Can Liars Ever Prosper.

The paper compares the optimal financial contracts of a firm which has private information over its expost revenues when the finance can be provided by either a single or two groups of investors. When they are the only investors we use a financial contract with non-contractible monitoring, in which the probabilities of cheating by the entrepreneur/firm and monitoring by investors are mutual best responses. The contract is written by the entrepreneur knowing that this equilibrium will subsequently occur. With a second group of investors who have no monitoring rights, we analyse a truth telling contract and a misrepresentation contract in which cheating and monitoring probabilities are chosen in a similar way to those of the single investor contract. The non monitoring investors learn the results of any monitoring for free. Our main results are that: the two investor group truth-telling contract achieves the second best despite the lack of commitment; this contract is only feasible under limited liability of investors if low state revenues are high enough. When low state revenues are too low for this then the two investor misrepresentation contract is optimal. This contract has a negative correlation between repayments to the two investor groups: the contract uses the non-monitoring group to smooth out the repayments of the entrepreneur optimally. This reduces his incentive to make false reports and mitigates the investor's incentive to monitor. A second result is that the two investor scenario is Pareto superior to the single investor model. We show that with unlimited liability on investor groups, the two investor misrepresentation contract is as good as the second best. Generally in this misrepresentation contract investors may have to make repayments to the firm rather than receive them. A further result is that the three party contract is always renegotiation-proof, as well as collusion-proof so long as the low state revenues are below the expected repayments of the monitor. Last we show that under limited liability the share of finance provided by the two is strictly positive and uniquely determined.financial contracts; multiple investors; no commitment.

06N-P63\u3b1 and TA-P63\u3b1 exhibit intrinsic differences in transactivation specificities that depend on distinct features of DNA target sites.

TP63 is a member of the TP53 gene family that encodes for up to ten different TA and 06N isoforms through alternative promoter usage and alternative splicing. Besides being a master regulator of gene expression for squamous epithelial proliferation, differentiation and maintenance, P63, through differential expression of its isoforms, plays important roles in tumorigenesis. All P63 isoforms share an immunoglobulin-like folded DNA binding domain responsible for binding to sequence-specific response elements (REs), whose overall consensus sequence is similar to that of the canonical p53 RE. Using a defined assay in yeast, where P63 isoforms and RE sequences are the only variables, and gene expression assays in human cell lines, we demonstrated that human TA- and 06N-P63\u3b1 proteins exhibited differences in transactivation specificity not observed with the corresponding P73 or P53 protein isoforms. These differences 1) were dependent on specific features of the RE sequence, 2) could be related to intrinsic differences in their oligomeric state and cooperative DNA binding, and 3) appeared to be conserved in evolution. Since genotoxic stress can change relative ratio of TA- and 06N-P63\u3b1 protein levels, the different transactivation specificity of each P63 isoform could potentially influence cellular responses to specific stresses

PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53.

PRIMA-1 is a chemical compound identified as a growth suppressor of tumor cells expressing mutant p53. We previously found that in the MDA-MB-231 cell line expressing high level of the mutant p53-R280K protein, PRIMA-1 induced p53 ubiquitination and degradation associated to cell death. In this study, we investigated the ability of PRIMA-1 to induce autophagy in cancer cells. In MDA-MB-231 and HCT116 cells, expressing mutant or wild type p53, respectively, autophagy occurred following exposure to PRIMA-1, as shown by acridine orange staining, anti-LC3 immunofluorescence and immunoblots, as well as by electron microscopy. Autophagy was triggered also in the derivative cell lines knocked-down for p53, although to a different extent than in the parental cells expressing mutant or wild type p53. In particular, while wild type p53 limited PRIMA-1 induced autophagy, mutant p53 conversely promoted autophagy, thus sustaining cell viability following PRIMA-1 treatment. Therefore, the autophagic potential of PRIMA-1, besides being cell context dependent, could be modulated in a different way by the presence of wild type or mutant p53. Furthermore, since both cell lines lacking p53 were more sensitive to the cytotoxic effect of PRIMA-1 than the parental ones, our findings suggest that a deregulated autophagy may favor cell death induced by this drug

Human Vitreous Collagen Fragments Dimension As a Function of Vitrectomy Cut Rate

Purpose: To study the dimensions and distribution of human vitreous collagen type II fragments collected after vitrectomy performed at varying cut rates and to evaluate if increasing the cut rate produces smaller collagen fragments, thus reducing retinal traction and/or viscosity. Methods: Fluid was collected during core vitrectomies performed for macular surgery at cut rates from 1000 to 16,000 cuts per minute (CPM) and immediately refrigerated. Protein fractions were separated by molecular weight (MW; >100 kDa, 50–100 kDa, 50– 30 kDa, 30–10 kDa, and <10 kDa) through centrifugal filters. The Human Collagen II ELISA Kit colorimetric assay was then used to measure the COL2A1 in unfiltered and filtered samples. Results: Vitreous samples collected after vitrectomy performed at 16,000 CPM contained a higher concentration of protein with MW over 100 kDa than at any other cutting frequency (P < 0.01). No significant differences were found in fractions collected with a MW between 50 and 100 kDa. Collagen type II fragments over 100 kDa were significantly more represented than smaller fragments at each cut rate. The proportion of smaller (50–100 kDa) collagen fragments compared with those over 100 kDa was higher at 2000 CPM than at higher cut rates. Conclusions: Vitreous samples collected at different cut rates do not contain a significantly different proportion of collagen type II fragments of the tested MW. The extreme variability of vitreous flowthrough the cutter port may explain the uncertain predictability of collagen fragment MWs. Translational Relevance: Increasing the cut rate does not produce vitreous fragments of proportionally smaller dimension. It is necessary to achieve an invariant instantaneous flow through the cutter port in order to decrease retinal traction during vitrectomy

First-trimester prediction of gestational hypertension through the bioelectrical impedance analysis of the body composition

OBJECTIVE: Obesity is a risk factor for the development of gestational hypertension, with important consequences for both the mother and fetus. This prospective observational study aims to propose an early prediction model of hypertensive disorders in pregnancy among obese women, through the bioelectrical impedance analysis (BIA) at the first trimester, thus allowing early recognition of obese women that are at risk to develop gestational hypertension, in order to target preventive interventions. PATIENTS AND METHODS: Singleton obese women (BMI ≥ 30 kg/m2) between the 9th and 12th week of pregnancy were included in the study. The exclusion criteria were chronic diseases, like type 2 diabetes mellitus, hypertension, and other medical pre-existing conditions. Eligible women were followed up at 20, 28, and 36 weeks of gestation by measuring blood pressure, weight, and body composition with the use of the BIA. The diagnosis of gestational hypertension was made after the 20th week of gestation. Pregnancy and perinatal outcomes were then recorded. RESULTS: Of the 479 women included in the study, 85 (17.7%) developed gestational hypertension; the remaining 394 (82.3%) resulted to be normotensive. A higher rate of nulliparous women was found in the hypertensive group (50.6% vs. 37.6%, p = 0.02), together with a higher rate of induction of labor (55.3% vs. 40.9%, p = 0.02) and of small for gestational age (SGA) newborns (12.9% vs. 6.9%, p = 0.03). Significant differences emerged in the body composition between the two groups already from the first trimester, indeed women developing gestational hypertension showed elevated values of Total body Mass, FM, FFM, TBW (p < 0.02), and of leg's FM, FFM (p < 0.006). At the multivariate logistics regression, the risk of developing gestational hypertension resulted higher in women with elevated total body water levels in the first trimester (OR 1.10 95% CI 1.04 -1.92). CONCLUSIONS: The BIA is a rapid, easy, non-invasive, and inexpensive tool to evaluate the body composition of obese pregnant women. It represents a promising predictor of hypertensive disorders in pregnancy, which allows an early identification of the patients at risk of developing gestational hypertension, thus opening a window of opportunity for strictly monitoring and target preventive intervention

False-negative RT-PCR in SARS-CoV-2 disease: experience from an Italian COVID-19 unit

False-negative cases of COVID19 are being increasingly reported. Laboratory diagnosis through RT-PCR testing alone lacks adequate sensitivity to be recommended as the only valid criterion to confirm COVID-19 diagnosis

Chemical Composition of and Inhibition of Angiotensin-Converting Enzyme by Senecio samnitum huet

Abstract Extracts of Senecio samnitum Huet and derived methyl ester of chlorogenic acid have been shown to inhibit angiotensin-converting enzyme (ACE) by using an in vitro bioassay based on the enzymatic cleavage of the chromophore-fluorophore labeled substrate dansyltriglycine into dansylglycine, which is quantitatively measured by high-performance liquid chromatography (HPLC). GC=MS and NMR identified compounds present within the studied S. samnitum extracts. The most effective fraction was obtained in ethyl acetate, which gave 52.56 AE 0.23% (SD) inhibition at 300 mg=ml. The major constituent of this fraction, the methyl ester of chlorogenic acid, showed significant ACE inhibition of 56.78 AE 0.25% at a concentration of 82.5 mg=ml

Environmental risk analysis procedure applied to artificial turf sports fields

Introduction. Owing to the extensive use of artificial turfs worldwide, over the past ten years there has been much discussion about the possible health and environmental problems originating from Styrene-Butadiene Recycled rubber (SBRr). Materials and methods. In this paper the authors performed a Tier-2 environmental-sanitary risk analysis on five artificial turf sports fields located in the city of Turin (Italy) with the aid of RISC4 software. Two receptors (adult player and child player) and three routes of exposure (direct contact with crumb rubber, contact with rainwater soaking the rubber mat, inhalation of dusts and gases from the artificial turf fields) were considered in the conceptual model. Results and discussion. For all the fields and for all the routes, the cumulative carcinogenic risk proved to be lower than 10-6 and the cumulative non-carcinogenic risk lower than 1. The outdoor inhalation of dusts and gases was the main route of exposure for both carcinogenic and non-carcinogenic substances. The results given by the inhalation pathway were compared with those of a risk assessment carried out on a citizen breathing gases and dusts from traffic emissions every day in Turin. Conclusions. For both classes of substances and for both receptors, the inhalation of atmospheric dusts and gases from vehicular traffic gave risk values of one order of magnitude higher than those due to playing soccer on an artificial fiel