Clinical events in coronary patients who report low distress: Adverse effect of repressive coping.

Objective: Coronary artery disease (CAD) patients who report low distress are considered to be at low psychological risk for clinical events. However, patients with a repressive coping style may fail to detect and report signals of emotional distress. The authors hypothesized that repressive CAD patients are at risk for clinical events, despite low self-rated distress. Design: This was a prospective 5- to 10-year follow-up study, with a mean follow-up of 6.6 years. At baseline, 731 CAD patients filled out Trait-Anxiety (distress), Marlowe-Crowne (defensiveness), and Type D scales; 159 patients were classified as "repressive," 360 as "nonrepressive," and 212 as "Type D." Main Outcome Measures: The primary endpoint was a composite of total mortality or myocardial infarction (MI); the secondary endpoint was cardiac mortality/MI. Results: No patients were lost to follow-up; 91 patients had a clinical event (including 35 cardiac death and 32 MI). Repressive patients reported low levels of anxiety, anger and depression at baseline, but were at increased risk for death/MI (21/159 = 13%) compared with nonrepressive patients (22/360 = 6%), p = .009. Poor systolic function, poor exercise tolerance, 3-vessel disease, index MI and Type-D personality--but not depression, anxiety or anger--also independently predicted clinical events. After controlling for these variables, repressive patients still had a twofold increased risk of death/MI, OR = 2.17, 95% CI = 1.10-4.08, p = .025). These findings were replicated for cardiac mortality/MI. Conclusion: CAD patients who use a repressive coping style are at increased risk for clinical events, despite their claims of low emotional distress. This phenomenon may cause an underestimation of the effect of stress on the heart. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Surface Charge of Supramolecular Nanosystems for In Vivo Biodistribution: A MicroSPECT/CT Imaging Study

Bioimaging has revolutionized medicine by providing accurate information for disease diagnosis and treatment. Nanotechnology‐based bioimaging is expected to further improve imaging sensitivity and specificity. In this context, supramolecular nanosystems based on self‐assembly of amphiphilic dendrimers for single photon emission computed tomography (SPECT) bioimaging are developed. These dendrimers bear multiple In³⁺ radionuclides at their terminals as SPECT reporters. By replacing the macrocyclic 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid cage with the smaller 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid scaffold as the In³⁺ chelator, the corresponding dendrimer exhibits neutral In³⁺‐complex terminals in place of negatively charged In³⁺‐complex terminals. This negative‐to‐neutral surface charge alteration completely reverses the zeta‐potential of the nanosystems from negative to positive. As a consequence, the resulting SPECT nanoprobe generates a highly sought‐after biodistribution profile accompanied by a drastically reduced uptake in liver, leading to significantly improved tumor imaging. This finding contrasts with current literature reporting that positively charged nanoparticles have preferential accumulation in the liver. As such, this study provides new perspectives for improving the biodistribution of positively charged nanosystems for biomedical applications.     

More concise representation of regular languages by automata and regular expressions

We consider two formalisms for representing regular languages: constant height pushdown automata and straight line programs for regular expressions. We constructively prove that their sizes are polynomially related. Comparing them with the sizes of finite state automata and regular expressions, we obtain optimal exponential and double exponential gaps, i.e., a more concise representation of regular languages.     

On the numerical solution of a structured nonsymmetric algebraic Riccati equation

A class of nonsymmetric algebraic Riccati equation, where one of the two linear coefficients is block diagonal, is studied. These equations arise in the modeling of an adaptive MMAP[K]/PH[K]/1$MMAP\left[K\right]/PH\left[K\right]/1$ queue. Some theoretical results are proved, and two new algorithms are introduced that exploit the diagonal structure of the linear coefficient.     

Combining supervised and unsupervised learning for data clustering

Clustering aims to partition a data set into homogenous groups which gather similar objects. Object similarity, or more often object dissimilarity, is usually expressed in terms of some distance function. This approach, however, is not viable when dissimilarity is conceptual rather than metric. In this paper, we propose to extract the dissimilarity relation directly from the available data. To this aim, we train a feedforward neural network with some pairs of points with known dissimilarity. Then, we use the dissimilarity measure generated by the network to guide a new unsupervised fuzzy relational clustering algorithm. An artificial data set and a real data set are used to show how the clustering algorithm based on the neural dissimilarity outperforms some widely used (possibly partially supervised) clustering algorithms based on spatial dissimilarity.     

Multivariate statistical data analysis of cell-free protein synthesis toward monitoring and control

The optimization and control of cell free protein synthesis (CFPS) presents an ongoing challenge due to the complex synergies and nonlinearities that cannot be fully explained in first principle models. This article explores the use of multivariate statistical tools for analyzing data sets collected from the CFPS of Cereulide monoclonal antibodies. During the collection of these data sets, several of the process parameters were modified to investigate their effect on the end-point product (yield). Through the application of principal component analysis and partial least squares (PLS), important correlations in the process could be identified. For example, yield had a positive correlation with pH and NH₃ and a negative correlation with CO₂ and dissolved oxygen. It was also found that PLS was able to provide a long-term prediction of product yield. The presented work illustrates that multivariate statistical techniques provide important insights that can help support the operation and control of CFPS processes.     

Preparation of new ferroelectric glycine phosphite single crystals

An experimental procedure adopted to prepare the recent ferroelectric glycine phosphite single crystals is presented. As the crystal solubility in water depends on temperature, single crystals were grown from fine seed crystals in a saturated solution by employing the slow cooling technique. Transparent, colourless crystals with habit morphology weighing about 8 g were obtained within a month. The same procedure was used to grow single crystals with urea (UGPI). Powder X-ray diffraction studies as well as FTIR studies were carried out on both the crystals. The thermal properties of glycine phosphite (GPI) and UGPI across the ferroelectric phase transition temperature has been carried out. The results will be discussed in detail.     

Proteomic Analysis of Marinesco–Sjogren Syndrome Fibroblasts Indicates Pro-Survival Metabolic Adaptation to SIL1 Loss

Marinesco–Sjogren syndrome (MSS) is a rare multisystem pediatric disorder, caused by loss-of-function mutations in the gene encoding the endoplasmic reticulum cochaperone SIL1. SIL1 acts as a nucleotide exchange factor for BiP, which plays a central role in secretory protein folding. SIL1 mutant cells have reduced BiP-assisted protein folding, cannot fulfil their protein needs, and experience chronic activation of the unfolded protein response (UPR). Maladaptive UPR may explain the cerebellar and skeletal muscle degeneration responsible for the ataxia and muscle weakness typical of MSS. However, the cause of other more variable, clinical manifestations, such as mild to severe mental retardation, hypogonadism, short stature, and skeletal deformities, is less clear. To gain insights into the pathogenic mechanisms and/or adaptive responses to SIL1 loss, we carried out cell biological and proteomic investigations in skin fibroblasts derived from a young patient carrying the SIL1 R111X mutation. Despite fibroblasts not being overtly affected in MSS, we found morphological and biochemical changes indicative of UPR activation and altered cell metabolism. All the cell machineries involved in RNA splicing and translation were strongly downregulated, while protein degradation via lysosome-based structures was boosted, consistent with an attempt of the cell to reduce the workload of the endoplasmic reticulum and dispose of misfolded proteins. Cell metabolism was extensively affected as we observed a reduction in lipid synthesis, an increase in beta oxidation, and an enhancement of the tricarboxylic acid cycle, with upregulation of eight of its enzymes. Finally, the catabolic pathways of various amino acids, including valine, leucine, isoleucine, tryptophan, lysine, aspartate, and phenylalanine, were enhanced, while the biosynthetic pathways of arginine, serine, glycine, and cysteine were reduced. These results indicate that, in addition to UPR activation and increased protein degradation, MSS fibroblasts have profound metabolic alterations, which may help them cope with the absence of SIL1.     

Erbium(III) Triflate as an Extremely Active Acylation Catalyst

Erbium(III) triflate is a powerful catalyst for the acylation of alcohols and phenols. The reaction works well for a large variety of simple and functionalized substrates by using different kinds of acidic anhydrides {Ac₂O, (EtCO)₂O, [(CH₃)₃CO]₂O, Bz₂O, and (CF₃CO)₂O} without isomerisation of chiral centres. Moreover, the catalyst can be easily recycled and reused without significant loss of activity.     

Intervention with polyphenol-rich fruit juices results in an elevation of glutathione S-transferase P1 (hGSTP1) protein expression in human leucocytes of healthy volunteers

Polyphenols are probably antigenotoxic on account of their antioxidant activities and might alter phase I and II enzymes in a way that results in chemoprotection. We investigated the hypothesis that polyphenols enhance expression of glutathione S-transferases (GSTs), which increases carcinogen detoxification and thereby provides protection against oxidative stress. HGSTP1 protein expression and GST polymorphisms were determined in leucocytes obtained during an intervention study with healthy subjects consuming two fruit juices in an 8 wk trial (polyphenol-free run in phase, juice intervention phase, washout phase, second juice intervention phase, each treatment regime lasted for 2 wk). The study had originally shown that juice intervention significantly reduced oxidative DNA damage in leucocytes at week 8 (Bub, A., Watzl, B., Blockhaus, M., Briviba, K. et al., J. Nutr. Biochem. 2003, 14, 90-98). We reanalysed the levels of DNA damage based on GST genotypes. We also treated leucocytes in vitro with mixtures of polyphenols and determined cytotoxicity and expression of 96 genes related to drug metabolism. Key results with leucocytes of the intervention study were that the initial content of hGSTP1 protein was first suppressed at weeks 4 and 6. At week 8, however, hGSTP1 protein expression was significantly increased. HGSTP1 protein levels and DNA damage were inversely correlated (p = 0.005), but there was no difference for cells obtained from subjects with hGSTM1*1 and hGSTM1*0 genotypes, nor was there any difference between cells from subjects consuming the two different juices. The treatment of leucocytes with polyphenol mixtures in vitro did not result in modulated GST gene expression or total GST activity, but in an up-regulation of other biotransformation enzymes (e. g., members of the cytochrome P450 and the sulphotransferase family). In conclusion, in vitro treatment of leucocytes led to a modulated mRNA expression of selected genes, not directly related to oxidative defence systems. In vivo, however, we observed a delayed enhancement of hGSTP1, which could be associated with an initial repression of oxidative DNA damage in leucocytes from human subjects, consuming juices with high levels of polyphenols.