A Hybrid Platform Based on a Bispecific Peptide–Antibody Complex for Targeted Cancer Therapy

Peptide‐based therapeutics have suffered from a short plasma half‐life. On the other hand, antibodies suffer from poor penetration into solid tumors owing to their large size. Herein, we present a new molecular form, namely a hybrid complex between a hapten‐labeled bispecific peptide and an anti‐hapten antibody (“HyPEP‐body”), that may be able to overcome the aforementioned limitation. The bispecific peptide containing a cotinine tag was synthesized by linking a peptide specific to fibronectin extra domain B (EDB) and a peptide able to bind and inhibit vascular endothelial growth factor (VEGF), yielding cot‐biPEP_EDB‐VEGF. Simple mixing of cot‐biPEP_EDB‐VEGF and anti‐cotinine antibody (Ab^cot) yielded the hybrid complex, HyPEP_EDB‐VEGF. HyPEP_EDB‐VEGF retained the characteristics of the included peptides, and showed improved pharmacokinetic behavior. Moreover, HyPEP_EDB‐VEGF showed tumor growth inhibition with excellent tumor accumulation and penetration. These findings suggest that the hybrid platform described here offers a solution for most peptide therapeutics that suffer from a short circulation half‐life in blood.     

Changing the rules of the game: used fuel studies outside of a remote handling facility

Journal of Radioanalytical and Nuclear Chemistry - Pacific Northwest National Laboratory (PNNL) has leveraged focused ion beam capability at their Category II Nuclear Facility to facilitate nuclear...     

Single Metal Ohmic and Rectifying Contacts to ZnO Nanowires: A Defect Based Approach

Ohmic and rectifying metal contacts to semiconductor nanowires are integral to electronic device structures and typically require different metals and different process techniques to form. Here we show how a noble metal ion beam of Pt commonly used to pattern conducting contacts in electron microscopes can form both ohmic and Schottky/blocking contacts on ZnO nanowires by controlling native point defects at the intimate metal‐semiconductor interface. Spatially‐resolved cathodoluminescence spectroscopy on a nanoscale both laterally and in depth gauges the nature, density, and spatial distribution of specific native point defects inside the nanowires and at their metal interfaces. Combinations of electron and ion beam deposition, annealing, and sculpting of the same nanowire provide either low contact resistivity ohmic contacts or a high Schottky/blocking barrier with a single metal source. These results highlight the importance of native point defects distributed inside nanowires and their variation near interfaces with sculpting and annealing.     

The foreign language cocktail party problem: Energetic and informational masking effects in non-native speech perception

Studies comparing native and non-native listener performance on speech perception tasks can distinguish the roles of general auditory and language-independent processes from those involving prior knowledge of a given language. Previous experiments have demonstrated a performance disparity between native and non-native listeners on tasks involving sentence processing in noise. However, the effects of energetic and informational masking have not been explicitly distinguished. Here, English and Spanish listener groups identified keywords in English sentences in quiet and masked by either stationary noise or a competing utterance, conditions known to produce predominantly energetic and informational masking, respectively. In the stationary noise conditions, non-native talkers suffered more from increasing levels of noise for two of the three keywords scored. In the competing talker condition, the performance differential also increased with masker level. A computer model of energetic masking in the competing talker condition ruled out the possibility that the native advantage could be explained wholly by energetic masking. Both groups drew equal benefit from differences in mean F0 between target and masker, suggesting that processes which make use of this cue do not engage language-specific knowledge.     

Geometry of optimality conditions and constraint qualifications

Certain types of necessary optimality conditions for mathematical programming problems are equivalent to corresponding regularity conditions on the constraint set. For any problem, a certain natural optimality condition, dependent upon the particular constraint set, is always satisfied. This condition can be strengthened in numerous ways by invoking appropriate regularity assumptions on the constraint set. Results are presented for Euclidean spaces and some extensions to Banach spaces are given.This work was supported in part by the Office of Naval Research, Contract No. N00014-67-A-0321-0003 (NR-047-095).     

The reaction of the cyclooctatetraenyl dianion and chlorotrimethylsilane; synthesis and decomposition studies of 5,8-bis(trimethylsilyl)cyclooctatriene

On the basis of PMR decoupling experiments and thermal decomposition studies, the reaction of the cyclooctatetraenyl dianion and chlorotrimethylsilane produces 5,8-bis(trimethylsilyl)-l,3,6-cyclooctatriene, in contrast to a previous report which suggested 7,8-bis(trimethylsilyl)-l,3,5-cyclooctatriene. The product is stable at room temperature in vacuo but undergoes decomposition (isomerization) reactions at higher temperatures or in contact with air.     

Fundamental relationships in the theory of electric multipole moments and multipole polarizabilities in static fields

New derivations are given of equations relating molecular electric multipole moments and polarizabilities of general order to the electrostatic energy. The unabridged moment convention is shown to yield relatively simple relations between derivatives of the energy with respect to field gradients and the multipole moments and polarizabilities. Care is taken to distinguish various forms of these derivatives, and one form leads to a proof of a general symmetry of polarizability tensors with respect to permutations of rank indices. The condition of internal equilibrium is shown to be fundamental to the existence of this symmetry. The transformation of multipole moment and polarizability tensors under translation of the coordinate origin is expressed in relatively simple general form. The traceless multipole and polarizability tensors of Buckingham and McLean and Yoshimine are obtained as linear combinations of the unabridged tensors and their traces.