bluuebunny/crossref_metadata_2025 huggingface dataset:
A modality‐independent approach to spatial normalization of tomographic images of the human brain
Authors: Lancaster Jack L. , Glass Thomas G. , Lankipalli Bhujanga R. , Downs Hunter , Mayberg Helen , Fox Peter T.
Published: May 2005

A modality‐independent approch for interactive spatial normalization of tomographic images of the human brain is described and its performance evaluated. Spatial normalization is accomplished using a nine‐parameter affine transformation to interactively align and adjust the shape of a subject brain to the reference brain detailed in the 1988 atlas of Talairach et al. A user‐friendly software application was developed using the X‐windows Motif environment to guide the user through this process. This software supports data types from a wide variety of tomographic imagers and produces output in spatially concise formats.

The parameters used for spatial alignment and shape normalization are presented and methods to apply them discussed. Where normalization parameters cannot be obtained directly from the image, as with positron emission tomography (PET), methods for estimating them are given. Evaluation of a new four‐landmark method to fit the AC‐PC line in 16 magnetic resonance imaging (MRI) studies indicated an average difference assessed as the distance between the true and fitted AC‐PC line at four locations of 0.82 mm when using a 2‐D weighted fit. The same landmarks were evaluated using lower spatial resolution PET‐like images simulated from the 16 MRI studies. The difference between the PET and MR image volumes following alignment was minimal, with mean rotational differences of less than 0.2 deg and mean translational differences of generally less than 2 mm. Spatial normalization is illustrated for single photon emission computed tomography (SPECT), X‐ray computed tomography (CT), PET, and MR image volumes. Modality‐independent spatial normalization can be consistently and reliably performed with the methods and software presented. © 1995 Wiley‐Liss, Inc.
Motion detection and correction in functional MR imaging
Authors: Jiang Aiping , Kennedy David N. , Baker John R. , Weisskoff Robert M. , Tootell Roger B. H. , Woods Roger P. , Benson Randall R. , Kwong Kenneth K. , Brady Thomas J. , Rosen Bruce R. , Belliveau John W.
Published: May 2005

Subject motion present during the time course of functional activation studies is a pervasive problem in mapping the spatial and temporal characteristics of brain activity. In functional MRI (fMRI) studies, the observed signal changes are small. Therefore, it is crucial to reduce the effect of subject motion during the acquisition of image data in order to differentiate true brain activation from artifactual signal changes due to subject motion. We have adapted a technique for automatic motion detection and correction which is based on the ratio‐variance minimization algorithm to the fMRI subject motion problem. This method was used for retrospective correction of subject motion in the acquired data and resulted in improved functional maps. In this paper we have designed and applied a series of tests to evaluate the performance of this technique which span the classes of image characteristics common to fMRI. These areas include tests of the accuracy and range of motion as well as measurement of the effect of image signal to noise ratio, focal activation, image resolution, and image coverage on the motion detection system. Also, we have evaluated the amount of residual motion remaining after motion correction, and the ability of this technique to reduce the motion‐induced artifacts and restore regions of activation lost due to subject motion. In summary, this method performed well in the range of image characteristics common for fMRI experiments, reducing motion to under 0.5 mm, and removed significant motion‐induced artifacts while restoring true regions of activation. Motion correction is expected to become a routine requirement in the analysis of fMRI experiments. © 1995 Wiley‐Liss, Inc.
High‐resolution functional magnetic resonance imaging of cortical activation during tactile exploration
Authors: Boecker Henning , Khorram‐Sefat Darius , Kleinschmidt Andreas , Merboldt Klaus‐Dietmar , Hänicke Wolfgnag , Requardt Martin , Frahm Jens
Published: May 2005

Cortical activation during tactile exploration of macrogeometric objects was investigated in six healthy individuals with the use of magnetic resonance imaging (MRI) sensitized to changes in cerebral blood oxygenation. Dynamic measurement of task‐related signal alterations were performed at 2.0 T using a rapid gradient‐echo MRI sequence (TR/TE=63/30 ms, flip angle 10°, measuring time 6 s) at high spatial resolution (0.8 × 1.6 mm2). Four contiguous sections (thickness 4 mm) parallel to the bicommissural plane covered the hand area of the primary sensorimotor cortex (M1, S1), the supplementary motor area (SMA), premotor areas (PMA), and superior parts of the parietal cortex (PC). Task‐related activation was determined by correlating signal intensity time courses with the stimulus protocol on a pixel‐by‐pixel basis. In contrast to predominantly contralateral M1 activation, effects in the hand area of S1 were not restricted to the contralateral side but were equally present in the posterior section of ispilateral S1. Furthermore, bilateral responses were encountered in SMA and PC, while observations within PMA remained inconsistent. These findings in single subjects readily demonstrate a highly resolved and interindividually reproducible pattern of cortical activation in relation to exploratory finger movements and associated intergration of somatosensory information. © 1995 Wiley‐Liss, Inc.
Frontal component of the somatosensory evoked potential
Authors: Bötzel Kai , Ecker Christian , Mayer Michael , Schulze Stefan , Straube Andreas
Published: May 2005

Electric stimulation of the median nerve at the wrist evokes a series of electric potentials that can be recorded from the scalp or directly from the cortex. These somatosensory evoked potentials (SEP) include a parietal negativity with a maximum 20 ms after the stimulus, which originates in the somatosensory cortex, probably area 3b (Allison et al. [1991a], Brain 114:2465–2503 and Desmedt et al. [1987], Electroenceph Clin Neurophysiol 68:1–19). Thirty milliseconds after the stimulus, a negative potential (N30) occurs at frontal recording sites. Recently it was observed that the amplitude of this potential is altered in patients with dystonia, Parkinson's disease, and Huntington's chorea. It has been argued that the N30 potential stems from cortical areas other than the somatosensory cortex, for example, the supplementary motor area. We used multichannel recordings to investigate the scalp distribution of the N20 and the N30 potentials in healthy subjects. We found that the N20 as well as the N30 potentials were accompanied by a corresponding positivity at frontal and parietal recording sites, respectively. The N20/P20 and the N30/P30 potential fields had a mirrorlike appearance, and both showed a polarity reversal near the central sulcus. This and the results of correlation analyses led us to the conclusion that the N30 generator is located near the central sulcus. © 1995 Wiley‐Liss, Inc.
Cortical surface modeling reveals gross morphometric correlates of individual differences
Authors: Loftus William C. , Tramo Mark Jude , Gazzaniga Michael S.
Published: May 2005

Advances in human neurobiology are now made possible through methods which combine structural magnetic resonance imaging (MRI), three‐dimensional reconstruction, and statistical analysis. MRI‐based reconstruction enables the in vivo quantification of regional cortical surface area (rCSA) while inter‐group comparisons uncover relationships of cortical morphometry with genotype, sex, and developmental abnormalities. In studies on normals we have found strong associations between the rCSA of monozygotic twins as compared to unrelated pairings. Further analysis of this data uncovered significant differences between the male and female twins in left hemisphere rCSA. When these methods were applied to brains of dyslexic subjects and controls, we identified a pattern of differences involving all major subdivisions of both hemispheres. Taken together, these techniques can illuminate structurefunction issues in both normal and diseased brains. ©1996 Wiley‐Liss, Inc.
A PET investigation of implicit and explicit sequence learning
Authors: Rauch Scott L. , Savage Cary R. , Brown Halle D. , Curran Tim , Alpert Nathaniel M. , Kendrick Adair , Fischman Alan J. , Kosslyn Stephen M.
Published: May 2005

The purpose of this study was to determine the mediating neuroanatomy of implicit and explicit sequence learning using a modified version of the serial reaction time (SRT) paradigm. Subjects were seven healthy, right‐handed adults (three male, four female, mean age 26.7, range 18–43 yr). PET data were acquired via the oxygen‐15‐labeled‐carbon dioxide inhalation method while subjects performed the SRT. Subjects were scanned during two blocks each of (1) no sequence (Random), (2) single‐blind, 12‐item sequence (Implicit), and (3) unblinded, same sequence (Explicit). Whole‐brain‐normalized images reflecting relative regional cerebral blood flow (rCBF) were transformed to Talairach space, and statistical parametric maps (SPMs) of z‐scores were generated for comparisons of interest. The threshold for significant activation was defined as z‐score ≥ 3.00. Behavioral data demonstrated significant learning (P < .05) for Implicit and Explicit conditions. Tests of explicit knowledge reflected non‐significant explicit contamination during the Implicit condition. Foci of significant activation in the Implicit condition were found in right ventral premotor cortex, right ventral caudate/nucleus accumbens, right thalamus, and bilateral area 19; activation in the Explicit condition included primary visual cortex, peri‐sylvian cortex, and cerebellar vermis. Activations in visual and language areas during the Explicit condition may reflect conscious learning strategies including covert verbal rehearsal and visual imagery. Right‐sided premotor, striatal, and thalamic activations support the notion that implicit sequence learning is mediated by cortico‐striatal pathways, preferentially within the right hemisphere. © 1996 Wiley‐Liss, Inc.
Clustered pixels analysis for functional MRI activation studies of the human brain
Authors: Xiong Jinhu , Gao Jia‐Hong , Lancaster Jack L. , Fox Peter T.
Published: May 2005

Conventional t‐statistics and cross‐correlation coefficients are commonly used for analysis of functional magnetic resonance images. The sensitivity of these statistics is usually low because severe Bonferroni‐type corrections are required for multiple statistical comparisons to minimize the false‐positive error. In the human brain, most functional areas are larger in size than a single image pixel, and coactivation of numerous contiguous pixels is expected. The probability of occurrence of clusters due to random noise is small and can be modeled. Cluster size and intensity thresholding can be used to assess statistical significance. Previous cluster analysis strategies used Gaussian models, working best with low spatial resolution images (e.g., positron emission tomography). We present a new cluster analysis model applicable to data with little or even no covariance between adjacent pixels. Computer simulations and phantom experiments were used to verify this strategy. Our new method is substantially more sensitive than both the conventional intensity‐only thresholding (IOT) method and the previous cluster method for signal change less than 6%, with maximum significant enhancement in sensitivity of 12.8 and 3.8 times, respectively. The results obtained from normal volunteers with visual stimulation further confirm the effectiveness of our new approach and show an average increase in detected activation area of 3.1 times over the IOT method and of 1.6 times over the previous cluster method using the new approach. ©1996 Wiley‐Liss, Inc.
Characterising the complexity of neuronal interactions
Authors: Friston Karl J. , Tononi G. , Sporns O. , Edelman G. M.
Published: May 2005

This work addresses the complexity of neuronal interactions, the nature of this complexity and how it can be characterised in real neurophysiological processes. A measure of complexity has been introduced recently (Tononi et al. [1994]: Proc Natl Acad Sci USA 91:5033–5037) that is sensitive to the joint constraints imposed by two principles of brain organisation: functional segregation and functional integration. Functional segregation implies that the dynamics of a cortical area should reflect the multidimensional attributes for which that area is specialised (in other words, regional dynamics should show a relatively high entropy). Conversely, functional integration implies a distributed and divergent influence of every cortical area on the remaining areas (i.e., the overall dynamics should show a low entropy). Our measure is based on the profile of entropies of different sized regions of the brain. Complexity is high when smaller regions have (on average) a relatively high entropy with respect to the entropy of the whole system. This measure is equivalent to the (average) mutual information between all small regions and the rest of the system in question.

We have applied this measure to nonlinear simulations and to neurophysiological data obtained with fMRI during photic stimulation. Because patterns of activity in the brain are intermediate between a state of incoherence, with regionally specific dynamics and a state of global coherence, we predicted that simulated nonlinear processes with similar characteristics would have a high complexity. In the language of nonlinear dynamics we hypothesised that the greatest complexity would be found somewhere between high‐dimensional, chaotic behaviour and low‐dimensional, orderly behaviour. Equivalently, using the metaphor of loosely coupled oscillators, we predicted that complexity would be highest in the domain between asynchronous oscillations and global synchrony. This hypothesis was confirmed using nonlinear neuronal simulations. In addition, we demonstrate that the complexity of neurophysiological data is easily measured and can show a significant complexity when compared to suitable control processes. © 1996 Wiley‐Liss, Inc.
New and fast statistical‐thermodynamic method for computation of protein‐ligand binding entropy substantially improves docking accuracy
Authors: Ruvinsky A. M. , Kozintsev A. V.
Published: May 2005

We present a novel method to estimate the contributions of translational and rotational entropy to protein‐ligand binding affinity. The method is based on estimates of the configurational integral through the sizes of clusters obtained from multiple docking positions. Cluster sizes are defined as the intervals of variation of center of ligand mass and Euler angles in the cluster. Then we suggest a method to consider the entropy of torsional motions. We validate the suggested methods on a set of 135 PDB protein‐ligand complexes by comparing the averaged root‐mean square deviations (RMSD) of the top‐scored ligand docked positions, accounting and not accounting for entropy contributions, relative to the experimentally determined positions. We demonstrate that the method increases docking accuracy by 10–21% when used in conjunction with the AutoDock docking program, thus reducing the percent of incorrectly docked ligands by 1.4‐fold to four‐fold, so that in some cases the percent of ligands correctly docked to within an RMSD of 2 Å is above 90%. We show that the suggested method to account for entropy of relative motions is identical to the method based on the Monte Carlo integration over intervals of variation of center of ligand mass and Euler angles in the cluster. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1089–1095, 2005
Building cavities in a fluid of spherical or rod‐like particles: A contribution to the solvation free energy in isotropic and anisotropic polarizable continuum model
Authors: Benzi Caterina , Cossi Maurizio , Improta Roberto , Barone Vincenzo
Published: May 2005

A general formalism for the calculation of cavitation energies in the framework of the scaled particle theory has been implemented in the Polarizable Continuum Model (PCM), contributing to the nonelectrostatic part of the molecular free energy in solution. The solute cavity and the solvent molecules are described as hard spherocylinders, whose radius and length are related to the actual molecular shape, while the solvent density is estimated from experimental data, or from the solvent molecular volume, suitably scaled. The present model can describe isotropic solutions of spherical and rod‐like molecules in spherical or rod‐like solvents, and also anisotropic solutions in which the solvent molecules are oriented in space: in this case, the cavitation energy also depends on the relative orientation of solute and solvent molecules. Test calculations have been performed on simple systems to evaluate the accuracy of the present approach, in comparison with other methods and with the available experimental estimates of the cavitation energy, giving encouraging results. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1096–1105, 2005
Determination of the gas‐phase acidities of halogen‐substituted aromatic compounds using the silane‐cleavage method
Authors: Wenthold Paul G. , Squires Robert R.
Published: May 2005

The gas‐phase acidities of halogen‐substituted aromatic compounds have been determined in a flowing afterglowtriple quadrupole apparatus with use of the silane cleavage method developed by DePuy and co‐workers [C. H. DePuy, S. Gronert, S. E. Barlow, V. M. Bierbaum and R. Damrauer, J. Am. Chem. Soc., 111, 1968 (1989)]. In this method the relative yields of siloxide ion products produced in reactions of OH− with trimethylsilyl‐ or phenyldimethylsilyl‐substituted aromatic compounds are correlated with the difference in gas‐phase acidity of the accompanying neutral products. Acidities are reported for different ring‐positions in fluoro‐, chloro‐ and bromobenzene, chloro‐ and bromonaphthalene and benzyl chloride. Excellent precision is achieved in most cases, with assigned uncertainties less than 2–3 kcal/mol. Good agreement is obtained between the acidities determined with use of two different types of silane precursor. Halogen‐substitution increases the gas‐phase acidities of benzene and naphthalene by similar amounts (13–14 kcal/mol). The effects on different ring‐positions in benzene and naphthalene are shown to be primarily inductive in nature, falling‐off by a consistent 2.5–3.5 kcal/mol per bond separating the acidic site from the halogen‐bearing carbon in the chlorine and bromine‐substituted systems. Larger effects are evident in the positional acidities of fluorobenzene. The meta and para position acidities of halobenzenes are shown to be linearly correlated with the acidities of the corresponding meta and para halophenols, haloanilines and halotoluenes.
Methionine specific sequence ions formed by the dissociation of protonated peptides at high collision energies
Authors: Downard Kevin M. , Biemann Klaus
Published: May 2005

Two methionine‐specific sequence ions are described that are formed upon the dissociation of protonated methionine‐containing peptides at high (keV) collision energies. These ions, hiherto unassigned, are denoted an + 1 − CH3S⋅ and zn + 1 − CH3S⋅. Precursor ion scans reveal that these species originate from the an + 1 and zn + 1 ions, respectively, where methionine resides at position n‐1 relative to the N‐ or C‐terminus. A comparison of the collision‐induced dissociation (CID) spectra for several related peptides demonstrates that methionine residues are involved in the genesis of these species and mechanisms for their formation are proposed. Several structural features of a peptide that are important to the formation of these species are described. The importance of identifying these ions in order to correctly sequence a methionine‐containing peptide based on its CID spectrum is illustrated.
Identification of the neutral products from the unimolecular dissociation of singly and multiply charged C60 fullerene ions
Authors: McHale Kevin J. , Polce Michael J. , Wesdemiotis Chrys
Published: May 2005

The neutral products eliminated upon the collisionally activated dissociation (CAD) of C ions (z = 1–4) are post‐ionized to cations or anions and collected in neutral fragment‐reionization (+NfR+,−) mass spectra. These spectra provide conclusive evidence that the decompositions C → C + C2n (where x >30 and 2n < 30) proceed by cleavage of whole C2n clusters, not consecutive losses of nC2. As teh charge of the fullerene precursor ion increases, the largest detectable neutral loss decreases, from C28 for z = 1 to C12 for z = 4. Post‐ionization of C2n to cations preferentially produces odd‐carbon cluster ions (e.g., C5+, C7+, C11+, C+15) whereas post‐ionization to anions yields abundant even‐carbon cluster ions (C6−, C8−).
High‐resolution tandem mass spectra of 37‐67 kDa proteins
Authors: Speir J. Paul , Senko Michael W. , Little Daniel P. , Loo Joseph. A. , McLafferty Fred W.
Published: May 2005

By dissociating noncovalent adducts with infrared radiation and minimizing ion charge density during measurement, Fourier‐transform mass spectrometry with electrospray ionization yields 160 000 resolving power for porcine albumin. Its molecular weight calculated from the published sequence is 66 740, but values found for two different samples are MW = 66 736 and 66 886. The spectrum of their mixture confirms this mass difference. Similar measurements of two Protein A (45 kDa) samples also give molecular weights in substantial disagreement with literature sequences. Tandem mass spectrometry gives partial sequence information that demonstrates errors in some of the reported sequences.
Ion–neutral complex formation and hydrogen‐shifts in the alkene loss from ionized alkyl phenyl thioethers in the gas phase
Authors: Van Amsterdam Margot W. , Ingemann Steen , Nibbering Nico M. M.
Published: May 2005

The mechanistic aspects of alkene loss from ionized ethyl‐and n‐propyl phenyl thioethers have been studied by use of deuterium labelling and tandem mass spectrometry. Loss of ethene from the molecular ion of ethyl phenyl thioether proceeds predominantly by a specific H‐shift from the β‐position of the ethyl group to the remaining part of the ion. In contrast, deuterium labelling reveals that elimination of propene from the molecular ions of the n‐propyl phenyl and n‐propyl 2,6‐dimethylphenyl thioethers involves three competing reactions: (i) a 1,2‐hydride shift assisted cleavage of the bond between the propyl group and the sulfur atom yielding an ion–neutral complex of a thiophenyoxy radical and a secondary propyl carbenium ion, which reacts further by proton transfer prior to dissociation; (ii) a partially reversible 1,5‐H shift from the β‐position to the 2‐ or 6‐position of the ring; and (iii) a 1,3‐H shift from the β‐position to the sulfur atom. The preference for transfer of a hydrogen atom from the β‐position is particularly pronounce for the reactions of the metastable molecular ions of the n‐propyl phenyl and n‐propyl 2,6‐dimethylphenyl thioethers. This indicates that the critical energies of the processes involving H‐shifts are lower than the critical energy for propene loss with intermediate formation of an ion–neutral complex. In addition to ethene elimination, ionized ethyl phenyl thioether expels a HS+· radical. This reaction is preceded by an interchange between the hydrogen atoms at the α‐methylene group and the hydrogen atoms at the 2‐ and 6‐positions of the ring as observed also for ionized methyl phenyl thioether.
Collision‐induced photon emissions from 8 ke V O and CO ion beams
Authors: Holmes J. L. , Mayer P. M.
Published: May 2005

The optical emission spectra between 190 and 680 nm of 8 keV O and CO collisions with He and N2 target gases were obtained and analyzed on a modified commercial VG ZAB‐2F mass spectrometer. Emissions observed were from O, O+, He, N (B2∑+u → X2∑+g) and N2 (C3∏u → B3∏g) in the case of O projectiles and C, CO (B2∑+u, A 2∏u → X 2∏g), CO+· (B2∑+ → X2∑+), N (B2 ∑+g → X2∑g) and N2 (C3∏u → B 3∏g) in the case of CO projectiles. The results are discussed in relation to previous reports on N–target collisions and the collision–induced dissociation mass spectral characteristics of O and CO.
Studies on the formation of reactive intermediates from the antineoplastic agent N,N′Bis(2‐chloroethyl)‐N‐nitrosourea (BCNU) in vitro and in Vivo. Characterization of novel glutathione adducts by ionspray tandem mass spectrometry
Authors: Davis Margaret R. , Baillie Thomas A.
Published: May 2005

In a study designed to examine the nature of short‐lived, electrophilic intermediates liberated during decomposition of N,N′‐bis(2‐chloroethyl)‐N‐nitrosourea (BCNU) in vitro and also on administration of BCNU (140 μmol i.p.) to rats in vivo, both on‐line and off‐line LC/MS/MS techniques were employed to detect and characterize the corresponding glutathione (GSH) adducts present in incubation media and excreted into bile, respectively. In vitro, four GSH conjugates were formed and these were identified, on the basis of their product ion spectra, as products of S‐and N‐carbamoylation and alkylation reactions. Although the relative proportions of these in vitro adducts were found to depend on the molar ratios of GSH and BCNU, the major adduct under all conditions studied proved to be S‐(2‐chloroethylcarbamoyl)glutathione (SCG). Analysis of untreated bile samples by means of on‐line LC/MS/MS with constant neutral loss (129 u) and precursor ion (m/z 179) scanning techniques again led to the detection of four GSH conjugates, although only one of these (SCG) was common to the group of adducts identified in vitro. All of the GSH conjugates detected in bile represented products of S‐carbamoylation, indicating that the alkylating moiety released from BCNU undergoes reactions in vivo with nucleophiles other than GSH.
Gas‐phase reactions of the 4‐dehydroanilinium ion and its isomers
Authors: Chyall Leonard J. , Kenttämaa Hilkka I.
Published: May 2005

Collisional activation of protonated 2‐, 3‐ and 4‐iodoanilines in a dual‐cell Fourier transform ion cyclotron resonance spectrometer results in the loss of an iodine atom to yield product ions of m/z 93. Ion–molecule reactions and energy‐resolved collision‐activated dissociation experiments demonstrate that these three ions are structurally distinct, and that they are distonic ions. The ions were identified as the 2‐, 3‐ and 4‐dehydroanilinium ions, the high‐energy distonic isomers of ionized aniline. The reactivity of these charged phenyl radicals is largely analogous to that of the phenyl radical. For example, the 4‐dehydroanilinium ion abstracts an iodine atom from isopropyl iodide, a thiomethyl group from dimethyl disulfide, and adds to cyclohexene. Comparison of the collision‐activated dissociation product abundances of the ion formed upon CH3S abstraction to that of a reference ion suggests that bond formation occurs at the formal radical site upon CH3S abstraction. Hence, the reaction probably occurs via a simple radical abstraction mechanism similar to that of the phenyl radical. However, some neutral reagents react with the charge site of the 4‐dehydroanilinium ion, and yet others undergo a two‐step reaction sequence involving the charge site in addition to the radical site. For example, certain basic molecules induce isomerization of the 4‐dehydroanilinium ion to the significantly more stable ionized aniline by deprotonating the charge site and then donating a hydrogen atom to the radical site.
Tandem mass specatrometry of carbonic anhydrase (29 kDa)
Authors: O'Connor Peter B. , Speir J. Paul , Senko Michael W. , Little Daniel P. , McLafferty Fred W.
Published: May 2005

Using electrospray ionization with a Fourier‐transform mass spectrometer, MS/MS of molecular ions and seven fragment ions of carbonic anhydrase (259 amino acids) yields 74 identifiable fragment ions, including 23 amino acid spacings. Such sensitive and specific direct characterization of proteins appears to be complementary to conventional techniques including LC/MS/MS sequencing of oligopeptides from protein degradation.
Peptide amino acid sequence analysis using matrix‐assisted laser desorption/ionization and fourier transform mass spectrometry
Authors: Castoro John A. , Wilkins Charles L. , Woods Amina S. , Cotter Robert J.
Published: May 2005

High‐performance matrix‐assisted laser desorption/ionization (MALDI) using 7 T Fourier transform mass spectrometry (FTMS) was investigated for peptide amino acid sequence analysis. Two synthetic peptides representative of the type which would be displayed by major histocompatibility complex molecules from tumor cells were investigated by MALDI/FTMS. Molecular ions of the two 9‐amino acids peptides were detected with resolving power of 8000–17 900 and mass measurement accuracy between 8 and 81 ppm for the all 12C isotope ions. An ultra‐high resolution spectrum (RP 300 000) for the molecular ion of one of the two peptides was obtained. Structurally useful sequence information was obtained by use of surface‐induced dissociation (SID) of the molecular ion species. Interestingly, SID of a sodium‐attached peptide molecular ion resulted in the production of numerous sodium‐attached sequence ions.
Direct mass spectrometric sequencing of low‐picomole amounts of oligodeoxynucleotides with up to 21 bases by matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Nordhoff E. , Karas M. , Cramer R. , Hahner S. , Hillenkamp F. , Kirpekar F. , Lezius A. , Muth J. , Meier C. , Engels J. W.
Published: May 2005

UV and IR matrix‐assisted laser desorption/ionization mass spectrometry (UV‐ and IR‐MALDI) have demonstrated their potential for the accurate and sensitive mass determination of oligonucleotides. Metastable molecule ion fragmentation was found to be the main limitation in both desorption schemes for the analysis of larger nucleic acid sequences. Fragment ions from additional prompt decays, observed only in IR‐MALDI, offer structural data, which allow sequence information to be derived for low‐picomole amounts of oligodeoxynucleotides with up to 21 bases from a single mass spectrum. Two examples demonstrating the feasibility of this new sequencing technique are given. A model is introduced and discussed, which proposes a reaction scheme for the observed fragment ion patterns of nucleic acids and differentiates prompt and metastable fragmentation mechanisms. The role of fragmentation in direct mass spectrometric sequencing schemes and as a limitation for the accessible mass range in nucleic acid MALDI mass spectrometry is discussed.
Cation‐exchange resins for removal of alkali metal cations from oligonucleotide samples for fast atom bombardment mass spectrometry
Authors: Vollmer David L. , Gross Michael L.
Published: May 2005

Cation‐exchange resins are useful matrix additives for the positive and negative ion FAB‐MS determination of nucleotides. Several factors including the amount and type of matrix, the amount and type of the resin, the molecular weight of the nucleotide, and the salt content of the nucleotide sample are investigated. For positive ions, the most abundant [M + H]+ ions are obtained with 1 μL of DTT/DTE with 75–100 resin beads in the H+ form is used. For negative ions, the most abundant [M − H]− ions are produced from 1 μL TEA and 75–100 resin beads in the NH4+ form. In several cases, the use of cation‐exchange resins give superiors results compared to those obtained with other matrix additives.
Charge state assignment from schiff‐base adducts in low resolution electrospray mass spectra of protein mixtures and dissociation products
Authors: Guan Ziqiang , Campbell Victoria L. , Laude David A.
Published: May 2005

Schiff‐bases formed by reaction between ketones and free amine sites in proteins yield mass‐shifted ions that are useful in assigning charge states in low resolution electrospray ionization mass spectra of mixtures and dissociation products. The technique is attractive for those mass analyzers incapable of achieving sufficient resolving power to distinguish the 13C‐isotope distribution within an individual charge state. Instead, acetone is used here to append a C3H4 group to the protein and achieve a forty‐fold reduction in the necessary mass resolution for charge state determination. The utility of Schiff‐base adducts for assigning charge states among a mixture of proteins is demonstrated; here, the molecular weights for horse myoglobin (MW 16 950) and cytochrome c (MW 12 360) in a two component mixture are unambiguously determined from a mass spectrum with a mass resolution of only 800. The CN bond formed by the Schiff base is sufficiently strong to survive ion dissociation processes and permit assignment of charge state to fragment ions in tandem mass spectrometry experiments. For example, adducted sequence ions are observed in high yield when a melittin/acetone solution is subjected to nozzle‐skimmer dissociation conditions in the electrospray process. Other advantages of Schiff‐base reaction include site‐specificity and minimal alteration to the charge state. This site‐specific binding feature appears to be promising method for locating the lysine groups in structural characterization by tandem mass spectrometry.
Selected ion accumulation of noncovalent complexes in a fourier transform ion cyclotron resonance mass spectrometer
Authors: Bruce James E. , Van Orden Steven L. , Anderson Gordon A. , Hofstadler Steven A. , Sherman Michael G. , Rockwood Alan L. , Smith Richard D.
Published: May 2005

An electrospray ionization–Fourier transform ion cyclotron resonance (ESI–FTICR) mass spectrometer has been used in conjunction with the technique of selected‐ion accumulation (SIA) to investigate its utility for the study of the gas phase behavior of noncovalent complexes from solution. SIA is demonstrated to provide the selective accumulation of weakly bound species, providing a significant enhancement in the attainable signal‐to‐noise ratio and dynamic range. The frequency response of quadrupole excitation was first determined by selectively accumulating single charge states of large, highly adducted, highly charged molecules such as bovine albumin and bovine albumin dimer. Under the conditions employed, the response (selective accumulation) was found to be as narrow as 500 Hz. Additionally the SIA was found to be sufficiently gentle to allow accumulation of both specific and nonspecific weak noncovalent complexes, such as the myoglobin–heme complex observed in basic solutions and complexes of myoglobin and single amino acids, such as tryptophan. This result is probably due to the continual application of quadrupole excitation during the high pressure accumulation event, preventing any significant growth of magnetron motion, and subsequently, allowing interconversion to form only small cyclotron radii. We also demonstrate the simultaneous application of SIA with dipolar sustained off‐resonance irradiation (SORI) during the ion accumulation period so as to allow selective accumulation of dissociation products. The SIA/SORI combination promises to greatly extend (MS)n capabilities by allowing the selective accumulation of any dissociation product in any step along a given dissociation pathway.
Tunable degree of fragmentation of volatile organic compounds with a low‐pressure penning ion source
Authors: Kohler M. , Schlunegger U. P.
Published: May 2005

The properties of a low‐pressure ion source based on the principle of the Penning cell (Penning ion source) were investigated. At low discharge currents, spectra similar to standard electron impact ionization (EI at 70 eV) spectra were obtained (positive‐ion‐mode). However, at high discharge currents, it was found by experiments carried out partly with labelled compounds that molecules are decomposed to small fragments and even single atoms. Species such H2+, C+, CH+, CH2+, CH3+, O+, OH+, H2O+, C2 +, C2H+, C2H2+, C2H3+, O2+, Cl+ and Cl2+ have been obtained from various organic compounds. The degree of fragmentation of the molecular ion has been found to be directly dependent on the discharge current. These observation demonstrate that the Penning ion source allows one to tune the degree of framentation. In the negative‐ion mode, halogenated organic compounds yielded spectra dominated by the signals of the halogen atoms they contain. High abundances of F−, Cl−, Br−, and Br2− were observed, next to weak signals for O−, C−, C2−, C2H−, C2−, and C4−, orginating from the CHO skeleton of the sample molecule. In contrast to the results found in the positive‐ion mode, intense fragmentation, even at low discharge currents, was found.
Massive cluster impact ionization on a four sector tandem mass spectrometer
Authors: Fabris D. , Wu Z. , Fenselau C. C.
Published: May 2005

High energy gycerol cluster ions from an electrohydrodynamic ion gun have been used as a primary ion beam to generate secondary ions of proteins with molecular weights up to 29 kDa and oligonucleotides. The technique not only demonstrated good performance in the picomole/nanomole range for the desorbtion of highly polar and fragile molecules such as proteins and deoxyoligonucleotides, but it also allowed the observation of a non‐covalent complex in the form of a deoxyoligonucleotide duplex. We have also shown that it is feasible to carry out structural analysis of oligonucleotides by collisional activation in a four sector tandem instrument.
Differentiation of olefin isomers by survivor‐ion mass spectrometry
Authors: Tureček František , Gu Ming
Published: May 2005

Survivor‐ion mass spectrometry is a method that relies on the selective monitoring of non‐dissociating ions that underwent collisional neutralization and reionization. These charge‐permutation processes are found to modulate the relative intensities of precursor ions, both molecular ions and fragments, formed by electron impact from C6H10, C6H12, C6H12O, and xylene isomers. The relative intensities of highly‐unsaturated ions, such as C5H5+, C4H, C3H3+, and C2H, and enol ions are enhanced in the survivor‐ion spectra in dependence on the neutralization gas. Isomer differentiation through survivor‐ion spectra is achieved for conjugated hexadienes, 1,4‐hexadiene and cyclohexene, but not for hexenols and xylenes.
Effect of metal cationization on the collision‐induced decomposition of 2,3‐diphenylpropenoic acid derivatives
Authors: Madhusudanan K. P.
Published: May 2005

The effect of metal cationization on the collision‐induced decomposition of 2,3‐diphenylpropenoic acid derivatives was studied with the help of linked scan (B/E = constant) spectra of their [M + H]+, [M − H]−, [M + Met]+, [M + 2Met − H]+ and [M + Met − H]+ ions using metal ions such as Li+, Na+, K+, Cs+, Ag+ and Ba2+. Decarboxylation is triggered by metal cationization.
Fragmentation of (η5‐cyclopentadienyl)dicarbonyl‐acyliron complexes under electron impact
Authors: Baranowska ElżBieta , Danikiewicz Witold , Pakulski Zbigniew , Zamojski Aleksander
Published: May 2005

Fragmentation patterns under electron impact of selected (η5‐cyclopentadienyl)dicarbonylacyliron complexes were studied. Fragmentation pathways were confirmed using accurate mass measurements and B/E = constant and mass‐analysed ion kinetic energy fragment ion spectra.
Beam‐induced dehalogenation in LSIMS: Effect of halogen type and matrix chemistry
Authors: Théberge R. , Bertrand M. J.
Published: May 2005

The LSIMS beam‐induced dehalogenation of several 4‐halo‐phenylalanine methyl esters (I, Br, Cl, F) was investigated and compared to that of atrazine using 12 different matrix compounds including diethyl phthalate for which the empirical electron affinity was known. The extent of dehalogenation, induced by a one‐electron reduction process, is in agreement with the leaving group ability of the corresponding halogens (I >Br >Cl >F) and the dehalogenation inhibiting efficiency of the matrices. The latter is rationalized in terms of electron scavenging capacity and matrix structural features relating to that capacity. The extent of dehalogenation observed for 4‐I‐phenylalanine methyl ester is similar to that of atrazine, a chlorinated compound, which indicates that the halogen effect is not overwhelming in determining the extent of dehalogenation. The bracketing of matrix reduction potential was attempted based on the propensity of the matrices to induce M+· formation from analytes of known oxidation potentials. The ability of matrices to induce M+· formation parallels their dehalogenation and reduction inhibiting efficiencies. The last observation underlines the importance of matrix redox properties in effecting or inhibiting beam‐induced processes, be they reductive or oxidative.
Formation and fragmentations of organometallic complexes involving aliphatic α‐amino acids and transition metal cations—a plasma desorption mass spectrometry study
Authors: Bouchonnet Stéphane , Hoppilliard Yannik , Ohanessian Gilles
Published: May 2005

Amino acid/transition metal chloride mixtures were studied by plasma desorption mass spectrometry. The six aliphatic α‐amino acids were considered: glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile) and proline (Pro), together with four transition metal chloride salts: CoCl2, NiCl2, CuCl2 and FeCl2. Mixtures spectra show that MCat+ complexes are formed where M = amino acid and Cat = Co, Ni, Cu or FeCl. Fragmentations of MCat+ ions lead to both organometallic and organic ions. Isotopic labelling has allowed to demonstrate some fragmentation mechanisms.
Observation of large subunit protein complexes by electrospray ionization mass spectrometry
Authors: Loo Joseph A.
Published: May 2005

Mass spectrometry with electrospray ionization and a magnetic sector instrument was used to detect multiply charged molecules for the non‐covalently bound dimeric subunit protein complexes of horse liver alcohol dehydrogenase (Mr ∼ 80 000) and the tetrameric complexes of yeast alcohol dehydrogenase (Mr ∼ 147 000) and rabbit muscle pyruvate kinase (Mr ∼ 232 000). Ions for the pyruvate kinase complex represent one of the largest intact protein complexes resolved by mass spectrometry. Solvation of the large gas phase complexes is indicated by the mass spectrometric results.
Relative cyanide cation (+CN) affinities of pyridines determined by the kinetic method using multiple‐stage (MS3) mass spectrometry
Authors: Yang Sheng S. , Bortolini Olga , Steinmetz Annick , Cooks R. Graham
Published: May 2005

Ion–molecule reactions occurring in a pentaquadrupole mass spectrometer are used to generate and characterize ions in which one or two pyridine molecules are bound by a +CN cation. Cyanide cation binds strongly to the nitrogen atom of pyridine to generate a mono‐adduct, which undergoes pyridine exchange reactions and from which one can generate the dipyridine adduct in low abundance. The dimeric ions have two structures, loosely bound and covalently bound, and both fragment to yield the constituent cyanide‐bound monomers. In the case of dimers comprised of meta‐substituted alkylpyridines, there is a quantitative correlation between relative cyanide cation affinity, as measured using the kinetic method, and literature values of relative proton affinities. These dimers fragment analogously to the corresponding H+‐ and Cl+‐ bound dimers, and on this basis are assigned analogous structures, viz. the loosely bound form Py1+CNPy2. Semi‐empirical molecular orbital calculations show that both pyridines are bound to the carbon atom of the cyanide cation. Making the assumption that the effective temperatures of the activated cyanide‐bound dimers are similar to those of the corresponding Cl+‐ and H+‐bound dimers, relative +CN cation affinities are estimated to be 1.5 kcal mol−1 (3‐MePy), 1.7 kcal mol−1 (4‐MePy), 2.6 kcal mol−1 (3‐EtPy), 3.5 kcal mol−1 (3‐n‐BuPy) and 3.6 kcal mol−1 (3,5‐diMePy), all expressed relative to pyridine (1 kcal = 4.184 kJ). A linear relationship between the relative +CN affinity and relative proton affinity (PA) is derived as Δ +CN affinity (kcal mol−1) = 0.78 (ΔPA), with the assumption that the +CN dimer effective temperature is 600 K. The estimated uncertainty is 0.5 kcal mol−1. Relative +CN affinities of pairs of pyridines are smaller by ca. 1 kcal mol−1 than the corresponding Cl+ affinities. Dimers in which one of the pyridines is meta‐chlorine‐ or para‐alkyl‐substituted have the covalently bound, ring‐carbon‐substituted structure, in which the +CN group is attached to the pyridine nitrogen and the second pyridine molecule is bound to a ring carbon. The fragmentation of these isomeric dimers yields the corresponding monomers, in addition to other minor ions, but the distribution of the cyanide cation between the two pyridines does not correlate with Cl+ affinity or proton affinity. In the special cases of the 3‐methylpyridine–3‐n‐butylpyridine and the 4‐methylpyridine–pyridine cyanide cation adducts, both the loosely bound dimer and the covalently bound adduct are generated and distinguished by their fragmentation behavior. Evidence for the formation of the covalently bound, ring‐carbon‐substituted structure was also obtained in semi empirical AMI calculations.
Formation of buckministerfullerene phenylene derivatives in the gas phase
Authors: Kan Steven Z. , Byun Yong G. , Lee Samuel A. , Freiser Ben S.
Published: May 2005

The gas‐phase chemistry of Fe(C6H4)n+ (n = 1–6) with C60 is studied by using Fourier transform ion cyclotron resonance mass spectrometry. The formation of some ionic phenylene derivatives and metallacyclic derivatives of C60 is observed. Specifically, Fe+, generated by laser desorption, reacts with chlorobenzene to form iron‐benzyne, FeC6H4+, which initiates further reactions with chlorobenzene to form Fe(C6H4) and (C6H4). Fe(C6H4) react with C60 to form metalated fullerene derivatives, C60Fe(C6H4). C60Fe(C6H4) undergo a demetalation reaction with chlorobenzene to yield the fullerene phenylene derivatives C60(C6H4), 8 and 9, through formation of CC bonds with C60. CID experiments and kinetic analysis indicate that each of the C60Fe(C6H4) species consists of a single isomer, presumably the metallacycles 12 and 14. Consistent with the typical reactions of metal‐benzyne complexes with alkenes in the condensed phase, these metallacyclic structures are believed to be formed through coupling of one of the double bonds at the 6,6 ring junction in C60 with an FeC σ bond of Fe(benzyne)+. These results are consistent with the notion that C60 acts like an electron deficient alkene rather than an aromatic molecule, and suggest a possible synthetic route to prepare this type of metallo‐C60 derivatives in the condensed phase. Finally, ligand displacement reactions yield a bond dissociation energy of D°(Fe+C60) = 44 ± 7 kcal/mol.
Solanum alkaloids. 132—Electron impact mass spectrometry of solanidane N‐oxides
Authors: Quyen Le Thi , Schmidt Jürgen , Schreiber Klaus
Published: May 2005

The electron impact mass spectra of nine solanidane N‐oxides show, in addition to the known typical fragmentation pattern of the solanidane moiety, the fragment ions [M – C5H9]+ and [C6H12NO]+, due to thermal Cope syn‐eliminations caused by the N‐oxide function and subsequent cleavage of the bonds between C(22) and C(23) and between C(20) and C(22), respectively, in the so‐obtained cyclic N,N‐dialkylhydroxylamines.
Sample morphology effects in matrix‐assisted laser desorption/ionization mass spectrometry of proteins
Authors: Westman A. , Huth‐Fehre T. , Demirev P. , Sundqvist B. U. R.
Published: May 2005

Millimetre‐sized crystals of 2,5‐dihydroxybenzoic acid and 3,5‐dimethoxy‐4‐hydroxycinnamic acid (sinapinic acid) were grown from a cytochrome c/matrix solution. Effects of sample exposure to UV laser irradiation on the matrix‐assisted laser desorption ionization mass spectra are reported for such single crystals. The exposure was varied by irradiating the same sample spot with different numbers of UV‐laser pulses. The ion yield and mass resolution were monitored as a function of the sample exposure. Further, the minimum deposited laser energy needed for protein ion production (the threshold energy) for single crystals was determined for incidence angles between 35° and 60° with respect to the target surface normal. The results were compared with those obtained for polycrystalline samples containing micrometre‐sized crystals.