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Kern, Andreas, and Thomas Aigner. "Facies model for the Kieselsandstein (Keuper, Upper Triassic) in SW-Germany: A terminal alluvial plain." Neues Jahrbuch für Geologie und Paläontologie - Monatshefte 1997, no. 5 (May 23, 1997): 267–85. http://dx.doi.org/10.1127/njgpm/1997/1997/267.
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Vachard, Daniel, and Marc Roche. "Oxyhexactines de lyssakides(spongiaires hexactinellides) dans des préparations palynologiques du Rhétien (Trias terminal) de l'Est de la France." Geobios 29, no. 2 (January 1996): 171–76. http://dx.doi.org/10.1016/s0016-6995(96)80042-8.
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Brătucu, Gabriel, Gheorghiţa Dincă, Marius Sorin Dincă, and Alexandra (Palade) Zamfirache. "Opportunity of Constructing a Cargo Terminal – Case Study Brașov International Airport, Romania." Transylvanian Review of Administrative Sciences 2017, no. 50E (February 10, 2017): 38–53. http://dx.doi.org/10.24193/tras.2017.0003.
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Ouarhache, D., A. Charriere, F. Chalot-Prat, and M. El-Wartiti. "Sédimentation détritique continentale synchrone d'un volcanisme explosif dans le Trias terminal à infra-Lias du domaine atlasique (Haute Moulouya, Maroc) (Late Triassic to infra-Liassic continental detrital sedimentation synchronous with an explosive volcanic event in the Atlas area [Hgh Moulouya, Morocco])." Journal of African Earth Sciences 31, no. 3-4 (October 2000): 555–70. http://dx.doi.org/10.1016/s0899-5362(00)80007-x.
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Tan, Caimao, and Junliang He. "Integrated Yard Space Allocation and Yard Crane Deployment Problem in Resource-Limited Container Terminals." Scientific Programming 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/6421943.
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Yard storage space and yard crane equipment are the core resources in the container terminal yard area. This paper studies the integrated yard space allocation (outbound container space) and yard crane deployment problem in resource-limited container terminals where yard space and yard cranes are extremely scarce. Two corresponding counterstrategies are introduced, respectively, and the integrated problem is solved as mixed integer programming. The model this paper formulated considers the container volume fluctuation of the service line, and the objective is a trade-off between yard sharing space and terminal operation cost. In numerical experiments, this paper tries to reveal the management meaning in practical operation of container terminal and provides decision support for terminal managers; therefore a series of scenarios are presented to analyze the relations among the yard sharing space, the number of yard cranes, the size of yard subblock, and the cost of terminal operation.
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Anbazhagan, Krithika, Pooja Bhatnagar-Mathur, Kiran K. Sharma, Rekha Baddam, P. B. Kavi Kishor, and Vincent Vadez. "Changes in timing of water uptake and phenology favours yield gain in terminal water stressed chickpea AtDREB1A transgenics." Functional Plant Biology 42, no. 1 (2015): 84. http://dx.doi.org/10.1071/fp14115.
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Terminal drought causes major yield loss in chickpea, so it is imperative to identify genotypes with best suited adaptive traits to secure yield in terminal drought-prone environments. Here, we evaluated chickpea (At) rd29A:: (At) DREB1A transgenic events (RD2, RD7, RD9 and RD10) and their untransformed C235 genotype for growth, water use and yield under terminal water-stress (WS) and well-watered (WW) conditions. The assessment was made across three lysimetric trials conducted in contained environments in the greenhouse (2009GH and 2010GH) and the field (2010F). Results from the greenhouse trials showed genotypic variation for harvest index (HI), yield, temporal pattern of flowering and seed filling, temporal pattern of water uptake across crop cycle, and transpiration efficiency (TE) under terminal WS conditions. The mechanisms underlying the yield gain in the WS transgenic events under 2009GH trial was related to conserving water for the reproductive stage in RD7, and setting seeds early in RD10. Water conservation also led to a lower percentage of flower and pod abortion in both RD7 and RD10. Similarly, in the 2010GH trial, reduced water extraction during vegetative stage in events RD2, RD7 and RD9 was critical for better seed filling in the pods produced from late flowers in RD2, and reduced percentage of flower and pod abortion in RD2 and RD9. However, in the 2010F trial, the increased seed yield and HI in RD9 compared with C235 came along only with small changes in water uptake and podding pattern, probably not causal. Events RD2 (2010GH), RD7 (2010GH) and RD10 (2009GH) with higher seed yield also had higher TE than C235. The results suggest that DREB1A, a transcription factor involved in the regulation of several genes of abiotic stress response cascade, influenced the pattern of water uptake and flowering across the crop cycle, leading to reduction in the percentage of flower and pod abortion in the glasshouse trials.
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Kramer, J. W., and A. M. Corbett. "Comparison of Ca2+ loading and retention in isolated skeletal muscle triads and terminal cisternae." American Journal of Physiology-Cell Physiology 270, no. 6 (June 1, 1996): C1602—C1610. http://dx.doi.org/10.1152/ajpcell.1996.270.6.c1602.
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Ca2+ loading and retention were examined in isolated skeletal muscle triads and terminal cisternae to determine 1) whether excessive loading altered the response of triads to depolarization-induced Ca2+ release and 2) whether these vesicles were similar in their ability to load and retain Ca2+. A mixture of triads and terminal cisternae was loaded with variable amounts of Ca2+ and then subjected to maximal depolarization. Ca2+ release was monitored by changes in extravesicular fura 2 fluorescence using 340/380-nm excitation and 510-nm emission wavelengths. The amount of Ca2+ released from triads due to maximal depolarization increases with increasing Ca2+ loads until a maximal response is obtained, indicating triad saturation. At pH 7, triadic vesicles preferentially loaded and retained Ca2+ at low Ca2+ loads, but, with increasing loads, nontriadic vesicles began to retain Ca2+. At pH 6.5, which should close all open uncoupled ryanodine receptors, triadic and isolated terminal cisternae vesicles loaded and retained Ca2+ in a similar manner. A population of triads, which have some uncoupled ryanodine receptors, did not retain their loaded Ca2+ at pH 7.0 but did retain Ca2+ at pH 6.5; this resulted in a doubling of the amount of Ca2+ released on maximal depolarization after loading at pH 6.5.
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Yun, Xialun, Xuesong Mei, Gedong Jiang, Zhenbang Hu, and Zunhao Zhang. "Investigation on a No Trial Weight Spray Online Dynamic Balancer." Shock and Vibration 2018 (November 1, 2018): 1–15. http://dx.doi.org/10.1155/2018/7021215.
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In order to suppress the spindle vibration with high efficiency and high precision, a no without trial weight spray online balance method is proposed in this paper. By analyzing the relationship between the unbalanced excitation and the unbalanced response of the spindle, the relationship between the dynamic influence coefficient and the system model is studied. A high-speed spindle finite element analysis model was established, and the dynamic influence coefficient matrix was identified. A no trial weight spray online dynamic balancing system was developed, which has the advantages of without trial weight and high-precision loading. A new type of integrated balancing terminal that was formed using 3D printing technology was first proposed by our research group, and its advantages in various aspects are significantly higher than traditional assembly balanced terminals. The experimental verification of the without trial weight spray online dynamic balancing system was performed on a high-speed spindle test stand. Experiments show that the no trial weight spray online balancing method proposed in this paper can achieve high-efficiency and high-precision vibration suppression, greatly reducing balance time and cost of the spindle. At the same time, the online balance test also verified the reliability of the integrated balanced terminal.
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Hlubocky, Fay J., Nancy E. Kass, Debra Roter, Susan Larson, Kristen E. Wroblewski, Jeremy Sugarman, and Christopher K. Daugherty. "Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials." Journal of Oncology Practice 14, no. 6 (June 2018): e357-e367. http://dx.doi.org/10.1200/jop.18.00028.
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Purpose: Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding. Methods: Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall. Results: PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05). Conclusion: Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials.
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Cranshaw, Whitney, and Dayna Cooper. "Striped Pine Scale Control, Golden, Co, 1992." Arthropod Management Tests 20, no. 1 (January 1, 1995): 317. http://dx.doi.org/10.1093/amt/20.1.317.
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Abstract Trials were conducted at a golf course in Golden, CO on Scotch pine heavily infested with striped pine scale. Applications were made 17 Jun to point of run-off on individual infested terminal branches. Plot design was a RCB with 4 replications. At the time of treatment most nymphs had recently settled on the needles; few crawlers were present. Plots were evaluated by counting the number of dead and living nymphs on 10 needle bundles collected from terminals 5 Aug. Plots of SunSpray and Volck were retreated 5 Aug. Samples (10 needle bundles/plot) were again taken from all plots 10 Sep.
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Mitchell, JH, S. Fukai, and M. Cooper. "Influence of phenology on grain yield variation among barley cultivars grown under terminal drought." Australian Journal of Agricultural Research 47, no. 5 (1996): 757. http://dx.doi.org/10.1071/ar9960757.
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We investigated the influence of sowing time and genotypic variation for phenology on grain yield of barley in south-eastern Queensland. Over 3 seasons, 8 trials with 10 cultivars and 1 trial with 4 cultivars were conducted under either irrigated or terminal drought conditions at 2 locations. Rainout shelters ensured the development of severe terminal water stress. Trials were either sown on a common date, as conducted in traditional multi-environment trials, or over 3 weeks to synchronise anthesis among cultivars of different phenologies. Within the common sowing date trials, variation (P < 0.01) existed among cultivars for grain yield. From the 6 common sowing trials there was a negative correlation (P < 0.05) between grain yield and days to anthesis; that is, the shorter duration cultivars expressed the highest grain yield. Variation in days to anthesis accounted for 48-72% of the variation for grain yield. In the staggered sowing trials, where anthesis of all cultivars occurred within 4 or 2 days of the mean anthesis date, variation for grain yield was small or non-significant, and there was no association between grain yield and days to anthesis. The staggered sowing experiment with 10 cultivars indicated that duration of the vegetative phase was important in determining total dry matter production at maturity when cultivars were grown under terminal drought. Long-duration cultivars sown earlier had greater total dry matter at maturity than short-duration cultivars. This was associated with a greater water extraction by the long-duration cultivars, especially at depth, which remained inaccessible to later sown, short-duration cultivars. However, due to the low harvest index of the long-duration cultivars, grain yield of long- and short-duration cultivars was comparable when anthesis of cultivars was synchronised. When sown at the same time, a short-duration cultivar is advantageous because of a high chance of escaping water stress that develops during the critical development stage of anthesis. The results from the staggered sowing date experiments, however, indicated that the long-duration cultivars, when sown earlier in the season, had no yield disadvantage in comparison with the short-duration cultivars sown later in the season. Therefore, there is scope to develop barley cultivars of later phenology than is currently available to provide Queensland farmers with the option of utilising early rainfall events which are sometimes the only planting opportunity.
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Rossi, Daniela, Angela Maria Scarcella, Enea Liguori, Stefania Lorenzini, Enrico Pierantozzi, Candice Kutchukian, Vincent Jacquemond, Mirko Messa, Pietro De Camilli, and Vincenzo Sorrentino. "Molecular determinants of homo- and heteromeric interactions of Junctophilin-1 at triads in adult skeletal muscle fibers." Proceedings of the National Academy of Sciences 116, no. 31 (July 17, 2019): 15716–24. http://dx.doi.org/10.1073/pnas.1820980116.
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In adult skeletal muscles, 2 junctophilin isoforms (JPH1 and JPH2) tether the sarcoplasmic reticulum (SR) to transverse tubule (T-tubule) membranes, generating stable membrane contact sites known as triads. JPHs are anchored to the membrane of the SR by a C-terminal transmembrane domain (TMD) and bind the T-tubule membrane through their cytosolic N-terminal region, which contains 8 lipid-binding (MORN) motifs. By combining expression of GFP-JPH1 deletion mutants in skeletal muscle fibers with in vitro biochemical experiments, we investigated the molecular determinants of JPH1 recruitment at triads in adult skeletal muscle fibers. We found that MORN motifs bind PI(4,5)P2 in the sarcolemma, but do not mediate the selective localization of JPH1 at the T-tubule compartment of triads. On the contrary, fusion proteins containing only the TMD of JPH1 were able to localize at the junctional SR compartment of the triad. Bimolecular fluorescence complementation experiments indicated that the TMD of JPH1 can form dimers, suggesting that the observed localization at triads may result from dimerization with the TMDs of resident JPH1. A second domain, capable of mediating homo- and heterodimeric interactions between JPH1 and JPH2 was identified in the cytosolic region. FRAP experiments revealed that removal of either one of these 2 domains in JPH1 decreases the association of the resulting mutant proteins with triads. Altogether, these results suggest that the ability to establish homo- and heterodimeric interactions with resident JPHs may support the recruitment and stability of newly synthesized JPHs at triads in adult skeletal muscle fibers.
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Daugherty, C., N. E. Kass, D. Roter, S. Larson, J. Sugarman, K. Kasza, M. J. Ratain, and F. J. Hlubocky. "A study of physician investigator (PI) disclosure of alternatives of care and prognostic information to advanced cancer patients (ACP) enrolling in phase I trials." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 6508. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.6508.
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6508 Background: ACP in phase I trials have been described as having an inadequate understanding of several elements of informed consent. However, actual PI disclosure of alternatives to trial participation and prognostic information, and subsequent ACP understanding of these elements, have not been described. Methods: Clinical encounters between 131 ACP entering phase I trials and 25 oncologists at three institutions (University of Chicago; Johns Hopkins; and Duke University) were audio-taped. ACP completed follow-up questionnaires one week later to assess understanding of informed consent elements. Audiotapes were analyzed using the Roter Interaction Analysis System (RIAS) and specifically coded for terms associated with trial alternatives and patient prognosis. Results: To date, 85 encounters have been analyzed. Average encounters length: 30.4 min (range: 5.7–77.8 min). For ACP: median age 60y (33–83); 55% female; 88% Ca; 55% <college educ; 52% income <$60,000. The PI was recorded as discussing options other than anticancer treatment in 47% of encounters. The terms “palliative” or “hospice” were used in 1% and 2.3% of encounters respectively. In 29% of encounters the PI described the option of “doing nothing”. The PI used the terms “death” or “terminal” in 5.8% encounters. The PI was never recorded using the term “dying”. Within these encounters, no ACP was recorded as using any of the following terms: “palliative,” “hospice,” “terminal,” “death,” “dying.” Within follow-up interviews, 30% reported no alternatives to trial participation were discussed; 1% reported that palliative care/hospice was discussed. Based on coding of qualitative responses, 53% of ACP said that either their prognosis was excellent or they didn't know their prognosis. An association was found between recorded physician statements regarding general prognosis and ACP subsequently reporting having discussion regarding life expectancy (59% v. 33%, p = 0.04). Conclusions: PI communication and subsequent measured understanding regarding alternatives to trial participation and prognosis remain inadequate in the setting of phase I trial enrollment. [Table: see text]
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Boland, M. R., R. Miotto, J. Gao, and C. Weng. "Feasibility of Feature-based Indexing, Clustering, and Search of Clinical Trials." Methods of Information in Medicine 52, no. 05 (2013): 382–94. http://dx.doi.org/10.3414/me12-01-0092.
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SummaryBackground: When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space.Objectives: This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes.Methods: We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively.Results: We extracted 1,437 distinct eligi -bility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction.Conclusions: It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.
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Selden, Nathan R. "Minimal tethered cord syndrome: what's necessary to justify a new surgical indication?" Neurosurgical Focus 23, no. 2 (August 2007): 1–5. http://dx.doi.org/10.3171/foc-07/08/e1.
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✓Traditionally, surgical division of the terminal filum (filum terminale) has been reserved for patients with imaging-apparent spinal cord tethering. The occurrence of medically refractory voiding dysfunction of neurogenic origin, without magnetic resonance (MR) imaging documentation of abnormality in the spine, has been termed “minimal” tethered cord syndrome (TCS). The rationale for and utility of using surgical division of the terminal filum in the treatment of minimal TCS are unproven. Six studies that involved surgical division of the terminal filum for minimal TCS were identified and reviewed. A seventh study conducted prior to the MR imaging era, in which authors used myelography, was also included. In addition, two investigations of the clinicopathological findings in such cases were analyzed. A tripartite criterion for justifying the introduction of a new surgical indication is proposed and analyzed in light of this evidence. In children with minimal TCS there are definite pathological changes in the terminal filum that are not visible on routine spinal MR imaging. These changes suggest that the pathophysiology of minimal TCS, like TCS that is demonstrated on neuroimaging, may involve abnormal traction on the distal spinal cord. Additional data are needed regarding the sensitivity and specificity of various clinical studies intended to identify children with minimal TCS. All existing data supporting the efficacy of surgery for minimal TCS have been generated by Class III studies. Clinical equipoise exists for this surgical indication, and, therefore, a prospective randomized trial should be completed.
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SCHEIN, STAN, IVY TRAN NGO, TERESA M. HUANG, KARL KLUG, PETER STERLING, and STEVE HERR. "Cone synapses in macaque fovea: I. Two types of non-S cones are distinguished by numbers of contacts with OFF midget bipolar cells." Visual Neuroscience 28, no. 1 (January 2011): 3–16. http://dx.doi.org/10.1017/s0952523810000477.
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AbstractL and M cones, divided into two groups by absorption spectra, have not been distinguished by structure. Here, we report what may be such a difference. We reconstructed the synaptic terminals of 16 non-S cones and the dendritic arbors of their ON and OFF midget bipolar cells from high-magnification electron micrographs of serial thin sections of a small region of macaque fovea. Each cone terminal contacted a similar number (~16) of invaginating central elements provided by its ON midget bipolar cell. By contrast, the numbers of connections between a cone terminal and its OFF midget bipolar cell were grouped into two clusters: 30–37 versus 43–50 basal contacts in the triad-associated position and 41–47 versus 61–74 Outer Densities within those basal contacts. The coefficients of variation of these distributions were all in the range of 10% or lower, characteristic of single populations. If these two clusters correspond to M- and L-cone circuits, the results reveal structural differences between M and L cones and between their corresponding OFF midget bipolar cells.
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SCHROETER, ERIC H., RACHEL O. L. WONG, and RONALD G. GREGG. "In vivo development of retinal ON-bipolar cell axonal terminals visualized in nyx::MYFP transgenic zebrafish." Visual Neuroscience 23, no. 5 (September 2006): 833–43. http://dx.doi.org/10.1017/s0952523806230219.
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Axonal differentiation of retinal bipolar cells has largely been studied by comparing the morphology of these interneurons in fixed tissue at different ages. To better understand how bipolar axonal terminals develop in vivo, we imaged fluorescently labeled cells in the zebrafish retina using time-lapse confocal and two photon microscopy. Using the upstream regulatory sequences from the nyx gene that encodes nyctalopin, we constructed a transgenic fish in which a subset of retinal bipolar cells express membrane targeted yellow fluorescent protein (MYFP). Axonal terminals of these YFP-labeled bipolar cells laminated primarily in the inner half of the inner plexiform layer, suggesting that they are likely to be ON-bipolar cells. Transient expression of MYFP in isolated bipolar cells indicates that two or more subsets of bipolar cells, with one or two terminal boutons, are labeled. Live imaging of YFP-expressing bipolar cells in the nyx::MYFP transgenic fish at different ages showed that initially, filopodial-like structures extend and retract from their primary axonal process throughout the inner plexiform layer (IPL). Over time, filopodial exploration becomes concentrated at discrete foci prior to the establishment of large terminal boutons, characteristic of the mature form. This sequence of axonal differentiation suggests that synaptic targeting by bipolar cell axons may involve an early process of trial and error, rather than a process of directed outgrowth and contact. Our observations represent the first in vivo visualization of axonal development of bipolar cells in a vertebrate retina.
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Anderson, Deverick J., Lauren P. Knelson, Rebekah W. Moehring, Sarah S. Lewis, David J. Weber, Luke F. Chen, Patricia F. Triplett, et al. "Implementation Lessons Learned From the Benefits of Enhanced Terminal Room (BETR) Disinfection Study: Process and Perceptions of Enhanced Disinfection with Ultraviolet Disinfection Devices." Infection Control & Hospital Epidemiology 39, no. 2 (January 14, 2018): 157–63. http://dx.doi.org/10.1017/ice.2017.268.
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OBJECTIVETo summarize and discuss logistic and administrative challenges we encountered during the Benefits of Enhanced Terminal Room (BETR) Disinfection Study and lessons learned that are pertinent to future utilization of ultraviolet (UV) disinfection devices in other hospitalsDESIGNMulticenter cluster randomized trialSETTING AND PARTICIPANTSNine hospitals in the southeastern United StatesMETHODSAll participating hospitals developed systems to implement 4 different strategies for terminal room disinfection. We measured compliance with disinfection strategy, barriers to implementation, and perceptions from nurse managers and environmental services (EVS) supervisors throughout the 28-month trial.RESULTSImplementation of enhanced terminal disinfection with UV disinfection devices provides unique challenges, including time pressures from bed control personnel, efficient room identification, negative perceptions from nurse managers, and discharge volume. In the course of the BETR Disinfection Study, we utilized several strategies to overcome these barriers: (1) establishing safety as the priority; (2) improving communication between EVS, bed control, and hospital administration; (3) ensuring availability of necessary resources; and (4) tracking and providing feedback on compliance. Using these strategies, we deployed ultraviolet (UV) disinfection devices in 16,220 (88%) of 18,411 eligible rooms during our trial (median per hospital, 89%; IQR, 86%–92%).CONCLUSIONSImplementation of enhanced terminal room disinfection strategies using UV devices requires recognition and mitigation of 2 key barriers: (1) timely and accurate identification of rooms that would benefit from enhanced terminal disinfection and (2) overcoming time constraints to allow EVS cleaning staff sufficient time to properly employ enhanced terminal disinfection methods.TRIAL REGISTRATIONClinical trials identifier: NCT01579370Infect Control Hosp Epidemiol 2018;39:157–163
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Adak, Alper, Seth C. Murray, Sofija Božinović, Regan Lindsey, Shakirah Nakasagga, Sumantra Chatterjee, Steven L. Anderson, and Scott Wilde. "Temporal Vegetation Indices and Plant Height from Remotely Sensed Imagery Can Predict Grain Yield and Flowering Time Breeding Value in Maize via Machine Learning Regression." Remote Sensing 13, no. 11 (May 29, 2021): 2141. http://dx.doi.org/10.3390/rs13112141.
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Unoccupied aerial system (UAS; i.e., drone equipped with sensors) field-based high-throughput phenotyping (HTP) platforms are used to collect high quality images of plant nurseries to screen genetic materials (e.g., hybrids and inbreds) throughout plant growth at relatively low cost. In this study, a set of 100 advanced breeding maize (Zea mays L.) hybrids were planted at optimal (OHOT trial) and delayed planting dates (DHOT trial). Twelve UAS surveys were conducted over the trials throughout the growing season. Fifteen vegetative indices (VIs) and the 99th percentile canopy height measurement (CHMs) were extracted from processed UAS imagery (orthomosaics and point clouds) which were used to predict plot-level grain yield, days to anthesis (DTA), and silking (DTS). A novel statistical approach utilizing a nested design was fit to predict temporal best linear unbiased predictors (TBLUP) for the combined temporal UAS data. Our results demonstrated machine learning-based regressions (ridge, lasso, and elastic net) had from 4- to 9-fold increases in the prediction accuracies and from 13- to 73-fold reductions in root mean squared error (RMSE) compared to classical linear regression in prediction of grain yield or flowering time. Ridge regression performed best in predicting grain yield (prediction accuracy = ~0.6), while lasso and elastic net regressions performed best in predicting DTA and DTS (prediction accuracy = ~0.8) consistently in both trials. We demonstrated that predictor variable importance descended towards the terminal stages of growth, signifying the importance of phenotype collection beyond classical terminal growth stages. This study is among the first to demonstrate an ability to predict yield in elite hybrid maize breeding trials using temporal UAS image-based phenotypes and supports the potential benefit of phenomic selection approaches in estimating breeding values before harvest.
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Borer, Katarina T., Qingyun Zheng, Akram Jafari, Saba Javadi, and Thomas Kernozek. "Nutrient Intake Prior to Exercise Is Necessary for Increased Osteogenic Marker Response in Diabetic Postmenopausal Women." Nutrients 11, no. 7 (June 30, 2019): 1494. http://dx.doi.org/10.3390/nu11071494.
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Type 2 diabetes increases bone fracture risk in postmenopausal women. Usual treatment with anti-resorptive bisphosphonate drugs has some undesirable side effects, which justified our interest in the osteogenic potential of nutrition and exercise. Since meal eating reduces bone resorption, downhill locomotion increases mechanical stress, and brief osteogenic responsiveness to mechanical stress is followed by several hours of refractoriness, we designed a study where 40-min of mechanical stress was manipulated by treadmill walking uphill or downhill. Exercise preceded or followed two daily meals by one hour, and the meals and exercise bouts were 7 hours apart. Fifteen subjects each performed two of five trials: No exercise (SED), uphill exercise before (UBM) or after meals (UAM), and downhill exercise before (DBM) or after meals (DAM). Relative to SED trial, osteogenic response, defined as the ratio of osteogenic C-terminal propeptide of type I collagen (CICP) over bone-resorptive C-terminal telopeptide of type-I collagen (CTX) markers, increased in exercise-after-meal trials, but not in exercise-before-meal trials. CICP/CTX response rose significantly after the first exercise-after-meal bout in DAM, and after the second one in UAM, due to a greater CICP rise, and not a decline in CTX. Post-meal exercise, but not the pre-meal exercise, also significantly lowered serum insulin response and homeostatic model (HOMA-IR) assessment of insulin resistance.
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Hersh, Andrew, and Scott K. Aberegg. "N-Terminal Pro–Brain Natriuretic Peptide Trial Design." American Journal of Respiratory and Critical Care Medicine 196, no. 4 (August 15, 2017): 530. http://dx.doi.org/10.1164/rccm.201610-2139le.
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Slovin, Susan F., Karen E. Knudsen, Susan Halabi, Emily Carbone, Celina Fernandez, Yu Chen, Karen A. Autio, et al. "Circulating tumor cells (CTCs) N-terminal androgen receptor expression to identify patients (pts) with castrate resistant prostate cancer (CRPC) who are more sensitive to chemotherapy." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 5034. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.5034.
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5034 Background: Loss of the retinoblastoma tumor suppressor (RB) function was identified as a major means to develop CRPC; the expression of the androgen receptor (AR) is under stringent RB control; and tumors devoid of RB function are hypersensitive to treatment with chemotherapy. Exploratory analysis evaluated baseline N-terminal AR expression in CTCs in men with chemotherapy-naïve CPRC and correlated to changes in PSA, leading us to inquire if this biomarker may identify pts sensitive to chemotherapy. Methods: In a multicenter phase II randomized trial of approved doses of abiraterone acetate/prednisone (AA-Arm 1) or combination AA and standard doses of cabazitaxel (AA/CBZ-Arm 2). Patients on AA received CBZ upon progression. Baseline CTCs were obtained on all pts and expression of N-terminal AR expression was performed by Epic Sciences. Positive AR N-terminal expression (AR+) was based on the presence of at least 1 CTC or CK- cell with AR N-terminal signal expression above the 3.0 positivity threshold. Serial PSAs were determined at baseline and every 3 weeks with routine labs and imaging every 12 weeks. Results: To date, 42 of 80 pts have been enrolled: 22 pts to AA, and 20 pts to AA/CBZ. Both regimens were well tolerated with 8/42 (19%) pts experiencing treatment-related grade 3 or 4 toxicities. Blood from 35 patients underwent CTC analysis. Seventy-seven percent of pts (27/35) had detectable CTCs; 11 of 35 pts (31%) had AR overexpression. Of the pts with AR+ CTCs, 1/5 pts treated with AA, and 5/6 pts treated with AA/CBZ had a PSA decline > 50% from baseline. Conclusions: Real-time CTC analysis of N-terminal AR expression was feasible and data suggests that this may identify a cohort of pts who may benefit from the combination of CBZ with AA. Further studies are ongoing to evaluate whether cellular heterogeneity and RB expression in CTCs play a role in identifying pts who would benefit from chemotherapy. The trial is coordinated by the Prostate Cancer Clinical Trials Consortium, LLC and funded by Sanofi US Services Inc. and Prostate Cancer Foundation. Clinical trial information: NCT02218606.
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Hill, Shannon E., Hayeon Cho, Priyam Raut, and Raquel L. Lieberman. "Calcium-ligand variants of the myocilin olfactomedin propeller selected from invertebrate phyla reveal cross-talk with N-terminal blade and surface helices." Acta Crystallographica Section D Structural Biology 75, no. 9 (August 22, 2019): 817–24. http://dx.doi.org/10.1107/s205979831901074x.
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Olfactomedins are a family of modular proteins found in multicellular organisms that all contain five-bladed β-propeller olfactomedin (OLF) domains. In support of differential functions for the OLF propeller, the available crystal structures reveal that only some OLF domains harbor an internal calcium-binding site with ligands derived from a triad of residues. For the myocilin OLF domain (myoc-OLF), ablation of the ion-binding site (triad Asp, Asn, Asp) by altering the coordinating residues affects the stability and overall structure, in one case leading to misfolding and glaucoma. Bioinformatics analysis reveals a variety of triads with possible ion-binding characteristics lurking in OLF domains in invertebrate chordates such as Arthropoda (Asp–Glu–Ser), Nematoda (Asp–Asp–His) and Echinodermata (Asp–Glu–Lys). To test ion binding and to extend the observed connection between ion binding and distal structural rearrangements, consensus triads from these phyla were installed in the myoc-OLF. All three protein variants exhibit wild-type-like or better stability, but their calcium-binding properties differ, concomitant with new structural deviations from wild-type myoc-OLF. Taken together, the results indicate that calcium binding is not intrinsically destabilizing to myoc-OLF or required to observe a well ordered side helix, and that ion binding is a differential feature that may underlie the largely elusive biological function of OLF propellers.
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Rodrigo, Chaturaka, Senaka Rajapakse, and Sumadhya Deepika Fernando. "Tafenoquine for primary and terminal prophylaxis of malaria in apparently healthy people: a systematic review." Transactions of The Royal Society of Tropical Medicine and Hygiene 113, no. 10 (June 21, 2019): 579–86. http://dx.doi.org/10.1093/trstmh/trz052.
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Abstract Primaquine was the only licenced antimalarial hypnozoiticidal drug available until recently. Now there is a newly approved alternative: tafenoquine. This review explores the efficacy of tafenoquine as a primary and terminal prophylactic agent in malaria. Multiple databases (Cochrane Central Register of Controlled Trials [CENTRAL], MEDLINE [PubMed], Embase [Ovid], Scopus, CINAHL [EBSCOhost] and LILACS) were searched for clinical randomised controlled trials that had used tafenoquine for prophylaxis without language or time restrictions. The last date of searching was 13 August 2018. For primary prophylaxis, tafenoquine reduced episodes of malaria compared with placebo, at a dose range from 50 mg weekly to 400 mg monthly in three trials conducted in Ghana, Kenya and Thailand. Two trials compared tafenoquine vs mefloquine, but malaria episodes were too few to reach a conclusion. For terminal prophylaxis, evidence from two trials suggest that tafenoquine may have equal or better efficacy compared with primaquine. All trials excluded pregnant participants or those with G6PD deficiency. Tafenoquine is effective for both primary and terminal prophylaxis. If used for primary prophylaxis it may continue to offer protection against vivax relapses after exposure has ended (as terminal prophylaxis).
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Lam, Y. W., C. L. Cox, C. Varela, and S. Murray Sherman. "Morphological Correlates of Triadic Circuitry in the Lateral Geniculate Nucleus of Cats and Rats." Journal of Neurophysiology 93, no. 2 (February 2005): 748–57. http://dx.doi.org/10.1152/jn.00256.2004.
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We used an in vitro slice preparation of the lateral geniculate nucleus in cats and rats to study morphological correlates of triadic circuitry in relay cells. The three triadic elements involve a retinal synapse onto a GABAergic dendritic terminal of an interneuron, a synapse from the same retinal terminal onto a relay cell dendrite, and a synapse from the same interneuron terminal onto the same relay cell dendrite. We made whole cell recordings and labeled cells with biocytin. Previous methods were used to identify triadic circuitry based on evidence that the retinal terminal activates a metabotropic glutamate receptor on the interneuronal terminal. Thus application of (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid (an agonist to that receptor) increases the rate of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in the relay cell, and if some of this increase remains with further addition of TTX (a TTX-insensitive response), a triad is indicated. We quantified the extent of the TTX-insensitive response and sought morphological correlates. In both rats and cats, this response correlated (negatively) with the number of primary dendrites and (positively) with polarity of the dendritic arbor. There was no correlation with cell size. Curiously, in cats, this response correlated with the presence of appendages at primary dendritic branches, but there was no such correlation in rats. These observations in cats map onto the X/Y classification, with X cells having triads, but it is not clear from our results if a comparable classification exists for rats.
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Li, Zhigang, H. R. Frost, Qian Yang, Marie Bakitas, and Tor Tosteson. "Joint modeling, quality of life, and survival in fast-track (or delayed-start) palliative care trials." Journal of Clinical Oncology 32, no. 31_suppl (November 1, 2014): 49. http://dx.doi.org/10.1200/jco.2014.32.31_suppl.49.
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49 Background: Randomized “early intervention” or “fast-track” trials (also sometimes called delayed intervention, delayed-start, or wait list designs) have been proposed as an alternative to traditional RCTs comparing palliative care interventions to non-palliative or other supportive care groups. The fast-track arm receives intervention immediately after randomization and the control arm receiving intervention after a certain period following randomization during which time standard care is provided. Such trials are more acceptable to patients, families and physicians because no one is denied access to the intervention, while still allowing for a rigorous assessment of a palliative care intervention. Many issues remain with respect to implementing such designs and analyzing the longitudinal quality of life and survival. Methods: We have developed a terminal decline model (Li et al. 2013) for jointly modeling quality of life and survival in palliative care studies. This model can be implemented on an intention to treat basis for the overall comparison in fast track design. For time periods beyond the delayed start period, we modify the model to include a time-varying treatment variable in the model to account for the treatment change in the control arm, including an interaction between the treatment and the time period. Terminal declines and quality-adjusted life years are estimated for both the intention to treat and the modified model. Results: ENABLE III is a recently completed fast-track trial in our institution at Dartmouth. After applied to ENABLE III study, the novel statistical joint modeling approach indicates that the effect of the ENABLE intervention on the terminal decline increases when combined with intervention effect seen for fast track arm. Conclusions: The terminal decline joint modeling approach is an efficient and interpretable method for fast-track study designs.
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Tosteson, Tor D., Zhigang Li, Qian Yang, H. Robert Frost, and Marie Bakitas. "Analysis of palliative care studies with joint models for quality-of-life measures and survival." Journal of Clinical Oncology 32, no. 31_suppl (November 1, 2014): 41. http://dx.doi.org/10.1200/jco.2014.32.31_suppl.41.
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41 Background: In palliative care studies, the primary outcomes are often health related quality of life measures (HRLQ). Randomized trials and prospective cohorts typically recruit patients with advanced stage of disease and follow them until death or end of the study. During this time, HRLQ measures are collected at regular intervals. The typical analysis involves comparing the means of two or more intervention or exposure groups at specific times from entry into the study. An important feature of such studies is that, by design, some patients, but not all, are likely to die during the course of the study. For instance, in the Dartmouth ENABLE II study (Bakitas et al., 2009), 60% of patients died during the study. This feature affects the interpretation of the conventional analysis of palliative care trials and suggests the need for specialized methods of analysis. Methods: We have developed a “terminal decline model” for palliative care trials that, by jointly modeling the time until death and the HRQL measures, leads to flexible interpretation and efficient analysis of the trial data (Li, Tosteson, Bakitas, 2012). Importantly, it allows the estimation of the quality of life in the months preceding death, and specifically incorporates data for patients not dying during the study. At the same time, it permits the efficient estimation and interpretation of HRQL effects as measured in the conventional analysis as the difference in HRQL at specified times from enrollment conditional on being alive. Finally, it allows the estimation of the HRQL weighted survival or quality adjusted life years (QALY). Results: Based on the terminal decline model, survival distributions are shown affect the conventional estimates of HRQL trends in palliative care trials. A direct estimate for quality of life at specified times prior to death is provided. The methods are illustrated with ENABLE II data as an approach for improving the conduct of palliative care studies. Conclusions: Proper interpretation of palliative care studies requires consideration of the joint distribution of quality of life measures and survival as in the terminal decline model.
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Chapman, S. C., G. L. Hammer, D. G. Butler, and M. Cooper. "Genotype by environment interactions affecting grain sorghum. III. Temporal sequences and spatial patterns in the target population of environments." Australian Journal of Agricultural Research 51, no. 2 (2000): 223. http://dx.doi.org/10.1071/ar99022.
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The variable nature of rainfall in north-eastern Australia confounds the process of selecting sorghum hybrids that are broadly adapted. This paper uses a crop simulation model to characterise the drought environment types (ET) that occur in the target population of environments (TPE) for dryland sorghum. Seventy seasons (1921–1990) of simulations of the yield of a sorghum genotype and the associated within-season sequence of a stress index were conducted for a small TPE of 6 locations and also for a large TPE of 211 locations that attempted to represent the entire sorghum region. Previously, using the small dataset of 6 locations, pattern analysis enabled us to group seasonal stress indices from each trial into major ETs: ‘low terminal stress’ (ET1), severe terminal stress (ET2), and intermediate mid-season/terminal stress (ET3) in the ratio 33 : 38 : 29. When the dataset was broken into a sequence of 16 multi-environment trials (METs), each of 3 years and 6 locations, the ratios of ET1 : ET2 : ET3 differed greatly among METs, i.e. any single MET was not randomly sampling the TPE. Hence, for any MET, the average yield (GVu) was not the same as the overall mean of the entire 70-year dataset. If the trial yields were weighted according to the ratio of ET1 : ET2 : ET3 in the overall TPE, then GVw (s.d. = 0.13) for a single MET was much closer to the overall mean than was GVu (0.38). For different METs, the values of GVw were up to 30% higher or 15% lower than GVu. Across METs, the difference between GVu and GVw was positively correlated (r = 0.88, n = 16, P < 0.05) with the frequency of ET1 (‘low terminal stress’) encountered within the MET and negatively correlated (r = −0.82) with the frequency of ET2. The value of weighting was confirmed by its ability to verify that two simulated genotypes had the same mean yield over many trials, even though they differed in their specific adaptation to the different ETs. The large TPE consisted of more than 15 000 simulations and was classified in 2 stages (within/among locations), repeated for each of 3 soil types. In years in which the simulation sowing criteria were met, the ratios of ET1 : ET2 : ET3 were about 4:2:4, 4:5:1, and 6:3:1 in the shallow, intermediate, and deep soils, respectively. Hence, over all soil types and locations, the sorghum TPE for northern Australia consists of at least 30% each of low terminal stress (ET1) or severe terminal stress (ET2) and these environment types need to be sampled. The incidence and nature of the ‘intermediate midseason/terminal stress’ environment type (ET3) varies with soil type and location. Weighting genotype performance should improve the precision of the estimate of its broadly adapted value, and be of practical use in breeding programs in these variable environments. Although the ‘boundary conditions’ of the TPE are not yet resolved, this paper also shows that simulation and pattern analyses can be used to determine the structure of the abiotic TPE. Taking other factors into account (e.g. soil type distribution, shire production levels, and farm profit), selection trials could be weighted to improve selection for narrow or broad adaptation, depending on the purpose of the breeding program.
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Zidon, Terese M., and Don D. Sheriff. "Diversion of blood flow from noncompliant to compliant vasculature in awake dogs: mechanical impact on right atrial pressure." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 1 (January 2006): H217—H223. http://dx.doi.org/10.1152/ajpheart.00482.2005.
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The distribution of cardiac output between compliant vasculature (e.g., splanchnic organs and skin) and noncompliant vasculature (e.g., skeletal muscle) is proposed to constitute an important determinant of the amount of blood available to the heart (central blood volume and pressure). The aim here was to directly test the hypothesis that diversion of blood flow from a relatively noncompliant vasculature (muscle) to compliant vasculature (splanchnic organs and skin) acts to reduce right atrial pressure. The approach was to inflate an occluder cuff on the terminal aorta for 30 s in one of two modes of ventricular pacing in five awake dogs with atrioventricular block and autonomic blockade. In one trial, cardiac output was maintained constant, meaning cuff inflation caused a portion of terminal aortic flow (a noncompliant circulation) to be diverted to the splanchnic and skin circulations (compliant circulations). In the other trial, arterial pressure was maintained constant, meaning blood flow to these other regions did not change. The response of right atrial pressure (corrected for differences in arterial pressure between the two trials) fit our hypothesis, being lower when blood flow was diverted to compliant regions. We conclude that a small (4% of cardiac output) diversion of blood flow from a noncompliant region to a compliant region reduces right atrial pressure by 0.7 mmHg.
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Wang, Jue, and Sheng Luo. "Joint modeling of multiple repeated measures and survival data using multidimensional latent trait linear mixed model." Statistical Methods in Medical Research 28, no. 10-11 (October 11, 2018): 3392–403. http://dx.doi.org/10.1177/0962280218802300.
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Impairment caused by Amyotrophic lateral sclerosis (ALS) is multidimensional (e.g. bulbar, fine motor, gross motor) and progressive. Its multidimensional nature precludes a single outcome to measure disease progression. Clinical trials of ALS use multiple longitudinal outcomes to assess the treatment effects on overall improvement. A terminal event such as death or dropout can stop the follow-up process. Moreover, the time to the terminal event may be dependent on the multivariate longitudinal measurements. In this article, we develop a joint model consisting of a multidimensional latent trait linear mixed model (MLTLMM) for the multiple longitudinal outcomes, and a proportional hazards model with piecewise constant baseline hazard for the event time data. Shared random effects are used to link together two models. The model inference is conducted using a Bayesian framework via Markov chain Monte Carlo simulation implemented in Stan language. Our proposed model is evaluated by simulation studies and is applied to the Ceftriaxone study, a motivating clinical trial assessing the effect of ceftriaxone on ALS patients.
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Shaw, Lee, and Oliver Wiedow. "Therapeutic potential of human elafin." Biochemical Society Transactions 39, no. 5 (September 21, 2011): 1450–54. http://dx.doi.org/10.1042/bst0391450.
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Elafin is an endogenous human protein composed of an N-terminal transglutaminase substrate motif and a C-terminal WAP (whey acidic protein)-domain with antiproteolytic properties. Elafin is expressed predominantly in epithelial tissue and potently inhibits the neutrophil-derived serine proteases elastase and proteinase-3 by a competitive tight-binding mechanism. Furthermore, it inhibits EVE (endogenous vascular elastase). Studies on several animal models show that antiprotease augmentation with human elafin is an effective strategy in the treatment of inflammatory vascular, systemic and pulmonary diseases and of inflammation triggered by reperfusion injury. This raises the possibility that elafin might be effective in the treatment of a variety of human inflammatory diseases. In a Phase I clinical trial, elafin was well tolerated. Phase II trials are underway to investigate the therapeutic effects of elafin on post-operative inflammation and the clinical consequences of major surgery. Of particular interest is the reduction of post-operative morbidity after oesophagus cancer surgery, coronary artery bypass surgery and kidney transplantation.
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Sanchez, Jackee, Trever R. Carter, Mark S. Cohen, and Brian S. J. Blagg. "Old and New Approaches to Target the Hsp90 Chaperone." Current Cancer Drug Targets 20, no. 4 (April 30, 2020): 253–70. http://dx.doi.org/10.2174/1568009619666191202101330.
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The 90-kDa heat shock protein (Hsp90) is a molecular chaperone that ensures cellular proteostasis by maintaining the folding, stabilization, activation, and degradation of over 400 client proteins. Hsp90 is not only critical for routine protein maintenance in healthy cells, but also during states of cellular stress, such as cancer and neurodegenerative diseases. Due to its ability to affect phosphorylation of numerous client proteins, inhibition of Hsp90 has been an attractive anticancer approach since the early 1990’s, when researchers identified a druggable target on the amino terminus of Hsp90 for a variety of cancers. Since then, 17 Hsp90 inhibitors that target the chaperone’s Nterminal domain, have entered clinical trials. None, however, have been approved thus far by the FDA as a cancer monotherapy. In these trials, a major limitation observed with Hsp90 inhibition at the N-terminal domain was dose-limiting toxicities and relatively poor pharmacokinetic profiles. Despite this, preclinical and clinical research continues to show that Hsp90 inhibitors effectively target cancer cell death and decrease tumor progression supporting the rationale for the development of novel Hsp90 inhibitors. Here, we present an in-depth overview of the Hsp90 inhibitors used in clinical trials. Finally, we present current shifts in the field related to targeting the carboxy-terminal domain of Hsp90 as well as to the development of isoform-selective inhibitors as a means to bypass the pitfalls of current Hsp90 inhibitors and improve clinical trial outcomes.
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Stevens, Rebecca V., Diego Esposito, and Katrin Rittinger. "Characterisation of class VI TRIM RING domains: linking RING activity to C-terminal domain identity." Life Science Alliance 2, no. 3 (April 26, 2019): e201900295. http://dx.doi.org/10.26508/lsa.201900295.
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TRIM E3 ubiquitin ligases regulate multiple cellular processes, and their dysfunction is linked to disease. They are characterised by a conserved N-terminal tripartite motif comprising a RING, B-box domains, and a coiled-coil region, with C-terminal domains often mediating substrate recruitment. TRIM proteins are grouped into 11 classes based on C-terminal domain identity. Class VI TRIMs, TRIM24, TRIM33, and TRIM28, have been described as transcriptional regulators, a function linked to their C-terminal plant homeodomain and bromodomain, and independent of their ubiquitination activity. It is unclear whether E3 ligase activity is regulated in family members where the C-terminal domains function independently. Here, we provide a detailed biochemical characterisation of the RING domains of class VI TRIMs and describe the solution structure of the TRIM28 RING. Our study reveals a lack of activity of the isolated RING domains, which may be linked to the absence of self-association. We propose that class VI TRIMs exist in an inactive state and require additional regulatory events to stimulate E3 ligase activity, ensuring that associated chromatin-remodelling factors are not injudiciously degraded.
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Masuno, M., K. Imaizumi, N. Aida, Y. Tanaka, K. Sekido, Y. Ohhama, T. Nishi, and Y. Kuroki. "Currarino triad with a terminal deletion 7q35-->qter." Journal of Medical Genetics 33, no. 10 (October 1, 1996): 877–78. http://dx.doi.org/10.1136/jmg.33.10.877.
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den Exter, Paul L., Frederikus A. Klok, and Menno V. Huisman. "Reply: N-Terminal Pro–Brain Natriuretic Peptide Trial Design." American Journal of Respiratory and Critical Care Medicine 196, no. 4 (August 15, 2017): 531–32. http://dx.doi.org/10.1164/rccm.201701-0252le.
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Ööpik, Vahur, Saima Timpmann, Anthony C. Hackney, Kadri Kadak, Luule Medijainen, and Kalle Karelson. "Ingestion of sodium citrate suppresses aldosterone level in blood at rest and during exercise." Applied Physiology, Nutrition, and Metabolism 35, no. 3 (June 2010): 278–85. http://dx.doi.org/10.1139/h10-018.
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The purpose of this study was to determine if the ingestion of sodium citrate (CIT) alters blood levels of fluid and electrolyte regulatory hormones at rest and during exercise. Using a randomized, double-blinded, crossover design, 13 young, male well-trained runners performed continuous incremental running tests to volitional exhaustion on a treadmill 2 h after ingestion of 0.5 g·kg–1 body mass of CIT or placebo (PLC) in 1000 mL of solution. These trials were separated by 2 weeks. Baseline (before ingestion) aldosterone concentration did not differ between the 2 trials; however, it was 36.5% (p = 0.003) lower in the CIT trial compared with the PLC trial before the running test (i.e., after ingestion). The extent of the running-induced increase in aldosterone was 33% (p = 0.009) smaller in the CIT trial. There were no between-trial differences in the levels of adrenocorticotropic hormone, N-terminal pro-B-type natriuretic peptide, or renin activity at any stage of the study. However, a greater relative increase in plasma volume (mean ± SD, 6.41% ± 3.78% vs. 4.08% ± 3.33%; p = 0.042) was observed after administering the CIT compared with the PLC drink. Serum Na+ concentration increased (by 3.1 ± 1.2 mmol·L–1; p < 0.0001) after ingestion of the CIT but not the PLC drink. A higher Na+ level was observed in the CIT trial than in the PLC trial (142.4 ± 1.6 vs. 139.3 ± 1.4 mmol·L–1, p = 0.00001) after completion of the run. In conclusion, pre-exercise ingestion of CIT induces a decrease in serum aldosterone concentration in the resting condition and a blunting of the aldosterone response during incremental running exercise to volitional exhaustion. The observed effect of CIT on the serum aldosterone level may be mediated by an acute increase in plasma volume and serum Na+ concentration alterations.
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Bruce, J. Y., F. J. Hlubocky, and C. K. Daugherty. "“Was it worth it?” A pilot study of advanced cancer patients’ retrospective perceptions of benefit from phase I trial participation." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 19670. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.19670.
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19670 Background: Subjects who enroll in phase I cancer trials generally are those with advanced and terminal disease. Although all such patients (pts) undergo an informed consent process, there is evidence that these pts may not appreciate the primary aims of a phase I trial and have unrealistic expectations of therapeutic benefit. However, these perceptions of benefit have not been described in pts after trial enrollment. Methods: As a pilot study, pts previously enrolled on Phase I trials were interviewed regarding their retrospective perceptions of benefit. A total of 9 pts have been interviewed to date: median age: 72 yr (range: 59–82 yr); 55% male; 77% Caucasian. The interview included open-ended questions assessing patient experiences with the trial, including reasons for enrollment, impressions of quality of life, costs incurred, and other benefits. Pts’ qualitative responses were recorded and analyzed for content and themes. Results: Reasons for enrollment included hope, prior treatment failure, altruism, and family influence. Described perceptions of anticipated benefit included stabilization of disease and close monitoring of their disease. Unexpected costs involved time spent during clinic visits, financial costs, time taken off work by family members, time spent away from family, and additional trial procedures. Issues of quality of life revolved around side effects from the investigational agent. Many interviewed pts (44%) described improved quality of life off the trial as compared to during trial participation. The majority of interviewed pts (67%) believed that the trial had no effect on their survival. Conclusions: Our data suggest that pts’ perceptions of therapeutic benefit after trial enrollment may be different from pre-enrollment expectations. There would also appear to be potentially significant and otherwise undescribed out-of-pocket expenses incurred by subjects as a result of phase I enrollment. Further research is needed to examine how side effects, unexpected costs, and lack of improved survival contribute to these pts’ perceptions of trial benefit. No significant financial relationships to disclose.
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Inborr, J., M. Näsi, and K. Suomi. "The effect of enzyme treatment of cooked barley and supplementation of piglet diets on the digestibility of barley and piglet performance." Agricultural and Food Science 60, no. 7 (December 1, 1988): 685–99. http://dx.doi.org/10.23986/afsci.72337.
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A digestibility trial, designed as a 5*5 Latin square, with growing pigs was conducted to investigate the effect of cooking and enzyme treatment of barley on digestibility and nitrogen utilization. In addition, two piglet performance trials were conducted to investigate the effect of hydrothermal processing of barley and soybean meal and enzyme supplementation of piglet feeds on performance and health status. Five pigs, averaging 40 kg LW, were fitted with T-shaped cannulas in the terminal ileum and fed the experimental diets for five consequtive 12-day experimental periods. Chromic oxide was used as marker. Cooking of barley significantly improved the apparent faecal digestibility (AD) of DM, OM, CP and EE (p
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Fares, Fuad, Avri Havron, and Eyal Fima. "Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic GonadotropinβSubunit to theN-Terminal andC-Terminal Coding Sequence." International Journal of Cell Biology 2011 (2011): 1–7. http://dx.doi.org/10.1155/2011/275063.
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A new analog of EPO was designed by fusing one and two CTPs to theN-terminal andC-terminal ends of EPO (EPO-(CTP)3), respectively. This analog was expressed and secreted efficiently in CHO cells. Thein vitrotest shows that the activity of EPO-(CTP)3in TFI-1 cell proliferation assay is similar to that of EPO-WT and commercial rHEPO. However,in vivostudies indicated that treatment once a week with EPO-(CTP)3(15 μg/kg) dramatically increased (~8 folds) haematocrit as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP)3is more effective than rHuEPO and Aranesp in increasing reticulocyte number in mice blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP)3following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These data established the rational for using this chimera as a long-acting EPO analog in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.
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Hill, Patsy-Anne, Sofoklis Panteleimonitis, Graham McKay, Carol Watson, Andre Prach, and Angus Macdonald. "Sublingual glyceryl trinitrate during colonoscopy and terminal ileal intubation: a randomized controlled trial." Scottish Medical Journal 62, no. 1 (January 22, 2017): 11–15. http://dx.doi.org/10.1177/0036933017690465.
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Background and aims Sublingual glyceryl trinitrate has been used as an aid to cannulate the Sphincter of Oddi during endoscopic retrograde cholangiopancreatography. Its role in terminal ileal intubation during colonoscopy is unknown. This study examines the role of sublingual glyceryl trinitrate in terminal ileal intubation during colonoscopy. Methods A triple-blind randomized controlled trial comparing sublingual glyceryl trinitrate (800 µg) vs. placebo (saline) in relation to terminal ileal intubation during colonoscopy was performed. Following caecal intubation, participants received sublingual glyceryl trinitrate/placebo followed by a 2-min observation period before intubation was attempted. Data on time to intubate the terminal ileum and intubation rate were collected. Results A total of 110 patients (age: 58 years (18–75)) were recruited and randomised as per protocol: 54 received sublingual glyceryl trinitrate. Terminal ileal intubation was successful in all patients receiving sublingual glyceryl trinitrate and in 53 (94.6%) of those receiving saline ( p = 0.243: Fischer’s exact). The median time taken for ileal intubation after application of spray was 72.5 (7–900) s in the glyceryl trinitrate group compared with 125 (5–900) s in the placebo group ( p = 0.150: Mann–Whitney). There were no major adverse events reported in either group. Conclusions Terminal ileal intubation rates and timing were very good in both groups. Routine sublingual glyceryl trinitrate was not proven to be beneficial in improving terminal ileal intubation or intubation success rates in the hands of experienced colonoscopists. However, trends in this small study might suggest that glyceryl trinitrate could be useful in the hands of less experienced colonoscopists or in difficult terminal ileal intubation cases.
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Miao, Yang, Changan Li, Zhan Li, Yipeng Yang, and Xinghu Yu. "A novel algorithm of ship structure modeling and target identification based on point cloud for automation in bulk cargo terminals." Measurement and Control 54, no. 3-4 (February 15, 2021): 155–63. http://dx.doi.org/10.1177/0020294021992804.
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Achieving port automation of machinery at bulk terminals is a challenging problem due to the volatile operation environments and complexity of bulk loading compared to the situations in container terminals. In order to facilitate port automation, we present a method of hull modeling (reconstruction of hull’s structure) and operation target (cargo holds under loading) identification based on 3D point cloud collected by Laser Measurement System mounted on the ship loader. In the hull modeling algorithm, we incrementally register pairs of point clouds and reconstruct the 3D structure of bulk ship’s hull blocks in details through process of encoder data of the loader, FPFH feature matching and ICP algorithm. In the identification algorithm, we project real-time point clouds of the operation zone to spherical coordinate and transforms the 3D point clouds to 2D images for fast and reliable identification of operation target. Our method detects and complements four edges of the operation target through process of the 2D images and estimates both posture and size of operation target in the bulk terminal based on the complemented edges. Experimental trials show that our algorithm allows us to achieve the reconstruction of hull blocks and real-time identification of operation target with high accuracy and reliability.
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Finucane, A., L. Jones, B. Leurent, E. Sampson, P. Stone, A. Tookman, and B. Candy. "52 Drug therapy for delirium in terminally ill adults: a cochrane systematic review." BMJ Supportive & Palliative Care 8, no. 3 (September 2018): 379.2–380. http://dx.doi.org/10.1136/bmjspcare-2018-mariecurie.52.
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IntroductionDelirium is a complex neuropsychiatric syndrome common in palliative care occurring in up to 88% of patients in the weeks or hours preceding death. Our Cochrane review on drug therapy for delirium in 2012 identified one trial (Candy et al. 2012). New trials have been conducted and an updated review is now recognised as a Cochrane priority.AimTo evaluate the evidence from randomised controlled trials (RCTs) examining the effectiveness and safety of drug therapies to treat delirium in adults with a terminal illness.MethodsWe searched for RCTs comparing any drug treatment with any other treatment for delirium in terminally ill adults. Primary outcomes included delirium symptoms at 24 hours and between 24–48 hours; and adverse events. Risk of bias assessment was conducted; we assessed overall quality of evidence using GRADE.ResultsWe retrieved 9431 citations. Four studies were included in the final review. All trials were vulnerable to bias most commonly due to small sample size or incomplete outcome data. Figures 1 and 2 illustrate the mean difference between trial arms at 24 hours and between 24–48 hours respectively. Three studies reported adverse events revealing mixed results.Abstract 52 Figure 1Abstract 52 Figure 2ConclusionThis review identified four trials. It found low quality evidence examining the impact of drug therapy on delirium symptoms and adverse events in terminally ill adults. Results for each comparison were based on single studies. Undertaking trials on delirium in this patient group is methodologically complex. Only one study compared drug therapy with placebo. This limited our ability to answer our review questions.Reference. Candy B, Jackson KC, Jones L, Leurent B, Tookman A, King M. Drug therapy for delirium in terminally ill adult patients. Cochrane Database of Systematic Reviews2012;(11). Art. No. CD004770. doi:10.1002/14651858.CD004770.pub2
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Wu, Longyang, and Richard J. Cook. "The Design of Intervention Trials Involving Recurrent and Terminal Events." Statistics in Biosciences 5, no. 2 (February 22, 2013): 261–85. http://dx.doi.org/10.1007/s12561-013-9083-z.
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Park, Daesik, and Heather L. Eisthen. "Gonadotropin Releasing Hormone (GnRH) Modulates Odorant Responses in the Peripheral Olfactory System of Axolotls." Journal of Neurophysiology 90, no. 2 (August 2003): 731–38. http://dx.doi.org/10.1152/jn.01162.2002.
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Peripheral signal modulation plays an important role in sensory processing. Activity in the vertebrate olfactory epithelium may be modulated by peptides released from the terminal nerve, such as gonadotropin releasing hormone (GnRH). Here, we demonstrate that GnRH modulates odorant responses in aquatic salamanders (axolotls, Ambystoma mexicanum). We recorded electrical field potentials (electro-olfactograms, or EOGs) in response to stimulation with four different amino acid odorants, l-lysine, l-methionine, l-cysteine, and l-glutamic acid. EOG responses were recorded from the main olfactory epithelium before, during, and after application of 10 μM GnRH. This protocol was repeated for a total of three trials with 60–80 min between trials. The effect of GnRH on EOG responses was broadly similar across odorants and across trials. In general, EOG responses were reduced to 79% of the initial magnitude during application of GnRH; in some trials in which glutamic acid served as the odorant, EOG responses were enhanced during the wash period. Although the 4-min inter-stimulus interval did not lead to adaptation of EOG responses during the first trial, we frequently observed evidence of adaptation during the second and third trials. In addition, we found that lower concentrations of GnRH produced a smaller effect. These results demonstrate that GnRH can modulate odorant responses in the peripheral olfactory system.
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Rogers, Robert S., Andrew W. Dawson, Ze Wang, John P. Thyfault, and Pamela S. Hinton. "Acute response of plasma markers of bone turnover to a single bout of resistance training or plyometrics." Journal of Applied Physiology 111, no. 5 (November 2011): 1353–60. http://dx.doi.org/10.1152/japplphysiol.00333.2011.
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The time course of changes in plasma bone turnover markers following an acute bout of resistance training (RT) or plyometrics (PLY) has not been well characterized. This study is the first to compare the acute response of bone formation and resorption markers to a single bout of RT or PLY. Using a partially randomized, cross-over study design, 12 recreationally active men, aged 43 ± 5 yr, each completed four exercise trials: RT (Fed/Fasted) and PLY (Fed/Fasted). In addition to the RT and PLY trials, 5 of the original 12 participants also completed a fasted, no-exercise control trial to examine time-of-day variation. For each trial, blood was drawn immediately before exercise (PRE), immediately following exercise, and 15 min, 30 min, 1 h, 2 h, and 24 h following PRE for determination of plasma bone-specific alkaline phosphatase (BAP), osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRAP5b), COOH-terminal telopeptide of type I collagen (CTX), testosterone, parathyroid hormone, and cortisol. A one-factor repeated-measures ANOVA was performed for each trial to detect changes in bone markers during the 2 h following RT or PLY. TRAP5b transiently decreased during the 2 h following all exercise trials (main effect for time, P < 0.05), but returned to PRE concentrations 2 h postexercise. BAP, CTX, and OC remained unchanged, except for reductions in BAP and CTX following PLY-Fasted and PLY-Fed, respectively. During the control trial, BAP decreased, while TRAP5b, CTX, and OC remained unchanged. In general, plasma hormone concentrations decreased during the 2 h following PLY or RT, and cumulative decreases in TRAP5b during the 2 h following exercise were positively correlated with cumulative decreases in parathyroid hormone. The results of the present study suggest that the timing of the measurement of bone turnover markers relative to the last exercise bout is important for detection of exercise-associated changes in bone turnover markers, as the markers returned to preexercise values within 2 h of RT or PLY.
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Herrero Sáenz, Rebeca, and Trevor Hoppe. "Disease on trial: Medical risk and molecular responsibility in HIV exposure and disclosure jury trials (1994–2015)." Current Sociology 68, no. 1 (December 17, 2018): 97–115. http://dx.doi.org/10.1177/0011392118815936.
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More than 30 years have passed since the first HIV-specific criminal laws were enacted, generally making it a crime for people living with HIV to have sex with another person without disclosing their HIV-status. This study examines the tensions between medicine and criminal justice discourses in the application of laws governing a once terminal disease that medicine has transformed, over the past three decades, into a manageable condition. Has medical progress affected courtroom discussion? To answer this question, the authors analyze court transcripts from nine criminal HIV nondisclosure jury trials between 1994 and 2015 in Michigan, Tennessee, and Missouri. The analysis focuses on how shifting medical discourses of risk influence the way prosecutors and counsels construct notions of individual responsibility and, thus, culpability for HIV exposure. The authors argue that antiretroviral therapy and sophisticated clinical testing technologies have led to increasingly medicalized notions of criminal responsibility that they term ‘molecular responsibility.’ Over time, arguments over the defendant’s responsibility shift from the realm of morality to incorporate the defendant’s capacity and willingness to medically control the microbiological dimension of their condition.
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Yin, Guosheng, Chenyang Zhang, and Huaqing Jin. "Statistical Issues and Lessons Learned From COVID-19 Clinical Trials With Lopinavir-Ritonavir and Remdesivir." JMIR Public Health and Surveillance 6, no. 3 (July 10, 2020): e19538. http://dx.doi.org/10.2196/19538.
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Background Recently, three randomized clinical trials on coronavirus disease (COVID-19) treatments were completed: one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. Objective The aim of this paper is to, from a statistical perspective, identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. Methods The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al failed to reach the planned sample size due to a lack of eligible patients, and the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al reported the median recovery time of the remdesivir and placebo groups, and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. Results For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was –1.67 days (95% CI –3.62 to 0.28; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al, the difference of RMTIs at day 28 was –0.89 days (95% CI –2.84 to 1.06; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the hazard ratio estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al, the difference of RMTRs between the remdesivir and placebo groups at day 30 was –2.7 days (95% CI –4.0 to –1.2; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI –3 to 0; P=.65) was insignificant, while the differences became more statistically significant at larger percentiles. Conclusions Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis of ongoing and future COVID-19 trials.
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Kouvelioti, R., N. Kurgan, B. Falk, W. E. Ward, A. R. Josse, and P. Klentrou. "Response of Sclerostin and Bone Turnover Markers to High Intensity Interval Exercise in Young Women: Does Impact Matter?" BioMed Research International 2018 (November 1, 2018): 1–8. http://dx.doi.org/10.1155/2018/4864952.
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This study examined potential exercise-induced changes in sclerostin and in bone turnover markers in young women following two modes of high intensity interval exercise that involve impact (running) or no-impact (cycling). Healthy, recreationally active, females (n=20; 22.5±2.7 years) performed two exercise trials in random order: high intensity interval running (HIIR) on a treadmill and high intensity interval cycling (HIIC) on a cycle ergometer. Trials consisted of eight 1 min running or cycling intervals at ≥90% of maximal heart rate, separated by 1 min passive recovery intervals. Blood samples were collected at rest (pre-exercise) and 5 min, 1h, 24h, and 48h following each exercise trial. Serum was analyzed for sclerostin, cross linked telopeptide of type I collagen (CTXI), and procollagen type I amino-terminal propeptide (PINP). A significant time effect was found for sclerostin, which increased from pre-exercise to 5 min after exercise in both trials (100.2 to 131.6 pg/ml in HIIR; 102.3 to 135.8 pg/ml in HIIC, p<0.001) and returned to baseline levels by 1h, with no difference between exercise modes and no exercise mode-by-time interaction. CTXI did not significantly change following either trial. PINP showed an overall time effect following HIIR, but none of the post hoc pairwise comparisons were statistically significant. In young women, a single bout of high intensity exercise induces an increase in serum sclerostin, irrespective of exercise mode (impact versus no-impact), but this response is not accompanied by a response in either bone formation or resorption markers.
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Gunia, Stanisław, Jan Łukaszewicz, and Henryk Szeligowski. "The first Polish provenance experiments with silver fir Abies alba Mill." Forest Research Papers 80, no. 3 (September 1, 2019): 201–12. http://dx.doi.org/10.2478/frp-2019-0018.
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AbstractSilver fir Abies alba Mill. provenance trials started in Poland a few years after Pavari (1951) proved that the origin of this tree species influences its genetic variability. Further confirmation came from provenance trials, which selected provenances for cultivation in Denmark and showed provenance-dependent genetic variability even within a relatively small area such as the Czech Republic. The Polish trial, started in 1960, compared 6 provenances from the West and Central Carpathian region (4 from Poland, 2 from Slovakia) and 3 from the Hercinic region (Czech Republic). The trial was established in the Experimental Forests of the Warsaw University of Life Sciences in Rogów, at the northern border of the natural silver fir range. Results from the nursery stage experiments proved the existence of latitudinal and altitudinal clines based on data for seed weight, height growth, number of terminal buds as well as bud and needle development. The Polish provenance ‘Stary Sącz’ and two Slovak provenances, ‘Čierný Váh’ and ‘Beňuš’, were early flushing, whereas the Polish provenance ‘Rogów’ behaved differently and was late flushing. Even at the nursery stage, the positive influence of tree selection on height growth and progeny characteristics of the two Czech provenances was evident. The Carpathian provenances were furthermore evaluated according to the index of cultivation and breeding: very good – ‘Rogów’; good ‘ŚPN (Świętokrzyski PN)’, ‘Stary Sącz’ and ‘Skarżysko’; poor – ‘Čierný Váh’ and ‘Beňuš’.
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Hollebeke, Jolien, Petra Van Damme, and Kris Gevaert. "N-terminal acetylation and other functions of Nα-acetyltransferases." Biological Chemistry 393, no. 4 (April 1, 2012): 291–98. http://dx.doi.org/10.1515/hsz-2011-0228.
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Abstract Protein N-terminal acetylation by Nα-acetyltransferases (NATs) is an omnipresent protein modification that affects a large number of proteins. The exact biological role of N-terminal acetylation has, however, remained enigmatic for the overall majority of affected proteins, and only for a rather small number of proteins, N-terminal acetylation was linked to various protein features including stability, localization, and interactions. This minireview tries to summarize the recent progress made in understanding the functionality of N-terminal protein acetylation and also focuses on noncanonical functions of the NATs subunits.