Spectral reflectances of natural targets for use in remote sensing studies

A collection of spectral reflectances of 156 natural targets is presented in a uniform format. For each target both a graphical plot and a digital tabulation of reflectance is given. The data were taken from the literature and include laboratory, field, and aircraft measurements. A discussion of the different measurements of reflectance is given, along with the changes in apparent reflectance when targets are viewed through the atmosphere. The salient features of the reflectance curves of common target types are presented and discussed

Assessing the Emergency Response Unit of the Mount Pleasant Police Department

Assesses the need for and usefulness of the Emergency Response Unit

Voltage-independent SK-channel dysfunction causes neuronal hyperexcitability in the hippocampus of Fmr1 knock-out mice

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (

Extensive dynamics of Plasmodium falciparum densities, stages and genotyping profiles

<p>Abstract</p> <p>Background</p> <p>Individuals living in areas of high malaria transmission often have different <it>Plasmodium falciparum </it>clones detected in the peripheral blood over time. The aim of this study was to assess the dynamics of asymptomatic <it>P. falciparum </it>infections in a few hours intervals.</p> <p>Methods</p> <p>Capillary blood samples were collected 6-hourly during five days from asymptomatic children in a highly endemic area in Tanzania. Parasite densities and maturation stages were investigated by light microscopy. Types and number of clones were analysed by PCR based genotyping of the polymorphic merozoite surface proteins 1 and 2 genes. Results: Parasite densities and maturation stages fluctuated 48-hourly with a gradual shift into more mature forms. Various genotyping patterns were observed in repeated samples over five days with only few samples with identical profiles. Up to six alleles differed in samples collected six hours apart in the same individual.</p> <p>Conclusion</p> <p>This detailed assessment highlights the extensive within-host dynamics of <it>P. falciparum </it>populations and the limitations of single blood samples to determine parasite densities, stages and genotyping profiles in a malaria infected individual.</p

C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and α-tubulin hyperacetylation both in vitro and in vivo

Histone deacetylase inhibitors (HDACIs) have shown promising anti-tumor effects for a variety of malignancies, however, many tumors are reportedly resistant to them. In this study, we made a novel discovery that co-administration of HDACIs (Trichostatin A (TSA) and others) and exogenous cell-permeable short-chain ceramide (C6) results in striking increase in cancer cell death and apoptosis in multiple cancer cells. These events are associated with perturbations in diverse cell signaling pathways, including inactivation of Akt/mTOR and increase in α-tubulin acetylation (both in vivo and in vitro). TSA interacts in a highly synergistic manner with C6-ceramide to disrupt HDAC6/protein phosphatase 1 (PP1)/tubulin complex, to induce α-tubulin hyperacetylation, and to release and activate PP1, which then leads to AKT dephosphorylation and eventually causes cancer cell death. Interestingly, TSA itself results in short-term ceramide accumulation, which as a result of metabolic (glycosylation) removal, does not result in evident increase of cancer cell death. However, adding C6-ceramide led to a very pronounced increase in ceramide level and marked increase in cell death. Importantly, the effective synergistic anti-tumor activity of TSA plus C6-ceramide is also seen in in vivo mice xenograft pancreatic and ovarian cancer models, indicating that this regimen (HDACI plus C6-ceramide) may represent a more effective form of therapy against pancreatic and ovarian carcinoma

piggyBac is an effective tool for functional analysis of the Plasmodium falciparum genome

<p>Abstract</p> <p>Background</p> <p>Much of the <it>Plasmodium falciparum </it>genome encodes hypothetical proteins with limited homology to other organisms. A lack of robust tools for genetic manipulation of the parasite limits functional analysis of these hypothetical proteins and other aspects of the <it>Plasmodium </it>genome. Transposon mutagenesis has been used widely to identify gene functions in many organisms and would be extremely valuable for functional analysis of the <it>Plasmodium </it>genome.</p> <p>Results</p> <p>In this study, we investigated the lepidopteran transposon, <it>piggyBac</it>, as a molecular genetic tool for functional characterization of the <it>Plasmodium falciparum </it>genome. Through multiple transfections, we generated 177 unique <it>P. falciparum </it>mutant clones with mostly single <it>piggyBac </it>insertions in their genomes. Analysis of <it>piggyBac </it>insertion sites revealed random insertions into the <it>P. falciparum </it>genome, in regards to gene expression in parasite life cycle stages and functional categories. We further explored the possibility of forward genetic studies in <it>P. falciparum </it>with a phenotypic screen for attenuated growth, which identified several parasite genes and pathways critical for intra-erythrocytic development.</p> <p>Conclusion</p> <p>Our results clearly demonstrate that <it>piggyBac </it>is a novel, indispensable tool for forward functional genomics in <it>P. falciparum </it>that will help better understand parasite biology and accelerate drug and vaccine development.</p

Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans

Opioid neurotransmission has a key role in mediating reward-related behaviours. Opioid receptor (OR) antagonists, such as naltrexone (NTX), can attenuate the behaviour-reinforcing effects of primary (food) and secondary rewards. GSK1521498 is a novel OR ligand, which behaves as an inverse agonist at the μ-OR sub-type. In a sample of healthy volunteers, we used [11C]-carfentanil positron emission tomography to measure the OR occupancy and functional magnetic resonance imaging (fMRI) to measure activation of brain reward centres by palatable food stimuli before and after single oral doses of GSK1521498 (range, 0.4–100 mg) or NTX (range, 2–50 mg). GSK1521498 had high affinity for human brain ORs (GSK1521498 effective concentration 50=7.10 ng ml−1) and there was a direct relationship between receptor occupancy (RO) and plasma concentrations of GSK1521498. However, for both NTX and its principal active metabolite in humans, 6-β-NTX, this relationship was indirect. GSK1521498, but not NTX, significantly attenuated the fMRI activation of the amygdala by a palatable food stimulus. We thus have shown how the pharmacological properties of OR antagonists can be characterised directly in humans by a novel integration of molecular and functional neuroimaging techniques. GSK1521498 was differentiated from NTX in terms of its pharmacokinetics, target affinity, plasma concentration–RO relationships and pharmacodynamic effects on food reward processing in the brain. Pharmacological differentiation of these molecules suggests that they may have different therapeutic profiles for treatment of overeating and other disorders of compulsive consumption

The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study

<p>Abstract</p> <p>Background</p> <p>Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) are the three components of the once-daily, single tablet regimen (Atripla) for treatment of HIV-1 infection. Previous cell culture studies have demonstrated that the double combination of tenofovir (TFV), the parent drug of TDF, and FTC were additive to synergistic in their anti-HIV activity, which correlated with increased levels of intracellular phosphorylation of both compounds.</p> <p>Results</p> <p>In this study, we demonstrated the combinations of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV synergistically inhibit HIV replication in cell culture and synergistically inhibit HIV-1 reverse transcriptase (RT) catalyzed DNA synthesis in biochemical assays. Several different methods were applied to define synergy including median-effect analysis, MacSynergy^®II and quantitative isobologram analysis. We demonstrated that the enhanced formation of dead-end complexes (DEC) by HIV-1 RT and TFV-terminated DNA in the presence of FTC-triphosphate (TP) could contribute to the synergy observed for the combination of TFV+FTC, possibly through reduced terminal NRTI excision. Furthermore, we showed that EFV facilitated efficient formation of stable, DEC-like complexes by TFV- or FTC-monophosphate (MP)-terminated DNA and this can contribute to the synergistic inhibition of HIV-1 RT by TFV-diphosphate (DP)+EFV and FTC-TP+EFV combinations.</p> <p>Conclusion</p> <p>This study demonstrated a clear correlation between the synergistic antiviral activities of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV combinations and synergistic HIV-1 RT inhibition at the enzymatic level. We propose the molecular mechanisms for the TFV+FTC+EFV synergy to be a combination of increased levels of the active metabolites TFV-DP and FTC-TP and enhanced DEC formation by a chain-terminated DNA and HIV-1 RT in the presence of the second and the third drug in the combination. This study furthers the understanding of the longstanding observations of synergistic anti-HIV-1 effects of many NRTI+NNRTI and certain NRTI+NRTI combinations in cell culture, and provides biochemical evidence that combinations of anti-HIV agents can increase the intracellular drug efficacy, without increasing the extracellular drug concentrations.</p

Comorbid mental disorders in substance users from a single catchment area - a clinical study

<p>Abstract</p> <p>Background</p> <p>The optimal treatment of patients with substance use disorders (SUDs) requires an awareness of their comorbid mental disorders and vice versa. The prevalence of comorbidity in first-time-admitted SUD patients has been insufficiently studied. Diagnosing comorbidity in substance users is complicated by symptom overlap, symptom fluctuations, and the limitations of the assessment methods. The aim of this study was to diagnose all mental disorders in substance users living in a single catchment area, without any history of treatment for addiction or psychiatric disorders, admitted consecutively to the specialist health services. The prevalence of substance-induced versus substance-independent disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), in SUD patients will be described.</p> <p>Methods</p> <p>First-time consecutively admitted patients from a single catchment area, aged 16 years or older, admitted to addiction clinics or departments of psychiatry as outpatients or inpatients will be screened for substance-related problems using the Alcohol Use Disorder Identification Test and the Drug Use Disorder Identification Test. All patients with scores above the cutoff value will be asked to participate in the study. The patients included will be diagnosed for SUD and other axis I disorders by a psychiatrist using the Psychiatric Research Interview for Substance and Mental Disorders. This interview was designed for the diagnosis of primary and substance-induced disorders in substance users. Personality disorders will be assessed according to the Structured Clinical Interview for DSM-IV axis II disorders. The Symptom Checklist-90-Revised, the Inventory of Depressive Symptoms, the Montgomery Asberg Depression Rating Scale, the Young Mania Rating Scale, and the Angst Hypomania Check List will be used for additional diagnostic assessments. The sociodemographic data will be recorded with the Stanley Foundation's Network Entry Questionnaire. Biochemical assessments will reveal somatic diseases that may contribute to the patient's symptoms.</p> <p>Discussion</p> <p>This study is unique because the material represents a complete sample of first-time-admitted treatment seekers with SUD from a single catchment area. Earlier studies have not focused on first-time-admitted patients, so chronically ill patients, may have been overrepresented in those samples. This study will contribute new knowledge about mental disorders in first-time-admitted SUD patients.</p