Development of a highly sensitive direct microtiter plate ELISA for human serum testosterone

A simple, highly sensitive, direct, competitive ELISA for human serum testosterone has been indigenously developed. Specific antisera against testosterone were raised in rabbits using testosterone—3carboxymethyl oxime (CMO)—bovine serum albumin (BSA) as the antigen. For the enzyme conjugate, testoterone—3CMO was coupled with horse raddish peroxidase by the active ester method. The standard curve covered a wide range from 3.9 pg/ml to 500 pg/ml. The inter and intra-assay variation were found to be low and within the acceptable limits. Specificity and accuracy for the assay was established by having negligible crossreactivity with the related steroids and an excellent parallelism between the sample and standard dilution curve. Samples measured by RIA and ELISA showed very high degree of correlation (r=0.991).     

Fault detection for a class of nonlinear networked control systems with Markov sensors assignment and random transmission delays

The paper investigates the fault detection problem for a class of nonlinear networked control systems with both communication constraints and random transmission delays. The access status of the sensors is governed by a stochastic event, which is modeled as a Markov chain taking matrix values in a certain set. The main task of this paper is to design a mode-dependent fault detection filter, such that for Markov sensors assignment, random network-induced delays and the unknown input signal, the error between the fault and the residual signal is minimized. And the resulting fault detection dynamics is formulated as an _H∞$H_{\infty }$ filtering problem of a Markov jump system. The linear matrix inequality-based sufficient conditions for the existence of the fault detection filter are obtained. Finally, two examples are given to show the effectiveness of the developed method.     

Numerical study of in situ preconcentration for rapid and sensitive nanoparticle detection

This paper presents a numerical study of a preconcentrator design that can effectively increase the binding rate at the sensor in a real time manner. The particle enrichment is realized by the ac electrothermal (ACET) effect, which induces fluid movement to carry nanoparticles toward the sensor. The ACET is the only electrical method to manipulate a biological sample of medium to high ionic strength (>0.1 S∕m, e.g., 0.06× phosphate buffered saline). The preconcentrator consists of a pair of electrodes striding over the sensor, simple to implement as it is electrically controlled. This preconcentrator design is compatible and can be readily integrated with many types of micro- to nanosensors. By applying an ac signal over the electrodes, local vortices will generate a large velocity perpendicular to the reaction surface, which enhances transport of analytes toward the sensor. Our simulation shows that the binding rate at the sensor surface is greatly enhanced. Our study also shows that the collection of analytes will be affected by various parameters such as channel height, inlet velocity, and sensor size, and our results will provide guidance in optimization of the preconcentrator design.     

Fabrication of a gel particle array in a microfluidic device for bioassays of protein and glucose in human urine samples

This paper describes a simple method for fabricating a series of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel microstructures inside microfluidic channels as probe for proteins and glucose. In order to demonstrate the feasibility of this newly developed system, bovine serum albumin (BSA) was chosen as a model protein. PEG microcolumns were used for the parallel detection of multiple components. Using tetrabromophenol blue (TBPB) and the horseradish peroxidase/glucose oxidase reaction system, bovine serum albumin (BSA) and glucose in human urine were detected by color changes. The color changes for BSA within a concentration range of 1-150 μM, and glucose within a range of 50 mM-2 M could be directly distinguished by eyes or precisely identified by optical microscope. To show the practicability of the gel particle array, protein and glucose concentrations of real human urine samples were determined, resulting in a good correlation with hospital analysis. Notably, only a 5 μL sample was needed for a parallel measurement of both analytes. Conveniently, no special readout equipment or power source was required during the diagnosis process, which is promising for an application in rapid point-of-care diagnosis.     

Electrokinetic trapping and surface enhanced Raman scattering detection of biomolecules using optofluidic device integrated with a microneedles array

In this study, microneedles which possess sharp tips were utilized to trap and detect the biomolecules. Owing to the large curvature, the tips of the microneedles created a substantially high gradient of electric field under the non-uniform electric field which served as not only the trapping sites but also the substrate for surface enhanced Raman scattering (SERS). Separation of polystyrene microparticles with different sizes and two kinds of biomolecules (Staphylococcus aureus (S. aureus) and the red blood cells (RBCs)) were demonstrated. Moreover, in situ detection of S. aureus was performed immediately after separation was completed. The results showed that, after 15 s of sample collection, the Raman signals of S. aureus were detected and greatly enhanced through SERS effect.     

Utility of serum lysosomal enzyme assay in the detection of cerebral sphingolipidoses in patients with progressive neurologic dysfunction

The cerebral sphingolipidoses which form part of a larger group of lysosomal disorders can be detected and conclusively confirmed by the demonstration of the relevent enzyme deficiency in easily available tissue samples like serum. We have assayed acid β-galactosidase, β-hexosaminidase and its isozymes hexosaminidase A and B, and arylsulfatase A in the serum of patients with progressive cerebral dysfunction and detected 18 patients with enzyme defects, thereby confirming the diagnosis of a specific type of cerebral lipidosis in these patients. The assay of serum lysosomal enzymes was of immense diagnostic use as it obviated the need for highly invasive techniques like a brain biopsy.     

Reconfigurable microfluidic device with integrated antibody arrays for capture,multiplexed stimulation,and cytokine profiling of human monocytes

Monocytes represent a class of immune cells that play a key role in the innate and adaptive immune response against infections. One mechanism employed by monocytes for sensing foreign antigens is via toll-like receptors (TLRs)—transmembrane proteins that distinguish classes of foreign pathogens, for example, bacteria (TLR4, 5, and 9) vs. fungi (TLR2) vs. viruses (TLR3, 7, and 8). Binding of antigens activates a signaling cascade through TLR receptors that culminate in secretion of inflammatory cytokines. Detection of these cytokines can provide valuable clinical data for drug developers and disease investigations, but this usually requires a large sample volume and can be technically inefficient with traditional techniques such as flow cytometry, enzyme-linked immunosorbent assay, or luminex. This paper describes an approach whereby antibody arrays for capturing cells and secreted cytokines are encapsulated within a microfluidic device that can be reconfigured to operate in serial or parallel mode. In serial mode, the device represents one long channel that may be perfused with a small volume of minimally processed blood. Once monocytes are captured onto antibody spots imprinted into the floor of the device, the straight channel is reconfigured to form nine individually perfusable chambers. To prove this concept, the microfluidic platform was used to capture monocytes from minimally processed human blood in serial mode and then to stimulate monocytes with different TLR agonists in parallel mode. Three cytokines, tumor necrosis factor-α, interleukin (IL)-6, and IL-10, were detected using anti-cytokine antibody arrays integrated into each of the six chambers. We foresee further use of this device in applications such as pediatric immunology or drug/vaccine testing where it is important to balance small sample volume with the need for high information content.     

Comparative study of serum myoglobin and creatine kinase MB isoenzyme in the detection of acute myocardial infarction

Serum creatine kinase MB isoenzyme (CKMB) and myoglobin have been studied in 35 cases with myocardial infarction. Increased values for both serum CKMB and myoglobin have been found in all the patients in the second sample collected 4 hr. after admission while in 22 patients in the first sample collected immediately after admission. Thus, the present study shows a good correlation between serum CKMB and myoglobin and therefore, suggests the possibility of using the serum myoglobin estimation in early detection of myocardial infarction either alone or in combination with the serum CKMB.     

A microfluidic device for simultaneous measurement of viscosity and flow rate of blood in a complex fluidic network

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis.     

基于协同视角的京津冀科技资源优化配置机制体系构建*

科技资源的优化配置与有效利用已成为各级政府支持科技创新的重要战略手段,其中,科技资源配置机制作为区域科技创新体系管理运行的核心问题之一,日益受到科技管理部门的高度重视。本文基于协同视角构建京津冀科技资源配置系统的分析框架,建立主体、空间、环境、市场、服务“五位一体”的京津冀科技资源优化配置机制体系,并基于京津冀地区当前在科技资源配置机制体系建设中的存在问题,从产学研合作、科技资源空间优化、科技成果市场化、科技创新服务联动、创新环境协同提升等方面提出对策建议。     

企业再造中的信息技术作用机理及其相互关系研究

在概述企业再造的基础上,研究了信息技术(IT)在企业再造中的6大作用机理:消除信息不对称与不完全,减少管理层次,降低委托—代理成本,降低内部交易成本,降低管理成本,降低运作成本。最后,探析了企业再造与IT的互动关系:IT是企业再造的“使能器”、“加速器”,企业再造是IT固化流程的前提。     

Comparing age-wise reference intervals for serum creatinine concentration in a “Reality check” of the recommended cut-off

An increase in the communication within the healthcare services, both nationally and internationally, has strengthened the need for harmonization of measurements and reference intervals in laboratory medicine. In the present report, the calculated reference interval for serum creatinine (sCr) levels of healthy normal individuals (n=1121) in different sex and age groups are compared with the established interval. The calculated reference interval for sCr level was 0.4–1.3 mg/dL and 0.6 to 1.3 mg/dL in the age groups of 21–40 and 41–60 years respectively. The difference between the mean sCr values in total males and total females (age range 21–60 years) was statistically significant (p<0.0001); When male and female subjects were analyzed age-group wise, the data showed a significant difference in mean sCr values (p<0.0001) in three age groups (21–30, 31–40 and 41–50 years) however, in older age group (51–60 years), the difference was non-significant (p=0.07). The reference ranges were 0.7–1.3 and 0.4–1.0 mg/dL for males and females respectively where the lower limit was 0.1–0.2 units less than that of standard limits. An increase in the mean value of sCr was observed particularly in females with an increase in age. Hence it is of interest to validate an age specific reference ranges for sCr in our population.     

内陆地区构建科创中心城市的机制与路径研究

分析我国内陆地区形成科技创新中心城市的基本态势，指出部分内陆地区大城市正在面临发展科创产业的历史性机遇，初步具备孕育科创产业的科技资源与经济基础，但也普遍存在创新氛围不浓、创新投入不足、缺少科创企业和创新配套服务机构等问题。提出构建内陆科创中心城市的机制与路径，即要构建有利于科技创新的制度与政策环境，形成以研究型大学和科研机构为创新动力源，以科创企业为龙头，以一流的法律、会计、审计、信息服务、融资机构为中介的区域创新生态系统，并与发达国家及沿海地区紧密互动以获得创新溢出效应。并进一步提出在构建内陆科创中心城市时，应注意避免过度投资、重复投资、经济金融化等现象，实现包容性发展。     

建立高校科研课题管理中的监控机制探讨

从高校科研课题管理中存在的问题入手,分析高校科研课题管理中建立监控机制必要性,提出在高校科研课题管理中建立激励与约束机制、实施动态管理、建立与完善管理制度等监控机制,加强科研课题管理.     

Adjustments of serum lactate dehydrogenase isoenzymes and their significance in monitoring the treatment in patients with tubercular pyothorax

The adjustments and diagnostic significance of polyacrylamide gel electrophoretic (PAGE) profiles of lactate dehydrogenase isoenzymes (LDH: 1.1.1.27) was evaluated in the sera and pleural fluid of patients with tubercular pyothorax. Sera and pleural fluid samples were randomly collected from 72 and 18 patients respectively at two different timings; first, when patients were admitted to the Hospital and second, after an intensive phase of treatment. Sera of 20 healthy individuals served as control. Our results demonstrate significant differences in sera LDH (sLDH) and pleural fluid LDH (pfLDH) isoenzymes. In patients the order of LDH isoenzyme in sera and pleural fluid followed: LDH−5>−4>−2>−3>−1 and LDH-5>−4>−3>−2>−1 respectively. The ranking of activity levels in control was LDH−2>−1>−3>−5>−4. In the second phase of sampling from 31 patients, values of sLDH isoenzymes showed recovery and resembled profiles of controls. Therefore, the sLDH zymograms of patients can be used as the prognostic marker, since they tend to reach the normal level during recovery signifying the effect of chemotherapy in hospitalized patients. Moreover, according to the present findings on LDH-PAGE profiles, the levels of LDH-5 and-4 rise in pyothorax patients significantly (P<0.05). This elevation along with the rise in total LDH activity may, therefore, be used in the diagnosis and monitoring of tubercular pyothorax.     

Robot minds and human ethics: the need for a comprehensive model of moral decision making

Building artificial moral agents (AMAs) underscores the fragmentary character of presently available models of human ethical behavior. It is a distinctly different enterprise from either the attempt by moral philosophers to illuminate the “ought” of ethics or the research by cognitive scientists directed at revealing the mechanisms that influence moral psychology, and yet it draws on both. Philosophers and cognitive scientists have tended to stress the importance of particular cognitive mechanisms, e.g., reasoning, moral sentiments, heuristics, intuitions, or a moral grammar, in the making of moral decisions. However, assembling a system from the bottom-up which is capable of accommodating moral considerations draws attention to the importance of a much wider array of mechanisms in honing moral intelligence. Moral machines need not emulate human cognitive faculties in order to function satisfactorily in responding to morally significant situations. But working through methods for building AMAs will have a profound effect in deepening an appreciation for the many mechanisms that contribute to a moral acumen, and the manner in which these mechanisms work together. Building AMAs highlights the need for a comprehensive model of how humans arrive at satisfactory moral judgments.     

Establishment of gender- and age-specific reference intervals for serum liver function tests among the elderly population in northeast China: a retrospective study

IntroductionReference intervals (RIs) for younger population may not apply to the elderly population. The aim of this study was to establish gender- and age-specific RIs for serum liver function tests among the elderly population and to compare with younger population RIs currently used in China and other countries.Materials and methodsThis was a retrospective study, and subjects (≥ 18 year-old) were recruited from the laboratory information system (LIS) at the First Hospital of Jilin University between April 2020 and April 2021. The following parameters were collected: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), total bilirubin (TBIL), and direct bilirubin (DBIL). The Tukey method was used to eliminate outliers. Reference intervals were established by the nonparametric method.ResultsA total of 23,597 healthy individuals were enrolled in the study. From all parameters AST, ALT, TP and ALB required no gender partition, while ALT, GGT, TP, ALB and DBIL required different partitions for age. Activities and concentrations of ALT, ALB, and TP showed a downward trend in the elderly aged 60-89. In contrast, DBIL showed a gradual upward trend.ConclusionThe RIs for liver function tests among healthy elderly population were different from those among young population in China. There were apparent gender and age differences in the RIs of liver function for elderly and significant differences compared with national standards and RIs in other countries. Therefore, it is necessary to establish gender- and age-specific RIs for serum liver function tests among the elderly population.     

Assessing the effectiveness of a three-way decision-making framework with multiple features in simulating human judgement of opinion classification

Three-way opinion classification (3WOC) models are based on a human perspective of opinion classification and offer human-like decision-making capabilities. The purpose of this study was to determine the effectiveness of a three-way decision-making framework with multiple features (fuzzy features and semantic features) in simulating human judgement of opinions. This was an quantitative study. A simple prototype of the three-way decision model was run against the Amazon Musical Instrument dataset to evaluate the model. The data used to verify the results were collected from 125 respondents via an online survey. The participants tested the model in context, then immediately filled in the online questionnaire. Results show that the statistical correlation between semantic features and fuzzy feature is low. Therefore, classification coverage and accuracy can be increased when both types of features are used together rather than using one type of feature alone. With the integration of semantic features and fuzzy features, we found that our three-way decision model performs better than a two-way classification model. Furthermore, the 3WOC model is a simulation of human judgements executed when people make decisions. Finally, we offer usability recommendations based on our analysis. A three-way decision-making framework is a better solution to simulate human judgement of opinion classification than a two-way decision model. The research outcomes will help in the development of better opinion classification systems that can support businesses and organisations to make strategic plans to improve their products or services based on customer preference patterns.     

湖北省社科类社会团体现状调查及其管理问题研究

改革开放二十多年来,我国的社会团体呈现出蓬勃发展的兴旺局面,各类社会团体团结组织起社会各界的力量,为中国的改革开放和经济社会发展服务,为构建社会主义和谐社会做出了巨大贡献。社科类社会团体作为社会团体中一支独特而重要的力量,受到党中央、国务院以及各省党委和政府的     

A negative-pressure-driven microfluidic chip for the rapid detection of a bladder cancer biomarker in urine using bead-based enzyme-linked immunosorbent assay

This paper describes an integrated microfluidic chip that is capable of rapidly and quantitatively measuring the concentration of a bladder cancer biomarker, apolipoprotein A1, in urine samples. All of the microfluidic components, including the fluid transport system, the micro-valve, and the micro-mixer, were driven by negative pressure, which simplifies the use of the chip and facilitates commercialization. Magnetic beads were used as a solid support for the primary antibody, which captured apolipoprotein A1 in patients'' urine. Because of the three-dimensional structure of the magnetic beads, the concentration range of the target that could be detected was as high as 2000 ng ml⁻¹. Because this concentration is 100 times higher than that quantifiable using a 96-well plate with the same enzyme-linked immunosorbent assay (ELISA) kit, the dilution of the patient''s urine can be avoided or greatly reduced. The limit of detection was determined to be approximately 10 ng ml⁻¹, which is lower than the cutoff value for diagnosing bladder cancer (11.16 ng ml⁻¹). When the values measured using the microfluidic chip were compared with those measured using conventional ELISA using a 96-well plate for five patients, the deviations were 0.9%, 6.8%, 9.4%, 1.8%, and 5.8%. The entire measurement time is 6-fold faster than that of conventional ELISA. This microfluidic device shows significant potential for point-of-care applications.