1,087 research outputs found

    One-electron states and interband optical absorption in single-wall carbon nanotubes

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    Explicit expressions for the wave functions and dispersion equation for the band p - electrons in single-wall carbon nanotubes are obtained within the method of zero-range potentials. They are then used to investigate the absorption spectrum of polarized light caused by direct interband transitions in isolated nanotubes. It is shown that, at least, under the above approximations, the circular dichroism is absent in chiral nanotubes for the light wave propagating along the tube axis. The results obtained are compared with those calculated in a similar way for a graphite plane.Comment: 16 pages, 8 figures, 1 tabl

    The glucose transporter PfHT1 is an antimalarial target of the HIV protease inhibitor lopinavir

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    Malaria and HIV infection are coendemic in a large portion of the world and remain a major cause of morbidity and mortality. Growing resistance of Plasmodium species to existing therapies has increased the need for new therapeutic approaches. The Plasmodium glucose transporter PfHT is known to be essential for parasite growth and survival. We have previously shown that HIV protease inhibitors (PIs) act as antagonists of mammalian glucose transporters. While the PI lopinavir is known to have antimalarial activity, the mechanism of action is unknown. We report here that lopinavir blocks glucose uptake into isolated malaria parasites at therapeutically relevant drug levels. Malaria parasites depend on a constant supply of glucose as their primary source of energy, and decreasing the available concentration of glucose leads to parasite death. We identified the malarial glucose transporter PfHT as a target for inhibition by lopinavir that leads to parasite death. This discovery provides a mechanistic basis for the antimalarial effect of lopinavir and provides a direct target for novel drug design with utility beyond the HIV-infected population

    A novel FRET-based screen in high-throughput format to identify inhibitors of malarial and human glucose transporters

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    The glucose transporter PfHT is essential to the survival of the malaria parasite Plasmodium falciparum and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose sensor. This allows assessment of the ability of small molecules to inhibit glucose uptake with high accuracy (Z′ factor of >0.8), thereby eliminating the need for radiolabeled substrates. Furthermore, we have adapted this assay to counterscreen PfHT hits against the human orthologues GLUT1, -2, -3, and -4. We report the identification of several hits after screening the Medicines for Malaria Venture (MMV) Malaria Box, a library of 400 compounds known to inhibit erythrocytic development of P. falciparum. Hit compounds were characterized by determining the half-maximal inhibitory concentration (IC(50)) for the uptake of radiolabeled glucose into isolated P. falciparum parasites. One of our hits, compound MMV009085, shows high potency and orthologue selectivity, thereby successfully validating our assay for antimalarial screening

    A life story in three parts: the use of triptychs to make sense of personal digital data

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    Many social media platforms support the curation of personal digital data, and, more recently, the use of that data for review and reflection. We explored the process of reflection by asking users to create a meaningful ‘triptych’ of photographs drawn from their Facebook accounts. In a first study, we asked participants to manually trawl their own accounts and select three relevant images, which we then framed and used as an interview probe. In a second study, we designed an automated triptych generation system and assessed participants’ experiences of using this system. We conducted qualitative analyses of participant interviews from both studies. Consistent with other ‘slow technology’ work, we found the act of creating a physical artefact from social media data gave that data new meaning, albeit with notable differences between manual vs automatically generated triptychs. We conclude by discussing possible improvements to the design of the automated triptych system

    MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

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    AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

    Demonstrable Evidence of Beneficial Physical Outcomes from University Physical Education Activity Courses

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    Introduction: Engagement in physical activity (PA) is often dramatically reduced during the transition from high school into college. There appears to be more stability in PA patterns during the transition from college into post-graduate life. Consequently, researchers have highlighted the years in higher education as pivotal for shaping lasting PA habits. Sadly, there is a widespread lack of evidence regarding the outcomes from physical education activity courses (PEAC) offered on campuses of higher education. Thus, their overall value lacks validation. The purpose of this work was to offer evidence of outcomes from engagement in a single, semester-long university PEAC class. Methods: Students were recruited from a variety of classes. There were no directions provided to the instructors of the courses. For grouping, classes were categorized as aerobic- (aerobics, jogging, and walking) or sport-activity (badminton, pickle ball, self-defense, strength training, and ultimate frisbee). Students in the aerobic-activity arm were randomized to aerobic testing where they underwent a submaximal treadmill protocol and grip strength (GS) testing or body composition testing (air displacement plethysmography) and GS. Those in the sport-activity arm underwent vertical jump and GS testing. Students reported to the human performance lab in the first two and final two weeks of the semester. Paired t-tests were conducted to identify differences in pre-post outcomes. Values were carried forward, not dropped, when a subject failed to return at post-test. Results: A total of 46 students (age = 21.7 ± 4.1) were randomized into the aerobic (n=25; m/f = 11/14) or body composition arms (n=21; m/f = 7/14). Additionally, 45 students (age = 20.8 ± 3.2; m/f = 23/22) from sport-activity classes were enrolled. Participation in aerobic-activity classes resulted in improvements in estimated maximal aerobic ability (p = 0.030; 42.9 ± 9.9 vs. 44.6 ± 10.1). Participation also resulted in increases in GS for those allocated to both the aerobic (p = 0.010; 56.4 ± 21.5 vs. 60.3 ± 22.3) and body composition (p = 0.022; 54.1 ± 22.1 vs. 58.1 ± 24.6) arms. Participation did not result in changes in body composition (p = 0.817; 24.7 ± 8.5 vs. 24.6 ± 7.4) despite a near-significant increase in weight (p = 0.057; 152.7 ± 38.5 vs. 154.5 ± 37.7). Participation in sport-activity classes resulted in an improvement in vertical jump (p = 0.007; 18.2 ± 6.1 vs. 18.9 ± 6.0) and GS (p = 0.002; 65.3 ± 25.6 vs. 70.0 ± 27.8). Discussion: An important first step in rebutting challenges about the credibility and worthiness of PEAC offerings is evidencing beneficial outcomes. These results represent simple, but important, markers of change. Additional demonstrable evidence is needed to ascertain elements such as what outcomes are achievable, what classes are most effective classes, and what components from class support lasting change

    Survey Responses From “Wellness for Life” Classes: Overall Value and Barriers, Motivators, and Motives Towards Physical Activity

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    Introduction: Skill-based sport activity classes were the historical trend, but greater numbers of higher education institutions now offer courses that encompass “wellness for life” concepts. The goal of these offerings is to guide students in the development of knowledge, skills, and behaviors to adopt and maintain healthful behaviors. There is a need to amass evidence of the outcomes arising from engagement in these classes. Purpose: The purpose of this work was to document outcomes from participation in a single, semester-long, university wellness for life class. Methods: Students were recruited from courses at two universities. Survey responses were collected in the first two and final two weeks of class. The survey items included identification of: engagement in regular physical activity (PA), perceptions about PA (“view of self as an exerciser”, “contentment with current PA level”, among others), and barriers, motivators, and motives towards PA. There were no intervention suggestions provided to instructors. Results: A total of 173 students (m/f/not identified = 51/118/4; age 19.6 ± 1.4) participated. When questioned, many students identified as being an “exerciser.” Some perceived “no need to change their program” (n=37) but most “wanted more regular exercise” (n=88). A lesser number of students identified as being a “non-exerciser.” Most all “wanted more regular exercise” (n=46), but two had “no desire to start a program.” At post-test, the respective numbers were: 37, 95, 41, and 3. Numbers did not always align due to incomplete survey responses. The perceived value of the class to current and future health, rated on a scale from 0 (no impact)-100 (most influential), improved pre-post class (p \u3c 0.001) from 61.7 (±24.5) to 67.8 (±23.5). The top barrier, motivator, and motive at pre-test were: “I need to do better at managing my time to exercise more often,” “If I better organized my time or schedule I could exercise more,” and “I get pleasure or enjoy sports so I exercise,” respectively. There was shuffling among the top choices from pre- to post-test, but the top barrier remained the same. The top motivator became, “If I had more time I would exercise more,” and the top motive became, “I feel less stress after I exercise.” Discussion: Evidenced by the pre-post responses, students feel that wellness for life classes have some benefit and that perception improves after experiencing the class. There appears to be consistency in those who view themselves as “exercisers” and “non-exercisers,” which might represent a precarious situation. There is constancy in the primary barrier to exercise – the socially acceptable answer – time. It is obvious that time management is a critical element for inclusion in these classes. Students may also benefit more if instructors would offer insight on the use of motivators and motives in overcoming personal barriers
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