bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing’s disease
Authors: Storr Helen L , Afshar Farhad , Matson Matthew , Sabin Ian , Davies Kate M , Evanson Jane , Plowman P Nicholas , Besser G Michael , Monson John P , Grossman Ashley B , Savage Martin O 
Published: June 2005

Objective: Early diagnosis and effective treatment of paediatric Cushing’s disease (CD) is necessary to minimise associated morbidity. Accepted first-line treatment is selective transsphenoidal microadenomectomy (TSS), which can be technically difficult, and cure rates vary considerably between centres. In our paediatric CD patient group we have assessed the possible factors which may influence cure by TSS.
Subjects and methods: From 1983–2004, 27 paediatric patients (16 males, 11 females; mean age±s.d., 13.1±3.2 yr; range, 6.4–17.8 yr) with CD were managed in our centre and underwent TSS. Sixteen patients (59%), seven males and nine females (mean age±s.d., 14.2±2.5 yr; range, 8.2–17.8 yr), were cured (post-operative serum cortisol < 50 nM). Eleven patients, nine males and two females (mean age±s.d., 11.5±3.6 yr; range, 6.4–17.8 yr) had post-operative cortisol levels above 50 nM (2–20 days), with mean serum cortisol levels at 09:00 h of 537 nM (range 269–900 nM) indicating a lack of cure. These 11 patients received external beam pituitary radiotherapy (RT). One patient with a pituitary macroadenoma had a post-operative cortisol level of < 50 nM but 0.8 yr later showed an elevated cortisol and residual disease.
Results: The patients cured by TSS alone were significantly older than those not cured (P = 0.038; Student’s t test). All patients had CT/MRI pituitary imaging: 14 were reported to have microadenomas and one macroadenoma, while 12 were reported as normal. Bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with i.v. corticotropin-releasing hormone (CRH) administration was introduced as a pre-operative investigation in 1986 and was performed in 21 patients (78%), on BSIPSS, 16 (76%) had evidence suggesting pituitary adrenocorticotropic hormone (ACTH) secretion (central to peripheral (IPS:P) ACTH ratio after CRH of ≥ 3.0) and 16 (76%) showed lateralisation of ACTH secretion (IPSG of ≥ 1.4). There was concordance between the BSIPSS finding and the position of the microadenoma at surgery in 17/21 (81%) patients. Of the 16 patients showing lateralisation of ACTH secretion, 12 (75%) were cured by TSS. Of the four without lateralisation of ACTH, suggesting a midline lesion, 3 (75%) were cured by TSS. Post-operative pituitary hormone deficiencies in the patients cured by TSS were: pan-hypopituitarism 1/16, isolated growth hormone deficiency (GHD) (peak GH on glucagon/ITT < 1–17.9 mU/l) 9/16 and diabetes insipidus 3/16.
Conclusion: Over a 21-year period selective adenomectomy by TSS cured 59% of all paediatric CD patients, with higher age favouring cure. Introduction of BSIPSS resulted in the demonstration of a high rate of lateralisation of ACTH secretion consistent with the surgical identification of the adenoma, and therefore appears likely to have contributed to the higher surgical cure rate.
Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males
Authors: Thiele Susanne , Hoppe Ute , Holterhus Paul-Martin , Hiort Olaf 
Published: June 2005

Objective: 5alpha-reductase enzymes reduce testosterone (T) to the most potent androgen dihydrotestosterone (DHT). Two isoenzymes are known to day. While the type 2-enzyme (5RII) is predominantly expressed in male genital tissues and mutations are known to cause a severe virilization disorder in genetic males, the role of the type 1-enzyme (5RI) in normal male androgen physiology is unclear. We investigated whether 5RI is transcribed in normal male genital skin fibroblasts (GSFs) and if the transcription is regulated by age or by androgens themselves.Methods: GSF from 14 normally virilized males of different ages, ranging from 8 months to 72 years, obtained at circumcision were cultured. Total RNA was isolated after incubation for 48 h with 100 nM T or without androgens. Each sample was amplified in triplicate by real-time PCR with porphobilinogen desaminase as a housekeeping gene used for semiquantification. Selected cultures were analyzed after incubation with 10 and 100 nM T and 1 and 100 nM DHT for 24, 48 and 120 h.Results: 5RI was transcribed in all investigated samples with a 4.5-fold variability in the mRNA concentration of different individuals. However, neither age-related regulation nor significant influence of T or DHT on the transcription rate was discovered.Conclusion: Since 5RI is abundantly transcribed in GSFs, we hypothesize that this isoenzyme may play important roles in the androgen physiology of normally virilized males and may contribute to masculinization in 5RII-deficient males at the time of puberty.
The secretion and effect of inhibin A, activin A and follistatin on first-trimester trophoblasts in vitro
Authors: Bearfield C , Jauniaux E , Groome N , Sargent I L , Muttukrishna S 
Published: June 2005

Objective: The objectives of this study were to investigate the effect of activin A and follistatin on first-trimester cytotrophoblast invasion in culture and to study the secretion of inhibin A, activin A and follistatin by these cellsin vitro.Design and methods: Cytotrophoblasts were isolated from human placental chorionic villous tissue obtained from 6–8, 8–10 and 10–12 weeks gestation. Cells were cultured for 3 days on cell-culture inserts coated with gelatine for invasion studies and in 24-well culture plates for secretion studies. The effects of activin A (10 ng/ml), follistatin (100 ng/ml), interleukin 1β (IL-1β; 10 ng/ml) and epidermal growth factor (EGF; 10 ng/ml) on cytotrophoblast invasion were investigated using a non-radioactive invasion assay. Secretion of inhibin A, activin A and follistatin in the presence of EGF, IL-1β, activin A and follistatin were measured using in-house ELISAs.Results and conclusion: Activin A, follistatin and EGF had a significant stimulatory effect on cytotrophoblast invasion from 6–10 weeks gestation. IL-1β had a significant stimulatory effect at 8–10 weeks and a significant inhibitory effect on invasion at 10–12 weeks gestation. Follistatin also had a significant inhibitory effect on invasion at 10–12 weeks gestation. In the secretion study, activin A secretion at 8–10 weeks was significantly stimulated by IL-1β and EGF. At 10–12 weeks, follistatin and EGF had a significant inhibitory effect on activin A secretion. Follistatin secretion was significantly increased in the presence of IL-1β at 6–8 weeks gestation. Inhibin A secretion was not significantly altered by EGF, IL-1β, activin A and follistatin. These results show that activin A promotes invasion of first-trimester cytotrophoblasts until 10 weeks gestation. There is a difference in the control of secretion of these proteins dependent on the gestation, suggesting that there is a tight regulation in the function of first-trimester trophoblasts depending on the gestational age.
Adding Confidence to Gene Expression Clustering
Authors: Munneke B , Schlauch K A , Simonsen K L , Beavis W D , Doerge R W 
Published: June 2005

Abstract
It has been well established that gene expression data contain large amounts of random variation that affects both the analysis and the results of microarray experiments. Typically, microarray data are either tested for differential expression between conditions or grouped on the basis of profiles that are assessed temporally or across genetic or environmental conditions. While testing differential expression relies on levels of certainty to evaluate the relative worth of various analyses, cluster analysis is exploratory in nature and has not had the benefit of any judgment of statistical inference. By using a novel dissimilarity function to ascertain gene expression clusters and conditional randomization of the data space to illuminate distinctions between statistically significant clusters of gene expression patterns, we aim to provide a level of confidence to inferred clusters of gene expression data. We apply both permutation and convex hull approaches for randomization of the data space and show that both methods can provide an effective assessment of gene expression profiles whose coregulation is statistically different from that expected by random chance alone.
DNA Sequence Polymorphism and Divergence at the erect wing and suppressor of sable Loci of Drosophila melanogaster and D. simulans
Authors: Braverman John M , Lazzaro Brian P , Aguadé Montserrat , Langley Charles H 
Published: June 2005

Abstract
Several evolutionary models of linked selection (e.g., genetic hitchhiking, background selection, and random environment) predict a reduction in polymorphism relative to divergence in genomic regions where the rate of crossing over per physical distance is restricted. We tested this prediction near the telomere of the Drosophila melanogaster and D. simulans X chromosome at two loci, erect wing (ewg) and suppressor of sable [su(s)]. Consistent with this prediction, polymorphism is reduced at both loci, while divergence is normal. The reduction is greater at ewg, the more distal of the two regions. Two models can be discriminated by comparing the observed site frequency spectra with those predicted by the models. The hitchhiking model predicts a skew toward rare variants in a sample, while the spectra under the background-selection model are similar to those of the neutral model of molecular evolution. Statistical tests of the fit to the predictions of these models require many sampled alleles and segregating sites. Thus we used SSCP and stratified DNA sequencing to cover a large number of randomly sampled alleles (∼50) from each of three populations. The result is a clear trend toward negative values of Tajima's D, indicating an excess of rare variants at ewg, the more distal of the two loci. One fixed difference among the populations and high FST values indicate strong population subdivision among the three populations at ewg. These results indicate genetic hitchhiking at ewg, in particular, geographically localized hitchhiking events within Africa. The reduction of polymorphism at su(s) combined with the excess of high-frequency variants in D. simulans is inconsistent with the hitchhiking and background-selection models.
The Heterotrimeric G-Protein GanB(α)-SfaD(β)-GpgA(γ) Is a Carbon Source Sensor Involved in Early cAMP-Dependent Germination inAspergillus nidulans
Authors: Lafon Anne , Seo Jeong-Ah , Han Kap-Hoon , Yu Jae-Hyuk , d'Enfert Christophe 
Published: June 2005

AbstractThe role of heterotrimeric G-proteins in cAMP-dependent germination of conidia was investigated in the filamentous ascomycete Aspergillus nidulans. We demonstrate that the Gα-subunit GanB mediates a rapid and transient activation of cAMP synthesis in response to glucose during the early period of germination. Moreover, deletion of individual G-protein subunits resulted in defective trehalose mobilization and altered germination kinetics, indicating that GanB(α)-SfaD(β)-GpgA(γ) constitutes a functional heterotrimer and controls cAMP/PKA signaling in response to glucose as well as conidial germination. Further genetic analyses suggest that GanB plays a primary role in cAMP/PKA signaling, whereas the SfaD-GpgA (Gβγ) heterodimer is crucial for proper activation of GanB signaling sensitized by glucose. In addition, the RGS protein RgsA is also involved in regulation of the cAMP/PKA pathway and germination via attenuation of GanB signaling. Genetic epistatic analyses led us to conclude that all controls exerted by GanB(α)-SfaD(β)-GpgA(γ) on conidial germination are mediated through the cAMP/PKA pathway. Furthermore, GanB may function in sensing various carbon sources and subsequent activation of downstream signaling for germination.
Construction of Linkage Maps in Full-Sib Families of Diploid Outbreeding Species by Minimizing the Number of Recombinations in Hidden Inheritance Vectors
Authors: Jansen J 
Published: June 2005

AbstractThis article investigates the construction of linkage maps by means of the reconstruction of hidden inheritance vectors. An inheritance vector provides a description of the origin of marker alleles in an individual in terms of a binary code indicating the grandparental origin of the alleles. The practical application that is considered is the full-sib family of a diploid outbreeding species. Essentially, map construction is considered as an optimization problem in which marker data are used as restrictions on hidden inheritance vectors. Simulated annealing, a form of combinatorial optimization, is used to minimize the number of recombinations between adjacent markers. The new algorithm is applied to simulated data as well as to practical data obtained from a cross between two apple cultivars. For the practical data, a detailed procedure for examining the reliability of individual markers and their positions on the map is presented. Extensions of the method for more complicated population structures are discussed.
The Impact of Using Related Individuals for Haplotype Reconstruction in Population Studies
Authors: Schouten Michael T , Williams Christopher K I , Haley Chris S 
Published: June 2005

Abstract
Recent studies have highlighted the dangers of using haplotypes reconstructed directly from population data for a fine-scale mapping analysis. Family data may help resolve ambiguity, yet can be costly to obtain. This study is concerned with the following question: How much family data (if any) should be used to facilitate haplotype reconstruction in a population study? We conduct a simulation study to evaluate how changes in family information can affect the accuracy of haplotype frequency estimates and phase reconstruction. To reconstruct haplotypes, we introduce an EM-based algorithm that can efficiently accommodate unrelated individuals, parent-child trios, and arbitrarily large half-sib pedigrees. Simulations are conducted for a diverse set of haplotype frequency distributions, all of which have been previously published in empirical studies. A wide variety of important results regarding the effectiveness of using pedigree data in a population study are presented in a coherent, unified framework. Insight into the different properties of the haplotype frequency distribution that can influence experimental design is provided. We show that a preliminary estimate of the haplotype frequency distribution can be valuable in large population studies with fixed resources.
Cross-Species Comparison of Drosophila Male Accessory Gland Protein Genes
Authors: Mueller J L , Ram K Ravi , McGraw L A , Bloch Qazi M C , Siggia E D , Clark A G , Aquadro C F , Wolfner M F 
Published: June 2005

Abstract
Drosophila melanogaster males transfer seminal fluid proteins along with sperm during mating. Among these proteins, ACPs (Accessory gland proteins) from the male's accessory gland induce behavioral, physiological, and life span reduction in mated females and mediate sperm storage and utilization. A previous evolutionary EST screen in D. simulans identified partial cDNAs for 57 new candidate ACPs. Here we report the annotation and confirmation of the corresponding Acp genes in D. melanogaster. Of 57 new candidate Acp genes previously reported in D. melanogaster, 34 conform to our more stringent criteria for encoding putative male accessory gland extracellular proteins, thus bringing the total number of ACPs identified to 52 (34 plus 18 previously identified). This comprehensive set of Acp genes allows us to dissect the patterns of evolutionary change in a suite of proteins from a single male-specific reproductive tissue. We used sequence-based analysis to examine codon bias, gene duplications, and levels of divergence (via dN/dS values and ortholog detection) of the 52 D. melanogaster ACPs in D. simulans, D. yakuba, and D. pseudoobscura. We show that 58% of the 52 D. melanogaster Acp genes are detectable in D. pseudoobscura. Sequence comparisons of ACPs shared and not shared between D. melanogaster and D. pseudoobscura show that there are separate classes undergoing distinctly dissimilar evolutionary dynamics.
Surface jumping in a harmonic model of trans‐octatetraene: Franck—condon factors and accepting vibrational modes in s1→S0 non‐vertical radiationless transition
Authors: Shem‐Tov Sharona , Segev Bilha 
Published: June 2005

AbstractA phase‐space method for finding the accepting modes in a non‐vertical radiationless vibronic transition and for recognizing the final state with the largest Franck—Condon factor is applied to a harmonic model of the S1 → S0 relaxation in trans‐octatetraene. Input required for the analysis includes the energy gap between S1 and S0, normal mode frequencies, reduced masses, and eigenvectors (including the Duschinsky rotation matrix), and the molecule equilibrium configurations (bond lengths and angles) in S1 and S0. Some of these data are taken from published experimental results and some are calculated in this work. The energy gap of 0.132 au is much larger than the energy of a vertical transition, which is only 0.047 au. The phase‐space method gives a closed‐form analytic solution for how to divide the excess energy between the accepting modes. The final distribution includes a large excitation of the two CH2 end groups, where the motion of the two hydrogen atoms within each quasilocal CH2 group is antisymmetric; a symmetric stretch of the two central C‐H bonds of the molecule; and small totally symmetric bending of the whole molecule. Comparison of Franck‐Condon factors (exact within the harmonic model) of the final state obtained by the phase‐space analysis and of other similar isoenergetic states shows that the phase‐space method indeed chooses the most probable final energy distribution. Possible modifications of these results due to anharmonic effects are discussed.
Nonadiabatic vibronic dynamics as a tool. From surface nanochemistry to coherently driven molecular machines
Authors: Seideman Tamar 
Published: June 2005

AbstractResonances are ubiquitous in molecular heterojunctions and in scanning tunneling microscopy (STM) experiments. In the former environment, resonance tunneling is essential for favorable wire‐length‐dependence of the conductance and is often the mechanism underlying conductance enhancement through application of a gate voltage. In the latter environment, resonance tunneling has served to develop a powerful vibrational spectroscopy.Resonance conductance is often strongly nonadiabatic; in the course of the tunneling event, electron energy is channelled into vibrational modes and triggers molecular dynamics. The qualitative physics underlying current‐driven, resonance‐mediated dynamics in molecular electronics is very simple, and is familiar from related phenomena such as gas phase electron‐molecule scattering and photochemistry on conducting surfaces. Equilibrium displacement between the initial and resonant states translates into vibronic coupling in the language of the Marcus theory of electron transfer; it produces a nonstationary superposition in the nuclear subspace that evolves during the resonance lifetime. Upon relaxation the system is internally excited and interesting dynamics is likely to ensue.While the underlying physics is very general, the single‐molecule STM and molecular heterojunction environments open unique and exciting opportunities. The former introduces the possibility of determining resonance lifetimes through fit of experimental voltage dependencies to a quantum mechanical theory. The latter introduces the possibility of developing coherently driven molecular machines, a new form of nanolithography, and a new means of manipulating the conductivity of molecular‐scale devices.We briefly review the theory of current‐driven dynamics in molecular‐scale devices, discuss the results of ongoing research on surface nanochemistry and molecular machines, and sketch a variety of potential applications.
Femtosecond dynamics of electron transfer, localization, and solvation processes at the ice—metal interface
Authors: Bovensiepen Uwe , Gahl Cornelius , Stähler Julia , Loukakos Panagiotis A. , Wolf Martin 
Published: June 2005

AbstractThe ultrafast dynamics of excess electrons in amorphous ice layers on single‐crystal metal surfaces are investigated by femtosecond time‐ and angle‐resolved two‐photon‐photoemission spectroscopy. Photoexcited electrons are injected from the metal substrate into delocalized states of the conduction band of ice and localize in the ice layer within 100 fs. Subsequently, energetic stabilization of this localized species is observed on a time scale of ∼1 ps, which is attributed to electron solvation by nonadiabatic coupling to nuclear degrees of freedom of the surrounding polar molecular environment. Concomitant with this stabilization process, residual wave function overlap of the solvated electron with the metal substrate results in back‐transfer by tunneling through the solvation shell. At such interfaces the correlation of electronic and molecular structure with the resulting solvation dynamics can be explored using different substrates as a template. Here we compare data on molecularly thin D2O ice layers grown on Cu(111) and Ru(001). On Ru(001) both the stabilization and back‐transfer proceed about three times faster compared to Cu(111), which is attributed to different interfacial structures and the role of d‐states, and projected band gaps in the electron transfer process.
Valence Shell Charge Concentrations at Pentacoordinate d0Transition‐Metal Centers: Non‐VSEPR Structures of Me2NbCl3and Me3NbCl2
Authors: McGrady G. Sean , Haaland Arne , Verne Hans Peter , Volden Hans Vidar , Downs Anthony J. , Shorokhov Dmitry , Eickerling Georg , Scherer Wolfgang 
Published: June 2005

AbstractThe molecular structures of the monomeric, pentacoordinated methylchloroniobium(IV) compounds Me3NbCl2and Me2NbCl3have been determined by gas electron diffraction (GED) and density functional theory (DFT) calculations, and, for Me3NbCl2, by single crystal X‐ray diffraction. Each of the molecules is found to have a heavy‐atom skeleton in the form of a trigonal bipyramid (TBP) with Cl atoms in the axial positions, in accord with their vibrational spectra. The TBP is somewhat distorted in the case of Me2NbCl3with the two axial NbCl bonds bentawayfrom the equatorial, slightly shorter NbCl bond. In the case of Me3NbCl2, moreover, the X‐ray model suggests structural distortions away from the idealizedC3hgeometry, in line with the results of quantum chemical calculations. Structure optimizations by DFT calculations and least‐squares refinement to the GED data yield the following structural parameters (calcd/exptl; eq=equatorial; ax=axial; distances in Å, angles in degrees; average values in 〈〉 brackets): Me3NbCl2, inC3vsymmetry, NbCl 〈2.370〉/〈2.319(3)〉, NbC 2.173/2.152(4), CH 〈1.096〉/1.124(5), ∢NbCH 〈109.3〉/105.2(8), ∢ClNbC 92.2/93.3(2), ∢CNbC 119.9/119.7(1); Me2NbCl3, inC2vsymmetry, NbClax2.361/2.304(5), NbCleq2.321/2.288(9), NbC 2.180/2.135(9), CH 〈1.094〉/1.12(1), ∢ClaxNbCleq98.5/96.5(6), ∢CNbC 121.0/114(2), ∢NbCH 〈108.9〉/109(2). The electronic structures of Me2NbCl3and Me3NbCl2have been explored by rigorous analysis of both the wavefunction and the topology of the electron density, employing DFT calculations. Hence the structures of these compounds are shown to reflect repulsion between the NbC and NbCl bonding electron density and charge concentrations induced by the methyl ligands in the valence shell of the Nb atom and arising mainly from use of Nb(4d) functions in the NbC bonds.