As central regulators of asthma pathogenesis, allergen- specific CD4+ T cells are recruited to the lungs and secrete sustained levels of Th2 cytokines upon reencounter with inhaled allergen leading to the development of the hallmark indicators of asthma including airway hyperresponsiveness, mucus production and the recruitment of eosinophils to the affected lung tissue. Selectively upregulated in Th2 cells, Itk is a member of the Tec familiy of non-receptor tyrosine kinases and is required for Th2 cell development and effector function. Upon stimulation through the TCR, Itk associates with the adaptor protein SLP-76 and is recruited to the immunological synapse as part of a stable signaling complex leading to its subsequent enzymatic activation. As previously discovered using purified domain fragments, the Itk SH3 domain binds to its specific polyproline ligand represented by the amino acid sequence QQPPVPPQRPMA located on SLP-76 with a reported affinity of 0.77 mM (1). By modifying this sequence with the addition of a polyarginine cell penetration motif, Grasis et al. recently demonstrated that the engineered peptide designated R9-QQP was effective as a competitive inhibitor of Itk activation (2). In the current work, R9-QQP was translated to an OVA-inducible model of experimental asthma. Upon delivery in vivo, R9-QQP was demonstrated to specifically inhibit physiologically relevant parameters of airway inflammation and was further characterized as affecting the recruitment of eosinophils to the lung mucosa. Consistent with the role of Itk, Th2 cytokine secretion by lung draining lymph node cells was reduced upon restimulation with OVA in vitro. While current treatments are effective for most patients with clinical asthma, undesirable side effects as well as lack of effectiveness for some patients underscores the need to develop additional therapeutic strategies that target the immunological basis of allergic disease progression. By blocking an inducible and T cell-specific interaction, this study establishes the importance of the Itk-SLP-76 interaction in an allergic disease model as an attractive therapeutic target for the future development of biologically active small molecules inhibitors

The United States’ long-standing approach to the People’s Republic of China—“engagement”—is at an end, replaced by a tougher approach, labeled “strategic competition.” Foregrounding the role of knowledge communities in the making of US foreign policy, I show that engagement’s demise followed less a rational process responding to shifts in Chinese behavior and the balance of power, and more a paradigmatic turnover in key individuals’ views of China within the government and the China expert community. Adopting a sociological perspective attuned to the social and professional underpinnings of US foreign policy, I trace the paradigmatic turnover in US views of China to three processes: politicization, professional status competition, and personalization. Drawing on a range of sources, including over one hundred original interviews with members of the US China expert community, this article traces the entanglement of engagement at once political, professional, and deeply personal.

[No abstract]

Convective entrainment is a process that is poorly represented in existing convective parameterizations. By many estimates, convective entrainment is the leading source of error in global climate models. As a potential remedy, an Eulerian implementation of the Stochastic Parcel Model (SPM) is presented here as a convective parameterization that treats entrainment in a physically realistic and computationally efficient way. Drawing on evidence that convecting clouds comprise air parcels subject to Poisson-process entrainment events, the SPM calculates the deterministic limit of an infinite number of such parcels. For computational efficiency, the SPM groups parcels at each height by their purity, which is a measure of their total entrainment up to that height. This reduces the calculation of convective fluxes to a sequence of matrix multiplications. The SPM is implemented in a single-column model and compared with a large-eddy simulation of deep convection.

Before you can evaluate the suitability of a compost for a particular application, you need to have an understanding of several compost properties. This publication describes these properties and proposes reasonable limits for five common types of compost

We demonstrate a technique to nanofabricate nitrogen vacancy (NV) centers in diamond based on broad-beam nitrogen implantation through apertures in electron beam lithography resist. This method enables high-throughput nanofabrication of single NV centers on sub-100-nm length scales. Secondary ion mass spectroscopy measurements facilitate depth profiling of the implanted nitrogen to provide three-dimensional characterization of the NV center spatial distribution. Measurements of NV center coherence with on-chip coplanar waveguides suggest a pathway for incorporating this scalable nanofabrication technique in future quantum applications.