Emerging Therapies for Advanced Clear Cell Renal Cell Carcinoma

Multiple combinational regimens have recently been approved and are now considered the standard of care for patients with advanced clear cell renal cell carcinoma (RCC). Several additional combinational regimens are deep in clinical assessment and are likely to soon join the crowded front-line therapeutic landscape. Most of these regimens are combinations of agents already approved as single-agents in RCC including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors. While these new front-line regimens are associated with reliably high response rates and prolonged survival, complete and durable remissions remain limited to a small subset of patients and the vast majority of patients continue to require subsequent therapy. The need for the continued development of novel agents in RCC persists and efforts have focused on agents targeting the molecular biology of clear cell RCC and novel immunotherapies including cytokines. In this review, we discuss the progress in the development of these novel therapies in the context of the evolving standard of care for patients with advanced clear cell RCC

Faint Infrared Flares from the Microquasar GRS 1915+105

We present simultaneous infrared and X-ray observations of the Galactic microquasar GRS 1915+105 using the Palomar 5-m telescope and Rossi X-ray Timing Explorer on July 10, 1998 UT. Over the course of 5 hours, we observed 6 faint infrared (IR) flares with peak amplitudes of $\sim 0.3-0.6$ mJy and durations of $\sim 500-600$ seconds. These flares are associated with X-ray soft-dip/soft-flare cycles, as opposed to the brighter IR flares associated with X-ray hard-dip/soft-flare cycles seen in August 1997 by Eikenberry et al. (1998). Interestingly, the IR flares begin {\it before} the X-ray oscillations, implying an ``outside-in'' origin of the IR/X-ray cycle. We also show that the quasi-steady IR excess in August 1997 is due to the pile-up of similar faint flares. We discuss the implications of this flaring behavior for understanding jet formation in microquasars.Comment: 10 pages, 4 figures Accepted for publication in ApJ Letter

Climate-modulated range expansion of reef-building coral communities off southeast Florida during the late Holocene

The Holocene reefs off southeast Florida provide unique insights into the biogeographical and ecological response of western Atlantic coral reefs to past climate change that can be used to evaluate future climate impacts. However, previous studies have focused on millennial-scale change during the stable mid-Holocene, making it difficult to make inferences about the impact of shorter-term variability that is relevant to modern climate warming. Using uranium-series dating of newly discovered subfossil coral rubble deposits, we establish a new high-resolution record of coral community development off southeast Florida during a period of variable climate in the late Holocene. Our results indicate that coral communities dominated by reef-building Acropora palmata and Orbicella spp. persisted in the nearshore environments off southeast Florida ~75 km north of their primary historical ranges between ~3500 and 1800 years before present. This timing coincides with regional warming at the northern extent of the Atlantic Warm Pool, suggesting a likely link between regional oceanographic climate and the expansion of cold-sensitive reef-building coral communities to the high-latitude reefs off southeast Florida. These findings not only extend the record of coral-reef development in southeast Florida into the late Holocene, but they also have important implications for future range expansions of reef-building coral communities in response to modern climate change

Non-invasive detection of the evolution of the charge states of a double dot system

Coupled quantum dots are potential candidates for qubit systems in quantum computing. We use a non-invasive voltage probe to study the evolution of a coupled dot system from a situation where the dots are coupled to the leads to a situation where they are isolated from the leads. Our measurements allow us to identify the movement of electrons between the dots and we can also identify the presence of a charge trap in our system by detecting the movement of electrons between the dots and the charge trap. The data also reveals evidence of electrons moving between the dots via excited states of either the single dots or the double dot molecule.Comment: Accepted for publication in Phys. Rev. B. 4 pages, 4 figure

A model of diffuse Galactic Radio Emission from 10 MHz to 100 GHz

Understanding diffuse Galactic radio emission is interesting both in its own right and for minimizing foreground contamination of cosmological measurements. Cosmic Microwave Background experiments have focused on frequencies > 10 GHz, whereas 21 cm tomography of the high redshift universe will mainly focus on < 0.2 GHz, for which less is currently known about Galactic emission. Motivated by this, we present a global sky model derived from all publicly available total power large-area radio surveys, digitized with optical character recognition when necessary and compiled into a uniform format, as well as the new Villa Elisa data extending the 1.4 GHz map to the entire sky. We quantify statistical and systematic uncertainties in these surveys by comparing them with various global multi-frequency model fits. We find that a principal component based model with only three components can fit the 11 most accurate data sets (at 10, 22, 45 & 408 MHz and 1.4, 2.3, 23, 33, 41, 61, 94 GHz) to an accuracy around 1%-10% depending on frequency and sky region. Both our data compilation and our software returning a predicted all-sky map at any frequency from 10 MHz to 100 GHz are publicly available at http://space.mit.edu/home/angelica/gsm .Comment: Accuracy improved with 5-year WMAP data. Our data, software and new foreground-cleaned WMAP map are available at https://ascl.net/1011.01

The Molecular Clockwork of the Fire Ant Solenopsis invicta

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8(+) T cells (CD44(hi)CD62L(hi)CCR7(+)). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8(+) T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8(+) central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured