Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation

Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects. Here, we paired nanotechnology with an established dimeric glycoprotein VI-Fc (GPVI-Fc) and a GPVI-CD39 fusion protein, thereby combining site-specific delivery and new antithrombotic drugs. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles, NP-BSA, NP-GPVI and NP-GPVI-CD39 were characterized through electron microscopy, atomic force measurements and flow cytometry. Light transmission aggregometry enabled analysis of platelet aggregation. Thrombus formation was observed through flow chamber experiments. NP-GPVI and NP-GPVI-CD39 displayed a characteristic surface coating pattern. Fluorescence properties were identical amongst all samples. NP-GPVI and NP-GPVI-CD39 significantly impaired platelet aggregation. Thrombus formation was significantly impaired by NP-GPVI and was particularly impaired by NP-GPVI-CD39. The receptor-coated nanoparticles NP-GPVI and the bifunctional molecule NP-GPVI-CD39 demonstrated significant inhibition of in vitro thrombus formation. Consequently, the nanoparticle-mediated antithrombotic effect of GPVI-Fc, as well as GPVI-CD39, and an additive impact of CD39 was confirmed. In conclusion, NP-GPVI and NP-GPVI-CD39 may serve as a promising foundation for a novel therapeutic approach regarding targeted antithrombotic therapy.     

Novel Homozygous Missense Variant in GJA3 Connexin Domain Causing Congenital Nuclear and Cortical Cataracts

Congenital cataracts (CC) are responsible for approximately one-tenth of childhood blindness cases globally. Here, we report an African American family with a recessively inherited form of CC. The proband demonstrated decreased visual acuity and bilateral cataracts, with nuclear and cortical cataracts in the right and left eye, respectively. Exome sequencing revealed a novel homozygous variant (c.563A > G; p.(Asn188Ser)) in GJA3, which was predicted to be pathogenic by structural analysis. Dominantly inherited variants in GJA3 are known to cause numerous types of cataracts in various populations. Our study represents the second case of recessive GJA3 allele, and the first report in African Americans. These results validate GJA3 as a bona fide gene for recessively inherited CC in humans.     

从8位、16位微控制器到ARM处理器

前言 ARM7 SoC(Systems-on-chip,系统芯片)价格的下调,给了那些考虑使用此种芯片的嵌入式开发人员更好的选择.ARM7提供了非常好的机会推动那些原来使用8位或16位机的开发人员转而使用32位处理器.     

Solubility of TiO2 in ZrO2

The solubility of TiO₂ in tetragonal ZrO₂ is 13.8±0.3 mol% ui 1300°C, 14.9±0.2 mol% at 1400°C, and 16.1±0.2 mol% at 1500°C. These solid solutions transform to metastable monoclinic solid solutions without compositional change on cooling to room temperature.     

Tuning of defects in ZnO nanorod arrays used in bulk heterojunction solar cells

With particular focus on bulk heterojunction solar cells incorporating ZnO nanorods, we study how different annealing environments (air or Zn environment) and temperatures impact on the photoluminescence response. Our work gives new insight into the complex defect landscape in ZnO, and it also shows how the different defect types can be manipulated. We have determined the emission wavelengths for the two main defects which make up the visible band, the oxygen vacancy emission wavelength at approximately 530 nm and the zinc vacancy emission wavelength at approximately 630 nm. The precise nature of the defect landscape in the bulk of the nanorods is found to be unimportant to photovoltaic cell performance although the surface structure is more critical. Annealing of the nanorods is optimum at 300°C as this is a sufficiently high temperature to decompose Zn(OH)₂ formed at the surface of the nanorods during electrodeposition and sufficiently low to prevent ITO degradation.     

Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption

Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60 d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na⁺-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep intestinal segments to saccharin or neohesperidin dihydrochalcone evokes secretion of GLP-2, the gut hormone known to enhance intestinal glucose absorption and mucosal growth. Artificial sweeteners, such as Sucram, at small concentrations are potent activators of T1R2-T1R3 (600-fold > glucose). This, combined with oral bioavailability of T1R2-T1R3 and the understanding that artificial sweetener-induced receptor activation evokes GLP-2 release (thus leading to increased SGLT1 expression and mucosal growth), make this receptor a suitable target for dietary manipulation.     

Minimalist counting in sensor networks (Noise helps)

We propose a novel algorithm for counting N indistinguishable objects, called targets, by a collection of sensors. We adopt a minimalist scenario where sensors are unaware of the (non-empty) intersections of sensing regions, and so simple addition of all sensor counts inflates estimates of the total number of targets. The multiple counting in intersections must be accounted for, but with nothing more than the sensor counts, this is clearly impossible. However, noise is typically present in the target counting of many, if not most, applications. We make the key observation that if there is a (target-dependent) noise source affecting all sensors simultaneously, then it couples those with non-empty intersections. Exploitation of this coupling allows us to extract multiple-counting statistics from stochastic correlation patterns, and hence to compute accurate estimates of N via the classical inclusion–exclusion formula. Cumulants are the correlation measures of choice. Our analysis brings out and resolves certain technicalities that arise in our statistical counting algorithm. Examples are worked out to show the potential of the new algorithm. The paper concludes with a discussion of alternative models and open problems.     

双域可重构CIOS模乘器的研究与设计

为提高ECC处理器中模乘的运算速度,并支持长度可重构的双域(素域和二元域)模乘计算,分析了CIOS模乘算法的并行性,提出了适用于硬件并行加速的双参数CIOS算法,设计了6级流水线以及多字数据并行运算的模乘硬件电路,可实现1 152位以内任意长度的双域模乘运算。在CMOS 0.18 μm工艺库下综合并布局布线,电路最大时钟频率为238 MHz。与其他文献的运算时间相比,160～1 024位模乘运算时间减少了17%～40%。     

基于DTW和改进匈牙利算法的句子语义相似度研究

句子语义相似度的研究在自然语言处理等领域发挥着重要的作用.针对现有汉语句子相似度研究中存在的语义特征难以分析以及语序影响的问题,提出了一种基于DTW和匈牙利算法相结合的语义句子相似度处理模型.模型首先使用Word2vec深度学习模型训练百度新闻语料,得到200维的包含语义特征的词向量词典,并建立词向量空间,根据词向量组...     

Resisting tempting foods and smoking behavior: Implications from a self-control theory perspective.

Objective: Individuals may desire to diet or restrain from eating certain foods while attempting to quit smoking out of concern for weight gain. However, previous research and clinical tobacco treatment guidelines suggest that concurrent dieting may undermine attempts to quit smoking. The current study applied the self-control strength model, which posits that self-regulation relies on a limited strength that is consumed with use, to test whether resisting tempting sweets would lead to a greater likelihood of subsequent smoking. Design: Participants were 101 cigarette smokers randomly assigned to resist eating either from a tempting plate of sweets or from a plate of less tempting vegetables. All participants were then given a 10-min recess. Main Outcome Measures: Whether participants smoked during the break, measured with a breath carbon monoxide sample, served as the primary dependent variable. Results: As predicted, participants who resisted sweets were more likely to smoke during the break (53.2%) than those who resisted vegetables (34.0%), χ2(1, N = 101) = 3.65 p