The Human Monocyte-A Circulating Sensor of Infection and a Potent and Rapid Inducer of Inflammation

Monocytes were previously thought to be the precursors of all tissue macrophages but have recently been found to represent a unique population of cells, distinct from the majority of tissue macrophages. Monocytes and intestinal macrophages seem now to be the only monocyte/macrophage populations that originate primarily from adult bone marrow. To obtain a better view of the biological function of monocytes and how they differ from tissue macrophages, we have performed a quantitative analysis of its transcriptome in vivo and after in vitro stimulation with E. coli LPS. The monocytes rapidly responded to LPS by producing extremely high amounts of mRNA for the classical inflammatory cytokines, IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha, but almost undetectable amounts of other cytokines. IL-6 was upregulated 58,000 times, from almost undetectable levels at baseline to become one of the major transcripts already after a few hours of cultivation. The cells also showed very strong upregulation of a number of chemokines, primarily IL-8, Ccl2, Ccl3, Ccl3L3, Ccl20, Cxcl2, Cxcl3 and Cxcl4. IL-8 became the most highly expressed transcript in the monocytes already after four hours of in vitro culture in the presence of LPS. A high baseline level of MHC class II chains and marked upregulation of super oxide dismutase (SOD2), complement factor B, complement factor C3 and coagulation factor 3 (F3; tissue factor) at four hours of in vitro culture were also observed. This indicates a rapid protective response to high production of oxygen radicals, to increase complement activation and possibly also be an inducer of local coagulation. Overall, these findings give strong support for monocytes acting primarily as potent mobile sensors of infection and rapid activators of a strong inflammatory response

DMC-Net: Generating Discriminative Motion Cues for Fast Compressed Video Action Recognition

Motion has shown to be useful for video understanding, where motion is typically represented by optical flow. However, computing flow from video frames is very time-consuming. Recent works directly leverage the motion vectors and residuals readily available in the compressed video to represent motion at no cost. While this avoids flow computation, it also hurts accuracy since the motion vector is noisy and has substantially reduced resolution, which makes it a less discriminative motion representation. To remedy these issues, we propose a lightweight generator network, which reduces noises in motion vectors and captures fine motion details, achieving a more Discriminative Motion Cue (DMC) representation. Since optical flow is a more accurate motion representation, we train the DMC generator to approximate flow using a reconstruction loss and a generative adversarial loss, jointly with the downstream action classification task. Extensive evaluations on three action recognition benchmarks (HMDB-51, UCF-101, and a subset of Kinetics) confirm the effectiveness of our method. Our full system, consisting of the generator and the classifier, is coined as DMC-Net which obtains high accuracy close to that of using flow and runs two orders of magnitude faster than using optical flow at inference time.Comment: Accepted by CVPR'1

The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes

A wide variety of steric and electronic features can be incorporated into transition metal coordination complexes, offering the prospect of rationally-designed therapeutic agents with novel mechanisms of action. Here we compare the chemical reactivity and anticancer activity of organometallic OsII complexes [Os(η6-arene)(XY)Z]PF6 where arene = p-cymene or biphenyl, XY = N,N′-chelated phenyliminopyridine or phenylazopyridine derivatives, and Z = Cl or I. The X-ray crystal structure of [Os(η6-p-cym)(Impy-OH)I]PF6·0.5CH2Cl2·H2O (Impy-OH = 4-[(2-pyridinylmethylene)amino]-phenol) is reported. Like the azopyridine complexes we reported recently (Dalton Trans., 2011, 40, 10553–10562), some iminopyridine complexes are also potently active towards cancer cells (nanomolar IC50 values). However we show that, unlike the azopyridine complexes, the iminopyridine complexes can undergo aquation, bind to the nucleobase guanine, and oxidize coenzyme nicotine adenine dinucleotide (NADH). We report the first detection of an Os-hydride adduct in aqueous solution by 1H NMR (−4.2 ppm). Active iminopyridine complexes induced a dramatic increase in the levels of reactive oxygen species (ROS) in A549 lung cancer cells. The anticancer activity may therefore involve interference in the redox signalling pathways in cancer cells by a novel mechanism

The relation between metallicity, stellar mass and star formation in galaxies: an analysis of observational and model data

We study relations between stellar mass, star formation and gas-phase metallicity in a sample of 177,071 unique emission line galaxies from the SDSS-DR7, as well as in a sample of 43,767 star forming galaxies at z=0 from the cosmological semi-analytic model L-GALAXIES. We demonstrate that metallicity is dependent on star formation rate at fixed mass, but that the trend is opposite for low and for high mass galaxies. Low-mass galaxies that are actively forming stars are more metal-poor than quiescent low-mass galaxies. High-mass galaxies, on the other hand, have lower gas-phase metallicities if their star formation rates are small. Remarkably, the same trends are found for our sample of model galaxies. We find that massive model galaxies with low gas-phase metallicities have undergone a gas-rich merger in the past, inducing a starburst which exhausted their cold gas reservoirs and shut down star formation. This led to a gradual dilution in the gas-phase metallicities of these systems via accretion of gas. These model galaxies have lower-than-average gas-to-stellar mass ratios and higher-than-average central black hole masses. We confirm that massive galaxies with low gas-phase metallicities in our observational sample also have very massive black holes. We propose that accretion may therefore play a significant role in regulating the gas-phase metallicities of present-day massive galaxies.Comment: 18 pages, 18 figures, 2 tables. Submitted to MNRA

β-Herpesviruses in Febrile Children with Cancer

These viruses should be included in the differential diagnosis of febrile disease

Micro-reflectance and transmittance spectroscopy: a versatile and powerful tool to characterize 2D materials

Optical spectroscopy techniques such as differential reflectance and transmittance have proven to be very powerful techniques to study 2D materials. However, a thorough description of the experimental setups needed to carry out these measurements is lacking in the literature. We describe a versatile optical microscope setup to carry out differential reflectance and transmittance spectroscopy in 2D materials with a lateral resolution of ~1 micron in the visible and near-infrared part of the spectrum. We demonstrate the potential of the presented setup to determine the number of layers of 2D materials and to characterize their fundamental optical properties such as excitonic resonances. We illustrate its performance by studying mechanically exfoliated and chemical vapor-deposited transition metal dichalcogenide samples.Comment: 5 main text figures + 1 table with all the part numbers to replicate the experimental setup + 4 supp. info. figure

Designing organometallic compounds for catalysis and therapy

Bioorganometallic chemistry is a rapidly developing area of research. In recent years organometallic compounds have provided a rich platform for the design of effective catalysts, e.g. for olefin metathesis and transfer hydrogenation. Electronic and steric effects are used to control both the thermodynamics and kinetics of ligand substitution and redox reactions of metal ions, especially Ru II. Can similar features be incorporated into the design of targeted organometallic drugs? Such complexes offer potential for novel mechanisms of drug action through incorporation of outer-sphere recognition of targets and controlled activation features based on ligand substitution as well as metal- and ligand-based redox processes. We focus here on η 6-arene, η 5-cyclopentadienyl sandwich and half-sandwich complexes of Fe II, Ru II, Os II and Ir III with promising activity towards cancer, malaria, and other conditions. © 2012 The Royal Society of Chemistry

Redox-active and DNA-binding coordination complexes of clotrimazole

DNA interactions of anticancer mononuclear Cu2+, Co2+, Zn2+, and Ni2+ complexes with the biologically active ligand clotrimazole (clotri) are reported. To fully characterize DNA binding modes for these complexes of the formulae [M(clotri)2Cl2]·nH2O (1–4), [M(clotri)2Br2]·nH2O (5,6), [M(clotri)3NO3]NO3·nH2O (9), and [M(clotri)3(NO3)2] (10), circular dichroism (CD) and linear dichroism (LD) spectroscopy, UV melting experiments, atomic force microscopy (AFM) and ethidium bromide (EtBr) displacement methods were used. Results indicate mixed electrostatic interactions, possibly through groove binding, that result in accretion and coiling of DNA. Electrochemical studies indicate that the Cu2+ complex 9 readily reduces to the reactive-oxygen-species-generating Cu+, which oxidatively damages DNA. There is a subtle correlation between log P values, calculated electrostatic potentials, and cytotoxicity of the complexes. The extent of cell-nucleus DNA-metal adduct formation in the HeLa cervix-uterine carcinoma cell line does not necessarily correlate with cytotoxicity, indicating that the nature of DNA lesions may be crucial to activity

Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

Different Without Disagreement: Understanding Polarization in the United States

A prevailing belief is that Americans hold a shared set of values that finds expression in and is informed by our nation’s founding documents. It is puzzling, then, to acknowledge that the United States is more polarized now than at any time since Reconstruction. Our research examined possible explanations for the tension between Americans holding a shared set of values and their being highly polarized, especially concerning the following issues: abortion, capital punishment, gun control, and same-sex marriage. We found evidence that suggests there could be two types of polarization: substantive and superficial. Based on a metric we term ‘scattering,’ a measure of consensus regarding the most pertinent value for a given issue, we argue that polarization on capital punishment and gun control is substantive, while polarization on abortion and same-sex marriage is merely superficial. We argue that substantive polarization is to be preferred to superficial polarization