Guadecitabine, in combination with Cyclophosphamide, promotes anti- cancer immunity in BALB/c mice bearing 4T1 mouse mammary carcinoma

Background: The extremely high mortality rate of patients diagnosed with triple negative breast cancer makes it one of the deadliest forms of cancer. Due to the heterogenous nature of tumors, complete clearance is not achieved and clonal selection occurs resulting in tumor cells evading the immune system. I aim to design a therapeutic intervention that is able to elicit an effective immune response against the tumor and instill immunological memory to eradicate primary and metastatic lesions. I hypothesize that the combination of Guad and Cyp will synergize and promote anticancer immunity via increased expression of neo-tumor antigens and depletion of MDSCs and T-regs. Methods: Guadecitabine (Guad), is a second-generation DNA methyltransferase inhibitor (DMNTi) that has been reported to increase antigenicity and deplete myeloid-derived suppressor cells (MDSC’s). Cyclophosphamide (Cyp) is a chemotherapy that has been shown to deplete regulatory T-cells (T-regs). Both MDSD’s and T-regs suppress antitumor immunity. BALB/c mice were challenged with 4T1 tumor cells subcutaneously in the mammary fat pad region. 4T1-bearing mice were administered low-dose Guad and Cyp for ten consecutive days. Tumor growth curves, tumor-infiltrating lymphocytes (TILs) were measured and MDSC’s and T- regs levels were assessed by flow cytometry. Results: Results from this experiment showed significant synergy between Guad and Cyp with both drugs reducing the tumor size over monotherapy. Conclusions: Further analysis of the data along with future experiments will elucidate if this synergy is driven by the depletion of MDSC’s and T-regs alone or the increase in tumor antigenicity inducing increased numbers of TILs.https://scholarscompass.vcu.edu/gradposters/1078/thumbnail.jp

Optical Gravitational Lensing Experiment. OGLE-1999-BUL-32: the Longest Ever Microlensing Event -- Evidence for a Stellar Mass Black Hole?

We describe the discovery of the longest microlensing event ever observed, OGLE-1999-BUL-32, also independently identified by the MACHO collaboration as MACHO-99-BLG-22. This unique event has an Einstein radius crossing time of 641 days. The high quality data obtained with difference image analysis shows a small but significant parallax signature. This parallax effect allows one to determine the Einstein radius projected onto the observer plane as rE^hat ~ 29.2AU. The transverse velocity projected onto the observer plane is about 79km/s. We argue that the lens is likely to be have a mass of at least a few solar masses, i.e., it could be a stellar black hole. The black hole hypothesis can be tested using the astrometric microlensing signature with the soon-to-be installed Advanced Camera for Surveys on board the Hubble Space Telescope. Deep X-ray and radio images may also be useful for revealing the nature of the object.Comment: submitted to Monthly Notice

Deliquescence, efflorescence, and phase miscibility of mixed particles of ammonium sulfate and isoprene-derived secondary organic material

The hygroscopic phase transitions of ammonium sulfate mixed with isoprene-derived secondary organic material were investigated in aerosol experiments. The organic material was produced by isoprene photo-oxidation at 40% and 60% relative humidity. The low volatility fraction of the photo-oxidation products condensed onto ammonium sulfate particles. The particle-phase organic material had oxygen-to-carbon ratios of 0.67 to 0.74 (±0.2) for mass concentrations of 20 to 30 μg m<sup>−3</sup>. The deliquescence, efflorescence, and phase miscibility of the mixed particles were investigated using a dual arm tandem differential mobility analyzer. The isoprene photo-oxidation products induced deviations in behavior relative to pure ammonium sulfate. Compared to an efflorescence relative humidity (ERH) of 30 to 35% for pure ammonium sulfate, efflorescence was eliminated for aqueous particles having organic volume fractions <i>ϵ</i> of 0.6 and greater. Compared to a deliquescence relative humidity (DRH) of 80% for pure ammonium sulfate, the DRH steadily decreased with increasing <i>ϵ</i>, approaching a DRH of 40% for <i>ϵ</i> of 0.9. Parameterizations of the DRH(<i>ϵ</i>) and ERH(<i>ϵ</i>) curves were as follows: DRH(<i>ϵ</i>)= ∑<sub><i>i</i></sub> <i>c</i><sub><i>i,d</i></sub> <i>ϵ</i><sup><i>i</i></sup> valid for 0 ≤ <i>ϵ</i> ≤0.86 and ERH(<i>ϵ</i>)= ∑ <sub><i>i</i></sub> <i>c</i><sub><i>i,e</i></sub> <i>ϵ</i><sup><i>i</i></sup> valid for 0 ≤ <i>ϵ</i> ≤ 0.55 for the coefficients <i>c</i><sub>0,<i>d</i></sub>= 80.67, <i>c</i><sub>0,<i>e</i></sub> = 28.35, <i>c</i><sub>1,<i>d</i></sub> = −11.45, <i>c</i><sub>1,<i>e</i></sub> = −13.66, <i>c</i><sub>2,<i>d</i></sub> = 0, <i>c</i><sub>2,<i>e</i></sub> = 0, <i>c</i><sub>3,<i>d</i></sub> = 57.99, <i>c</i><sub>3,<i>e</i></sub> = -83.80, <i>c</i><sub>4,<i>d</i></sub> = −106.80, and <i>c</i><sub>4,<i>e</i></sub> = 0. The molecular description that is thermodynamically implied by these strongly sloped DRH(<i>ϵ</i>) and ERH(<i>ϵ</i>) curves is that the organic isoprene photo-oxidation products, the inorganic ammonium sulfate, and water form a miscible liquid phase even at low relative humidity. This phase miscibility is in contrast to the liquid-liquid separation that occurs for some other types of secondary organic material. These differences in liquid-liquid separation are consistent with a prediction recently presented in the literature that the bifurcation between liquid-liquid phase separation versus mixing depends on the oxygen-to-carbon ratio of the organic material. The conclusions are that the influence of secondary organic material on the hygroscopic properties of ammonium sulfate varies with organic composition and that the degree of oxygenation of the organic material, which is a measurable characteristic of complex organic materials, is an important variable influencing the hygroscopic properties of mixed organic-inorganic particles

Pair Interactions in Red-Faced Warblers

Forty pairs of breeding Red-faced Warblers (Cardellina rubrifrons) were observed in 1992 and 1993 on the Mogollon Rim, Arizona. Intrusions by extra-pair males, interactions between pair members, and other pair interaction behaviors were recorded. The majority of intrusions occurred during the building stage of the nesting cycle. Males responded to intrusions during nest building by decreasing intra-pair distance. Males maintained shorter intra-pair distances by following the female when she initiated movements and by not initiating pair movements themselves. Intra-pair distances were as short or shorter during the incubation period as during nest building, and were shorter during incubation than during egg laying. Males continued to follow females beyond the expected fertile period. Possible explanations for continued mate following include: males guard their mates against predators, males guard their paternity for future nesting attempts, and males respond to extra-pair male intrusions, which continue during incubation

Grindr Users Take More Risks, but Are More Open to Human Immunodeficiency Virus (HIV) Pre-exposure Prophylaxis: Could This Dating App Provide a Platform for HIV Prevention Outreach?

BackgroundTechnology has changed the way that men who have sex with men (MSM) seek sex. More than 60% of MSM in the United States use the internet and/or smartphone-based geospatial networking apps to find sex partners. We correlated use of the most popular app (Grindr) with sexual risk and prevention behavior among MSM.MethodsA nested cohort study was conducted between September 2018 and June 2019 among MSM receiving community-based human immunodeficiency virus (HIV) and sexually transmitted infection (STI) screening in central San Diego. During the testing encounter, participants were surveyed for demographics, substance use, risk behavior (previous 3 months), HIV pre-exposure prophylaxis (PrEP) use, and Grindr usage. Participants who tested negative for HIV and who were not on PrEP were offered immediate PrEP.ResultsThe study included 1256 MSM, 1090 of whom (86.8%) were not taking PrEP. Overall, 580 of 1256 (46%) participants indicated that they used Grindr in the previous 7 days. Grindr users reported significantly higher risk behavior (greater number of male partners and condomless sex) and were more likely to test positive for chlamydia or gonorrhea (8.6% vs 4.7% of nonusers; P = .005). Grindr users were also more likely to be on PrEP (18.7% vs 8.7% of nonusers; P < .001) and had fewer newly diagnosed HIV infections (9 vs 26 among nonusers; P = .014). Grindr users were also nearly twice as likely as nonusers to initiate PrEP (24.6% vs 14%; P < .001).ConclusionsGiven the higher risk behavior and greater acceptance of PrEP among MSM who used Grindr, Grindr may provide a useful platform to promote HIV and STI testing and increase PrEP uptake

Photon pressure induced test mass deformation in gravitational-wave detectors

A widely used assumption within the gravitational-wave community has so far been that a test mass acts like a rigid body for frequencies in the detection band, i.e. for frequencies far below the first internal resonance. In this article we demonstrate that localized forces, applied for example by a photon pressure actuator, can result in a non-negligible elastic deformation of the test masses. For a photon pressure actuator setup used in the gravitational wave detector GEO600 we measured that this effect modifies the standard response function by 10% at 1 kHz and about 100% at 2.5 kHz

The Weak Clustering of Gas-Rich Galaxies

We examine the clustering properties of HI-selected galaxies through an analysis of the HI Parkes All-Sky Survey Catalogue (HICAT) two-point correlation function. Various sub-samples are extracted from this catalogue to study the overall clustering of HI-rich galaxies and its dependence on luminosity, HI gas mass and rotational velocity. These samples cover the entire southern sky Dec < 0 deg, containing up to 4,174 galaxies over the radial velocity range 300-12,700 km/s. A scale length of r_0 = 3.45 +/- 0.25 Mpc/h and slope of gamma = 1.47 +/- 0.08 is obtained for the HI-rich galaxy real-space correlation function, making gas-rich galaxies among the most weakly clustered objects known. HI-selected galaxies also exhibit weaker clustering than optically selected galaxies of comparable luminosities. Good agreement is found between our results and those of synthetic HI-rich galaxy catalogues generated from the Millennium Run CDM simulation. Bisecting HICAT using different parameter cuts, clustering is found to depend most strongly on rotational velocity and luminosity, while the dependency on HI mass is marginal. Splitting the sample around v_rot = 108 km/s, a scale length of r_0 = 2.86 +/- 0.46 Mpc/h is found for galaxies with low rotational velocities compared to r_0 = 3.96 +/- 0.33 Mpc/h for the high rotational velocity sample.Comment: Accepted for publication in the Astrophysical Journa

Coulomb induced positive current-current correlations in normal conductors

In the white-noise limit current correlations measured at different contacts of a mesoscopic conductor are negative due to the antisymmetry of the wave function (Pauli principle). We show that current fluctuations at capacitive contacts induced via the long range Coulomb interaction as consequence of charge fluctuations in the mesoscopic sample can be {\it positively} correlated. The positive correlations are a consequence of the extension of the wave-functions into areas near both contacts. As an example we investigate in detail a quantum point contact in a high magnetic field under conditions in which transport is along an edge state.Comment: Revtex, 4 pages includes 2 figure

Canopy nitrogen, carbon assimilation, and albedo in temperate and boreal forests: Functional relations and potential climate feedbacks

The availability of nitrogen represents a key constraint on carbon cycling in terrestrial ecosystems, and it is largely in this capacity that the role of N in the Earth\u27s climate system has been considered. Despite this, few studies have included continuous variation in plant N status as a driver of broad-scale carbon cycle analyses. This is partly because of uncertainties in how leaf-level physiological relationships scale to whole ecosystems and because methods for regional to continental detection of plant N concentrations have yet to be developed. Here, we show that ecosystem CO2 uptake capacity in temperate and boreal forests scales directly with whole-canopy N concentrations, mirroring a leaf-level trend that has been observed for woody plants worldwide. We further show that both CO2 uptake capacity and canopy N concentration are strongly and positively correlated with shortwave surface albedo. These results suggest that N plays an additional, and overlooked, role in the climate system via its influence on vegetation reflectivity and shortwave surface energy exchange. We also demonstrate that much of the spatial variation in canopy N can be detected by using broad-band satellite sensors, offering a means through which these findings can be applied toward improved application of coupled carbon cycle–climate models

The XMM-Newton view of the Crab

Aims. We discuss the current X-ray view of the Crab Nebula and Pulsar, summarising our analysis of observations of the source with the EPIC-pn camera on board the XMM-Newton observatory. Different modes of EPIC-pn were combined in order to yield a complete scenario of the spectral properties of the Crab resolved in space and time (pulse phase). In addition we give a description of the special EPIC-pn Burst mode and guidance for data reduction in that mode. Methods. We analysed spectra for the nebula and pulsar separately in the 0.6−12.0 keV energy band. All data were processed with the SAS 6.0.0 XMM-Newton Scientific Analysis System package; models were fitted to the data with XSPEC 11. The high time resolution of EPIC-pn in its Burst mode (7 μs) was used for a phase resolved analysis of the pulsar spectrum, after determination of the period with epoch folding techniques. Data from the SmallWindow mode were processed and corrected for pile-up allowing for spectroscopy simultaneously resolved in space and time. Results. The spatial variation of the spectrum over the entire region of the Crab shows a gradual spectral softening from the inner pulsar region to the outer nebula region with a variation in photon index, Γ, from 2.0 to 2.4. Pulse phase resolved spectroscopy of the Crab Pulsar reveals a phase dependent modulation of the photon index in form of a significant hardening of the spectrum in the inter-peak phase from Γ = 1.7 during the pulse peak to Γ = 1.5