13 research outputs found
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Fleet and owner-operator capacity for utilizing idle reduction technology: a report to the US Environmental Protection Agency
In order to reduce long-term idling along the Oregon I-5 corridor, the US Environmental Agency entered into a collaborative research and implementation program with Oregon State University, the Oregon Climate Trust, and Shurepower (producers of truckstop electrification equipment) to install Shurepower stations at truck stops in Oregon. This research component
• characterizes the existing capacity of the fleets and owner-operators who idle in Oregon to use the Shurepower technology and
• describes the incentives and constraints for fleets and owner-operators to invest in technology that allows their drivers to use Shurepower technology.
In-depth, face-to-face interviews were completed with owner-operator truck drivers at three truck stops in Oregon and phone interviews with equipment buyers at fleets with trucks driving in Oregon. Notes were taken during the interviews and analyzed to answer the research questions described above.
In general, we found that all respondents were concerned about long-term idling for a variety of reasons including cost, driver health, noise, and pollution. The most widely used idle reduction technology currently in use by owner-operators are additional batteries and inverters that allow the use of on-board amenities including (among other things) microwaves, TVs, VCR-DVDs and computers. About 40% of the respondents were familiar with Idleaire technology; and while most respondents have heard of Shurepower, none have ever used it and only a few have even seen it. One fleet has equipped their trucks with Shurepower retrofits, the other fleets were experimenting with other idle reduction options including incentive programs, APUs, and automatic shut-off technology.
Both fleet representatives and owner-operators perceive the largest drawback to the Shurepower technology is the small number of planned spaces at a few truck stops. They see this place-based technology as limiting to drivers who cannot find a technology equipped space, cannot reach an equipped truck stop due to rest regulations, and/or who are not driving regularly along the I-5 corridor. Once a truck is equipped with the enabling technology, however, Shurepower is perceived as an inexpensive, easy to use
option for reducing idling.
Recommendation for promoting and increasing the use of Shurepower technology in
Oregon include targeted marketing of the benefits, services, and locations of
Shurepower- equipped sites, low-interest loan programs for retrofitting trucks, and
promotion of the anti-pollution and health benefits of Shurepower over currently used
technologies
Effect of bovine milk fat-based infant formulae on microbiota, metabolites and stool parameters in healthy term infants in a randomized, crossover, placebo-controlled trial
Background: Natural enrichment of sn-2 palmitate content of infant formulae by using bovine milk fat is known to reduce formation of faecal fatty acid soaps and to improve stool consistency, but effects on gut microbiota composition are unknown. The purpose of this study was to test the influence of milk fat-based formula high in sn-2 palmitate on the infants’ gut microbiota composition and to confirm the beneficial effects of the formula on formation of faecal fatty acid soaps and stool consistency. Methods: Twenty-two healthy term, formula-fed infants were enrolled in a single-blinded randomized, crossover, placebo-controlled trial. After a 2-week run-in period, infants received either a 50% milk fat-based formula containing 39% sn-2 palmitate (MF) or a vegetable fat-based formula (VF) containing 10% sn-2 palmitate in a 2 × 2-week crossover design. Faecal microbiota composition was the primary outcome of the study. Other outcomes included faecal fatty acid soap excretion, calcium excretion, gut comfort parameters and faecal metabolites. Results: Microbiota analysis showed that bifidobacteria dominated the gut microbiota of most infants. Neither alpha- nor beta-diversity was significantly influenced by the intervention. Also, abundance of metabolic pathways was independent of the intervention. The MF formula resulted in significantly lower faecal levels of palmitic acid soap (p = 0.0002) and total fatty acid soaps (p = 0.0001) than the VF formula. Additionally, calcium excretion and palmitic acid concentration were significantly (p = 0.0335) lower in stool samples after MF intervention. Furthermore, a significant physiological effect on softer stools was observed in the MF intervention compared to the VF intervention (p = 0.02). Of the 870 measured faecal metabolites, 190 were significantly different after MF and VF intervention (FDR corrected p < 0.05). Most of these were found at higher levels after MF intervention, potentially indicative of the complex structure of milk fat. Metabolites with more than twofold change between interventions were mostly lipid-derived and included several milk fat-specific fatty acids. Conclusions: Replacing part of the vegetable fat in infant formula with bovine milk fat with high sn-2 palmitate levels did not change the microbiota composition, although a reduction in faecal palmitate soaps, total fatty acid soaps and calcium excretion while improving stool consistency in the MF intervention was confirmed. In addition, 190 faecal metabolites were significantly different, many related to the fat source. Trial registration: Netherlands Trial Registry Identifier: NL7815 19/06/2019.</p
Pro-Arrhythmic Potential of Accumulated Uremic Toxins Is Mediated via Vulnerability of Action Potential Repolarization
Chronic kidney disease (CKD) is represented by a diminished filtration capacity of the kidneys. End-stage renal disease patients need dialysis treatment to remove waste and toxins from the circulation. However, endogenously produced uremic toxins (UTs) cannot always be filtered during dialysis. UTs are among the CKD-related factors that have been linked to maladaptive and pathophysiological remodeling of the heart. Importantly, 50% of the deaths in dialysis patients are cardiovascular related, with sudden cardiac death predominating. However, the mechanisms responsible remain poorly understood. The current study aimed to assess the vulnerability of action potential repolarization caused by exposure to pre-identified UTs at clinically relevant concentrations. We exposed human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and HEK293 chronically (48 h) to the UTs indoxyl sulfate, kynurenine, or kynurenic acid. We used optical and manual electrophysiological techniques to assess action potential duration (APD) in the hiPSC-CMs and recorded I Kr currents in stably transfected HEK293 cells (HEK-hERG). Molecular analysis of K V11.1, the ion channel responsible for I Kr, was performed to further understand the potential mechanism underlying the effects of the UTs. Chronic exposure to the UTs resulted in significant APD prolongation. Subsequent assessment of the repolarization current I Kr, often most sensitive and responsible for APD alterations, showed decreased current densities after chronic exposure to the UTs. This outcome was supported by lowered protein levels of K V11.1. Finally, treatment with an activator of the I Kr current, LUF7244, could reverse the APD prolongation, indicating the potential modulation of electrophysiological effects caused by these UTs. This study highlights the pro-arrhythmogenic potential of UTs and reveals a mode of action by which they affect cardiac repolarization
The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells
INTRODUCTION: Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. METHOD: A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacking or containing progesterone receptor and/or androgen receptor. RESULTS: In progesterone receptor-positive cells, MPA was found to be an effective progestin through both progesterone receptor isoforms in transient transcription assays. Interestingly, DHT signaled through progesterone receptor type B. Expression profiling of endogenous progesterone receptor-regulated genes comparing progesterone and MPA suggested that although MPA may be a somewhat more potent progestin than progesterone, it is qualitatively similar to progesterone. To address effects of MPA through androgen receptor, expression profiling was performed comparing progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene regulatory overlap between DHT and MPA through androgen receptor and none with progesterone. Interestingly, there was no difference between pharmacological MPA and physiological MPA, suggesting that high-dose therapeutic MPA may be superfluous. CONCLUSION: Our comparison of the gene regulatory profiles of MPA and progesterone suggests that, for physiologic hormone replacement therapy, the actions of MPA do not mimic those of endogenous progesterone alone. Clinically, the complex pharmacology of MPA not only influences its side-effect profile; but it is also possible that the increased breast cancer risk and/or the therapeutic efficacy of MPA in cancer treatment is in part mediated by androgen receptor
Multiparametric Analysis of Oncology Drug Screening with Aqueous Two-Phase Tumor Spheroids
Spheroids present
a biologically relevant three-dimensional model
of avascular tumors and a unique tool for discovery of anticancer
drugs. Despite being used in research laboratories for several decades,
spheroids are not routinely used in the mainstream drug discovery
pipeline primarily due to the difficulty of mass-producing uniformly
sized spheroids and intense labor involved in handling, drug treatment,
and analyzing spheroids. We overcome this barrier using a polymeric
aqueous two-phase microtechnology to robotically microprint spheroids
of well-defined size in standard 384-microwell plates. We use different
cancer cells and show that resulting spheroids grow over time and
display characteristic features of solid tumors. We demonstrate the
feasibility of robotic, high-throughput screening of 25 standard chemotherapeutics
and molecular inhibitors against tumor spheroids of three different
cancer cell lines. This screening uses over 7000 spheroids to elicit
high quality dose-dependent drug responses from spheroids. To quantitatively
compare performance of different drugs, we employ a multiparametric
scoring system using half-maximum inhibitory concentration (IC<sub>50</sub>), maximum inhibition (<i>E</i><sub>max</sub>),
and area under the dose–response curve (AUC) to take into account
both potency and efficacy parameters. This approach allows us to identify
several compounds that effectively inhibit growth of spheroids and
compromise cellular viability, and distinguish them from moderately
effective and ineffective drugs. Using protein expression analysis,
we demonstrate that spheroids generated with the aqueous two-phase
microtechnology reliably resolve molecular targets of drug compounds.
Incorporating this low-cost and convenient-to-use tumor spheroid technology
in preclinical drug discovery will make compound screening with realistic
tumor models a routine laboratory technique prior to expensive and
tedious animal tests to dramatically improve testing throughput and
efficiency and reduce costs of drug discovery
Effect of bovine milk fat-based infant formulae on microbiota, metabolites and stool parameters in healthy term infants in a randomized, crossover, placebo-controlled trial
Background: Natural enrichment of sn-2 palmitate content of infant formulae by using bovine milk fat is known to reduce formation of faecal fatty acid soaps and to improve stool consistency, but effects on gut microbiota composition are unknown. The purpose of this study was to test the influence of milk fat-based formula high in sn-2 palmitate on the infants’ gut microbiota composition and to confirm the beneficial effects of the formula on formation of faecal fatty acid soaps and stool consistency. Methods: Twenty-two healthy term, formula-fed infants were enrolled in a single-blinded randomized, crossover, placebo-controlled trial. After a 2-week run-in period, infants received either a 50% milk fat-based formula containing 39% sn-2 palmitate (MF) or a vegetable fat-based formula (VF) containing 10% sn-2 palmitate in a 2 × 2-week crossover design. Faecal microbiota composition was the primary outcome of the study. Other outcomes included faecal fatty acid soap excretion, calcium excretion, gut comfort parameters and faecal metabolites. Results: Microbiota analysis showed that bifidobacteria dominated the gut microbiota of most infants. Neither alpha- nor beta-diversity was significantly influenced by the intervention. Also, abundance of metabolic pathways was independent of the intervention. The MF formula resulted in significantly lower faecal levels of palmitic acid soap (p = 0.0002) and total fatty acid soaps (p = 0.0001) than the VF formula. Additionally, calcium excretion and palmitic acid concentration were significantly (p = 0.0335) lower in stool samples after MF intervention. Furthermore, a significant physiological effect on softer stools was observed in the MF intervention compared to the VF intervention (p = 0.02). Of the 870 measured faecal metabolites, 190 were significantly different after MF and VF intervention (FDR corrected p < 0.05). Most of these were found at higher levels after MF intervention, potentially indicative of the complex structure of milk fat. Metabolites with more than twofold change between interventions were mostly lipid-derived and included several milk fat-specific fatty acids. Conclusions: Replacing part of the vegetable fat in infant formula with bovine milk fat with high sn-2 palmitate levels did not change the microbiota composition, although a reduction in faecal palmitate soaps, total fatty acid soaps and calcium excretion while improving stool consistency in the MF intervention was confirmed. In addition, 190 faecal metabolites were significantly different, many related to the fat source. Trial registration: Netherlands Trial Registry Identifier: NL7815 19/06/2019
ADAP Promotes Degranulation and Migration of NK Cells Primed During vivo Listeria monocytogenes Infection in Mice.
The adhesion and degranulation-promoting adaptor protein (ADAP) serves as a multifunctional scaffold and is involved in the formation of immune signaling complexes. To date only limited and moreover conflicting data exist regarding the role of ADAP in NK cells. To extend existing knowledge we investigated ADAP-dependency of NK cells in the context of in vivo infection with the intracellular pathogen Listeria monocytogenes (Lm). Ex vivo analysis of infection-primed NK cells revealed impaired cytotoxic capacity in NK cells lacking ADAP as indicated by reduced CD107a surface expression and inefficient perforin production. However, ADAP-deficiency had no global effect on NK cell morphology or intracellular distribution of CD107a-containing vesicles. Proteomic definition of ADAPko and wild type NK cells did not uncover obvious differences in protein composition during the steady state and moreover, similar early response patterns were induced in NK cells upon infection independent of the genotype. In line with protein network analyses that suggested an altered migration phenotype in naĂŻve ADAPko NK cells, in vitro migration assays uncovered significantly reduced migration of both naĂŻve as well as infection-primed ADAPko NK cells compared to wild type NK cells. Notably, this migration defect was associated with a significantly reduced expression of the integrin CD11a on the surface of splenic ADAP-deficient NK cells 1 day post-Lm infection. We propose that ADAP-dependent alterations in integrin expression might account at least in part for the fact that during in vivo infection significantly lower numbers of ADAPko NK cells accumulate in the spleen i.e., the site of infection. In conclusion, we show here that during systemic Lm infection in mice ADAP is essential for efficient cytotoxic capacity and migration of NK cells
Biographies of international women leaders in neurosurgery
We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as “first” of their country or color or other achievement. All of them are included as outstanding—in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life’s work, they chose service, often of the most neglected—those with pain, trauma, and disability. These women inspire and point the way to a time when the term “women leaders” as an exception is unnecessary