Awareness of genetic testing for increased cancer risk in the year 2000 National Health Interview Survey

OBJECTIVES: This study explores factors associated with differential awareness of genetic tests for increased cancer risk in the US. METHODS: 27,405 respondents from the 2000 National Health Interview Survey, ages 25+, were asked if they had heard of these tests. RESULTS: 44.4% said 'yes', including 49.9% of whites, 32.9% of African-Americans, 32.3% of American Indians/Alaskan Natives, 28.0% of Asian/Pacific Islanders, and 20.6% of Hispanics. In multivariate analysis, test awareness was significantly associated with higher education, white race, age <60 years, female gender, private health insurance, personal or parent's history of certain cancers, physical activity, and vitamin/supplement use, among other factors. CONCLUSIONS: The survey showed which population subgroups may lack access to cancer genetics information and may therefore benefit from targeted strategies to ensure risk-appropriate utilization of genetic counseling and testing.     

Design,Synthesis and Structural Analysis of Glucocerebrosidase Imaging Agents

Gaucher disease (GD) is a lysosomal storage disorder caused by inherited deficiencies in β-glucocerebrosidase (GBA). Current treatments require rapid disease diagnosis and a means of monitoring therapeutic efficacy, both of which may be supported by the use of GBA-targeting activity-based probes (ABPs). Here, we report the synthesis and structural analysis of a range of cyclophellitol epoxide and aziridine inhibitors and ABPs for GBA. We demonstrate their covalent mechanism-based mode of action and uncover binding of the new N-functionalised aziridines to the ligand binding cleft. These inhibitors became scaffolds for the development of ABPs; the O6-fluorescent tags of which bind in an allosteric site at the dimer interface. Considering GBA's preference for O6- and N-functionalised reagents, a bi-functional aziridine ABP was synthesized as a potentially more powerful imaging agent. Whilst this ABP binds to two unique active site clefts of GBA, no further benefit in potency was achieved over our first generation ABPs. Nevertheless, such ABPs should serve useful in the study of GBA in relation to GD and inform the design of future probes.     

Sterically demanding macrocyclic Eu(iii) complexes for selective recognition of phosphate and real-time monitoring of enzymatically generated adenosine monophosphate

The design of molecular receptors that bind and sense anions in biologically relevant aqueous solutions is a key challenge in supramolecular chemistry. The recognition of inorganic phosphate is particularly challenging because of its high hydration energy and pH dependent speciation. Adenosine monophosphate (AMP) represents a valuable but elusive target for supramolecular detection because of its structural similarity to the more negatively charged anions, ATP and ADP. We report two new macrocyclic Eu(iii) receptors capable of selectively sensing inorganic phosphate and AMP in water. The receptors contain a sterically demanding 8-(benzyloxy)quinoline pendant arm that coordinates to the metal centre, creating a binding pocket suitable for phosphate and AMP, whilst excluding potentially interfering chelating anions, in particular ATP, bicarbonate and lactate. The sensing selectivity of our Eu(iii) receptors follows the order AMP > ADP > ATP, which represents a reversal of the order of selectivity observed for most reported nucleoside phosphate receptors. We have exploited the unique host–guest induced changes in emission intensity and lifetime for the detection of inorganic phosphate in human serum samples, and for monitoring the enzymatic production of AMP in real-time.

We present two new europium-based anion receptors that selectively bind to inorganic phosphate and AMP in aqueous media. Their sensing selectivity follows the order AMP > ADP > ATP, representing a reversal of the selectivity order observed for most nucleoside phosphate receptors.     

A Krasnosel’skii theorem for orthogonal polygons starshaped via staircase (n + 1)-paths

Let S be a simply connected orthogonal polygon in the plane, and let n be fixed, n ≥ 1. If every two points of S are visible via staircase n-paths from a common point of S, then S is starshaped via staircase (n + 1)-paths. Moreover, the associated staircase (n + 1)-kernel is staircase (n + 1)-convex. The number two is best possible, and the number n + 1 is best possible for n ≥ 2.     

Intersections and Unions of Orthogonal Polygons Starshaped Via Staircase n-Paths

For n ≥ 1, define p (n) to be the smallest natural number r for which the following is true: For any finite family of simply connected orthogonal polygons in the plane and points x and y in , if every r (not necessarily distinct) members of contain a common staircase n-path from x to y, then contains such a path. We show that p(1) = 1 and p(n) = 2 (n − 1) for n ≥ 2. The numbers p(n) yield an improved Helly theorem for intersections of sets starshaped via staircase n-paths. Moreover, we establish the following dual result for unions of these sets: Let be any finite family of orthogonal polygons in the plane, with simply connected. If every three (not necessarily distinct) members of have a union which is starshaped via staircase n-paths, then T is starshaped via staircase (n + 1)-paths. The number n + 1 in the theorem is best for every n ≥ 2.     

New dialkyldithiophosphinic acid self-assembled monolayers (SAMs): influence of gold substrate morphology on adsorbate binding and SAM structure

We report the fabrication and characterization of new self-assembled monolayers (SAMs) formed from dihexadecyldithiophosphinic acid [(C(16))(2)DTPA] molecules on gold substrates. In these SAMs, the ability of the (C(16))(2)DTPA headgroup to chelate to the gold surface depends on the morphology of the gold substrate. Gold substrates fabricated by electron-beam evaporation (As-Dep gold) consist of ～50-nm grains separated by deep grain boundaries (～10 nm). These grain boundaries inhibit the chelation of (C(16))(2)DTPA adsorbates to the surface, producing SAMs in which there is a mixture of monodentate and bidentate adsorbates. In contrast, gold substrates produced by template stripping (TS gold) consist of larger grains (～200-500 nm) with shallower grain boundaries (<2 nm). On these substrates, the low density of shallow grain boundaries allows (C(16))(2)DTPA molecules to chelate to the surface, producing SAMs in which all molecules are bidentate. The content of bidentate adsorbates in (C(16))(2)DTPA SAMs formed on As-Dep and TS gold substrates strongly affects the SAM properties: Alkyl chain organization, wettability, frictional response, barrier properties, thickness, and thermal stability all depend on whether a SAM has been formed on As-Dep or TS gold. This study demonstrates that substrate morphology has an important influence on the structure of SAMs formed from these chelating adsorbates.     

Practical limitations on astrophysical observations of methanol to investigate variations in the proton-to-electron mass ratio

The possibility of using astrophysical observations of rotational transitions in the methanol molecule to measure, or constrain temporal and spatial variations in the proton-to-electron mass ratio (μ) has recently been investigated by several groups. Here we outline some of the practical considerations of making such observations, including both the instrumental and astrophysical limitations which exist at present. This leads us to conclude that such observations are unlikely to be able to improve evidence either for, or against the presence of variations in the proton-to-electron mass ratio by more than an order of magnitude beyond current limits.     

A visible shoreline theorem for staircase paths

Let C be an orthogonal polygon in the plane, bounded by a simple closed curve, and assume that C is starshaped via staircase paths. Let P í \mathbbR²\(int C)P \subseteq {\mathbb{R}}^2\backslash({\rm int} C). If every four points of P see a common boundary point of C via staircase paths in \mathbbR²\(int C){\mathbb{R}}^2\backslash({\rm int} C), then there is a boundary point b of C such that every point of P sees b (via staircase paths in \mathbbR²\(int C){\mathbb{R}}^2\backslash({\rm int} C)). The number four is best possible, even if C is orthogonally convex.