The International Research and Educational Programs of Clark Atlanta University's Center for Functional Nanoscale Materials

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Flashlights: Properties of Highly Magnified Images Near Cluster Critical Curves in the Presence of Dark Matter Subhalos

Dark matter subhalos with extended profiles and density cores, and globular stars clusters of mass $10^6-10^8 M_\odot$, that live near the critical curves in galaxy cluster lenses can potentially be detected through their lensing magnification of stars in background galaxies. In this work we study the effect such subhalos have on lensed images, and compare to the case of more well studied microlensing by stars and black holes near critical curves. We find that the cluster density gradient and the extended mass distribution of subhalos are important in determining image properties. Both lead to an asymmetry between the image properties on the positive and negative parity sides of the cluster that is more pronounced than in the case of microlensing. For example, on the negative parity side, subhalos with cores larger than about $50\,$pc do not generate any images with magnification above $\sim 100$ outside of the immediate vicinity of the cluster critical curve. We discuss these factors using analytical and numerical analysis, and exploit them to identify observable signatures of subhalos: subhalos create pixel-to-pixel flux variations of $\gtrsim 0.1$ magnitudes, on the positive parity side of clusters. These pixels tend to cluster around (otherwise invisible) subhalos. Unlike in the case of microlensing, signatures of subhalo lensing can be found up to $1''$ away from the critical curves of massive clusters.Comment: ApJ, submitted, 21 pages, 17 figure

Rapidly Measured Indicators of Recreational Water Quality Are Predictive of Swimming-Associated Gastrointestinal Illness

Standard methods to measure recreational water quality require at least 24 hr to obtain results, making it impossible to assess the quality of water within a single day. Methods to measure recreational water quality in ≤ 2 hr have been developed. Application of rapid methods could give considerably more accurate and timely assessments of recreational water quality. We conducted a prospective study of beachgoers at two Great Lakes beaches to examine the association between recreational water quality, obtained using rapid methods, and gastrointestinal (GI) illness after swimming. Beachgoers were asked about swimming and other beach activities and 10–12 days later were asked about the occurrence of GI symptoms. We tested water samples for Enterococcus and Bacteroides species using the quantitative polymerase chain reaction (PCR) method. We observed significant trends between increased GI illness and Enterococcus at the Lake Michigan beach and a positive trend for Enterococcus at the Lake Erie beach. The association remained significant for Enterococcus when the two beaches were combined. We observed a positive trend for Bacteroides at the Lake Erie beach, but no trend was observed at the Lake Michigan beach. Enterococcus samples collected at 0800 hr were predictive of GI illness that day. The association between Enterococcus and illness strengthened as time spent swimming in the water increased. This is the first study to show that water quality measured by rapid methods can predict swimming-associated health effects

Novel Inhibitors of E. coli RecA ATPase Activity

The bacterial RecA protein has been implicated as a bacterial drug target not as an antimicrobial target, but as an adjuvant target with the potential to suppress the mechanism by which bacteria gain drug resistance. In order to identify small molecules that inhibit RecA/ssDNA nucleoprotein filament formation, we have adapted the phosphomolybdate-blue ATPase assay for high throughput screening to determine RecA ATPase activity against a library of 33,600 compounds, which is a selected representation of diverse structure of 350,000. Four distinct chemotypes were represented among the 40 validated hits. SAR and further chemical synthesis is underway to optimize this set of inhibitors to be used as antimicrobial adjuvant agents

Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse

MEKK2 mediates aberrant ERK activation in neurofibromatosis type I

Neurofibromatosis type I (NF1) is characterized by prominent skeletal manifestations caused by NF1 loss. While inhibitors of the ERK activating kinases MEK1/2 are promising as a means to treat NF1, the broad blockade of the ERK pathway produced by this strategy is potentially associated with therapy limiting toxicities. Here, we have sought targets offering a more narrow inhibition of ERK activation downstream of NF1 loss in the skeleton, finding that MEKK2 is a novel component of a noncanonical ERK pathway in osteoblasts that mediates aberrant ERK activation after NF1 loss. Accordingly, despite mice with conditional deletion of Nf1 in mature osteoblasts (Nf1(fl/fl);Dmp1-Cre) and Mekk2(-/-) each displaying skeletal defects, Nf1(fl/fl);Mekk2(-/-);Dmp1-Cre mice show an amelioration of NF1-associated phenotypes. We also provide proof-of-principle that FDA-approved inhibitors with activity against MEKK2 can ameliorate NF1 skeletal pathology. Thus, MEKK2 functions as a MAP3K in the ERK pathway in osteoblasts, offering a potential new therapeutic strategy for the treatment of NF1

Flashlights: An Off-Caustic Lensed Star at Redshift zz = 1.26 in Abell 370

We report the discovery of a transient seen in a strongly lensed arc at redshift $z_{\rm s}=1.2567$ in \emph{Hubble Space Telescope} imaging of the Abell 370 galaxy cluster. The transient is detected at $29.51\pm0.14$ AB mag in a WFC3/UVIS F200LP difference image made using observations from two different epochs, obtained in the framework of the \emph{Flashlights} program, and is also visible in the F350LP band ($m_{\rm F350LP}\sim30.53$ AB). The transient is observed on the negative-parity side of the critical curve at a distance of $\sim 0.6''$ from it, greater than previous examples of lensed stars. The large distance from the critical curve yields a significantly smaller macro-magnification, but our simulations show that bright, O/B-type supergiants can reach sufficiently high magnifications to be seen at the observed position and magnitude. In addition, the observed transient image is a trailing image with an observer-frame time delay of $\sim+0.8$ days from its expected counterpart, so that any transient lasting for longer than that should have also been seen on the minima side and is thus excluded. This, together with the blue color we measure for the transient ($m_{\rm F200LP} - m_{\rm F350LP} \sim [-0.7,-1]$ AB mag), rules out most other transient candidates such as (kilo)novae, for example, and makes a lensed star the prime candidate. Assuming the transient is indeed a lensed star as suggested, many more such events should be detected in the near future in cluster surveys with the \emph{Hubble Space Telescope} and \emph{James Webb Space Telescope}.Comment: 11 pages. 5 figures. Comments are welcom

Flashlights: More than A Dozen High-Significance Microlensing Events of Extremely Magnified Stars in Galaxies at Redshifts z=0.7-1.5

Once only accessible in nearby galaxies, we can now study individual stars across much of the observable universe aided by galaxy-cluster gravitational lenses. When a star, compact object, or multiple such objects in the foreground galaxy-cluster lens become aligned, they can magnify a background individual star, and the timescale of a magnification peak can limit its size to tens of AU. The number and frequency of microlensing events therefore opens a window into the population of stars and compact objects, as well as high-redshift stars. To assemble the first statistical sample of stars in order to constrain the initial mass function (IMF) of massive stars at redshift z=0.7-1.5, the abundance of primordial black holes in galaxy-cluster dark matter, and the IMF of the stars making up the intracluster light, we are carrying out a 192-orbit program with the Hubble Space Telescope called "Flashlights," which is now two-thirds complete owing to scheduling challenges. We use the ultrawide F200LP and F350LP long-pass WFC3 UVIS filters and conduct two 16-orbit visits separated by one year. Having an identical roll angle during both visits, while difficult to schedule, yields extremely clean subtraction. Here we report the discovery of more than a dozen bright microlensing events, including multiple examples in the famous "Dragon Arc" discovered in the 1980s, as well as the "Spocks" and "Warhol" arcs that have hosted already known supergiants. The ultradeep observer-frame ultraviolet-through-optical imaging is sensitive to hot stars, which will complement deep James Webb Space Telescope infrared imaging. We are also acquiring Large Binocular Telescope LUCI and Keck-I MOSFIRE near-infrared spectra of the highly magnified arcs to constrain their recent star-formation histories

Puromycin-sensitive aminopeptidase protects against aggregation-prone proteins via autophagy

A major function of proteasomes and macroautophagy is to eliminate misfolded potentially toxic proteins. Mammalian proteasomes, however, cannot cleave polyglutamine (polyQ) sequences and seem to release polyQ-rich peptides. Puromycin-sensitive aminopeptidase (PSA) is the only cytosolic enzyme able to digest polyQ sequences. We tested whether PSA can protect against accumulation of polyQ fragments. In cultured cells, Drosophila and mouse muscles, PSA inhibition or knockdown increased aggregate content and toxicity of polyQ-expanded huntingtin exon 1. Conversely, PSA overexpression decreased aggregate content and toxicity. PSA inhibition also increased the levels of polyQ-expanded ataxin-3 as well as mutant α-synuclein and superoxide dismutase 1. These protective effects result from an unexpected ability of PSA to enhance macroautophagy. PSA overexpression increased, and PSA knockdown or inhibition reduced microtubule-associated protein 1 light chain 3-II (LC3-II) levels and the amount of protein degradation sensitive to inhibitors of lysosomal function and autophagy. Thus, by promoting autophagic protein clearance, PSA helps protect against accumulation of aggregation-prone proteins and proteotoxicity