The Cambridge World Shakespeare Encyclopedia: An International Digital Resource for Study, Teaching, and Research

The Cambridge World Shakespeare Encyclopedia, an innovative digital reference source and workspace, is designed for collaboration among scholars, teachers, students and performers worldwide. This project addresses three challenges for the transnational humanities today. It aggregates a wealth of dispersed resources in an encyclopedic, rational and dynamic way, mapping paths of discovery. It proposes a public-private partnership that balances copyright constraints with open access to primary and secondary materials. It combines user-generated content with peer review, modeling new modes of publication for the field. An international team is developing core content, commissioned by Cambridge University Press, who will build and host the site, making it sustainable. The Center for Transformative Scholarship (USC) will support prototype design and planning. The International Shakespeare Association will partner on the project, advancing intellectual exchange among its global membership

The Day After Tomorrow

Katherine A. Rowe and A. Benjamin Spencer discuss how college leaders can help restore civil discourse after the election

Ancilla-based quantum simulation

We consider simulating the BCS Hamiltonian, a model of low temperature superconductivity, on a quantum computer. In particular we consider conducting the simulation on the qubus quantum computer, which uses a continuous variable ancilla to generate interactions between qubits. We demonstrate an O(N^3) improvement over previous work conducted on an NMR computer [PRL 89 057904 (2002) & PRL 97 050504 (2006)] for the nearest neighbour and completely general cases. We then go on to show methods to minimise the number of operations needed per time step using the qubus in three cases; a completely general case, a case of exponentially decaying interactions and the case of fixed range interactions. We make these results controlled on an ancilla qubit so that we can apply the phase estimation algorithm, and hence show that when N \geq 5, our qubus simulation requires significantly less operations that a similar simulation conducted on an NMR computer.Comment: 20 pages, 10 figures: V2 added section on phase estimation and performing controlled unitaries, V3 corrected minor typo

LPS-TLR4 Signaling to IRF-3/7 and NF-κB Involves the Toll Adapters TRAM and TRIF

Toll–IL-1–resistance (TIR) domain–containing adaptor-inducing IFN-β (TRIF)–related adaptor molecule (TRAM) is the fourth TIR domain–containing adaptor protein to be described that participates in Toll receptor signaling. Like TRIF, TRAM activates interferon regulatory factor (IRF)-3, IRF-7, and NF-κB-dependent signaling pathways. Toll-like receptor (TLR)3 and 4 activate these pathways to induce IFN-α/β, regulated on activation, normal T cell expressed and secreted (RANTES), and γ interferon–inducible protein 10 (IP-10) expression independently of the adaptor protein myeloid differentiation factor 88 (MyD88). Dominant negative and siRNA studies performed here demonstrate that TRIF functions downstream of both the TLR3 (dsRNA) and TLR4 (LPS) signaling pathways, whereas the function of TRAM is restricted to the TLR4 pathway. TRAM interacts with TRIF, MyD88 adaptor–like protein (Mal)/TIRAP, and TLR4 but not with TLR3. These studies suggest that TRIF and TRAM both function in LPS-TLR4 signaling to regulate the MyD88-independent pathway during the innate immune response to LPS

All Six Planets Known to Orbit Kepler-11 Have Low Densities

The Kepler-11 planetary system contains six transiting planets ranging in size from 1.8 to 4.2 times the radius of Earth. Five of these planets orbit in a tightly-packed configuration with periods between 10 and 47 days. We perform a dynamical analysis of the system based upon transit timing variations observed in more than three years of \ik photometric data. Stellar parameters are derived using a combination of spectral classification and constraints on the star's density derived from transit profiles together with planetary eccentricity vectors provided by our dynamical study. Combining masses of the planets relative to the star from our dynamical study and radii of the planets relative to the star from transit depths together with deduced stellar properties yields measurements of the radii of all six planets, masses of the five inner planets, and an upper bound to the mass of the outermost planet, whose orbital period is 118 days. We find mass-radius combinations for all six planets that imply that substantial fractions of their volumes are occupied by constituents that are less dense than rock. The Kepler-11 system contains the lowest mass exoplanets for which both mass and radius have been measured.Comment: 39 pages, 10 figure

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Characterization of Defects in Ion Transport and Tissue Development in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Knockout Rats

Animal models for cystic fibrosis (CF) have contributed significantly to our understanding of disease pathogenesis. Here we describe development and characterization of the first cystic fibrosis rat, in which the cystic fibrosis transmembrane conductance regulator gene (CFTR) was knocked out using a pair of zinc finger endonucleases (ZFN). The disrupted Cftr gene carries a 16 base pair deletion in exon 3, resulting in loss of CFTR protein expression. Breeding of heterozygous (CFTR+/−) rats resulted in Mendelian distribution of wild-type, heterozygous, and homozygous (CFTR−/−) pups. Nasal potential difference and transepithelial short circuit current measurements established a robust CF bioelectric phenotype, similar in many respects to that seen in CF patients. Young CFTR−/− rats exhibited histological abnormalities in the ileum and increased intracellular mucus in the proximal nasal septa. By six weeks of age, CFTR−/− males lacked the vas deferens bilaterally. Airway surface liquid and periciliary liquid depth were reduced, and submucosal gland size was abnormal in CFTR−/− animals. Use of ZFN based gene disruption successfully generated a CF animal model that recapitulates many aspects of human disease, and may be useful for modeling other CF genotypes, including CFTR processing defects, premature truncation alleles, and channel gating abnormalities

Superior Immunogenicity of Inactivated Whole Virus H5N1 Influenza Vaccine is Primarily Controlled by Toll-like Receptor Signalling

In the case of an influenza pandemic, the current global influenza vaccine production capacity will be unable to meet the demand for billions of vaccine doses. The ongoing threat of an H5N1 pandemic therefore urges the development of highly immunogenic, dose-sparing vaccine formulations. In unprimed individuals, inactivated whole virus (WIV) vaccines are more immunogenic and induce protective antibody responses at a lower antigen dose than other formulations like split virus (SV) or subunit (SU) vaccines. The reason for this discrepancy in immunogenicity is a long-standing enigma. Here, we show that stimulation of Toll-like receptors (TLRs) of the innate immune system, in particular stimulation of TLR7, by H5N1 WIV vaccine is the prime determinant of the greater magnitude and Th1 polarization of the WIV-induced immune response, as compared to SV- or SU-induced responses. This TLR dependency largely explains the relative loss of immunogenicity in SV and SU vaccines. The natural pathogen-associated molecular pattern (PAMP) recognized by TLR7 is viral genomic ssRNA. Processing of whole virus particles into SV or SU vaccines destroys the integrity of the viral particle and leaves the viral RNA prone to degradation or involves its active removal. Our results show for a classic vaccine that the acquired immune response evoked by vaccination can be enhanced and steered by the innate immune system, which is triggered by interaction of an intrinsic vaccine component with a pattern recognition receptor (PRR). The insights presented here may be used to further improve the immune-stimulatory and dose-sparing properties of classic influenza vaccine formulations such as WIV, and will facilitate the development of new, even more powerful vaccines to face the next influenza pandemic