Primary Founder Mutations in the PRKDC Gene Increase Tumor Mutation Load in Colorectal Cancer

The clonal composition of a malignant tumor strongly depends on cellular dynamics influenced by the asynchronized loss of DNA repair mechanisms. Here, our aim was to identify founder mutations leading to subsequent boosts in mutation load. The overall mutation burden in 591 colorectal cancer tumors was analyzed, including the mutation status of DNA-repair genes. The number of mutations was first determined across all patients and the proportion of genes having mutation in each percentile was ranked. Early mutations in DNA repair genes preceding a mutational expansion were designated as founder mutations. Survival analysis for gene expression was performed using microarray data with available relapse-free survival. Of the 180 genes involved in DNA repair, the top five founder mutations were in PRKDC (n = 31), ATM (n = 26), POLE (n = 18), SRCAP (n = 18), and BRCA2 (n = 15). PRKDC expression was 6.4-fold higher in tumors compared to normal samples, and higher expression led to longer relapse-free survival in 1211 patients (HR = 0.72, p = 4.4 × 10⁻³). In an experimental setting, the mutational load resulting from UV radiation combined with inhibition of PRKDC was analyzed. Upon treatments, the mutational load exposed a significant two-fold increase. Our results suggest PRKDC as a new key gene driving tumor heterogeneity.     

Cranberry and Recurrent Cystitis: More than Marketing?

Epidemiologic studies indicate that millions of people suffer from recurrent cystitis, a pathology requiring antibiotic prophylaxis and entailing high social costs. Cranberry is a traditional folk remedy for cystitis and, which, in the form of a variety of products and formulations has over several decades undergone extensive evaluation for the management of urinary tract infections (UTI). The aim of this retrospective study is to summarize and review the most relevant and recent preclinical and clinical studies on cranberries for the treatment of UTIs. The scientific literature selected for this review was identified by searches of Medline via PubMed. A variety of recent experimental evidence has shed light on the mechanism underlying the anti-adhesive properties of proanthrocyanidins, their structure–activity relationships, and pharmacokinetics. Analysis of clinical studies and evaluation of the cranberry efficacy/safety ratio in the prevention of UTIs strongly support the use of cranberry in the prophylaxis of recurrent UTIs in young and middle-aged women. However, evidence of its clinical use among other patients remains controversial.     

Inductive study of confidentiality: for everyone

The Inductive Method is among the most established tools to analyse security protocols formally. It has successfully coped with large, deployed protocols, and its findings are widely published. However, perhaps due to its embedding in a theorem prover or to the lack of tutorial publications, it is at times criticised to require super-specialised skills and hence to be rather impractical. This paper aims at showing that criticism to be stereotypical. It pursues its aim by presenting the first tutorial-style paper to using the Inductive Method. This paper cannot cover every aspect of the method. It focuses on a key one, that is how the Inductive Method treats one of the main goals of security protocols: confidentiality against a threat model. The treatment of that goal, which may seem elegant in the Inductive Method, in fact forms a key aspect of all protocol analysis tools, hence the paper motivation rises still. With only standard skills as a requirement, the reader is guided step by step towards design and proof of significant confidentiality theorems. These are developed against two threat models, the standard Dolev–Yao and a more up-to-date one, the General Attacker, the latter turning out particularly useful also for didactic purposes.     

A comparison of higher order auditory processes in younger and older adults.

The authors conducted 3 experiments investigating the effects of aging on higher order auditory processes. They compared younger and older adults with respect to (a) their auditory channel capacity, (b) the extent of their top-down control over auditory gain, and (c) their ability to focus attention on a narrow band of frequencies. To ensure that subclinical cochlear processing deficits in older adults (e.g., higher thresholds, poorer discrimination of frequency and intensity differences) did not limit performance, the authors used only stimuli that were perfectly discriminable by all participants. No age differences were found in any of these experiments, suggesting that some higher order auditory processes (e.g., top-down control over auditory gain, auditory attention) are preserved in normal aging, despite numerous age-related declines in peripheral auditory functionality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of stimulus range on perceived contrast: Evidence for contrast gain control.

Investigated whether the stimulus range affected the perceived contrast of vertical gratings whose spatial frequencies were either 1 or 4 cycles/deg to determine if adjustive processes apply to the contrast sensitivity of spatial frequency channels in a vision task. Nine Ss judged the perceived contrasts of 1 and 4 cycle/deg gratings intermixed within a session. Four different conditions were created by combining either a set of low-contrast or high-contrast gratings at 1 frequency with a broad range of contrasts at the other frequency. When the broad-range set was at 1 cycle/deg, contrast-matches across spatial frequencies were unaffected by changing the range of the 4-cycle/deg gratings. When the broad-range set was 4 cycles/deg, contrast matches were changed by changing the range of the 1 cycle/deg gratings. This asymmetry in the range effect was shown to be consistent with the characteristics of the 2 channels' receptive-field profiles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the deposition parameters and aging on the optical and photoluminescence properties of C70 films

We have investigated the influence of the growth parameters (substrate temperature and deposition rate) and the aging process on the optical properties of C₇₀ thin films, by means of absorption and photoluminescence spectra. The Urbach energy, obtained from the absorption spectra, indicates that the substrate temperature influences the film optical properties more than the deposition rate. The luminescence spectra suggest the important role of the disorder in the radiative efficiency. The main structures of the emission spectra have been assigned to an intramolecular polaron-exciton. The analysis of the temperature dependence of the photoluminescence spectra of the as-deposited samples shows that the vibronic transitions are dominant at low temperature, whereas the singlet purely electronic recombination (due to Frenkel-type exciton) is visible at a sufficiently high temperature. On the contrary, in the aged samples this purely electronic transition is well resolved from low to high temperature. This anomalous behaviour is discussed and attributed to the disorder introduced in the film.     

Model checking RAISE applicative specifications

Ensuring the correctness of a given software component has become a crucial aspect in software engineering and model checking provides an almost fully automatic way of achieving this goal. Due to the scalability problems of the model checking technique, it has become popular to apply it at early stages in the development process, when the size of the model is much smaller than the final code. Properties proved in this way can be shown to hold at the implementation level provided that the final code refines the original specification. In this paper we focus on the main issues for adding model checking functionality to the RAISE specification language (RSL) and present the semantic foundations of our current approach for doing so. We also describe a way to use model checking to verify RAISE confidence conditions, ensuring the soundness and completeness of the results checked in this way. We then present the most interesting details of the implementation of a tool that follows the described approach. Finally, we illustrate the application of the technique with two case studies: a Digital Multiplexed Radio Telephone System and the Mondex electronic purse.     

Experimental evaluation of ventilated walls with an external clay cladding

The paper presents the results of an experimental study on ventilated walls with an external clay cladding in a temperate Mediterranean climate.The aim of this work is to assess the actual thermal performance of the ventilated façade with a complete thermo-fluid dynamic analysis.The paper describes the experimental work carried out on walls with different exposure and various heights of the ventilation channel (6 m and 12 m) with controlled internal air temperature. The air velocities, temperatures and heat fluxes in the ventilated facade were monitored and correlations between the thermo-physical parameters were identified.The study showed that, on sunny days, the external surface temperatures, temperatures in the air cavity and air velocity in the gap are considerably higher for the 12 m wall, while during the nighttime lower temperatures are found for the various layers of the wall.The data obtained allowed us to calculate the Reynolds number and to identify the airflow rate in the channel. Correlations were found between the air velocity in the gap, the airflow rate, the Reynolds number and the sun–air temperature. These correlations are useful for modelling ventilated walls, which are generally very complex, with simplified equivalent walls. Finally it was possible to identify the peak temperatures with respect to exposure and thermal lag. The thermo-graphic analysis showed that the behaviour of the walls is almost uniform without thermal bridges.     

Hydrogen production in an upflow anaerobic packed bed reactor used to treat cheese whey

In this work, an upflow anaerobic packed bed reactor configuration to produce hydrogen using cheese whey as the substrate was tested. The microbiological composition was linked to the reactor operation.     

Phenolic content and antioxidant capacity versus consumer acceptance of soaked and vacuum impregnated frozen nectarines

Nectarines (Prunus persica L. cv. Maria Laura) were manually selected, cut in slices and divided into four groups: fresh, untreated frozen, soaked in osmotic solution and subsequently frozen, and vacuum impregnated (VI) and subsequently frozen. This investigation was focused on evaluation of consumer acceptance with respect to treated versus untreated frozen nectarine slices. In a preliminary acceptance test of untreated frozen nectarine slices, fruits were generally rejected on the basis of a darkened appearance and “oxidized” taste. These negative attributes were probably linked to the activity of polyphenol oxidase (PPO) and depletion of phenols due to cell rupture during freeze–thaw procedures. For these reasons, in order to evaluate the tendency of fruit to oxidation, several analyses were performed: the antioxidant capacity of phenolic fraction and the o-diphenol content were estimated by spectrophotometric assays, whereas the hydroxycinnamic acid (chlorogenic and neochlorogenic acids) composition was evaluated by high performance liquid chromatography (HPLC). Phenolic content and antioxidant capacity were found to correlate well with the acceptance level of frozen nectarine slices. In this regard a higher phenolic content associated with a higher acceptance level of nectarine samples.