A concise synthesis of a methyl ester 2-resorcinarene: A chair-conformation macrocycle

Anions are important hydrogen bond acceptors in a range of biological, chemical, environ-mental and medical molecular recognition processes. These interactions have been exploited for the design and synthesis of ditopic resorcinarenes as the hydrogen bond strength can be tuned through the modification of the substituent at the 2-position. However, many potentially useful compounds, especially those incorporating electron-withdrawing functionalities, have not been prepared due to the challenge of their synthesis: their incorporation slows resorcinarene formation that is accessed by electrophilic aromatic substitution. As part of our broader campaign to employ resorcinarenes as selective recognition elements, we need access to these specialized materials. In this article, we report a straightforward synthetic pathway for obtaining a 2-(carboxymethyl)-resorcinarene, and resorcinarene esters in general. We discuss the unusual conformation it adopts and propose that this arises from the electron-withdrawing nature of the ester substituents that renders them better hydrogen bond acceptors than the phenols, ensuring that each of them acts as a donor only. Density Functional Theory (DFT) calculations show that this conformation arises as a consequence of the unusual configurational isomerism of this compound and interruption of the archetypal hydrogen bonding by the ester functionality

The High Energy Solar Physics mission (HESP): Scientific objectives and technical description

The High Energy Solar Physics mission offers the opportunity for major breakthroughs in the understanding of the fundamental energy release and particle acceleration processes at the core of the solar flare problem. The following subject areas are covered: the scientific objectives of HESP; what we can expect from the HESP observations; the high energy imaging spectrometer (HEISPEC); the HESP spacecraft; and budget and schedule

MetaCyc: a multiorganism database of metabolic pathways and enzymes

MetaCyc is a database of metabolic pathways and enzymes located at . Its goal is to serve as a metabolic encyclopedia, containing a collection of non-redundant pathways central to small molecule metabolism, which have been reported in the experimental literature. Most of the pathways in MetaCyc occur in microorganisms and plants, although animal pathways are also represented. MetaCyc contains metabolic pathways, enzymatic reactions, enzymes, chemical compounds, genes and review-level comments. Enzyme information includes substrate specificity, kinetic properties, activators, inhibitors, cofactor requirements and links to sequence and structure databases. Data are curated from the primary literature by curators with expertise in biochemistry and molecular biology. MetaCyc serves as a readily accessible comprehensive resource on microbial and plant pathways for genome analysis, basic research, education, metabolic engineering and systems biology. Querying, visualization and curation of the database is supported by SRI's Pathway Tools software. The PathoLogic component of Pathway Tools is used in conjunction with MetaCyc to predict the metabolic network of an organism from its annotated genome. SRI and the European Bioinformatics Institute employed this tool to create pathway/genome databases (PGDBs) for 165 organisms, available at the website. These PGDBs also include predicted operons and pathway hole fillers

Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies

PURPOSE: Sotatercept may represent a novel approach to the treatment of chemotherapy-induced anemia (CIA). We report the results from two phase 2 randomized studies examining the use of sotatercept for the treatment of CIA in patients with metastatic cancer. METHODS: In study A011-08, patients with metastatic breast cancer were randomized to 2:2:2:1 to receive sotatercept 0.1, 0.3, or 0.5 mg/kg, or placebo, respectively, every 28 days. In study ACE-011-NSCL-001, patients with solid tumors treated with platinum-based chemotherapy received sotatercept 15 or 30 mg every 42 days. The primary endpoint for both studies was hematopoietic response, defined as a hemoglobin (Hb) increase of \u3e/=1 g/dL from baseline. RESULTS: Both studies were terminated early due to slow patient accrual. Among patients treated with sotatercept in the A011-08 and ACE-011-NSCL-001 studies, more patients achieved a mean Hb increase of \u3e/=1 g/dL in the combined sotatercept 0.3 mg/kg and 15 mg (66.7 %) group and sotatercept 0.5 mg/kg and 30 mg (38.9 %) group versus the sotatercept 0.1 mg/kg (0 %) group. No patients achieved a mean Hb increase of \u3e/=1 g/dL in the placebo group. The incidence of treatment-related adverse events (AEs) was low in both studies, and treatment discontinuations due to AEs were uncommon. CONCLUSIONS: Although both studies were terminated early, these results indicate that sotatercept is active and has an acceptable safety profile in the treatment of CIA

Spawning rings of exceptional points out of Dirac cones

The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformations of the Dirac cone often reveal intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. These two fields of research are in fact connected: here we discover the ability of a Dirac cone to evolve into a ring of exceptional points, which we call an "exceptional ring." We experimentally demonstrate this concept in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation that exists in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain

Difficult Scenarios for NMSSM Higgs Discovery at the LHC

We identify scenarios not ruled out by LEP data in which NMSSM Higgs detection at the LHC will be particularly challenging. We first review the `no-lose' theorem for Higgs discovery at the LHC that applies if Higgs bosons do not decay to other Higgs bosons - namely, with L=300 fb^-1, there is always one or more `standard' Higgs detection channel with at least a 5 sigma signal. However, we provide examples of no-Higgs-to-Higgs cases for which all the standard signals are no larger than 7 sigma implying that if the available L is smaller or the simulations performed by ATLAS and CMS turn out to be overly optimistic, all standard Higgs signals could fall below 5 sigma even in the no-Higgs-to-Higgs part of NMSSM parameter space. In the vast bulk of NMSSM parameter space, there will be Higgs-to-Higgs decays. We show that when such decays are present it is possible for all the standard detection channels to have very small significance. In most such cases, the only strongly produced Higgs boson is one with fairly SM-like couplings that decays to two lighter Higgs bosons (either a pair of the lightest CP-even Higgs bosons, or, in the largest part of parameter space, a pair of the lightest CP-odd Higgs bosons). A number of representative bench-mark scenarios of this type are delineated in detail and implications for Higgs discovery at various colliders are discussed.Comment: 31 pages, 5 figure