99 research outputs found
Engineering meter-scale porous media flow experiments for quantitative studies of geological carbon sequestration
This technical note describes the FluidFlower concept, a new laboratory
infrastructure for geological carbon storage research. The highly controlled
and adjustable system produces a strikingly visual physical ground truth of
studied processes for model validation, comparison, and forecasting, including
detailed physical studies of the behavior and storage mechanisms of carbon
dioxide and its derivative forms in relevant geological settings for subsurface
carbon storage. The design, instrumentation, structural aspects and methodology
are described. Furthermore, we share engineering insights on construction,
operation, fluid considerations, and fluid resetting in the porous media. The
new infrastructure enables researchers to study variability between repeated
CO2 injections, making the FluidFlower concept a suitable tool for sensitivity
studies on a range of determining carbon storage parameters in varying
geological formations
Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat
This study aims to investigate whether orexigenic antipsychotic drugs may induce dyslipidemia and glucose disturbances in female rats through direct perturbation of metabolically active peripheral tissues, independent of prior weight gain. Methods In the current study, we examined whether a single intraperitoneal injection of clozapine or olanzapine induced metabolic disturbances in adult female outbred Sprague–Dawley rats. Serum glucose and lipid parameters were measured during time-course experiments up to 48 h. Real-time quantitative PCR was used to measure specific transcriptional alterations in lipid and carbohydrate metabolism in adipose tissue depots or in the liver. Results Our results demonstrated that acute administration of clozapine or olanzapine induced a rapid, robust elevation of free fatty acids and glucose in serum, followed by hepatic accumulation of lipids evident after 12–24 h. These metabolic disturbances were associated with biphasic patterns of gluconeogenic and lipid-related gene expression in the liver and in white adipose tissue depots. Conclusion Our results support that clozapine and olanzapine are associated with primary effects on carbohydrate and lipid metabolism associated with transcriptional changes in metabolically active peripheral tissues prior to the development of drug-induced weight gain
Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan
INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases
Aggression and social experience: genetic analysis of visual circuit activity in the control of aggressiveness in Drosophila
Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen
Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma
Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients
BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor
(PAI-1) play essential roles in tumor invasion and metastasis. High levels
of both uPA and PAI-1 are associated with poor prognosis in breast cancer
patients. To confirm the prognostic value of uPA and PAI-1 in primary
breast cancer, we reanalyzed individual patient data provided by members
of the European Organization for Research and Treatment of Cancer-Receptor
and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets
involving 8377 breast cancer patients. During follow-up (median 79
months), 35% of the patients relapsed and 27% died. Levels of uPA and
PAI-1 in tumor tissue extracts were determined by different immunoassays;
values were ranked within each dataset and divided by the number of
patients in that dataset to produce fractional ranks that could be
compared directly across datasets. Associations of ranks of uPA and PAI-1
levels with relapse-free survival (RFS) and overall survival (OS) were
analyzed by Cox multivariable regression analysis stratified by dataset,
including the following traditional prognostic variables: age, menopausal
status, lymph node status, tumor size, histologic grade, and steroid
hormone-receptor status. All P values were two-sided. RESULTS: Apart from
lymph node status, high levels of uPA and PAI-1 were the strongest
predictors of both poor RFS and poor OS in the analyses of all patients.
Moreover, in both lymph node-positive and lymph node-negative patients,
higher uPA and PAI-1 values were independently associated with poor RFS
and poor OS. For (untreated) lymph node-negative patients in particular,
uPA and PAI-1 included together showed strong prognostic ability (all
P<.001). CONCLUSIONS: This pooled analysis of the EORTC-RBG datasets
confirmed the strong and independent prognostic value of uPA and PAI-1 in
primary breast cancer. For patients with lymph node-negative breast
cancer, uPA and PAI-1 measurements in primary tumors may be especially
useful for designing individualized treatment strategies
Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs
BACKGROUND: The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP) transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1) in four CNS-relevant human cell lines. RESULTS: There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines) displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. CONCLUSION: Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs
Sp1 Expression Is Disrupted in Schizophrenia; A Possible Mechanism for the Abnormal Expression of Mitochondrial Complex I Genes, NDUFV1 and NDUFV2
The prevailing hypothesis regards schizophrenia as a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed in schizophrenia, and consequently can affect the expression of genes implicated in this disorder. promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin.These findings suggest that abnormality in Sp1, which can be the main activator/repressor or act in combination with additional transcription factors and is subjected to environmental stimuli, can contribute to the polygenic and clinically heterogeneous nature of schizophrenia
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