Pollution, mortality and optimal environmental policy

We study an overlapping generations economy in which environmental degradation results from economic activity and affects agents' uncertain lifetimes. Life expectancy depends positively on economic activity and negatively on the stock of pollution. This can make the growth-survival relationship convex over some region and lead to two non-trivial steady states, with one a poverty trap. Uniform abatement taxes can cause the poverty trap to widen while increasing incomes at the high steady state. We also study the properties and dynamics of an optimal second-best abatement tax. It is non-homogeneous and increasing in the capital stock, and leads to a variety of dynamic possibilities, including non-existence and multiplicity of steady states, and cycles around some of the steady states, where there were none under exogenous taxes. Thus, optimal taxes can be an independent source of non-linearities

Pollution, Mortality and Optimal Environmental Policy

We study pollution, mortality and growth in an overlapping generations economy with uncertain lifetimes. Economic activity creates pollution: the stock of pollution has a negative effect on life expectancy while higher income (proxying either for better nutrition and immunity or for better availability of public health) has a prophylactic effect on mortality. These counteracting effects can make the growth-survival relationship non-concave and lead to multiple steady states and a poverty trap. An increase in exogenous abatement taxes can increase the basin of the poverty trap. We study a dynamically consistent sequence of secondbest abatement taxes. The optimal tax is shown to be a non-homogeneous and increasing function of the current capital stock with the optimal tax zero for low levels of capital. The feedback effect from the capital stock to the optimal tax can make optimal abatement policy an independent source of non-linearities leading to non-existence and multiplicity of steady states, as well as oscillations around some steady states when there are none under exogenous taxes

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

IL-4 impairs wound healing potential in the skin by repressing fibronectin expression

BACKGROUND: Atopic dermatitis (AD) is characterized by intense pruritis and is a common childhood inflammatory disease. Many factors are known to affect AD development, including the pleiotropic cytokine IL-4. Yet little is known regarding the direct effects of IL-4 on keratinocyte function. OBJECTIVE AND METHODS: In this report RNA sequencing and functional assays were used to define the effect of the allergic environment on primary keratinocyte function and wound repair in mice. RESULTS: Acute or chronic stimulation by IL-4 modified expression of more than 1000 genes expressed in human keratinocytes that are involved in a broad spectrum of nonoverlapping functions. Among the IL-4-induced changes, repression of fibronectin critically impaired the human keratinocyte wound response. Moreover, in mouse models of spontaneous and induced AD-like lesions, there was delayed re-epithelialization. Importantly, topical treatment with fibronectin restored the epidermal repair response. CONCLUSION: Keratinocyte gene expression is critically shaped by IL-4, altering cell fate decisions, which are likely important for the clinical manifestations and pathology of allergic skin disease

Pollution, Mortality and Time-Consistent Abatement Taxes

We study dynamically consistent policy in a neoclassical overlapping generations growth model where pollution externalities undermine health but are mitigated via tax- nanced abatement. With arbitrarily constant taxation, two steady states arise: an unstable `poverty trap' and a `neoclassical' steady state near which the dynamics might either be monotonically convergent or oscillating. When the planner chooses a time consistent abatement path that maximises a weighted intergenerational sum of expected utility, the optimal tax is zero at low levels of capital and then a weakly increasing function of the capital stock. The non-homogeneity of the tax function along with its feedback e ect on savings induces additional steady states, stability reversals and oscillations

Probing dispersion and re-agglomeration phenomena upon melt-mixing of polymer-functionalized graphite nanoplates

A one-step melt-mixing method is proposed to study dispersion and re-agglomeration phenomena of the as-received and functionalized graphite nanoplates in polypropylene melts. Graphite nanoplates were chemically modified via 1,3-dipolar cycloaddition of an azomethine ylide and then grafted with polypropylene-graft-maleic anhydride. The effect of surface functionalization on the dispersion kinetics, nanoparticle re-agglomeration and interface bonding with the polymer is investigated. Nanocomposites with 2 or 10 wt% of as-received and functionalized graphite nanoplates were prepared in a small-scale prototype mixer coupled to a capillary rheometer. Samples were collected along the flow axis and characterized by optical microscopy, scanning electron microscopy and electrical conductivity measurements. The as-received graphite nanoplates tend to re-agglomerate upon stress relaxation of the polymer melt. The covalent attachment of a polymer to the nanoparticle surface enhances the stability of dispersion, delaying the re-agglomeration. Surface modification also improves interfacial interactions and the resulting composites presented improved electrical conductivity.The authors acknowledge the financial support to Project Matepro Optimizing Materials and Processes, with reference NORTE-07-0124-FEDER-000037 by the Programa Operacional Regional do Norte (ON.2) and Portuguese Foundation for the Science and Technology (FCT) for PEst-C/CTM/LA0025/2013. EC acknowledges FCT for a PhD grant SFRH/BD/87214/2012

Improved Glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy ((1)H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA(1c) reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (-59.3, -16.5%). The relative reduction in IHL correlated with that in HbA(1)c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism

Lubricated revolute joints in rigid multibody systems

The main purpose of this work is to present a general methodology for modeling lubricated revolute joints in constrained rigid multibody systems. In the dynamic analysis of journal-bearings, the hydrodynamic forces, which include both squeeze and wedge effects, generated by the lubricant fluid, oppose the journal motion. The hydrodynamic forces are obtained by integrating the pressure distribution evaluated with the aid of Reynolds’ equation, written for the dynamic regime. The hydrodynamic forces built up by the lubricant fluid are evaluated from the system state variables and included into the equations of motion of the multibody system. Numerical examples are presented in order to demonstrate the use of the methodologies and procedures described in this work.Fundação para a Ciência e a Tecnologia (FCT

Implementation of Telehealth in Radiation Oncology: Rapid Integration During COVID-19 and its Future Role in our Practice.

Introduction: The widespread coronavirus disease 2019 (COVID-19) has resulted in significant changes in care delivery among radiation oncology practices and demanded the rapid incorporation of telehealth. However, the impact of a large-scale transition to telehealth in radiation oncology on patient access to care and the viability of care delivery are largely unknown. In this manuscript, we review our implementation and report data on patient access to care and billing implications. As telehealth is likely to continue after COVID-19, we propose a radiation oncology-specific algorithm for telehealth. Material and Methods: In March 2020, our department began to use telehealth for all new consults, post-treatment encounters, and follow-up appointments. Billable encounters from January to April 2020 were reviewed and categorized into one of the following visit types: in-person, telephonic, or two-way audio-video. Logistic regression models tested whether visit type differed by patient age, income, or provider. Results: There was a 35% decrease in billable activity from January to April. In-person visits decreased from 100% to 21%. Sixty percent of telehealth appointments in April were performed with two-way audio-video, and 40% by telephonic only. In-person consultation visits were associated with higher billing codes compared to two-way audio-video telehealth visits (p Conclusions: Since the onset of COVID-19 pandemic, we were able to move the majority of patient visits to telehealth but observed inconsistent utilization of the audio-video telehealth platform. We present guidelines and quality metrics for incorporating telehealth in radiation oncology practice, based on type of encounter and disease subsite

Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy

Despite the technological advancement in the biomedical science, cancer remains a life-threatening disease. In this study, we designed an anticancer nanodelivery system using graphene oxide (GO) as nanocarrier for an active anticancer agent gallic acid (GA). The successful formation nanocomposite (GOGA) was characterized using XRD, FTIR, HRTEM, Raman, and UV/Vis spectroscopy. The release study shows that the release of GA from the designed anticancer nanocomposite (GOGA) occurs in a sustained manner in phosphate-buffered saline (PBS) solution at pH 7.4. In in vitro biological studies, normal fibroblast (3T3) and liver cancer cells (HepG2) were treated with different concentrations of GO, GOGA, and GA for 72 h. The GOGA nanocomposite showed the inhibitory effect to cancer cell growth without affecting normal cell growth. The results of this research are highly encouraging to go further for in vivo studies