600 research outputs found
Rage From Within the Machine: Protest Music, Social Justice, and Educational Reform, a Collective Case Study
School reform initiatives in the United States have been occurring since the launching of Sputnik by the U.S.S.R. in 1957. These efforts have largely been internal, within school reforms, with little consideration given to external variables such as poverty that affect student achievement. Given the pervasive link between poverty and student achievement, the author argues for an expanded leadership lens which includes social justice. In an effort to learn more about social justice, three socially conscious activist musicians/groups were studied in a qualitative collective case study. The formative influences of the artists were analyzed. The activist activity of the bands was also examined.
Six emergent themes were identified from the study of the musicians, and each theme had educational implications. Lastly, suggestions for further research were listed
Numerical experiments on scalar transport and mixing in turbulent boundary layers
In this work, we present numerical experiments aimed at dynamically establishing the separate role of the inner and outer cycles on the scalar transport in the configuration of a temporally evolving boundary layer. The experiments are based on the study of the evolution of passive scalars driven by velocity fields where inner and outer cycles are alternately suppressed. Two different approaches are implemented. In the first, the discrimination between inner and outer cycle activities is based on the scale dimension of the involved motions. The second instead, discriminates on the basis of the distance from the wall of the turbulent motions. The two approaches depict the same scenario. Both the inner and outer cycles appear to be autonomous and, in a sense, independent, since their dynamics remain qualitatively unaltered despite facing two different conditions. The outer cycle faces a free boundary at the top and simply rescales according to what is supplied by the inner cycle. The inner cycle, on the other hand, resides between the wall and the outer region. As a result, the reduction of the scalar fluxes in the outer region due to the suppression of the outer cycle causes a damping in the near-wall region activities
Pulmonary tuberculosis followed by sarcoidosis in an HIV-infected patient: a case report and a simplified diagnostic flowchart for diagnosis and treatment of sarcoidosis
The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started
JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients
Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LT
GPS Digital Nudge to Limit Road Crashes in Non-Expert Drivers
Many automotive industries are developing technologies to assist human drivers in sug-gesting wiser choices to improve drivers’ behaviour. The technology that makes use of this modality is defined as a “digital nudge”. An example of a digital nudge is the GPS that is installed on smart-phones. Some studies have demonstrated that the use of GPS negatively affects environmental learning because of the transformation of some spatial skills. The main purpose of this study was to investigate the use of the GPS nudge and its relationship with spatial ability, together with its function in supporting the driving behaviour of non-expert drivers, in order to reduce the number of road crashes. A total of 88 non-expert drivers (M age = 21 years) filled in questionnaires and carried out tasks to measure spatial abilities, sense of direction, driver behaviour, and six different real-life driving scenarios. The results reveal that the higher the spatial skills are, the greater the GPS use is, and that drivers who use GPS improve their sense of direction. Moreover, people with high visuospatial abilities use GPS more extensively. Finally, young drivers do not consider the GPS aid to be useful when they have no time pressure. The results are discussed by taking into account the familiarity-and-spatial-ability model
1991-05-04
Abstract
OBJECTIVES:
To analyse the virological and clinical efficacy of cidofovir combined with highly active antiretroviral therapy (HAART) in AIDS-related progressive multifocal leukoencephalopathy (PML).
DESIGN:
Multicentre observational study of consecutive HIV-positive patients with histologically or virologically-proven PML. Group A, 26 patients treated with HAART; group B, 14 patients treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and alternate weeks thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR.
RESULTS:
Baseline virological, immunological and clinical characteristics were homogeneous between the groups. In one case cidofovir was discontinued because of severe proteinuria. There was no significant difference in HIV RNA responses and changes in the number of CD4 cells between group A and B. After 2 months of therapy, five out of 12 (42%) patients from group A and seven out of eight (87%) from group B reached undetectable JC virus DNA in the CSF (Chi-square P = 0.04); moreover, 24% of group A and 57% of group B patients showed neurological improvement or stability (P = 0.038). One-year cumulative probability of survival was 0.67 with cidofovir and 0.31 without (log-rank test, P = 0.01). Variables independently associated with longer survival were the use of cidofovir, HAART prior to the onset of PML, a baseline JC virus DNA load in CSF or = 60.
CONCLUSIONS:
In AIDS-related PML, cidofovir added to HAART is associated with a more effective control of JCV replication, with improved neurological outcome and survival compared with HAART alone
Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4
Guanine-rich nucleic acid sequences can adopt G-quadruplex structures stabilized by layers of four Hoogsteen-paired guanine residues. Quadruplex-prone sequences are found in many regions of human genome and in the telomeres of all eukaryotic organisms. Since small molecules that target G-quadruplexes have been found to be effective telomerase inhibitors, the identification of new specific ligands for G-quadruplexes is emerging as a promising approach to develop new anticancer drugs. Distamycin A is known to bind to AT-rich sequences of duplex DNA, but it has recently been shown to interact also with G-quadruplexes. Here, isothermal titration calorimetry (ITC) and NMR techniques have been employed to characterize the interaction between a dicationic derivative of distamycin A (compound 1) and the [d(TGGGGT)]4 quadruplex. Additionally, to compare the
binding behaviour of netropsin and compound 1 to the same target, a calometric study of the interaction between
netropsin and [d(TGGGGT)]4 has been performed. Experiments show that netropsin and compound 1 are
able to bind to [d(TGGGGT)]4 with good affinity and comparable thermodynamic profiles. In both cases the interactions
are entropically driven processes with a small favourable enthalpic contribution. Interestingly, the structural modifications of compound 1 decrease the affinity of the ligand toward the duplex, enhancing the selectivity
Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolopyrimidinones Tethered with Hydrazide-Hydrazones.
Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compound
CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model
Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs
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