Clinical applications of pharmacologic therapies for spinal cord injury

We review the evidence supporting the role of glucocorticosteroids, trilazad, and GM1 ganglioside in spinal cord injury and provide our critique of the published studies, along with our recommendations for pharmacologic therapy for this complex and difficult problem.     

Probing protein structure by amino acid‐specific covalent labeling and mass spectrometry

For many years, amino acid‐specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. These covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. The reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label and the reactivity of the amino acid side chain. Peptide mass mapping with ESI‐ or MALDI‐MS and peptide sequencing with tandem MS are typically employed to identify modification sites to provide site‐specific structural information. In this review, we describe the reagents that are most commonly used in these residue‐specific modification reactions, details about the proper use of these covalent labeling reagents, and information about the specific biochemical problems that have been addressed with covalent labeling strategies. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 28:785–815, 2009     

Gadolinium-containing copolymeric chelates—a new potential MR contrast agent

Rationale and objectives: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents.Methods: Various copolymeric chelates of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium-DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd-copolymers.Results: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2% on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. Ther ₁ (1/T1, mM⁻¹ s⁻¹) for Gd-DTPA=4.1. Ther ₁ values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowestr ₁ for the polymer prepared with the lowest-molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd-DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement—a reflection of distribution into extravascular fluid space—was observed.Conclusions: Relative to Gd-DTPA monomers, PEG-containing Gd-DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50% increase inr ₁ relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd-copolymers are promising agents that merit additional study.     

On-line restricted assignment of temporary tasks with unknown durations

We consider load balancing of temporary tasks on m machines in the restricted assignment model. It is known that the best competitive ratio for this problem is . This bound is not achieved by the greedy algorithm whose competitive ratio is known to be Ω(m2/3). We give an alternative analysis to the greedy algorithm which is better than the known analysis for relatively small values of m. We also show that for a small number of machines, namely m?5, the greedy algorithm is optimal.     

Tight Bounds on the Competitive Ratio on Accommodating Sequences for the Seat Reservation Problem

The unit price seat reservation problem is investigated. The seat reservation problem is the problem of assigning seat numbers on-line to requests for reservations in a train traveling through k stations. We are considering the version where all tickets have the same price and where requests are treated fairly, that is, a request which can be fulfilled must be granted.For fair deterministic algorithms, we provide an asymptotically matching upper bound to the existing lower bound which states that all fair algorithms for this problem are -competitive on accommodating sequences, when there are at least three seats.Additionally, we give an asymptotic upper bound of for fair randomized algorithms against oblivious adversaries.We also examine concrete on-line algorithms, First-Fit and Random for the special case of two seats. Tight analyses of their performance are given.     

Optical and MRI multifunctional nanoprobe for targeting gliomas

A multifunctional nanoprobe capable of targeting glioma cells, detectable by both magnetic resonance imaging and fluorescence microscopy, was developed. The nanoprobe was synthesized by coating iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG) polymer, which were subsequently functionalized with chlorotoxin and the near-infrared fluorescing molecule Cy5.5. Both MR imaging and fluorescence microscopy showed significant preferential uptake of the nanoparticle conjugates by glioma cells. Such a nanoprobe could potentially be used to image resections of glioma brain tumors in real time and to correlate preoperative diagnostic images with intraoperative pathology at cellular-level resolution.     

Schizophrenic patterns of arousal and stimulus barrier functioning.

Investigated the psychophysiological arousal and psychological stimulus barrier functioning in 20 male chronically hospitalized schizophrenics, 20 male outpatient schizophrenics with minimal institutionalization, and 20 male controls. Each S completed the Beck Depression Inventory (Short Form), the Structured Clinical Interview, and the Taylor Manifest Anxiety Scale. Also, each S was administered a stimulus barrier assessment interview, and skin conductance characteristics were measured in response to a standardized sequence of 15 1,000-Hz, 75-db tones. After 6 wks, the procedure was repeated. All schizophrenics exhibited either of 2 abnormal patterns of arousal that were never shown by the normal controls. Overresponders were slow to habituate and exhibited a high number of orienting responses, a high baseline skin conductance level, and a high incidence of spontaneous fluctuations. Underresponders exhibited low baseline skin conductance levels, few spontaneous fluctuations, and either an absence of orienting activity or only an isolated initial orienting response. The stimulus barrier ratings were highly correlated with these psychophysiological patterns. Certain schizophrenics alternated between these response patterns. Change status and response pattern were related to a number of psychological variables. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do response time limitations counteract the effect of faking on personality inventory validity?

Different models of lying on personality scales make discrepant predictions on the association between faking and item response time. The current research investigated response time restriction as a method for reducing the influence of faking on personality scale validity. In 3 assessment simulations involving 540 university undergraduates responding to 2 common, psychometrically strong personality inventories, no evidence emerged to indicate that limiting respondents' answering time can attenuate the effects of faking on validity. Results were interpreted as failing to support a simple model of personality test item response dissimulation that predicts that lying takes time. Findings were consistent with models implying that lying involves primitive cognitive processing or that lying may be associated with complex processing that includes both primitive responding and cognitive overrides. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tool vs. agent: attributing agency to natural language generation systems

This paper argues that we should shift our consideration of natural language generation systems as tools for manifesting human intent to natural language generation systems as agents in themselves. Such a semantic shift would permit a more holistic conversation about the transformative social power of these systems’ output.