Algorithmic Modality Analysis for Parabolic Groups

For an algebraic group R acting morphically on an algebraic variety X the modality of the action, mod (R:X), is the maximal number of parameters upon which a family of R-orbits on X depends. Let G be a reductive algebraic group defined over an algebraically closed field K. Let P be a parabolic subgroup of G. Then P acts on its unipotent radical P_u via conjugation and on , the Lie algebra of P_u, via the adjoint action. The modality of P is defined as mod P:=mod (P: ). In this paper we discuss an algorithm which is used to compute upper bounds for mod P along with some results obtained by this algorithm. One is a classification of parabolic subgroups P of simple algebraic groups G of semisimple rank 2 and modality 0. For parabolic subgroups of semisimple rank 3 we present some partial results. This extends the results of Kashin and Popov and Röhrle, where the cases of semisimple rank 0 and 1 are handled. For exceptional groups G we show that P G has modality zero provided the class of nilpotency of P_u is at most two. The analogous result for classical groups is proved by Röhrle. For Borel subgroups B of simple groups we are able to determine the value for mod B in some small rank cases by combining lower bounds for mod B of Röhrle with upper bounds provided by the algorithm.     

Designing potential siRNA molecule for the nucleocapsid(N) gene silencing of different SARS-CoV-2 strains of Bangladesh: Computational approach

SARS-CoV-2 is a single-stranded RNA (+) virus first identified in China and then became an ongoing global outbreak. In most cases, it is fatal in humans due to respiratory malfunction. Extensive researches are going to find an effective therapeutic technique for the treatment of SARS-CoV-2 infected individuals. In this study, we attempted to design a siRNA molecule to silence the most suitable nucleocapsid(N) gene of SARS-CoV-2, which play a major role during viral pathogenesis, replication, encapsidation and RNA packaging. At first, 270 complete N gene sequences of different strains in Bangladesh of these viruses were retrieved from the NCBI database. Different computational methods were used to design siRNA molecules. A siRNA molecule was built against these strains using the SiDirect 2.0 server. Using Mfold and the OligoCalc server, the siRNA molecule was tested for its secondary structure and GC material. The Clustal Omega tool was employed to evaluate any off-target harmony of the planned siRNA molecule. Herein, we proposed a duplex siRNA molecule that does not fit any off-target sequences for the gene silencing of SARS-CoV-2. To treat SARS-CoV-2 infections, currently, any effective therapy is not available. Our engineered siRNA molecule could give an alternative therapeutic approach against various sequenced SARS-CoV-2 strains in Bangladesh.     

Nanobubbles for therapeutic delivery: Production,stability and current prospects

Nanobubbles (NBs) have recently garnered widespread attention for their potential use as dual diagnostic and therapeutic agents. Similar to their micron-sized relatives (microbubbles), NBs are shell-stabilized, gas-cored bubbles that in conjunction with ultrasound can be used to increase imaging contrast, as well as provide a mechanism for trigger drug release and increased therapeutic delivery.In this review, we specifically focus on their development as agents to enhance drug delivery, discussing theory, characterization techniques, key formulations and prospects for translation into clinical use.     

LC with Column-Switching and Spectrophotometric Detection for Determination of Risperidone and 9-Hydroxyrisperidone in Human Serum

An automated high performance liquid chromatography with column-switching and ultraviolet detection was developed for the analysis of risperidone and 9-hydroxyrisperidone. The method needs minimum sample preparation and is useful for the detection down to a limit of 1 ng mL⁻¹. Sample clean-up of serum was carried out on a CN 20 μm SPE-column using 8% (v/v) acetonitrile in water. Chromatographic separation was performed on ODS Hypersil C18 material with 38% (v/v) acetonitrile and 0.4% (v/v) TEMED in water. Application of the method to the analysis of serum samples confirmed its suitability for therapeutic drug monitoring of risperidone and 9-hydroxyrisperidone.     

Combination of SDS‐PAGE and intact mass analysis for rapid determination of heterogeneities in monoclonal antibody therapeutics

mAbs are currently mainstream in biopharmaceuticals, and their market has been growing due to their high target specificity. Characterization of heterogeneities in mAbs is performed to secure their quality and safety by physicochemical analyses. However, they require time‐consuming task, which often strain the resources of drug development in pharmaceuticals. Rapid and direct method to determine the heterogeneities should be a powerful tool for pharmaceutical analysis. Considering the advantages of electrophoresis and MS, this study addresses the combination of SDS‐PAGE and intact mass analysis, which provides direct, rapid, and orthogonal determination of heterogeneities in mAb therapeutics. mAb therapeutics that migrated in SDS‐PAGE were recovered from gel by treatment with SDC‐containing buffer. Usage of SDC‐containing buffer as extraction solvent and ethanol‐based staining solution enhanced the recovery of intact IgG from SDS‐PAGE gels. Recovery of mAbs reached more than 86% with 0.2% SD. The heterogeneities, especially N ‐glycan variants in the recovered mAb therapeutics, were clearly determined by intact mass analysis. We believe that the study is important in pharmaceuticals‧ perspective since orthogonal combination of gel electrophoresis and intact mass analysis should be pivotal role for rapid and precise characterization of mAbs.     

Vertical-flow paper SERS system for therapeutic drug monitoring of flucytosine in serum

A number of life-saving drugs require therapeutic drug monitoring (TDM) for safe and effective use. Currently, however, TDM is performed using sophisticated analytical techniques relegated to central labs, increasing the cost per test and time to answer. Here, using a novel vertical flow membrane system with inkjet-printed surface enhanced Raman sensors, along with a portable spectrometer, we demonstrate a low cost and easy to use device to quantify levels of flucytosine, an antifungal that requires TDM for effective patient care, from undiluted human serum. To our knowledge, this work represents the first report of a passive vertical flow sample cleanup method with surface enhanced Raman detection. We first investigated and optimized the parameters of the vertical flow system for the detection of flucytosine in spiked serum samples. Then, using an optimized vertical-flow system utilizing nitrocellulose membranes and a paper SERS sensor, we achieved detection of down to 10 μg mL⁻¹ flucytosine in undiluted serum, with quantitative detection across the entire therapeutic range. This system reduces the assay time to about 15 min, far quicker than the current gold standards. We anticipate that this novel system will enable near-patient therapeutic drug monitoring, leading to the safe and effective administration of a number of life-saving drugs. Furthermore, it will spawn the development of SERS detection systems capable of separating target analytes from real-world biological matrices.     

Challenges in the determination of aminoglycoside antibiotics,a review

Residues of antibiotics (ABs) in the aquatic environment and in food of animal origin represent a major concern, as prolonged exposure to ABs is a serious health hazard, related to both the side effects of prolonged use and the risk of developing bacterial resistance to various ABs. Given the low levels of the AB residues in complex matrices, the development of sensitive analytical methods represents a major challenge. This is certainly true for the aminoglycoside ABs (AGs) which lack a chromophore and show poor chromatographic properties in reversed-phase liquid chromatography. This paper reviews the current state of the art in the determination of AGs. Attention is paid to extraction, sample clean-up, chromatographic separation, and detection of AGs in both environmental and food samples and in plasma and serum. A general workflow for the analysis of AGs is presented which takes into account the matrix and required level of information.     

动荷载反分析的模态选择方法

提出了动态载荷识别中新的确定模态的准则与实施方法.提出了模态选取概念,在此基础上提出了反分析中模态选取的准则,并给出了相应的公式.大量算例表明,采用该文准则和公式可以防止因模态选取不当而产生的伪解,避免计算中的数值病态,明显提高了动态载荷识别的成功率和精度.     

ZnO‐Functionalized Upconverting Nanotheranostic Agent: Multi‐Modality Imaging‐Guided Chemotherapy with On‐Demand Drug Release Triggered by pH

Limited therapeutic efficiency and severe side effects in patients are two major issues existing in current chemotherapy of cancers in clinic. To design a proper theranostic platform seems thus quite needed to target cancer cells accurately by bioimaging and simultaneously release drugs on demand without premature leakage. A novel ZnO‐functionalized upconverting nanotheranostic platform has been fabricated for clear multi‐modality bioimaging (upconversion luminescence (UCL), computed tomography (CT), and magnetic resonance imaging (MRI)) and specific pH‐triggered on‐demand drug release. In our theranostic platform multi‐modality imaging provides much more detailed and exact information for cancer diagnosis than single‐modality imaging. In addition, ZnO can play the role of a “gatekeeper” to efficiently block the drug in the mesopores of the as‐prepared agents until it is dissolved in the acidic environment around tumors to realize sustained release of the drug. More importantly, the biodegradable ZnO, which is non‐toxic against normal tissues, endows the as‐prepared agents with high therapeutic effectiveness but very low side effects. These findings are of great interests and will inspire us much to develop novel effective imaging‐guided on‐demand chemotherapies in cancer treatment.     

多色彩可视化半定量检测方法用于COVID-19患者治疗过程中抗体浓度变化的快速监测

现场快速定量检测新型冠状病毒(SARS-CoV-2)抗体对于监测新型冠状病毒感染的肺炎患者治疗过程具有重要作用. 目前, 大多数抗体检测采用基于金纳米粒子的免疫层析定性检测, 但该方法仅表现出一种颜色变化, 无法实现现场快速定量检测. 本文采用特异性刻蚀金纳米棒(Au NRs)的方法, 实现了SARS-CoV-2抗体多色彩可视化的现场快速定量检测. 首先, 将SARS-CoV-2重组抗原固定在96孔酶标板上; 随后, 将辣根过氧化物酶标记的酶标抗体与待测抗体结合, 形成抗原-待测抗体-酶标抗体的复合三明治结构, 且酶标抗体与待测抗体浓度呈正相关; 由于酶标抗体可与3,3',5,5'-四甲基联苯胺(TMB)发生特异性反应, 生成TMB²⁺, 而TMB²⁺可选择性刻蚀Au NRs, 使得溶液产生丰富多彩的颜色, 即可通过观察溶液颜色变化实现SARS-CoV-2抗体浓度半定量检测. 在最佳条件下, 该方法对SARS-CoV-2 IgM抗体在5.00~200 IU浓度范围内呈良好线性关系, 检出限为1.29 IU, 并具有较高的灵敏度和特异性. 上述方法成功用于COVID-19患者治疗过程中SARS-CoV-2 IgM抗体浓度半定量快速检测.