Effect of doxorubicin on cytokine production by lymphocytes and the Th1/Th2 balance

Doxorubicin (DOXO) is a potent chemotherapeutic used mainly against solid tumours; however, it has several side effects that can limit its clinical use. On the other hand, the effect of DOXO upon lymphocyte function is controversial. Some studies demonstrate that DOXO administration in vitro suppresses T-cell activation, while the cellular function has been shown to increase in vitro. The objective of this study was to investigate the effect of DOXO on lymphocyte cytokine production in rats. The animals were divided into: SAL (control, n = 10) and DOX (DOXO treated, n = 10). The DOX group received only one DOXO dose at 15 kg Kg(-1) by intraperitoneal injection. Forty-eight hours after DOXO administration, the animals were killed by decapitation. IL-2 production was significantly enhanced (p < 0.05) in lymphocytes from rats treated with DOXO (169.17 +/- 21.73 pg mL 10(5) cell) as compared to cells from SAL (45.92 +/- 10.53 pg mL 10(5) cell). The administration of DOXO decreased (<0.05) IL-4 production in the DOXO group (29.85 +/- 13.09 pg mL 10(5) cell) relative to the SAL group (75.08 +/- 15.31 pg mL 10(5) cell). The IL-2/IL-4 ratio was higher (<0.05) in the DOX group (5.99 +/- 0.44), as compared to SAL group (0.73 +/- 0.12). In conclusion, our results suggest that a dose of DOXO promotes an alteration in the Th1/Th2 balance, promoting a shift towards a Th1-dominant cytokine response. (C) 2010 Elsevier Masson SAS. All rights reserved.

Notch signaling controls the balance of ciliated and secretory cell fates in developing airways

Although there is accumulated evidence of a role for Notch in the developing lung, it is still unclear how disruption of Notch signaling affects lung progenitor cell fate and differentiation events in the airway epithelium. To address this issue, we inactivated Notch signaling conditionally in the endoderm using a Shh-Cre deleter mouse line and mice carrying floxed alleles of the Pofut1 gene, which encodes an O-fucosyltransferase essential for Notch-ligand binding. We also took the same conditional approach to inactivate expression of Rbpjk, which encodes the transcriptional effector of canonical Notch signaling. Strikingly, these mutants showed an almost identical lung phenotype characterized by an absence of secretory Clara cells without evidence of cell death, and showed airways populated essentially by ciliated cells, with an increase in neuroendocrine cells. This phenotype could be further replicated in cultured wild-type lungs by disrupting Notch signaling with a gamma-secretase inhibitor. Our data suggest that Notch acts when commitment to a ciliated or non-ciliated cell fate occurs in proximal progenitors, silencing the ciliated program in the cells that will continue to expand and differentiate into secretory cells. This mechanism may be crucial to define the balance of differentiated cell profiles in different generations of the developing airways. It might also be relevant to mediate the metaplastic changes in the respiratory epithelium that occur in pathological conditions, such as asthma and chronic obstructive pulmonary disease.

Fast heuristics for the Steiner tree problem with revenues, budget and hop constraints

This article describes and compares three heuristics for a variant of the Steiner tree problem with revenues, which includes budget and hop constraints. First, a greedy method which obtains good approximations in short computational times is proposed. This initial solution is then improved by means of a destroy-and-repair method or a tabu search algorithm. Computational results compare the three methods in terms of accuracy and speed. (C) 2007 Elsevier B.V. All rights reserved.

Longitudinal scaling property of the charge balance function in Au plus Au collisions at root s(NN)=200 GeV

We present measurements of the charge balance function, from the charged particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au collisions at root S(NN) = 200 GeV using the STAR detector at RHIC. We observe that the balance function is boost-invariant within the pseudorapidity coverage vertical bar-1.3, 1.3 vertical bar. The balance function properly scaled by the width of the observed pseudorapidity window does not depend on the position or size of the pseudorapidity window. This scaling property also holds for particles in different transverse momentum ranges. In addition, we find that the width of the balance function decreases monotonically with increasing transverse momentum for all centrality classes. (c) 2010 Elsevier B.V. All rights reserved.

Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity

Caloric restriction is the most effective non-genetic intervention to enhance lifespan known to date. A major research interest has been the development of therapeutic strategies capable of promoting the beneficial results of this dietary regimen. In this sense, we propose that compounds that decrease the efficiency of energy conversion, such as mitochondrial uncouplers, can be caloric restriction mimetics. Treatment of mice with low doses of the protonophore 2,4-dinitrophenol promotes enhanced tissue respiratory rates, improved serological glucose, triglyceride and insulin levels, decrease of reactive oxygen species levels and tissue DNA and protein oxidation, as well as reduced body weight. Importantly, 2,4-dinitrophenol-treated animals also presented enhanced longevity. Our results demonstrate that mild mitochondrial uncoupling is a highly effective in vivo antioxidant strategy, and describe the first therapeutic intervention capable of effectively reproducing the physiological, metabolic and lifespan effects of caloric restriction in healthy mammals.

The connectivity paradox: Students’ use of technology as both help and hindrance, and the challenge of striking a balance.

While there is research supporting the use of technology in classrooms, there is also evidence that technology often disrupts student learning. Examples of technology use in classrooms by both teachers and students will be explored, including the benefits and risks of each to the learning process. Research findings on cognition, attention, and classroom technologies will inform strategies for best practices for classroom technology use.

Literary Love Making in Nicholas Sparks Novels: Finding the Balance Between the Writer's Life and Writer's Work in Bestselling Romantic Love

For almost a decade now Nicholas Sparks has been writing love stories. Not only has he been publishing his stories, but they have received high acclaim in each of their installments. Several of his novels have been made into major motion pictures and increased his popularity quite significantly. His status as a successful romantic fiction writer is undeniable, but the question is, why? What is it about Nicholas Sparks that makes his novels so engaging, and personally, what do I need to do as an aspiring novelist to try and acquire the same literary status? Sparks’s novels reach readers at a number of different levels, thus giving them appeal no matter the intellectual intent of the reader. Theoretically, Sparks engages reader response techniques as well as formalist processes such as “habitualization” and “defamiliarization,” while also developing engaging plot lines that represent many of the experiences from his own life. His writing is not only academically redeemable, but it is also creatively stimulating; between the two, Sparks represents the thunder and lightning combination all writers strive for while trying to achieve literary success. This project also offers a creative element in which I attempt to exemplify many of the traits discussed in the analytical sections of this document, by recreating them in a creative, fictitious fashion. Themes such as: motion versus stasis, life versus death, and the ordinary versus the extraordinary all exist within the narrative structure of my short story “Trip to Fall.” Besides these thematic elements, the creative section strives to represent the balance Sparks achieves between the experiences of his own life and the fictitious world he creates. Overall, this project delves into the life of Nicholas Sparks to better understand the inspiration for his writing at the level of form as well as content, while also paying tribute to Sparks’s style through a representation of his work in my own words.

Literary love making in Nicholas Sparks novels: Finding the balance between the writer’s life and the writer’s work in bestselling Romantic Literature

For almost a decade now Nicholas Sparks has been writing love stories. Not only has he been publishing his stories, but they have received high acclaim in each of their installments. Several of his novels have been made into major motion pictures and increased his popularity quite significantly. His status as a successful romantic fiction writer is undeniable, but the question is, why? What is it about Nicholas Sparks that makes his novels so engaging, and personally, what do I need to do as an aspiring novelist to try and acquire the same literary status? Sparks’s novels reach readers at a number of different levels, thus giving them appeal no matter the intellectual intent of the reader. Theoretically, Sparks engages reader response techniques as well as formalist processes such as “habitualization” and “defamiliarization,” while also developing engaging plot lines that represent many of the experiences from his own life. His writing is not only academically redeemable, but it is also creatively stimulating; between the two, Sparks represents the thunder and lightning combination all writers strive for while trying to achieve literary success. This project also offers a creative element in which I attempt to exemplify many of the traits discussed in the analytical sections of this document, by recreating them in a creative, fictitious fashion. Themes such as: motion versus stasis, life versus death, and the ordinary versus the extraordinary all exist within the narrative structure of my short story “Trip to Fall.” Besides these thematic elements, the creative section strives to represent the balance Sparks achieves between the experiences of his own life and the fictitious world he creates. Overall, this project delves into the life of Nicholas Sparks to better understand the inspiration for his writing at the level of form as well as content, while also paying tribute to Sparks’s style through a representation of his work in my own words.