Rounding the expanded uncertainty

Accreditation and Quality Assurance - When reporting expanded uncertainty, rounding the number of significant figures can affect the associated level of confidence. A simple numerical method is...     

Specific Design of Titanium(IV) Phenolato Chelates Yields Stable and Accessible,Effective and Selective Anticancer Agents

Octahedral titanium(IV) complexes of phenolato hexadentate ligands were developed and showed very high stability for days in water solutions. In vitro cytotoxicity studies showed that, whereas tetrakis(phenolato) systems are generally of low activity presumably due to inaccessibility, smaller bis(phenolato)bis(alkoxo) complexes feature high anticancer activity and accessibility even without formulations, also toward a cisplatin‐resistant cell line. An all‐aliphatic control complex was unstable and inactive. A leading phenolato complex also revealed: 1) high durability in fully aqueous solutions; accordingly, negligible loss of activity after preincubation for three days in medium or in serum; 2) maximal cellular accumulation and induction of apoptosis following 24–48 h of administration; 3) reduced impact on noncancerous fibroblast cells; 4) in vivo efficacy toward lymphoma cells in murine model; 5) high activity in NCI‐60 panel, with average GI₅₀ of 4.6±2 μm . This newly developed family of Ti^IV complexes is thus of great potential for anticancer therapy.     

Detoxification of Chemical Warfare Agents Using a Zr6‐Based Metal–Organic Framework/Polymer Mixture

Owing to their high surface area, periodic distribution of metal sites, and water stability, zirconium‐based metal–organic frameworks (Zr₆‐MOFs) have shown promising activity for the hydrolysis of nerve agents GD and VX, as well as the simulant, dimethyl 4‐nitrophenylphosphate (DMNP), in buffered solutions. A hurdle to using MOFs for this application is the current need for a buffer solution. Here the destruction of the simulant DMNP, as well as the chemical warfare agents (GD and VX) through hydrolysis using a MOF catalyst mixed with a non‐volatile, water‐insoluble, heterogeneous buffer is reported. The hydrolysis of the simulant and nerve agents in the presence of the heterogeneous buffer was fast and effective.     

Identification of Structure–Activity Relationships from Screening a Structurally Compact DNA‐Encoded Chemical Library

Methods for the rapid and inexpensive discovery of hit compounds are essential for pharmaceutical research and DNA‐encoded chemical libraries represent promising tools for this purpose. We here report on the design and synthesis of DAL‐100K, a DNA‐encoded chemical library containing 103 200 structurally compact compounds. Affinity screening experiments and DNA‐sequencing analysis provided ligands with nanomolar affinities to several proteins, including prostate‐specific membrane antigen and tankyrase 1. Correlations of sequence counts with binding affinities and potencies of enzyme inhibition were observed and enabled the identification of structural features critical for activity. These results indicate that libraries of this type represent a useful source of small‐molecule binders for target proteins of pharmaceutical interest and information on structural features important for binding.     

Allenyl esters as quenching agents for ruthenium olefin metathesis catalysts

In the attempt to synthesize substituted allenyl esters through a metathesis coupling of unsubstituted allenyl esters and alkenes using a variety of ruthenium catalysts, it was discovered that allenyl esters themselves cleanly arrested the activity of the catalysts. Further studies suggests possible utility of allene esters as general quenching agents for metathesis reactions. To explore this idea, several representative olefin metathesis reactions, including ring closing, were successfully terminated by the addition of simple allenyl esters for more convenient purification.     

On the receptivity and nonparallel stability of traveling disturbances in rotating-disk flow

The generation and evolution of small amplitude long wavelength traveling disturbances in rotating-disk flow is the subject of this paper. The steady rotational speed of the disk is perturbed so as to introduce high-frequency oscillations in the flow field. Secondly, we introduce surface imperfections on the disk such as roughness elements. The interaction of these two disturbances will generate the instability waves whose evolution is governed by parabolic partial differential equations which are solved numerically. It is found that, for the class of disturbances considered here (wavelength on the order of Reynolds number), eigensolutions exist which decay or grow algebraically in the radial direction. However, these solutions grow only for frequencies larger than 4.58 times the steady rotational speed of the disk. The computed receptivity coefficient shows that there is an optimum size of roughness for which these modes are preferentially excited. The width of these roughness elements in the radial direction is about 0.1r ₀ ^* where r ₀ ^* is the radial location of the roughness. It is also found that the receptivity coefficient is larger for a negative spanwise wave number than for a positive one. The cumulative wave pattern produced from the roughness site shows that the typical wave angles for these disturbances are about –26° with about seven waves around the circumference. This is in contrast with the wave angles of 10°–14° found for the 30 or so inviscid cross-flow vortices.This work was sponsored by NASA Langley Research Center under Contracts NAS1-18240 (P.B. and M.R.M.) and NAS1-18605 (P.H.).