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Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+(DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b−(SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4β7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.

We describe the flattening of scientific CCD imaging data using a dome flat-field system. The system uses light emitting diodes (LEDs) to illuminate a carefully constructed dome flat-field screen. LEDs have several advantages over more traditional illumination sources: they are available in a wide range of output wavelengths, are inexpensive, have a very long source lifetime, and are straightforward to control digitally. The circular dome screen is made of a material with Lambertian scattering properties that efficiently reflects light of a wide range of wavelengths and incident angles. In this paper, we compare flat fields obtained using this system with two types of traditionally-constructed flat fields: twilight sky flats and nighttime sky flats. Using photometric standard stars as illumination sources, we test the quality of each flat field by applying it to a set of standard star observations. We find that the dome flat-field system produces flat fields that are superior to twilight or nighttime sky flats, particularly for photometric calibration. We note that a ratio of the twilight sky flat to the nighttime sky flat is flat to within the expected uncertainty; but since both of these flat fields are inferior to the dome flat, this common test is not an appropriate metric for testing a flat field. Rather, the only feasible and correct method for determining the appropriateness of a flat field is to use standard stars to measure the reproducibility of known magnitudes across the detector.

In order to guide the adaptive optics design and aid in performance predictions, optical turbulence at the site of the future Giant Magellan Telescope (GMT) is characterized using MooSci, a lunar scintillometer, and MASS-DIMM, a combination differential image motion monitor and multiaperture scintillation sensor. As a new instrument, MooSci, is verified as a reliable ground-layer turbulence profiler. The GMT can expect an improvement of approximately 0.1? over the site testing results as measured with a DIMM. Turbulence below 30 m is horizontally nonhomogeneous, dependent on wind speed and direction, and on average accounts for 60% of the full ground-layer (up to 500 m) turbulence.

The Kilodegree Extremely Little Telescope (KELT) project is a survey for planetary transits of bright stars. It consists of a small-aperture, wide-field automated telescope located at Winer Observatory near Sonoita, Arizona. The telescope surveys a set of 26° × 26° fields that together cover about 25% of the northern sky, and targets stars in the range of 8

We present extensive u'g'r'i'BVRIYJHKsphotometry and optical spectroscopy of the Type Ia supernova (SN) 2005hk. These data reveal that SN 2005hk was nearly identical in its observed properties to SN 2002cx, which has been called "the most peculiar known Type Ia supernova." Both supernovae exhibited high-ionization SN 1991T-like premaximum spectra, yet low peak luminosities like that of SN 1991bg. The spectra reveal that SN 2005hk, like SN 2002cx, exhibited expansion velocities that were roughly half those of typical Type Ia supernovae. The Rand Ilight curves of both supernovae were also peculiar in not displaying the secondary maximum observed for normal Type Ia supernovae. Our YJHphotometry of SN 2005hk reveals the same peculiarity in the near-infrared. By combining our optical and near-infrared photometry of SN 2005hk with published ultraviolet light curves obtained with the Swiftsatellite, we are able to construct a bolometric light curve from ?15 days before to ?60 days after Bmaximum. The shape and unusually low peak luminosity of this light curve, plus the low expansion velocities and absence of a secondary maximum at red and near-infrared wavelengths, are all in reasonable agreement with model calculations of a three-dimensional deflagration that produces ?0.2 M?of 56Ni.

Tumor development, growth, and progression depend on some combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. Understanding the complex molecular mechanisms that underlie these processes should therefore lead to the identification of potential targets for therapeutic intervention. The estrogen receptor and HER-2 / neu were among the earliest targets investigated, ultimately leading to the widespread use of tamoxifen and trastuzumab, respectively, in the treatment of breast cancer. Major research advances have since led to other classes of targeted therapies, including cyclin-dependent kinase inhibitors, histone deactylase inhibitors, and receptor tyrosine kinase inhibitors. The following review provides a discussion of the molecular biology associated with each of these types of therapies as well as a detailed summary of the preclinical and clinical data published on selected compounds from each of these subgroups.

The Submillimeter Polarimeter for Antarctic Remote Observations (SPARO) employs two nine-element arrays of 3He-cooled bolometers to measure linear polarization at ? = 450 ?m. It is operated at the focal plane of the Viper telescope, located at the Amundsen-Scott South Pole Station. SPARO obtains better sensitivity to degree-scale polarized submillimeter emission than can be currently achieved with any other experiment. We describe the design of SPARO's optics, detectors, and electronics. We also review the design of the SPARO cryostat, which has already been discussed in a previous paper. We discuss the performance of SPARO and Viper during observations at the South Pole in 2000, and we present polarimetric observations of NGC 6334 made with SPARO. Finally, we compare these observations with submillimeter polarimetric observations of the same source made at the Caltech Submillimeter Observatory and the James Clerk Maxwell Telescope, and we discuss the implications of these three data sets for the magnetic field in NGC 6334.

Synthetic detergents produce deleterious effects on human skin as the result of being taken up by the stratum corneum (SC). The present study aimed to determine to what extent a typical detergent enters the SC lipid lamellae, and what effect this might have on the physical properties of the lipids. These effects were studied in large unilamellar liposomes prepared from SC lipids (50% by weight of epidermal ceramides, 28% cholesterol, 17% free fatty acids, and 5% cholesteryl sulfate) by extrusion through successive polycarbonate filters of decreasing pore size, finally 400 nm. Freeze-fracture electron microscopy and light-scattering particle size analysis indicated a uniform liposome diameter averaging 230 nm. Partitioning of sodium dodecyl sulfate (SDS) into the lipid phase from aqueous buffer solutions was measured using the SC lipid liposomes and [U-14C]SDS. The partition coefficient was 416, 450, and 588 at pH 8.5 and 524, 507, and 807 at pH 7 for three different concentrations (0.1%, 0.02%, and 0.004%) of SDS. This high degree of partitioning into the liposomes is consistent with the high level of SDS partitioning seen in full SC. At the maximum, the SDS represented 18% of the liposomal lipids. Preparation of stable liposomes from SC lipids to which 10% or 20% of SDS had been added confirmed the ability of the liposomes to survive these high concentrations of surfactant. The permeability of the liposomes was enhanced as a result of SDS partitioning into the bilayers, as measured by the increased release of trapped [U-14C]glucose from these vesicles, and by their increased permeability to water in osmotic shock experiments. These studies demonstrate that SDS in dilute solution can partition into lipid bilayers at high concentration so as to affect the properties of the lipid lamellae that constitute the epidermal permeability barrier.

Mercury (II) forms a covalent, 1:1 complex with NADPH which is indicated by the disappearance of the chromophore at 340 nm. With the use of NMNH as an analogue, the spectral changes were attributed to the reaction of Hg(II) with the nicotinamide ring. This reaction is reversed by the addition of sulfhydryl groups or other metal-chelating agents. The structure of the Hg(II) . NADPH complex was determined with 1H and 13C NMR spectroscopy and homonuclear decoupling and was shown to have Hg covalently attached to C-5 of the nicotinamide ring. From these results, we propose that Hg(II) reacts with the double bond between C-5 and C-6 to form a mercuronium ion which is opened by the nucleophilic attack of water on C-6. Two conformations of the Hg(II) . NADPH complex were detected, corresponding to the formation of the mercuronium ion on either the a or b side of the nicotinamide ring. Fluorescence quenching studies with the Hg(II) . NADPH complex and the flavoenzyme mercuric reductase showed that the complex could effectively bind (Kd = 2.3 microM), but could not reduce the enzyme.

Populations of Chinese hamster ovary cells selected for resistance to diphtheria toxin were found to be highly enriched for mutants deficient in the uptake of lysosomal hydrolases via the mannose 6-phosphate receptor. One doubly defective mutant, DTF 1-5-1, exhibited increased resistance to Sindbis virus, although it was able to bind and internalize virus normally. Normal production of virus was obtained when, subsequent to virus binding, the mutant was exposed for 2 min to acidic pH. Similarly, a shift to acidic pH increased the sensitivity of DTF 1-5-1 to diphtheria toxin 12-fold. Decreased uptake of lysosomal hydrolases by the mutant correlated with decreased mannose 6-phosphate receptor activity at the cell surface; results of lactoperoxidase-catalyzed iodination indicated that the surface-associated receptor was present but inactive on DTF 1-5-1. Total mannose 6-phosphate receptor activity was also decreased in the mutant and this decrease was reflected by increased secretion of lysosomal hydrolases. The phenotype of DTF 1-5-1 resembles in many ways that of cells treated with ammonia. We suggest that the defect in DTF 1-5-1 stems from an inability to deliver virus, diphtheria toxin, and lysosomal hydrolases to an acidic compartment. Other ligands may be endocytosed through a different pathway since the defect of DTF 1-5-1 did not decrease the endocytosis of ricin, modeccin, or Pseudomonas toxin and had minimal effects on uptake and degradation of low density lipoprotein.

In this paper we investigate how implementing machine learning could improve the efficiency of the search for Trans-Neptunian Objects (TNOs) within Dark Energy Survey (DES) data when used alongside orbit fitting. The discovery of multiple TNOs that appear to show a similarity in their orbital parameters has led to the suggestion that one or more undetected planets, an as yet undiscovered "Planet 9", may be present in the outer solar system. DES is well placed to detect such a planet and has already been used to discover many other TNOs. Here, we perform tests on eight different supervised machine learning algorithms, using a data set consisting of simulated TNOs buried within real DES noise data. We found that the best performing classifier was the Random Forest which, when optimized, performed well at detecting the rare objects. We achieve an area under the receiver operating characteristic (ROC) curve, (AUC) = 0.996 ± 0.001. After optimizing the decision threshold of the Random Forest, we achieve a recall of 0.96 while maintaining a precision of 0.80. Finally, by using the optimized classifier to pre-select objects, we are able to run the orbit-fitting stage of our detection pipeline five times faster.

Several letters to the editor are presented in response to articles in previous issues including "The Brother-Sister Vow," by Claire McAuley in the previous issue, "Spirit v. Reality" in the previous issue, and "The Americanists" in the previous issue.

We characterize the ability of the Dark Energy Camera (DECam) to perform relative astrometry across its 500 Mpix, 3-deg2science field of view and across four years of operation. This is done using internal comparisons of ?4 × 107measurements of high signal-to-noise ratio stellar images obtained in repeat visits to fields of moderate stellar density, with the telescope dithered to move the sources around the array. An empirical astrometric model includes terms for optical distortions; stray electric fields in the CCD detectors; chromatic terms in the instrumental and atmospheric optics; shifts in CCD relative positions of up to ?10 ?m when the DECam temperature cycles; and low-order distortions to each exposure from changes in atmospheric refraction and telescope alignment. Errors in this astrometric model are dominated by stochastic variations with typical amplitudes of 10-30 mas (in a 30 s exposure) and 5'-10' coherence length, plausibly attributed to Kolmogorov-spectrum atmospheric turbulence. The size of these atmospheric distortions is not closely related to the seeing. Given an astrometric reference catalog at density e.g., from Gaia, the typical atmospheric distortions can be interpolated to ?7 mas rms accuracy (for 30 s exposures) with coherence length in residual errors. Remaining detectable error contributors are 2-4 mas rms from unmodelled stray electric fields in the devices, and another 2-4 mas rms from focal plane shifts between camera thermal cycles. Thus the astrometric solution for a single DECam exposure is accurate to 3-6 mas (?0.02 pixels, or ?300 nm) on the focal plane, plus the stochastic atmospheric distortion.

The intramolecular electron‐transfer reactions are investigated for the donor‐acceptor systems (I).