Apoptosis in the failing human heart

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.     

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.     

CCD传感器实时检测系统在微细电火花加工机床上校正法的研究

CCD(Charge-Couple Device)传感器实时检测系统是一套基于光电检测技术的质量监测仪器,可用于实时观测和测量被加工工件,特别适合安装应用于微细电火花加工机床.本文就该系统安装在电火花加工机床上后如何提高检测精度进行研究,提出了3种方法对该检测系统进行校正,如,整体校准常数、C值校正、D值校正.此后设计实验来检验校准后该系统的稳定性和精确度,从而验证了所提出的三步校正法的可靠性.     

Cytokines from Bench to Bedside: A Retrospective Study Identifies a Definite Panel of Biomarkers to Early Assess the Risk of Negative Outcome in COVID-19 Patients

The main aim of this study was to identify the most relevant cytokines which, when assessed in the earliest stages from hospital admission, may help to select COVID-19 patients with worse prognosis. A retrospective observational study was conducted in 415 COVID-19 patients (272 males; mean age 68 ± 14 years) hospitalized between May 2020 and March 2021. Within the first 72 h from hospital admission, patients were tested for a large panel of biomarkers, including C-reactive protein (CRP), Mid-regional proadrenomedullin (MR-proADM), Interferon-γ, interleukin 6 (IL-6), IL-1β, IL-8, IL-10, soluble IL2-receptor-α (sIL2Rα), IP10 and TNFα. Extensive statistical analyses were performed (correlations, t-tests, ranking tests and tree modeling). The mortality rate was 65/415 (15.7%) and a negative outcome (death and/or orotracheal intubation) affected 98/415 (23.6%) of cases. Univariate tests showed the majority of biomarkers increased in severe patients, but ranking tests helped to select the best variables to put on decisional tree modeling which identified IL-6 as the first dichotomic marker with a cut-off of 114 pg/mL. Then, a good synergy was found between IL-10, MR-proADM, sIL2Rα, IP10 and CRP in increasing the predictive value in classifying patients at risk or not for a negative outcome. In conclusion, beside IL-6, a panel of other cytokines representing the degree of immunoparalysis and the anti-inflammatory response (IP10, sIL2Rα and IL-10) showed synergic role when combined to biomarkers of systemic inflammation and endothelial dysfunction (CRP, MR-proADM) and may also better explain disease pathogenesis and suggests targeted intervention.     

Performance of genetic algorithms in search for water splitting perovskites

We examine the performance of genetic algorithms (GAs) in uncovering solar water light splitters over a space of almost 19,000 perovskite materials. The entire search space was previously calculated using density functional theory to determine solutions that fulfill constraints on stability, band gap, and band edge position. Here, we test over 2500 unique GA implementations in finding these solutions to determine whether GA can avoid the need for brute force search, and thereby enable larger chemical spaces to be screened within a given computational budget. We find that the best GAs tested offer almost a 6 times efficiency gain over random search, and are comparable to the performance of a search based on informed chemical rules. In addition, the GA is almost 10 times as efficient as random search in finding half the solutions within the search space. By employing chemical rules, the performance of the GA can be further improved to approximately 12–17 better than random search. We discuss the effect of population size, selection function, crossover function, mutation rate, fitness function, and elitism on the final result, finding that selection function and elitism are especially important to GA performance. In addition, we determine that parameters that perform well in finding solar water splitters can also be applied to discovering transparent photocorrosion shields. Our results indicate that coupling GAs to high-throughput density functional calculations presents a promising method to rapidly search large chemical spaces for technological materials.     

Emerging specializations,competences and firms' proximity in digital industries: The case of London

In order to overcome the limitations of defining industrial specializations in digital industries through SIC codes, this paper suggests measuring the specializations and competences of these industries on the basis of the degree of digital technologies present in the products and services supplied. Metadata from CrunchBase are employed, as proxies of firms' specializations and competences which are defined as the fields of activity in which firms are involved. Applying a network analysis, these specializations and competences are linked to the recognition of emerging digital technologies and the strongest combinations of products and services. We tested the proposed methodology on London, a leading centre for the digital economy.     

CCD传感器实时检测技术在微细电火花加工机床上应用的优势

CCD传感器实时检测系统是一套基于光电检测技术的质量监测仪器,可用于实时观测和测量被加工工件,特别适合安装应用于微细电火花加工机床。此系统利用CCD（Charge-CoupleDevice）传感器对工件进行非接触式测量,提高了微细电火花加工机床的工作效率和质量。此文对这一系统进行讨论,分析了其特点和优越性。     

Estimation of dietary intake of pesticide residues by the Italian population during 1997

In 1997 the Italian monitoring programme for pesticide residues in food comprised 7951 samples of 152 different foods for which a total of 275 pesticides were analysed. For 90 pesticides, the National Estimated Daily Intakes (NEDIs) were calculated by using the 90th percentile value and the food consumption data for the general Italian population. The calculated NEDIs were found to represent only a small portion of the respective Acceptable Daily Intake (ADI).     

Evaluation of lysozyme stability in young red wine and model systems by a validated HPLC method

Hen’s egg lysozyme (LYZ) is added to red wine for preventing malolactic activity. Sulphur dioxide and polyphenolic compounds can depress LYZ solubility and effectiveness, likely by sulphonation of enzyme disulphide bonds or protein binding, respectively. These phenomena were evaluated in either young red wine or model wine systems. A reliable and validated HPLC method was first developed in order to quantify soluble LYZ in wine (r_95% = 10.7 mg l⁻¹). The amount of insolubilized LYZ in red wine was related to the content of non-anthocyan flavonoids of low molecular weight and enzyme precipitation occurred in few minutes when flavonoid concentration exceeded 50 mg l⁻¹. Interaction between sulphur dioxide and LYZ occurred in polyphenol-free model wine systems and for the first time the formation of mono-thiosulphonated LYZ was demonstrated. This reaction was favoured by increasing pH value and sulphur dioxide concentration. Nevertheless, sulphonation alone did not fully explain LYZ instability in model wine systems.