Model-Based Systems Engineering Approach to Design a Human Settlement to Better Serve Displaced People

The challenge of transitioning from temporary humanitarian settlements to more sustainable human settlements is due to a significant increase in the number of forcibly displaced people over recent decades, difficulties in providing social services that meet the required standards, and the prolongation of emergencies. Despite this challenging context, short-term considerations continue to guide their planning and management rather than more integrated, longer-term perspectives, thus preventing viable, sustainable development. Over the years, the design of humanitarian settlements has not been adapted to local contexts and perspectives, nor to the dynamics of urbanization and population growth and data. In addition, the current approach to temporary settlement harms the environment and can strain limited resources. Inefficient land use and ad hoc development models have compounded difficulties and generated new challenges. As a result, living conditions in settlements have deteriorated over the last few decades and continue to pose new challenges. The stakes are such that major shortcomings have emerged along the way, leading to disruption, budget overruns in a context marked by a steady decline in funding. However, some attempts have been made to shift towards more sustainable approaches, but these have mainly focused on vague, sector-oriented themes, failing to consider systematic and integration views. This study is a contribution in addressing these shortcomings by designing a model-driving solution, emphasizing an integrated system conceptualized as a system of systems. This paper proposes a new methodology for designing an integrated and sustainable human settlement model, based on Model-Based Systems Engineering and a Systems Modeling Language to provide valuable insights toward sustainable solutions for displaced populations aligning with the United Nations 2030 agenda for sustainable development.

Human induced pluripotent stem cell based in vitro models of the blood-brain barrier： the future standard？

There is an urgent and tremendous need for human dis- ease models in drug development in order to improve pre- clinical predictability. In the case of brain disorders drugs have to cross the blood-brain barrier （BBB） to enter the central nervous system （CNS）. It was estimated that more than 95% of the drugs cannot cross the BBB.

Plasmid-based generation of neural cells from human fibroblasts using non-integrating episomal vectors

Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine.

Construction of three-dimensional atlas of the lenticular nuclei and its subnucleus based on the cryosection images from Chinese visible human:a preliminary study

Objective To establish a 3D atlas of the lenticular nuclei and its subnucleus with the cryosection images of the male from "Atlas of Chinese Visible Human". Methods The lenticular nuclei and its subnucleus were segmented from the cryosection images and reconstructed with the software

Human Rights Connotations and Contemporary Values of Traditional Chinese People-Based Thinking

The time-honored traditional Chinese minben(people-based) thinking has rich implications for human rights. The concepts of min and minben are much in line with their contemporary counterparts of "human" and "people orientation". Upholding the belief of "people as the foundation of states", minben advocates the fundamental political status of the people, and requires leaders to implement "people-oriented" policies. Its encapsulation of the theoretical foundation and basic requirements for the protection of human rights enabled it to promote the protection of people’s livelihoods and civil rights in ancient China. Its sublimation in contemporary China has had, and will continue to have, a far-reaching impact on the development of human rights in China.

An In-depth Interpretation of the Universal Declaration of Human Rights With the Common Values of Humanity As the Research Paradigm

Interpreting the Universal Declaration of Human Rights from political,juridical and philosophical perspectives is es-sential for promoting the guiding principles of the Declaration,build-ing consensus on human rights,and advancing human rights practice in the new historical context.To conduct an academic,systematic in-terpretation of the Declaration that conforms to the trends of the times and answers the fundamental questions of the world,it is necessary to find a new research paradigm.The common values of humanity,namely peace,development,equity,justice,democracy and freedom,put forward by Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,provide the most explanatory and penetrating scientific paradigm for reaching the issue.This paper an-alyzes and reflects on the views,value foundation and principled(con-tractual)consensus of human rights in the Declaration,and narrates and foresees the far-reaching significance of the three global initia-tives(namely,the Global Development Initiative,the Global Security Initiative,and the Global Civilization Initiative)with the common val-ues of humanity as the soul in advancing the modernization of global human rights governance and building a new form of human rights civilization.

A 330-500 GHz Zero-Biased Broadband Tripler Based on Terahertz Monolithic Integrated Circuits

A 330-500 GHz zero-biased broadband monolithic integrated tripler is reported. The measured results show that the maximum efficiency and the maximum output power are 2% and 194μW at 348 GHz. The saturation characteristic test shows that the output i dB compression point is about -8.5 dBm at 334 GHz and the maximum efficiency is obtained at the point, which is slightly below the 1 dB compression point. Compared with the conventional hybrid integrated circuit, a major advantage of the monolithic integrated circuit is the significant improvement of reliability and consistency. In this work, a terahertz monolithic frequency multiplier at this band is designed and fabricated.

Finite Element Method Computations of the Acoustics of the Human Head Based on the Projection Based Interpolation Data

In this paper we present the Projection Based Interpolation (PBI) technique for construction of continuous approximation of MRI scan data of the human head. We utilize the result of the PBI algorithm to perform three dimensional (3D) Finite Element Method (FEM) simulations of the acoustics of the human head. The computational problem is a multi-physics problem modeled as acoustics coupled with linear elasticity. The computational grid contains tetrahedral finite elements with the number of equations and polynomial orders of approximation varying locally on finite element edges, faces, and interiors. We utilize our own out-of-core parallel direct solver for the solution of this multi-physics problem. The solver minimizes the memory usage by dumping out all local systems from all nodes of the entire elimination tree during the elimination phase.

SELECTING CLUSTER MODEL IN Sn - BASED SOLDER ALLOY DESIGN WITH DV - X_α CALCULATION METHOD

Applying calculation method in alloy design should be an important tendency due to its characters of inexpensive cost, high efficiency and prediction. DOS calculations of AuSn, AsSn and SbSn Sn- based alloys have been investigated by employing DV - Xa method, in which different cluster models were adopted to calculate electron structure.It is proved that some regulations must be taken into ac- count in order to carry out alloy design calculation successfully,which are described in this paper in detail.

Preparation and the Pore Structure of Viscose-based Activated Carbon Fibers Treated with Pretreatment Reagents

The viscose rayon was pretreated with four different pre-treatment reagents respectively, and the preparation ofactivated carbon fibers (ACF) was performed undersame carbonizing and activating conditions. The poresize distribution, the specific surface area, and the porestructure parameter of these viscose - based ACF werestudied by using quartz spring balance BET- weightmethod. The experiment result indicates that the poresize distribution and the pore structure parameter ofACF is varied by using different pretreatment reagents.

GRAPHICAL COMPUTING METHOD ON FOUR-BAR LINKAGE(1)——Inflexion Circle,Focal Axis,Ball's Point,Centering-point Curve and Circling-point Curve For Four ISPs,Coupler Curves Based on Ball's Points——

By means of programs GTMPAC based- on generalized triangle method,analysis and synthesis of mechanism design in accordance with absolutely graphicalmethod( absolutely germetrical method) are developed.In this paper,we make aspecial study about centering- point curve and circling- point curve and couplercurves based on Ball’s points.

Altered profiles of nuclear matrix proteins during the differentiation of human gastric mucous adenocarcinoma MGc80-3 cells

AIM： To find and identify specific nuclear matrix proteins associated with proliferation and differentiation of carcinoma cells, which will be potential markers for cancer diagnosis and targets in cancer therapy. METHODS： Nuclear matrix proteins were selectively extracted from MGcS0-3 cells treated with or without hexamethylamine bisacetamide （HMBA）, and subjected to 2-D gel electrophoresis. The resulted protein patterns were analyzed by Melanie software. Spots of nuclear matrix proteins differentially expressed were excised and subjected to in situ digestion with trypsin. Peptide masses were obtained by matrix-assisted laser-desorption/ ionization time of flight mass spectrometry （MALDI-TOFMS） analysis and submitted for database searching using Mascot tool. RESULTS： The MGc80-3 cells were induced into differentiation by HMBA. There were 22 protein spots which changed remarkably in the nuclear matrix, from differentiation of MGcS0-3 cells compared to control. Eleven of which were identified. Seven proteinsactin, prohibitin, porin 31HL, heterogeneous nuclear dbonucleoprotein A2/B1, vimentin, ATP synthase, and heat shock protein 60 were downregulated, whereas three proteins - heat shock protein gp96, heat shock protein 90-beta, and valosin-containing protein were upregulated, and the oxygen-regulated protein was only found in the differentiated MGc80-3 cells. CONCLUSION： The induced differentiation of carcinoma cells is accompanied by the changes of nuclear matrix proteins. Further characterization of those proteins will show the mechanism of cellular proliferation and differentiation, as well as cancer differentiation.

Neuroprotective effects of human telomerase reverse transcriptase on beta-amyloid fragment 25-35-treated human embryonic cortical neurons

BACKGROUND： Numerous current studies have suggested that human telomerase reverse transcriptase （hTERT） gene has neuroprotective effects and can inhibit apoptosis induced by various cytotoxic stresses; however, the mechanism of action remains unknown. OBJECTIVE： To evaluate the neuroprotective effects and possible mechanism of action of hTERT gene transfection in human embryonic cortical neurons treated with beta-amyloid fragment 25-35 （AI325-35）. DESIGN, TIME AND SETTING： The randomized, controlled and molecular biological studies were performed at the Department of Anatomy and Brain Research, Zhongshan School of Medicine, Sun Yat-sen University, China, from September 2005 to June 2008. MATERIALS： AdEasy-1 Expression System was gifted by Professor Guoquan Gao from Sun Yat-Sen University, China. Human cortical neurons were derived from 12-20 week old aborted fetuses, obtained from the Guangzhou Maternal and Child Health Hospital, China. Mouse anti-Odk5 and mouse anti-p16 monoclonal antibodies （Lab Vision, USA）, and mouse anti-hTERT monoclonal antibody （Epitomics, USA）, were used in this study. METHODS： （1） Recombinant adenovirus vectors, encoding hTERT （Ad-hTERT） and green fluorescent protein （Ad-GFP）, were constructed using the AdEasy-1 Expression System. Human embryonic cortical neurons in the Ad-hTERT group were transfected with Ad-hTERT for 1-21 days. Likewise, human embryonic cortical neurons in the Ad-GFP group were transfected with Ad-GFP for 1-21 days. Human embryonic cortical neurons in the control group were cultured as normal. （2） Human embryonic cortical neurons in the Ad-hTERT group were treated with 10 pmol/L Aβ25-35 for 24 hours. Normal human embryonic cortical neurons treated with 10 pmol/Lβ25.35 for 24 hours served as a model group. Human embryonic cortical neurons in the Ad-GFP and control groups were not treated with Aβ25-35. MAIN OUTCOME MEASURES： Expression of hTERT in human embryonic cortical neurons was evaluated by immunocytochemical staining and Western blot assay. Telomerase activity was measured using a PCR-based telomeric repeat amplification protocol （TRAP） ELISA kit. Neural activity in human embryonic cortical neurons was examined by MTT assay; apoptosis was measured using TUNEL assay; and Cdk5 and p16 protein expressions were measured by Western blot. RESULTS： Expression of hTERT protein was significantly increased and peaked at day 3 post-transfection in the Ad-hTERT group. No hTERT expression was detected in the Ad-GFP and control groups. Telomerase activity was significantly greater in the Ad-hTERT group compared with the Ad-GFP and control groups （P 〈 0.01）. Compared with the control group, cell activity was significantly decreased （P 〈 0.05）, and cell apoptotic rate, Cdk5 and p16 expression were significantly increased （P 〈 0.01） in the model group. Compared with the model group, cell activity was increased in the Ad-hTERT group, and peaked at day 3 post-transfection （P 〈 0.05）. Neuroprotective effects also peaked at day 3 post-transfection; and the apoptotic rate, Cdk5 and p16 expression significantly decreased （P 〈 0.01）. CONCLUSION： Expression of hTERT in human embryonic cortical neurons can relieve Aβ25-35-induced neuronal apoptosis. The possible mechanism by which hTERT produces these neuroprotective effects may be associated with inhibition of Cdk5 and p16 expression.

Development of a sensitive and rapid method for quantitation of (S)-(-)- and (R)-(+)-metoprolol in human plasma by chiral LC–ESI–MS/MS

A selective, sensitive and high throughput liquid chromatography-tandem mass spectro-metry （LC-ESI-MS/MS） method has been developed for separation and quantification of metoprolol enantiomers on a chiral Lux Amylose-2 （250 mm＆#215;4.6 mm, 5 mm） column. Solid phase extraction of （S）-（-）- and （R）-（t）-metoprolol and rac-metoprolol-d6 as an internal standard （IS） was achieved on Lichrosep DVB HL cartridges employing 200 mL human plasma. Both the analytes were chromatographically separated with a resolution factor of 2.24 using 15 mM ammonium acetate in water, pH 5.0 and 0.1% （v/v） diethyl amine in acetonitrile （50：50, v/v） as the mobile phase within 7.0 min. The precursor-product ion transitions for the enantiomers and IS were monitored in the multiple reaction monitoring and positive ionization mode. The method was validated over the concentration range of 0.500-500 ng/mL for both the enantiomers. Matrix effect was assessed by post-column analyte infusion experiment and the mean extraction recovery was greater than 94.0% for both the enantiomers at all quality control levels. The stability of analytes was evaluated in plasma and whole blood under different storage conditions. The method was successfully applied to a clinical study in 14 healthy volunteers after oral administration of 200 mg metoprolol tablet under fasting conditions. The assay reproducibility is shown by reanalysis of 68 incurred samples. The suitability of the developed method was assessed in comparison with＆amp;nbsp;different chromatographic methods developed for stereoselective analysis of metoprolol in biological matrices.

Applying a highly specific and reproducible cDNA RDA method to clone garlic up-regulated genes in human gastric cancer cells

AIM: To develop and optimize cDNA representational difference analysis (cDNA RDA) method and to identify and clone garlic up-regulated genes in human gastric cancer (HGC) cells. METHODS: We performed cDNA RDA method by using abundant double-stranded cDNA messages provided by two self-constructed cDNA libraries (Allitridi-treated and paternal HGC cell line BGC823 cells cDNA libraries respectively). Bam H I and Xho I restriction sites harbored in the library vector were used to select representations. Northern and Slot blots analyses were employed to identify the obtained difference products. RESULTS: Fragments released from the cDNA library vector after restriction endonuclease digestion acted as good marker indicating the appropriate digestion degree for library DNA. Two novel expressed sequence tags (ESTs) and a recombinant gene were obtained. Slot blots result showed a 8-fold increase of glia-derived nexin/protease nexin 1 (GDN/PN1) gene expression level and 4-fold increase of hepatitis B virus x-interacting protein (XIP) mRNA level in BGC823 cells after Allitridi treatment for 72h. CONCLUSION: Elevated levels of GDN/PN1 and XIP mRNAs induced by Allitridi provide valuable molecular evidence for elucidating the garlic's efficacies against neurodegenerative and inflammatory diseases. Isolation of a recombinant gene and two novel ESTs further show cDNA RDA based on cDNA libraries to be a powerful method with high specificity and reproducibility in cloning differentially expressed genes.

THE DIFFERENTIATION OF HUMAN GASTRIC ADENOCAR-CINOMA CELL LINE MGc80-3 INDUCED BY DIBUTYRYL cAMP IN VITRO

For providing some experimental basis in establishing malignant phenotypic reversed indexes of gastric carcinoma cells, human gastric adenocar-cinoma cell line MGc80-3 was induced by dBcAMP in vitro to appraise the effect of gastric carcinoma cell differentiation by chemical inducers.Under light microscope, MGc80-3 cells, after treated with 1 mM dBcAMP, tended to be flat and disperse, and their volume gradually enlarged, with their uncleus relatively smaller and their shape rather regular. Morphological changes, like norma differentiated epithelial cells, were observed. The cells attached firmly, grew slowly, their growth curve showed inhibitory rate amounted to 52.87%, and cellular division exponent displayed their peak value 1.5 times less than that of MGc80-3 cells. It was clear that dBcAMP could effectively inhibit the multiplication activity of MGc80-3 cells. After dBcAMP treatment, remarkable changes of cell surface charges was indicated by cell electrophoresis, the ratio dropped to 3.043 from 3.988, and their re-tardant ratio reached up to 31.2%. cAMP content in cells after this treatment, detected by cAMP and cGMP radioimmunoassay, was enhanced by 2.42 times, and cAMP/cGMP ratio, by 1.73 times. Thus, cAMP level within MGc80-3 cells was raised obviously by dBcAMP. Heterotransplantation experiments showed that tuntorigenic rate of MGc80-5 cells (transplanted subcutaneously to BALB/c mice) amounted to 100%, and that of the cells after this treatment was only 5.6%. Their tumorigenic ability was extremely reduced.These results confirmed that dBcAMP was able to change malignant phenotypic characteristics of MGc80-3 cells and produce a reversed alteration: Thus, it has a remarkable inductive effect in differentiating gastric carcinoma cells. All these characteristics were also considered as the reference indexes in appraising reversed effect for the homologous cancer cells.

circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

Human adipose-derived stem cells(hASCs)are a promising cell type for bone tissue regeneration.Circular RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis.However,how circRNAs regulate hASCs in osteogenesis is still unclear.Herein,we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs.Knockdown of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs.We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p.We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 m RNA.The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis.Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model,while overexpression of circ_0003204 inhibited bone defect repair.Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

Combining Multi-scale Directed Depth Motion Maps and Log-Gabor Filters for Human Action Recognition

Recognition of the human actions by computer vision has become an active research area in recent years. Due to the speed and the high similarity of the actions, the current algorithms cannot get high recognition rate. A new recognition method of the human action is proposed with the multi-scale directed depth motion maps(MsdDMMs) and Log-Gabor filters. According to the difference between the speed and time order of an action, MsdDMMs is proposed under the energy framework. Meanwhile, Log-Gabor is utilized to describe the texture details of MsdDMMs for the motion characteristics. It can easily satisfy both the texture characterization and the visual features of human eye. Furthermore, the collaborative representation is employed as action recognition by the classification. Experimental results show that the proposed algorithm, which is applied in the MSRAction3 D dataset and MSRGesture3 D dataset, can achieve the accuracy of 95.79% and 96.43% respectively. It also has higher accuracy than the existing algorithms, such as super normal vector(SNV), hierarchical recurrent neural network(Hierarchical RNN).

A novel xeno-free culture system for human retinal pigment epithelium cells

AIM: To find out an animal-free, xeno-free culture method for human fetal retinal pigment epithelium(fRPE) cells aiming for cell-replacement therapy. METHODS: Human AB serum, knock-out serum replacement(KSR) and B27 were supplemented as a substitute of fetal bovine serum(FBS) in culture medium of human fRPE cells. Cell morphology was examined by light microscope and transmission electron microscope. Proliferation ability was detected by cell cycle analysis and examination of KI67 expression. Apoptosis was analyzed using FACS. The expression ofRPE-specific markers was demonstrated by quantitative real-time polymerase chain reaction(qPCR), Western blot(WB) and immunocytochemistry. Paracrine function was determined using enzyme-linked immunosorbent assay method.RESULTS: Our results indicated that the optimum concentration of KSR was 15%, the optimum concentration of B27 was 2%, and the optimum concentration of human AB serum was 10%. fRPE cells cultured in 15% KSR and 2% B27 media showed repressed propagation and differentiation ability, and gradually lost epithelial morphology and RPE function. While fRPE cells cultured in 10% human AB serum media showed a typical cobblestone morphology with pigmentation, elevated proliferation ability, satisfying paracrine function and expressed RPE-specific markers. CONCLUSION: Our study indicates that culturing fRPE cells in 10% human AB serum-supplemented medium is more favorable compared with KSR, B27 and traditional FBS-supplemented mediums when fRPE cells are to be applied in cell-based therapy.

HPV检测、液基细胞学及p16/Ki-67三重检测在宫颈高级别病变筛查中的诊断价值研究

目的探讨HPV检测、液基细胞学及p16/Ki-67三重检测在宫颈高级别病变筛查中的诊断价值。方法收集2021-2023年北京天坛医院病理科宫颈活检病例共1839例,回顾性分析HPV检测、液基细胞学(LBC)及p16/Ki-67三重检测的CIN2+检出率,并对比组间的差异,探讨高效而特异的检测方法。结果1839例宫颈活检病例中,CIN2+的总检出率为29.6%;仅HPV阳性、HPV及LBC双检阳性、HPV、LBC及p16/Ki-67三重检测阳性CIN2+检出率依次升高,分别为20.1%、32.3%、54.1%;亚组分析显示HPV16/18阳性,3组的CIN 2+检出率分别是24.4%、45.7%、70.4%;其他12种高危HPV阳性,3组的CIN 2+阳性检出率分别是14.6%、27.4%、45.3%。总体及亚组分析均显示HPV、LBC及p16/Ki-67三重检测的CIN 2+检出率最高,差异具有统计学意义(P<0.001)。结论本研究认为对于HPV阳性的女性,建议进行HPV、LBC及p16/Ki-67三重检测,提高CIN2+阳性检出率,减少漏诊,提升阴道镜的利用效率。