bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug development costs when financial risk is measured using the Fama–French three‐factor model
Authors: Vernon John A. , Golec Joseph H. , Dimasi Joseph A. 
Published: August 2009

AbstractIn a widely cited article, DiMasi, Hansen, and Grabowski (2003) estimate the average pre‐tax cost of bringing a new molecular entity to market. Their base case estimate, excluding post‐marketing studies, was $802 million (in $US 2000). Strikingly, almost half of this cost (or $399 million) is the cost of capital (COC) used to fund clinical development expenses to the point of FDA marketing approval. The authors used an 11% real COC computed using the capital asset pricing model (CAPM). But the CAPM is a single factor risk model, and multi‐factor risk models are the current state of the art in finance. Using the Fama–French three factor model we find that the cost of drug development to be higher than the earlier estimate. Copyright © 2009 John Wiley & Sons, Ltd.
Nicotinic receptor mechanism in supramammillary nucleus mediates physiological regulation of neural activity in dorsal hippocampal field CA1 of anaesthetized rat
Authors: Ariffin Mohammed Zacky , Jiang Fengli , Low Chian‐Ming , Khanna Sanjay 
Published: August 2009

AbstractEvidence suggests that stimulation of the region of the rostral pontine oralis (RPO) nucleus and the peripheral application of a noxious stimulus activates an ascending system that also modulates hippocampal neural responses during behavioral arousal. Indeed, the two stimuli and behavioral arousal elicit theta activation and the suppression of population spikes (PS) in dorsal hippocampus field CA1. Interestingly, such neural responses in CA1 are also elicited by microinjection of the cholinergic agonist carbachol into the hypothalamic supramammillary nucleus (SuM). In the present in vivo electrophysiological study, we tested the hypothesis that cholinergic neural elements in the SuM modulate the neural drive to CA1 on RPO stimulation or the peripheral application of a noxious stimulus. Pharmacological investigation showed that intra‐SuM microinjection of either a muscarinic or a nicotinic receptor antagonist attenuated the SuM carbachol‐induced neural effects in CA1, namely, theta activation and PS suppression. However, neither antagonist attenuated the CA1 effects of intra‐SuM microinjection of the excitatory neurotransmitter glutamate. Subsequent investigations revealed that microinjection of only the nicotinic antagonist, mecamylamine, into the lateral SuM selectively attenuated the responses elicited in CA1 by stimulation of the RPO or on nociceptive stimulation with hind paw injection of formalin (5%, 0.05 ml); whereas, microinjection of mecamylamine into the medial SuM did not affect the hippocampal responses elicited by either type of stimulation. Furthermore, application of mecamylamine into the lateral SuM attenuated the CA1 responses induced by injection of formalin into the contralateral, but not the ipsilateral hind paw. The lateralization of drug effect is consistent with the predominant unilateral anatomical connections between the SuM and the septohippocampal region. These findings provide novel evidence that nicotinic cholinoceptive neurons in the lateral SuM are common elements of the neural drive(s) to the hippocampus on RPO activation and noxious stimulation. © 2009 Wiley‐Liss, Inc.
Factors controlling groundwater chemistry in an agricultural area with complex topographic and land use patterns in mid‐western South Korea
Authors: Koh Dong‐Chan , Kim Eun‐Young , Ryu Jong‐Sik , Ko Kyung‐Seok 
Published: August 2009

AbstractShallow and bedrock groundwater from granitic aquifers were investigated for the hydrogeochemistry of major and minor constituents in an agricultural area. Nitrate concentrations were observed up to 49 mg/l as NO3‐N, with 22% of samples exceeding the drinking water standard, which could pose a significant threat because most residents rely on groundwater as their drinking water source. Principal component analysis revealed three principal components (PCs): (1) nitrate contamination, contributed by major cations, Cl−, SO$_{4}^{2-}$ and NO$_{3}^{-}$, (2) reduction processes positively involving Fe, Mn and B, and negatively involving dissolved oxygen and NO$_{3}^{-}$ and (3) natural mineralization, involving HCO$_{3}^{-}$ and F−. Cluster analysis, performed on the PC scores, resulted in seven sample groups, which were successfully identified by total depth, elevation and land use. The nitrate‐contaminated groups had mixed land uses, with locally concentrated residential areas. Uncontaminated groundwater groups were found in the natural environment, including high‐altitude spring water and bedrock groundwater with a higher degree of natural mineralization. Shallow groundwater groups in paddy fields in lowlands were affected by reducing environments, of which one group was characterized by high Fe, Mn and B, and negligible nitrate. Groundwater with intermediate nitrate and lower Cl− and SO$_{4}^{2-}$ was found primarily in hilly terrains with orchards and vegetable gardens, indicating lower contaminant loadings than lowland areas. Higher concentrations of F− and nitrate were observed in the nitrate‐contaminated water, which seemed unlikely to be explained by groundwater mixing. The strong acidity generated from nitrification may infiltrate deeper into the aquifer, induce accelerated weathering of bedrock and result in the coexistence of F− and nitrate, which may be an evidence of intense nitrate loading, leading to soil acidification. Multivariate statistical analysis successfully delineated hydrochemical characteristics of groundwater attained by natural and anthropogenic processes in an agriculturally stressed area with complex topographic land use patterns. Copyright © 2009 John Wiley & Sons, Ltd.
What you match does matter: the effects of data on DSGE estimation
Authors: Guerron‐Quintana Pablo A. 
Published: August 2009

AbstractThis paper explores the effects of using alternative combinations of observables for the estimation of Dynamic Stochastic General Equilibrium (DSGE) models. I find that the estimation of structural parameters describing the Taylor rule and sticky contracts in prices and wages is particularly sensitive to the set of observables. In terms of the model's predictions, the exclusion of some observables may lead to estimated parameters with unexpected outcomes, such as recessions following a positive technology shock. More importantly, two ways to assess different sets of observables are proposed. These measures favor a dataset consisting of seven observables. Copyright © 2009 John Wiley & Sons, Ltd.
Interaction energy and the shift in OH stretch frequency on hydrogen bonding for the H2O → H2O, CH3OH → H2O, and H2O → CH3OH dimers
Authors: Campen Richard Kramer , Kubicki James D. 
Published: August 2009

AbstractThe ability to use calculated OH frequencies to assign experimentally observed peaks in hydrogen bonded systems hinges on the accuracy of the calculation. Here we test the ability of several commonly employed model chemistries—HF, MP2, and several density functionals paired with the 6‐31+G(d) and 6‐311++G(d,p) basis sets—to calculate the interaction energy (De) and shift in OH stretch fundamental frequency on dimerization (δ(ν)) for the H2O → H2O, CH3OH → H2O, and H2O → CH3OH dimers (where for X → Y, X is the hydrogen bond donor and Y the acceptor). We quantify the error in De and δ(ν) by comparison to experiment and high level calculation and, using a simple model, evaluate how error in De propagates to δ(ν). We find that B3LYP and MPWB1K perform best of the density functional methods studied, that their accuracy in calculating δ(ν) is ≈ 30–50 cm−1 and that correcting for error in De does little to heighten agreement between the calculated and experimental δ(ν). Accuracy of calculated δ(ν) is also shown to vary as a function of hydrogen bond donor: while the PBE and TPSS functionals perform best in the calculation of δ(ν) for the CH3OH → H2O dimer their performance is relatively poor in describing H2O → H2O and H2O → CH3OH. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Electronic properties for small tin clusters Snn (n ≤ 20) from density functional theory and the convergence toward the solid state
Authors: Assadollahzadeh Behnam , Schäfer Sascha , Schwerdtfeger Peter 
Published: August 2009

AbstractGlobal minimum structures of neutral tin clusters with up to 20 atoms obtained recently from genetic algorithm simulations within a density‐functional approach (Schäfer et al., J Phys Chem A 2008, 112, 12312) were used to evaluate the corresponding electronic properties. The evolution of these properties with increasing cluster size is discussed in detail and compared with the lighter silicon and germanium clusters. We also discuss the extrapolation of these properties to the bulk limit. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Sonographic findings in a case of tetrasomy 9p associated with increased nuchal translucency and Dandy‐Walker malformation
Authors: Nakamura‐Pereira Marcos , Cima Luciana Carneiro do , Llerena Juan Clinton , Guerra Fernando Antonio Ramos , Peixoto‐Filho Fernando Maia 
Published: August 2009

AbstractWe report a case of a 23‐year‐old pregnant woman, who underwent amniocentesis after ultrasound (US) examination in the first trimester which revealed a nuchal translucency thickness of 2.9 mm. Cytogenetic analysis revealed complete tetrasomy of the short arm of chromosome 9. Further US evaluation in the second trimester revealed Dandy‐Walker malformation, ventriculomegaly, bilateral clubfoot, lip and palate clefts, arthrogryposis and hyperechoic kidneys with bilateral pelvic dilatation. At 30 weeks of gestation, a placental abruption was noted and a Cesarean section was performed. The infant died shortly after birth. A review of previous cases of tetrasomy 9p shows that the remarkable sonographic findings are ventriculomegaly, intrauterine growth restriction, genitourinary anomaly, Dandy‐Walker malformation, cleft lip/palate and limb malformation, but the association of tetrasomy 9p and increased nuchal translucency had not been reported. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009.
Partial hydatidiform mole in septate uterus
Authors: Taori Kishor , Sharbidre Kedar G. , Bopche Sneha , Kulkarni Bipin , Krishnan Vijay , Disawal Amit 
Published: August 2009

AbstractPartial mole is a form of gestational trophoblastic disease that may be associated with serious medical complications and occasionally progresses to the second trimester of pregnancy. We present a case report of a partial mole diagnosed at 18 weeks of gestation in a septate uterus with molar placenta in one horn and a dead fetus in the other. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
Follicular thyroid adenoma with eggshell calcification presenting as an intensely hypermetabolic lesion on 18F‐FDG PET/CT
Authors: Lee Sang Kwon , Rho Byung Hak 
Published: August 2009

AbstractWe report herein a case of follicular thyroid adenoma with an eggshell calcification presenting as an intensely hypermetabolic lesion on combined 18F‐fluorodeoxyglucose whole‐body PET and CT (18F‐FDG PET/CT) performed for staging work‐up in a 68‐year‐old woman who had undergone distal gastrectomy with Billroth II anastomosis for early gastric carcinoma. The mass was intensely hypermetabolic (SUVmax = 21.3 g/mL) on combined 18F‐FDG PET/CT, hypoechoic with an interrupted eggshell calcification on gray‐scale ultrasonography (US), and showed intranodular vascularity on power Doppler US. Follicular adenoma should be considered in the differential diagnosis of a mass with an eggshell calcification on US and intense hypermetabolism on 18F‐FDG PET/CT. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2010
Anatomic variations between Japanese and Caucasian populations in the healthy young adult knee joint
Authors: Hovinga Kristen R. , Lerner Amy L. 
Published: August 2009

AbstractOur objective was to characterize variations in mechanical knee alignment, tibial torsion, tibial width, and ACL laxity measurements between Japanese and Caucasian populations in the healthy, young adult knee joint. Seventy young adult subjects participated in this study, including 23 Japanese and 47 Caucasian subjects. Coronal magnetic resonance images of the hip, knee, and ankle were acquired for analysis. Japanese subjects had a significantly higher (p = 0.04) varus alignment (1.64 ± 0.43° standard error) than Caucasians (0.55 ± 0.33°), while women exhibited a more valgus alignment (0.16 ± 0.52°) than men (0.94 ± 0.42°, p = 0.04). Significant differences were found in tibial torsion and ACL laxity (p < 0.01) between ethnicities, with Japanese exhibiting lower tibial torsion (33.4 ± 10.0°) and higher ACL laxity (7.5 ± 0.4 mm) measurements compared to Caucasians (38.9 ± 9.5° and 5.7 ± 0.3 mm, respectively). Significant differences between genders were found in hip‐knee‐ankle alignment (p = 0.04), tibial width (p < 0.0001), and ACL laxity (p < 0.01) measurements. Measurements were reliable between observers and for repeated positioning. Our study provides new insight into anatomical and geometric differences in the knee joint between Japanese and Caucasians, as well as between females and males. Further consideration of these results may improve development of implants to accommodate for these differences, and understanding of characteristics leading to increased prevalence of knee OA in certain populations. The use of magnetic resonance imaging to obtain these measurements also allows soft tissue structure characterization without exposure to ionizing radiation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Mechanical stimulation alters tissue differentiation and molecular expression during bone healing
Authors: Palomares Kristy T. Salisbury , Gleason Ryan E. , Mason Zachary D. , Cullinane Dennis M. , Einhorn Thomas A. , Gerstenfeld Louis C. , Morgan Elise F. 
Published: August 2009

AbstractFurther understanding of how mechanical cues modulate skeletal tissue differentiation can identify potential means of enhancing repair following injury or disease. Prior studies examined the effects of mechanical loading on osteogenesis, chondrogenesis, and fibrogenesis in an effort to enhance bony union. However, exploring how mechanical stimuli can divert the bone healing process towards formation of other mesenchymal tissues, as an endpoint, may elucidate new avenues for repair and regeneration of tissues such as cartilage and fibrous tissue. This study investigated the use of mechanical stimulation to promote cartilage rather than bone formation within an osteotomy. Our overall goal was to define skeletal tissue distribution and molecular expression patterns induced by the stimulation. Retired breeder Sprague‐Dawley rats (n = 85) underwent production of a mid‐diaphyseal, transverse femoral osteotomy followed by external fixation. Beginning on postoperative day 10 and continuing for 1, 2, or 4 weeks, a cyclic bending motion (+35°/−25° at 1 Hz) was applied in the sagittal plane for 15 min/day for 5 consecutive days/week. Control animals experienced continuous rigid fixation. Histological and molecular analyses indicated that stimulation substantially altered normal bone healing. Stimulated specimens exhibited an increase in cartilage volume over time, while control specimens demonstrated bony bridging. Stimulation induced upregulation of cartilage‐related genes (COL2A1 and COL10A1) and downregulation of bone morphogenetic proteins (BMPs) ‐4, ‐6 and ‐7. However, BMP‐3 was upregulated with stimulation. These findings illustrate that mechanical cues can selectively modulate osteogenesis and chondrogenesis in vivo, and suggest a potential basis for treatment regimens for injured or diseased cartilaginous tissues. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Desmoid cell motility is induced in vitro by rhEGF
Authors: Joyner David E. , Trang Sylvia H. , Damron Timothy A. , Aboulafia Albert J. , Cummings Judd E. , Randall R. Lor 
Published: August 2009

AbstractDesmoid tumors are benign but locally invasive myofibroblastic lesions that arise predominantly in the abdominal wall or shoulder and are prone to aggressive local recurrences. A perceived association between desmoid activity and the expression of growth factors during pregnancy or following trauma suggests a cause‐and‐effect relationship between growth factor stimulation and desmoid invasiveness. We used Boyden Chambers to quantify cell motility in order to determine the effect of growth factor stimulation on desmoid cell migration. Desmoid cell cultures were treated under serum‐free conditions with epidermal growth factor (rhEGF) or transforming growth factor alpha (rhTGFα). Additional cell cultures were pretreated under serum‐free conditions with the EGF receptor (EGFR) inhibitor AG1478, alone or in combination with the TGFβ1 receptor inhibitor SB431542, and then stimulated with growth factor prior to being assayed for cell motility. The experiments demonstrated a direct dose‐dependent relationship between rhEGF stimulation and desmoid motility. In contrast, rhTGFα was less effective at inducing cell migration. rhEGF‐induced cell migration could be diminished, but not reduced to control levels, by inhibiting EGFR. When EGF and TGFβ1 receptors were inhibited simultaneously, the level of rhEGF‐induced cell migration was reduced significantly beyond the level of cell migration generated by inhibition of EGFR alone. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Improved quality assessment of proprietary Chinese medicines based on multi‐chemical class fingerprinting
Authors: Chen Dan , Zhao Sandy Shuo , Leung Kelvin Sze‐Yin 
Published: August 2009

AbstractOur present study constitutes the first successful attempt to employ eight distinctive chemical groups of compounds for the quality evaluation of a complex traditional Chinese herbal medicine (TCHM) material: BaZhen YiMu (BZYM). Due to the complexity of its matrix, which is composed of nine different herbal ingredients, five representative chemical groups encompassing representative bioactive markers were initially chosen as targets for the quality assessment of this preparation. Furthermore, with the aid of LC‐ESI‐MS, three additional chemical groups were characterized. In summary, a total of nineteen markers belonging to eight different chemical groups were selectively displayed in the chromatographic fingerprint of BZYM preparation. With this fingerprint, the overall quality of any BZYM preparation can be comprehensively authenticated. The chromatographic separation was performed on an HP C18 AQ column with a gradient elution of ACN and aqueous solution containing 0.1% phosphoric acid at the optimal detection wavelength of 230 nm. The established method was rigorously validated with respect to the ICH guidelines and represents the most extensive and facile HPLC quality control technique for this formulation. Compared with the conventional method of using a single or only a few markers of the same chemical group, this technique provides a new dimension for TCHM quality control.
Curcumin: A potential radio‐enhancer in head and neck cancer
Authors: Khafif Avi , Lev‐Ari Shahar , Vexler Akiva , Barnea Itai , Starr Alex , Karaush Vicki , Haif Sasha , Ben‐Yosef Rami 
Published: August 2009

AbstractObjectives/Hypothesis:To investigate whether curcumin enhances the cytotoxic effect of radiotherapy in head and neck squamous cell carcinoma (HNSCC).Methods:HNSCC cell lines SCC‐1, SCC‐9, KB, as well as A431 cell line were treated with curcumin, irradiation, or their combination. Cell viability was evaluated by XTT assay. Cyclooxygenase‐2 (COX‐2), epithelial growth factor receptor (EGFR), and p‐Erk1/2 were measured by Western blot analysis. CD‐1 athymic nude mice with orthotopic implanted SCC‐1 cells, were treated with control diet, curcumin containing diet, local single‐dose radiation, or combination.Results:Curcumin (IC50 range, 15–22 μM) and radiation inhibited cell viability in all cell lines were tested. The combination of curcumin and radiation resulted in additive effect. Curcumin decreased COX‐2 expression and inhibited phosphorylation of EGFR in SCC‐1 cells. In tumor‐bearing mice the combination regimen showed a decrease in both tumor weight (25%, P = .09) and tumor size (15%, P = .23) compared to the nontreated mice.Conclusions:Curcumin inhibited HNSCC cell growth and augmented the effect of radiation in vitro and in vivo. A possible mechanism is inhibition of COX‐2 expression and EGFR phosphorylation. Laryngoscope, 2009
Survival impact of treatment options for papillary microcarcinoma of the thyroid
Authors: Lin Harrison W. , Bhattacharyya Neil 
Published: August 2009

AbstractObjectives/Hypothesis:Evaluate the impact of medical and surgical interventions on the survival of patients with papillary microcarcinoma (PMC) of the thyroid, a common tumor with an increasing worldwide incidence.Study Design:Cross‐sectional population analysis of a prospectively maintained database.Methods:Cases of nonmetastatic PMC treated with cancer‐directed surgery with or without postoperative radioactive iodine (RAI) therapy were extracted from the Surveillance, Epidemiology and End Results Database (1988–2005). Kaplan‐Meier disease‐specific survival (DSS) and overall survivals were compared according to extent of thyroidectomy and use of RAI therapy. Cox regression analysis was performed to determine the influence of these factors on survival.Results:A total of 7,818 cases of PMC were identified. Overall actuarial survival rates at 10 and 15 years were 96.6% and 96.3%, respectively. DSS was 99.9% at both time intervals, with a total of 10 thyroid cancer‐related deaths. There were no significant differences in DSS for patients who underwent total thyroidectomy, near‐total/subtotal thyroidectomy, or lobectomy (P = .239). DSS for patients receiving RAI therapy was not significantly different than that of patients who did not (P = .504). On multivariate analysis, only increasing age at diagnosis, successfully predicted poor DSS (P = .001), whereas gender (P = .481), use of RAI therapy (P = .633), and extent of thyroidectomy (P = .104) did not.Conclusions:PMC carries an excellent prognosis with respect to both overall and disease‐specific survival that is independent of surgical extent and the use of RAI therapy. An isolated, fine‐needle–aspiration proven unilateral PMC focus in a patient lacking evidence of metastatic disease may be treated with lobectomy alone. Laryngoscope, 2009
Functional Polymers for Targeted Delivery of Nucleic Acid Drugs
Authors: Mok Hyejung , Park Tae Gwan 
Published: August 2009

AbstractCationic polymers have been chemically modified with a variety of targeting molecules such as peptides, proteins, antibodies, sugars and vitamins for targeted delivery of nucleic acid drugs to specific cells. Stimuli‐sensitive polymers exhibiting different size, charge and conformation in response to physiological signals from specific cells have also been utilized for targeted delivery. To achieve target‐specific delivery of nucleic acids, conjugation chemistry is critical to produce stable nanosized polyplexes tethered with cell‐recognizable ligands for facile cellular uptake via a receptor‐mediated endocytic pathway. In this review, synthetic strategies of functional cationic polymers with various targeting ligands are presented.magnified image