Double and triple calix[4]arenis connected via the oxygen functions

New macrocyclic molecules are described containing two or three p-tert-butylcalix[4]arene subunits connected via their oxygen atoms. These macrocycles are available by two general methods which are capable of producing assemblies with bridges of varying rigidity and length

Robust Machine Learning Applied to Astronomical Datasets I: Star-Galaxy Classification of the SDSS DR3 Using Decision Trees

We provide classifications for all 143 million non-repeat photometric objects in the Third Data Release of the Sloan Digital Sky Survey (SDSS) using decision trees trained on 477,068 objects with SDSS spectroscopic data. We demonstrate that these star/galaxy classifications are expected to be reliable for approximately 22 million objects with r < ~20. The general machine learning environment Data-to-Knowledge and supercomputing resources enabled extensive investigation of the decision tree parameter space. This work presents the first public release of objects classified in this way for an entire SDSS data release. The objects are classified as either galaxy, star or nsng (neither star nor galaxy), with an associated probability for each class. To demonstrate how to effectively make use of these classifications, we perform several important tests. First, we detail selection criteria within the probability space defined by the three classes to extract samples of stars and galaxies to a given completeness and efficiency. Second, we investigate the efficacy of the classifications and the effect of extrapolating from the spectroscopic regime by performing blind tests on objects in the SDSS, 2dF Galaxy Redshift and 2dF QSO Redshift (2QZ) surveys. Given the photometric limits of our spectroscopic training data, we effectively begin to extrapolate past our star-galaxy training set at r ~ 18. By comparing the number counts of our training sample with the classified sources, however, we find that our efficiencies appear to remain robust to r ~ 20. As a result, we expect our classifications to be accurate for 900,000 galaxies and 6.7 million stars, and remain robust via extrapolation for a total of 8.0 million galaxies and 13.9 million stars. [Abridged]Comment: 27 pages, 12 figures, to be published in ApJ, uses emulateapj.cl

Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism

Table S1. Demographic and clinical features of human subjects used in this study. Figure S1. Aβ deposition in microvessels in AD patients and APPSw/0 mice. Figure S2. Biochemical analysis of Aβ42 aggregates. Figure S3. Cy3-Aβ42 cellular uptake in wild type mouse brain slices within 30 min. Figure S4. Pericyte coverages in Lrp1lox/lox and Lrp1lox/lox; Cspg4-Cre mice. Figure S5.. LRP1 and apoE suppression with siRNA. (DOCX 1454 kb

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1β, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs. CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies

Anaerobic Digestion in a Flooded Densified Leachbed

A document discusses the adaptation of a patented biomass-digesting process, denoted sequential batch anaerobic composting (SEBAC), to recycling of wastes aboard a spacecraft. In SEBAC, high-solids-content biomass wastes are converted into methane, carbon dioxide, and compost

Structural Characterization of Phosphatidyl-myo-Inositol Mannosides from Mycobacterium bovis Bacillus Calmette Gúerin by Multiple-Stage Quadrupole Ion-Trap Mass Spectrometry with Electrospray Ionization. II. Monoacyl- and Diacyl-PIMs

The multiple-stage ion-trap mass spectrometric approaches towards to the structural characterization of the monoacyl-PIM (triacylated PIM) and the diacyl-PIM (tetracylated PIM), namely, the PIM (diacylated PIM) consisting of one or two additional fatty acid substituents attached to the glycoside, respectively, were described. While the assignment and confirmation of the fatty acid substituents on the glycerol backbone can be easily achieved by the methods described in the previous article, the identity of the glycoside moiety and its acylation state can be determined by the observation of a prominent acylglycoside ion arising from cleavage of the diacylglycerol moiety ([M − H − diacylglycerol]−) in the MS2-spectra of monoacyl-PIM and diacyl-PIM. The distinction of the fatty acid substituents on the 2-O-mannoside (i.e., R3CO2H) from that on the inositol (i.e., R4CO2H) is based on the findings that the MS3-spectrum of [M − H − diacylglycerol]− contains a prominent ion arising from further loss of the fatty acid at the 2-O-mannoside (i.e., the [M − H − diacylglycerol − R3CO2H]− ion), while the ion arising from loss of the fatty acid substituent at the inositol (i.e., the [M − H − diacylglycerol − R4CO2H]− ion) is of low abundance. The fatty acyl moiety on the inositol can also be identified by the product-ion spectrum from MS4 of the [M − H − diacylglycerol − R3CO2H]− ion, which gives rise to a prominent ion corresponding to loss of R4CO2H. An [M − H − acylmannose]− ion was also observed in the MS2-spectra and, thus, the identity of the fatty acid substituent attached to 2-O-mannoside can be confirmed. The combined information obtained from the multiple-stage product-ion spectra from MS2, MS3, and MS4 permit the assignment of the complex structures of monoacyl-PIMs and diacyl-PIMs in a mixture isolated from M. bovis Bacillus Calmette Guérin

Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania

Hybrid genotypes have been repeatedly described among natural isolates of Leishmania, and the recovery of experimental hybrids from sand flies co-infected with different strains or species of Leishmania has formally demonstrated that members of the genus possess the machinery for genetic exchange. As neither gamete stages nor cell fusion events have been directly observed during parasite development in the vector, we have relied on a classical genetic analysis to determine if Leishmania has a true sexual cycle. Here, we used whole genome sequencing to follow the chromosomal inheritance patterns of experimental hybrids generated within and between different strains of L. major and L. infantum. We also generated and sequenced the first experimental hybrids in L. tropica. We found that in each case the parental somy and allele contributions matched the inheritance patterns expected under meiosis 97–99% of the time. The hybrids were equivalent to F1 progeny, heterozygous throughout most of the genome for the markers that were homozygous and different between the parents. Rare, non-Mendelian patterns of chromosomal inheritance were observed, including a gain or loss of somy, and loss of heterozygosity, that likely arose during meiosis or during mitotic divisions of the progeny clones in the fly or culture. While the interspecies hybrids appeared to be sterile, the intraspecies hybrids were able to produce backcross and outcross progeny. Analysis of 5 backcross and outcross progeny clones generated from an L. major F1 hybrid, as well as 17 progeny clones generated from backcrosses involving a natural hybrid of L. tropica, revealed genome wide patterns of recombination, demonstrating that classical crossing over occurs at meiosis, and allowed us to construct the first physical and genetic maps in Leishmania. Altogether, the findings provide strong evidence for meiosis-like sexual recombination in Leishmania, presenting clear opportunities for forward genetic analysis and positional cloning of important genes.</div

Seasonal Variation in Terrestrial Invertebrate Subsidies to Tropical Streams and Implications for the Feeding Ecology of Hart’s Rivulus (Anablepsoides hartii)

Terrestrial invertebrates are important subsidies to fish diets, though their seasonal dynamics and importance to tropical stream consumers are particularly understudied. In this year-round study of terrestrial invertebrate input to two Trinidadian headwater streams with different forest canopy densities, we sought to (a) measure the mass and composition of terrestrial inputs with fall-in traps to evaluate the influences of seasonality, canopy cover, and rainfall intensity, and; (b) compare terrestrial and benthic prey importance to Anablepsoides hartii(Hart’s Rivulus), the dominant invertivorous fish in these streams, by concurrently measuring benthic and drifting invertebrate standing stocks and the volume and composition of invertebrates in Rivulus guts throughout the year. The biomass of terrestrial invertebrate fall-in was 53% higher in the wet versus dry season; in particular, ant input was 320% higher. Ant biomass fall-in also increased with the density of canopy cover among sampling locations within both streams. Greater precipitation correlated with increased ant inputs to the more open-canopied stream and increased inputs of winged insects in the more closed canopy stream. Concurrently, the biomass of benthic invertebrates was reduced by more than half in the wet season in both streams. We detected no differences in the total volume of terrestrial prey in Rivulus diets between seasons, though ants were a greater proportion of their diet in the wet season. In contrast, benthic prey were nearly absent from Rivulus diets in the wet season in both streams. We conclude that terrestrial invertebrates are a substantial year-round prey subsidy for invertivores in tropical stream ecosystems like those we studied, which may contrast to most temperate streams where such terrestrial inputs are significantly reduced in the cold season. Interestingly, the strongest seasonal pattern in these tropical streams was observed in benthic invertebrate biomass which was greatly reduced and almost absent from Rivulus diets during the wet season. This pattern is essentially the inverse of the pattern observed in many temperate streams and highlights the need for additional studies in tropical ecosystems to better understand how spatial and temporal variation in terrestrial subsidies and benthic prey populations combine to influence consumer diets and the structure of tropical stream food webs

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo

207-nm UV Light—A Promising Tool for Safe Low-Cost Reduction of Surgical Site Infections. II: In-Vivo Safety Studies

Background UVC light generated by conventional germicidal lamps is a well-established anti-microbial modality, effective against both bacteria and viruses. However, it is a human health hazard, being both carcinogenic and cataractogenic. Earlier studies showed that single-wavelength far-UVC light (207 nm) generated by excimer lamps kills bacteria without apparent harm to human skin tissue in vitro. The biophysical explanation is that, due to its extremely short range in biological material, 207 nm UV light cannot penetrate the human stratum corneum (the outer dead-cell skin layer, thickness 5–20 μm) nor even the cytoplasm of individual human cells. By contrast, 207 nm UV light can penetrate bacteria and viruses because these cells are physically much smaller. Aims To test the biophysically-based hypothesis that 207 nm UV light is not cytotoxic to exposed mammalian skin in vivo. Methods Hairless mice were exposed to a bactericidal UV fluence of 157 mJ/cm2 delivered by a filtered Kr-Br excimer lamp producing monoenergetic 207-nm UV light, or delivered by a conventional 254-nm UV germicidal lamp. Sham irradiations constituted the negative control. Eight relevant cellular and molecular damage endpoints including epidermal hyperplasia, pre-mutagenic UV-associated DNA lesions, skin inflammation, and normal cell proliferation and differentiation were evaluated in mice dorsal skin harvested 48 h after UV exposure. Results While conventional germicidal UV (254 nm) exposure produced significant effects for all the studied skin damage endpoints, the same fluence of 207 nm UV light produced results that were not statistically distinguishable from the zero exposure controls. Conclusions As predicted by biophysical considerations and in agreement with earlier in vitro studies, 207-nm light does not appear to be significantly cytotoxic to mouse skin. These results suggest that excimer-based far-UVC light could potentially be used for its anti-microbial properties, but without the associated hazards to skin of conventional germicidal UV lamps