Nolanbroe7941

This work identifies a specific therapeutic target for the treatment or prevention of atherosclerosis and improves our understanding of the role of cAMP signaling in modulating mechanosensory signal transduction in the vascular endothelium.The preparation of Agrobacterium tumefaciens cultures with strains encoding proteins intended for therapeutic or industrial purposes is an important activity prior to treatment of plants for transient expression of valuable protein products. The rising demand for biologic products such as these underscores the expansion of molecular pharming and warrants the need to produce transformed plants at an industrial scale. This requires large quantities of A. tumefaciens culture, which is challenging using traditional growth methods (e.g., shake flask). To overcome this limitation, we investigate the use of bioreactors as an alternative to shake flasks to meet production demands. Here, we observe differences in bacterial growth among the tested parameters and define conditions for consistent bacterial culturing between shake flask and bioreactor. Quantitative proteomic profiling of cultures from each growth condition defines unique growth-specific responses in bacterial protein abundance and highlights the functional roles of these proteins, which may influence bacterial processes important for effective agroinfiltration and transformation. Overall, our study establishes and optimizes comparable growth conditions for shake flask versus bioreactors and provides novel insights into fundamental biological processes of A. tumefaciens influenced by such growth conditions.We investigated the cardiorespiratory responses to semi-supine exercise with (SS+45°) and without (SS-0°) a left-lateral tilt in 15 adults at fixed power output (70 W) and matched heart rates. At 70 W, oxygen uptake and heart rate reduced from upright to SS-0° then increased to SS+45° (p less then 0.05). At matched heart rates, oxygen uptake and efficiency were lowest in SS+45° (p less then 0.05). Left-lateral tilting should not be performed under the assumption that each position replicates the same cardiorespiratory responses. Novelty Cardiorespiratory responses to exercise are influenced by left-lateral tilting, which should not be performed under the assumption that physiological responses are replicated between left-lateral positions.Lactoferrin as a nutritional enteral supplement has emerged as a novel preventative therapy against serious infections in preterm infants, although neonatal studies have demonstrated variable results, in part due to the lack of pharmacokinetic data and differences in the products tested. We conducted a prospective, dose escalation (100, 200, and 300 mg·kg-1·day-1) safety study of bovine lactoferrin (Glanbia Nutritionals, USA) dissolved in sterile water (100 mg·mL-1) for 30 days in preterm infants with birth weight less then 1500 g. Safety related to adverse events (AEs), tolerability, and exposure-response of lactoferrin was assessed. We enrolled 31 patients [10, 10, and 11 patients, for the lactoferrin treatment groups (100, 200, and 300 mg·kg-1·day-1, respectively)] over a 10-month period. No AEs related to the study solution occurred, and lactoferrin was tolerated by each group. During lactoferrin supplementation, one bloodstream infection occurred in each group, but there were no incidences of urinary tract infections and no cases of necrotizing enterocolitis. Postnatal cytomegalovirus acquisition was detected in the group treated with 200 mg·kg-1·day-1 (n = 2). There were no adverse effects on hepatic, renal, or hematologic function. All of the patients survived to discharge. Bovine lactoferrin at doses up to 300 mg·kg-1·day-1 is safe in preterm infants. Future studies examining higher doses of lactoferrin, length of treatment, and potency of different products will aid in determining the optimal approach for the use of lactoferrin to prevent infections in preterm infants.

The optimal technique to administer image-guided radiation therapy for prostate cancer remains poorly defined. This study assessed outcomes after multiparametric prostate MRI-based planning was delivered with image-guided radiation therapy using prostatic calculi observed on cone beam CT (CBCT).

Between January 2015 and December 2017, 94 consecutive patients were treated with CBCT-based image-guided radiation therapy (IGRT) without fiducial markers. MRI was routinely incorporated for target delineation and intraprostatic tumor nodules were boosted to allow reduced doses to normal appearing prostate. The primary endpoint was the prevalence of prostatic calcifications while toxicity and biochemical control were secondary endpoints.

Median follow-up was 39.7 months with 82% NCCN intermediate to very high risk. Intraprostatic calculi were noted in 68% of patients. The 3-year biochemical control, late grade ≥2 rectal toxicity and late grade ≥2 urinary toxicity rates were 96%, 3 and 7%, respectively. Biochemical control and toxicity were not significantly impacted by the presence of prostatic calculi.

Prostatic calcifications can serve as natural fiducial markers to allow for non-invasive IGRT for prostate cancer with promising early disease control and toxicity outcomes.

Prostate calcification-guided IGRT is technically feasible.

Prostate calcification-guided IGRT is technically feasible.Kgengwe fruits are commonly consumed in sub-Saharan countries. Recent reports indicated low coronary artery disease rates in those regions. To investigate anti-atherogenic properties and potential mechanisms of action of Kgengwe seed powder (KSP), male low-density lipoprotein receptor knockout (LDL-r-KO) mice were fed with an atherogenic diet supplemented with (treated, n = 10) or without (controls, n = 10) 10% (w/w) KSP for 20 weeks. Proximate analysis revealed that KSP contained 38% fibre and 15% lipids. KSP supplementation was not associated with significant changes in body weight gain rate, food intake, and plasma lipid levels. However, the average atherosclerotic lesion size in the aortic roots in the KSP-treated group was 58% smaller than that in the control group (0.26 vs 0.11 mm2, p less then 0.05). This strong anti-atherogenic effect was associated with significant increases in the average plasma levels of certain cytokines such as IL-10 (6 vs 13 pg/mL, p less then 0.05), GM-CSF (0.1 vs 0.2 pg/mL, p less then 0.05), and EPO (7 vs 16 pg/mL, p less then 0.05) along with reductions in the average levels of plasma MCP-1 (19 vs 14 pg/mL, p less then 0.05) and MIP-2 (28 vs 13 pg/mL, p less then 0.05). Except for relatively high levels of saturated fatty acids, KSP possesses balanced nutrient compositions with strong anti-atherogenic properties, which may be mediated through alterations in inflammatory pathways. Additional studies warrant confirmation and mechanism(s) of action of such effects. Novelty Kgengwe seeds prevent atherogenesis in LDL-r-KO mice. Kgengwe seeds increase circulating levels of IL-10 and EPO. No reduction in plasma total cholesterol levels.The incarcerated population has little or no access to science education programs, STEM resources, or scientists. We explored the effects of a low-cost, potentially high-impact informal science education program that enabled NASA scientists to provide astrobiology lectures to adults inside 16 correctional institutions in three states. Post- versus pre-lecture surveys suggest that presentations significantly increased science content knowledge, positively shifted attitudes about science and scientists, increased a sense of science self-identity, and enhanced behavioral intentions about communicating science. These were significant across ethnicity, gender, education level, and institution type, size, location, and state. Men scored higher than women on pre-lecture survey questions. Among men, participants with greater levels of education and White non-Hispanics scored higher than those with less educational attainment and African American and other minority participants. Increases in science content knowledge were greater for women than men and, among men, for those with lower levels of education and African American participants. AZD5069 datasheet Women increased more in science identity than did men. Thus, even limited exposure to voluntary, non-credit science lectures delivered by scientists can be an effective way to broker a relationship to science for this underserved public group and can potentially serve as a step to broaden participation in science.We report a transition-metal-free trans-selective semireduction of alkynes with pinacolborane and catalytic potassium tert-butoxide. A variety of 3-substituted primary and secondary propiolamides, including an analog of FK866, a potent nicotinamide mononucleotide adenyltransferase (NMNAT) inhibitor, are reduced to the corresponding (E)-3-substituted acrylamide derivatives in up to 99% yield with >991 E/Z selectivity. Mechanistic studies suggest that an activated Lewis acid-base complex transfers a hydride to the α-carbon followed by rapid protonation in a trans fashion.Selected configuration interaction (SCI) methods are currently enjoying a resurgence due to several recent developments which improve either the overall computational efficiency or the compactness of the resulting SCI vector. These recent advances have made it possible to get full CI (FCI) quality results for much larger orbital active spaces compared to conventional approaches. However, due to the starting assumption that the FCI vector has only a small number of significant Slater determinants, SCI becomes intractable for systems with strong correlation. This paper introduces a method for developing SCI algorithms in a way which exploits local molecular structure to significantly reduce the number of SCI variables. The proposed method is defined by first grouping the orbitals into clusters over which we can define many-particle cluster states. We then directly perform the SCI algorithm in a basis of tensor products of cluster states instead of Slater determinants. While the approach is general for arbitrarily defined cluster states, we find significantly improved performance by defining cluster states through a Tucker decomposition of the global (and sparse) SCI vector. To demonstrate the potential of this method, called tensor product selected configuration interaction (TPSCI), we present numerical results for a diverse set of examples (1) modified Hubbard model with different inter- and intracluster hopping terms, (2) less obviously clusterable cases of bond breaking in N2 and F2, and (3) ground state energies of large planar π-conjugated systems with active spaces of up to 42 electrons in 42 orbitals. These numerical results show that TPSCI can be used to significantly reduce the number of SCI variables in the variational space, thus paving a path for extending these deterministic and variational SCI approaches to a wider range of physical systems.The applications of a newly designed chiral naphthyl-C2-indole bifunctional phosphine organocatalyst in stereoselective formal [4 + 2] cycloaddition reactions were reported. The chiral naphthyl-C2-indole skeleton was introduced to bifunctional phosphine organocatalysis for the first time, and excellent stereocontrol was achieved in two types of formal [4 + 2] cycloaddition reactions. With the optimal catalyst, a series of chiral spirooxindole and hydrodibenzofuran architectures were produced in moderate to good yields with excellent stereoselectivities (up to >99% ee, >201 dr).