5,014 research outputs found
Investigating the Molecular Mechanism of DCM-MJ-I-21 as an Agent in Combination Chemotherapy Against Human Pancreatic Cancer
No full textPancreatic cancer is the third leading cause of cancer-related deaths, with a 1-year survival rate of 29% and a 5-year survival rate of 7%. Pancreatic cancer often goes undiagnosed until its late stages, at which point treatment options become limited to chemotherapy and radiation therapy, which are often ineffective at substantially prolonging life. Thus, there is a pressing need for improved pharmacologic treatment for pancreatic cancer. DCM-MJ-I-21, a compound developed in our laboratory, exhibits cytotoxicity against the human pancreatic cancer cell line PANC-1, with preferential cytotoxicity under nutrient deprived conditions, which mimic the tumor microenvironment. This study investigated the mechanism of action of DCM-MJ-I-21. Data revealed DCM-MJ-I-21 inhibits one or more late-stage steps of the autophagy pathway in PANC-1 cells. This study also explored the effects of DCM-MJ-I-21 as an agent in combination chemotherapy with etoposide, a topoisomerase II inhibitor. Results revealed that these compounds synergize in PANC-1 cells, with differing dose and time effects following 24 versus 48 hours of treatment. Future research ought to explore the effects of combination chemotherapy at more frequent time points in order to fine-tune dosage and timing data. Data should also be evaluated in PANC-1 spheroid assays to determine whether two-dimensional data recapitulates in three-dimensional conditions
A qualitative process evaluation of electronic session-by-session outcome measurement in child and adolescent mental health services
No full textBackground: Regular monitoring of patient progress is important to assess the clinical effectiveness of an intervention. Recently, initiatives within UK child and adolescent mental health services (CAMHS) have advocated the use of session-by-session monitoring to continually evaluate the patient’s outcome throughout the course of the intervention. However, the feasibility and acceptability of such regular monitoring is unknown. Method: Semi-structured qualitative interviews were conducted with clinicians (n= 10), administrative staff (n=8) and families (n= 15) who participated in a feasibility study of an electronic session-by-session outcome monitoring tool, (SxS), which is based on the Strengths and Difficulties Questionnaire (SDQ). This study took place in three CAMHS clinics in Nottinghamshire. The interview transcripts were thematically analysed. Results: We found clinicians accepted the need to complete outcome measures, particularly valuing those completed by the patient. However, there were some difficulties with engaging clinicians in this practice and in the training offered. Generally, patients were supportive of completing SxS in the waiting room prior to the clinic session and assistance with the process from administrative staff was seen to be a key factor
Self-compression of 4.9 µm pulses to sub-40 fs with 2 mJ energy in Zinc Sulfide
No full textNonlinear self-compression of few-cycle multi-mJ pulses at 4.9 µm in ZnS is presented. 80 fs input pulses are compressed to 37 fs with 2.1 mJ energy at a 1 kHz repetition rate. © 2024 The Author(s
Improved stable isotope dilution-gas chromatography-mass spectrometry method for serum or plasma free 3-hydroxy-fatty acids and its utility for the study of disorders of mitochondrial fatty acid ??-oxidation
No full textPathfinding by neuronal growth cones in grasshopper embryos. III. Selective affinity of the G growth cone for the P cells within the A/P fascicle
No full textThe growth cone of the G neuron selectively fasciculates upon specific axon bundles in a stereotypic sequence as it navigates through the developing central nervous system of the grasshopper embryo. It turns and extends anteriorly in the contralateral neuropil of the second thoracic ganglion at a specific choice point where it fasciculates with the A/P axon bundle which contains the axons of the A1, A2, P1, and P2 neurons. We previously hypothesized (Raper, J. A., M. J. Bastiani, and C. S. Goodman (1983) J. Neurosci. 3: 20–41) that this fascicle, or subsets of axons within it, were specifically labeled and that the G neuron was determined to follow this labeled pathway. Here we report on an ultrastructural analysis of the interactions between the G growth cone and its filopodia with the cells of the A/P fascicle at the choice point. As G reaches its choice point, its filopodia are in more frequent contact with the A/P fascicle in comparison to the other longitudinal axon fascicles. Within the A/P fascicle, the tip of G's growth cone is found to be closely associated with the P and not the A axons. Furthermore, before the G growth cone climbs onto the A/P fascicle, its filopodia show a selective affinity for the P axons as compared to the A axons. Another specific interaction involves selective filopodial insertions; only filopodia from the P cells were found to insert into the G growth cone and induce coated pits and vesicles. These findings suggest that G is able to distinguish the A/P fascicle from other axon bundles and, moreover, is able to distinguish the P axons from the A axons. The companion paper (Raper, J. A., M. J. Bastiani, and C. S. Goodman (1984) J. Neurosci. 4: 2329–2345) presents experimental results based on specific axon ablations that further support this hypothesis.</jats:p
Correction to: Chamoun et al., Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection
No full textChamoun MN, Blumenthal A, Sullivan MJ, Schembri MA, Ulett GC. 2018. Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection. Critical Reviews in Microbiology. https://doi.org/10.1080/1040841X.2018.1426556.
When the above article was first published online, the below three corrections were missed.
The author ‘Antje Blumenthal’ was wrongly affiliated to the affiliation “cSchool of Chemistry and Molecular Biosciences, and Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Australia”. Now this affiliation has been removed for this author.
The affiliation ‘bTranslational Research Institute, The University of Queensland Diamantina Institute, Woolloongabba, Australia’ of the author ‘Antje Blumenthal’ should read ‘bThe University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia’.
In Table 3, the sentence ‘Benefit of manipulating IL-17 levels to improve immunization strategies M. tuberculosis’ should read “Benefit of manipulating IL-17 levels to improve immunization strategies against M. tuberculosis”.No Full Tex
Generation of 22-mJ, 2.0-ps Pulses from a 1-kHz Ho:YLF Regenerative Chirped Pulse Amplifier
No full textWe report a CW-pumped Ho:YLF regenerative amplifier (RA) delivering pulses with 22.5-mJ energy and 2.0-ps duration at 1 kHz. The RA emitting at 2051 nm is broadband-seeded and implemented in a chirped pulse amplification system. © 2024 The Author(s
Pure-rotational 1D-CARS spatiotemporal thermometry with a single regenerative amplifier system
No full textWe report spatiotemporal pure-rotational coherent anti-Stokes Raman spectroscopy (CARS) in a one-dimensional imaging arrangement obtained with a single ultrafast regenerative amplifier system. The femtosecond pump/Stokes photon pairs, used for impulsive excitation, are delivered by an external compressor operating on a ∼35% beam split of the uncompressed amplifier output (2.5 mJ/pulse). The picosecond 1.2 mJ probe pulse is produced via the second-harmonic bandwidth compression (SHBC) of the ∼65% remainder of the amplifier output (4.5 mJ/pulse), which originates from the internal compressor. The two pump/Stokes and probe pulses are spatially, temporally, and repetition-wise correlated at the measurement, and the signal generation plane is relayed by a wide-field coherent imaging spectrometer onto the detector plane, which is refreshed at the same repetition rate as the ultrafast regenerative amplifier system. We demonstrate 1 kHz cinematographic 1D-CARS gas-phase thermometry across an unstable premixed methane/air flame-front, achieved with a single-shot precision <1% and accuracy <3%, 1.4 mm field of view, and an excellent <20 µm line-spread function.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Flight Performance and Propulsio
Pathfinding by neuronal growth cones in grasshopper embryos. IV. The effects of ablating the A and P axons upon the behavior of the G growth cone
No full textIn the companion paper (Bastiani, M. J., J. A. Raper, and C. S. Goodman (1984) J. Neurosci. 4: 2311–2328), we show that as the G growth cone reaches its choice point and turns anteriorly on the A/P fascicle, its filopodia demonstrate selective affinity for the A/P fascicle as compared to the other approximately 25 longitudinal axon fascicles, and within the A/P fascicle itself, G's filopodia selectively contact the P axons as compared to the A axons. These results support the hypothesis that the A/P fascicle, and, moreover, subsets of axons within it (Ps versus As), are specifically labeled and that the G growth cone is determined to follow a particular labeled pathway. We tested the “labeled pathways” hypothesis by specifically ablating these axons and examining the subsequent behavior of the G growth cone in embryos grown in culture. Ablation of the A and P axons prevents G from growing more than a short distance anteriorly, although the G growth cone is within grasp of many other longitudinal axon fascicles. Ablation of only the P axons has a similar effect; the G growth cone behaves normally if only the A axons are ablated. Transmission electron micrograph semiserial section reconstructions of experimental embryos further indicate that G's growth cone behaves abnormally when the A and P axons, or only the P axons, are ablated. The G growth cone branches extensively in the lateral and ventral neuropil without it or its filopodia showing a high affinity for any other axon fascicle. These results indicate that the G growth cone is able to distinguish the A/P fascicle from the other longitudinal axon fascicles in the developing neuropil. Moreover, the results suggest that within the A/P fascicle the G growth cone is able to distinguish the P axons from the A axons.</jats:p
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