Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action,Pharmacology, Safety,and Efficacy

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.     

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Farmers' preferences for adopting on-farm concentration of raw milk: Results from a discrete choice experiment in Germany

Milk concentrates are used in the manufacturing of dairy products such as yogurt and cheese or are processed into milk powder. Processes for the nonthermal separation of water and valuable milk ingredients are becoming increasingly widespread at farm level. The technical barriers to using farm-manufactured milk concentrate in dairies are minimal, hence the suspicion that the practice of on-farm raw milk concentration is still fairly uncommon for economic reasons. This study, therefore, set out to investigate farmers' potential willingness to adopt a raw milk concentration plant. The empirical analysis was based on discrete choice experiments with 75 German dairy farmers to identify preferences and the possible adoption of on-farm raw milk concentration. The results showed that, in particular, farmers who deemed the current milk price to be insufficient viewed on-farm concentration using membrane technology as an option for diversifying their milk sales. We found no indication that adoption would be impeded by a lack of trustworthy information on milk processing technologies or capital.     

蛋类礼盒包装结构的缓冲性能研究

目的研究蛋类礼盒包装结构的缓冲性能。方法以蛋类尺寸为基础,建立可发性聚乙烯(expandable polyethylene. EPE)缓冲单元结构和组合结构,进行静态仿真分析和实验验证,比较结构在形状、叠合层数、组合形式等参数变化时的载荷与位移。结果结构层数变化相同时,单元结构的极限载荷从143N增加到236 N,组合结构的极限载荷从224 N增加到476 N,均呈近线性增长。结论蛋类礼盒包装中,组合结构的承载能力优于单元结构,通过单元结构的组合,可满足不同蛋类的包装要求。     

Science fiction reduces the eeriness of android robots: A field experiment

As suggested by the uncanny valley hypothesis, robots that resemble humans likely elicit feelings of eeriness. Based on the psychological model of meaning maintenance, we expected that the uncanny valley experience could be mitigated through a fictional story, due to the meaning-generating function of narratives. A field experiment was conducted, in which 75 participants interacted with the humanlike robot Telenoid. Prior to the interaction, they either read a short story, a non-narrative leaflet about the robot, or they received no preliminary information. Eeriness ratings were significantly lower in the science fiction condition than in both other conditions. This effect was mediated by higher perceived human-likeness of the robot. Our findings suggest that science fiction may provide meaning for otherwise unsettling future technologies.     

Efficacy of alpha-cypermethrin and thiamethoxam against Trogoderma granarium Everts (Coleoptera: Dermestidae) and Tenebrio molitor L. (Coleoptera: Tenebrionidae) on concrete

Laboratory bioassays were conducted to evaluate alpha-cypermethrin and thiamethoxam for the control of adults, small larvae and large larvae of the khapra beetle Trogoderma granarium, and the yellow mealworm beetle Tenebrio molitor, on concrete. Factors such as dose (0.025 and 0.1 mg alpha-cypermethrin or thiamethoxam/cm²), exposure interval (1, 3 and 7 d), and formulation (alpha-cypermethrin SC and thiamethoxam WG) were evaluated. Apart from immediate assessment at end of exposure, an assessment of delayed mortality was performed with the survivors of the 7-d exposure by removing them from the treated substrate and keeping them on untreated surfaces for 7 more days. After the 7-d exposure, more T. granarium adults were dead on dishes treated with alpha-cypermethrin than with thiamethoxam. Small larvae were generally less susceptible than adults. After 7 d, small larval mortality reached 64.4% for alpha-cypermethrin, while for thiamethoxam it was <6%. Large T. granarium larvae were more tolerant than the small ones. Delayed mortality of T. granarium adults was generally high for both insecticides and doses, and ranged between 43.3 and 63.3% of those that were still alive immediately after the 7-d treatment. For both larval categories, delayed mortality was higher for larvae that had been previously exposed to alpha-cypermethrin, than with thiamethoxam. For T. molitor, after the 7-d exposure, significantly more adults were dead on dishes treated with alpha-cypermethrin than with thiamethoxam. For small larvae mortality was 38.9% at the lowest thiamethoxam dose, but in the other cases ranged between 88.9 and 95.6%. In the case of large larvae, the overall mortality was low in all tested combinations. Regarding delayed mortality of this species, it remained at low levels, for both adults and small larvae. Our results indicate that T. molitor was more susceptible than T. granarium in both insecticides tested, but alpha-cypermethrin was more effective than thiamethoxam.     

面向草莓抓取的气动四叶片软体抓手研制

农林业中果蔬的自动化采摘需求日趋强烈,末端抓手是实现无损采摘的关键。传统的末端抓手以刚性结构居多,现有的各种柔性抓手也存在抓取力不足、包覆性不佳等缺点。本文以草莓的无损采摘为研究对象,提出将草莓外部轮廓曲线作为设计曲线,设计了一种新型气动四叶片软体抓手。首先,对软体抓手的结构做仿真优化,提出一种安全地附着在目标物表面的设想。然后,在进行草莓表面的最小破坏应力试验的基础上,测试了软体抓手的末端力,验证了其实现无损抓取的可行性。再次,利用动态捕捉技术,研究了软体抓手叶面的弯曲变形规律。最后,选择使用弧线型气体通道的软体抓手进行了草莓抓取测试,结果证明了气动四叶片软体抓手可以实现草莓的无损抓取,抓取成功率达90%,破损率为2%,表明所研制的四叶片软体抓手用于草莓抓取时具有良好的稳定性和实用性,可用于草莓采摘的末端执行器。本研究也可为其他易损果蔬的采摘技术提供理论基础和技术支撑。