Mixed population of competing TASEPs with a shared reservoir of particles

We introduce a mean-field theoretical framework to describe multiple totally asymmetric simple exclusion processes (TASEPs) with different lattice lengths, entry and exit rates, competing for a finite reservoir of particles. We present relations for the partitioning of particles between the reservoir and the lattices: these relations allow us to show that competition for particles can have non-trivial effects on the phase behavior of individual lattices. For a system with non-identical lattices, we find that when a subset of lattices undergoes a phase transition from low to high density, the entire set of lattice currents becomes independent of total particle number. We generalize our approach to systems with a continuous distribution of lattice parameters, for which we demonstrate that measurements of the current carried by a single lattice type can be used to extract the entire distribution of lattice parameters. Our approach applies to populations of TASEPs with any distribution of lattice parameters, and could easily be extended beyond the mean-field case.Comment: 12 pages, 8 figure

Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.

HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans

883 An anti-carcinoma monoclonal antibody (mAb) NEO-201 can also target human acute myeloid leukemia (AML) cell lines in vitro

BackgroundNEO-201 is an IgG1 mAb targeting variants of CEACAM5/6 and has demonstrated tumor sensitivity and specificity in epithelial cells. Functional analysis has revealed that NEO-201 can engage innate immune effector mechanisms including ADCC and CDC to directly kill tumor cells expressing its target. A recent Phase 1 clinical trial at the NCI has determined both safety and recommended Phase 2 dosing. We have also seen the expression of the NEO-201 target on hematologic cells, specifically Tregs and neutrophils. Due to epitope being expressed both on malignant epithelial cells as well as several hematologic cells, we designed this study to explore the reactivity of NEO-201 against hematological neoplastic cells in vitro.MethodsPhenotypic analysis was conducted by flow cytometry. Cell lines used were six AML (HL60, U937, MOLM13, AML2, IMS-M2 and OCL-AML3), two multiple myelomas (MM) (OPM2, MM1.S), two acute lymphoblastic leukemia (ALL) (SUP-B15, RPMI8402) and four mantle cell lymphoma (MCL) (Jeko-1, Z138, JVM2 and JVM13). Markers used for flow cytometry analysis were CD15, CD45, CD38, CD138, CD14, CD19 and NEO-201. Functional analysis was performed by evaluating the ability of NEO-201 to mediate ADCC activity against AML cell lines using human NK cells as effector cells.Results5 of 6 AML cell lines tested bind to NEO-201 and the% of positive cells were 47%, 99.5%,100%,100% and 97.8% for HL60, U937, MOLM13, AML3 and IMS-M2, respectively. The% of positive cells in the two MM cell line were 99% and 18% for OPM2 and MM1.S, respectively. NEO-201 binding was not detected in the two ALL and the four MCL cell lines tested. Functional analysis has demonstrated that NEO-201 can mediate ADCC activity against the AML cell line (HL60) tested.ConclusionsThis study demonstrates that NEO-201 mAb's target is expressed in most of the AML cell lines tested in vitro. In addition, we have shown it can mediate ADCC activity against HL60 cells (AML). Together, these findings provide a rationale for further investigation of the role of NEO-201 in AML as well as MM, further exploring patient PBMCs and bone marrow samples

The Wolf-Rayet Content of M33

Wolf-Rayet stars (WRs) are evolved massive stars, and the relative number of WC-type and WN-type WRs should vary with metallicity, providing a sensitive test of stellar evolutionary theory. The observed WC/WN ratio is much higher than that predicted by theory in some galaxies but this could be due to observational incompleteness for WN-types, which have weaker lines. Previous studies of M33's WR content show a galactocentric gradient in the relative numbers of WCs and WNs, but only small regions have been surveyed with sufficient sensitivity to detect all of the WNs. Here we present a sensitive survey for WRs covering all of M33, finding 55 new WRs, mostly of WN type. Our spectroscopy also improves the spectral types of many previously known WRs, establishing in one case that the star is actually a background quasar. The total number of spectroscopically confirmed WRs in M33 is 206, a number we argue is complete to approximately 5%, with most WRs residing in OB associations, although approximately 2% are truly isolated. The WC/WN ratio in the central regions (<2 kpc) of M33 is much higher than that predicted by the current Geneva evolutionary models, while the WC/WN ratios in the outer regions are in good accord, as are the values in the SMC and LMC. The WC/WN ratio and the WC subtype distribution both argue that the oxygen abundance gradient in M33 is significantly larger than found by some recent studies, but are consistent with the two-component model proposed by Magrini et al.Comment: ApJ, in pres

A Survey of Local Group Galaxies Currently Forming Stars: III. A Search for Luminous Blue Variables and Other H-alpha Emission-Lined Stars

We describe a search for H-alpha emission-lined stars in M31, M33, and seven dwarfs in or near the Local Group (IC 10, NGC 6822, WLM, Sextans B, Sextans A, Pegasus and the Phoenix dwarf) using interference filter imaging with the KPNO and CTIO 4-m telescope and Mosaic cameras. The survey is aimed primarily at identifying new Luminous Blue Variables (LBVs) from their spectroscopic similarity to known LBVs, avoiding the bias towards photometric variability, which may require centuries to manifest itself if LBVs go through long quiescent periods. Followup spectroscopy with WIYN confirms that our survey detected a wealth of stars whose spectra are similar to the known LBVs. We "classify" the spectra of known LBVs, and compare these to the spectra of the new LBV candidates. We demonstrate spectacular spectral variability for several of the new LBV candidates, such as AM2, previously classified as a Wolf-Rayet star, which now shows FeI, FeII and Balmer emission lines but neither the NIII 4634,42 nor HeII 4686 emission that it did in 1982. Profound spectral changes are also noted for other suspected and known LBVs. Several of the LBV candidates also show >0.5 mag changes in V over the past 10-20 years. The number of known or suspected LBVs is now 24 in M31, 37 in M33, 1 in NGC 6822, and 3 in IC 10. We estimate that the total number of LBVs in M31 and M33 may be several hundred, in contrast to the 8 known historically through large-scale photometric variability. This has significant implications for the time scale of the LBV phase. We also identify a few new WRs and peculiar emission-lined objects.Comment: Accepted by the Astronomical Journal. Version with higher quality figures may be downloaded from http://www.lowell.edu/users/massey/has.pdf.g

Developing a reliable strategy to infer the effective soil hydraulic properties from field evaporation experiments for agro-hydrological models

The Richards equation has been widely used for simulating soil water movement. However, the take-up of agro-hydrological models using the basic theory of soil water flow for optimizing irrigation, fertilizer and pesticide practices is still low. This is partly due to the difficulties in obtaining accurate values for soil hydraulic properties at a field scale. Here, we use an inverse technique to deduce the effective soil hydraulic properties, based on measuring the changes in the distribution of soil water with depth in a fallow field over a long period, subject to natural rainfall and evaporation using a robust micro Genetic Algorithm. A new optimized function was constructed from the soil water contents at different depths, and the soil water at field capacity. The deduced soil water retention curve was approximately parallel but higher than that derived from published pedo-tranfer functions for a given soil pressure head. The water contents calculated from the deduced soil hydraulic properties were in good agreement with the measured values. The reliability of the deduced soil hydraulic properties was tested in reproducing data measured from an independent experiment on the same soil cropped with leek. The calculation of root water uptake took account for both soil water potential and root density distribution. Results show that the predictions of soil water contents at various depths agree fairly well with the measurements, indicating that the inverse analysis is an effective and reliable approach to estimate soil hydraulic properties, and thus permits the simulation of soil water dynamics in both cropped and fallow soils in the field accurately