218 research outputs found

    Education: Where It Pays

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    Post-secondary education is one of the most important decisions a student is faced with when leaving high school. There have been numerous studies as to whether the additional education is worthy of one\u27s time and attention but what has not been addressed where is important. If one plans to live in a certain area it would be extremely beneficial to know whether your education is going to benefit one\u27s financial situation or not. Utilizing incomes as the dependent variable and Ordinary Least Squares as the econometric method, this paper concludes having advanced degrees in the metropolitan areas are very beneficial whereas it is much less impactful in micropolitan areas. It also suggests the lack of an advanced degree will generate a negative impact on one\u27s income but when taking into consideration the inherent effects of the micropolitan area, there is a small premium to be obtained

    Decreased kidney mitochondrial content and PGC-1α following repeated low-dose cisplatin-induced kidney injury.

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    Cisplatin is highly effective and one of the most commonly used chemotherapeutic agents in the treatment of a number of different solid organ tumors. Unfortunately, the dose-limiting nephrotoxicity occurs in up to 30% of patients, which requires alterations to treatment regimens that are often less effective. The kidney’s function is to provide fluid homeostasis, and this is an energy-intensive process. Proper renal function is dependent on functional mitochondria. PGC-1α regulates mitochondrial number, respiratory capacity, and mitochondrial proteins in proximal tubule cells. We delivered low-dose cisplatin to mice via intraperitoneal injections once a week for 4 weeks. The mice were then euthanized, and the kidneys were immediately extracted and frozen. Our data show that repeated dosing of cisplatin results in reduced renal function, increased fibrosis, reduced mitochondrial content, and reduced PGC-1α in kidney cortices. We hypothesize that increasing PGC-1α will protect against cisplatin-induced kidney injury

    Lung cancer-kidney crosstalk enhances cisplatin-induced nephrotoxicity.

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    Cancer patients represent a unique patient population with increased susceptibility to kidney disease. Drug-induced acute kidney injury (AKI) in cancer patients is a common problem. Cisplatin is a highly effective treatment used in many solid organ cancers. However, cisplatin causes AKI in 30% of patients, increasing the risk of chronic kidney disease (CKD) development. The kidneys maintain homeostasis of the body’s extracellular fluids and removing waste products. The kidneys filter nearly 170 liters of fluid a day and must reabsorb over 99% of the filtrate. The reabsorption occurs in tubule cells throughout the nephron, which are highly enriched in mitochondria to complete this task. One mechanism by which cisplatin induces nephrotoxicity is by reducing mitochondrial content and biogenesis leading to loss of kidney function, kidney injury, inflammation, and development of fibrosis. Reduced kidney mitochondrial mass and respiration also impairs the tissue repair process. Historically, most preclinical cisplatin toxicity studies have been completed in mice without cancer. We believe the physiology of cancer patients is not adequately represented in these non-cancerous murine models. In this study we used multiple mouse models of lung cancer in combination with repeated low dose cisplatin (RLDC) regimen to determine if cancer alters the nephrotoxicity of cisplatin. Additionally, we pharmacologically induced mitochondrial biogenesis to increase kidney mitochondrial content to determine if this pathway will protect from cisplatin-induced nephrotoxicity. Our results show that lung cancer combined with cisplatin enhances the nephrotoxicity of cisplatin. Additionally, cancer alone without cisplatin reduced renal function, increased fibrosis, reduced mitochondrial content, and reduced PGC-1α of kidney cortices. Stimulating mitochondrial biogenesis increased kidney mitochondrial content and reduced loss of kidney function, kidney injury, inflammation, and development of fibrosis from RLDC in mice without cancer. However, these effects are nullified when the experiment was repeated in mice with subcutaneous lung cancer. Previous clinical trials on nephroprotective agents have failed, and we propose that poorly representative mouse models may be responsible for misleading preclinical research. Our development of clinically relevant models of cisplatin-induced nephrotoxicity provides a foundation for developing nephron-protective agents that can be used as an adjunctive therapy for cancer patients taking cisplatin

    Regression in a Verbal Conditioning Situation as a Function of Psychiatric Illness

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    The primary purpose of this study was to investigate regression among psychiatric groups in a verbal conditioning situation. Secondary purposes were to study the conditioning performance of the psychiatric groups and their awareness of the reinforcement contingency. The actual Ss were 30 male and 30 female patients selected from the resident population of the North Dakota State Hospital. Ss were selected on the basis of the official diagnosis of schizophrenia, psychoneurosis, or personality trait disturbance, age, and months of hospitalization. Sixteen individuals in each of the diagnosis x sex categories were randomly selected to serve in either an experimental or control group. The first 5 Ss in each of the diagnosis x sex categories to achieve the conditioning criterion were utilized in the investigation of regression. Of the 73 patients utilized, 13 did not achieve the criterion. These Ss were used only for comparisons between conditioners and nonconditioners. The Ss in the experimental group received 27 reinforcements for adjectives followed by 27 reinforcements for plural nouns. Reinforcement was a flash of green light and a point registering on a counter. Ss were instructed that the number of points they received would determine how much money they would receive when the session was completed. Punishment by means of a red light was then administered for all verbal responses in a 5-minute punishment period. Ss were instructed that red lights meant that points and money were being lost. The control group received 27 reinforcements for plural nouns only and then punishment during the 5-minute punishment period. The E administered all reinforcement and punishment from behind a one-way mirror and had no personal contact with the Ss prior to the experiment. Instructions to Ss were taped and transmitted to them over a speaker. The E\u27s research assistant had only minimal personal contact with the Ss prior to the experimental session and following this when a questionnaire was administered to assess awarenesss of the reinforcement contingency. Hypotheses advanced in this investigation were: 1. The experimental group would demonstrate significantly more regressed responses than the control group. 2. Schizophrenics in the experimental group would demonstrate significantly more regressed responses than neurotics who in turn would demonstrate significantly more regressed responses than character disorders. 3. Schizophrenics in the experimental group would regress more quickly to an earlier learned response than neurotics who in turn would regress more quickly than character disorders. 4. Neurotics and character disorders in the experimental and control groups would demonstrate greater conditionability than schizophrenics. 5. Operant levels for conditioners would be significantly higher than for nonconditioners. 6. More character disorders and neurotics would demonstrate awareness of the reinforcement contingency than schizophrenics. Analysis of the results supported the hypothesis that the experimental group would demonstrate regression when compared to the control group. Hypotheses concerning differential regression among the three diagnostic groups were not supported. the hypothesis involving differential conditionability among the diagnostic groups not only failed to receive full support, but there were nonsignificant trends in the opposite direction. Comparisons between conditioners and nonconditioners on base rate data suggested the importance of total verbal operant level in determining conditions. Since only 5 Ss were judged aware, no conclusions could be drawn concerning the awareness hypothesis. Failure of this research to support the hypothesis of differential regression among the diagnostic categories was discussed in relation to methodological inadequacies and the theory from which the hypotheses were derived. The absence of differential conditionability among the diagnostic categories was discussed in relation to pre-experimental E-S interaction. Suggestions were made for utilizing a verbal condition situation in furth studies of regression, stress, rigidity, and psychotherapy

    Foreword

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    Scalable Multi-Chain Coordination via the Hierarchical Longest Chain Rule

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    This paper introduces BlockReduce, a Proof-of-Work (PoW) based blockchain system which achieves high transaction throughput through a hierarchy of merged mined blockchains, each operating in parallel on a partition the overall application state. Most notably, the full PoW available within the network is applied to all blockchains in BlockReduce, and cross-blockchain state transitions are enabled seamlessly within the core protocol. This paper shows that, given a hierarchy of blockchains and its associated security model, the protocol scales superlinearly in transaction throughput with the number of blockchains operated by the protocol

    Bioinspired, Sizeâ Tunable Selfâ Assembly of Polymerâ Lipid Bilayer Nanodiscs

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    Polymerâ based nanodiscs are valuable tools in biomedical research that can offer a detergentâ free solubilization of membrane proteins maintaining their native lipid environment. Herein, we introduce a novel ca. 1.6â kDa SMAâ based polymer with styrene:maleic acid moieties that can form nanodiscs containing a planar lipid bilayer which are useful to reconstitute membrane proteins for structural and functional studies. The physicochemical properties and the mechanism of formation of polymerâ based nanodiscs are characterized by light scattering, NMR, FTâ IR, and TEM. A remarkable feature is that nanodiscs of different sizes, from nanometer to subâ micrometer diameter, can be produced by varying the lipidâ toâ polymer ratio. The smallâ size nanodiscs (up to ca. 30â nm diameter) can be used for solution NMR spectroscopy studies whereas the magneticâ alignment of macroâ nanodiscs (diameter of > ca. 40â nm) can be exploited for solidâ state NMR studies on membrane proteins.Lipiddoppelschichtâ Nanoscheiben unterschiedlicher Gröà e bilden sich aus einem modifizierten Styrolâ Maleinsäureâ Copolymer. Kleine Nanoscheiben (bis ca. 30â nm Durchmesser) eignen sich für NMRâ Studien in Lösung, während die magnetische Ausrichtung gröà erer Nanoscheiben (Durchmesser >40â nm) bei Festkörperâ NMRâ Studien an Membranproteinen von Vorteil ist.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138268/1/ange201705569_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138268/2/ange201705569.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138268/3/ange201705569-sup-0001-misc_information.pd

    Solid-state NMR study of the YadA membrane-anchor domain in the bacterial outer membrane.

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    MAS-NMR was used to study the structure and dynamics at ambient temperatures of the membrane-anchor domain of YadA (YadA-M) in a pellet of the outer membrane of E. coli in which it was expressed. YadA is an adhesin from the pathogen Yersinia enterocolitica that is involved in interactions with the host cell, and it is a model protein for studying the autotransport process. Existing assignments were sucessfully transferred to a large part of the YadA-M protein in the E. coli lipid environment by using 13C-13C DARR and PDSD spectra at different mixing times. The chemical shifts in most regions of YadA-M are unchanged relative to those in microcrystalline YadA-M preparations from which a structure has previously been solved, including the ASSA region that is proposed to be involved in transition-state hairpin formation for transport of the soluble domain. Comparisons of the dynamics between the microcrystalline and membrane-embedded samples indicate greater flexibility of the ASSA region in the outer-membrane preparation at physiological temperatures. This study will pave the way towards MAS-NMR structure determination of membrane proteins, and a better understanding of functionally important dynamic residues in native membrane environments
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