Functional expression of the yeast alpha-factor receptor in Xenopus oocytes

The STE2 gene of the yeast Saccharomyces cerevisiae encodes a 431- residue polypeptide that has been shown by chemical cross-linking and genetic studies to be a component of the receptor for the peptide mating pheromone, alpha-factor. To demonstrate directly that the ligand binding site of the alpha-factor receptor is comprised solely of the STE2 gene product, the STE2 protein was expressed in Xenopus oocytes. Oocytes microinjected with synthetic STE2 mRNA displayed specific surface binding for 35S-labeled alpha-factor (up to 40 sites/micron2/ng RNA). Oocytes injected with either STE2 antisense RNA or heterologous receptor mRNA (nicotinic acetylcholine receptor alpha, beta, gamma, and delta subunit mRNAs) showed no binding activity (indistinguishable from uninjected control oocytes). The apparent KD (7 nM) of the alpha-factor binding sites expressed on the oocyte surface, determined by competition binding studies, agreed with the values reported for intact yeast cells and yeast plasma membrane fractions. These findings demonstrate that the STE2 gene product is the only yeast polypeptide required for biogenesis of a functional alpha-factor receptor. Electrophysiological measurements indicated that the membrane conductance of oocytes injected with STE2 mRNA, or with both STE2 and GPA1 (encoding a yeast G protein alpha-subunit) mRNAs, did not change and was not affected by pheromone binding. Thus, the alpha-factor receptor, like mammalian G protein-coupled receptors, apparently lacks activity as an intrinsic or ligand-gated ion channel. This report is the first instance in which a membrane-bound receptor from a unicellular eukaryote has been expressed in a vertebrate cell

Gold substrate-induced single-mode lasing of GaN nanowires

We demonstrate a method for mode-selection by coupling a GaN nanowire laser to an underlying gold substrate. Multimode lasing of GaN nanowires is converted to single-mode behavior following placement onto a gold film. A mode-dependent loss is generated by the absorbing substrate to suppress multiple transverse-mode operation with a concomitant increase in lasing threshold of only ∼13%. This method provides greater flexibility in realizing practical single-mode nanowire lasers and offers insight into the design of metal-contacted nanoscale optoelectronics

The “Ayde of his Muses?”The Renaissance of John Florio and William Shakespeare

Jeremy Lester’s essay focuses on John Florio, arguing a far deeper implication of the prominent linguist and translator of Montaigne in the production of the Shakespearean oeuvre than previously thought. Although known by specialists, until not long ago, Florio was considered a secondary figure within the intellectual and artistic panorama of the Elizabethan and Jacobean times. After examining closely the life and works of Florio in accordance with Lamberto Tassinari’s book John Florio. The Man Who Was Shakespeare (Giano Books, 2009), Lester discusses the case of British scholar Saul Frampton of Westminster University who in two feature articles published in the London Guardian in July and August, 2013, asserted that John Florio was the editor-in-chief of Shakespeare’s collected plays (the First Folio, 1623). According to Frampton, this role allowed him to “censor,”“change” or “supplement” the original works of Shakespeare. Ben Jonson, the main instigator in the publication of the First Folio, was also a close friend and devotee of Florio, of whom he states in a dedication to a copy of his Volpone, that he was “an Ayde of his Muses.” Analyzing Tassinari’s theory, Lester comes to the conclusion that Florio, more than the editor and “Ayde” to the Bard, has a very good claim to be considered the author under the pseudonym Shakespeare. Tassinari’s book, now translated into French with the title John Florio alias Shakespeare (Le Bord de L’Eau, 2016), is sparking an animated debate within the French media

A high-resolution infrared spectroscopic investigation of the halogen atom-HCN entrance channel complexes solvated in superfluid helium droplets

Rotationally resolved infrared spectra are reported for the X-HCN (X = Cl, Br, I) binary complexes solvated in helium nanodroplets. These results are directly compared with that obtained previously for the corresponding X-HF complexes [J. M. Merritt, J. K\"upper, and R. E. Miller, PCCP, 7, 67 (2005)]. For bromine and iodine atoms complexed with HCN, two linear structures are observed and assigned to the $^{2}\Sigma_{1/2}$ and $^{2}\Pi_{3/2}$ ground electronic states of the nitrogen and hydrogen bound geometries, respectively. Experiments for HCN + chlorine atoms give rise to only a single band which is attributed to the nitrogen bound isomer. That the hydrogen bound isomer is not stabilized is rationalized in terms of a lowering of the isomerization barrier by spin-orbit coupling. Theoretical calculations with and without spin-orbit coupling have also been performed and are compared with our experimental results. The possibility of stabilizing high-energy structures containing multiple radicals is discussed, motivated by preliminary spectroscopic evidence for the di-radical Br-HCCCN-Br complex. Spectra for the corresponding molecular halogen HCN-X$_{2}$ complexes are also presented.Comment: 20 pages, 15 figures, 6 tables, RevTe

Gothic visions of classical architecture in Hablot Knight Browne’s “dark” illustrations for the novels of Charles Dickens

In the early gothic literature of the eighteenth century danger lurked in the darkness beneath the pointed arches of gothic buildings. During the nineteenth century there was a progressive, although never complete, dislocation of gothic literary readings from gothic architecture. This article explores a phase in that development through discussion of a series of ‘dark’ illustrations produced by Hablot Knight Browne to illustrate novels by Charles Dickens. These show the way in which the rounded arches of neo-classical architecture were depicted in the mid-nineteenth century as locales of oppression and obscurity. Such depictions acted, in an age of political and moral reform, to critique the values of the system of power and authority that such architecture represented

Entrance Channel X-HF (X=Cl, Br, and I) Complexes studied by High-Resolution Infrared Laser Spectroscopy in Helium Nanodroplets

Rotationally resolved infrared spectra are reported for halogen atom - HF free radical complexes formed in helium nanodroplets. An effusive pyrolysis source is used to dope helium droplets with Cl, Br and I atoms, formed by thermal dissociation of Cl$_2$, Br$_2$ and I$_2$. A single hydrogen fluoride molecule is then added to the droplets, resulting in the formation of the X-HF complexes of interest. Analysis of the resulting spectra confirms that the observed species have $^2\Pi_{3/2}$ ground electronic states, consistent with the linear hydrogen bound structures predicted from theory. Stark spectra are also reported for these species, from which the permanent electric dipole moments are determined.Comment: 41 pages, 16 figures, 5 table

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

The AI Institute for Engaged Learning

The EngageAI Institute focuses on AI‐driven narrative‐centered learning environments that create engaging story‐based problem‐solving experiences to support collaborative learning. The institute's research has three complementary strands. First, the institute creates narrative‐centered learning environments that generate interactive story‐based problem scenarios to elicit rich communication, encourage coordination, and spark collaborative creativity. Second, the institute creates virtual embodied conversational agent technologies with multiple modalities for communication (speech, facial expression, gesture, gaze, and posture) to support student learning. Embodied conversational agents are driven by advances in natural language understanding, natural language generation, and computer vision. Third, the institute is creating an innovative multimodal learning analytics framework that analyzes parallel streams of multimodal data derived from students’ conversations, gaze, facial expressions, gesture, and posture as they interact with each other, with teachers, and with embodied conversational agents. Woven throughout the institute's activities is a strong focus on ethics, with an emphasis on creating AI‐augmented learning that is deeply informed by considerations of fairness, accountability, transparency, trust, and privacy. The institute emphasizes broad participation and diverse perspectives to ensure that advances in AI‐augmented learning address inequities in STEM. The institute brings together a multistate network of universities, diverse K‐12 school systems, science museums, and nonprofit partners. Key to all of these endeavors is an emphasis on diversity, equity, and inclusion

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio