Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies.

PURPOSE ABI-007 is a novel solvent-free, albumin-bound, 130-nm particle formulation of paclitaxel designed to avoid solvent-related toxicities and to deliver paclitaxel to tumors via molecular pathways involving an endothelial cell-surface albumin receptor (gp60) and an albumin-binding protein expressed by tumor cells and secreted into the tumor interstitium (secreted protein acid rich in cysteine). This study determined the maximum-tolerated dose (MTD) of ABI-007 monotherapy administered weekly (three weekly doses, repeated every 4 weeks) and assessed the pharmacokinetics of paclitaxel administered as ABI-007. PATIENTS AND METHODS Patients with advanced nonhematologic malignancies received ABI-007 without premedication at dose levels from 80 to 200 mg/m(2) as a 30-minute intravenous infusion once a week for 3 weeks, followed by 1 week of rest (one cycle). RESULTS Thirty-nine patients were treated with an average of five cycles of ABI-007; 33% of patients received > or = six cycles of treatment. MTDs for heavily and lightly pretreated patients were 100 and 150 mg/m(2), respectively; and the dose-limiting toxicities were grade 4 neutropenia and grade 3 peripheral neuropathy, respectively. Maximum paclitaxel concentration and area under the curve increased linearly with dose. Dose-dependent changes in plasma clearance did not occur. Partial responses were observed in five patients with breast, lung, and ovarian cancers, all of whom had previously been treated with paclitaxel containing polyoxyethylated castor oil in the formulation. CONCLUSION This study demonstrated that weekly ABI-007 can be administered at doses exceeding those typically used for paclitaxel containing polyoxyethylated castor oil. Pharmacokinetics were linear over the dose range studied. Antitumor responses occurred in patients previously treated with paclitaxel containing polyoxyethylated castor oil.
Becoming an International Distance Learner: Cross-Cultural Perspectives on the Initial Period Study

Although internationalisation has been one of the central themes of Business and Management education research over the past two decades, student perspectives on the subject particularly in the context of distance learning context have been largely overlooked. This paper reports on the findings of a research project conducted at the Open University in the United Kingdom and at the International Institute of Management (IIM LINK) in Russia which analysed perceptions of the initial period of distance study in a sample of 25 Business and Management students. Interview analysis showed both similarities and variations in the themes that students studying on different types of courses raised in their responses. The paper calls for more comparative research on the subject using mixed-method approaches through cross-cultural comparisons and comparisons across different types of distance teaching and learning contexts.
Development of microglia in the postnatal rat hippocampus

During the prenatal development of the hippocampus, microglial cell precursors progressively occur in all subfields in accordance with known ontogenetic gradients of the region (Dalmau et al., J. Comp. Neurol. 1997a;377:70–84). The present study follows the regional distribution of these microglial cell precursors and their morphological differentiation in the rat hippocampus from birth to postnatal (P) day 18. The results demonstrate that the cellular differentiation and the subregional distribution of microglia follow the specific developmental gradients of the different parts of Ammon's horn and the dentate gyrus. Microglial cell distribution in the dentate gyrus is thus delayed compared with that in Ammon's horn. The appearance of microglia in the hippocampal subregions and differentiation of cell precursors into adult microglia occur earlier at temporal levels than at septal levels. Distribution of microglial cells follows an outside‐to‐inside pattern from the hippocampal fissure to the main cell layers in either Ammon's horn or the dentate gyrus. Meanwhile, the resident microglial cells located in the stratum oriens and dentate hilus at birth also increase in number and gradually disperse throughout the whole tissue of the two layers with age. In Ammon's horn, microglial differentiation occurs earlier in CA3 than in CA1. In the dentate gyrus, microglia appear earlier in relation to the external limb than to the internal limb, largely following a lateral‐to‐medial gradient. The differentiation and appearance of microglia in the various hippocampal and dentate subregions often correspond to the developmental stage of intrinsic and extrinsic afferent nerve fiber projections. Finally, in both Ammon's horn and the dentate gyrus, cells resembling reactive microglia are also observed and, in particular, in the perforant path projections from P9 to P18, suggesting their participation not only in phagocytosis of dead cells but also in axonal elimination and/or fiber reorganization. Hippocampus 1998;8:458–474. © 1998 Wiley‐Liss, Inc.
Analysis of the APETALA3- and PISTILLATA-like genes in Hedyosmum orientale (Chloranthaceae) provides insight into the evolution of the floral homeotic B-function in angiosperms.

BACKGROUND AND AIMS According to the floral ABC model, B-function genes appear to play a key role in the origin and diversification of the perianth during the evolution of angiosperms. The basal angiosperm Hedyosmum orientale (Chloranthaceae) has unisexual inflorescences associated with a seemingly primitive reproductive morphology and a reduced perianth structure in female flowers. The aim of this study was to investigate the nature of the perianth and the evolutionary state of the B-function programme in this species. METHODS A series of experiments were conducted to characterize B-gene homologues isolated from H. orientale, including scanning electron microscopy to observe the development of floral organs, phylogenetic analysis to reconstruct gene evolutionary history, reverse transcription-PCR, quantitative real-time PCR and in situ hybridization to identify gene expression patterns, the yeast two-hybrid assay to explore protein dimerization affinities, and transgenic analyses in Arabidopsis thaliana to determine activities of the encoded proteins. KEY RESULTS The expression of HoAP3 genes was restricted to stamens, whereas HoPI genes were broadly expressed in all floral organs. HoAP3 was able to partially restore the stamen but not petal identity in Arabidopsis ap3-3 mutants. In contrast, HoPI could rescue aspects of both stamen and petal development in Arabidopsis pi-1 mutants. When the complete C-terminal sequence of HoPI was deleted, however, no or weak transgenic phenotypes were observed and homodimerization capability was completely abolished. CONCLUSIONS The results suggest that Hedyosmum AP3-like genes have an ancestral function in specifying male reproductive organs, and that the activity of the encoded PI-like proteins is highly conserved between Hedyosmum and Arabidopsis. Moreover, there is evidence that the C-terminal region is important for the function of HoPI. Our findings indicate that the development of the proposed perianth in Hedyosmum does not rely on the B homeotic function.
Loss of mismatch repair activity in simian virus 40 large T antigen–immortalized BPH‐1 human prostatic epithelial cell line

Simian virus 40 large T antigen (SVLTAg) has been used to immortalize cells; however, the mechanism leading to immortalization is still unclear. We hypothesize that DNA mismatch repair (MMR) activity is important during SVLTAg‐induced immortalization. To test this hypothesis, we used the SVLTAg‐immortalized cell line BPH‐1 derived from human benign prostate epithelial cells to analyze MMR activity and the expression of MMR genes (hMLH1, hPMS1, hPMS2, hMSH2, hMSH3, and hMSH6). The results demonstrated that BPH‐1 cells were deficient in repairing G:T, A:C, and G:G mispairs in bacteriophage M13mp2. Reverse‐transcription polymerase chain reaction experiments indicated MMR genes (hMSH3, hMSH6, and hPMS1) were expressed at a low level in BPH‐1 cells. In contrast, all six MMR genes were expressed in human benign prostate hyperplasia tissues. Downregulation of hMSH3, hMSH6, and hPMS1 genes is not a result of the hypermethylation mechanism because demethylation with 5‐aza‐2′‐deoxycytidine did not restore expression of these genes. Although the hMLH1 gene is expressed in BPH‐1 cells, western blotting and exon analyses demonstrated that hMLH1 was mutated and/or deleted in BPH‐1 cells. © 2001 Wiley‐Liss, Inc.
Effects of tiagabine and diazepam on operant ethanol self-administration in the rat.

OBJECTIVE Benzodiazepines (BDZ) are widely used in the treatment of anxiety and ethanol withdrawal. It has been suggested that this class of compounds may increase the reinforcing value of ethanol; however, the literature is scarce. Tiagabine has recently been introduced into clinical use as an anti-epileptic drug. It acts through inhibiting gamma-aminobutyric acid (GABA) reuptake, and thus represents a pharmacodynamically novel principle for potentiating GABAergic transmission. The objective of the present study was to examine whether these two manners of modulating GABAergic transmission would affect ethanol self-administration in rats. METHOD Rats were trained on an operant oral ethanol self-administration task in a two-lever free-choice paradigm. When trained, subjects were treated with tiagabine (2, 6 and 18 mg/kg, intraperitoneally [i.p.]) or diazepam (0.5, 1.5 and 4.5 mg/kg, i.p.). Postsession blood alcohol concentrations and locomotor activity measures also were obtained. RESULTS At nonsedating doses, neither tiagabine nor diazepam affected operant ethanol self-administration. At the highest doses (18 and 4.5 mg/kg, respectively), both drugs suppressed ethanol self-administration but also induced significant suppression of locomotion, indicative of sedation. CONCLUSIONS Systemic administration of either the GABA-uptake blocker, tiagabine, or the GABA/BDZ agonist, diazepam, at nonsedating doses does not seem to affect oral ethanol self-administration.
Quantifying Species Diversity with a DNA Barcoding-Based Method: Tibetan Moth Species (Noctuidae) on the Qinghai-Tibetan Plateau

With the ongoing loss of biodiversity, there is a great need for fast and effective ways to assess species richness and diversity: DNA barcoding provides a powerful new tool for this. We investigated this approach by focusing on the Tibetan plateau, which is one of the world's top biodiversity hotspots. There have been few studies of its invertebrates, although they constitute the vast majority of the region's diversity. Here we investigated species diversity of the lepidopteran family Noctuidae, across different environmental gradients, using measurements based on traditional morphology as well as on DNA barcoding. The COI barcode showed an average interspecific K2P distance of , which is about four times larger than the mean intraspecific distance (). Using six diversity indices, we did not detect any significant differences in estimated species diversity between measurements based on traditional morphology and on DNA barcoding. Furthermore, we found strong positive correlations between them, indicating that barcode-based measures of species diversity can serve as a good surrogate for morphology-based measures in most situations tested. Eastern communities were found to have significantly higher diversity than Western ones. Among 22 environmental factors tested, we found that three (precipitation of driest month, precipitation of driest quarter, and precipitation of coldest quarter) were significantly correlated with species diversity. Our results indicate that these factors could be the key ecological factors influencing the species diversity of the lepidopteran family Noctuidae on the Tibetan plateau.
Limitations in Orthodox Economic Analysis of Urban Realty

Orthodox economic analysis cannot identify how to provide affordable housing on a sustainable basis because it: (i) Considers the nature of property rights as a given rather than as a policy variable; (ii) Focuses its analysis on the production and exchange of goods and services to neglect values that arise from the ownership and control of assets and liabilities; (iii) Does not identify Surplus Profits; (iv) Neglects how government investment in urban infrastructure creates private profits for land owners and so also neglects; (v) How windfall gains and surplus profits can be used to cross subsidize housing and commercial investors. Duplex property rights are described that separate the value of buildings from the values created in their land by neighboring infrastructure investment. This allows uplift in land values created by infrastructure expenditure to be used to make all neighborhood sites self-financing to halve the cost of urban housing and eliminate the cost of land for commercial developments. The resulting increase in economic efficiency improves equity by providing eight ways to distribute wealth to citizens without government taxes or welfare. The paper recommends that approval for public infrastructure expenditure and/or development be made conditional upon adopting duplex ownership of urban realty.
Understanding the Behaviour of Capital Flow and its Components: The Indian Experience

The article analyses the behaviour of net total capital inflow and its components since the introduction of liberalisation in India in 1991. An introspective analysis of capital flow reveals that capital inflow in India is volatile in nature and it is volatile in exactly the wrong direction, in a sense that it is pro-cyclical rather than countercyclical. However, all types of flows should not be treated equally. Being the most volatile and least persistent components, FPI and commercial bank inflow should be monitored very cautiously. The volatility of foreign direct investment (FDI) and commercial borrowing has gradually increased, although it has declined recently. External assistance has declined steadily and lost its dominance relative to the other counterparts. There is ample evidence of complementarity among the components of capital flows though we get a glimpse of substitutability between FDI and FPI—the two most voluminous components of capital flows. Contrary to a-cyclical, non-debt creating flows, commercial borrowings and commercial bank flows are found to be pro-cyclical in nature. The net total capital inflow series contain three structural breakpoints, at 1995Q4, 2002Q4 and 2006Q2. Domestic growth performance, policy changes and external shocks are the key factors behind these obtained structural breaks. There was a noticeable change in the behaviour of total capital flow and its components over the four phases identified in the article. JEL Classification: F21, F32, F41
Susceptibility of Biofilms to Bdellovibrio bacteriovorus Attack

ABSTRACT Biofilms are communities of microorganisms attached to a surface, and the growth of these surface attached communities is thought to provide microorganisms with protection against a range of biotic and abiotic agents. The capability of the gram-negative predatory bacterium Bdellovibrio bacteriovorus to control and reduce an existing Escherichia coli biofilm was evaluated in a static assay. A reduction in biofilm biomass was observed as early as 3 h after exposure to the predator, and an 87% reduction in crystal violet staining corresponding to a 4-log reduction in biofilm cell viability was seen after a 24-h exposure period. We observed that an initial titer of Bdellovibrio as low as 102 PFU/well or an exposure to the predator as short as 30 min is sufficient to reduce a preformed biofilm. The ability of B. bacteriovorus to reduce an existing biofilm was confirmed by scanning electron microscopy. The reduction in biofilm biomass obtained after the first 24 h of exposure to the predator remained unchanged even after longer exposure periods and reinoculation of the samples with fresh Bdellovibrio; however, no genetically stable resistant population of the host bacteria could be detected. Our data suggest that growth in a biofilm does not prevent predation by Bdellovibrio but allows a level of survival from attack greater than that observed for planktonic cells. In flow cell experiments B. bacteriovorus was able to decrease the biomass of both E. coli and Pseudomonas fluorescens biofilms as determined by phase-contrast and epifluorescence microscopy.
Estrogen and Stroke: A Review of the Current Literature

ABSTRACT Stroke is one of the leading causes of death and disability annually, and one of the larger populations for which neuroscience nurses care. Differences in gender have been identified as a risk factor for stroke repeatedly throughout the literature. The purpose of this evidence-based literature review is to provide information to healthcare professionals regarding stroke and its relationship with estrogen, the major female sex hormone. Background information on the three types of stroke is outlined, and information on estrogen compounds and hormone replacement therapy is detailed. A review of articles relating estrogen and/or hormone replacement therapy with stroke was performed. Fifty-seven articles met the criteria for inclusion in the review, 19 articles support the use of estrogen and/or an estrogen-related compound in the prevention or treatment of stroke, 6 articles claim estrogen and/or estrogen-related compounds are risk factors for stroke, and 11 articles remain inconclusive with regard to an estrogen and stroke relationship.
Arthritic temporomandibular joint: correlation of macromolecular contrast-enhanced MR imaging parameters and histopathologic findings.

PURPOSE To assess the utility of macromolecular contrast material-enhanced magnetic resonance (MR) imaging parameters for determining the histopathologic severity of temporomandibular joint (TMJ) arthritis. MATERIALS AND METHODS Ovalbumin was used to induce arthritis in the TMJs of 10 previously sensitized adult white rabbits. Five rabbits composed the sham-treated control group. Dynamic spin-echo imaging was performed immediately before and for 30 minutes after injection of macromolecular contrast medium. Histologic specimens of TMJ were assessed quantitatively for arthritis. Changes in MR signal intensity were derived from the synovial and subsynovial tissues of the TMJ, and plasma volume (PV) and permeability surface area product (PS) were calculated. These MR parameters and the arthritic scores were compared between sham-treated and antigen-challenged TMJs. The relationships between MR parameters and histopathologic indexes were also determined. RESULTS Arthritic TMJs showed marked enhancement of the synovial and subsynovial tissues over the imaging period. PS and all histopathologic indexes of arthritis were significantly greater (P < .005) in antigen-challenged than in sham-treated TMJs. PS demonstrated strong positive relationships with all histologic parameters of arthritis, indicating its utility for assessing the severity of joint inflammation. CONCLUSION Macromolecular contrast-enhanced MR imaging enables quantification of PS and PV in inflamed joints. This technique may provide insights into the pathogenesis of joint inflammation and noninvasive monitoring of disease severity and treatment response in arthritis.
Quantitative imaging of pO2 in orthotopic murine gliomas: hypoxia correlates with resistance to radiation

Abstract Hypoxia is considered one of the microenvironmental factors associated with the malignant nature of glioblastoma. Thus, evaluating intratumoural distribution of hypoxia would be useful for therapeutic planning as well as assessment of its effectiveness during the therapy. Electron paramagnetic resonance imaging (EPRI) is an imaging technique which can generate quantitative maps of oxygen in vivo using the exogenous paramagnetic compound, triarylmethyl and monitoring its line broadening caused by oxygen. In this study, the feasibility of EPRI for assessment of oxygen distribution in the glioblastoma using orthotopic U87 and U251 xenograft model is examined. Heterogeneous distribution of pO2 between 0 and 50 mmHg was observed throughout the tumours except for the normal brain tissue. U251 glioblastoma was more likely to exhibit hypoxia than U87 for comparable tumour size (median pO2; 29.7 and 18.2 mmHg, p = .028, in U87 and U251, respectively). The area with pO2 under 10 mmHg on the EPR oximetry (HF10) showed a good correlation with pimonidazole staining among tumours with evaluated size. In subcutaneous xenograft model, irradiation was relatively less effective for U251 compared with U87. In conclusion, EPRI is a feasible method to evaluate oxygen distribution in the brain tumour.
Ribonuclease III Processing of Coaxially Stacked RNA Helices*

The RNase III family of endoribonucleases participates in maturation and decay of cellular and viral transcripts by processing of double-stranded RNA. RNase III degradation is inherent to most antisense RNA-regulated gene systems in Escherichia coli. In the hok/sok system from plasmid R1, Sok antisense RNA targets the hok mRNA for RNase III-mediated degradation. An intermediate in the pairing reaction between Sok RNA and hok mRNA forms a three-way junction. A complex between a chimeric antisense RNA andhok mRNA that mimics the three-way junction was cleaved by RNase III both in vivo and in vitro. Footprinting using E117A RNase III binding to partially complementary RNAs showed protection of the 13 base pairs of interstrand duplex and of the bottom part of the transcriptional terminator hairpin of the antisense RNA. This suggests that the 13 base pairs of RNA duplex are coaxially stacked on the antisense RNA terminator stem-loop and that each stem forms a monomer half-site, allowing symmetrical binding of the RNase III dimer. This processing scheme shows an unanticipated diversity in RNase III substrates and may have a more general implication for RNA metabolism.
Increased circulating interleukin‐6 (IL‐6) activity in endotoxin‐challenged mice pretreated with anti‐IL‐6 antibody is due to IL‐6 accumulated in antigen‐antibody complexes

Mice pretreated with monoclonal anti‐interleukin‐6 (IL‐6) antibody and then challenged with lipopolysaccharide (LPS), paradoxically develop higher levels of circulating biological IL‐6 activity, as measured by the hybridoma growth promotion assay, than mice similarly challenged but not pretreated with antibody. Here we provide evidence that this increased biological activity was entirely accounted for by the presence of increased amounts of IL‐6 protein, which could be isolated by immunoaffinity chromatography and subsequently visualized after gel electrophoresis. Chromatography on a protein G matrix and a sandwich ELISA allowed to demonstrate that all IL‐6 present in the serum was in the form of antigen‐antibody complexes. Serum samples of antibody‐treated animals which contained the highest biological activity typically contained near equimolar concentrations of IL‐6 and antibody. In vitro neutralization tests with pure antibody and IL‐6 demonstrated that, with both antibodies tested, more than 1000‐fold molar excess of antibody is needed for neutralization in the hybridoma growth assay. It is concluded that increased biological activity in serum of the anti‐IL‐6 antibody‐treated mice is due to sequestration of the endogenous IL‐6 in the form of antigen‐antibody complexes which, due to the lack of sufficient antibody excess, produce nearly full activity in the hybridoma growth assay.