bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of 12‐month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease
Authors: Kalliokoski R. J. , Kantola I. , Kalliokoski K. K. , Engblom E. , Sundell J. , Hannukainen J. C. , Janatuinen T. , Raitakari O. T. , Knuuti J. , Penttinen M. , Viikari J. , Nuutila P. 
Published: April 2006

SummaryFabry disease (McKusick 301500) is an X‐linked lysosomal storage disorder secondary to deficient α‐galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids, especially in vascular smooth‐muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19–49 years) with confirmed Fabry disease were approved for this uncontrolled, open‐label study. Myocardial perfusion was measured at rest and during dipyridamole‐induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human α‐galactosidase A (Fabrazyme, Genzyme). Plasma Gb3 concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole‐stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = −0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb3 concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.
Neuropsychometric outcome predictors for adults with maple syrup urine disease
Authors: le Roux C. , Murphy E. , Hallam P. , Lilburn M. , Orlowska D. , Lee P. 
Published: April 2006

SummaryWe describe 14 adult MSUD patients (3 with intermediate MSUD) with varied clinical and neuropsychometric outcomes. Age at diagnosis appears to be a predictor of IQ even in adults, while long‐term blood leucine does not correlate with IQ.
Acid sphingomyelinase deficiency: Cardiac dysfunction and characteristic findings of the coronary arteries
Authors: Ishii H. , Takahashi T. , Toyono M. , Tamura M. , Harada K. , Yoshida M. , Nishikawa Y. , Enomoto K. , Takada G. 
Published: April 2006

SummaryTwo sisters with type B Niemann–Pick disease (genotype: S436R/S436R) showed cardiac dysfunctions, not secondary to pulmonary disease, at the beginning of the third decade. In the younger sister, myocardial dysfunction was refractory to treatment, resulting in death. At autopsy, the distal branches of the coronary arteries showed narrowing of the arterial lumina due to swelling of the medial and intimal smooth‐muscle cells. This is the first report describing characteristic findings of coronary arteries in type B Niemann–Pick disease.
The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005
Authors: Frazier D. M. , Millington D. S. , McCandless S. E. , Koeberl D. D. , Weavil S. D. , Chaing S. H. , Muenzer J. 
Published: April 2006

SummaryNorth Carolina (NC) was the first US state to initiate universal tandem mass spectrometry (MS/MS) newborn screening. This began as a statewide pilot project in 1997 to determine the incidence and feasibility of screening for fatty acid oxidation, organic acid and selected amino acid disorders. The MS/MS analyses were done by a commercial laboratory and all follow‐up and confirmatory testing was performed through the NC Newborn Screening (NBS) Program. In April 1999, the NC NBS Laboratory began the MS/MS analyses in‐house. Between 28 July 1997 and 28 July 2005, 944 078 infants were screened and 219 diagnoses were confirmed on newborns with elevated screening results, for an overall incidence of 1:4300. Ninety‐nine infants were identified with fatty acid oxidation disorders, 58 with organic acidaemias and 62 with aminoacidopathies. Medium‐chain acyl‐CoA dehydrogenase deficiency, 3‐methylcrotonyl‐CoA carboxylase deficiency and disorders of phenylalanine metabolism were the most common disorders detected. Identification of affected infants has allowed retrospective testing of other family members, resulting in an additional 16 diagnoses. Seven neonates died from complications of their metabolic disorders/prematurity despite timely MS/MS screening. In addition, there were six infants who were not identified by elevated NBS results but who presented with symptoms later in infancy. The NC MS/MS NBS Program uses a two‐tier system, categorizing results as either ‘borderline’ or ‘diagnostic’ elevated, for both the cutoffs and follow‐up protocol. Infants with an initial borderline result had only a repeat screen. Infants with a diagnostic or two borderline results were referred for confirmatory testing. The positive predictive value of the NC MS/MS NBS for those infants requiring confirmatory testing was 53% for 2003 and 2004. The success of the NC MS/MS NBS Program in identifying infants with metabolic disorders was dependent on a comprehensive follow‐up protocol integrating the public health laboratory and the academic metabolic centres.
Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency
Authors: Donarum Elizabeth A. , Stephan Dietrich A. , Larkin Kay , Murphy Eric J. , Gupta Maneesh , Senephansiri Henry , Switzer Robert C. , Pearl Phillip L. , Snead O. Carter , Jakobs C. , Gibson K. Michael 
Published: April 2006

SummarySuccinic semialdehyde dehydrogenase (SSADH) deficiency, a rare genetic defect of GABA degradation recently modelled in mice (SSADH−/− mice), manifests early absence seizures that evolve into generalized convulsive seizures and lethal status epilepticus in gene‐ablated mice. Disrupted GABA homeostasis, in conjunction with the epileptic phenotype and increased gamma‐hydroxybutyric acid (GHB), suggested that expression profiling with the U74Av2 Affymetrix system would reveal dysregulation of receptor genes associated with GABAergic and glutamatergic neurotransmission. Unexpectedly, we found significant downregulation for genes associated with myelin biogenesis and compaction, predominantly in hippocampus and cortex. These results were confirmed by: (1) myelin basic protein (MBP) immunohistochemistry; (2) western blotting of myelin‐associated glycoprotein (MAG) and MBP; (3) qRT‐PCR analyses of myelin‐associated oligodendrocytic basic protein (MOBP), MAG, MBP and proteolipid protein (PLP) in hippocampus, cortex and spinal cord; (4) quantitation of ethanolamine and choline plasmalogens, all core myelin components; (5) evaluation of myelin content in brain sections employing toluidine blue staining; and (6) ultrastructural evaluation of myelin sheath thickness via electron microscopy. We speculate that increased GABA/GHB, acting through GABAergic systems, results in decreased levels of the neurosteroids progesterone and allopregnanolone [Gupta et al (2003) Ann Neurol54(Supplement 6): S81–S90] and phosphorylation of mitogen‐activated protein (MAP) kinase, with resulting myelin protein abnormalities primarily in the cortex of SSADH−/− mice.
Multilevel Model Prediction
Authors: Frees Edward W. , Kim Jee-Seon 
Published: April 2006

Multilevel models are proven tools in social research for modeling complex, hierarchical systems. In multilevel modeling, statistical inference is based largely on quantification of random variables. This paper distinguishes among three types of random variables in multilevel modeling—model disturbances, random coefficients, and future response outcomes—and provides a unified procedure for predicting them. These predictors are best linear unbiased and are commonly known via the acronym BLUP; they are optimal in the sense of minimizing mean square error and are Bayesian under a diffuse prior.For parameter estimation purposes, a multilevel model can be written as a linear mixed-effects model. In this way, parameters of the many equations can be estimated simultaneously and hence efficiently. For prediction purposes, we show that it is more convenient to retain the multiple equation feature of multilevel models. In this way, the efficient BLUPs are easy to compute and retain their intuitively appealing recursive form. We also derive explicit equations for standard errors of these different types of predictors.Prediction in multilevel modeling is important in a wide range of applications. To demonstrate the applicability of our results, this paper discusses prediction in the context of a study of school effectiveness.
Can a sexually dimorphic index of prenatal hormonal exposure be used to examine cold pressor pain perception in men and women?
Authors: Keogh Edmund , Mounce Charlotte , Brosnan Mark 
Published: April 2006

AbstractThere is considerable evidence to suggest that important differences exist between men and women in their experience of pain. Research has now turned to determine what the mechanisms of such differences actually are. One potential explanation is the effect of sex hormones, especially those typically found in greater concentration within women, e.g., estrogen, progesterone. However, it is also possible that other hormones, such as testosterone may be important. The current study employed a non‐invasive sexually dimorphic index (digit ratio) that is believed to reflect prenatal exposure to testosterone, and related this to the cold pressor pain experiences of 23 men and 27 healthy women. As expected, females had greater symmetry between the second and fourth digits, and also reported lower pain tolerance levels. Although some significant relationships were found between digit ratio/digit length and cold pressor pain reports they were relatively inconsistent. Furthermore, the main finding, that pain thresholds were positively related to digit ratio in women but not men, is somewhat inconsistent with predictions. The results are discussed in light of methods for investigating the effect of prenatal hormonal exposure on pain sensitivity in men and women.
GPS Satellite Velocity and Acceleration Determination using the Broadcast Ephemeris
Authors: Zhang Jason , Zhang Kefei , Grenfell Ron , Deakin Rod 
Published: April 2006

Satellite velocity determination using the broadcast ephemeris is discussed and it is pointed out that the conventional rotation matrix method involves a complicated process of computation. This paper proposes an alternative method using a simple differentiator to derive satellite Earth-Centred-Earth-Fixed (ECEF) velocity from the ECEF satellite positions that are calculated using the standard ICD-GPS-200 algorithm. The proposed algorithm simplifies the velocity transformation procedure, and therefore provides a good alternative. It is demonstrated that ±1 mm/s per axis ECEF satellite velocity is achievable by using the first-order central difference of a Taylor series approximation.A closed-form formula is also derived for the determination of GPS satellite ECEF acceleration using the broadcast ephemeris. This formula is capable of accuracies better than ±0·1 mm per second squared in each axis. With such a high accuracy of satellite acceleration in real-time, it is possible to detect the line-of-sight range acceleration precisely and as such it is concluded that a GPS receiver can be considered as a precise accelerometer.The success of the position differential method implies that real-time satellite ECEF velocities can be directly derived through numerical differentiation of the position polynomials. This is desirable for GPS velocity determination applications which require high output rate results in real-time. The derived closed-form formula for GPS satellite ECEF acceleration would benefit those who attempt to use a GPS receiver as an accurate accelerometer in real-time.
Flying EGNOS Approaches in the Swiss Alps
Authors: Perrin Olivier , Scaramuzza Maurizio , Buchanan Thomas , Brocard Daniel 
Published: April 2006

The European Geostationary Navigation Overlay Service (EGNOS) system is being developed in Europe to provide Global Positioning System (GPS) and GLONASS regional augmentation services to aviation, maritime and land users. The EGNOS system, as any other Wide Area Augmentation System (WAAS), relies on the broadcast of differential correction and integrity information in the pseudo-range domain, which are then used to provide a solution in the position domain. EGNOS is a major element of the European Satellite Navigation Program, which is jointly being implemented by the Commission of the European Union, the European Space Agency (ESA) and Eurocontrol (the European Organisation for the Safety of Air Navigation). It is also the first European step to the GALILEO system.As part of the EGNOS validation activities, flight trials have been organised by ESA and the EGNOS Industrial Consortium at various locations in Europe during Spring 2005. To demonstrate the system capability in a challenging mountainous environment, tests have been conducted at Lugano airport in the Swiss Alps. Due to the difficult topography of the airport and its surroundings, the use of conventional ground based navigation aids present some limitations. For the trials, a new Satellite Based Augmentation System (SBAS) procedure has been designed to take advantage of the system flexibility. In particular, a reduction of the approach glide path angle has been achieved, potentially allowing more aircraft types to fly the approach than today. This article presents the operational benefits that could be obtained with the new test procedure. The very impressive EGNOS performance is also described in details, showing that it can support Approach Procedure with Vertical guidance (APV) operations even in a very challenging environment.
Simple models for containment of a pandemic
Authors: Arino Julien , Brauer Fred , van den Driessche P , Watmough James , Wu Jianhong 
Published: April 2006

Stochastic simulations of network models have become the standard approach to studying epidemics. We show that many of the predictions of these models can also be obtained from simple classical deterministic compartmental models. We suggest that simple models may be a better way to plan for a threatening pandemic with location and parameters as yet unknown, reserving more detailed network models for disease outbreaks already underway in localities where the social networks are well identified.
We formulate compartmental models to describe outbreaks of influenza and attempt to manage a disease outbreak by vaccination or antiviral treatment. The models give an important prediction that may not have been noticed in other models, namely that the number of doses of antiviral treatment required is extremely sensitive to the number of initial infectives. This suggests that the actual number of doses needed cannot be estimated with any degree of reliability. The model is applicable to pre-epidemic vaccination, such as annual vaccination programs in anticipation of an ‘ordinary’ influenza outbreak with limited drift, and as a combination of treatment both before and during an epidemic.
Solution structure of the antifreeze‐like domain of human sialic acid synthase
Authors: Hamada Toshiyuki , Ito Yoko , Abe Takamasa , Hayashi Fumiaki , Güntert Peter , Inoue Makoto , Kigawa Takanori , Terada Takaho , Shirouzu Mikako , Yoshida Mayumi , Tanaka Akiko , Sugano Sumio , Yokoyama Shigeyuki , Hirota Hiroshi 
Published: April 2006

AbstractThe structure of the C‐terminal antifreeze‐like (AFL) domain of human sialic acid synthase was determined by NMR spectroscopy. The structure comprises one α‐ and two single‐turn 310‐helices and two β‐strands, and is similar to those of the type III antifreeze proteins. Evolutionary trace analyses of the type III antifreeze protein family suggested that the class‐specific residues in the human and bacterial AFL domains are important for their substrate binding, while the class‐specific residues of the fish antifreeze proteins are gathered on the ice‐binding surface.
Secondary structure and dynamics of micelle bound β‐ and γ‐synuclein
Authors: Sung Yoon‐hui , Eliezer David 
Published: April 2006

AbstractWe have used solution state NMR spectroscopy to characterize the secondary structure and backbone dynamics of the proteins β‐ and γ‐synuclein in their detergent micelle‐bound conformations. Comparison of the results with those previously obtained for the Parkinson's disease‐linked protein α‐synuclein shows that structural differences between the three homologous synuclein family members are directly related to variations in their primary amino acid sequences. An 11‐residue deletion in the lipid‐binding domain of β‐synuclein leads to the destabilization of an entire segment of the micelle‐bound helical structure containing the deletion site. The acidic C‐terminal tail region of γ‐synuclein, which displays extensive sequence divergence, is more highly disordered than the corresponding regions in the other two family members. The observed structural differences are likely to mediate functional variations between the three proteins, with differences between α‐ and β‐synuclein expected to revolve around their lipid interactions, while differences in γ‐synuclein function are expected to result from different protein–protein interactions mediated by its unique C‐terminal tail.
pK values of the ionizable groups of proteins
Authors: Thurlkill Richard L. , Grimsley Gerald R. , Scholtz J. Martin , Pace C. Nick 
Published: April 2006

AbstractWe have used potentiometric titrations to measure the pK values of the ionizable groups of proteins in alanine pentapeptides with appropriately blocked termini. These pentapeptides provide an improved model for the pK values of the ionizable groups in proteins. Our pK values determined in 0.1 M KCl at 25°C are: 3.67±0.03 (α‐carboxyl), 3.67±0.04 (Asp), 4.25±0.05 (Glu), 6.54±0.04 (His), 8.00±0.03 (α‐amino), 8.55±0.03 (Cys), 9.84±0.11 (Tyr), and 10.40±0.08 (Lys). The pK values of some groups differ from the Nozaki and Tanford (N&T) pK values often used in the literature: Asp (3.67 this work vs. 4.0 N&T); His (6.54 this work vs. 6.3 N&T); α‐amino (8.00 this work vs. 7.5 N&T); Cys (8.55 this work vs. 9.5 N&T); and Tyr (9.84 this work vs. 9.6 N&T). Our pK values will be useful to those who study pK perturbations in folded and unfolded proteins, and to those who use theory to gain a better understanding of the factors that determine the pK values of the ionizable groups of proteins.
The IclR family of transcriptional activators and repressors can be defined by a single profile
Authors: Krell Tino , Molina‐Henares Antonio Jesús , Ramos Juan Luis 
Published: April 2006

AbstractIn the last decade enormous advances in life sciences have been possible due to the information obtained from DNA sequencing projects. The optimal interpretation and analysis of genome sequence data requires the precise annotation and classification of proteins deduced from open reading frames, which is usually done with the help of family‐specific signatures. Here we report a novel profile for the IclR type of transcriptional activators and repressors. In contrast to profiles for other families of transcriptional regulators, the new IclR profile is located outside the helix‐turn‐helix DNA‐binding motif. We provide evidence that the new profile is more specific than any of the existing signatures for this family of regulators. More than 500 representatives of this family were identified with this profile. A database on bacterial regulators (http://www.bactregulators.org) was built to compile and regroup the sequences with the aid of the new profile.
Bacterial display using circularly permuted outer membrane protein OmpX yields high affinity peptide ligands
Authors: Rice Jeffrey J. , Schohn Aaron , Bessette Paul H. , Boulware Kevin T. , Daugherty Patrick S. 
Published: April 2006

AbstractA bacterial display methodology was developed for N‐ and C‐terminal display and demonstrated to enable rapid screening of very large peptide libraries with high precision and efficiency. To overcome limitations of insertional fusion display libraries, a new scaffold was developed through circular permutation of the Escherichia coli outer membrane protein OmpX that presents both N and C termini on the external cell surface. Circularly permuted OmpX (CPX) display was directly compared to insertional fusion display by screening comparable peptide libraries in each format using magnetic and fluorescence activated cell sorting. CPX display enabled in situ measurement of dissociation rate constants with improved accuracy and, consequently, improved affinity discrimination during screening and ranking of isolated clones. Using streptavidin as a model target, bacterial display yielded the well‐characterized HPQ/M motif obtained previously using several alternative peptide display systems, as well as three additional motifs (LI/V CQNVCY, CGWMYF/YxEC, ERCWYVMHWPCNA). Using CPX display, a very high affinity streptavidin‐binding peptide was isolated having a dissociation rate constant koff = 0.002sec−1 even after grafting to the C terminus of an unrelated protein. Comparison of individual clones obtained from insertional fusion and terminal fusion libraries suggests that the N‐terminal display yields sequences with greater diversity, affinity, and modularity. CPX bacterial display thus provides a highly effective method for screening peptide libraries to rapidly generate ligands with high affinity and specificity.
Secondary structure, orientation, and oligomerization of phospholemman, a cardiac transmembrane protein
Authors: Beevers Andrew J. , Kukol Andreas 
Published: April 2006

AbstractHuman phospholemman (PLM) is a 72‐residue protein, which is expressed at high density in the cardiac plasma membrane and in various other tissues. It forms ion channels selective for K+, Cl−, and taurine in lipid bilayers and colocalizes with the Na+/K+‐ATPase and the Na+/Ca2+‐exchanger, which may suggest a role in the regulation of cell volume. Here we present the first structural data based on synthetic peptides representing the transmembrane domain of PLM. Perfluoro‐octaneoate‐PAGE of reconstituted proteoliposomes containing PLM reveals a tetrameric homo‐oligomerization. Infrared spectroscopy of proteoliposomes shows that the PLM peptide is completely α‐helical, even beyond the hydrophobic core residues. Hydrogen/deuterium exchange experiments reveal that a core of 20–22 residues is not accessible to water, thus embedded in the lipid membrane. The maximum helix tilt is 17° ± 2° obtained by attenuated total reflection infrared spectroscopy. Thus, our data support the idea of ion channel formation by the PLM transmembrane domain.