Explore the vast range of titles available.

Pyridoxal phosphate (PLP)-dependent enzymes are unrivaled in the diversity of reactions that they catalyze. New structural data have paved the way for targeted mutagenesis and mechanistic studies and have provided a framework for interpretation of those results. Together, these complementary approaches yield new insight into function, particularly in understanding the origins of substrate and reaction type specificity. The combination of new sequences and structures enables better reconstruction of their evolutionary heritage and illuminates unrecognized similarities within this diverse group of enzymes. The important metabolic roles of many PLP-dependent enzymes drive efforts to design specific inhibitors, which are now guided by the availability of comprehensive structural and functional databases. Better understanding of the function of this important group of enzymes is crucial not only for inhibitor design, but also for the design of improved protein-based catalysts.

Fosmidomycin and related molecules comprise a family of phosphonate natural products with potent antibacterial, antimalarial and herbicidal activities. To understand the biosynthesis of these compounds, we characterized the fosmidomycin producer, Streptomyces lavendulae , using biochemical and genetic approaches. We were unable to elicit production of fosmidomycin, instead observing the unsaturated derivative dehydrofosmidomycin, which we showed potently inhibits 1-deoxy- d -xylulose-5-phosphate reductoisomerase and has bioactivity against a number of bacteria. The genes required for dehydrofosmidomycin biosynthesis were established by heterologous expression experiments. Bioinformatics analyses, characterization of intermediates and in vitro biochemistry show that the biosynthetic pathway involves conversion of a two-carbon phosphonate precursor into the unsaturated three-carbon product via a highly unusual rearrangement reaction, catalyzed by the 2-oxoglutarate dependent dioxygenase DfmD. The required genes and biosynthetic pathway for dehydrofosmidomycin differ substantially from that of the related natural product FR-900098, suggesting that the ability to produce these bioactive molecules arose via convergent evolution. The biosynthetic pathway for the phosphonate natural product dehydrofosmidomycin differs from that of the related compound FR-900098, involving rearrangement of a two-carbon phosphonate precursor catalyzed by a 2-oxoglutarate-dependent dioxygenase.

We conduct a systematic tidal disruption event (TDE) demographics analysis using the largest sample of optically selected TDEs. A flux-limited, spectroscopically complete sample of 33 TDEs is constructed using the Zwicky Transient Facility over 3 yr (from 2018 October to 2021 September). We infer the black hole (BH) mass (M BH) with host galaxy scaling relations, showing that the sample M BH ranges from 105.1 M ⊙ to 108.2 M ⊙. We developed a survey efficiency corrected maximum volume method to infer the rates. The rest-frame g-band luminosity function can be well described by a broken power law of ϕ(Lg)∝Lg/Lbk0.3+Lg/Lbk2.6−1 , with L bk = 1043.1 erg s−1. In the BH mass regime of 105.3 ≲ (M BH/M ⊙) ≲ 107.3, the TDE mass function follows ϕ(MBH)∝MBH−0.25 , which favors a flat local BH mass function ( dnBH/dlogMBH≈constant ). We confirm the significant rate suppression at the high-mass end (M BH ≳ 107.5 M ⊙), which is consistent with theoretical predictions considering direct capture of hydrogen-burning stars by the event horizon. At a host galaxy mass of M gal ∼ 1010 M ⊙, the average optical TDE rate is ≈3.2 × 10−5 galaxy−1 yr−1. We constrain the optical TDE rate to be [3.7, 7.4, and 1.6] × 10−5 galaxy−1 yr−1 in galaxies with red, green, and blue colors.

We describe a public data release of the FIRE-2 cosmological zoom-in simulations of galaxy formation (available at http://flathub.flatironinstitute.org/fire) from the Feedback In Realistic Environments (FIRE) project. FIRE-2 simulations achieve parsec-scale resolution to explicitly model the multiphase interstellar medium while implementing direct models for stellar evolution and feedback, including stellar winds, core-collapse and Type Ia supernovae, radiation pressure, photoionization, and photoelectric heating. We release complete snapshots from three suites of simulations. The first comprises 20 simulations that zoom in on 14 Milky Way (MW)–mass galaxies, five SMC/LMC-mass galaxies, and four lower-mass galaxies including one ultrafaint; we release 39 snapshots across z = 0–10. The second comprises four massive galaxies, with 19 snapshots across z = 1–10. Finally, a high-redshift suite comprises 22 simulations, with 11 snapshots across z = 5–10. Each simulation also includes dozens of resolved lower-mass (satellite) galaxies in its zoom-in region. Snapshots include all stored properties for all dark matter, gas, and star particles, including 11 elemental abundances for stars and gas, and formation times (ages) of star particles. We also release accompanying (sub)halo catalogs, which include galaxy properties and member star particles. For the simulations to z = 0, including all MW-mass galaxies, we release the formation coordinates and an “ex situ” flag for all star particles, pointers to track particles across snapshots, catalogs of stellar streams, and multipole basis expansions for the halo mass distributions. We describe publicly available python packages for reading and analyzing these simulations.

Gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, but most MBHs are considered dormant. Occasionally, a star passing too near an MBH is torn apart by gravitational forces, leading to a bright tidal disruption flare (TDF). Although the high-energy transient Sw 1644+57 initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that observations suggest a sudden accretion event onto a central MBH of mass about 10 6 to 10 7 solar masses. There is evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 to a temporary smaller-scale blazar.

The end of the Cold War has brought about significant changes in the political, economic, social, and cultural structure of the international system. Absent a distinct enemy and the threat of global thermonuclear war, the United States today faces a host of new security challenges that require policymakers to make difficult decisions with significant domestic and international implications. The range of conflicting goals, expectations, and capabilities demands fresh solutions to international conflicts and civil unrest, new strategies for conducting peace support operations, and the preparation of America's forces for completing operational assignments under increasingly uncertain conditions. The case studies and exercises constructed for this book examine some of the most pertinent management, leadership, and accountability issues related to U.S. national security. Each case places readers at the center of difficult decisions, illustrates more general policy dilemmas, and is designed to stimulate discussion of those issues beyond the classroom. Cases highlight dilemmas at two levels: pertaining specifically to the case and pertaining to its larger policy implications. The absence of a one-sided argument, specific policy recommendations, or logical conclusions, enables readers to recognize the importance of the issues at hand and their greater policy implications and to discern lessons that might apply more generally to public policy, administration, and management. Particularly useful in courses dealing with national security, international relations, public/policy administration, civil-military relations, and organizational management. An instructor's manual is available upon request.

In bulk heterojunction organic photovoltaics, electron-donating and electron-accepting materials form a distributed network of heterointerfaces in the photoactive layer, where critical photo-physical processes occur. However, little is known about the structural properties of these interfaces due to their complex three-dimensional arrangement and the lack of techniques to measure local order. Here, we report that molecular orientation relative to donor/acceptor heterojunctions is an important parameter in realizing high-performance fullerene-based, bulk heterojunction solar cells. Using resonant soft X-ray scattering, we characterize the degree of molecular orientation, an order parameter that describes face-on (+1) or edge-on (−1) orientations relative to these heterointerfaces. By manipulating the degree of molecular orientation through the choice of molecular chemistry and the characteristics of the processing solvent, we are able to show the importance of this structural parameter on the performance of bulk heterojunction organic photovoltaic devices featuring the electron-donating polymers PNDT–DTBT, PBnDT–DTBT or PBnDT–TAZ. X-ray scattering experiments indicate that the molecular orientation at the interfaces of bulk heterojunction organic solar cells influences the cells’ fill factor and short-circuit current.

Flares produced following the tidal disruption of stars by supermassive black holes can reveal the properties of the otherwise dormant majority of black holes and the physics of accretion. In the past decade, a class of optical-ultraviolet tidal disruption flares has been discovered whose emission properties do not match theoretical predictions. This has led to extensive efforts to model the dynamics and emission mechanisms of optical-ultraviolet tidal disruptions in order to establish them as probes of supermassive black holes. Here we present the optical-ultraviolet tidal disruption event AT 2022dbl, which showed a nearly identical repetition 700 days after the first flare. Ruling out gravitational lensing and two chance unrelated disruptions, we conclude that at least the first flare represents the partial disruption of a star, possibly captured through the Hills mechanism. Since both flares are typical of the optical-ultraviolet class of tidal disruptions in terms of their radiated energy, temperature, luminosity, and spectral features, it follows that either the entire class are partial rather than full stellar disruptions, contrary to the prevalent assumption, or some members of the class are partial disruptions, having nearly the same observational characteristics as full disruptions. Whichever option is true, these findings could require revised models for the emission mechanisms of optical-ultraviolet tidal disruption flares and a reassessment of their expected rates.

The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation 1 . In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation 2 . Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction 3 , 4 , share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse ( Ltap , also called Vangl2 ) and zebrafish ( vangl2 ). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.