2,163 research outputs found

    Social welfare under Chinese socialism---a case study of the Ministry of Civil Affairs.

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    All complex human societies mate social provisions to ensure the wellbeing and security of their citizens and to facilitate social integration. As in other societies, China's formal welfare system is embedded in its social structure and its informal networks of self help and mutual aid. This thesis explores the development of one of China's major welfare bureaucracies - the Ministry of Civil Affairs and the local agencies which it supervises from 1949, with especial reference to the period between 1978 to 1988. The study begins by surveying the theories, both Western and socialist, that purport to explain the determinants of welfare. Richard Rose's welfare mix concept (1986) is modified to yield a framework that posits welfare development in terms of the role of the state, the family, the collective and the traditional culture of welfare. The operational definition in the Chinese context is then set out with reference to the programmes of social amelioration established under the aegis of the Minstry of Civil Affairs in order to assist those social groups that lack the capacity and resources for independent living. Before 1978, Civil Affairs Departments functioned as agencies of last resort, playing a small but vitally important role in meeting the needs of the poorest members of Chinese society. This remains true at the present time. Then policy developments in the current period are analysed in both the national context and in the province of Guangdong, where the economic reforms have gone furthest in reshaping Chinese social life. Emerging from the review is the interaction between social and economic policies, including the impact of the transformation of the institutional context and the changes in broader political objectives. In the final section, attention is drawn to the narrowly residualist character of the Ministry's approach to welfare. Several institutional factors, it is suggested, account for the degree of residualism - the state's narrow conception of the role of statutory welfare, the cultural importance of utilitarian Chinese familism, the all-embracing nature of the collective canopy and the general influence of the cultural legacy. The Chinese welfare system, it is argued, is what it is because it fits the structural requirements of Chinese socialism

    Translational research in South Africa: evaluating implementation quality using a factorial design

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    Background: HealthWise South Africa: Life Skills for Adolescents (HW) is an evidence- based substance use and sexual risk prevention program that emphasizes the positive use of leisure time. Since 2000, this program has evolved from pilot testing through an efficacy trial involving over 7,000 youth in the Cape Town area. Beginning in 2011, through 2015, we are undertaking a new study that expands HW to all schools in the Metro South Education District. Objective: This paper describes a research study designed in partnership with our South African collaborators that examines three factors hypothesized to affect the quality and fidelity of HW implementation: enhanced teacher training; teacher support, structure and supervision; and enhanced school environment. Methods: Teachers and students from 56 schools in the Cape Town area will participate in this study. Teacher observations are the primary means of collecting data on factors affecting implementation quality. These factors address the practical concerns of teachers and schools related to likelihood of use and cost-effectiveness, and are hypothesized to be "active ingredients" related to high-quality program implementation in real-world settings. An innovative factorial experimental design was chosen to enable estimation of the individual effect of each of the three factors. Results: Because this paper describes the conceptualization of our study, results are not yet available. Conclusions: The results of this study may have both substantive and methodological implications for advancing Type 2 translational research

    Validation of vessel size imaging (VSI) in high-grade human gliomas using magnetic resonance imaging, image-guided biopsies, and quantitative immunohistochemistry.

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    To evaluate the association between a vessel size index (VSIMRI) derived from dynamic susceptibility contrast (DSC) perfusion imaging using a custom spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence and quantitative estimates of vessel morphometry based on immunohistochemistry from image-guided biopsy samples. The current study evaluated both relative cerebral blood volume (rCBV) and VSIMRI in eleven patients with high-grade glioma (7 WHO grade III and 4 WHO grade IV). Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature. Measures of rCBV and VSIMRI were then compared to histological measures. We demonstrate good agreement between VSI measured by MRI and histology; VSIMRI = 13.67 μm and VSIHistology = 12.60 μm, with slight overestimation of VSIMRI in grade III patients compared to histology. rCBV showed a moderate but significant correlation with vessel density (r = 0.42, p = 0.03), and a correlation was also observed between VSIMRI and VSIHistology (r = 0.49, p = 0.01). The current study supports the hypothesis that vessel size measures using MRI accurately reflect vessel caliber within high-grade gliomas, while traditional measures of rCBV are correlated with vessel density and not vessel caliber

    Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

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    BackgroundTemozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 μM).MethodsMGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500 μM. Clonogenic GSC surviving 500 μM TMZ (GSC-500 μM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.ResultsThe molecular signatures characterized an activation of protective stress responses in GSC-500 μM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500 μM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500 μM TMZ and GSC-parental to 35 μM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489).ConclusionsThese data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT

    Monoclinic paracetamol vs. paracetamol-4,4'-bipyridine co-crystal; what is the difference? a charge density study

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    Paracetamol (PCM) has two well-documented polymorphic forms at room temperature; monoclinic Form I is more stable than the other orthorhombic Form II. Form II exhibits improved tabletting properties compared to Form I due to low shearing forces; however, difficulties in its manufacture have limited its use in industrial manufacture. Previous studies have found that the introduction of a co-former to form co-crystals would allow the PCM molecule to exist in a conformation similar to that of the orthorhombic form while being more stable at room temperature. Experimental charge density analysis of the paracetamol-4,4′-bipyridine (PCM-44BP) co-crystal system, and its constituent molecules, has been carried out to examine the forces that drive the formation and stabilisation of the co-crystal, while allowing PCM to maintain a packing motif similar to that found in Form II. It is hoped studies on this well-known compound will help apply the knowledge gained to other drug molecules that are less successful. The PCM molecules in the co-crystal were found to exhibit similar packing motifs to that found in Form I, however, intercalation of the 44BP molecule between the PCM layers resulted in a shallower angle between molecular planes, which could result in the required lateral shear. Topological analysis identified more weak interactions in the co-crystal compared to the individual molecules, thus allowing for greater stability as evidenced by the lattice energies. Weak interactions in the PCM-44BP co-crystal were found to range in strength from 4.08–84.33 kJ mol−1, and this variety allowed the PCM-44BP planes to be held together, while a weak π–π interaction (15.14 kJ mol−1) allowed lateral shear to occur, thus mimicking the planes found in Form II PCM and offering the possibility of improved tabletting properties. A comparison of integrated atomic charges between partitions of the PCM molecules in the single and co-crystal found that the hydroxyl and amide groups were involved in greater hydrogen bonding in the co-crystal, resulting in a charge redistribution across the molecule evidenced by a larger molecular dipole moment (µ = 12.34D). These findings, in addition to the co-crystal having the largest lattice energy, form a potential basis with which to predict that the co-crystal exhibits improved solubility and stability profiles. It is anticipated that these findings will contribute to improvements in the formulation and other physical properties of PCM and other pharmaceutical compounds

    Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients.

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    Glioblastoma stem cells (GSC) co-exhibiting a tumor-initiating capacity and a radio-chemoresistant phenotype, are a compelling cell model for explaining tumor recurrence. We have previously characterized patient-derived, treatment-resistant GSC clones (TRGC) that survived radiochemotherapy. Compared to glucose-dependent, treatment-sensitive GSC clones (TSGC), TRGC exhibited reduced glucose dependence that favor the fatty acid oxidation pathway as their energy source. Using comparative genome-wide transcriptome analysis, a series of defense signatures associated with TRGC survival were identified and verified by siRNA-based gene knockdown experiments that led to loss of cell integrity. In this study, we investigate the prognostic value of defense signatures in glioblastoma (GBM) patients using gene expression analysis with Probeset Analyzer (131 GBM) and The Cancer Genome Atlas (TCGA) data, and protein expression with a tissue microarray (50 GBM), yielding the first TRGC-derived prognostic biomarkers for GBM patients. Ribosomal protein S11 (RPS11), RPS20, individually and together, consistently predicted poor survival of newly diagnosed primary GBM tumors when overexpressed at the RNA or protein level [RPS11: Hazard Ratio (HR) = 11.5, p<0.001; RPS20: HR = 4.5, p = 0.03; RPS11+RPS20: HR = 17.99, p = 0.001]. The prognostic significance of RPS11 and RPS20 was further supported by whole tissue section RPS11 immunostaining (27 GBM; HR = 4.05, p = 0.01) and TCGA gene expression data (578 primary GBM; RPS11: HR = 1.19, p = 0.06; RPS20: HR = 1.25, p = 0.02; RPS11+RPS20: HR = 1.43, p = 0.01). Moreover, tumors that exhibited unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) or wild-type isocitrate dehydrogenase 1 (IDH1) were associated with higher RPS11 expression levels [corr (IDH1, RPS11) = 0.64, p = 0.03); [corr (MGMT, RPS11) = 0.52, p = 0.04]. These data indicate that increased expression of RPS11 and RPS20 predicts shorter patient survival. The study also suggests that TRGC are clinically relevant cells that represent resistant tumorigenic clones from patient tumors and that their properties, at least in part, are reflected in poor-prognosis GBM. The screening of TRGC signatures may represent a novel alternative strategy for identifying new prognostic biomarkers

    On-Wafer Measurement of a Multi-Stage MMIC Amplifier with 10 dB of Gain at 475 GHz

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    JPL has measured and calibrated a WR2.2 waveguide wafer probe from GGB Industries in order to allow for measurement of circuits in the 325-500 GHz range. Circuits were measured, and one of the circuits exhibited 10 dB of gain at 475 GHz. The MMIC circuit was fabricated at Northrop Grumman Corp. (NGC) as part of a NASA Innovative Partnerships Program, using NGC s 35-nm-gatelength InP HEMT process technology. The chip utilizes three stages of HEMT amplifiers, each having two gate fingers of 10 m in width. The circuits use grounded coplanar waveguide topology on a 50- m-thick substrate with through substrate vias. Broadband matching is achieved with coplanar waveguide transmission lines, on-chip capacitors, and open stubs. When tested with wafer probing, the chip exhibited 10 dB of gain at 475 GHz, with over 9 dB of gain from 445-490 GHz. Low-noise amplifiers in the 400-500 GHz range are useful for astrophysics receivers and earth science remote sensing instruments. In particular, molecular lines in the 400-500 GHz range include the CO 4-3 line at 460 GHz, and the CI fine structure line at 492 GHz. Future astrophysics heterodyne instruments could make use of high-gain, low-noise amplifiers such as the one described here. In addition, earth science remote sensing instruments could also make use of low-noise receivers with MMIC amplifier front ends. Present receiver technology typically employs mixers for frequency down-conversion in the 400-500 GHz band. Commercially available mixers have typical conversion loss in the range of 7-10 dB with noise figure of 1,000 K. A low-noise amplifier placed in front of such a mixer would have 10 dB of gain and lower noise figure, particularly if cooled to low temperature. Future work will involve measuring the noise figure of this amplifier

    Linking Life Skills and Norms with adolescent substance use and delinquency in South Africa

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    We examined factors targeted in two popular prevention approaches with adolescent drug use and delinquency in South Africa. We hypothesized adolescent life skills to be inversely related, and perceived norms to be directly related to later drug use and delinquency. Multiple regression and a relative weights approach were conducted for each outcome using a sample of 714 South African adolescents ages 15 to 19 years (M = 15.8 years, 57% female). Perceived norms predicted gateway drug use. Conflict resolution skills (inversely) and perceived peer acceptability (directly) predicted harder drug use and delinquency. The “culture of violence” within some South African schools may make conflict resolution skills more salient for preventing harder drug use and delinquency.Department of HE and Training approved lis
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