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The American West, from the beginning of Euro-American settlement, has been shaped by diverse ideas about how to utilize physical space and natural environments to create cohesive, sometimes exclusive community identities. When westerners developed their towns, they constructed spaces and cultural identities that reflected alternative understandings of modern urbanity. The essays in City Dreams, Country Schemes utilize an interdisciplinary approach to explore the ways that westerners conceptualized, built, and inhabited urban, suburban, and exurban spaces in the twentieth century. The contributors examine such topics as the attractions of open space and rural gentrification in shaping urban development; the role of tourism in developing national parks, historical sites, and California's Napa Valley; and the roles of public art, gender, and ethnicity in shaping urban centers. City Dreams, Country Schemes reveals the values and expectations that have shaped the West and the lives of the people who inhabit it.

Following World War II, Americans drastically changed how they built cities and how they used urban space for work, home, and play. Suburban growth and central city decline comprised two of the most pressing domestic challenges during Eisenhower's presidency. When Eisenhower took office, the nation was recovering from a severe postwar housing shortage. As middle‐class Americans created new communities on the urban rim, most turned their backs on the nation's declining city centers. During the Eisenhower era, the West epitomized the promises and perils of postwar suburban growth and metropolitan decentralization. By the mid‐1950s, cities had become the proving grounds for a national mass movement for African American civil rights. The simultaneous urbanization and politicization of Native Americans in the post‐ World War II period provides another striking example of how urban transformations sparked social movements that propelled the nation into the rights revolution of the 1960s.

Were political radicalism, political violence, and criminal behavior-which Americans increasingly conflated-rooted in historical, social, and biological causes or determined by individual choice and free will? \"These questions,\" writes Graebner, \"had deep resonance for a society caught in a post-Vietnam, post-Watergate climate of malaise, midway between the liberal zeitgeist of the 1960s and the emerging conservatism of the 1980s, between a culture that valued the endurance of the survivor and had compassion for the victim and one that longed for the transcendence of the hero\" (p. 8). In university towns like Berkeley, young people had spent the decade crafting an alternative political culture and building social spaces that allowed one to adopt a new identity and choose an alternative lifestyle: the urban guerilla, a contemporary version of the outlaw antihero, was one option.

Recently, the Vaccines to Vaccinate (v2V) initiative was reconfigured into the Partnership for Dengue Control (PDC), a multi-sponsored and independent initiative. This redirection is consistent with the growing consensus among the dengue-prevention community that no single intervention will be sufficient to control dengue disease. The PDC's expectation is that when an effective dengue virus (DENV) vaccine is commercially available, the public health community will continue to rely on vector control because the two strategies complement and enhance one another. Although the concept of integrated intervention for dengue prevention is gaining increasingly broader acceptance, to date, no consensus has been reached regarding the details of how and what combination of approaches can be most effectively implemented to manage disease. To fill that gap, the PDC proposed a three step process: (1) a critical assessment of current vector control tools and those under development, (2) outlining a research agenda for determining, in a definitive way, what existing tools work best, and (3) determining how to combine the best vector control options, which have systematically been defined in this process, with DENV vaccines. To address the first step, the PDC convened a meeting of international experts during November 2013 in Washington, DC, to critically assess existing vector control interventions and tools under development. This report summarizes those deliberations.

Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that directly target HIV-1 capsid (CA) via a novel mechanism of action. The compounds exhibit potent antiviral activity against HIV-1 laboratory strains, clinical isolates, and HIV-2, and inhibit both early and late events in the viral replication cycle. We present mechanistic studies indicating that these early and late activities result from the compound affecting viral uncoating and assembly, respectively. We show that amino acid substitutions in the N-terminal domain of HIV-1 CA are sufficient to confer resistance to this class of compounds, identifying CA as the target in infected cells. A high-resolution co-crystal structure of the compound bound to HIV-1 CA reveals a novel binding pocket in the N-terminal domain of the protein. Our data demonstrate that broad-spectrum antiviral activity can be achieved by targeting this new binding site and reveal HIV CA as a tractable drug target for HIV therapy.

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple nonhuman mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here, we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine virus, and we show that a mutation present in some recent H5 HAs causes a large antigenic change. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies,methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.

Despite estimates that, each year, as many as 300 million dengue virus (DENV) infections result in either no perceptible symptoms (asymptomatic) or symptoms that are sufficiently mild to go undetected by surveillance systems (inapparent), it has been assumed that these infections contribute little to onward transmission. However, recent blood-feeding experiments with Aedes aegypti mosquitoes showed that people with asymptomatic and pre-symptomatic DENV infections are capable of infecting mosquitoes. To place those findings into context, we used models of within-host viral dynamics and human demographic projections to (1) quantify the net infectiousness of individuals across the spectrum of DENV infection severity and (2) estimate the fraction of transmission attributable to people with different severities of disease. Our results indicate that net infectiousness of people with asymptomatic infections is 80% (median) that of people with apparent or inapparent symptomatic infections (95% credible interval (CI): 0-146%). Due to their numerical prominence in the infectious reservoir, clinically inapparent infections in total could account for 84% (CI: 82-86%) of DENV transmission. Of infections that ultimately result in any level of symptoms, we estimate that 24% (95% CI: 0-79%) of onward transmission results from mosquitoes biting individuals during the pre-symptomatic phase of their infection. Only 1% (95% CI: 0.8-1.1%) of DENV transmission is attributable to people with clinically detected infections after they have developed symptoms. These findings emphasize the need to (1) reorient current practices for outbreak response to adoption of pre-emptive strategies that account for contributions of undetected infections and (2) apply methodologies that account for undetected infections in surveillance programs, when assessing intervention impact, and when modeling mosquito-borne virus transmission.

Wearable robotic devices can restore and enhance mobility. There is growing interest in designing devices that reduce the metabolic cost of walking; however, designers lack guidelines for which joints to assist and when to provide the assistance. To help address this problem, we used musculoskeletal simulation to predict how hypothetical devices affect muscle activity and metabolic cost when walking with heavy loads. We explored 7 massless devices, each providing unrestricted torque at one degree of freedom in one direction (hip abduction, hip flexion, hip extension, knee flexion, knee extension, ankle plantarflexion, or ankle dorsiflexion). We used the Computed Muscle Control algorithm in OpenSim to find device torque profiles that minimized the sum of squared muscle activations while tracking measured kinematics of loaded walking without assistance. We then examined the metabolic savings provided by each device, the corresponding device torque profiles, and the resulting changes in muscle activity. We found that the hip flexion, knee flexion, and hip abduction devices provided greater metabolic savings than the ankle plantarflexion device. The hip abduction device had the greatest ratio of metabolic savings to peak instantaneous positive device power, suggesting that frontal-plane hip assistance may be an efficient way to reduce metabolic cost. Overall, the device torque profiles generally differed from the corresponding net joint moment generated by muscles without assistance, and occasionally exceeded the net joint moment to reduce muscle activity at other degrees of freedom. Many devices affected the activity of muscles elsewhere in the limb; for example, the hip flexion device affected muscles that span the ankle joint. Our results may help experimentalists decide which joint motions to target when building devices and can provide intuition for how devices may interact with the musculoskeletal system. The simulations are freely available online, allowing others to reproduce and extend our work.