Design study and evaluation of a hypergolic engine for a space power system, phase 2 Final report, 1 Jul. 1964 - 10 Feb. 1966

Design feasibility of hypergolic engine for space power syste

G-type antiferromagnetism and orbital ordering due to the crystal field from the rare-earth ions induced by the GdFeO_3-type distortion in RTiO_3 with R=La, Pr, Nd and Sm

The origin of the antiferromagnetic order and puzzling properties of LaTiO_3 as well as the magnetic phase diagram of the perovskite titanates are studied theoretically. We show that in LaTiO_3, the t_{2g} degeneracy is eventually lifted by the La cations in the GdFeO_3-type structure, which generates a crystal field with nearly trigonal symmetry. This allows the description of the low-energy structure of LaTiO_3 by a single-band Hubbard model as a good starting point. The lowest-orbital occupation in this crystal field stabilizes the AFM(G) state, and well explains the spin-wave spectrum of LaTiO_3 obtained by the neutron scattering experiment. The orbital-spin structures for RTiO_3 with R=Pr, Nd and Sm are also accounted for by the same mechanism. We point out that through generating the R crystal field, the GdFeO_3-type distortion has a universal relevance in determining the orbital-spin structure of the perovskite compounds in competition with the Jahn-Teller mechanism, which has been overlooked in the literature. Since the GdFeO_3-type distortion is a universal phenomenon as is seen in a large number of perovskite compounds, this mechanism may also play important roles in other compounds of this type.Comment: 20 pages, 15 figure

Design study and evaluation of a multifuel engine for a space power system final report, 19 apr. - 4 jun. 1965

Evaluation testing of modified hypergolic ignition engine operating on gaseous hydrogen and oxyge

<i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release

Colorectal carcinoma (CRC) is one of the most common causes of cancer-related mortality. Short-chain fatty acids secreted by dietary propionibacteria from the intestine, such as acetate, induce apoptosis in CRC cells and may therefore be relevant in CRC prevention and therapy. We previously reported that acetic acid-induced apoptosis in Saccharomyces cerevisiae cells involves partial vacuole permeabilization and release of Pep4p, the yeast cathepsin D (CatD), which has a protective role in this process. In cancer cells, lysosomes have emerged as key players in apoptosis through selective lysosomal membrane permeabilization (LMP) and release of cathepsins. However, the role of CatD in CRC survival is controversial and has not been assessed in response to acetate. We aimed to ascertain whether LMP and CatD are involved in acetate-induced apoptosis in CRC cells. We showed that acetate per se inhibits proliferation and induces apoptosis. More importantly, we uncovered that acetate triggers LMP and CatD release to the cytosol. Pepstatin A (a CatD inhibitor) but not E64d (a cathepsin B and L inhibitor) increased acetateinduced apoptosis of CRC cells, suggesting that CatD has a protective role in this process. Our data indicate that acetate induces LMP and subsequent release of CatD in CRC cells undergoing apoptosis, and suggest exploiting novel strategies using acetate as a prevention/therapeutic agent in CRC, through simultaneous treatment with CatD inhibitors.This work was supported by the Fundação para a Ciência e Tecnologia (FCT) research project PTDC/BIA-BCM/69448/2006 and FCT PhD grants for SA (SFRH/BD/64695/2009) and CO (SFRH/BD/77449/2011). This work was also supported by FEDER through POFC—COMPETE, and by national funds from FCT through the project PEst-C/BIA/UI4050/2011

The impact of anxiety and depression on migraine patients’ journey to a tertiary headache center

Objetivo: Avaliar o papel da comorbidade psiquiátrica no número de procedimentos diagnósticos, tratamentos farmacológicos agudos e preventivos e intervenções não farmacológicas em pacientes com enxaqueca experimentados antes de visitar um Centro Terciário de Cefaleia em São Paulo, Brasil. Métodos: Realizamos um estudo retrospectivo observacional de 465 pacientes consecutivos diagnosticados com enxaqueca e avaliados em um centro especializado em cefaleia terciária em São Paulo, Brasil. Coletamos os dados com base em revisões de prontuários médicos e em um questionário autoaplicado rotineiramente realizado durante a primeira consulta médica. Dois instrumentos padronizados foram utilizados para o diagnóstico de depressão e ansiedade, respectivamente: o Questionário de Saúde do Paciente-9 (PHQ-9) e o Transtorno de Ansiedade Generalizada (GAD-7). Resultados: Foram estudados 465 pacientes com diagnóstico de enxaqueca. A idade média dos pacientes foi de 37,3 anos (± 13,1) e 72,7% dos pacientes eram mulheres. A idade média do início da dor de cabeça foi de 17,1 anos (± 11,4) antes da primeira consulta em nosso Centro Terciário de Cefaleia, e 51,7% dos pacientes apresentavam enxaqueca crônica. A maioria dos pacientes (65,8%) apresentou um PHQ-9 ≥ 5, indicando pelo menos alguns sintomas depressivos, enquanto 152 pacientes (34,2%) foram considerados deprimidos (PHQ-9 ≥ 9). Os sintomas de ansiedade foram observados em 68,2% dos pacientes com base no instrumento GAD-7, e 209 pacientes (47,0%) foram diagnosticados com ansiedade (GAD-7 ≥ 8). As enxaquecas crônicas foram mais comuns que as enxaquecas episódicas em pacientes com comorbidade psiquiátrica: 63,2% dos pacientes depressivos, 61,2% dos ansiosos e 43,5% dos pacientes sem nenhum transtorno psiquiátrico. A maioria dos pacientes foi submetida a exames laboratoriais e imagens cerebrais (62,4% e 70,5%, respectivamente) em proporção semelhante entre os subgrupos com e sem ansiedade ou depressão. O tratamento não farmacológico foi frequente em todos os subgrupos e 342 pacientes (73,5%) realizaram pelo menos uma modalidade. No geral, a acupuntura foi o tratamento não farmacológico mais comum (55,2% dos pacientes), e não encontramos diferença entre os subgrupos. Pacientes depressivos e ansiosos foram submetidos a psicoterapia com mais frequência (54,2% e 50,8%, respectivamente) quando comparados aos pacientes sem depressão nem ansiedade (34,7%). A depressão foi associada a uma probabilidade reduzida de fisioterapia prévia (OR 0,39, IC 0,16 - 0,99). Pacientes com ansiedade grave usavam 10,7 vezes mais medicamentos do que pacientes não graves. Conclusão: Pacientes deprimidos foram submetidos a mais psicoterapia do que pacientes não deprimidos, embora tivessem uma chance reduzida de fisioterapia anterior. A ansiedade também foi associada à psicoterapia anterior e a um risco de 10,7 vezes do uso de tratamento farmacológico agudo, o que pode levar a questões relacionadas ao abuso de analgésicos. Ansiedade e depressão afetam a jornada de pacientes com enxaqueca antes de chegarem a um Centro Terciário de Cefaleia.Objective: To evaluate the role of psychiatric comorbidity in the number of diagnostic procedures, acute and preventive pharmacological treatments, and non-pharmacological interventions in migraine patients experienced before visiting a tertiary headache center in São Paulo, Brazil. Methods: We conducted a retrospective, observational study of 465 consecutive patients diagnosed with migraines and evaluated in a specialized tertiary headache center in São Paulo, Brazil. We collected the data based on medical chart reviews and a self-administered questionnaire routinely performed during the first medical visit. Two standardized instruments were used for the diagnosis of depression and anxiety, respectively: the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder (GAD-7). Results: We studied 465 patients diagnosed with migraines. The patients’ mean age was 37.3 years (±13.1), and 72.7% of patients were women. The average age of headache onset was 17.1 years (±11.4) before the first appointment at our tertiary headache center, and 51.7% of patients had chronic migraines. Most patients (65.8%) had a PHQ-9 ≥ 5, indicating at least some depressive symptoms, whereas 152 patients (34.2%) were considered depressed (PHQ-9 ≥ 9). Anxiety symptoms were observed in 68.2% of patients based on the GAD-7 instrument, and 209 patients (47.0%) were diagnosed with anxiety (GAD-7 ≥ 8). Chronic migraines were more common than episodic migraines among patients with psychiatric comorbidity: 63.2% of depressive patients, 61.2% of anxious patients, and 43.5% of patients without any psychiatric disorder. Most patients underwent laboratory tests and brain imaging (62.4% and 70.5%, respectively) in a similar proportion among subgroups with and without anxiety or depression. Nonpharmacological treatment was frequent in all subgroups, and 342 patients (73.5%) performed at least one modality. Overall, acupuncture was the most common non-pharmacological treatment (55.2% of patients), and we found no difference between the subgroups. Depressive and anxious patients more frequently underwent psychotherapy (54.2% and 50.8%, respectively) when compared to patients with neither depression nor anxiety (34.7%). Depression was associated with a reduced likelihood of previous physiotherapy (OR 0.39, CI 0.16 – 0.99). Patients with severe anxiety used 10.7 times more medicines than non-severe patients. Conclusion: Depressed patients underwent more psychotherapy than non-depressed patients, although they had a reduced chance of previous physiotherapy. Anxiety was also associated with previous psychotherapy and a risk of 10.7 times of using acute pharmacological treatment, which may lead to issues related to analgesic abuse. Anxiety and depression affect the journey of patients with migraines before arriving at a tertiary headache center

Effects of air abrasion with alumina or glass beads on surface characteristics of CAD/CAM composite materials and the bond strength of resin cements

ABSTRACT Objective The study aimed to evaluate effects of air abrasion with alumina or glass beads on bond strengths of resin cements to CAD/CAM composite materials. Material and Methods CAD/CAM composite block materials [Cerasmart (CS) and Block HC (BHC)] were pretreated as follows: (a) no treatment (None), (b) application of a ceramic primer (CP), (c) alumina-blasting at 0.2 MPa (AB), (d) AB followed by CP (AB+CP), and (e) glass-beads blasting at 0.4 MPa (GBB) followed by CP (GBB+CP). The composite specimens were bonded to resin composite disks using resin cements [G-CEM Cerasmart (GCCS) and ResiCem (RC)]. The bond strengths after 24 h (TC 0) and after thermal cycling (TC 10,000 at 4–60°C) were measured by shear tests. Three-way ANOVA and the Tukey compromise post hoc tests were used to analyze statistically significant differences between groups (α=0.05). Results For both CAD/CAM composite materials, the None group exhibited a significant decrease in bond strength after TC 10,000 (p0.05). The AB+CP group showed a significantly higher bond strength after TC 10,000 than did the AB group for RC (p<0.05), but not for GCCS. The GBB+CP group showed the highest bond strength for both thermal cyclings (p<0.05). Conclusions Air abrasion with glass beads was more effective in increasing bond durability between the resin cements and CAD/CAM composite materials than was using an alumina powder and a CP

Students and academics working in partnership to embed cultural competence as a graduate quality

Since 2014, the University of Sydney has been experimenting with a new initiative motivated by the research on “students as partners”. In 2014, six students were selected as Ambassadors of the Sydney Teaching Colloquium (STC)-the University’s annual learning and teaching conference-as undergraduate researchers. In that year, the focus was on assessment standards

Clinical Validation of Integrated Nucleic Acid and Protein Detection on an Electrochemical Biosensor Array for Urinary Tract Infection Diagnosis

BACKGROUND: Urinary tract infection (UTI) is a common infection that poses a substantial healthcare burden, yet its definitive diagnosis can be challenging. There is a need for a rapid, sensitive and reliable analytical method that could allow early detection of UTI and reduce unnecessary antibiotics. Pathogen identification along with quantitative detection of lactoferrin, a measure of pyuria, may provide useful information towards the overall diagnosis of UTI. Here, we report an integrated biosensor platform capable of simultaneous pathogen identification and detection of urinary biomarker that could aid the effectiveness of the treatment and clinical management. METHODOLOGY/PRINCIPAL FINDINGS: The integrated pathogen 16S rRNA and host lactoferrin detection using the biosensor array was performed on 113 clinical urine samples collected from patients at risk for complicated UTI. For pathogen detection, the biosensor used sandwich hybridization of capture and detector oligonucleotides to the target analyte, bacterial 16S rRNA. For detection of the protein biomarker, the biosensor used an analogous electrochemical sandwich assay based on capture and detector antibodies. For this assay, a set of oligonucleotide probes optimized for hybridization at 37°C to facilitate integration with the immunoassay was developed. This probe set targeted common uropathogens including E. coli, P. mirabilis, P. aeruginosa and Enterococcus spp. as well as less common uropathogens including Serratia, Providencia, Morganella and Staphylococcus spp. The biosensor assay for pathogen detection had a specificity of 97% and a sensitivity of 89%. A significant correlation was found between LTF concentration measured by the biosensor and WBC and leukocyte esterase (p<0.001 for both). CONCLUSION/SIGNIFICANCE: We successfully demonstrate simultaneous detection of nucleic acid and host immune marker on a single biosensor array in clinical samples. This platform can be used for multiplexed detection of nucleic acid and protein as the next generation of urinary tract infection diagnostics

Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA)

Gefitinib (IRESSA), an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor, has antitumour activity in the advanced non-small-cell lung cancer (NSCLC) setting. However, in chemotherapy-naïve patients with advanced NSCLC, the addition of gefitinib to standard chemotherapy regimens failed to increase survival. These results suggest the need for improved patient selection and combination rationales for targeted therapies. We have identified subpopulations of an adenocarcinoma cell line that are naturally resistant to gefitinib, and have analysed the cDNA expression profiles, genomic status of EGFR gene and the effect of gefitinib on signalling pathways in these cell lines in order to identify key mechanisms for naturally acquired resistance to gefitinib. Gefitinib-resistant subpopulations demonstrated increased Akt phosphorylation (not inhibited by gefitinib), reduced PTEN protein expression and loss of the EGFR gene mutation when compared with parental cell lines. These differences in Akt and PTEN protein expression were not evident from the cDNA array profiles. These data suggests that (1) the EGFR gene mutation may be possibly lost in some cancer cells with other additional mechanisms for activating Akt, (2) reintroduction of PTEN or pharmacological downregulation of the constitutive PI3K–Akt-pathway activity may be an attractive therapeutic strategy in cancers with gefitinib resistance