bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Intensity Focused Ultrasound (HIFU) for Specific Therapeutic Treatments: A Literature Review
Authors: Evans Kevin D. , Weiss Brandon , Knopp Michael
Published: December 2007

A literature review is provided concerning the scientific studies that have been published involving high-intensity focused ultrasound (HIFU) as a therapeutic treatment for tumors of the prostate, uterus, and brain. This is a revival of earlier work that now focuses on targeted therapy with sonography, but the studies that have been conducted vary in their level of evidence and translation to clinical practice. The review arranges the published studies by levels of evidence and provides a meta-analysis of the potential for using HIFU to treat prostate cancer, fibroids, and glioblastomas. Human studies are needed that provide clear levels of frequency, intensity, temperature, and treatment patterns. The bioeffects of sonography play a huge role in the destruction of these tumors as well as the potential to cause collateral damage in the surrounding healthy tissue. The hope is that with continued research, a fusion of technology with HIFU can provide patients with a noninvasive, nonionizing therapy for these lesions.
Incidental Finding of a Large Cystic Mass in the Left Upper Quadrant
Authors: Akhverdiev Dmitry
Published: December 2007

Solitary cystic masses are less common in the middle-aged than in the elderly patient group. A woman in her mid-30s presented with a history of mild hypertension that had been treated for the past 3 months. An abdominal sonogram was performed, which revealed a large cystic mass in the left upper quadrant between the spleen, pancreatic tail, and left kidney. The differentials included cortical cyst of left kidney, pancreatic pseudocyst, and splenic and adrenal cyst. A computed tomography scan was ordered to help determine the origin of this cyst, which narrowed the differential to adrenal cyst or pancreatic pseudocyst. Lab findings, such as serum amylase, serum lipase, and urinary catecholamines, were unremarkable. Fine-needle aspiration of the cyst under sonographic guidance did not reveal any malignancy or pancreatic enzymes; therefore, clinicians assumed it was adrenal in origin.
Uterine Leiomyosarcoma Mimicking Benign Submucosal Leiomyoma
Authors: Reif Patricia A.
Published: December 2007

Uterine leiomyosarcoma is a rare, aggressive tumor of the smooth muscle with a typical intramural location. Patients present with abnormal uterine bleeding and an enlarged pelvic mass with clinical signs and symptoms that are virtually indistinguishable from benign leiomyoma. Sonographically, leiomyosarcoma presents as a large solitary tumor that closely resembles a benign leiomyoma that may be undergoing degenerative changes. Because of the infiltrative nature of leiomyosarcoma, invasion into the myometrium may be demonstrated. Leiomyosarcoma has a poor prognosis due to local pelvic recurrences and spread to distant sites. This case report demonstrates a fast-growing submucosal leiomyosarcoma with characteristic sonographic echo enhancement and infiltration into the myometrium.
Sirenomelia in the First Trimester
Authors: Heflin David
Published: December 2007

This case report demonstrates an early detection of sirenomelia at 12 weeks' gestation. Sirenomelia, also known as “mermaid syndrome,” has been noted since the Greco-Roman period. As with the mermaid mythology, sirenomelia is characterized by a single lower extremity with varying appearances of severity of the lower extremity anatomy. Mermaid syndrome is not considered a genetic defect but is associated with monozygotic twinning and maternal diabetes. Sirenomelia is a rare disorder that is difficult to diagnosis by sonography due to oligiohydramnios usually associated with the disorder. This case represents a late first-trimester diagnosis of sirenomelia without oligiohydramnios.
PAX2 expression by HHV-8–infected endothelial cells induced a proangiogenic and proinvasive phenotype
Authors: Fonsato Valentina , Buttiglieri Stefano , Chiara Deregibus Maria , Bussolati Benedetta , Caselli Elisabetta , Di Luca Dario , Camussi Giovanni
Published: December 2007

In the present study, we evaluated whether infection of microvascular endothelial cells (HMECs) with HHV-8 can trigger the expression of PAX2 oncogene and whether PAX2 protein is involved in HHV-8–induced transformation of HMECs. We found that HHV-8 infection induced the expression of both the PAX2 gene and PAX2 protein in HMECs but failed to induce PAX2 protein in HMECs stably transfected with PAX2 antisense (HMEC-AS). HHV-8–infected HMECs but not HMEC-AS acquired proinvasive proadhesive properties, enhanced survival and in vitro angiogenesis, suggesting a correlation between PAX2 expression and the effects triggered by HHV-8 infection. When HMEC-expressing PAX2 by stable transfection with PAX2 sense gene or by HHV-8 infection were implanted in vivo in severe combined immunodeficient (SCID) mice, enhanced angiogenesis and proliferative lesions resembling KS were observed. HHV-8–infected HMEC-AS failed to induce angiogenesis and KS-like lesions. These results suggest that the expression of PAX2 is required for the proangiogenic and proinvasive changes induced by HHV-8 infection in HMECs. In conclusion, HHV-8 infection may activate an embryonic angiogenic program in HMECs by inducing the expression of PAX2 oncogene.
The sugar-binding ability of ERGIC-53 is enhanced by its interaction with MCFD2
Authors: Kawasaki Norihito , Ichikawa Yoko , Matsuo Ichiro , Totani Kiichiro , Matsumoto Naoki , Ito Yukishige , Yamamoto Kazuo
Published: December 2007

Combined deficiency of factors V and VIII (F5F8D) is a bleeding disorder caused by mutations in LMAN1 or MCFD2. LMAN1 encodes ERGIC-53, a cargo receptor with an L-type lectin domain, and MCFD2 is a EF-hand-containing protein. We prepared a biotinylated, soluble form of ERGIC-53, which we labeled with R-phycoerythrin conjugated streptavidin. By flow cytometry, sERGIC-53-SA bound to HeLaS3 cells in the presence of calcium but only after preincubation with MCFD2. Treating the cells with endo H or incubating them with high mannose-type oligosaccharides, especially M8B, abrogated sERGIC-53-SA binding. Surface plasmon resonance experiments demonstrated that MCFD2 specifically bound to sERGIC-53 and 2 MCFD2 mutants found in F5F8D patients had a Ka that was 3 or 4 orders of magnitude lower for sERGIC-53 than for wild-type MCFD2. The Ka of sERGIC-53 and MCFD2 was measured at several pH values and calcium concentrations, and we found that at a calcium concentration less than 0.2 mM, this interaction became significantly weaker. These results demonstrate that the binding of ERGIC-53 to sugar is enhanced by its interaction with MCFD2, and defects in this interaction in F5F8D patients may be the cause for reduced secretion of factors V and VIII.
Lipopolysaccharide binding protein promoter variants influence the risk for Gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation
Authors: Chien Jason W. , Boeckh Michael J. , Hansen John A. , Clark Joan G.
Published: December 2007

Lipopolysaccharide binding protein (LBP) function is dependent on circulating LBP levels. Disturbance of LBP transcription regulation may influence the risk for clinical events. In a nested case-control study using a single nucleotide polymorphism haplotype tagging (tagSNP) approach, we assessed whether genetic variation in the LBP gene influences the risk for Gram-negative (GN) bacteremia after allogeneic hematopoietic cell transplantation (HCT), then validated the association in a prospective cohort by correlating genetic variation with basal serum LBP levels and mortality. Presence of the tagSNP 6878 C allele among patients was associated with a 2-fold higher risk for GN bacteremia (odds ratio = 2.15; 95% confidence interval [CI], 1.31-3.52, P = .002). TagSNP 6878 was in strong linkage disequilibrium with 3 SNPs in the LBP promoter, one of which was SNP 1683 (r2 = 0.8), located in a CAAT box that regulates LBP promoter efficiency. SNP 1683 was associated with higher median basal serum LBP levels (TT 8.07 μg/mL; TC 10.40 μg/mL; CC 17.39 μg/mL; P = .002), and a 5-fold increase in GN bacteremia related mortality after HCT (hazard ratio = 4.83; 95% CI, 1.38-16.75, P = .013). These data suggest that transcriptional regulation of the LBP gene contributes to the risk for developing GN bacteremia and death after HCT.
Predicting and improving the protein sequence alignment quality by support vector regression
Authors: Lee Minho , Jeong Chan-seok , Kim Dongsup
Published: December 2007

Background

For successful protein structure prediction by comparative modeling, in addition to identifying a good template protein with known structure, obtaining an accurate sequence alignment between a query protein and a template protein is critical. It has been known that the alignment accuracy can vary significantly depending on our choice of various alignment parameters such as gap opening penalty and gap extension penalty. Because the accuracy of sequence alignment is typically measured by comparing it with its corresponding structure alignment, there is no good way of evaluating alignment accuracy without knowing the structure of a query protein, which is obviously not available at the time of structure prediction. Moreover, there is no universal alignment parameter option that would always yield the optimal alignment.

Results

In this work, we develop a method to predict the quality of the alignment between a query and a template. We train the support vector regression (SVR) models to predict the MaxSub scores as a measure of alignment quality. The alignment between a query protein and a template of lengthnis transformed into a (n+ 1)-dimensional feature vector, then it is used as an input to predict the alignment quality by the trained SVR model. Performance of our work is evaluated by various measures including Pearson correlation coefficient between the observed and predicted MaxSub scores. Result shows high correlation coefficient of 0.945. For a pair of query and template, 48 alignments are generated by changing alignment options. Trained SVR models are then applied to predict the MaxSub scores of those and to select the best alignment option which is chosen specifically to the query-template pair. This adaptive selection procedure results in 7.4% improvement of MaxSub scores, compared to those when the single best parameter option is used for all query-template pairs.

Conclusion

The present work demonstrates that the alignment quality can be predicted with reasonable accuracy. Our method is useful not only for selecting the optimal alignment parameters for a chosen template based on predicted alignment quality, but also for filtering out problematic templates that are not suitable for structure prediction due to poor alignment accuracy. This is implemented as a part in FORECAST, the server for fold-recognition and is freely available on the web athttp://pbil.kaist.ac.kr/forecast
Requirement of Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase for Long-Term Potentiation in Adult Mouse Anterior Cingulate Cortex
Authors: Toyoda Hiroki , Zhao Ming-Gao , Xu Hui , Wu Long-Jun , Ren Ming , Zhuo Min
Published: December 2007

Long-term potentiation (LTP) in the anterior cingulate cortex (ACC) is believed to be critical for higher brain functions including emotion, learning, memory and chronic pain. N-methyl-D-aspartate (NMDA) receptor-dependent LTP is well studied and is thought to be important for learning and memory in mammalian brains. As the downstream target of NMDA receptors, the extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinase (MAPK) cascade has been extensively studied for its involvement in synaptic plasticity, learning and memory in hippocampus. By contrast, the role of ERK in cingulate LTP has not been investigated. In this study, we examined whether LTP in ACC requires the activation of ERK. We found that P42/P44 MAPK inhibitors, PD98059 and U0126, suppressed the induction of cingulate LTP that was induced by presynaptic stimulation with postsynaptic depolarization (the pairing protocol). We also showed that cingulate LTP induced by two other different protocols was also blocked by PD98059. Moreover, we found that these two inhibitors had no effect on the maintenance of cingulate LTP. Inhibitors of c-Jun N-terminal kinase (JNK) and p38, other members of MAPK family, SP600125 and SB203850, suppressed the induction of cingulate LTP generated by the pairing protocol. Thus, our study suggests that the MAPK signaling pathway is involved in the induction of cingulate LTP and plays a critical role in physiological conditions.
Cerebellum morphogenesis: the foliation pattern is orchestrated by multi-cellular anchoring centers
Authors: Sudarov Anamaria , Joyner Alexandra L
Published: December 2007

Background

The cerebellum has a striking morphology consisting of folia separated by fissures of different lengths. Since folia in mammals likely serve as a broad platform on which the anterior-posterior organization of the sensory-motor circuits of the cerebellum are built, it is important to understand how such complex morphology arises.

Results

Using a combination of genetic inducible fate mapping, high-resolution cellular analysis and mutant studies in mouse, we demonstrate that a key event in initiation of foliation is the acquisition of a distinct cytoarchitecture in the regions that will become the base of each fissure. We term these regions 'anchoring centers'. We show that the first manifestation of anchoring centers when the cerebellar outer surface is smooth is an increase in proliferation and inward thickening of the granule cell precursors, which likely causes an associated slight invagination of the Purkinje cell layer. Thereafter, granule cell precursors within anchoring centers become distinctly elongated along the axis of the forming fissure. As the outer cerebellar surface begins to fold inwards, Bergmann glial fibers radiate in towards the base of the immature fissure in a fan shape. Once the anchoring center is formed, outgrowth of folia seems to proceed in a self-sustaining manner driven by granule cell migration along Bergmann glial fibers. Finally, by analyzing a cerebellum foliation mutant (Engrailed 2), we demonstrate that changing the timing of anchoring center formation leads to predictable changes in the shape and size of the surrounding folia.

Conclusion

We present a new cellular model of the initial formation of cerebellar fissures with granule cells providing the driving physical force. Both the precise timing of the appearance of anchoring centers at the prospective base of each fissure and the subsequent coordinated action of granule cells and Bergmann glial fibers within the anchoring centers dictates the shape of the folia.
Bioinformatics process management: information flow via a computational journal
Authors: Feagan Lance , Rohrer Justin , Garrett Alexander , Amthauer Heather , Komp Ed , Johnson David , Hock Adam , Clark Terry , Lushington Gerald , Minden Gary , Frost Victor
Published: December 2007

This paper presents the Bioinformatics Computational Journal (BCJ), a framework for conducting and managing computational experiments in bioinformatics and computational biology. These experiments often involve series of computations, data searches, filters, and annotations which can benefit from a structured environment. Systems to manage computational experiments exist, ranging from libraries with standard data models to elaborate schemes to chain together input and output between applications. Yet, although such frameworks are available, their use is not widespread–ad hocscripts are often required to bind applications together. The BCJ explores another solution to this problem through a computer based environment suitable for on-site use, which builds on the traditional laboratory notebook paradigm. It provides an intuitive, extensible paradigm designed for expressive composition of applications. Extensive features facilitate sharing data, computational methods, and entire experiments. By focusing on the bioinformatics and computational biology domain, the scope of the computational framework was narrowed, permitting us to implement a capable set of features for this domain. This report discusses the features determined critical by our system and other projects, along with design issues. We illustrate the use of our implementation of the BCJ on two domain-specific examples.
Hypercalcemia after transplant nephrectomy in a hemodialysis patient: a case report
Authors: Quack Ivo , Woznowski Magdalena , Schieren Gisela , Weiner Stefan M , Winnekendonk Guido , Tokmak Faruk , Rump Lars C , Rattensperger Dirk
Published: December 2007

Introduction

Hypercalcemia is a complication often seen in chronic hemodialysis patients. A rare cause of this condition is sarcoidosis. Its highly variable clinical presentation is challenging. Especially in patients suffering chronic kidney graft failure the nonspecific constitutional symptoms of sarcoidosis like fever, weight loss, arthralgia and fatigue may be easily misleading.

Case presentation

A 51 year old male developed hypercalcemia, arthralgia and B-symptoms after explantation of his kidney graft because of suspected acute rejection. The removed kidney showed vasculopathy and tubulointerstitial nephritis, which had not been overt in the biopsy taken half a year earlier. Despite explantation and withdrawal of the immunosuppression the patient's general condition deteriorated progressively. A rapid rise in serum calcium finally provoked us to check for sarcoidosis. CT scans of the lungs, broncho-alveolar-lavage and further lab tests confirmed the diagnosis.

Conclusion

This case demonstrates that withdrawal of immunosuppressive drugs sometimes unmasks sarcoidosis. It should be considered as differential diagnosis even in hemodialysis patients, in whom other reasons for hypercalcemia are much more common.
The IL-4Rα pathway in macrophages and its potential role in silica-induced pulmonary fibrosis
Authors: Migliaccio Christopher T , Buford Mary C , Jessop Forrest , Holian Andrij
Published: December 2007

Crystalline silica exposure can result in pulmonary fibrosis, where the pulmonary macrophage is key as a result of its ability to react to silica particles. In the mouse silicosis model, there is initial Th1-type inflammation, characterized by TNF-α and IFN-γ. Previous studies determined that Th2 mediators (i.e., IL-13) are vital to development of pulmonary fibrosis. The present study, using in vivo and in vitro techniques, compares silica exposures between Balb/c and Th2-deficient mice in an effort to determine the link between Th2 immunity and silicosis. In long-term experiments, a significant increase in fibrosis and activated interstitial macrophages was observed in Balb/c but not IL-4Rα−/− mice. Additionally, a significant increase in Ym1 mRNA levels, a promoter of Th2 immunity, was determined in the interstitial leukocyte population of silica-exposed Balb/c mice. To elucidate the effects of silica on macrophage function, bone marrow-derived macrophages (BMdM) were exposed to particles and assayed for T cell (TC) stimulation activity. As a control, Ym1 mRNA expression in Balb/c BMdM was determined using IL-4 stimulation. In the in vitro assay, a significant increase in TC activation, as defined by surface markers and cytokines, was observed in the cultures containing the silica-exposed macrophages in wild-type and IL-4Rα−/− mice, with one exception: IL-4Rα−/− BMdM were unable to induce an increase in IL-13. These results suggest that crystalline silica alters cellular functions of macrophages, including activation of TC, and that the increase in Th2 immunity associated with silicosis is via the IL-4Rα-Ym1 pathway.
Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling
Authors: Farhat Katja , Riekenberg Sabine , Heine Holger , Debarry Jennifer , Lang Roland , Mages Jörg , Buwitt-Beckmann Ute , Röschmann Kristina , Jung Günther , Wiesmüller Karl-Heinz , Ulmer Artur J
Published: December 2007

TLR are primary triggers of the innate immune system by recognizing various microorganisms through conserved pathogen-associated molecular patterns. TLR2 is the receptor for a functional recognition of bacterial lipopeptides (LP) and is up-regulated during various disorders such as chronic obstructive pulmonary disease and sepsis. This receptor is unique in its ability to form heteromers with TLR1 or TLR6 to mediate intracellular signaling. According to the fatty acid pattern as well as the assembling of the polypeptide tail, LP can signal through TLR2 in a TLR1- or TLR6-dependent manner. There are also di- and triacylated LP, which stimulate TLR1-deficient cells and TLR6-deficient cells. In this study, we investigated whether heterodimerization evolutionarily developed to broaden the ligand spectrum or to induce different immune responses. We analyzed the signal transduction pathways activated through the different TLR2 dimers using the three LP, palmitic acid (Pam)octanoic acid (Oct)2C-(VPGVG)4VPGKG, fibroblast-stimulating LP-1, and Pam2C-SK4. Dominant-negative forms of signaling molecules, immunoblotting of MAPK, as well as microarray analysis indicate that all dimers use the same signaling cascade, leading to an identical pattern of gene activation. We conclude that heterodimerization of TLR2 with TLR1 or TLR6 evolutionarily developed to expand the ligand spectrum to enable the innate immune system to recognize the numerous, different structures of LP present in various pathogens. Thus, although mycoplasma and Gram-positive and Gram-negative bacteria may activate different TLR2 dimers, the development of different signal pathways in response to different LP does not seem to be of vital significance for the innate defense system.
Protein Biomarker Identification in the CSF of Patients With CNS Lymphoma
Authors: Roy Sushmita , Josephson S. Andrew , Fridlyand Jane , Karch Jon , Kadoch Cigall , Karrim Juliana , Damon Lloyd , Treseler Patrick , Kunwar Sandeep , Shuman Marc A. , Jones Ted , Becker Christopher H. , Schulman Howard , Rubenstein James L.
Published: December 2007

Purpose

Elucidation of the CSF proteome may yield insights into the pathogenesis of CNS disease. We tested the hypothesis that individual CSF proteins distinguish CNS lymphoma from benign focal brain lesions.

Methods

We used a liquid chromatography/mass spectrometry–based method to differentially quantify and identify several hundred CSF proteins in CNS lymphoma and control patients. We used enzyme-linked immunosorbent assay (ELISA) to confirm one of these markers in an additional validation set of 101 cases.

Results

Approximately 80 CSF proteins were identified and found to be present at significantly different concentrations, both higher and lower, in training and test studies, which were highly concordant. To further validate these observations, we defined in detail the expression of one of these candidate biomarkers, antithrombin III (ATIII). ATIII RNA transcripts were identified within CNS lymphomas, and ATIII protein was localized selectively to tumor neovasculature. Determination of ATIII concentration by ELISA was significantly more accurate (> 75% sensitivity; > 98% specificity) than cytology in the identification of cancer. Measurement of CSF ATIII levels was found to potentially enhance the ability to diagnose and predict outcome.

Conclusion

Our findings demonstrate for the first time that proteomic analysis of CSF yields individual biomarkers with greater sensitivity in the identification of cancer than does CSF cytology. We propose that the discovery of CSF protein biomarkers will facilitate early and noninvasive diagnosis in patients with lesions not amenable to brain biopsy, as well as provide improved surrogates of prognosis and treatment response in CNS lymphoma and brain metastasis.
Influence of Electric Field Strength and Emitter Temperature on Dehydrogenation and C—C Cleavage in Field Desorption Mass Spectrometry of Polyethylene Oligomers
Authors: Gross Jürgen H. , Weidner Steffen M.
Published: December 2007

The influence of electric field strength and emitter temperature on dehydrogenation and C–C cleavage in field desorption (FD) mass spectrometry of polyethylene (PE) oligomers of average molecular weights ranging from 500 to 2000 is examined. Low mass oligomers yield molecular weight (MW) distributions that are basically in accordance with results from gel-permeation chromatography. For these materials, dehydrogenation can be greatly reduced by reduction of the emitter potential. Furthermore, the influence of emitter potential on MW distributions indicates the occurrence of field-induced C–C cleavages. Reliable MW distributions are more difficult to obtain from higher mass oligomers by FD-MS because of the need for higher field strength and higher emitter temperatures to effect their desorption/ionization. Experiments reveal that the application of FD-MS to PE oligomers is limited not only by field-induced but also by thermally-induced fragmentations. Even then, FD mass spectra contain valuable information on mass range and homogeneity of PE samples up to about m/z 3600.
Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Study of Mesomeric Heterocyclic Betainium Ions
Authors: Mäkinen Marko , Vainiotalo Pirjo , Schmidt Andreas
Published: December 2007

Mesomeric heterocyclic betainium ions derived from 4-aminopyrimidine-2,6-bis(pyridinium) salts, were examined in the gas phase by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with electrospray ionisation. The purpose of the study was to clarify the general gas-phase properties and reactions of these novel ions. Collision-induced dissociation (CID) was used to investigate fragment ion formation and fragmentation pathways. The ions have an unusual tripolar structure with one negative and two positive charges that are in cross-conjugation within a common -electron system. Resonance stabilisation within the ions makes them relatively unreactive in ion–molecule reactions under the conditions in the FT-ICR cell. CID spectra showed that the charged pyridinium groups are easily lost as neutral pyridine. Otherwise the fragmentation depends on the substituent on the aniline moiety.
Gas-Phase Basicity of Formaldehyde by the Thermokinetic Method
Authors: Bouchoux Guy , Leblanc Danielle
Published: December 2007

A series of proton transfer reactions monitored in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer allows the determination of the gas-phase basicity ( GB) and the proton affinity ( PA) of formaldehyde. The values determined by the thermokinetic method, GB(CH2O) = 681.5 ± 0.7 kJ mol−1 and PA(CH2O) = 711.5 ± 2.1 kJ mol−1 are in excellent agreement with data originating from proton transfer equilibrium constant determinations or from G2 calculations.
Letter: Fast Atom Bombardment, Electrospray, Ionspray and Tandem Mass Spectrometry of 1:1 β-Cyclodextrin/5-Methoxytryptamine Hydrochloride Host—Guest Complex: Host Protonation and Fragmentation Due to Guest Deamination
Authors: Mele Andrea , Panzeri Walter , Selva Antonio , Mauri Pierluigi
Published: December 2007

The 1:1 inclusion complex of β-cyclodextrin (βCD) with 5-methoxytryptamine (5MTA) hydrochloride was studied by mass spectrometry (MS) and tandem-MS with fast atom bombardment (FAB), electrospray (ES) and ionspray (IS) ionisation and triple quadrupole or ion trap analysers. A protonated 1:1 βCD/MTA gaseous association was always observed; the protonated species of deaminated 5MTA and of some typical βCD fragments were obtained, in addition to the expected protonated 5MTA, as tandem-MS dissociation products. A reaction pattern starting from the deamination of protonated 5MTA, as a recently described high pressure chemical ionisation or ES process of primary amines, was suggested, which accounts for the formation of excited protonated βCD and its fragmentation by tandem-MS, even under unimolecular conditions.
Unimolecular Chemistry of •CH2-O-C•=O (Methylenecarboxyldiradical) and HO—CH=C=O (Hydroxyketene) and of the Corresponding Radical Cations and Anions in the Gas Phase
Authors: Polce Michael J. , Song Wei , Cerda Blas A. , Wesdemiotis Chrys
Published: December 2007

The C2H2O2+• isomers •CH2–O–C+=O (1+•, methylenecarboxyl radical cation) and HO–CH=C=O+• (2+•, hydroxyketene radical cation) are produced in the gas phase and their spontaneous and collision-induced decompositions are compared to those of the known glyoxal radical cation, O=CH–CH=O+• (3+•). At threshold, all three ions yield CH2=O+• + CO via unique pathways. 1+• undergoes direct CO rupture with substantial reverse-activation energy, 2+•, after H-rearrangement to •O–CH2–C+=O, loses CO without appreciable reverse-activation energy, and 3+• eliminates CO via the ion–dipole complex +•O=CH2•••CO. The fragmentations of collisionally-activated 1+•–3+• differ substantially, consistent with these ions being distinct C2H2O2+• radical cations. Charge reversal of 1+•–3+• shows that 1−• and 2−• are viable radical anions. The stabilities and reactivities of the corresponding neutral species are determined by neutralization of 1+•–3+• followed by reionization to either cations (+NR+) or anions (+NR−). Diradical 1 is found to be weakly bound by kinetic barriers and dissociates largely in the microsecond time scale to CH2 + CO2 and to CH2=O + CO. In contrast, ketene 2 mainly survives intact within the same time window, decomposing only to a small extent to H• + •O–CH=C=O. The extensive fragmentation observed upon +NR+ of 3+• is shown to occur in the reionization step and primarily reflects the low decomposition threshold of 3+•.
Evidence for an Alkene Metathesis Reaction during the Unimolecular Dissociation of (CH3)3COCHCH2•+
Authors: van der Rest G. , Denhez J.P. , Chamot-Rooke J. , Mourgues P. , Audier H.E.
Published: December 2007

The unimolecular reaction of the metastable tert-butyl vinyl ether radical cation leads mainly to elimination of ethylene. From metastable ion studies as well as Fourier transform ion cyclotron resonance measurements and by using isotopic labeling, it is proposed that the fragmentation begins with the cleavage of the O–C(butyl) bond. This behavior, which contrasts with that of ionized alkylethers, is the consequence of the presence of a vinyl group that allows the formation of a neutral allylic radical. The key intermediate of the fragmentation is likely to be a [CH2CHOH, (CH3)2CCH2]•+ complex in which a cycloaddition–cycloreversion reaction occurs. This intermediate is the same as that produced by a McLafferty rearrangement in appropriate aldehyde radical cations.
Correlation between Alkyl Cation Affinities and Proton Affinities—A Means to Rationalise Alkyl Group Substituent Effects
Authors: Uggerud Einar
Published: December 2007

Using literature thermochemical data it is demonstrated that the known linear relationship between proton affinities and methyl cation affinities can be extended to other alkyl groups (ethyl, i-propyl, t-butyl). It is suggested that the slopes of the straight lines can be used to define a new set of alkyl substituent constants.
Structural Features of Large Molecular Mass Material in Coal-Derived Liquids: Catalytic Hydrocracking of the Pyridine-Insoluble Fraction of a Coal-Tar Pitch
Authors: Begon V. , Islas C. , Lazaro M.J. , Suelves I. , Herod A.A. , Dugwell D.R. , Kandiyoti R.
Published: December 2007

The pyridine-insoluble fraction of a coal-tar pitch has been catalytically hydrocracked. The starting sample contained no material that could be observed by gas chromatography/mass spectrometry (GC/MS) or by heated-probe mass spectrometry. The aim of the study was to generate structural information on this narrow cut of large-molecular-mass material, which consisted mainly of compounds boiling above 450°C. A much broader boiling-point distribution was found for hydrocracked products; evidence from all analytical techniques used (size-exclusion chromatography, UV-fluorescence spectroscopy and heated-probe mass spectrometry) indicated a significant reduction of the molecular mass range. A wide variety of aromatic groups was identified in hydrocracked products by heated-probe mass spectrometry, ranging from phenanthrene ( m/z 178) to beyond dibenzocoronene ( m/z 400). Ions corresponding to alkyl ( m/z 43, 57, 71 and 85) and alkenyl groups ( m/z 41, 55, 69 and 83) were detected. The results reflect the ability of the hydrocracking process to cleave bonds within large pitch molecules, releasing the structural units which form the molecules. The structure of the original pyridine-insoluble material may thus be seen as a series of aromatic groups linked by short bridges or small groups, but with some longer aliphatic bridges (C12 and C17) as shown by pyrolysis-GC/MS. Clearly, some molecular species were reduced in mass but still lay above the range of detection by heated-probe mass spectrometry and could not be identified. Although the extent to which large polycyclic aromatic entities themselves have been cracked (or otherwise reduced to smaller polycyclic aromatic groups) cannot be quantitatively discerned from the present data, the hydrocracking of isolated fractions of intractable coal-derived material appears to offer a useful method for probing their structural features.
Letter: The Use of 2-[(2E)-3-(4-Tert-Butylphenyl)-2-Methylprop-2-Enylidene]Malononitrile as a Matrix for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
Authors: Ulmer Lars , Mattay Jochen , Torres-Garcia H. Gregorio , Luftmann Heinrich
Published: December 2007

2-[(2 E)-3-(4- tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile (DCTB, dicyano. tert-butyl …) has proven to be an excellent nonprotic matrix for very labile compounds, especially for substituted fullerenes. This is mainly due to its extremely low onset of ion production. This matrix works mainly as an electron transfer agent, i.e. the ions produced are radical anions or cations, respectively. It works equally well to transfer evaporation energy to charged oligomers and with proton labile compounds (not shown here).
Thermochemistry of Organic and Heteroorganic Species. Part IX. Photoionization Studies of Isomerization and Fragmentation of Polysubstituted Cyclopropenes: Phenyl-Substituted Cyclopropenes
Authors: Takhistov V.V. , Domnin I.N. , Ponomarev D.A.
Published: December 2007

Ionization and appearance energies of some fragment ions from 1,2,3-trimethy1-3-phenyl-, 3-methyl-1,2,3-triphenyl-, 1,2-diphenyl-3-methoxycarbonyl-, 1,2,3-triphenyl-3-methoxycarbonyl- and 1,3,3-triphenyl-2-methoxycarbonyl-cyclopropenes were measured by photoionization mass spectrometry. It was shown that in none of these compounds did the fragment ions possess the expected stable substituted cyclopropenium ion structure. Accordingly, possible schemes of molecular ion isomerization are given. The enthalpies of formation of nearly 50 substituted cyclopropenium ions, and ions of related structure, were estimated using series of isodesmic reactions. This publication, together with the previous works of the authors in this Journal, demonstrates the general methodology for estimation of the enthalpy of formation for even-electron ions. It is suggested that the present methodology can provide a good alternative to other estimation or computation procedures applied to the thermochemistry of ions.
Study of Ion—Molecule Reactions and Collisionally-Activated Dissociation of Dopamine and Adrenaline by an Ion Trap Mass Spectrometer with An External Ionization Source
Authors: Wu Hui-Fen , Lin Ya-Ping
Published: December 2007

Study of the reaction mechanisms for ion–molecule reactions and for collisionally-activated dissociations (CAD) of dopamine and adrenaline has been performed using an external chemical ionization source quadrupole ion trap mass spectrometer. This work demonstrates the possibility of applying an external source ion trap instrument to perform selective ion–molecule reactions in the gas phase, due to its high sensitivity and low detection limits in mass spectrometry/mass spectrometry (MS/MS) mode. CAD experiments on ions with relative intensity as low as 0–2%, formed as ion–molecule products of dopamine and adrenaline, have been successfully performed. Study of some fragment ions of M+• and [M + H]+, observed in the chemical ionization (CI) spectra, by CAD techniques, permits elucidation of a series of mechanisms for the sequential dissociations of the M+• and [M + H]+ ions. Thus, the structural information obtained from this method is similar to that which would have been obtained if MS n had been performed for M+• and [M + H]+ ions. From the proposed CAD reaction mechanisms and the semi-empirical calculations, the favored reactive sites for formation of the adduct ions could be determined. The reactive site for protonation of dopamine is on the amino group, but for adrenaline, it is on the benzylic hydroxyl group. As to the reactive site for the CH3O=C2H+ ion addition, dopamine is either on the amino group or on the phenyl ring. However, adrenaline is only on the benzylic hydroxyl group. Temperature effects on the formation of the ion–molecule products were also investigated. It was shown that the best source temperature for formation of [M + H]+ and [M + 13]+ ions of dopamine is 200°C. Information about use of dimethyl ether (DME) as the reagent gas in the external chemical ionization of an ion trap mass spectrometer is provided.
Laser Ion Kinetics: Dynamics of Intramolecular Reactions in Substituted Benzalacetones
Authors: Heinicke R. , Grun C. , Grotemeyer J.
Published: December 2007

Measurements of a single shot femtosecond laser pump-probe technique on substituted benzalacetones are reported. The technique is based on counter propagating femtosecond laser pulses in a supersonic beam of low density of sample molecules and simultaneous probe detection by ion or fragment ion formation through a reflectron time-of-flight mass spectrometer. It will be shown that the range of the pump-probe delays covers the time span between 100 fs and 10 ps depending on the pulse width of the laser used and the stability of the voltages of the mass spectrometer. The application of this technique to medium-sized organic molecules reveals some insight into the electron transfer process during ionisation through a 1 + 1 multi-photon absorption procedure. Furthermore it is demonstrated that this technique is also applicable to the investigation of ultra-fast isomerisation and fragmentation processes.
A New Electrostatic Transfer Line for Improved Transmission in Fourier Transform Laser Microprobe Mass Spectrometry with External Ion Source
Authors: Van Vaeck Luc , Van Espen Piet , Gijbels Renaat , Baykut Gökhan , Laukien Frank H.
Published: December 2007

The efficient extraction and transfer of ions from an external ion source outside the magnet and their injection through the inhomogeneous fringing field becomes a key factor in the micro-analytical application of Fourier transform mass spectrometry (FTMS) instruments with an external ion source. This paper reports on a new ion transfer line with static electrical fields for a source at a distance of 131 cm from the cylindrical ion cyclotron resonance (ICR) “Infinity” cell in an unshielded 4.7 Tesla superconducting magnet. Basically, ions are accelerated to 2–3 kV, transported through a time-of-flight (TOF) system and decelerated at the entrance of the magnet. The size of the system, the magnetic stray field and the significant electrical field gradients require careful optimisation of the simulations with the SIMION software. According to our calculations, the new ion transfer line should allow transport and trapping of ions initially emitted with an angle of up to 35° with the normal, as opposed to 5° with the former commercial transfer line with improved cylindrical front optics. The design has been experimentally verified using focused laser desorption/ionisation of solids. The data on reference compounds have demonstrated that the sensitivity with the new transfer line increases by a factor of 10. A substantial gain of sensitivity is also expected for other ionisation methods producing ions with a more isotropic angular emission than focused laser irradiation. The new ion optics are fully compatible with the existing hardware so that conversion becomes a minor operation.
Hyperthermal Surface Ionization in a Time-of-Flight Mass Spectrometer
Authors: Weickhardt Christian , Draack Lars , Grotemeyer Jürgen
Published: December 2007

An apparatus is described which couples hyperthermal surface ionization (HSI) with time-of-flight mass spectrometry. In order to adapt HSI to the non-continuously working time-of-flight mass spectrometer, it is performed in a pulsed supersonic molecular beam. The ion bunch formed by the surface scattering process is accelerated from a specially-designed ion source into a reflectron time-of-flight mass spectrometer. In this way features of HSI such as high ionization yield and tunable degree of fragmentation are combined with the advantages of the time-of-flight mass spectrometer, namely its high transmission, its in principle unlimited mass range, and the simultaneous detection of the entire mass range. The resulting instrument thereby opens up hyperthermal surface ionization to applications demanding high temporal resolution.
Quantitative Capability of Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for a Complex Mixture
Authors: Miyabayashi Keiko , Naito Yasuhide , Miyake Mikio , Tsujimoto Kazuo
Published: December 2007

Electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been evaluated for the quantitation of complex mixtures, by using a crude oil (Taching vacuum residue) and polyethylene glycol (PEG600) as model analytes. The crude oil is an extremely complex mixture consisting of hundreds of organic compounds, which are mostly non-polar hydrocarbons. The crude oil ESI FT-ICR mass spectrum contained approximately five hundred distinguishable peaks accompanied by plenty of isobars. These ionic species were singly charged but not protonated. Although the crude oil response line was saturated at high concentration, the linearly responding range was extended by shortening the duration of the external accumulation which was carried out in the hexapole ion guide. No improvement in the linear response was observed for the exclusively trapped crude oil ions in a narrow m/z range which was trimmed by a correlated sweep ejection event. The crude oil mass distribution pattern shifted toward higher m/z as the analyte concentration became higher. A linear relationship was observed between the analyte concentrations and the average molecular weights, in both the crude oil and PEG600 experiments. The average molecular weights increased on extending the external accumulation time. This phenomenon was attributable to a novel space charge effect taking place for externally accumulated ions. Optimizing the external accumulation period was vital to get a linear response up to a reasonably high concentration region. Basically, complexity and plurality of mixture samples need not significantly affect quantitation by means of ESI FT-ICR MS.
Letter: Electron-Impact Mass Spectrometry in Analysis of Isomeric Alkoxycarbonylalkylthiouracils—A Correlation of M+• Intensities and Selected Fragment Ions
Authors: Wybieralska Jadwiga
Published: December 2007

The correlation between the intensities of M+• and the selected fragment ions on basis the mass spectral fragmentation of thirty-two 2- and 4-alkoxycarbonylalkylthiouracils were discussed. The data obtained create the basis for distinguishing isomers.
A 9.4 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: Description and Performance
Authors: Palmblad Magnus , Håkansson Kristina , Håkansson Per , Feng Xidong , Cooper Helen J. , Giannakopulos Anastassios E. , Green Philip S. , Derrick Peter J.
Published: December 2007

9.4 Tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers (Bruker BioAPEX-94e) have been installed at the Division of Ion Physics, Uppsala University, and at the Department of Chemistry, University of Warwick. The BioAPEX-94e FT-ICR instrument is built around a high-field, superconducting magnet and a platform with easily interchangeable ion sources [matrix-assisted laser desorption/ionisation (MALDI), secondary ion mass spectrometry (SIMS), electrospray ionisation (ESI) and electron impact/chemical ionisation (EI/CI)]. In this paper a technical description of the instrument is given. Outstanding performance characteristics are demonstrated, notably clear resolution of C59N+ and C5813C2+ (mass difference 3.65 mDa) and mass measurement accuracy at the low ppm level. A wide range of applications in Warwick and Uppsala is described, demonstrating the versatility and high performance of the instrument.
Some Practical Aspects of the Acceleration—Deceleration Method for Ion Kinetic Energy Focusing in Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
Authors: Pikver Rein , Past Jaan , Subbi Juhan , Aguraiuja Reet , Lippmaa Endel
Published: December 2007

A new acceleration–deceleration (AD) method for reducing and focusing ion kinetic energies in matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR) mass spectrometry has been developed. The aim of the method is to equalize and then reduce the initial kinetic energy of the MALDI-produced ions, distributed over a broad energy range, by means of delayed acceleration and deceleration of the ions. The focusing of the energy results in a more efficient trapping of high mass ions and, at the same time, improves the precision of mass measurements in the ICR trap. The experimental parameters for the acceleration–deceleration ion kinetic energy focusing were predicted by means of the SIMION 3D software, incorporating both the electric and magnetic fields. The deceleration of ions both outside and inside the ICR trap was studied. The theoretical treatment shows that by applying the acceleration–deceleration method it is possible to focus the initially high kinetic energies of 100,000 Da ions into a 1 eV range and register their mass spectrum at low trapping potentials. In order to put the new method into practice, the existing FTICR mass spectrometer was equipped with a MALDI source inside the magnet. To compare the acceleration– deceleration method with other methods, the optimal mass spectrum measurement conditions for several proteomic biopolymers were studied. By means of the acceleration–deceleration method, the MALDI-FTICR mass spectrum of substance P (protonated mass 1347.736 Da) was registered at 3 × 10−8 mbar with mass resolution close to 70,000. A resolution of 45,000 was achieved by the gated trapping method. Bovine insulin B-chain (protonated mass 3494.65 Da) was used to compare the gated trapping method with the deceleration and acceleration–deceleration methods (which also include the gated trapping method as an essential part) at different matrix-to-analyte ratios. The acceleration–deceleration method does not reject high energy ions and has therefore inherently high sensitivity particularly at low analyte concentration. Bovine insulin (protonated mass 5732.6 Da) is so far the highest mass ion registered in our spectrometer. It was possible to measure this ion only by the acceleration–deceleration method.