Detection and recognition of cancer cells in vivo

A fundamentally new recognition method of bio-objects (e.g., cancer cells as the most important case of them) that escape the immune system supervision control is suggested. It is proposed to use a unified complex consisting of several molecular groups (e.g., antibodies or their fragments) bound with each other. Binding targets are localized on the surface of this bio-object. The choice of the targets is determined by antigen profiling being expressed on the surface of these bio-objects. The recognition efficiency appears to be notably higher than in a situation when molecular groups do not form a unified complex and act separately.     

集中式多传感器模糊联合概率数据互联算法

为解决集中式多传感器系统中多目标跟踪问题,提出了集中式多传感器模糊联合概率数据互联算法。该算法应用模糊数学的方法计算测量点迹与航迹测量预测之间的模糊综合相似度,运用阈值判别及经验概率法则给出模糊联合互联概率的计算方法,提出了集中式多传感器模糊联合概率数据互联算法的状态估计模型。对该算法与已有集中式多传感器联合概率数据互联算法进行仿真比较,仿真结果显示该算法的跟踪精度较后者提高了43.7%,同时有效地降低了周期耗时,综合性能更优越。     

多台CCD电视经纬仪交会测量系统的多目标信息融合

基于多台CCD电视经纬仪交会测量原理,深入分析了交会计算误差来源对系统测量的影响。针对离散落点和弹道采样点多目标数据,首先通过目标信息源合成来提高多目标数据录取率;然后,通过误差加权平均,融合处理测量数据,以降低多台电视经纬仪对同一组多目标的测量误差;进而,基于系统数据后处理,抽象多目标统计特性;借助系统熵标准,评估多目标信息融合效果。实验结果证明：该多台CCD电视经纬仪交会测量系统的多目标信息融合具有简单、有效、鲁棒等优点,并为相关多目标识别与定位领域内的应用提供了宝贵的参考价值。     

基于因素空间的多传感器决策融合方法

基于因素空间理论,建立一种多传感器多目标识别方法。根据多传感器探测与控制网络系统的决策特性提出了传感器模糊矩阵的建立方法,根据对概念的反馈外延计算提出多目标识别方法。仿真结果表明该方法能使系统的识别错误率低于１０％。多传感器多目标决策融合的工程方法为其决策融合方法的建立提供了一条新的途径。     

一种适于工程应用的多目标跟踪快速数据关联算法

提出了一种新的多目标跟踪快速数据关联算法,重点分析了关联门相交区域中的公共回波对航迹更新的影响,并综合考虑了关联门内其余侯选回波对航迹更新的作用,以很小的计算代价完成了后验概率的计算。仿真表明,新算法以与ＰＤＡＦ算法接近的计算量,达到了接近于ＪＰＤＡＦ算法的目标跟踪成功率。     

Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer

The enzyme soluble epoxide hydrolase (sEH) plays a central role in metabolism of bioactive lipid signaling molecules. The substrate-specific hydrolase activity of sEH converts epoxyeicosatrienoic acids (EETs) to less bioactive dihydroxyeicosatrienoic acids. EETs exhibit anti-inflammatory, analgesic, antihypertensive, cardio-protective and organ-protective properties. Accordingly, sEH inhibition is a promising therapeutic strategy for addressing a variety of diseases. In this review, we describe small molecule architectures that have been commonly deployed as sEH inhibitors with respect to angiogenesis, inflammation and cancer. We juxtapose commonly used synthetic scaffolds and natural products within the paradigm of a multitarget approach for addressing inflammation and inflammation induced carcinogenesis. Structural insights from the inhibitor complexes and novel strategies for development of sEH-based multitarget inhibitors are also presented. While sEH inhibition is likely to suppress inflammation-induced carcinogenesis, it can also lead to enhanced angiogenesis via increased EET concentrations. In this regard, sEH inhibitors in combination chemotherapy are described. Urea and amide-based architectures feature prominently across multitarget inhibition and combination chemotherapy applications of sEH inhibitors.     

Multitarget‐Directed Ligands Combining Cholinesterase and Monoamine Oxidase Inhibition with Histamine H3R Antagonism for Neurodegenerative Diseases

The therapy of complex neurodegenerative diseases requires the development of multitarget‐directed drugs (MTDs). Novel indole derivatives with inhibitory activity towards acetyl/butyrylcholinesterases and monoamine oxidases A/B as well as the histamine H₃ receptor (H3R) were obtained by optimization of the neuroprotectant ASS234 by incorporating generally accepted H3R pharmacophore motifs. These small‐molecule hits demonstrated balanced activities at the targets, mostly in the nanomolar concentration range. Additional in vitro studies showed antioxidative neuroprotective effects as well as the ability to penetrate the blood–brain barrier. With this promising in vitro profile, contilisant (at 1 mg kg⁻¹ i.p.) also significantly improved lipopolysaccharide‐induced cognitive deficits.     

Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative,Leishmanicidal and Anti-Inflammatory Properties

sp²-Iminosugar glycolipids (sp²-IGLs) represent a consolidated family of glycoconjugate mimetics encompassing a monosaccharide-like glycone moiety with a pseudoamide-type nitrogen replacing the endocyclic oxygen atom of carbohydrates and an axially-oriented lipid chain anchored at the pseudoanomeric position. The combination of these structural features makes them promising candidates for the treatment of a variety of conditions, spanning from cancer and inflammatory disorders to parasite infections. The exacerbated anomeric effect associated to the putative sp²-hybridized N-atom imparts chemical and enzymatic stability to sp²-IGLs and warrants total α-anomeric stereoselectivity in the key glycoconjugation step. A variety of O-, N-, C- and S-pseudoglycosides, differing in glycone configurational patterns and lipid nature, have been previously prepared and evaluated. Here we expand the chemical space of sp²-IGLs by reporting the synthesis of α-d-gluco-configured analogs with a bicyclic (5N,6O-oxomethylidene)nojirimycin (ONJ) core incorporating selenium at the glycosidic position. Structure–activity relationship studies in three different scenarios, namely cancer, Leishmaniasis and inflammation, convey that the therapeutic potential of the sp²-IGLs is highly dependent, not only on the length of the lipid chain (linear aliphatic C₁₂ vs. C₈), but also on the nature of the glycosidic atom (nitrogen vs. sulfur vs. selenium). The ensemble of results highlights the α-dodecylseleno-ONJ-glycoside as a promising multitarget drug candidate.     

Multifunctional Small Molecules as Potential Anti-Alzheimer’s Disease Agents

Alzheimer’s disease (AD) is a severe multifactorial neurodegenerative disorder characterized by a progressive loss of neurons in the brain. Despite research efforts, the pathogenesis and mechanism of AD progression are not yet completely understood. There are only a few symptomatic drugs approved for the treatment of AD. The multifactorial character of AD suggests that it is important to develop molecules able to target the numerous pathological mechanisms associated with the disease. Thus, in the context of the worldwide recognized interest of multifunctional ligand therapy, we report herein the synthesis, characterization, physicochemical and biological evaluation of a set of five (1a–e) new ferulic acid-based hybrid compounds, namely feroyl-benzyloxyamidic derivatives enclosing different substituent groups, as potential anti-Alzheimer’s disease agents. These hybrids can keep both the radical scavenging activity and metal chelation capacity of the naturally occurring ferulic acid scaffold, presenting also good/mild capacity for inhibition of self-Aβ aggregation and fairly good inhibition of Cu-induced Aβ aggregation. The predicted pharmacokinetic properties point towards good absorption, comparable to known oral drugs.     

Multitarget Detection Using a Hybrid Optical Joint Transform Correlator with Power Spectrum Subtraction

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