Symmetry properties and bifurcation analysis of a class of periodically forced chemical reactors

In this work, we discuss how periodic forcing may induce symmetry properties into mathematical models of chemical reactors. We define a class of reactors subjected to discontinuous periodic forcing, and show that all the reactors belonging to this class have spatio-temporal symmetry. This symmetry and its influence on the possible bifurcation scenarios are discussed. The bifurcation analysis is carried out with suitable discrete systems that exploit a property of the Poincaré map. In fact, it is shown that the spatio-temporal symmetry induced by the forcing makes the Poincaré map of the continuous system an iterate of another map. On this basis, a technique to implement parameter continuation methods is proposed. With such a technique, it is also possible to characterize symmetric and nonsymmetric regimes and unstable limit sets otherwise undetected with “bruteforce” approaches. Examples for reverseflow reactors and networks of n-reactors with periodically switched feed and discharge positions are presented.     

Transplantectomy today: indications and complications

Analysis of the indications for transplantectomy and its complications over a 12-year period. Over a total of 159 failure grafts, we performed 53 transplantectomies (33.3%). The percentage of complications was 16.9%. Three patients died (5.6%) during the more or less immediate post-operative period. In our experience, consistent and prolonged maintenance of immunosuppression should avoid the need for transplantectomy in a high percentage of grafts. Only 15 transplantectomies were made on 104 failure grafts after 6 months (14.4%). Our short but successful experience with embolization of 2 rejected grafts confirms the validity of this conservative alternative versus conventional surgical transplantectomy in selected cases.     

General review of recent activities in acoustic emission technology in Italy

This paper describes the present situation in Italy in the field of Acoustic Emission researches and applications.Information on the level of instrumentation development is given. Both multichannel and multiparameter systems for large structure examination in real time and data logging systems for continuous surveillance purposes are considered.The expertise accumulated in the application of AE to pressure vessel examination during hydrotest is mentioned, this being oriented to pressure components of conventional power stations and chemical plants.Particular attention is recently paid to mechanical fatigue tests. These were conducted on intermediate PWR nuclear pressure vessel, reduced scale offshore nodes and full scale prototype aircraft.A considerable activity has been carried out on application of AE technique to the detection of fluid leakages in power plant components. Both intrusive and non-intrusive methods have been considered. Many boilers and pre-heaters of thermal power plants have been instrumented for an on-line AE monitoring during operation. The problem of the loose part monitoring has been also considered.Several basic researches for material characterization by AE have been also conducted. Different composite material, carbon and austenitic steels, metal alloys have been studied.     

Female and male emotional dependency and its implications for the therapist-client relationship.

Women and men both struggle to achieve a healthy integration of passive dependent and active autonomous strivings. However, how dependent strivings are labeled and become manifest differ for women and men. I first describe the different conceptions of male and female dependency and how such conceptions are related to sex role socialization and to societal norms and practices. I then relate these concepts to the problem of eroticism in psychotherapeutic settings and make specific recommendations for the education and training of psychologists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cell Therapies in Bladder Cancer Management

Currently, bladder cancer (BC) represents a challenging problem in the field of Oncology. The high incidence, prevalence, and progression of BC have led to the exploration of new avenues in its management, in particular in advanced metastatic stages. The recent inclusion of immune checkpoint blockade inhibitors as a therapeutic option for BC represents an unprecedented advance in BC management. However, although some patients show durable responses, the fraction of patients showing benefit is still limited. Notwithstanding, cell-based therapies, initially developed for the management of hematological cancers by infusing immune or trained immune cells or after the engineering of chimeric antigen receptor (CAR) expressing cells, are promising tools to control, or even cure, solid tumors. In this review, we summarize recent cell-based immunotherapy studies, with a special focus on BC.     

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

Immune Checkpoint Inhibitors: A Promising Treatment Option for Metastatic Castration-Resistant Prostate Cancer?

Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.     

Detection of the First Epoxyalcohol Synthase/Allene Oxide Synthase (CYP74 Clan) in the Lancelet (Branchiostoma belcheri,Chordata)

The CYP74 clan cytochromes (P450) are key enzymes of oxidative metabolism of polyunsaturated fatty acids in plants, some Proteobacteria, brown and green algae, and Metazoa. The CYP74 enzymes, including the allene oxide synthases (AOSs), hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases (EASs) transform the fatty acid hydroperoxides to bioactive oxylipins. A novel CYP74 clan enzyme CYP440A18 of the Asian (Belcher’s) lancelet (Branchiostoma belcheri, Chordata) was biochemically characterized in the present work. The recombinant CYP440A18 enzyme was active towards all substrates used: linoleate and α-linolenate 9- and 13-hydroperoxides, as well as with eicosatetraenoate and eicosapentaenoate 15-hydroperoxides. The enzyme specifically converted α-linolenate 13-hydroperoxide (13-HPOT) to the oxiranyl carbinol (9Z,11R,12R,13S,15Z)-11-hydroxy-12,13-epoxy-9,15-octadecadienoic acid (EAS product), α-ketol, 12-oxo-13-hydroxy-9,15-octadecadienoic acid (AOS product), and cis-12-oxo-10,15-phytodienoic acid (AOS product) at a ratio of around 35:5:1. Other hydroperoxides were converted by this enzyme to the analogous products. In contrast to other substrates, the 13-HPOT and 15-HPEPE yielded higher proportions of α-ketols, as well as the small amounts of cyclopentenones, cis-12-oxo-10,15-phytodienoic acid and its higher homologue, dihomo-cis-12-oxo-3,6,10,15-phytotetraenoic acid, respectively. Thus, the CYP440A18 enzyme exhibited dual EAS/AOS activity. The obtained results allowed us to ascribe a name “B. belcheri EAS/AOS” (BbEAS/AOS) to this enzyme. BbEAS/AOS is a first CYP74 clan enzyme of Chordata species possessing AOS activity.