bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen‐sensitive projections from the medial preoptic area to the dorsal pontine tegmentum, including Barrington's nucleus, in the rat
Authors: Rickey Leslie Minor , Sarkey Sara , DonCarlos Lydia L.
Published: October 2007

Aim

Urinary incontinence affects a significant number of post‐menopausal women. There is conflicting evidence whether voiding symptoms in these women are related to hypoestrogenism or aging itself. This neuroanatomical study was designed to determine whether a specific central nervous system (CNS) pathway that projects to the pontine micturition center (PMC, also known as “Barrington's nucleus”) is estrogen sensitive in a rat model.

Methods

A fluorescent retrograde tracer was injected into the dorsal pontine tegmentum of adult female Sprague‐Dawley rats to identify neurons in the medial preoptic area (MPA) that project to the PMC. Immunohistochemistry was performed using antibodies directed against estrogen receptor‐alpha (ERα) and estrogen receptor‐beta (ERβ) to identify estrogen‐sensitive neurons. The brain sections were examined using fluorescence microscopy to identify cells that project to the PMC (contain fluorescent tracer) and also express ER (are immunoreactive for ER).

Results

There are neurons in the MPA that are double labeled (contain fluorescent tracer and express ERα, but not ERβ), showing that a subset of neurons projecting from the MPA to the PMC is estrogen sensitive.

Conclusions

A subset of estrogen‐sensitive neurons projects from the MPA to the PMC in rats, raising the possibility that indirect estrogenic regulation of forebrain neuronal function may modulate the micturition reflex. Future development of drugs that alter the function of this estrogen‐sensitive CNS pathway may provide therapeutic strategies to treat post‐menopausal incontinence. Neurourol. Urodynam. 27:440–445, 2008. © 2007 Wiley‐Liss, Inc.
Reproducibility of single‐ and multi‐voxel 1H MRS measurements of intramyocellular lipid in overweight and lean subjects under conditions of controlled dietary calorie and fat intake
Authors: Shen Wei , Mao Xiangling , Wolper Carla , Heshka Stanley , Dashnaw Stephen , Hirsch Joy , Heymsfield Steven B. , Shungu Dikoma C.
Published: October 2007

The reproducibility of repeated single‐voxel 1H MRS (SV‐MRS) and spectroscopic imaging (MRSI) measurements of intramyocellular lipid (IMCL) in the tibialis anterior muscle of five lean and five overweight female Caucasians, during 7 days of controlled dietary fat and calorie intake, was assessed at 1.5 T. Duplicate measures of IMCL relative to total muscle creatine (IMCL/tCr) obtained 3 days apart by both SV‐MRS and MRSI correlated well (r = 0.65 and r = 0.95, respectively, P < 0.05). The coefficients of variation for repeated measures of IMCL/tCr by SV‐MRS and MRSI were 24.4% and 10.7%, respectively. IMCL/tCr measured by MRSI was higher in overweight subjects than in lean subjects (8.3 ± 3.8 vs 4.3 ± 2.4, P < 0.05). Although both methods achieved good reproducibility in measuring IMCL in vivo, MRSI was found to offer greater flexibility and reliability, and higher sensitivity to IMCL differences, whereas SV‐MRS was advantageous with respect to shorter scan time and ease of implementation. Copyright © 2007 John Wiley & Sons, Ltd.
Aptamere als Therapeutika und als Werkzeuge zur Wirkstoffsuche. Nukleinsäuren im Drug Discovery Prozess
Authors: Mayer Günter , Famulok Michael
Published: October 2007

Aptamere sind potente Proteininhibitoren und leisten, wie kaum eine andere Substanzklasse, einen wichtigen Beitrag zum Drug‐Discovery‐Prozess. Mit Macugen® ist das erste Aptamer als Therapeutikum verfügbar und kann zur Behandlung der AMD eingesetzt werden. Neben ihrem direkten Einsatz als Therapeutika werden Aptamere sowohl zur Validierung pharmakologisch relevanter Proteine als auch zur Identifizierung niedermolekularer Substanzen verwandt. Die Aptamertechnologie repräsentiert eine Technologieplattform, deren vielseitige Einsatzgebiete von der funktionellen Charakterisierung von Biomolekülen bis hin zur Identifikation niedermolekularer Substanzen reichen.
Vibrio harveyi sepsis in a child with cancer
Authors: Wilkins Simone , Millar Michael , Hemsworth Sue , Johnson Gemma , Warwick Simon , Pizer Barry
Published: October 2007

A paediatric oncology patient presented with central line sepsis caused by Vibrio harveyi, a gram negative bioluminescent marine bacterium known to be pathogenic to fish and marine invertebrates, after swimming in the sea. Pediatr Blood Cancer 2008;50:891–892. © 2007 Wiley‐Liss, Inc.
Thiol–norbornene materials: Approaches to develop high Tg thiol–ene polymers
Authors: Carioscia Jacquelyn A. , Schneidewind Lauren , O'Brien Casey , Ely Robert , Feeser Caitlin , Cramer Neil , Bowman Christopher N.
Published: October 2007

The ability to prepare high Tg low shrinkage thiol–ene materials is attractive for applications such as coatings and dental restoratives. However, thiol and nonacrylated vinyl materials typically consist of a flexible backbone, limiting the utility of these polymers. Hence, it is of importance to synthesize and investigate thiol and vinyl materials of varying backbone chemistry and stiffness. Here, we investigate the effect of backbone chemistry and functionality of norbornene resins on polymerization kinetics and glass transition temperature (Tg) for several thiol–norbornene materials. Results indicate that Tgs as high as 94 °C are achievable in thiol–norbornene resins of appropriately controlled chemistry. Furthermore, both the backbone chemistry and the norbornene moiety are important factors in the development of high Tg materials. In particular, as much as a 70 °C increase in Tg was observed in a norbornene–thiol specimen when compared with a sample prepared using allyl ether monomer of analogous backbone chemistry. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5686–5696, 2007
Kinetic study of the solution polymerization of methacrylamide initiated with potassium persulfate using in situ Raman spectroscopy and band‐target entropy minimization
Authors: Jiang Ying , Garland Marc , Carpenter Keith J. , Suresh Parappuveetil S. , Widjaja Effendi
Published: October 2007

In this paper, the use of in situ Raman spectroscopy together with a novel multivariate data analysis method, band‐target entropy minimization (BTEM), is discussed to monitor the solution polymerization of methacrylamide in aqueous medium. Although FTIR spectroscopy is a more popular spectroscopic technique for polymer characterization and in situ polymerization monitoring, Raman spectroscopy is selected over FTIR in the current study. This is because water has very strong and broad infrared absorption bands and thus masks most of the other infrared signals contributed from monomer and polymer. On the contrary, water has very weak Raman scattering and thus it does not interfere the other Raman signals. The polymerization was initiated with potassium persulfate (KPS). A series of experiments were carried out varying initial monomer concentration, initial KPS concentration, and polymerization temperature. In situ Raman spectroscopy was used to monitor the polymerizing mixture and measure the compositions. The collected reaction spectra were subjected to BTEM to elucidate the pure component spectra, and then determine the conversion of monomer. The conversion data was then used to obtain kinetic parameters for the polymerization. The rate of consumption of monomers was found to follow the expression R = keff [I]0.55[M]1.41. The activation energy of the system was estimated at 121 kJ/mol. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5697–5704, 2007
A novel method to characterize the compatibilizer effect in polymer blend
Authors: Liu Chun‐Yuan
Published: October 2007

Both components of a polymer blend were labeled slightly with donor (naphthalene) and acceptor (anthracene), respectively and were mixed with equal amounts of various amounts of diblock copolymer. Adding diblock copolymer as a compatibilizer would improve blend compatibility and the degree of mutual segmental penetration between both components was also increased. In contrast, adding random copolymer has very little effect. Making use of nonradiative energy transfer, we can evaluate the efficiency of a compatibilizer delicately and determine the optimum concentration of compatibilizer for a blend. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 3215–3219, 2007
Distress and its correlates in Korean cancer patients: pilot use of the distress thermometer and the problem list
Authors: Shim Eun‐Jung , Shin Yong‐Wook , Jeon Hong Jin , Hahm Bong‐Jin
Published: October 2007

The distress thermometer (DT), a one‐item measure for distress, provides a means for rapidly and effectively screening psychological distress in cancer patients. In this pilot study, a screening efficacy of the DT was investigated in a mixed cohort of 108 Korean cancer patients. Participants completed the DT, the problem list (PL), and the Hospital Anxiety and Depression Scale (HADS), and answered questions regarding supportive needs and their degree of satisfaction with several aspects of care. Receiver operating characteristic (ROC) curve analyses indicated that a DT cutoff score of 4 yielded an area under the ROC curve of 0.75 with a sensitivity of 0.83 and a specificity of 0.59 for HADS‐total score defined cases (⩾15). HADS—Anxiety and Depression subscale scores explained 27% of the variability in the DT scores, implying that ‘distress’ is a broader concept that includes anxiety and depressive symptoms but has a more comprehensive meaning that encompasses multiple contributory factors. Regarding the PL, distressed patients (DT⩾4) reported significantly more problems (23 of 35) in all categories, suggesting, although degrees differ, that a wide variety of problems contribute to distress in cancer patients. Distress as defined by DT and HADS subscale scores was also significantly associated with higher supportive needs, a poor ECOG performance status (both physician and patient‐rated), and a reduced level of satisfaction with treatment, staff, and communications.

In conclusion, the DT and the PL were found to be simple yet effective screening instruments for detecting psychosocial distress in Korean cancer patients, and for identifying problems that warrant intervention. Copyright © 2007 John Wiley & Sons, Ltd.
Standardization of the Korean version of Mini‐Mental Adjustment to Cancer (K‐Mini‐MAC) scale: factor structure, reliability and validity
Authors: Kang Jee In , Chung Hyun Cheol , Kim Se Joo , Choi Hye Jin , Ahn Joong Bae , Jeung Hei‐Cheul , Namkoong Kee
Published: October 2007

Mental adjustment and coping affect the physical outcome and survival as well as quality of life in cancer patients. The Mini‐Mental Adjustment to Cancer (Mini‐MAC) scale is a new refined, economical and reliable self‐rating instrument measuring cognitive and behavioral responses to cancer. The aim of this study was to evaluate the psychometric properties of the Mini‐MAC in Korean cancer patients. A total of 208 cancer patients recruited from the Yonsei Cancer Center were assessed with the Mini‐MAC and the Hospital Anxiety and Depression Scale (HADS). Principal component analysis with varimax rotation for the Korean version of Mini‐MAC (K‐Mini‐MAC) confirmed four factors. Three had psychometric properties similar to Helpless–Hopeless (HH), Anxious Preoccupation (AP) and Cognitive Avoidance (CA) of the original Mini‐MAC. A novel factor, named Positive Attitude, included items of both Fatalism (FA) and Fighting Spirit (FS) from the original version. The five subscales from the original version (AP, HH, FS, FA and CA) and Positive Attitude had acceptable internal reliabilities in our sample (Cronbach's alpha coefficient 0.50–0.86; correlation coefficient of test–retest 0.68–0.88). For the validity, significant interscale correlation was observed in the original five subscales and Positive Attitude. Each subscale including Positive Attitude was also significantly related to Depression and Anxiety of HADS. As a whole, the K‐Mini‐MAC was a reliable, valid and acceptable tool for Korean cancer patients. These findings can provide information about the cross‐cultural validity of Mini‐MAC scale's factor structure. Cultural differences were also discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Sensitivity and specificity of the Distress Thermometer for depression in newly diagnosed breast cancer patients
Authors: Hegel Mark T. , Collins E. Dale , Kearing Stephen , Gillock Karen L. , Moore Caroline P. , Ahles Tim A.
Published: October 2007

Background: Receiving a new diagnosis of breast cancer is a distressing experience that may precipitate an episode of major depressive disorder. Efficient screening methods for detecting depression in the oncology setting are needed. This study evaluated the receiver operating characteristics (ROC) of the single‐item Distress Thermometer (DT) for detecting depression in women newly diagnosed with Stage I–III breast cancer.

Methods: We assessed 321 patients (of 345 consecutive patients) at the time of their pre‐surgical consultation at a Comprehensive Breast Cancer Program. Patients were administered the DT along with the Patient Health Questionnaire 9‐Item Depression Module (PHQ‐9) as a gold standard diagnostic assessment of depression status.

Results: Mean DT scores (11‐point scale, 0–10) were significantly higher for depressed versus non‐depressed patients (8.1 versus 4.4). In ROC analyses the DT showed strong discriminatory power relative to the PHQ‐9‐derived diagnosis of depression, with an area under the curve of 0.87. Patient age, education, marital status and stage of disease resulted in similar operating characteristics. A score of 7 represented the optimal trade‐off between sensitivity (0.81) and specificity (0.85) characteristics for detecting depression.

Conclusions: The single‐item DT performs satisfactorily relative to the PHQ‐9 for detecting depression in newly diagnosed breast cancer patients. A cutoff score of 7 on the DT possesses the optimal sensitivity and specificity characteristics. The strength of these findings suggests that a careful psychosocial evaluation should follow a positive screen. Copyright © 2007 John Wiley & Sons, Ltd.
Structural rationalization of novel drug metabolizing mutants of cytochrome P450 BM3
Authors: Stjernschantz Eva , van Vugt‐Lussenburg Barbara M. A. , Bonifacio Alois , de Beer Stephanie B. A. , van der Zwan Gert , Gooijer Cees , Commandeur Jan N. M. , Vermeulen Nico P. E. , Oostenbrink Chris
Published: October 2007

Three newly discovered drug metabolizing mutants of cytochrome P450 BM3 (van Vugt‐Lussenburg et al., Identification of critical residues in novel drug metabolizing mutants of Cytochrome P450 BM3 using random mutagenesis, J Med Chem 2007;50:455–461) have been studied at an atomistic level to provide structural explanations for a number of their characteristics. In this study, computational methods are combined with experimental techniques. Molecular dynamics simulations, resonance Raman and UV–VIS spectroscopy, as well as coupling efficiency and substrate‐binding experiments, have been performed. The computational findings, supported by the experimental results, enable structural rationalizations of the mutants. The substrates used in this study are known to be metabolized by human cytochrome P450 2D6. Interestingly, the major metabolites formed by the P450 BM3 mutants differ from those formed by human cytochrome P450 2D6. The computational findings, supported by resonance Raman data, suggest a conformational change of one of the heme propionate groups. The modeling results furthermore suggest that this conformational change allows for an interaction between the negatively charged carboxylate of the heme substituent and the positively charged nitrogen of the substrates. This allows for an orientation of the substrates favorable for formation of the major metabolite by P450 BM3. Proteins 2008. © 2007 Wiley‐Liss, Inc.
YesT: A new rhamnogalacturonan acetyl esterase from Bacillus subtilis
Authors: Martínez‐Martínez Irene , Navarro‐Fernández José , Daniel Lozada‐Ramírez José , García‐Carmona Francisco , Sánchez‐Ferrer Álvaro
Published: October 2007

YesT, a putative protein from Bacillus subtilis ATCC 6633 that has been provisionally classified as a rhamnogalacturonan acetyl esterase (RGAE) in CE‐12 family, was cloned, expressed in Escherichiacoli Rosetta (DE3), and purified. The enzyme is monomeric with a molecular mass of 37 kDa and presents thermophilic properties similar to RGAE from Aspergillus aculeatus, although YesT is more alkaliphilic. The study of inhibitors confirmed the importance of the His and the nucleophilic Ser for the esterase activity, apart from the Asp from the catalytic triad. This enzyme also presents broad substrate specificity, and is active toward 7‐aminocephalosporanic acid, cephalosporin C, p‐nitrophenyl acetate, β‐naphthyl acetate, glucose pentaacetate, and acetylated xylan. Moreover, YesT achieves a synergistic effect together with xylanase A toward acetylated xylan. As a member of the SGNH family, it does not adopt the common α/β hydrolase fold. The primary sequence analysis and multiple sequence alignment revealed the lack of a two β‐stranded antiparallel sheet, which results in a clear change in the structure together with the disappearance of one of the three 310‐helices presented in RGAE structure. The similarities found in this article among the topological diagrams of RGAE, YesT, and Esterase A from Streptomyces scabies, Platelet‐Activating Factor AcetylHydrolase, isoform Ib, alpha subunit [PAF‐AH(Ib)α1], PAF‐AH(Ib)α2, the esterase domain from hemagglutinin esterase fusion glycoprotein (HEF1) from Influenza C virus, the thioesterase I (TAP) from E. coli, the hypothetical protein a1r1529 from Nostoc sp., and the hypothetical YxiM precursor that all belong to the SGNH family could indicate a possible divergence of such proteins from a common ancestor. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Flexible protein–flexible ligand docking with disrupted velocity simulated annealing
Authors: Huang Zunnan , Wong Chung F. , Wheeler Ralph A.
Published: October 2007

By docking flexible balanol to a rigid model of protein kinase A (PKA), we found that a new simulated annealing protocol termed disrupted velocity simulated annealing (DIVE‐SA) outperformed the replica‐exchange method and the traditional simulated annealing method in identifying the correct docking pose. In this protocol, the atomic velocities were reassigned periodically to encourage the system to sample a large conformational space. We also found that scaling potential energy surface to reduce structural transition barriers could further facilitate docking. The DIVE‐SA method was then evaluated on its ability to perform flexible ligand–flexible protein docking of three ligands (balanol, a balanol analog, and ATP) to PKA. To reduce computational time and to avoid possible unphysical structural changes resulting from the use of nonoptimal force fields, a soft restrain was applied to keep the root‐mean‐square‐deviation (RMSD) between instantaneous protein structures and a chosen reference structure small. Because the restrain was applied to the overall RMSD rather than to individual atoms, a protein could still experience relatively large conformational changes during docking. To examine the impact of applying such a restrain on docking, we constructed two semi‐flexible protein models by choosing two different crystal structures as reference. Both the balanol analog and ATP were able to dock to either one of these semi‐flexible protein models. On the other hand, balanol could only dock well to one of them. Further analysis indicated that the restrain on the glycine‐rich loop was too strong, preventing it to adjust its structure to accommodate balanol in the binding pocket of PKA. Removing the restrain on the glycine‐rich loop resulted in much better docking poses. This finding demonstrates the important role that the flexibility of the glycine‐rich loop play in accepting different ligands and should profitably not be restrained in molecular docking so that more diverse ligands can be studied. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Biomarker as a classifier in pharmacogenomics clinical trials: a tribute to 30th anniversary of PSI
Authors: Wang Sue‐Jane
Published: October 2007

Pharmacogenetics is one of many evolving sciences that have come to the fore since the formation of the Statisticians in the Pharmaceutical Industry (PSI) 30 years ago. Following the completion of the human genome project and the HapMap in the early 21st century, pharmacogenetics has gradually focused on studies of whole‐genome single‐nucleotide‐polymorphisms screening associating disease pathophysiology with potential therapeutic interventions. Around this time, transcription profiling aiming at similar objectives has also been actively pursued, known as pharmacogenomics. It has become increasingly apparent that treatment effects between different genomic patient subsets can be dissimilar, and the value and need for genomic biomarkers to help predict effects, particularly in cancer clinical studies, have become issues of paramount importance. Pharmacogenomics/pharmaogenetics has thus become intensely focused on the search for genomic biomarkers for use as classifiers to select patients in randomized‐controlled trials.

We highlight that thepredictiveutility of a genomic classifier has tremendous clinical appeal and that there will be growing examples in which use of a companion diagnostic will need to be considered and may become an integral part in the utilization of drugs in medical practice. The credible mechanism to test the clinical utility of a genomic classifier is to employ the study results from a prospective trial that recruits all patients. Such investigations, if well designed, will allow analysis of all relevant performance factors in the drug and diagnostic combination including the sensitivity, specificity, positive and negative predictive values of the diagnostic test and the efficacy of the drug. Published in 2007 by John Wiley & Sons, Ltd.
Characterization and identification of triterpenoid saponins in crude extracts from Clematis spp. by high‐performance liquid chromatography/electrospray ionization with multi‐stage tandem mass spectrometry
Authors: Sun Feng , He Qing , Shi Peiying , Xiao Peigen , Cheng Yiyu
Published: October 2007

High‐performance liquid chromatography coupled with electrospray ionization multi‐stage tandem mass spectrometry (HPLC/ESI‐MSn) was applied to characterize and identify triterpenoid saponins in crude extracts from nine species of Clematis L. After separation on a Zorbax SB‐C18 column, negative ESI‐MS experiments were performed. The quasi‐molecular ions [MH]−, [M+Cl]− and [M+HCOO]− were observed in the full‐scan MS spectra of all compounds. The MSn (n = 2–4) data of the [MH]− ions provided structural information on the sugar sequence of the oligosaccharide chains and on the aglycone of the saponins. In addition, the fragmentation mechanisms could be deduced from the fragment ions. As a result, eight saponins were unambiguously identified in C. ganpiniana by comparison with reference compounds. In addition, a new compound was tentatively identified as 3‐O‐ribopyranosyl → rhamnopyranosyl → (glucopyranosyl) → arabinopyranosylhederagenin 28‐O‐rhamnopyranosyl → glucopyranosyl → glucopyranosyl ester (peak 1), and another one was tentatively deduced to be 3‐O‐glucopyranosyl → ribopyranosyl → rhamnopyranosyl → arabinopyranosylhederagenin 28‐O‐rhamnopyranosyl → glucopyranosyl → glucopyranosyl ester (peak 5) from the genus Clematis L. for the first time. By ESI‐MSn, non‐isomeric saponins could be discriminated rapidly. It is of interest that cleavage preferentially occurrs at the ester bond at C‐28 and the charge is easy to transfer onto the oligosaccharide chain when the ester bond of a monodesmosidic saponin like HNH cleaves. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of oxygen triple isotope ratios of silicates without cryogenic separation of NF3 – technique with application to analyses of technical O2 gas and meteorite classification
Authors: Pack Andreas , Toulouse Christoph , Przybilla Reinhold
Published: October 2007

A novel technique is described to determine Δ′17OTFL with high accuracy and precision by using infrared (IR) laser fluorination with F2 as the reaction gas. The technique includes precise monitoring of the intensity ratio of the 14NF (m/z 52) to O2 signals. The correlation between the intensity of 14NF and positive error in δ17OVSMOW allows correction of measured data to obtain reliable Δ′17OTFL values. The resultant error in Δ′17OTFL of a single measurement after correction is in the range of ±0.06‰, i.e. sufficiently small to permit the technique to be useful for meteorite classification. Our data for technical O2, in combination with literature data, suggest a negative anomaly of tropospheric air O2 with Δ′17OTFL = –0.344 ± 0.015‰ (1σ). Copyright © 2007 John Wiley & Sons, Ltd.
Investigation of Range‐energy Relationships for Low‐energy Electron Beams in Silicon and Gallium Nitride
Authors: Kurniawan O. , Ong V. K. S.
Published: October 2007

The electron beam technique of the Scanning Electron Microscopy (SEM) has been widely used for the characterization of bipolar devices and photodiode materials. The resolution of an electron beam technique is affected by the interaction of the beam and the specimen. The size of this interaction volume, commonly termed the generation volume, is usually characterized by what is called the electron penetration range and is measured from the surface. Since there is currently no consensus on the expressions to use in the calculation of the electron range, this paper provides an analysis of the three most commonly used semiempirical expressions. They are the Gruen range, the universal curve of Everhart and Hoff, and the maximum range of Kanaya and Okayama. This analysis is done using data from the statistical method of Monte Carlo simulations. It was found that the Everhart and Hoff universal curve performs better at low beam energies than the equation of Kanaya and Okayama. However, the validity of all the three expressions is questionable below 5 keV. In order to overcome this, fitted expressions based on the extrapolated range are provided for beam energies below 5 keV in the case of Si and GaN materials. The accuracy of these expressions is affected by the physical parameters used in the Monte Carlo simulations. SCANNING 29: 280–286, 2007. © 2007 Wiley Periodicals, Inc.
Enhanced apomorphine sensitivity and increased binding of dopamine D2receptors in nucleus accumbens in prepubertal rats after neonatal blockade of the dopamine D3receptors by (+)‐S14297
Authors: Flores‐Tochihuitl Julia , Vargas Guillermo , Morales‐Medina Julio Cesar , Rivera Gustavo , De La Cruz Fidel , Zamudio Sergio , Flores Gonzalo
Published: October 2007

The role of dopamine (DA) D3receptors is controversial in early developmental stages of specially locomotor activity. Past studies have only tested behavioral changes induced by neonatal administration of nonselective dopamine antagonist such as haloperidol or sulpiride in adult rats. We investigated the role of neonatal blockade of DA D3receptors at (postnatal day, P1 to P12) using the DA D3receptor antagonist (+)‐S14297 on paradigms related to DA behaviors including locomotor activity in novel environment and after administration of the DA nonspecific agonistsd‐amphetamine, and apomorphine. Additionally, autoradiographic studies were performed to correlate behavioral alterations with DA D1‐like, D2‐like, and D3receptors. All studies were performed at two critical ages, prepubertal (P35) and postpubertal (P60). The quantitative autoradiogaphic study revealed increases in the expression of DA D2‐like receptor expression in the nucleus accumbens (NAcc) in prepubertal animals that received the DA D3antagonist (+)‐S14297 at neonatal age. In addition, novel environment and apomorphine administration (0.5 mg/kg, s.c.), induced increases of locomotor activity in prepubertal animals that received the DA D3antagonist (+)‐S14297. Autoradiographic and behavioral results suggest that blockade of DA D3receptors after birth may mediate different neurodevelopmental aspects of the dopaminergic pathway before and after puberty. Synapse 62:40–49, 2008. © 2007 Wiley‐Liss, Inc.
Methylmalonic acidaemia: Examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group
Authors: Merinero B. , Pérez B. , Pérez‐Cerdá C. , Rincón A. , Desviat L. R. , Martínez M. A. , Sala P. Ruiz , García M. J. , Aldamiz‐Echevarría L. , Campos J. , Cornejo V. , del Toro M. , Mahfoud A. , Martínez‐Pardo M. , Parini R. , Pedrón C. , Peña‐Quintana L. , Pérez M. , Pourfarzam M. , Ugarte M.
Published: October 2007

Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl‐CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin. The aim of this work was to examine the biochemical and clinical phenotype of 32 MMA patients according to their genotype, and to study the mutant mRNA stability by real‐time PCR analysis. Using cellular and biochemical methods, we classified our patient cohort as having the MMA formsmut(n = 19),cblA(n = 9) andcblB(n = 4). All themut0and some of thecblBpatients had the most severe clinical and biochemical manifestations, displaying non‐inducible propionate incorporation in the presence of hydroxocobalamin (OHCbl)in vitroand high plasma odd‐numbered long‐chain fatty acid (OLCFA) concentrations under dietary therapy. In contrast,mut−andcblApatients exhibited a milder phenotype with propionate incorporation enhanced by OHCbl and normal OLCFA levels under dietary therapy. No missense mutations identified in theMUTgene, includingmut0andmut−changes #Affected mRNA stability. A new sequence variation (c.562G>C) in theMMAAgene was identified. Most of thecblApatients carried premature termination codons (PTC) in both alleles. Interestingly, the transcripts containing the PTC mutations were insensitive to nonsense‐mediated decay (NMD).
Classic and late‐onset neurological disease in two siblings with glutaryl‐CoA dehydrogenase deficiency
Authors: López‐Laso E. , García‐Villoria J. , Martín E. , Duque P. , Cano A. , Ribes A.
Published: October 2007

Late‐onset neurological disease has rarely been reported in patients with glutaryl‐CoA dehydrogenase (GCDH) deficiency. We present two siblings with GCDH deficiency. One of them presented with the classic neurological disease (patient 1). Routine investigation of family members revealed that her apparently unharmed 13‐year‐old sister was also affected (patient 2). Patient 2 started to have academic difficulties in the months prior to our assessment. Her clinical examination was normal, with the exception of a cranial circumference of 57 cm (slightly over the 98th centile). A severe leukoencephalopathy was demonstrated on MRI. Neuropsychological assessment showed an IQ within the normal–low range and a mild impairment of memory and executive function. Previous reports on late‐onset neurological disease in GCDH deficiency have revealed that progressive leukoencephalopathy develops over time. Following the recently published guideline for the diagnosis and management of GCDH deficiency, both patients are receiving dietary treatment in combination with l‐carnitine supplementation. We emphasize the need to search for chronic neurological changes of late‐onset type in apparently unaffected GCDH deficiency cases diagnosed in routine family investigations.
Proximal Tibia Fracture after Anterior Cruciate Ligament Reconstruction Using Bone-Patellar Tendon-Bone Autograft: A Case Report
Authors: Voos James E. , Drakos Mark C. , Lorich Dean G. , Fealy Stephen
Published: October 2007

The optimal operative management of anterior cruciate ligament (ACL) injury continues to be debated. Many complications can occur, but fracture is often not routinely discussed. We present a complex intra-articular tibia fracture in a patient who had an autologous, ipsilateral bone-patellar-bone ACL reconstruction. While still advocating early, aggressive physical therapy, this case reminds us of the inherent susceptibility to injury in the immediate post-operative period.
The MINDACT trial: The first prospective clinical validation of a genomic tool
Authors: Cardoso Fatima , Piccart-Gebhart Martine , Veer Laura Van't , Rutgers Emiel
Published: October 2007

One of the main challenges in oncology today has become to distinguish accurately between those patients who need adjuvant treatment and those who do not. This, together with the identification of the best type of therapy for the individual patient and the development of drugs targeting specific characteristics of tumour cells, are the goals of treatment tailoring or personalized medicine.

The MINDACT trial (Microarray In Node negative Disease may Avoid ChemoTherapy) was recently launched with the aim of prospectively validating the superior performance of a new prognostic RNA‐based tool – the Amsterdam 70‐gene profiler MammaPrint™, in order to implement its use in clinical practice later on. This manuscript shortly reviews the rational, design and logistics of MINDACT.
Man and machine: a miraculous partnership
Authors: Kam-mei Jacqueline Lam
Published: October 2007

It was over 30 degrees centigrade on the 16th of June 2006, but hundreds of people from various backgrounds embraced the heat and patiently queued to enter the S. H. Ho Sports Hall at the Hong Kong University of Science and Technology (HKUST). Many had been waiting since early morning, because Professor Stephen Hawking – perhaps the best known and most influential living scientist – would be giving a lecture (‘The origin of the universe’) for the newly established Institute for Advanced Study. The IAS is dedicated to ‘the advancement of knowledge to meet the great challenges of the 21st century’, and will ‘bring together the world's most brilliant minds to drive cutting-edge discovery and scholarship for the betterment of mankind’ (IAS, 2006). The inaugural event was announced a month prior to the lecture and – despite its being broadcast live on both the TVB News Channel and Cable TV Live, as well as transmitted via an intranet relay to the seven other tertiary institutions in Hong Kong – the response for tickets was overwhelming.
English in Tamil: the language of advertising
Authors: Krishnasamy Kanthimathi
Published: October 2007

Advertising has come a long way, from pedlars in the market square extolling their goods to glossy mags full of innuendo and making extensive use of verbal and non-verbal devices to attract consumers. In India, copywriters make extensive use of English words and phrases in advertisements in a variety of ways. This paper examines the use of English in television and print advertising in the Tamil language. A cursory examination of Tamil advertising shows that the language of advertising does not follow rigid rules: it makes optimal use of possible resources from a wide variety of styles.
Direct simulation of fluid‐solid mechanics in porous media using the discrete element and lattice‐Boltzmann methods
Authors: Boutt David F. , Cook Benjamin K. , McPherson Brian J. O. L. , Williams J. R.
Published: October 2007

A detailed understanding of the coupling between fluid and solid mechanics is important for understanding many processes in Earth sciences. Numerical models are a popular means for exploring these processes, but most models do not adequately handle all aspects of this coupling. This paper presents the application of a micromechanically based fluid‐solid coupling scheme, lattice‐Boltzmann discrete element method (LBDEM), for porous media simulation. The LBDEM approach couples the lattice‐Boltzmann method for fluid mechanics and a discrete element method for solid mechanics. At the heart of this coupling is a previously developed boundary condition that has never been applied to coupled fluid‐solid mechanics in porous media. Quantitative comparisons of model results to a one‐dimensional analytical solution for fluid flow in a slightly deformable medium indicate a good match to the predicted continuum‐scale fluid diffusion‐like profile. Coupling of the numerical formulation is demonstrated through simulation of porous medium consolidation with the model capturing poroelastic behavior, such as the coupling between applied stress and fluid pressure rise. Finally, the LBDEM model is used to simulate the genesis and propagation of natural hydraulic fractures. The model provides insight into the relationship between fluid flow and propagation of fractures in strongly coupled systems. The LBDEM model captures the dominant dynamics of fluid‐solid micromechanics of hydraulic fracturing and classes of problems that involve strongly coupled fluid‐solid behavior.
Potential impact of changes in river nutrient supply on global ocean biogeochemistry
Authors: Cotrim da Cunha Leticia , Buitenhuis Erik T. , Le Quéré Corinne , Giraud Xavier , Ludwig Wolfgang
Published: October 2007

The growing world population increases the demand for water, energy, and land. This demand for natural resources impacts the transport of material and the supply of nutrients in the coastal ocean by rivers. We assess the potential impact of river N, Si, Fe, and organic carbon (OC) fluxes on the global and coastal ocean biogeochemistry, using an ocean biogeochemistry model and observations, in eight different scenarios. We assess two extreme scenarios, one with no river nutrients, corresponding to a complete stop of nutrient input by rivers, and one with high nutrient fluxes, corresponding to a world population of 12 billion people. Compared to today's scenario values, primary production (PP) changes from −5% to +5% for the open ocean, and from −16% to +5% for the coastal ocean. In the coastal ocean the impact of river nutrients on PP depends on regional nutrient limitation. River inputs have a larger impact on PP in areas where upwelling and high runoff are combined. The coastal ocean is typically N‐ or Si‐limited. River Fe not assimilated by the phytoplankton is exported to open ocean areas, and its fertilizing effect depletes coastal and open ocean surface waters from N and Si. The impact on PP is reflected on global ocean low‐O2areas whose extent changes from −16% to +23% across the range of scenarios. River nutrients have a modest impact on the global ocean CO2sink of up to 0.4 Pg C a−1, depending on the amount of inorganic and organic carbon transported by the rivers.
Understanding the origin of black carbon in the atmospheric brown cloud over the Indian Ocean
Authors: Stone Elizabeth A. , Lough Glynis C. , Schauer James J. , Praveen P. S. , Corrigan C. E. , Ramanathan V.
Published: October 2007

Atmospheric particulate matter samples were collected at two Maldives climate observatories from 30 August 2004 to 21 January 2005. This time period encompassed both wet and dry seasons, which correspond to low and high aerosol loadings. High aerosol loadings were observed in the northern sampling site in Hanimaadhoo, caused by long‐range transport from south and Southeast Asia, whereas the southern sampling site, Gan, was not subject to as much continental inflow. The polluted period began in mid‐November and lasted through the remainder of the sampling period. Fine particulate matter during this time was characterized by relatively high concentrations of aerosol mass and elemental carbon. Concentrations of water‐soluble potassium, sulfate, levoglucosan, polyaromatic hydrocarbons, aliphatic diacids, aromatic diacids, and trace metals increased over the clean, transition, and polluted dry season. Organic speciation suggested that significant secondary organic aerosol formation occurred during the polluted dry season, meaning that traditional methods of source identification relying on fixed elemental and organic carbon ratios between source and receptors are not sufficient. Well‐studied molecular markers for combustion sources were not adequate in fully attributing elemental carbon over the northern Indian Ocean to specific sources. Further source profiling of south and Southeast Asian biofuels and fossil fuels is recommended. A receptor‐based positive matrix factorization model was applied to fine particulate matter trace metal measurements and showed that biofuel burning and fossil fuel combustion were equally important sources of elemental carbon during the polluted dry season.
Interpreting transient carbonate compensation depth changes by marine sediment core modeling
Authors: Ridgwell Andy
Published: October 2007

With the advent of computationally fast “intermediate complexity” models of Earth's climate and carbon cycle the marine record can be interpreted much more directly than before. Specifically, the mechanistic simulation of deep‐sea sediment cores provides an important step in bridging the model‐data divide. Here I use this methodology to help interpret the excursion in carbonate compensation depth (CCD) during the Paleocene‐Eocene thermal maximum that is recorded in cores recovered from Walvis Ridge in the South Atlantic. By explicitly simulating the expected geological record of a massive CO2 release in an Earth system model I show how reduction in the intensity of subsurface mixing of the sediment by benthic animals substantially magnifies the recorded shoaling of the CCD. Conversely, to quantify correctly the carbon release consistent with the observed CCD changes, one must account for any bioturbational changes. A reduction in sediment mixing intensity also appears to be important to reproducing the sharpness of the contact between carbonate‐rich late Paleocene sediments and the overlying early Eocene clay layer at Walvis Ridge. Assuming a relatively rapid (approximately 1 ka duration) CO2 release further helps to account for some of the paleoceanographic observations. Finally, interbasin differences in bioturbational regime help resolve some of the observed disparity in carbonate preservation between Walvis Ridge and sites outside of the Atlantic, although changes in ocean ventilation and circulation are also likely to play a critical role in this.
Atmospheric forcing validation for modeling the central Arctic
Authors: Makshtas A. , Atkinson D. , Kulakov M. , Shutilin S. , Krishfield R. , Proshutinsky A.
Published: October 2007

We compare daily data from the National Center for Atmospheric Research and National Centers for Environmental Prediction “Reanalysis 1” project with observational data obtained from the North Pole drifting stations in order to validate the atmospheric forcing data used in coupled ice‐ocean models. This analysis is conducted to assess the role of errors associated with model forcing before performing model verifications against observed ocean variables. Our analysis shows an excellent agreement between observed and reanalysis sea level pressures and a relatively good correlation between observed and reanalysis surface winds. The observed temperature is in good agreement with reanalysis data only in winter. Specific air humidity and cloudiness are not reproduced well by reanalysis and are not recommended for model forcing. An example sensitivity study demonstrates that the equilibrium ice thickness obtained using NP forcing is two times thicker than using reanalysis forcing.
Grape harvest dates as a proxy for Swiss April to August temperature reconstructions back to AD 1480
Authors: Meier Nicole , Rutishauser This , Pfister Christian , Wanner Heinz , Luterbacher Jürg
Published: October 2007

We present an annually resolved record of grape harvest dates for Switzerland. The strong negative relationship between grape harvest dates and April–August temperatures allowed a new reconstruction, with associated uncertainties, to be derived back to 1480. Calibration (1928–1979) was performed with monthly data from the Basel and Geneva stations and verified over 1980–2006. Twelve days of grape harvest difference correspond to around 1°C April–August temperature difference. Periods cooler (late grape harvest dates) than the 1961–1990 mean are reconstructed during the 17th century and at the beginning of the 19th century. Warmer conditions were experienced in the early 18th century and during the recent decades, in agreement with grape harvest temperature reconstructions from France and other independent temperature estimates. On decadal (annual) time‐scales the earliest harvests were in the 1580s (2003) and the latest vintages in the 1740s (1816). Large tropical volcanic eruptions led to significantly later grape harvest dates (cooling) one to two years after the event.
Combining seismic reflection with multifold wide‐aperture profiling: An effective strategy for high‐resolution shallow imaging of active faults
Authors: Improta L. , Bruno P. P.
Published: October 2007

Shallow imaging of fault zones is a challenging task. We investigate if this issue can be successfully addressed by combining reflection seismics with non‐standard multifold wide‐aperture profiling, a strategy pertaining to crustal scale exploration so far. Near‐offset reflection and multifold wide‐aperture data are simultaneously recorded along two profiles in a small basin crossed by an active fault in Southern Italy. Imaging consists of multiscale seismic tomography complemented by CDP processing of near‐offset reflections and of data spanning a large offset range. By combining smooth Vp and reflectivity images we pinpoint the fault location and yield a valuable picture of the basin. Performance of each exploration technique strongly varies in the two surveys depending on the local geology. Thus, the combined exploration strategy not only yields complementary images for enhanced interpretation, but also allows extending the range of applicability of shallow seismics for fault detection, reducing the risk of unsuccessful investigations.
Ultrasoft pseudopotentials in time-dependent density-functional theory
Authors: Walker Brent , Gebauer Ralph
Published: October 2007

We describe an efficient formulation allowing the use of ultrasoft pseudopotentials (USPPs) in plane wave based time-dependent density-functional theory. The practical steps required to implement USPP functionality within real time propagation schemes and linear-response schemes based on Lanczos algorithms are provided. The functioning of the methodology is demonstrated by calculations of the optical absorption spectra of the fullerene C60, using both real time propagation and the Lanczos/linear-response approaches. Comparisons between the rates of convergence of the optical spectra with the number of applications of the Hamiltonian required in calculations with ultrasoft pseudopotentials and norm-conserving pseudopotentials show clearly the benefits provided by the use of USPP.
Cartesian formulation of the mobile block Hessian approach to vibrational analysis in partially optimized systems
Authors: Ghysels A. , Van Neck D. , Waroquier M.
Published: October 2007

Partial optimization is a useful technique to reduce the computational load in simulations of extended systems. In such nonequilibrium structures, the accurate calculation of localized vibrational modes can be troublesome, since the standard normal mode analysis becomes inappropriate. In a previous paper [A. Ghysels et al., J. Chem. Phys. 126, 224102 (2007)], the mobile block Hessian (MBH) approach was presented to deal with the vibrational analysis in partially optimized systems. In the MBH model, the nonoptimized regions of the system are represented by one or several blocks, which can move as rigid bodies with respect to the atoms of the optimized region. In this way unphysical imaginary frequencies are avoided and the translational/rotational invariance of the potential energy surface is fully respected. In this paper we focus on issues concerning the practical numerical implementation of the MBH model. The MBH normal mode equations are worked out for several coordinate choices. The introduction of a consistent group-theoretical notation facilitates the treatment of both the case of a single block and the case of multiple blocks. Special attention is paid to the formulation in terms of Cartesian variables, in order to provide a link with the standard output of common molecular modeling programs.