3,576 research outputs found
Learning While Black: A Qualitative Analysis of the Impact of Race in a U.S. High School
One of the major contributing factors to the Black-White achievement gap is school context. While many factors can affect academic achievement amongst Black youth, school climate and inter-racial relations are among the root causes which impact Black students’ development. In this qualitative study, we conducted secondary analysis of existing data consisting of interview transcripts and focus group discussions held in 2013 with 21 Black students who attended a public charter high school in Michigan. Open access data were downloaded from the University of Michigan Inter-University Consortium for Political and Social Research (ICPSR) database. We analyzed qualitative data for themes and constructs related to school context and such influences on Black youth development. The following three constructs were identified: racial identity of Black youth, the impact of teachers on Black students’ racial identity and development, and lastly, exploring the dominant culture of the U.S. education system. For researchers, this data highlights a need for more studies on the intersection of race, school environment, and youth development. For administrators and policy makers, the results emphasize the need for investment and engagement in the daily experiences of Black students, reducing racism, and increasing diversity of curriculum. Teachers and school administrators may benefit from specialized training to better address cultural, educational, and developmental needs of Black youth in the context of their role in school
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Inhibition of Sec61-dependent translocation by mycolactone uncouples the integrated stress response from ER stress, driving cytotoxicity via translational activation of ATF4
Mycolactone is the exotoxin virulence factor of Mycobacterium ulcerans that causes the neglected tropical disease Buruli ulcer. We recently showed it to be a broad spectrum inhibitor of Sec61-dependent co-translational translocation of proteins into the endoplasmic reticulum (ER). An outstanding question is the molecular pathway linking this to its known cytotoxicity. We have now used translational profiling to better understand the reprogramming that occurs in cells exposed to mycolactone. Gene ontology identified enrichment in genes involved in cellular response to stress, and apoptosis signalling among those showing enhanced translation. Validation of these results supports a mechanism by which mycolactone activates an integrated stress response meditated by phosphorylation of eIF2α via multiple kinases (PERK, GCN, PKR) without activation of the ER stress sensors IRE1 or ATF6. The response therefore uncouples the integrated stress response from ER stress, and features translational and transcriptional modes of genes expression that feature the key regulatory transcription factor ATF4. Emphasising the importance of this uncoupled response in cytotoxicity, downstream activation of this pathway is abolished in cells expressing mycolactone-resistant Sec61α variants. Using multiple genetic and biochemical approaches, we demonstrate that eIF2α phosphorylation is responsible for mycolactone-dependent translation attenuation, which initially protects cells from cell death. However, chronic activation without stress remediation enhances autophagy and apoptosis of cells by a pathway facilitated by ATF4 and CHOP. Our findings demonstrate that priming events at the ER can result in the sensing of stress within different cellular compartmentsWellcome Trus
Evaluating 5-nitrofurans as trypanocidal agents
The nitroheterocycle nifurtimox, as part of a nifurtimox-eflornithine combination therapy, represents one of a limited number of treatments targeting Trypanosoma brucei, the causative agent of human African trypanosomiasis. The mode of action of this prodrug involves an initial activation reaction catalysed by a type I nitroreductase (NTR), an enzyme found predominantly in prokaryotes, leading to the formation of a cytotoxic unsaturated open chain nitrile metabolite. Here, we evaluate the trypanocidal activity of a library of other 5-nitrofurans against bloodstream form T. brucei as a preliminary step in the identification of additional nitroaromatic compounds that could potentially partner eflornithine. Biochemical screening against purified enzyme revealed that all 5-nitrofurans were effective substrates for TbNTR with the preferred compounds having apparent kcat/KM values approximately 50-fold greater than nifurtimox. For several compounds, in vitro reduction by this nitroreductase yielded products characterized by mass spectroscopy as either unsaturated or saturated open chain nitriles. When tested against bloodstream form T. brucei, many of the derivatives displayed significant growth inhibitory properties with the most potent compounds generating IC50 values around 200 nM. The anti-parasitic activity of the most potent agents was demonstrated to be NTR dependent as parasites having reduced levels of the enzyme displayed resistance to the compounds while parasites over expressing TbNTR showed hypersensitivity. We conclude that other members of the 5-nitrofurans class of nitroheterocycles have potential to treat human African trypanosomiasis perhaps as an alternative partner prodrug to nifurtimox in the next generation of eflornithine-based combinational therapies
Coherent Moving States in Highway Traffic (Originally: Moving Like a Solid Block)
Recent advances in multiagent simulations have made possible the study of
realistic traffic patterns and allow to test theories based on driver
behaviour. Such simulations also display various empirical features of traffic
flows, and are used to design traffic controls that maximise the throughput of
vehicles in heavily transited highways. In addition to its intrinsic economic
value, vehicular traffic is of interest because it may throw light on some
social phenomena where diverse individuals competitively try to maximise their
own utilities under certain constraints.
In this paper, we present simulation results that point to the existence of
cooperative, coherent states arising from competitive interactions that lead to
a new phenomenon in heterogeneous highway traffic. As the density of vehicles
increases, their interactions cause a transition into a highly correlated state
in which all vehicles practically move with the same speed, analogous to the
motion of a solid block. This state is associated with a reduced lane changing
rate and a safe, high and stable flow. It disappears as the vehicle density
exceeds a critical value. The effect is observed in recent evaluations of Dutch
traffic data.Comment: Submitted on April 21, 1998. For related work see
http://www.theo2.physik.uni-stuttgart.de/helbing.html and
http://www.parc.xerox.com/dynamics
Chronology protection in stationary three-dimensional spacetimes
We study chronology protection in stationary, rotationally symmetric
spacetimes in 2+1 dimensional gravity, focusing especially on the case of
negative cosmological constant. We show that in such spacetimes closed timelike
curves must either exist all the way to the boundary or, alternatively, the
matter stress tensor must violate the null energy condition in the bulk. We
also show that the matter in the closed timelike curve region gives a negative
contribution to the conformal weight from the point of view of the dual
conformal field theory. We illustrate these properties in a class of examples
involving rotating dust in anti-de Sitter space, and comment on the use of the
AdS/CFT correspondence to study chronology protection.Comment: 20 pages. V2: minor corrections, Outlook expanded, references added,
published versio
Bell Correlations and the Common Future
Reichenbach's principle states that in a causal structure, correlations of
classical information can stem from a common cause in the common past or a
direct influence from one of the events in correlation to the other. The
difficulty of explaining Bell correlations through a mechanism in that spirit
can be read as questioning either the principle or even its basis: causality.
In the former case, the principle can be replaced by its quantum version,
accepting as a common cause an entangled state, leaving the phenomenon as
mysterious as ever on the classical level (on which, after all, it occurs). If,
more radically, the causal structure is questioned in principle, closed
space-time curves may become possible that, as is argued in the present note,
can give rise to non-local correlations if to-be-correlated pieces of classical
information meet in the common future --- which they need to if the correlation
is to be detected in the first place. The result is a view resembling Brassard
and Raymond-Robichaud's parallel-lives variant of Hermann's and Everett's
relative-state formalism, avoiding "multiple realities."Comment: 8 pages, 5 figure
HIV Transmission Rates in the United States, 2006-2008
National HIV incidence for a given year x [I(x)] equals prevalence [P(x)] times the transmission rate [T(x)]. Or, simply rearranging the terms, T(x) = [I(x)/P(x)]*100 (where T(x) is the number of HIV transmissions per 100 persons living with HIV in a given year). The transmission rate is an underutilized measure of the speed at which the epidemic is spreading. Here, we utilize recently updated information about HIV incidence and prevalence in the U.S. to estimate the national HIV transmission rate for 2006 through 2008, and present a novel method to express the level of uncertainty in these estimates. Transmission rate estimates for 2006 through 2008 are as follows (respectively): 4.39 (4.01 to 4.73); 4.90 (4.49 to 5.28); and 4.06 (3.70 to 4.38). Although there are methodological challenges inherent in making these estimates, they do give some indications that the U.S. HIV transmission rate is at a historically low level
Bodily relations and reciprocity in the art of Sonia Khurana
This article explores the significance of the ‘somatic’ and ‘ontological turn’ in locating the radical politics articulated in the contemporary performance, installation, video and digital art practices of New Delhi-based artist, Sonia Khurana (b. 1968). Since the late 1990s Khurana has fashioned a range of artworks that require new sorts of reciprocal and embodied relations with their viewers. While this line of art practice suggests the need for a primarily philosophical mode of inquiry into an art of the body, such affective relations need to be historicised also in relation to a discursive field of ‘difference’ and public expectations about the artist’s ethnic, gendered and national identity. Thus, this intimate, visceral and emotional field of inter- and intra-action is a novel contribution to recent transdisciplinary perspectives on the gendered, social and sentient body, that in turn prompts a wider debate on the ethics of cultural commentary and art historiography
Estimated HIV Incidence in the United States, 2006–2009
Background
The estimated number of new HIV infections in the United States reflects the leading edge of the epidemic. Previously, CDC estimated HIV incidence in the United States in 2006 as 56,300 (95% CI: 48,200–64,500). We updated the 2006 estimate and calculated incidence for 2007–2009 using improved methodology.
Methodology
We estimated incidence using incidence surveillance data from 16 states and 2 cities and a modification of our previously described stratified extrapolation method based on a sample survey approach with multiple imputation, stratification, and extrapolation to account for missing data and heterogeneity of HIV testing behavior among population groups.
Principal Findings
Estimated HIV incidence among persons aged 13 years and older was 48,600 (95% CI: 42,400–54,700) in 2006, 56,000 (95% CI: 49,100–62,900) in 2007, 47,800 (95% CI: 41,800–53,800) in 2008 and 48,100 (95% CI: 42,200–54,000) in 2009. From 2006 to 2009 incidence did not change significantly overall or among specific race/ethnicity or risk groups. However, there was a 21% (95% CI:1.9%–39.8%; p = 0.017) increase in incidence for people aged 13–29 years, driven by a 34% (95% CI: 8.4%–60.4%) increase in young men who have sex with men (MSM). There was a 48% increase among young black/African American MSM (12.3%–83.0%; p<0.001). Among people aged 13–29, only MSM experienced significant increases in incidence, and among 13–29 year-old MSM, incidence increased significantly among young, black/African American MSM. In 2009, MSM accounted for 61% of new infections, heterosexual contact 27%, injection drug use (IDU) 9%, and MSM/IDU 3%.
Conclusions/Significance
Overall, HIV incidence in the United States was relatively stable 2006–2009; however, among young MSM, particularly black/African American MSM, incidence increased. HIV continues to be a major public health burden, disproportionately affecting several populations in the United States, especially MSM and racial and ethnic minorities. Expanded, improved, and targeted prevention is necessary to reduce HIV incidence
Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics
<b>Background</b><p></p>
The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.<p></p>
<b>Methodology/Principal findings</b><p></p>
Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.<p></p>
<b>Conclusions/significance</b><p></p>
Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi
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