The synthesis of poly(isobutylene-b-s-caprolactone) diblock and poly(s-caprolactone-b-isobutylene-b-s-caprolactone) triblock copolymers was accomplished using a combination of living carbocationic ...polymerization of isobutylene (IB) with the ring-opening polymerization (ROP) of s-caprolactone (s-CL). OH-PIB-allyl was prepared by living carbocationic polymerization of IB initiated with 1,2-propylene oxide/TiCl4 followed by termination with allyltrimethylsilane. Hydroxyl telechelic HO-PIB-OH was obtained by living IB polymerization initiated by 2,4,4,6-tetramethyl-heptane-2,6diol/TiCl4, termination with allyltrimethylsilane and subsequent thiol-ene click reaction with mercaptoethanol. The structure of the hydroxyl PIBs was confirmed by 'H NMR (proton Nuclear Magnetic Resonance spectroscopy). OH-PIB-allyl and HO-PIB-OH were then successfully used as macroinitiators for the polymerization of s-CL catalyzed by Candida antarctica Lipase B (CALB), yielding poly(s-caprolactone-b-isobutylene) diblock and poly(s-caprolactone-b-isobutylene-b-s-caprolactone) triblock copolymers, respectively. Differential Scanning Calorimetry (DSC), Transition Electron Microscopy (TEM) and Atomic Force Microscopy (AFM) demonstrated that the amorphous PIB and the semicrystalline PCL block segments phase separated, creating nanostructured phase morphology.
Targeting drug delivery to invasive glioma cells is a particularly difficult challenge because these cells lie behind an intact blood-brain barrier (BBB) that can be observed using multimodality ...imaging. BBB-associated efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) influence drug distribution to these cells and may negatively impact efficacy. To test the hypothesis that efflux transporters influence brain pharmacokinetics/pharmacodynamics of molecularly targeted agents in glioma treatment, we assessed region-specific penetrance and molecular-targeting capacity for a PI3K/mTOR kinase inhibitor that has high substrate affinity for efflux transporters (GDC-0980) and an analog (GNE-317) that was purposely designed to have reduced efflux.
Brain tumor penetrance of GDC-0980 and GNE-317 was compared between FVB/n wild-type mice and Mdr1a/b(-/-)Bcrp(-/-) triple-knockout mice lacking P-gp and BCRP. C57B6/J mice bearing intracranial GL261 tumors were treated with GDC-0980, GNE-317, or vehicle to assess the targeted pharmacokinetic/pharmacodynamic effects in a glioblastoma model.
Animals treated with GNE-317 demonstrated 3-fold greater penetrance in tumor core, rim, and normal brain compared with animals dosed with GDC-0980. Increased brain penetrance correlated with decreased staining of activated p-Akt, p-S6, and p-4EBP1 effector proteins downstream of PI3K and mTOR.
GDC-0980 is subject to active efflux by P-gp and BCRP at the BBB, while brain penetrance of GNE-317 is independent of efflux, which translates into enhanced inhibition of PI3K/mTOR signaling. These data show that BBB efflux by P-gp and BCRP is therefore an important determinant in both brain penetrance and molecular targeting efficacy in the treatment of invasive glioma cells.
Objective. The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and ...physical activity strategies: a standard behavioral group intervention, the standard intervention supplemented with spiritual strategies, or self-help strategies. Methods. Women were screened at baseline and after one year of participation. The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering. Because spiritual strategies were added to the standard intervention by participants themselves, the results from both active groups were similar and, thus, combined for comparisons with the self-help group. Results. A total of 529 women from 16 churches enrolled. Intervention participants exhibited significant improvements in body weight (-1.1 lbs), waist circumference (-0.66 inches), systolic blood pressure (-1.6 mmHg), dietary energy (-117 kcal), dietary total fat (-8 g), and sodium intake (-145 mg). The self-help group did not. In the active intervention group, women in the top decile for weight loss at one year had even larger, clinically meaningful changes in risk outcomes (-19.8 lbs). Conclusions. Intervention participants achieved clinically important improvements in cardiovascular disease risk profiles one year after program initiation, which did not occur in the self-help group. Church-based interventions can significantly benefit the cardiovascular health of African American women.
Adhesion and the ability to form filaments are thought to contribute to the pathogenicity of Candida albicans, the leading cause of fungal disease in immunocompromised patients. Int1p is a C. ...albicans surface protein with limited similarity to vertebrate integrins. INT1 expression in Saccharomyces cerevisiae was sufficient to direct the adhesion of this normally nonadherent yeast to human epithelial cells. Furthermore, disruption of INT1 in C. albicans suppressed hyphal growth, adhesion to epithelial cells, and virulence in mice. Thus, INT1 links adhesion, filamentous growth, and pathogenicity in C. albicans and Int1p may be an attractive target for the development of antifungal therapies.
Astrochemistry is the discipline that studies physico-chemical processes in astrophysical environments. Such environments are characterized by conditions that are substantially different from those ...existing in usual chemical laboratories. Models which aim to explain the formation of molecular species in interstellar environments must take into account various factors, including many that are directly, or indirectly related to the populations of massive stars in galaxies. The aim of this paper is to review the influence of massive stars, whatever their evolution stage, on the physico-chemical processes at work in interstellar environments. These influences include the ultraviolet radiation field, the production of high energy particles, the synthesis of radionuclides and the formation of shocks that permeate the interstellar medium.
Abstract Aims Exercise training (ET) has been variably associated with body composition changes among persons with type 2 diabetes (T2DM). The degree to which these changes are related to ...hyperglycemia remains unclear. Our objective was to investigate the relationship of baseline fasting glucose (FG) to the magnitude of muscle gains and fat loss after ET in individuals with T2DM. Methods Participants were enrolled in the SHAPE-2 trial, a six month supervised aerobic and resistance training intervention (three days/week), at Johns Hopkins. This was a post-hoc single arm intervention study of participants who completed the exercise intervention (n=50). Participants were aged 40-65 years and had T2DM that was not treated with insulin. Body composition was assessed by DEXA. Results After 6 months of ET, total fat mass decreased (-2.1 ± 3.1 kg) and total lean body mass (LBM) increased (0.5 ± 2.0 kg) overall, but there was variability among individual participants. There was an increase in% total LBM (1.4 ± 1.9%) and decrease in% total body fat mass (-1.5±2.0%) after ET; group changes were non-significant. Interestingly, each standard deviation (SD) increase in baseline FG (mean=135.5 mg/dl; SD= 39.0 mg/dl) was related to a significant increase in% total LBM (0.54±0.26%, p=0.048) and decrease in% total body fat (-0.57±0.27%, p=0.04) after ET among individual participants. Conclusions Our data demonstrate that muscle gains and fat loss after ET are positively related to baseline hyperglycemia. Further studies are needed to characterize differences in metabolic response following ET among persons with diabetes.
According to Christopher Freeburg, this field has become too comfortable advancing theories that render the slave a knowable, predictable figure. According to Elkins, the enslaved person was ...completely absorbed into the racial stereotype of the Sambo, bereft of any mental or physical independence from the master's will. Chapter 2, "Kaleidoscope Views," explores the ambivalence that undergirds representations of enslaved life, beginning with Frederick Douglass's contradictory descriptions of Sandy's root across his autobiographies. Since Douglass's refusal of the physical root could be read as a denial of his metaphorical African roots, Douglass's decision to withhold his true feelings suggests that "his interior is his to express or withhold" (47) and is not reducible to his social position or his abolitionist conviction. ...Freeburg appraises the art of Radcliffe Bailey for signs of counterlife, and concludes that Bailey's "litany of colors, materials, fact, and memory asks us to confront slavery in a vulnerable position that unwinds and diminishes and edifies at the same time" (63).
Aims
A family history of premature coronary artery disease (CAD) in an apparently healthy individual conveys an increased risk of future CAD. The extent to which inducible myocardial ischaemia exists ...and is associated with long-term incident CAD in apparently healthy siblings of early-onset CAD patients is unknown.
Methods and results
Asymptomatic siblings (n = 1287, aged 30-59 years) of patients with onset of CAD <60 years of age underwent risk factor screening and maximal graded treadmill testing with nuclear perfusion imaging, and were followed for incident CAD events for up to 25 years. Incident CAD occurred in 15.2% of siblings (68% acute coronary syndromes); mean time to first CAD event was 8.2 ± 5.2 years. Inducible ischaemia was highly prevalent in male siblings (26.9%), and was independently associated with incident CAD. Male siblings ≥40 years of age who were low or intermediate risk by traditional risk assessment, had a prevalence of inducible ischaemia and a 10-year risk of incident CAD that were near or ≥20%. In female siblings ≥40 years of age, the presence of inducible ischaemia was also independently associated with incident CAD, but the prevalence of inducible ischaemia was markedly lower, as was the risk of incident CAD.
Conclusion
Inducible ischaemia is highly prevalent in male siblings, suggesting a previously unknown long quiescent period before the occurrence of a clinical event. While inducible ischaemia is associated with a worse prognosis, male siblings with negative tests still bear a high risk of incident disease, such that we propose that in male siblings over 40 years of age, aggressive primary prevention interventions be instituted without nuclear testing. For women, the prevalence of ischaemia was so low as to not warrant screening, but the incidence of CAD was high enough to at least warrant lifestyle interventions.
Severe working conditions, the cost reduction need and production growth justify the adoption of technological techniques in agricultural production. Currently, Global Navigation Satellite System ...(GNSS) based navigation systems are very popular in agriculture. However, relying only on GNSS data and the availability of crop maps that also need to be updated may become a problem. One may face lack of GNSS satellite signal during the path and the navigation system may fail. As an alternative, this paper presents the modeling, development and validation of a reactive navigation system for agricultural fields based on a frontal light detection and ranging (LiDAR) sensor and a H∞ robust controller. A small-scale mobile robot (Helvis3) was used to validate the controllers and carry out experiments in both controlled and farm scenarios. According to the experimental results, the proposed navigation system is capable of controlling the robot displacement between crop rows, keeping it in the middle of the corresponding path with minimum error, despite environmental disturbances.
PDF
