A synthetic Escherichia coli predator–prey ecosystem

We have constructed a synthetic ecosystem consisting of two Escherichia coli populations, which communicate bi-directionally through quorum sensing and regulate each other's gene expression and survival via engineered gene circuits. Our synthetic ecosystem resembles canonical predator–prey systems in terms of logic and dynamics. The predator cells kill the prey by inducing expression of a killer protein in the prey, while the prey rescue the predators by eliciting expression of an antidote protein in the predator. Extinction, coexistence and oscillatory dynamics of the predator and prey populations are possible depending on the operating conditions as experimentally validated by long-term culturing of the system in microchemostats. A simple mathematical model is developed to capture these system dynamics. Coherent interplay between experiments and mathematical analysis enables exploration of the dynamics of interacting populations in a predictable manner

Antiretroviral therapy to prevent HIV acquisition in serodiscordant couples in a hyperendemic community in rural South Africa

Background. Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other. Methods. Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships. Results. We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3-5.6), 1.4/100 PY (.4-3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5-8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI,. 07-.80). Conclusions. ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this "real-life" effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed

MicroRNAs Associated with Caste Determination and Differentiation in a Primitively Eusocial Insect

In eusocial Hymenoptera (ants, bees and wasps), queen and worker adult castes typically arise via environmental influences. A fundamental challenge is to understand how a single genome can thereby produce alternative phenotypes. A powerful approach is to compare the molecular basis of caste determination and differentiation along the evolutionary trajectory between primitively and advanced eusocial species, which have, respectively, relatively undifferentiated and strongly differentiated adult castes. In the advanced eusocial honeybee, Apis mellifera, studies suggest that microRNAs (miRNAs) play an important role in the molecular basis of caste determination and differentiation. To investigate how miRNAs affect caste in eusocial evolution, we used deep sequencing and Northern blots to isolate caste-associated miRNAs in the primitively eusocial bumblebee Bombus terrestris. We found that the miRNAs Bte-miR-6001-5p and -3p are more highly expressed in queen- than in worker-destined late-instar larvae. These are the first caste-associated miRNAs from outside advanced eusocial Hymenoptera, so providing evidence for caste-associated miRNAs occurring relatively early in eusocial evolution. Moreover, we found little evidence that miRNAs previously shown to be associated with caste in A. mellifera were differentially expressed across caste pathways in B. terrestris, suggesting that, in eusocial evolution, the caste-associated role of individual miRNAs is not conserved

Integrated spatial multiplexing of heralded single photon sources

The non-deterministic nature of photon sources is a key limitation for single photon quantum processors. Spatial multiplexing overcomes this by enhancing the heralded single photon yield without enhancing the output noise. Here the intrinsic statistical limit of an individual source is surpassed by spatially multiplexing two monolithic silicon correlated photon pair sources, demonstrating a 62.4% increase in the heralded single photon output without an increase in unwanted multi-pair generation. We further demonstrate the scalability of this scheme by multiplexing photons generated in two waveguides pumped via an integrated coupler with a 63.1% increase in the heralded photon rate. This demonstration paves the way for a scalable architecture for multiplexing many photon sources in a compact integrated platform and achieving efficient two photon interference, required at the core of optical quantum computing and quantum communication protocols.Comment: 10 pages, 3 figures, comments welcom

20 GB in 10 minutes: a case for linking major biodiversity databases using an open socio-technical infrastructure and a pragmatic, cross-institutional collaboration

Biodiversity information is made available through numerous databases that each have their own data models, web services, and data types. Combining data across databases leads to new insights, but is not easy because each database uses its own system of identifiers. In the absence of stable and interoperable identifiers, databases are often linked using taxonomic names. This labor intensive, error prone, and lengthy process relies on accessible versions of nomenclatural authorities and fuzzy-matching algorithms. To approach the challenge of linking diverse data, more than technology is needed. New social collaborations like the Global Unified Open Data Architecture (GUODA) that combines skills from diverse groups of computer engineers from iDigBio, server resources from the Advanced Computing and Information Systems (ACIS) Lab, global-scale data presentation from EOL, and independent developers and researchers are what is needed to make concrete progress on finding relationships between biodiversity datasets. This paper will discuss a technical solution developed by the GUODA collaboration for faster linking across databases with a use case linking Wikidata and the Global Biotic Interactions database (GloBI). The GUODA infrastructure is a 12-node, high performance computing cluster made up of about 192 threads with 12 TB of storage and 288 GB memory. Using GUODA, 20 GB of compressed JSON from Wikidata was processed and linked to GloBI in about 10–11 min. Instead of comparing name strings or relying on a single identifier, Wikidata and GloBI were linked by comparing graphs of biodiversity identifiers external to each system. This method resulted in adding 119,957 Wikidata links in GloBI, an increase of 13.7% of all outgoing name links in GloBI. Wikidata and GloBI were compared to Open Tree of Life Reference Taxonomy to examine consistency and coverage. The process of parsing Wikidata, Open Tree of Life Reference Taxonomy and GloBI archives and calculating consistency metrics was done in minutes on the GUODA platform. As a model collaboration, GUODA has the potential to revolutionize biodiversity science by bringing diverse technically minded people together with high performance computing resources that are accessible from a laptop or desktop. However, participating in such a collaboration still requires basic programming skills

RS1 Cosmology as Brane Dynamics in an AdS/Schwarzschild Bulk

We explore various facets of the cosmology of the Randall-Sundrum scenario with two branes by considering the dynamics of the branes moving in a bulk AdS/Schwarzschild geometry. This approach allows us both to understand in more detail and from a different perspective the role of the stabilization of the hierarchy in the brane cosmology, as well as to extend to the situation where the metric contains a horizon. In particular, we explicitly determine how the Goldberger-Wise stabilization mechanism perturbs the background bulk geometry to produce a realistic cosmology.Comment: 9 pages, uses ReVTeX, no figure

Orbital Solutions and Absolute Elements of the Short-Period Eclipsing Binary ES Librae

We have obtained new differential UBV photoelectric photometry and radial velocities of both components of the short-period eclipsing binary ES Lib. The system has a circular orbit with a period of 0.883040928 days and is seen at an inclination of 70.1°. With the Wilson-Devinney analysis program, we obtained a simultaneous solution of our photometric and spectroscopic observations that resulted in masses of M1 = 2.30 ± 0.03 M⊙ and M2 = 0.97 ± 0.01 M⊙ and the equal-volume radii of R1 = 2.69 ± 0.02 R⊙ and R2 = 1.83 ± 0.01 R⊙ for the primary and secondary, respectively. The secondary is oversized and overluminous for its mass. The effective temperatures of the primary and secondary are 8500 K (fixed) and 5774 ± 57 K, respectively. Despite the very large temperature difference, our photometric and spectroscopic data indicate that ES Lib is not semidetached but rather require it to be in an overcontact state, where both components exceed their critical Roche lobes. Given its nonthermal equilibrium state, if the overcontact solution correctly characterizes the system, the change from being semidetached to overcontact may have occurred recently. While the asymmetry of the light curves can be modeled well with a large, hot starspot or a large, cool one on the secondary component, we prefer the latter interpretation because cool spots are a typical feature on many contact binaries

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus–specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity

Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat

INTRODUCTION: Of the more than one million global cases of breast cancer diagnosed each year, approximately fifteen percent are characterized as triple-negative, lacking the estrogen, progesterone, and Her2/neu receptors. Lack of effective therapies, younger age at onset, and early metastatic spread have contributed to the poor prognoses and outcomes associated with these malignancies. Here, we investigate the ability of the histone deacetylase inhibitor panobinostat (LBH589) to selectively target triple-negative breast cancer (TNBC) cell proliferation and survival in vitro and tumorigenesis in vivo. METHODS: TNBC cell lines MDA-MB-157, MDA-MB-231, MDA-MB-468, and BT-549 were treated with nanomolar (nM) quantities of panobinostat. Relevant histone acetylation was verified by flow cytometry and immunofluorescent imaging. Assays for trypan blue viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation, and DNA fragmentation were used to evaluate overall cellular toxicity. Changes in cell cycle progression were assessed with propidium iodide flow cytometry. Additionally, qPCR arrays were used to probe MDA-MB-231 cells for panobinostat-induced changes in cancer biomarkers and signaling pathways. Orthotopic MDA-MB-231 and BT-549 mouse xenograft models were used to assess the effects of panobinostat on tumorigenesis. Lastly, flow cytometry, ELISA, and immunohistochemical staining were applied to detect changes in cadherin-1, E-cadherin (CDH1) protein expression and the results paired with confocal microscopy in order to examine changes in cell morphology. RESULTS: Panobinostat treatment increased histone acetylation, decreased cell proliferation and survival, and blocked cell cycle progression at G2/M with a concurrent decrease in S phase in all TNBC cell lines. Treatment also resulted in apoptosis induction at 24 hours in all lines except the MDA-MB-468 cell line. MDA-MB-231 and BT-549 tumor formation was significantly inhibited by panobinostat (10 mg/kg/day) in mice. Additionally, panobinostat up-regulated CDH1 protein in vitro and in vivo and induced cell morphology changes in MDA-MB-231 cells consistent with reversal of the mesenchymal phenotype. CONCLUSIONS: This study revealed that panobinostat is overtly toxic to TNBC cells in vitro and decreases tumorigenesis in vivo. Additionally, treatment up-regulated anti-proliferative, tumor suppressor, and epithelial marker genes in MDA-MB-231 cells and initiated a partial reversal of the epithelial-to-mesenchymal transition. Our results demonstrate a potential therapeutic role of panobinostat in targeting aggressive triple-negative breast cancer cell types