments. It is shown that the AMDF estimator can yield better performance in favorable noise conditions and is slightly more resilient to reverberation than the GCC method. The GCC approach, however, is found to outperform the AMDF method in strong noisy environments. Weighting the correlation function by the reciprocal of AMDF can improve the performance of the GCC estimator in reverberation conditions, yet its improvement in noisy environments is limited. The MAMDF algorithm can enhance the AMDF estimator in both reverberant and noisy environments.

  19. Anthropogenic carbon dioxide in the South Atlantic western basin

    Science.gov (United States)

    Ríos, Aida F.; Vázquez-Rodríguez, Marcos; Padin, X. A.; Pérez, Fiz F.

    2010-10-01

    The meridional WOCE line A17 was conducted during the austral summer of 1994 parallel to the eastern South American coast, from 55°S to 10°S, where one of the main limbs of the North Atlantic Deep Water (NADW), i.e., the southward-flowing Deep Western Boundary Current (DWBC) is found. Full-depth profiles of pH, total alkalinity and total inorganic carbon were measured and checked with analytical CO 2 certified reference materials (CRMs), providing a high-quality dataset with good internal consistency for the CO 2 system parameters that is well suited for anthropogenic CO 2 (C ANT) estimation. For the first time in the western Atlantic basin the C ANT has been calculated using four independent approaches and results are compared. The methods considered are the CFC-based TTD method and the φC T°, TrOCA and ∆C* carbon system-based back-calculation methods. All four methods have produced C ANT distribution patterns that are in general good agreement: maximum concentrations of C ANT (50-60 μmol kg - 1 ) are predicted for the upper warm South Atlantic central waters from the tropical gyres, while the minima (~ 5 μmol kg - 1 ) are located in the old northward-flowing branch of Circumpolar Deep Water. There are, however, some discrepancies detected. The TrOCA method yields the highest overall [C ANT] values, even over the theoretical limit of C ANT saturation for 1994 in the upper layers. The ∆C* approach consistently yielded negative estimates of C ANT below 2800 dbar, even after correcting a reported - 8 μmol kg - 1 bias in the alkalinity measurements of the WOCE A17 line. The main overall difference between the four methods corresponds to the relative C ANT maximum associated with the lower limb of NADW: this structure is well identified in the φC T° and TTD methods but seems to disappear in the case of TrOCA and ∆C*. In agreement with other intercomparison studies of C ANT, the specific inventories are significantly higher (~ 45%) than those reported in

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

    DEFF Research Database (Denmark)

    Andersen, Ole; Aaseth, Jan

    2016-01-01

    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...... 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...

  1. Reviews

    Directory of Open Access Journals (Sweden)

    Ramsey Baker

    1999-12-01

    Full Text Available This book is written from the viewpoint that learning technology, although perceived of immense value, is not being exploited to its full potential, nor are its effects on student learning fully understood. Obtaining as accurate a picture as possible in order to correctly to influence policy and practice is an activity that is rightly receiving increased attention. No one could expect a 'how to do it' book for this subject area.as outcomes (be they of learning, cost-effectiveness or of more abstract influence are dictated by a wide range of factors. Martin Oliver (from the LaTTD group at the University of North London has gathered a wide range of interesting papers (derived from the Evaluation of Learning Technologies conference, 1998 to demonstrate the diversity of approaches in this field. The book comprises some 242 pages that are arranged into 14 chapters, written by those involved in related projects.

  2. Global patterns of amphibian phylogenetic diversity

    DEFF Research Database (Denmark)

    Fritz, Susanne; Rahbek, Carsten

    2012-01-01

    phylogeny (2792 species). We combined each tree with global species distributions to map four indices of phylogenetic diversity. To investigate congruence between global spatial patterns of amphibian species richness and phylogenetic diversity, we selected Faith’s phylogenetic diversity (PD) index......Aim  Phylogenetic diversity can provide insight into how evolutionary processes may have shaped contemporary patterns of species richness. Here, we aim to test for the influence of phylogenetic history on global patterns of amphibian species richness, and to identify areas where macroevolutionary...... and the total taxonomic distinctness (TTD) index, because we found that the variance of the other two indices we examined (average taxonomic distinctness and mean root distance) strongly depended on species richness. We then identified regions with unusually high or low phylogenetic diversity given...

  3. Design of a Local Computer Network for the Air Force Institute of Technology Digital Engineering Laboratory.

    Science.gov (United States)

    1981-03-01

    4ver Pm&, N( 1.6.2 1.6.4Flace 1= I-Fraw b-sy N(R) v&kkw ?6n" n- in X.25 Link- -Fd.,e 3 ?OCIZOIL QLXxle - TArdaed I-Prane 1 6 5 IR C,37,.TTd sci, ;t Rad...n O2 C4t 01 0 14 00 0 o 0 NC Q 0 1, cZ 0 C, 11 0- OtI -S-t -- t w.L. iS r cr2-9214 0 . CCcc U. 0n In t 00 C2 at -A I 2 .4A 0 0 0 11- < C CC 4 CC(40 < o

  4. "Can you see me now?" An objective metric for predicting intelligibility of compressed American Sign Language video

    Science.gov (United States)

    Ciaramello, Francis M.; Hemami, Sheila S.

    2007-02-01

    For members of the Deaf Community in the United States, current communication tools include TTY/TTD services, video relay services, and text-based communication. With the growth of cellular technology, mobile sign language conversations are becoming a possibility. Proper coding techniques must be employed to compress American Sign Language (ASL) video for low-rate transmission while maintaining the quality of the conversation. In order to evaluate these techniques, an appropriate quality metric is needed. This paper demonstrates that traditional video quality metrics, such as PSNR, fail to predict subjective intelligibility scores. By considering the unique structure of ASL video, an appropriate objective metric is developed. Face and hand segmentation is performed using skin-color detection techniques. The distortions in the face and hand regions are optimally weighted and pooled across all frames to create an objective intelligibility score for a distorted sequence. The objective intelligibility metric performs significantly better than PSNR in terms of correlation with subjective responses.

  5. Prophylactic pinning for slipped capital femoral epiphysis: does it affect proximal femoral morphology?

    Science.gov (United States)

    Cousins, Gerard R; Campbell, Donald M; Wilson, Neil I L; Maclean, Jamie G B

    2016-05-01

    This study was designed to determine whether prophylactic pinning of the unaffected hip in unilateral slipped capital femoral epiphysis affects the proximal femoral morphology. Twenty-four hips prophylactically pinned were compared with 26 cases observed. The articulotrochanteric distance (ATD) and the trochanteric-trochanteric distance (TTD) were measured. Postoperative radiographs were compared with final follow-up radiographs. The final TTD : ATD ratio was higher (P=0.048) in the pinned group, suggesting relative coxa vara/breva. There was a smaller difference between the two hips in the prophylactically pinned group (0.7) as opposed to those observed (1.47). Prophylactic pinning does not cause growth to stop immediately but alters the proximal femoral morphology.

  6. Rapid culture-based detection of living mycobacteria using microchannel electrical impedance spectroscopy (m-EIS).

    Science.gov (United States)

    Kargupta, Roli; Puttaswamy, Sachidevi; Lee, Aiden J; Butler, Timothy E; Li, Zhongyu; Chakraborty, Sounak; Sengupta, Shramik

    2017-06-10

    Multiple techniques exist for detecting Mycobacteria, each having its own advantages and drawbacks. Among them, automated culture-based systems like the BACTEC-MGIT™ are popular because they are inexpensive, reliable and highly accurate. However, they have a relatively long "time-to-detection" (TTD). Hence, a method that retains the reliability and low-cost of the MGIT system, while reducing TTD would be highly desirable. Living bacterial cells possess a membrane potential, on account of which they store charge when subjected to an AC-field. This charge storage (bulk capacitance) can be estimated using impedance measurements at multiple frequencies. An increase in the number of living cells during culture is reflected in an increase in bulk capacitance, and this forms the basis of our detection. M. bovis BCG and M. smegmatis suspensions with differing initial loads are cultured in MGIT media supplemented with OADC and Middlebrook 7H9 media respectively, electrical "scans" taken at regular intervals and the bulk capacitance estimated from the scans. Bulk capacitance estimates at later time-points are statistically compared to the suspension's baseline value. A statistically significant increase is assumed to indicate the presence of proliferating mycobacteria. Our TTDs were 60 and 36 h for M. bovis BCG and 20 and 9 h for M. smegmatis with initial loads of 1000 CFU/ml and 100,000 CFU/ml respectively. The corresponding TTDs for the commercial BACTEC MGIT 960 system were 131 and 84.6 h for M. bovis BCG and 41.7 and 12 h for M smegmatis, respectively. Our culture-based detection method using multi-frequency impedance measurements is capable of detecting mycobacteria faster than current commercial systems.

  7. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy.

    Science.gov (United States)

    Felip, Enriqueta; Hirsh, Vera; Popat, Sanjay; Cobo, Manuel; Fülöp, Andrea; Dayen, Charles; Trigo, José M; Gregg, Richard; Waller, Cornelius F; Soria, Jean-Charles; Goss, Glenwood D; Gordon, James; Wang, Bushi; Palmer, Michael; Ehrnrooth, Eva; Gadgeel, Shirish M

    2017-06-23

    In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented. Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d). PROs were collected (baseline, every 28 days until progression, 28 days after discontinuation) using the European Organization for Research and Treatment of Cancer QoL questionnaire and lung cancer-specific module. The percentage of patients improved during therapy, time to deterioration (TTD), and changes over time were analyzed for prespecified lung cancer-related symptoms and global health status (GHS)/QoL. Questionnaire compliance was 77.3% to 99.0% and 68.7% to 99.0% with afatinib and erlotinib, respectively. Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL (36% vs. 28%; P = .041) and cough (43% vs. 35%; P = .029). Afatinib significantly delayed TTD in dyspnea (P = .008) versus erlotinib, but not cough (P = .256) or pain (P = .869). Changes in mean scores favored afatinib for cough (P = .0022), dyspnea (P = .0007), pain (P = .0224), GHS/QoL (P = .0320), and all functional scales. Differences in adverse events between afatinib and erlotinib, specifically diarrhea, did not affect GHS/QoL. In patients with SCC of the lung, second-line afatinib was associated with improved prespecified disease-related symptoms and GHS/QoL versus erlotinib, complementing PFS and OS benefits with afatinib. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Ventilation of the Arctic Ocean: Mean ages and inventories of anthropogenic CO2 and CFC-11

    Science.gov (United States)

    Tanhua, Toste; Jones, E. Peter; Jeansson, Emil; JutterströM, Sara; Smethie, William M.; Wallace, Douglas W. R.; Anderson, Leif G.

    2009-01-01

    The Arctic Ocean constitutes a large body of water that is still relatively poorly surveyed because of logistical difficulties, although the importance of the Arctic Ocean for global circulation and climate is widely recognized. For instance, the concentration and inventory of anthropogenic CO2 (Cant) in the Arctic Ocean are not properly known despite its relatively large volume of well-ventilated waters. In this work, we have synthesized available transient tracer measurements (e.g., CFCs and SF6) made during more than two decades by the authors. The tracer data are used to estimate the ventilation of the Arctic Ocean, to infer deep-water pathways, and to estimate the Arctic Ocean inventory of Cant. For these calculations, we used the transit time distribution (TTD) concept that makes tracer measurements collected over several decades comparable with each other. The bottom water in the Arctic Ocean has CFC values close to the detection limit, with somewhat higher values in the Eurasian Basin. The ventilation time for the intermediate water column is shorter in the Eurasian Basin (˜200 years) than in the Canadian Basin (˜300 years). We calculate the Arctic Ocean Cant inventory range to be 2.5 to 3.3 Pg-C, normalized to 2005, i.e., ˜2% of the global ocean Cant inventory despite being composed of only ˜1% of the global ocean volume. In a similar fashion, we use the TTD field to calculate the Arctic Ocean inventory of CFC-11 to be 26.2 ± 2.6 × 106 moles for year 1994, which is ˜5% of the global ocean CFC-11 inventory.

  9. Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Bussink, Johan, E-mail: j.bussink@rther.umcn.nl [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

    2012-08-01

    Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

  10. Dairy cows fed on tropical legume forages: effects on milk yield, nutrients use efficiency and profitability.

    Science.gov (United States)

    Castro-Montoya, J M; García, R A; Ramos, R A; Flores, J M; Alas, E A; Corea, E E

    2018-01-02

    Two trials with multiparous dairy cows were conducted. Experiment 1 tested the effects of increasing forage proportion in the diet (500, 600, and 700 g/kg DM) when a mixed sorghum (Sorghum bicolor) and jackbean (Cannavalia ensiformis) silage was used as forage. Experiment 2 studied the substitution of sorghum silage and soybean meal by jackbean silage or fresh cowpea (Vigna unguiculata) forage in the diet. All diets were iso-energetic and iso-proteic. In each experiment, 30 cows were used and separated into three groups. In experiment 1, there were no differences in dry matter intake (DMI), milk yield (MY), or apparent total tract digestibility (aTTd) among the three diets, but milk fat content increased with increasing forage proportion, even though the similar neutral detergent fiber of all diets. Nitrogen use efficiency was highest in the diet containing 600 g forage/kg DM, and some evidence was observed for a better profitability with this forage proportion. In experiment 2, feeding legumes increased DMI despite no effects on aTTd. Milk yield increased in line with DMI, with a larger increase for the fresh cowpea. Nitrogen use efficiency and milk composition were not affected by the diets. The increased MY and lower feed costs increased the economic benefits when feeding legumes, particularly when feeding fresh cowpea. Feeding fresh cowpea or jackbean silage to dairy cows appears to be an alternative to soybean as protein source, ideally at a forage proportions of 600 g/kg DM, without altering milk yield and quality and increasing the farm profitability.

  11. Using tracer-derived groundwater transit times to assess storage within a high-elevation watershed of the upper Colorado River Basin, USA

    Science.gov (United States)

    Georgek, Jennifer L.; Kip Solomon, D.; Heilweil, Victor M.; Miller, Matthew P.

    2017-08-01

    Previous watershed assessments have relied on annual baseflow to evaluate the groundwater contribution to streams. To quantify the volume of groundwater in storage, additional information such as groundwater mean transit time (MTT) is needed. This study determined the groundwater MTT in the West Fork Duchesne watershed in Utah (USA) with lumped-parameter modeling of environmental tracers (SF6, CFCs, and 3H/3He) from 21 springs. Approximately 30% of the springs exhibited an exponential transit time distribution (TTD); the remaining 70% were best characterized by a piston-flow TTD. The flow-weighted groundwater MTT for the West Fork watershed is about 40 years with approximately 20 years in the unsaturated zone. A cumulative distribution of these ages revealed that most of the groundwater is between 30 and 50 years old, suggesting that declining recharge associated with 5-10-year droughts is less likely to have a profound effect on this watershed compared with systems with shorter MTTs. The estimated annual baseflow of West Fork stream flow based on chemical hydrograph separation is 1.7 × 107 m3/year, a proxy for groundwater discharge. Using both MTT and groundwater discharge, the volume of mobile groundwater stored in the watershed was calculated to be 6.5 × 108 m3, or 20 m thickness of active groundwater storage and recharge of 0.09 m/year (assuming porosity = 15%). Future watershed-scale assessments should evaluate groundwater MTT, in addition to annual baseflow, to quantify groundwater storage and more accurately assess watershed susceptibility to drought, groundwater extraction, and land-use change.

  12. Population ageing and healthcare expenditure projections: new evidence from a time to death approach.

    Science.gov (United States)

    Geue, Claudia; Briggs, Andrew; Lewsey, James; Lorgelly, Paula

    2014-11-01

    Health care expenditure (HCE) is not distributed evenly over a person's life course. How much is spent on the elderly is important as they are a population group that is increasing in size. However other factors, such as death-related costs that are known to be high, need be considered as well in any expenditure projections and budget planning decisions. This article analyses, for the first time in Scotland, how expenditure projections for acute inpatient care are influenced when applying two different analytical approaches: (1) accounting for healthcare (HC) spending at the end of life and (2) accounting for demographic changes only. The association between socioeconomic status and HC utilisation and costs at the end of life is also estimated. A representative, longitudinal data set is used. Survival analysis is employed to allow inclusion of surviving sample members. Cost estimates are derived from a two-part regression model. Future population estimates were obtained for both methods and multiplied separately by cost estimates. Time to death (TTD), age at death and the interaction between these two have a significant effect on HC costs. As individuals approach death, those living in more deprived areas are less likely to be hospitalised than those individuals living in the more affluent areas, although this does not translate into incurring statistically significant higher costs. Projected HCE for acute inpatient care for the year 2028 was approximately 7% higher under the demographic approach as compared to a TTD approach. The analysis showed that if death is postponed into older ages, HCE (and HC budgets) would not increase to the same extent if these factors were ignored. Such factors would be ignored if the population that is in their last year(s) of life were not taken into consideration when obtaining cost estimates.

  13. PEMANFAATAN KOLAM PENGENDAP TAMBANG BATUBARA UNTUK BUDIDAYA IKAN LOKAL DALAM KERAMBA

    Directory of Open Access Journals (Sweden)

    Asfie Maidie

    2016-11-01

    Full Text Available Uji coba budidaya dalam keramba telah dilakukan untuk mengetahui kelayakan kolam pengendap tambang batubara untuk areal budidaya ikan bagi masyarakat sekitar apabila kegiatan tambang telah ditutup, serta untuk mengetahui apakah produk ikan yang dihasilkan cukup aman untuk dikonsumsi manusia. Percobaan dilakukan pada bekas kolam pengendap DS2 milik PT KPC, dengan mengunakan 5 buah keramba apung berukuran 3 m x 1 m x 1 m yang dalam setiap keramba ditebar benih dari alam untuk ikan repang (Barbodes schwanenfeldii ukuran rata-rata 20,2 g; puyau (Osteichilus kappenii ukuran 66,1 g; dan mas (Cyprinus carpio ukuran 28,96 g dari pemijahan di laboratorium sebanyak masing-masing 200 ekor, serta pepuyu (Anabas testudineus ukuran rata-rata 41,4 g dari alam sebanyak 50 ekor, udang galah (Macrobrachium rosenbergii ukuran 113,8 g juga dari alam sebanyak 50 ekor. Pakan diberikan secara sampai kenyang (ad libitum. DO, pH, suhu, DHL, dan kekeruhan diukur harian, sedangkan ikan diukur pertumbuhan bobotnya. Setelah dipelihara selama 4 bulan dan memenuhi ukuran konsumsi, ikan dan udang diperiksa kandungan Sb, Se, As, Hg, Mn, Cd, Fe, Cu, Pb, dan Zn. Hasil penelitian menunjukkan bahwa bekas kolam pengendap tambang batubara cukup layak untuk dikembangkan sebagai areal budidaya ikan dengan memberikan pertumbuhan bobot populasi sebesar 570,79% (repang, SR: 95%, 202,57% (puyau, SR: 97%, 573% (mas, SR: 2,5%, 238,92% (udang galah, SR: 10%, 447,10% (pepuyu, SR: 14% dan produknya cukup aman untuk dikonsumsi, dengan kandungan Sb (0,24-2,45 mg/L, rasio terdeteksi dari sample: 100%, Se (0,00-0,06, 57,14%, As (tidak terdeteksi/ttd, Hg (0,00-0,06 mg/L, 50%, Mn (ttd-1,68 mg/L, 14,29%, Cd (ttd, Fe (ttd-5,45 mg/L, 7,14%, Cu (ttd, Pb (ttd, dan Zn (7,82-61,50 mg/L, 100%. The experiment was conducted to study the feasibility of settling or sedimentation pond of coal mining to be used for culturing fish in net cage for local people post  mining activities. Experimental 3 m x 1 m x 1 m

  14. Slow and Fast Light in Semiconductor Quantum-Well and Quantum-Dot Devices

    Science.gov (United States)

    Chang-Hasnain, Connie J.; Chuang, Shun Lien

    2006-12-01

    The ability to manipulate the speed of light has recently become one of the most exciting emergent topics in optics. There are several experimental demonstrations showing the capability to slow down light more than six orders of magnitude in a variety of media, ranging from atomic vapor, solid state crystal, to semiconductors. These results have led to intensive research into new materials, devices, and system studies that examine their impact to new applications. It is believed that we are on the verge of a dramatic change in the way we envision and construct communication, processing and control systems. One direct application of slow and fast light devices is in the area of communications. One grand challenge remaining in information technology today is to store and buffer optical signals directly in optical format. As such, optical signals must be converted to electronic signals to route, switch, or be processed. This resulted in significant latencies and traffic congestions in current networks. In addition, keeping the data in optical domain during the routing process can greatly reduce the power, complexity and size of the routers. To this end, a controllable optical delay line can effectively function as an optical buffer, and the storage is proportional to the variability of the group velocity. In addition to optical buffers, slow and fast light devices can be used as tunable true-time delay elements in microwave photonics, which are important for remotely controlling phased array antenna. Other novel applications include nonlinear optics, optical signal processing, and quantum information processing. There are various approaches that can be used to vary the optical group velocity. Ultraslow or fast group velocity may result from a large material dispersion, waveguide dispersion, or both. In this paper, the authors provide a review of recent progress of slow and fast light using semiconductor devices. Specifically, they will discuss results obtained using

  15. Wideband aperture array using RF channelizers and massively parallel digital 2D IIR filterbank

    Science.gov (United States)

    Sengupta, Arindam; Madanayake, Arjuna; Gómez-García, Roberto; Engeberg, Erik D.

    2014-05-01

    Wideband receive-mode beamforming applications in wireless location, electronically-scanned antennas for radar, RF sensing, microwave imaging and wireless communications require digital aperture arrays that offer a relatively constant far-field beam over several octaves of bandwidth. Several beamforming schemes including the well-known true time-delay and the phased array beamformers have been realized using either finite impulse response (FIR) or fast Fourier transform (FFT) digital filter-sum based techniques. These beamforming algorithms offer the desired selectivity at the cost of a high computational complexity and frequency-dependant far-field array patterns. A novel approach to receiver beamforming is the use of massively parallel 2-D infinite impulse response (IIR) fan filterbanks for the synthesis of relatively frequency independent RF beams at an order of magnitude lower multiplier complexity compared to FFT or FIR filter based conventional algorithms. The 2-D IIR filterbanks demand fast digital processing that can support several octaves of RF bandwidth, fast analog-to-digital converters (ADCs) for RF-to-bits type direct conversion of wideband antenna element signals. Fast digital implementation platforms that can realize high-precision recursive filter structures necessary for real-time beamforming, at RF radio bandwidths, are also desired. We propose a novel technique that combines a passive RF channelizer, multichannel ADC technology, and single-phase massively parallel 2-D IIR digital fan filterbanks, realized at low complexity using FPGA and/or ASIC technology. There exists native support for a larger bandwidth than the maximum clock frequency of the digital implementation technology. We also strive to achieve More-than-Moore throughput by processing a wideband RF signal having content with N-fold (B = N Fclk/2) bandwidth compared to the maximum clock frequency Fclk Hz of the digital VLSI platform under consideration. Such increase in bandwidth is

  16. [Efficacy of albumin-bound paclitaxel in advanced gastric cancer patients].

    Science.gov (United States)

    Gong, Ji-fang; Lu, Ming; Li, Jie; Li, Yan; Zhou, Jun; Lu, Zhi-hao; Wang, Xi-cheng; Li, Jian; Zhang, Xiao-tian; Shen, Lin

    2014-02-18

    To evaluate the safety and efficacy of albumin-bound paclitaxel in patients with advanced gastric cancer (AGC). The patients with histopathologic or cytopathologic diagnosed advanced gastric cancer (AGC), Karnofsky performance status ≥ 60, and life expectancy >12 weeks, and with adequate organ functions of the bone marrow, liver, kidney and heart were recuited in our study. albumin-bound paclitaxel was administered alone or combined with capecitabine, TS-1, trastuzumab or cetuxizumb. The total doses of albumin-bound paclitaxel were 200-400 mg (130-260 mg/m(2)), divided on days 1, 8 or days 1,8, and 15, given intravenously during 30 minutes of a 21-day cycle. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The adverse events (AE) were graded according to National Cancer Institute-Common Toxicity Criteria (NCI-CTC) 3.0 version. From July 2009 to Octobor 2012, the total of 25 patients were treated and completed 65 cycles of chemotherapy (median: 2 cycles, and range: 0.5-7). The median age was 57 years (range: 38-79). The majority of the patients were with non-gastroesophageal junction cancers and had metastasic disease with lymph nodes and peritoneum. Eleven patients were chemotherapy naive and the others had accepted previous systemic therapy for advanced disease. 16 patients were evaluable for clinical response. No complete response was observed and partial response (PR) was achieved in 5 patients. Five patients had stable disease and 6 patients progressed. Among the chemotherapy naive patients, 8 patients were evaluable for response, 3 patients had partial response (37.5%) and 1 patient had stable disease (tumor shrink). The clinical response rate was 50%. Time to treatment failure (TTF)was 3.7 months(95% CI 2.32-5.08) and time to death (TTD)was 7.9 months (95% CI 5.17-10.63). No statistical differences in TTF and TTD were observed between the untreated and the retreated patients or the monotherapy and the

  17. Toward a definition and method of assessment of treatment failure and treatment effectiveness: the case of leflunomide versus methotrexate.

    Science.gov (United States)

    Wolfe, Frederick; Michaud, Kaleb; Stephenson, Barbara; Doyle, Joseph

    2003-08-01

    Time to treatment discontinuation (TTD) is an accepted method of assessing treatment effectiveness in the community, but is susceptible to channeling bias and secular and cohort effects. In addition, TTD does not consider the addition of new disease modifying antirheumatic drugs (DMARD) to insufficiently effective therapies. We expand the definition of treatment failure to include discontinuation or addition of a second DMARD (1) to examine leflunomide (LEF) versus methotrexate (MTX) effectiveness in clinical practice; (2) to obtain an estimate of overall clinical effectiveness; and (3) to identify factors associated with treatment successes and failure. In addition, (4) we test the feasibility of performing a clinical trial using a longitudinal data bank. Using the National Data Bank for Rheumatic Diseases longitudinal data bank, 1431 patients with rheumatoid arthritis (RA) who began taking LEF or MTX as part of their routine medical care were followed from 1998 through 2001. None of the 1431 patients had received either treatment previously. Patients were assessed at 6 month intervals for periods up to 36 months by mailed questionnaires concerning DMARD therapy and demographic and RA severity factors. Kaplan-Meier survivor functions and Cox regression analyses were used to assess treatment failure, defined as time to discontinuation or to the addition of a second DMARD. For 756 patients taking LEF, the failure rate was 55.5 per 100 patient-years, and the median time to failure was 15 (95% CI 13, 17) months. For 675 patients taking MTX the failure rate was 57.3 per 100 patient-years, and the median failure time was 14 (95% CI 12, 18) months. These differences were not statistically significant. The overall rate of discontinuation was 68.7% of the failure rate. Discontinuation was predicted by adverse effects [hazard ratio 1.76 (95% CI 1.51, 2.04)] and by clinical status prior to starting DMARD, and these results were not affected by specific DMARD treatment

  18. A toolbox for tuberculosis diagnosis: an Indian multicentric study (2006-2008: microbiological results.

    Directory of Open Access Journals (Sweden)

    Philippe H Lagrange

    Full Text Available BACKGROUND: The aim of this multicentric prospective study in India was to assess the value of several microbiological tools that contribute to the diagnosis of tuberculosis (TB according to HIV status. METHODS: Standard microbiological tools on individual specimens were analyzed. RESULTS: Among the 807 patients with active TB, 131 were HIV-infected, 316 HIV-uninfected and 360 had HIV-unknown status. Among the 980 non-active TB subjects, 559 were at low risk and 421 were at high risk of M. tuberculosis (Mtb exposure. Sensitivity of smear microscopy (SM was significantly lower in HIV-infected (42.2% than HIV-uninfected (75.9% (p = 0.0001 and HIV-unknown pulmonary TB patients (61.4% (p = 0.004. Specificity was 94.5% in non-TB patients and 100% in health care workers (HCW and healthy family contacts. Automated liquid culture has significantly higher diagnostic performances than solid culture, measured by sensitivity (74.7% vs. 55.9% (p = 0.0001 and shorter median time to detection (TTD (12.0 vs. 34.0 days (p = 0.0001. Specificity was 100% in HCW and cured-TB patients, but was lower in non-TB patients (89% due to isolation of Mycobacteria other than tuberculosis (MOTT. TTD by both methods was related to AFB score. Contamination rate was low (1.4%. AccuProbe hybridization technique detected Mtb in almost all culture-positive specimens, but MOTT were found in 4.7% with a significantly higher frequency in HIV-infected (15% than HIV-uninfected TB patients (0.5% (p = 0.0007. Pre-test classification significantly increased the diagnostic value of all microbiological tests in pulmonary TB patients (p<0.0001 but to a lesser degree in extrapulmonary TB patients. CONCLUSIONS: Conventional microbiological tools led to results similar to those already described in India special features for HIV-infected TB patients included lower detection by SM and culture. New microbiological assays, such as the automated liquid culture system, showed increased accuracy and

  19. Resistance to water pollution in natural gudgeon (Gobio gobio) populations may be due to genetic adaptation.

    Science.gov (United States)

    Knapen, Dries; Bervoets, Lieven; Verheyen, Erik; Blust, Ronny

    2004-04-14

    Anthropogenic disturbances cause the environment to change relatively fast. It is reasonable to assume that it is very unlikely for individuals to develop genetic adaptations to their polluted habitats, since adaptation through natural selection is a relatively slow process. Nevertheless, several studies have shown that such adaptations to changing environmental conditions may develop faster than anticipated. This study investigates the impact of historical metal pollution on a natural population of the gudgeon, Gobio gobio. Specimens from a contaminated site and a reference population were subjected to a series of three exposure experiments to cadmium after an acclimation period to reconstituted fresh water of 36 days. First, we performed an acute toxicity test on a sub-sample of both experimental groups to determine times-to-death (TTD) and lethal body burdens (LBB). The remaining individuals were used in a chronic Cd-exposure experiment, after which total Cd-body concentration, as well as Cd-concentrations and metallothionein-like protein (MTLP) levels in liver and gill tissue were determined. From the specimens that were not sacrificed for these measurements, a random subsample was subjected to a second acute toxicity test to evaluate the effect of chronic Cd-exposure (acclimation) on TTD and LBB. Our results show that, particularly after an extra acclimation period to a sublethal Cd-concentration, specimens originating from the contaminated sample area survived the acute exposure experiments better, despite the fact that neither the average Cd-accumulation rate, nor the lethal body concentrations differed between fishes from both groups. We also find that gudgeons from both populations translocated Cd from the gills (and probably also from other compartments) to the liver, where it can be more efficiently detoxified by MTLPs. Indeed, MTLP levels were found to increase faster in liver and gill tissue of specimens from the contaminated site, resulting in

  20. Inactive xylem can explain differences in calibration factors for thermal dissipation probe sap flow measurements.

    Science.gov (United States)

    Paudel, Indira; Kanety, Tal; Cohen, Shabtai

    2013-09-01

    Thermal dissipation probes (TDPs) were calibrated in three diffuse porous fruit trees and one ornamental species in the field by comparison with heat pulse probes (nectarine and persimmon), in a greenhouse on lysimeters (apple and persimmon) and in the laboratory by pushing water through cut branches (apple, Peltophorum and nectarine). Two operational methods were used: continuous (constant thermal dissipation, CTD) and discontinuous, or transient, heating (transient thermal dissipation, TTD). Correction for the radial distribution of sap flux density was with an analytical function derived from a linear decrease in flux density with depth, as measured with a multi-depth 'Tmax' heat pulse system. When analyzed with previous calibration factors, the measured sap flow was sap flow using heat dissipation probes. Tree Physiol 1999;19:681-687) almost completely compensated for the underestimations. Calibrations are given for each species both before and after corrections of temperature differentials, along with a multispecies calibration. These results should be an important step in reconciling many reports of different calibration factors for TDP probes.

  1. Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms

    Directory of Open Access Journals (Sweden)

    Diletta Edifizi

    2015-08-01

    Full Text Available DNA damage causally contributes to aging and cancer. Congenital defects in nucleotide excision repair (NER lead to distinct cancer-prone and premature aging syndromes. The genetics of NER mutations have provided important insights into the distinct consequences of genome instability. Recent work in mice and C. elegans has shed new light on the mechanisms through which developing and aging animals respond to persistent DNA damage. The various NER mouse mutants have served as important disease models for Xeroderma pigmentosum (XP, Cockayne syndrome (CS, and trichothiodystrophy (TTD, while the traceable genetics of C. elegans have allowed the mechanistic delineation of the distinct outcomes of genome instability in metazoan development and aging. Intriguingly, highly conserved longevity assurance mechanisms respond to transcription-blocking DNA lesions in mammals as well as in worms and counteract the detrimental consequences of persistent DNA damage. The insulin-like growth factor signaling (IIS effector transcription factor DAF-16 could indeed overcome DNA damage-driven developmental growth delay and functional deterioration even when DNA damage persists. Longevity assurance mechanisms might thus delay DNA damage-driven aging by raising the threshold when accumulating DNA damage becomes detrimental for physiological tissue functioning.

  2. Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms.

    Science.gov (United States)

    Edifizi, Diletta; Schumacher, Björn

    2015-08-13

    DNA damage causally contributes to aging and cancer. Congenital defects in nucleotide excision repair (NER) lead to distinct cancer-prone and premature aging syndromes. The genetics of NER mutations have provided important insights into the distinct consequences of genome instability. Recent work in mice and C. elegans has shed new light on the mechanisms through which developing and aging animals respond to persistent DNA damage. The various NER mouse mutants have served as important disease models for Xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD), while the traceable genetics of C. elegans have allowed the mechanistic delineation of the distinct outcomes of genome instability in metazoan development and aging. Intriguingly, highly conserved longevity assurance mechanisms respond to transcription-blocking DNA lesions in mammals as well as in worms and counteract the detrimental consequences of persistent DNA damage. The insulin-like growth factor signaling (IIS) effector transcription factor DAF-16 could indeed overcome DNA damage-driven developmental growth delay and functional deterioration even when DNA damage persists. Longevity assurance mechanisms might thus delay DNA damage-driven aging by raising the threshold when accumulating DNA damage becomes detrimental for physiological tissue functioning.

  3. Molecular regulation of UV-induced DNA repair.

    Science.gov (United States)

    Shah, Palak; He, Yu-Ying

    2015-01-01

    Ultraviolet (UV) radiation from sunlight is a major etiologic factor for skin cancer, the most prevalent cancer in the United States, as well as premature skin aging. In particular, UVB radiation causes formation of specific DNA damage photoproducts between pyrimidine bases. These DNA damage photoproducts are repaired by a process called nucleotide excision repair, also known as UV-induced DNA repair. When left unrepaired, UVB-induced DNA damage leads to accumulation of mutations, predisposing people to carcinogenesis as well as to premature aging. Genetic loss of nucleotide excision repair leads to severe disorders, namely, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS), which are associated with predisposition to skin carcinogenesis at a young age as well as developmental and neurological conditions. Regulation of nucleotide excision repair is an attractive avenue to preventing or reversing these detrimental consequences of impaired nucleotide excision repair. Here, we review recent studies on molecular mechanisms regulating nucleotide excision repair by extracellular cues and intracellular signaling pathways, with a special focus on the molecular regulation of individual repair factors. © 2014 The American Society of Photobiology.

  4. Actual state of knowledge in the field of diseases related with defective nucleotide excision repair.

    Science.gov (United States)

    Bukowska, Barbara; Karwowski, Bolesław T

    2018-02-15

    Xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS) are rare genetic diseases characterized by a large range of clinical symptoms. However, they are all associated with defects in nucleotide excision repair (NER), the system responsible for removing bulky DNA lesions such as those generated by UV light: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone photoproducts (6-4 PPs). Over the past years, detailed structural and biochemical information on NER-associated proteins has emerged. In the first part of the article we briefly present the main steps of the NER pathway with an emphasis on the precise role of certain proteins. Further, we focus on clinical manifestations of the disorders and describe the diagnostic procedures. Then we consider how current therapy and advanced technology could improve patients' quality of life. Although to date the discussed diseases remain incurable, effective sun protection, a well thought out diet, and holistic medical care provide longer life and better health. This review summarizes the current state of knowledge regarding the epidemiology of NER-associated diseases, their genetic background, clinical features, and treatment options. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. The forecast of anticancer targets of cryptotanshinone based on reverse pharmacophore-based screening technology.

    Science.gov (United States)

    Yuan, Dong-Ping; Long, Jun; Lu, Yin; Lin, Jie; Tong, Li

    2014-06-01

    Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The pathway analyses for the collection of anticancer targets screened were carried out based on the KEGG pathway database, followed by the forecast of potential pharmacological activities and pathways of the effects of cryptotanshinone, and verification of some of the targets screened using whole cell tests. The results showed that a total of eight targets with anticancer potential were screened, including MAP2K1, RARα, RXRα, PDK1, CHK1, AR, Ang-1 R, and Kif11. These targets are mainly related to four aspects of the cancer growth: the cell cycle, angiogenesis, apoptosis, and androgen receptor. The cell tests showed that cryptotanshinone can inhibit the viability of human hepatoma cells SMMC-7721, which is related to the reduction of expression of MAP2K1 mRNA. This method provides a strong clue for the study of the anticancer effects and mechanisms of action of cryptotanshinone in the future. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  6. Three coordination polymers based on 9,10-di(pyridine-4-yl)anthracene ligand: Syntheses, structures and fluorescent properties

    Science.gov (United States)

    Dong, Jun-Liang; Wang, Duo-Zhi; Jia, Yan-Yuan; Wang, Dan-Hong

    2017-08-01

    Three new mixed-ligand divalent coordination polymers (CPs) {[Zn3(L)(1,4-bdc)3]·2DMF}n (1), {[Zn2(L)(2,6-ndc)2]·3DMF}n (2) and {[Cd2(L)3(2,6-ndc)2]}n (3) [L = 9,10-di(pyridine-4-yl)anthracene, 1,4-H2bdc = 1,4-benzenedicarboxylic acid, 2,6-H2ndc = 2,6-naphthalenedicarboxylic acid] have been prepared and well characterized by elemental analyses, infrared spectroscopy, single-crystal X-ray diffraction techniques, powder X-ray diffraction patterns and thermogravimetric analyses. The crystal structure analyses of coordination polymers (CPs) reveal that all the complexes 1-3 have the three-dimensional (3D) coordination networks. The structure of 1 can be simplified as a sqc3 3D 8-connected framework with the point symbol of (424·64). Particularly, in the presence of the linear 2,6-H2ndc auxiliary ligand, a double-deck interpenetrating pcu 3D network of 2 is assembled by 6-connecting framework with the point symbol of (412·63). Complex 3 exhibits a ttd 3D 5-connected net with a point symbol of (46·64). Further, the solid-state luminescent properties of the complexes 1-3 were measured and studied at room temperature.

  7. Robustness of digitally modulated signal features against variation in HF noise model

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    Shoaib Mobien

    2011-01-01

    Full Text Available Abstract High frequency (HF band has both military and civilian uses. It can be used either as a primary or backup communication link. Automatic modulation classification (AMC is of an utmost importance in this band for the purpose of communications monitoring; e.g., signal intelligence and spectrum management. A widely used method for AMC is based on pattern recognition (PR. Such a method has two main steps: feature extraction and classification. The first step is generally performed in the presence of channel noise. Recent studies show that HF noise could be modeled by Gaussian or bi-kappa distributions, depending on day-time. Therefore, it is anticipated that change in noise model will have impact on features extraction stage. In this article, we investigate the robustness of well known digitally modulated signal features against variation in HF noise. Specifically, we consider temporal time domain (TTD features, higher order cumulants (HOC, and wavelet based features. In addition, we propose new features extracted from the constellation diagram and evaluate their robustness against the change in noise model. This study is targeting 2PSK, 4PSK, 8PSK, 16QAM, 32QAM, and 64QAM modulations, as they are commonly used in HF communications.

  8. DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination.

    Science.gov (United States)

    Qin, Weihua; Wolf, Patricia; Liu, Nan; Link, Stephanie; Smets, Martha; La Mastra, Federica; Forné, Ignasi; Pichler, Garwin; Hörl, David; Fellinger, Karin; Spada, Fabio; Bonapace, Ian Marc; Imhof, Axel; Harz, Hartmann; Leonhardt, Heinrich

    2015-08-01

    DNMT1 is recruited by PCNA and UHRF1 to maintain DNA methylation after replication. UHRF1 recognizes hemimethylated DNA substrates via the SRA domain, but also repressive H3K9me3 histone marks with its TTD. With systematic mutagenesis and functional assays, we could show that chromatin binding further involved UHRF1 PHD binding to unmodified H3R2. These complementation assays clearly demonstrated that the ubiquitin ligase activity of the UHRF1 RING domain is required for maintenance DNA methylation. Mass spectrometry of UHRF1-deficient cells revealed H3K18 as a novel ubiquitination target of UHRF1 in mammalian cells. With bioinformatics and mutational analyses, we identified a ubiquitin interacting motif (UIM) in the N-terminal regulatory domain of DNMT1 that binds to ubiquitinated H3 tails and is essential for DNA methylation in vivo. H3 ubiquitination and subsequent DNA methylation required UHRF1 PHD binding to H3R2. These results show the manifold regulatory mechanisms controlling DNMT1 activity that require the reading and writing of epigenetic marks by UHRF1 and illustrate the multifaceted interplay between DNA and histone modifications. The identification and functional characterization of the DNMT1 UIM suggests a novel regulatory principle and we speculate that histone H2AK119 ubiquitination might also lead to UIM-dependent recruitment of DNMT1 and DNA methylation beyond classic maintenance.

  9. Abuse and mental disorders among women at walk-in clinics in Trinidad: A cross-sectional study

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    Sanchez Sharlene

    2010-03-01

    Full Text Available Abstract Background To determine the prevalence of abuse by their partners and its association with mental disorders among female patients at walk-in clinics in Trinidad. Methods Female participants from 16 randomly selected walk-in clinics, previously stratified to represent all administrative regions and urban and rural settings, who were 18 years or older, were surveyed during May to August 2007 using the WAST-Short and PRIME-MD questionnaires. Results 432 women participated (a 92% response rate, Of these 16% were aged 20-29, 11.8% 30-39 and 19% 40-49; 37% were married, 25% single; 44.7% were Indo- and 35% Afro-Trinidadian; 67.8% had achieved education up to age 14 only. 30.3% were employed and 3.0% reported incomes more than $5,001 TTD (Trinidad and Tobago Dollars per month. Forty percent (173 of all respondents were positive for abuse as scored by the WAST-Short scale. Chi-square analysis suggested associations (p p Conclusion Among women of primarily lower socioeconomic status who attend walk-in clinics in Trinidad abuse as measured by the WAST-Short scale is high and there are statistically significant associations with mental disorders as determined by the PRIME-MD scale.

  10. Identifying candidates with favorable prognosis following liver transplantation for hepatocellular carcinoma: Data mining analysis.

    Science.gov (United States)

    Tanaka, Tomohiro; Kurosaki, Masayuki; Lilly, Leslie B; Izumi, Namiki; Sherman, Morris

    2015-07-01

    The optimal cutoff of each value in configuring selection criteria for pre-transplant assessment of hepatocellular carcinoma (HCC) remains uncertain. To build a predictive model for recurrent HCC, we performed data mining analysis on patients who underwent LT for HCC at University Health Network (n = 246). The model was externally validated using a cohort from the Scientific Registry of Transplant Recipients (SRTR) database (n = 9,769). Among 246 patients, 14.6% (n = 36) experienced recurrent HCC within 2.5 years post-LT. The risk prediction model for recurrent HCC identified two subgroups with low-risk (total tumor diameter [TTD] 4 cm and/or AFP >73 ng/ml, n = 111). The reproducibility of the model was validated through the SRTR database; overall patient survival rate was significantly better in low-risk group than high-risk group (P predict post-transplant survival independent of underlying characteristics (P data mining analysis efficiently classify patients according by the post-transplant prognosis. © 2015 Wiley Periodicals, Inc.

  11. In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Bruno J Neves

    2015-01-01

    Full Text Available Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD, DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.

  12. In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

    Science.gov (United States)

    Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

  13. In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni.

    Science.gov (United States)

    Neves, Bruno J; Braga, Rodolpho C; Bezerra, José C B; Cravo, Pedro V L; Andrade, Carolina H

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.

  14. Modeling and PSO optimization of Humidifier-Dehumidifier desalination

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Ahmadi

    2018-02-01

    Full Text Available The aim of this study is modeling a solar-air heater humidification-dehumidification unit with applying particle swarm optimization to find out  the maximum gained output ratio with respect to the mass flow rate of water and air entering humidifier, mass flow rate of cooling water entering dehumidifier, width and length of solar air heater and terminal temperature difference (TTD of dehumidifier representing temperature difference of inlet cooling water and saturated air to dehumidifier as its decision variable. A sensitivity analysis, furthermore, is performed to distinguish the effect of operating parameters including mass flow rate and streams’ temperature. The results showed that the optimum productivity decreases by decreasing the ratio of mass flow rate of water entering humidifier to air ones. Article History: Received: July 12th 2017; Revised: December 15th 2017; Accepted: 2nd February 2018; Available online How to Cite This Article: Afshar, M.A., Naseri, A., Bidi, M., Ahmadi, M.H. and Hadiyanto, H. (2018 Modeling and PSO Optimization of Humidifier-Dehumidifier Desalination. International Journal of Renewable Energy Development, 7(1,59-64. https://doi.org/10.14710/ijred.7.1.59-64

  15. Recent advances in chromosome breakage syndromes and their diagnosis.

    Science.gov (United States)

    Mathur, R; Chowdhury, M R; Singh, G

    2000-06-01

    Chromosome instability is a characteristic cytogenetic feature of a number of genetically determined disorders collectively called as the chromosome breakage syndromes or DNA-repair disorders. They are characterized by susceptibility to chromosomal breakages, increased frequency of breaks and interchanges occurring either spontaneously or following exposure to various DNA-damaging agents. These diseases are a group of genetic disorders sharing a number of features. They are all autosomal recessive, show an increased tendency for chromosomal aberrations and to develop malignancies. The principal diseases in this group having a diverse etiology and clinical manifestations include Fanconi anemia (FA), ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), Bloom syndrome (BS), xeroderma pigementosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). The underlying defect in these syndromes is the inability to repair a particular type of DNA damage. A number of repair disorder phenotypes are caused by more than one gene. The diagnosis of these syndromes is made by the characteristic clinical features specific to each disease, but the definitive diagnosis is achieved by laboratory investigations such as cytogenetic, biochemical and molecular methods. The importance of prenatal diagnosis and our experience are discussed in this article.

  16. TENSILE STRENGTH OF CIRCULAR FLAT AND CONVEX-FACED AVICEL PH102 TABLETS

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    I.HARIRIAN

    1999-09-01

    Full Text Available The mechanical properties of flat and convex-faced circular tablets made from a size fraction of microcrystalline cellulose (Avicel PH102, compacted under control conditions of pressures of 20 and 112 MPa have been assessed in term of tensile strength. The calculation of tensile strength (at, for flat-faced tablets was determined from the load (P in diametral compression test as described by Fell & Newton ot = 2P/ (7tDt. The material tensile strength of convex-faced tablets calculated from the observed fraction loads obtained in diametral compression testing, based on the equation derived by Pitt et al at= 10P/ [TTD2 (2.84I/D - 0.126t/W+ 3.15W/D + 0.01"1 ], where P is the fracture load, D is the tablet diameter, t is the overall tablet thickness and W is the central cylinder thickness. By comparing the tensile strength values of convex-faced tablets using porosity, tensile stress, and compaction pressure values, an optimum face-curvature in normal to unity range (D/R=0.67-1.0 and an optimum cylinder length of W/D=0.3, were found to be necessary for producing the overall strongest tablets. These optimum values varies with the formation pressure.

  17. Annealing Induced Re-crystallization in CH3NH3PbI3−xClx for High Performance Perovskite Solar Cells

    Science.gov (United States)

    Yang, Yingguo; Feng, Shanglei; Li, Meng; Xu, Weidong; Yin, Guangzhi; Wang, Zhaokui; Sun, Baoquan; Gao, Xingyu

    2017-01-01

    Using poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) as hole conductor, a series of inverted planar CH3NH3PbI3−xClx perovskite solar cells (PSCs) were fabricated based on perovskite annealed by an improved time-temperature dependent (TTD) procedure in a flowing nitrogen atmosphere for different time. Only after an optimum annealing time, an optimized power conversion efficiency of 14.36% could be achieved. To understand their performance dependence on annealing time, an in situ real-time synchrotron-based grazing incidence X-ray diffraction (GIXRD) was used to monitor a step-by-step gradual structure transformation from distinct mainly organic-inorganic hybrid materials into highly ordered CH3NH3PbI3 crystal during annealing. However, a re-crystallization process of perovskite crystal was observed for the first time during such an annealing procedure, which helps to enhance the perovskite crystallization and preferential orientations. The present GIXRD findings could well explain the drops of the open circuit voltage (Voc) and the fill factor (FF) during the ramping of temperature as well as the optimized power conversion efficiency achieved after an optimum annealing time. Thus, the present study not only illustrates clearly the decisive roles of post-annealing in the formation of solution-processed perovskite to better understand its formation mechanism, but also demonstrates the crucial dependences of device performance on the perovskite microstructure in PSCs. PMID:28429762

  18. Functionality and opposite roles of two interleukin 4 haplotypes in immune cells.

    Science.gov (United States)

    Anovazzi, G; Medeiros, M C; Pigossi, S C; Finoti, L S; Souza Moreira, T M; Mayer, M P A; Zanelli, C F; Valentini, S R; Rossa-Junior, C; Scarel-Caminaga, R M

    2017-01-01

    Cytokines expression can be influenced by polymorphisms in their respective coding genes. We associated the CTI/TTD haplotype (Hap-1) and TCI/CCI haplotype (Hap-2) in the IL4 gene formed by the -590, +33 and variable number of tandem repeat polymorphisms with the severity of chronic periodontitis in humans. The functionality of these IL4 haplotypes in the response of immune cells to phorbol 12-myristate 13-acetate (PMA) with Ionomycin and IL-1β (as inflammatory stimuli) was evaluated. Gene expression (quantitative real-time PCR), profile of secreted cytokines (multiplex) and phenotypic polarization of T cells (flow cytometry) were the outcomes assessed. Green fluorescent protein reporter plasmid constructs containing specific IL4 haplotype were transiently transfected into JM cells to assess the influence of the individual haplotypes on promoter activity. In response to inflammatory stimuli the immune cells from Hap-1 haplotype had increased expression of anti-inflammatory IL4; conversely, the Hap-2 haplotype showed higher levels of pro-inflammatory cytokines. The haplotype CTI proved to be the most important for the regulation of IL4 promoter, regardless of the nature of the inflammatory stimulation; whereas the polymorphism in the promoter region had the least functional effect. In conclusion, IL4 haplotypes studied are functional and trigger opposite immune responses: anti-inflammatory (Hap-1) and pro-inflammatory (Hap-2). In addition, we identified the CTI haplotype as the main responsible for the regulation of IL4 transcriptional activity.

  19. Analysis of low frequency noise characteristics in p-type polycrystalline silicon thin film transistors

    Science.gov (United States)

    Liu, Yuan; En, Yun-Fei; Fang, Wen-Xiao

    2017-07-01

    Low frequency noises in the p-type polycrystalline silicon thin film transistors are investigated. It shows a pure 1/fγ (with γ near one) noise behavior which can be explained by emission and trapping processes of carriers between trapping states. Subsequently, the gate voltage-dependent drain current noise power spectral densities closely follow the mobility fluctuation model, and the average Hooge’s parameter is then extracted. By considering traditional tunneling processes, the flat-band voltage spectral density is extracted and the concentration of traps in the grain boundary is calculated to be 7.17 × 1020cm-3eV-1. By converting the frequency to tunneling depth of carriers in the gate oxide, the spatial distribution of gate oxide trapped charges are obtained. Finally, the distribution of localized states in the energy band is extracted. The experimental results show an exponential deep states and tail states distribution in the band gap while NDD is about 1.5 × 1020cm-3eV-1, TDD is ˜617 K, NTD is ˜3.6 × 1021cm-3eV-1 and TTD is ˜265 K.

  20. The Lactose and Galactose Content of Cheese Suitable for Galactosaemia: New Analysis.

    Science.gov (United States)

    Portnoi, P A; MacDonald, A

    2016-01-01

    The UK Medical Advisory Panel of the Galactosaemia Support Group report the lactose and galactose content of 5 brands of mature Cheddar cheese, Comte and Emmi Emmental fondue mix from 32 cheese samples. The Medical Advisory Panel define suitable cheese in galactosaemia to have a lactose and galactose content consistently below 10 mg/100 g. A total of 32 samples (5 types of mature Cheddar cheese, Comte and "Emmi Swiss Fondue", an emmental fondue mix) were analysed by high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) technology used to perform lactose and galactose analysis. Cheddar cheese types: Valley Spire West Country, Parkham, Lye Cross Vintage, Lye Cross Mature, Tesco West Country Farmhouse Extra Mature and Sainsbury's TTD West Country Farmhouse Extra Mature had a lactose and galactose content consistently below 10 mg/100 g (range <0.05 to 12.65 mg). All Comte samples had a lactose content below the lower limit of detection (<0.05 mg) with galactose content from <0.05 to 1.86 mg/100 g; all samples of Emmi Swiss Fondue had lactose below the lower limit of detection (<0.05 mg) and galactose between 2.19 and 3.04 mg/100 g. All of these cheese types were suitable for inclusion in a low galactose diet for galactosaemia. It is possible that the galactose content of cheese may change over time depending on its processing, fermentation time and packaging techniques.

  1. HOW TO DETERMINE AN EXOMOON'S SENSE OF ORBITAL MOTION

    Energy Technology Data Exchange (ETDEWEB)

    Heller, René [Origins Institute, McMaster University, Hamilton, ON L8S 4M1 (Canada); Albrecht, Simon, E-mail: rheller@physics.mcmaster.ca, E-mail: albrecht@phys.au.dk [Stellar Astrophysics Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, DK-8000 Aarhus C (Denmark)

    2014-11-20

    We present two methods to determine an exomoon's sense of orbital motion (SOM), one with respect to the planet's circumstellar orbit and one with respect to the planetary rotation. Our simulations show that the required measurements will be possible with the European Extremely Large Telescope (E-ELT). The first method relies on mutual planet-moon events during stellar transits. Eclipses with the moon passing behind (in front of) the planet will be late (early) with regard to the moon's mean orbital period due to the finite speed of light. This ''transit timing dichotomy'' (TTD) determines an exomoon's SOM with respect to the circumstellar motion. For the 10 largest moons in the solar system, TTDs range between 2 and 12 s. The E-ELT will enable such measurements for Earth-sized moons around nearby Sun-like stars. The second method measures distortions in the IR spectrum of the rotating giant planet when it is transited by its moon. This Rossiter-McLaughlin effect (RME) in the planetary spectrum reveals the angle between the planetary equator and the moon's circumplanetary orbital plane, and therefore unveils the moon's SOM with respect to the planet's rotation. A reasonably large moon transiting a directly imaged planet like β Pic b causes an RME amplitude of almost 100 m s{sup –1}, about twice the stellar RME amplitude of the transiting exoplanet HD209458 b. Both new methods can be used to probe the origin of exomoons, that is, whether they are regular or irregular in nature.

  2. Dissecting the Hydrobiogeochemical Box

    Science.gov (United States)

    Wang, Y.; Alves Meira Neto, A.; Sengupta, A.; Root, R. A.; Dontsova, K.; Troch, P. A. A.; Chorover, J.

    2015-12-01

    Soil genesis is a coupled hydrologic and biogeochemical process that involves the interaction of weathering rock surfaces and water. Due to strong nonlinear coupling, it is extremely difficult to predict biogeochemical changes from hydrological modeling in natural field systems. A fully controlled and monitored system with known initial conditions could be utilized to isolate variables and simplify these natural processes. To investigate the initial weathering of host rock to soil, we employed a 10° sloping soil lysimeter containing one cubic meter of crushed and homogenized basaltic rock. A major experiment of the Periodic Tracer Hierarchy (PERTH) method (Harman and Kim, 2014) coupled with its bonus experiment were performed in the past two years. These experimental applications successfully described the transit-time distribution (TTD) of a tracer-enriched water breakthrough curve in this unique hydrological system (Harman, 2015). With intensive irrigation and high volume of water storage throughout the experiments, rapid biological changes have been observed on the soil surface, such as algal and grass growth. These observations imply that geochemical hotspots may be established within the soil lysimeter. To understand the detailed 2D spatial distribution of biogeochemical changes, 100 selected and undisturbed soil blocks, among a total 1000 sub-gridded equal sized, are tested with several geochemical tools. Each selected soil block was subjected to elemental analysis by pXRF to determine if elemental migration is detectable in the dynamic proto-soil development. Synchrotron XRD quantification with Reitveld refinement will follow to clarify mineralogical transformations in the soil blocks. The combined techniques aim to confirm the development of geochemical hotspots; and link these findings with previous hydrological findings from the PERTH experiment as well as other hydrological modeling, such as conducted with Hydrus and CATHY. This work provides insight to

  3. Simulation of anthropogenic CO2 uptake in the CCSM3.1 ocean circulation-biogeochemical model: comparison with data-based estimates

    Directory of Open Access Journals (Sweden)

    S. Khatiwala

    2012-04-01

    Full Text Available The global ocean has taken up a large fraction of the CO2 released by human activities since the industrial revolution. Quantifying the oceanic anthropogenic carbon (Cant inventory and its variability is important for predicting the future global carbon cycle. The detailed comparison of data-based and model-based estimates is essential for the validation and continued improvement of our prediction capabilities. So far, three global estimates of oceanic Cant inventory that are "data-based" and independent of global ocean circulation models have been produced: one based on the Δ C* method, and two that are based on constraining surface-to-interior transport of tracers, the TTD method and a maximum entropy inversion method (GF. The GF method, in particular, is capable of reconstructing the history of Cant inventory through the industrial era. In the present study we use forward model simulations of the Community Climate System Model (CCSM3.1 to estimate the Cant inventory and compare the results with the data-based estimates. We also use the simulations to test several assumptions of the GF method, including the assumption of constant climate and circulation, which is common to all the data-based estimates. Though the integrated estimates of global Cant inventories are consistent with each other, the regional estimates show discrepancies up to 50 %. The CCSM3 model underestimates the total Cant inventory, in part due to weak mixing and ventilation in the North Atlantic and Southern Ocean. Analyses of different simulation results suggest that key assumptions about ocean circulation and air-sea disequilibrium in the GF method are generally valid on the global scale, but may introduce errors in Cant estimates on regional scales. The GF method should also be used with caution when predicting future oceanic anthropogenic carbon uptake.

  4. Simulation of anthropogenic CO2 uptake in the CCSM3.1 ocean circulation-biogeochemical model: comparison with data-based estimates

    Science.gov (United States)

    Wang, S.; Moore, J. K.; Primeau, F. W.; Khatiwala, S.

    2012-04-01

    The global ocean has taken up a large fraction of the CO2 released by human activities since the industrial revolution. Quantifying the oceanic anthropogenic carbon (Cant) inventory and its variability is important for predicting the future global carbon cycle. The detailed comparison of data-based and model-based estimates is essential for the validation and continued improvement of our prediction capabilities. So far, three global estimates of oceanic Cant inventory that are "data-based" and independent of global ocean circulation models have been produced: one based on the Δ C* method, and two that are based on constraining surface-to-interior transport of tracers, the TTD method and a maximum entropy inversion method (GF). The GF method, in particular, is capable of reconstructing the history of Cant inventory through the industrial era. In the present study we use forward model simulations of the Community Climate System Model (CCSM3.1) to estimate the Cant inventory and compare the results with the data-based estimates. We also use the simulations to test several assumptions of the GF method, including the assumption of constant climate and circulation, which is common to all the data-based estimates. Though the integrated estimates of global Cant inventories are consistent with each other, the regional estimates show discrepancies up to 50 %. The CCSM3 model underestimates the total Cant inventory, in part due to weak mixing and ventilation in the North Atlantic and Southern Ocean. Analyses of different simulation results suggest that key assumptions about ocean circulation and air-sea disequilibrium in the GF method are generally valid on the global scale, but may introduce errors in Cant estimates on regional scales. The GF method should also be used with caution when predicting future oceanic anthropogenic carbon uptake.

  5. In Silico target fishing: addressing a “Big Data” problem by ligand-based similarity rankings with data fusion

    Science.gov (United States)

    2014-01-01

    Background Ligand-based in silico target fishing can be used to identify the potential interacting target of bioactive ligands, which is useful for understanding the polypharmacology and safety profile of existing drugs. The underlying principle of the approach is that known bioactive ligands can be used as reference to predict the targets for a new compound. Results We tested a pipeline enabling large-scale target fishing and drug repositioning, based on simple fingerprint similarity rankings with data fusion. A large library containing 533 drug relevant targets with 179,807 active ligands was compiled, where each target was defined by its ligand set. For a given query molecule, its target profile is generated by similarity searching against the ligand sets assigned to each target, for which individual searches utilizing multiple reference structures are then fused into a single ranking list representing the potential target interaction profile of the query compound. The proposed approach was validated by 10-fold cross validation and two external tests using data from DrugBank and Therapeutic Target Database (TTD). The use of the approach was further demonstrated with some examples concerning the drug repositioning and drug side-effects prediction. The promising results suggest that the proposed method is useful for not only finding promiscuous drugs for their new usages, but also predicting some important toxic liabilities. Conclusions With the rapid increasing volume and diversity of data concerning drug related targets and their ligands, the simple ligand-based target fishing approach would play an important role in assisting future drug design and discovery. PMID:24976868

  6. Modeling PCN-61 and PCN-66: Isostructural rht -Metal–Organic Frameworks with Distinct CO 2 Sorption Mechanisms

    KAUST Repository

    Pham, Tony

    2014-11-05

    © 2014 American Chemical Society. Simulations of CO2 sorption were performed in two members of the highly tunable rht-metal-organic framework (MOF) platform: PCN-61 and PCN-66. These MOFs differ only in the triisophthalate ligand used to synthesize the respective MOFs. In PCN-61, the center of the ligand contains a benzene ring; this ring is substituted with a triphenylamine group in PCN-66. There are two chemically distinct Cu2+ ions that comprise the copper paddlewheels, [Cu2(O2CR)4], in all rht-MOFs. One type of Cu2+ ion, denoted Cu1, projects into the truncated tetrahedral (T-Td) and truncated octahedral (T-Oh) cages, while the other Cu2+ ion, denoted Cu2, projects into the cuboctahedral (cub-Oh) cages. Electronic structure calculations revealed that, in PCN-61, the Cu2 ions have a significantly higher partial positive charge than the Cu1 ions, whereas the opposite was observed in PCN-66. The simulations revealed that the CO2 molecules sorb initially onto the Cu2+ ions that have the higher partial positive charge, i.e., the Cu2 ions in PCN-61 and the Cu1 ions in PCN-66. This was demonstrated by examining the radial distribution function, g(r), about both Cu2+ ions and the modeled structure at low loading for both MOFs. This study provided insights into how differences in the charge distributions about the copper paddlewheels between two isostructural MOFs, arising from the choice of functionality on the ligand, can lead to different CO2 binding sites at low loading and suggests a more general conceptual framework for controlling sorption through the tuning of MOF electronics.

  7. Insomnia predicts long-term all-cause mortality after acute myocardial infarction: A prospective cohort study.

    Science.gov (United States)

    Condén, Emelie; Rosenblad, Andreas

    2016-07-15

    Sleep impairment such as insomnia is an established risk factor for the development of cardiovascular disease and acute myocardial infarction (AMI). The aim of the current study was to examine the association between insomnia and all-cause mortality among AMI patients. This prospective cohort study used data on n=732 patients recruited from September 2006 to May 2011 as part of the Västmanland Myocardial Infarction Study (VaMIS), a prospective cohort study of AMI patients living in Västmanland County, Sweden. Participants were followed up for all-cause mortality until December 9, 2015. The outcome of interest was time-to-death (TTD), with the presence of insomnia being the risk factor of main interest. Data were analyzed using a piecewise Cox regression model with change point for insomnia at two years of follow-up, adjusted for socioeconomic, lifestyle and clinical risk factors. In total, n=175 (23.9%) of the participants suffered from insomnia. During a mean (SD) follow-up time of 6.0 (2.5) years (4392person-years), a total of n=231 (31.6%) participants died, n=77 (44.0%) in the insomnia group and n=154 (27.6%) in the non-insomnia group (log-rank test p<0.001). In a multiple adjusted piecewise Cox regression model, insomnia did not imply a higher risk of death during the first two years after AMI (HR 0.849; 95% CI 0.508-1.421; p=0.534). During the period after the first two years, however, insomnia implied a 1.6 times higher risk of death (HR 1.597; 95% CI 1.090-2.341; p=0.016). Insomnia implies a higher risk of death among AMI patients in the long term. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Diagnostic accuracy of whole-brain CT perfusion in the detection of acute infratentorial infarctions

    Energy Technology Data Exchange (ETDEWEB)

    Bollwein, Christine; Sommer, Wieland H.; Thierfelder, Kolja M.; Reiser, Maximilian F. [Ludwig-Maximilians-University Hospital of Munich, Institute for Clinical Radiology, Munich (Germany); Plate, Annika; Straube, Andreas; Baumgarten, Louisa von [Ludwig-Maximilians-University Hospital of Munich, Department of Neurology, Munich (Germany); Janssen, Hendrik [South Nuremberg Hospital, Department of Neuroradiology, Nuremberg (Germany)

    2016-11-15

    Although the diagnostic performance of whole-brain computed tomographic perfusion (WB-CTP) in the detection of supratentorial infarctions is well established, its value in the detection of infratentorial strokes remains less well defined. We examined its diagnostic accuracy in the detection of infratentorial infarctions and compared it to nonenhanced computed tomography (NECT), aiming to identify factors influencing its detection rate. Out of a cohort of 1380 patients who underwent WB-CTP due to suspected stroke, we retrospectively included all patients with MRI-confirmed infratentorial strokes and compared it to control patients without infratentorial strokes. Two blinded readers evaluated NECT and four different CTP maps independently for the presence and location of infratentorial ischemic perfusion deficits. The study was designed as a retrospective case-control study and included 280 patients (cases/controls = 1/3). WB-CTP revealed a greater diagnostic sensitivity than NECT (41.4 vs. 17.1 %, P = 0.003). The specificity, however, was comparable (93.3 vs. 95.0 %). Mean transit time (MTT) and time to drain (TTD) were the most sensitive (41.4 and 40.0 %) and cerebral blood volume (CBV) the most specific (99.5 %) perfusion maps. Infarctions detected using WB-CTP were significantly larger than those not detected (15.0 vs. 2.2 ml; P = 0.0007); infarct location, however, did not influence the detection rate. The detection of infratentorial infarctions can be improved by assessing WB-CTP as part of the multimodal stroke workup. However, it remains a diagnostic challenge, especially small volume infarctions in the brainstem are likely to be missed. (orig.)

  9. Decadal Changes in Ventilation and Anthropogenic Carbon in the Intermediate Depths of the Arctic Ocean

    Science.gov (United States)

    Rajasakaren, Balamuralli; Jeansson, Emil; Olsen, Are; Tanhua, Toste; Johannessen, Truls

    2017-04-01

    We use transient tracer (CFC-12) observations from the GLODAPv2 data product to investigate the decadal evolution of mean age and the amount of anthropogenic carbon (Cant) in the intermediate depths (200 - 2000 m) of the Arctic Ocean. Applying the transit time distribution (TTD) method, we find that ventilation has deepened in the upper 1600 m in the Eurasian Basin and Amerasian Basin from the 1990s to the 2000s. Ventilation in the Eurasian Basin mainly takes place via advection of upper Polar Deep Water (uPDW) and dense Atlantic Water (dAW) at about 500 - 1500 m. The ventilation during the studies period may be connected to an observed increased inflow of Atlantic Water, particularly from the Barents Sea Branch. Ventilation in the intermediate depths of the Amerasian Basin is mainly in the Arctic Atlantic Water (AAW) and dense Arctic Atlantic Water (dAAW) in both the Makarov and South Canadian Basins and uPDW in the South Canadian Basin, while the West Canadian Basin is more in a steady state. As a consequence of the ventilation in the Eurasian Basin, Cant has increased by about 4-7 μmol kg-1 from 1987 to the 1990s, and by about 6-9 μmol kg-1 from the 1990s to the 2000s. There is also an increase in anthropogenic carbon in the upper 1750 m in the Amerasian Basin of about 10 μmol kg-1 from the 1990s to the 2000s. The Arctic Ocean Cant inventory for the intermediate waters has significantly increased from the 1990s to the 2000s and the inventory for the 2000s is calculated to be about 2 Gt-C (specific inventory ≈ 40 mol C m-2).

  10. Truncated Transition Densities for Analysis of (Nonlinear) Optical Properties of carbo-Chromophores.

    Science.gov (United States)

    Poidevin, Corentin; Lepetit, Christine; Ben Amor, Nadia; Chauvin, Remi

    2016-08-09

    The optical properties of several quadrupolar carbo-benzene derivatives are investigated at various levels of calculation (TDDFT and CASPT2) and analyzed using a new theoretical tool here disclosed: The "visualization" of the transition dipole moment from the transition density truncated to the main monoexcitations involved in the electronic transition (TTD). The experimental or calculated one-photon UV-visible absorption spectra of the carbo-benzene derivatives fit with the Gouterman model originally proposed for porphyrins, where the first four excited states involve linear combinations of monoexcitations of the same four frontier molecular orbitals. The relative intensities of the absorption bands are analyzed from the transition dipole moments calculated from the TTDs and an analogy between porphyrins and carbo-benzenes is argued. The two-photon absorption (TPA) cross section related to the third-order nonlinear optical response is calculated for each two-photon-allowed excited state |f⟩ from the contribution of all possible intermediate excited states |i⟩ using the "sum-over-state" (SOS) scheme. The quadrupolar carbo-benzene derivatives fit into the three-level model, as their TPA cross section exhibits a dominant contribution of one of the intermediate excited states. The origin of TPA efficiency (enhancement) upon carbo-merisation of the C-C link to the para-substituents is discussed from the excitation energies of the intermediate and final excited states and from the two corresponding transition dipole moments (μ0i and μif). The latter may be calculated from the TTDs.

  11. TINDAK TUTUR ILOKUSI GURU BERLATAR BELAKANG BUDAYA JAWA: PERSPEKTIF GENDER

    Directory of Open Access Journals (Sweden)

    Ardina Kentary

    2016-02-01

    Full Text Available This study aims at describing the shape of illocutionary speech acts Javanese cultural background of teachers in school, describing the strategies and techniques politeness Javanese cultural background of teachers in school, describing the use of illocutionary speech acts teachers’ Javanese cultural backgrund based on gender perspective. Attention method is used by writer to collect the data by providing several techniques, namely: involved refer-free conversation techniques, recording techniques, and notes technique. The analysis of data by using a padan method. Based on the analysis of data can be retrieved 3 conclusions. First, all categories of illocutionary speech acts by Searle are found in formal activities in this study. Meanwhile, in a non-formal activity found three categories. Second, in the formal and non-formal activities, the strategy used by teachers to speak are direct strategy and indirect strategy. The technique used are literal and non literal. In addition, there is a combination between speech strategies and speech techniques. Third, based on a gender perspective, there are three things that discused in this study. (a in general, directive speech act is the dominant used in this research. The use of sub-utterances instructing, requesting, giving guidance, and advising in a formal activities are dominant by nGP than nGL. However, the sub-TTD to order the use of nGL is higher than nGP. In the non-formal activities, sub-utterances instructing is dominant used by nGL than nGP. (c teacher’s Javanese cultural background prefer to choose literal technique in their speech. (d the most dominant combination of strategies and techniques used is direct speech act strategie and literal speech act technique.

  12. Functional Haplotypes in Interleukin 4 Gene Associated with Periodontitis.

    Science.gov (United States)

    Anovazzi, Giovana; Medeiros, Marcell Costa de; Pigossi, Suzane Cristina; Finoti, Livia Sertori; Mayer, Marcia Pinto Alves; Rossa, Carlos; Scarel-Caminaga, Raquel Mantuaneli

    2017-01-01

    Chronic periodontitis (CP) is an infectious inflammatory disease that affects tooth-supporting structures and in which dental plaque bacteria, immune mechanisms and genetic predisposition play important roles. Interleukin 4 (IL-4) is a key anti-inflammatory cytokine with relevant action in imbalances in inflamed periodontal tissue. Individuals carrying the TCI/CCI genotype (S-haplotype) of the IL-4 gene are 5 times more susceptible to CP, whereas the CTI/TTD genotype (P-haplotype) confers protection against CP. Compared with the S-haplotype, subjects with the P-haplotype produce higher levels of the IL-4 protein after non-surgical periodontal therapy. The present in vitro study aimed to investigate the functionality of IL-4 haplotypes in immune cells to obtain insight into the influence of these genetic variations in regulating immune responses to CP-associated bacteria. Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens to compare responses of the different haplotypes with regard to gene expression, protein secretion and the immunophenotype of T helper responses. We found higher IL-4 mRNA and protein levels in the P-haplotype, which also presented higher levels of anti-inflammatory cytokines. In contrast, cells from S-haplotype subjects responded with higher levels of pro-inflammatory cytokines. S-haplotype individuals exhibited significantly greater polarization toward the Th1 phenotype, whereas the P-haplotype was associated with an attenuated response to periodontopathogens, with suggestive skewing toward Th2/M2 phenotypes. In conclusion, IL-4 genetic variations associated with susceptibility to or protection against chronic periodontitis are directly associated with influencing the response of immune cells to periodontopathogens.

  13. [Evaluation of combination of BACTEC mycobacteria growth indicator tube 960 system and Ogawa media for mycobacterial culture].

    Science.gov (United States)

    Bae, Eunsin; Im, Ji Hoon; Kim, Sung Won; Yoon, Nam Surp; Sung, Heungsup; Kim, Mi Na; Shim, Tae Sun

    2008-08-01

    The combined use of liquid media and solid media is recommended for mycobacterial culture. We evaluated diagnostic performance of combination of BACTEC Mycobacteria Growth Indicator Tube (MGIT; Becton Dickinson, USA) and 2% Ogawa media (Korean Institute of Tuberculosis, Korea) for recovery of mycobacteria. In September 2007, 1,764 specimens from 1,059 patients were cultured with MGIT and Ogawa. Acid fast bacilli (AFB) smear was fluorochrome-stained. The isolates were identified into Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM) with PCR using Seeplex TB Detection Kit (Seegene, Korea). Recovery rate, time to detection (TTD), contamination rate, mixed growth rate and species distribution were analyzed. Two hundred thirty-five specimens (13.3%) from 165 patients (15.6%) were positive for mycobacterial culture. Recovery rates of mycobacteria from the group using both media, MGIT only, and Ogawa only were 13.3%, 12.1%, and 7.8%, respectively. While MGIT recovered 98.9% of MTB and 79.7% of NTM, Ogawa recovered 65.9% of MTB and 54.1% of NTM. TTDs of total mycobacteria/MTB/NTM in MGIT and Ogawa were 10.6/11.4/9.7 days and 31/29/33 days, respectively. MGIT TTDs of total mycobacteria/MTB/NTM from AFB-positive specimens were significantly shorter than those of AFB-negative specimens; 8.2/9.5/4.4 days vs 11.6/12.7/10.7 days. Contamination and mixed growth rate of MGIT were 9.6% and 3.7%. Primary culture of Ogawa recovered 1 MTB and 1 NTM among the 170 MGIT-contaminated specimens and 38 mycobacteria among 66 specimens that showed mixed cultures of MGIT. MGIT warrants sensitive and rapid isolation of mycobacteria. However, the combination of MGIT and Ogawa is more desirable to recover mycobacteria in the case of contaminations or mixed cultures.

  14. Peran Intervensi Gizi Spesifik dan Sensitif dalam Perbaikan Masalah Gizi Balita di Kota Bogor

    Directory of Open Access Journals (Sweden)

    Bunga Ch Rosha

    2016-09-01

    yang telah dilakukan dalam menangulangi masalah gizi balita di Kota Bogor. Penelitian ini merupakan penelitian kualitatif pada 12 informan baik dari sektor kesehatan dan non–kesehatan. Data dikumpulkan melalui wawancara mendalam. Hasil penelitian menunjukkan intervensi gizi spesifik yaitu intervensi balita (pemantauan balita di posyandu, imunisasi, vitamin A, dan PMT. Intervensi ibu (kelas ibu hamil, PMT ibu hamil, seminar gizi dan kesehatan dan intervensi remaja (program tablet tambah darah/ TTD. Sedangkan intervensi gizi sensitive, yaitu : intervensi kesehatan lingkungan (program Jumat atau Minggu bersih, pembuatan biopori dan septictank komunal, intervensi kemiskinan (pemberian BLT, keluarga harapan, dana PNPM, dan intervensi pemberdayaan perempuan (penyuluhan kesehatan dan gizi, pemberian tanaman bibit untuk pemanfaatan lingkungan. Intervensi spesifik dan sensitif ini sebaiknya dipadukan agar penanganan masalah gizi dilakukan secara berkelanjutan.Kata kunci : penanggulangan masalah gizi, intervensi gizi spesifik, intervensi gizi sensitif.

  15. Electrostatic solvation free energies of charged hard spheres using molecular dynamics with density functional theory interactions

    Energy Technology Data Exchange (ETDEWEB)

    Duignan, Timothy T. [Physical Science Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, USA; Baer, Marcel D. [Physical Science Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, USA; Schenter, Gregory K. [Physical Science Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, USA; Mundy, Chistopher J. [Department of Chemical Engineering, University of Washington, Seattle, Washington 98185, USA

    2017-10-28

    Determining the solvation free energies of single ions in water is one of the most fundamental problems in physical chemistry and yet many unresolved questions remain. In particular, the ability to decompose the solvation free energy into simple and intuitive contributions will have important implications for coarse grained models of electrolyte solution. Here, we provide rigorous definitions of the various types of single ion solvation free energies based on different simulation protocols. We calculate solvation free energies of charged hard spheres using density functional theory interaction potentials with molecular dynamics simulation (DFT-MD) and isolate the effects of charge and cavitation, comparing to the Born (linear response) model. We show that using uncorrected Ewald summation leads to highly unphysical values for the solvation free energy and that charging free energies for cations are approximately linear as a function of charge but that there is a small non-linearity for small anions. The charge hydration asymmetry (CHA) for hard spheres, determined with quantum mechanics, is much larger than for the analogous real ions. This suggests that real ions, particularly anions, are significantly more complex than simple charged hard spheres, a commonly employed representation. We would like to thank Thomas Beck, Shawn Kathmann, Richard Remsing and John Weeks for helpful discussions. Computing resources were generously allocated by PNNL's Institutional Computing program. This research also used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. TTD, GKS, and CJM were supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. MDB was supported by MS3 (Materials Synthesis and Simulation Across

  16. Test of synthetic DNA tracers in a periodic hydrodynamic system for time-variable transit time distribution assessment

    Science.gov (United States)

    Dahlke, H. E.; Wang, C.; McNew, C.; McLaughlin, S.; Lyon, S. W.

    2016-12-01

    Recent research on time-varying transport through hydrologic systems proposed using decomposed over-printed tracer breakthrough curves to directly observe transport through complex flow systems. This method, also known as the PERTH (Periodic Tracer Hierarchy) method requires periodic flow and multiple tracer injections to reveal changes in flow pathways and transport behavior. Time-variable transit time distributions (TTD) estimated from tracer breakthrough curves often vary with the storage state of the system, which in turn is influenced by internal and external variabilities, such as the arrangement of flow pathways and fluctuations in system inputs. Deciphering internal from external variabilities in TTDs might help to advance the use of TTDs for estimating the physical state of a system; however, thus far the finite number of unique conservative tracers available for tracing has limited deeper insights. Synthetic DNA tracers consisting of short strands of synthetic DNA encapsulated by polylactic acid (PLA) microspheres could potentially provide multiple unique tracers with identical transport properties needed to explore time varying transport through hydrologic systems in more detail. An experiment was conducted on the miniLeo hillslope, a 1 m3 sloping lysimeter, within the Biosphere 2 Landscape Evolution Observatory near Tucson, AZ to investigate transit time variability. The goal of the experiment was to 1) test the suitability of using synthetic DNA tracers for estimating TTDs in a hydrologic system and 2) to determine the TTDs of individual tracer pulses under periodic steady-state conditions. Five DNA tracers, consisting of four unique, encapsulated DNA sequences and one free/non-encapsulated DNA sequence, were applied as reference and probe tracers together with deuterium, using the PERTH method. The lysimeter received three 2-hour pulses of rainfall at a rate of 30 mm/hr for 10 days. Initial results show that both the encapsulated and free DNA tracers

  17. PDTD: a web-accessible protein database for drug target identification

    Directory of Open Access Journals (Sweden)

    Gao Zhenting

    2008-02-01

    Full Text Available Abstract Background Target identification is important for modern drug discovery. With the advances in the development of molecular docking, potential binding proteins may be discovered by docking a small molecule to a repository of proteins with three-dimensional (3D structures. To complete this task, a reverse docking program and a drug target database with 3D structures are necessary. To this end, we have developed a web server tool, TarFisDock (Target Fishing Docking http://www.dddc.ac.cn/tarfisdock, which has been used widely by others. Recently, we have constructed a protein target database, Potential Drug Target Database (PDTD, and have integrated PDTD with TarFisDock. This combination aims to assist target identification and validation. Description PDTD is a web-accessible protein database for in silico target identification. It currently contains >1100 protein entries with 3D structures presented in the Protein Data Bank. The data are extracted from the literatures and several online databases such as TTD, DrugBank and Thomson Pharma. The database covers diverse information of >830 known or potential drug targets, including protein and active sites structures in both PDB and mol2 formats, related diseases, biological functions as well as associated regulating (signaling pathways. Each target is categorized by both nosology and biochemical function. PDTD supports keyword search function, such as PDB ID, target name, and disease name. Data set generated by PDTD can be viewed with the plug-in of molecular visualization tools and also can be downloaded freely. Remarkably, PDTD is specially designed for target identification. In conjunction with TarFisDock, PDTD can be used to identify binding proteins for small molecules. The results can be downloaded in the form of mol2 file with the binding pose of the probe compound and a list of potential binding targets according to their ranking scores. Conclusion PDTD serves as a comprehensive and

  18. Predictors of delayed culture conversion among Ugandan patients.

    Science.gov (United States)

    Atwine, Daniel; Orikiriza, Patrick; Taremwa, Ivan; Ayebare, Arnold; Logoose, Suzan; Mwanga-Amumpaire, Juliet; Jindani, Amina; Bonnet, Maryline

    2017-04-24

    Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda. Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion. Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion. The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2. ISRCTN ISRCTN55670677 . Registered 09th November 2010. Retrospectively registered.