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"Fletcher, Jared K"
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Wonder Woman. Volume 2, Guts
\"Wonder Woman goes to hell! After playing Posidon, Hades, and Hera against each other, Hades strikes back by kidnapping Zola and trapping her in the Underworld. It's up to Wonder Woman--with a little help from the God of Love and the God of Smiths--to break Zola out. But what is Hades' real game, and once you get into the land of the dead, how exactly do you get out?\"--Amazon.
Book
Is Running Power a Useful Metric? Quantifying Training Intensity and Aerobic Fitness Using Stryd Running Power Near the Maximal Lactate Steady State
We sought to determine the utility of Stryd, a commercially available inertial measurement unit, to quantify running intensity and aerobic fitness. Fifteen (eight male, seven female) runners (age = 30.2 [4.3] years; V·O2max = 54.5 [6.5] ml·kg−1·min−1) performed moderate- and heavy-intensity step transitions, an incremental exercise test, and constant-speed running trials to establish the maximal lactate steady state (MLSS). Stryd running power stability, sensitivity, and reliability were evaluated near the MLSS. Stryd running power was also compared to running speed, V·O2, and metabolic power measures to estimate running mechanical efficiency (EFF) and to determine the efficacy of using Stryd to delineate exercise intensities, quantify aerobic fitness, and estimate running economy (RE). Stryd running power was strongly associated with V·O2 (R2 = 0.84; p < 0.001) and running speed at the MLSS (R2 = 0.91; p < 0.001). Stryd running power measures were strongly correlated with RE at the MLSS when combined with metabolic data (R2 = 0.79; p < 0.001) but not in isolation from the metabolic data (R2 = 0.08; p = 0.313). Measures of running EFF near the MLSS were not different across intensities (~21%; p > 0.05). In conclusion, although Stryd could not quantify RE in isolation, it provided a stable, sensitive, and reliable metric that can estimate aerobic fitness, delineate exercise intensities, and approximate the metabolic requirements of running near the MLSS.
Journal Article
The path of most resistance
Set against the backdrop of an antibiotic apocalypse in near future London. Rosa Scott, a brilliant and obsessive surgeon becomes Surgeon X, a vigilante doctor who uses experimental surgery and black market drugs to treat patients. But as Surgeon X, Rosa soon develops a godlike-complex, deciding who will live and who will die. Ultimately, she believes that to survive in this compromised world her own warped moral code is the one she must follow--even if it endangers those closest to her.
Book
Propranolol treatment during repetitive mild traumatic brain injuries induces transcriptomic changes in the bone marrow of mice
There are 1.5 million new mild traumatic brain injuries (mTBI) annually in the US, with many of the injured experiencing long-term consequences lasting months after the injury. Although the post injury mechanisms are not well understood, current knowledge indicates peripheral immune system activation as a causal link between mTBI and long-term side effects. Through a variety of mechanisms, peripheral innate immune cells are recruited to the CNS after TBI to repair and heal the injured tissue; however, the recruitment and activation of these cells leads to further inflammation. Emerging evidence suggests sympathetic nervous system (SNS) activity plays a substantial role in the recruitment of immune cells post injury.
We sought to identify the peripheral innate immune response after repeated TBIs in addition to repurposing the nonselective beta blocker propranolol as a novel mTBI therapy to limit SNS activity and mTBI pathophysiology in the mouse. Mice underwent repetitive mTBI or sham injury followed by i.p. saline or propranolol. Isolated mRNA derived from femur bone marrow of mice was assayed for changes in gene expression at one day, one week, and four weeks using Nanostring nCounter
stem cell characterization panel.
Differential gene expression analysis for bone marrow uncovered significant changes in many genes following drug alone, mTBI alone and drug combined with mTBI.
Our data displays changes in mRNA at various timepoints, most pronounced in the mTBI propranolol group, suggesting a single dose propranolol injection as a viable future mTBI therapy in the acute setting.
Journal Article
Batman by Francis Manapul and Brian Buccellato, the deluxe edition
\"Francis Manapul and Brian Buccellato present their celebrated run on DETECTIVE COMICS, collected all together in this hardcover deluxe edition for the first time. Batman contends with the return of Anarky! As Gotham City decends into chaos at the hands of this new vigilante and his quest for revenge on both the villains and protectors of Gotham, Batman must team up with the cantankerous Harvey Bullock of the Gotham City PD to find Anarky's true motivation for bringing Gotham to its knees.\"-- Provided by publisher.
Book
Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys
Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC
50
: 0.20–0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identify a single amino acid substitution, I777L, in the L polymerase with reduced susceptibility (3.3-3.8-fold) to ODV and GS-441524, indicating a high barrier for resistance development. In an African green monkey RSV infection model, once-daily oral ODV doses of 30 or 90 mg/kg initiated ~24 hours post-infection significantly reduces log
10
viral RNA copies/mL × day area under the curve by 69–92% in the upper and lower respiratory tracts. Together, these preclinical data support the clinical evaluation of ODV for the treatment of RSV infection.
In this work, authors show that the nucleoside prodrug obeldesivir has potent antiviral activity across respiratory syncytial virus (RSV) clinical isolates with a high resistance barrier. Once-daily obeldesivir treatment was efficacious against RSV in a non-human primate model.
Journal Article
Batman. Battle for the cowl
Months after Batman disappeared, Gotham City sits on a precipice. Perhaps not even Nightwing, Robin, or Commissioner Gordon could save it now. As the fires, rioting, looting and gang warfare swirl, one question is on everyone's mind: where's Batman?
Book
Simulating the one-dimensional structure of Titan's upper atmosphere: 3. Mechanisms determining methane escape
This investigation extends the work presented by Bell et al. (2010a, 2010b). Using the one‐dimensional (1‐D) configuration of the Titan Global Ionosphere‐Thermosphere Model (T‐GITM), we quantify the relative importance of the different dynamical and chemical mechanisms that determine the CH4 escape rates calculated by T‐GITM. Moreover, we consider the implications of updated Huygens Gas Chromatograph Mass Spectrometer (GCMS) determinations of both the 40Ar mixing ratios and 15N/14N isotopic ratios in work by Niemann et al. (2010). Combining the GCMS constraints in the lower atmosphere with the Ion Neutral Mass Spectrometer (INMS) measurements in work by Magee et al. (2009), our simulation results suggest that the optimal CH4 homopause altitude is located at 1000 km. Using this homopause altitude, we conclude that topside escape rates of 1.0 × 1010 CH4 m−2 s−1 (referred to the surface) are sufficient to reproduce the INMS methane measurements in work by Magee et al. (2009). These escape rates of methane are consistent with the upper limits to methane escape (1.11 × 1011 CH4 m−2 s−1) established by both the Cassini Plasma Spectrometer (CAPS) and Magnetosphere Imaging Instrument (MIMI) measurements of Carbon‐group ions in the near Titan magnetosphere. Key Points Investigate the mechanisms determining the methane escape simulated by T‐GITM Investigate methane escape estimates calculated by a 1‐D diffusion model Evaluate the impacts of the new Huygens GCMS data
Journal Article
Wonder Woman. Volume 4, War
Wonder Woman's world is shocked to its core when her eldest brother, the First Born, is freed from his slumber. Now, with her family in ruins and her friends scattered, she must turn to Orion and the New Gods of New Genesis to save herself and Zola's newborn from the First Born's wrath!
Book
Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys
Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20-0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identified a single amino acid substitution, I777L, in the L polymerase with reduced susceptibility (3.3-3.8-fold) to ODV and GS-441524, indicating a high barrier for resistance development. In an African green monkey RSV infection model, once-daily oral ODV doses of 30 or 90 mg/kg initiated ~24 hours post-infection significantly reduced log10 viral RNA copies/mL×day area under the curve by 69-92% in the upper and lower respiratory tracts. Together, these preclinical data support the clinical evaluation of ODV for the treatment of RSV infection.Competing Interest StatementAll authors affiliated with Gilead Sciences may hold stock or stock options in Gilead Sciences, Inc. VA, PAP, KS, and PLD received funding from Gilead Sciences Inc. to support parts of this work. PAP received grant awards and ad hoc honoraria from Merck and Shionogi for consulting and scientific boards unrelated to the work presented here. All other authors declare no competing interests.
Paper