bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of small molecule aggregators from large compound libraries by support vector machines
Authors: Rao Hanbing , Li Zerong , Li Xiangyuan , Ma Xiaohua , Ung Choongyong , Li Hu , Liu Xianghui , Chen Yuzong 
Published: June 2009

AbstractSmall molecule aggregators non‐specifically inhibit multiple unrelated proteins, rendering them therapeutically useless. They frequently appear as false hits and thus need to be eliminated in high‐throughput screening campaigns. Computational methods have been explored for identifying aggregators, which have not been tested in screening large compound libraries. We used 1319 aggregators and 128,325 non‐aggregators to develop a support vector machines (SVM) aggregator identification model, which was tested by four methods. The first is five fold cross‐validation, which showed comparable aggregator and significantly improved non‐aggregator identification rates against earlier studies. The second is the independent test of 17 aggregators discovered independently from the training aggregators, 71% of which were correctly identified. The third is retrospective screening of 13M PUBCHEM and 168K MDDR compounds, which predicted 97.9% and 98.7% of the PUBCHEM and MDDR compounds as non‐aggregators. The fourth is retrospective screening of 5527 MDDR compounds similar to the known aggregators, 1.14% of which were predicted as aggregators. SVM showed slightly better overall performance against two other machine learning methods based on five fold cross‐validation studies of the same settings. Molecular features of aggregation, extracted by a feature selection method, are consistent with published profiles. SVM showed substantial capability in identifying aggregators from large libraries at low false‐hit rates. © 2009 Wiley Periodicals, Inc.J Comput Chem, 2010
Covalent hydration energies for purine analogs by quantum chemical methods
Authors: Wang Selina C. , Beal Peter A. , Tantillo Dean J. 
Published: June 2009

AbstractIn this work, covalent hydration energies for a variety of azanaphthalenes and purine analogs have been calculated using a variety of quantum chemical methods. On the basis of these results, we recommend the CPCM(UA0)‐B3LYP/6‐31+G(d,p) level for rapid prediction of covalent hydration energies. However, we caution the use of this methodology for computing covalent hydration energies for fluorine‐containing compounds. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Fast and accurate predictions of binding free energies using MM‐PBSA and MM‐GBSA
Authors: Rastelli Giulio , Rio Alberto Del , Degliesposti Gianluca , Sgobba Miriam 
Published: June 2009

AbstractIn the drug discovery process, accurate methods of computing the affinity of small molecules with a biological target are strongly needed. This is particularly true for molecular docking and virtual screening methods, which use approximated scoring functions and struggle in estimating binding energies in correlation with experimental values. Among the various methods, MM‐PBSA and MM‐GBSA are emerging as useful and effective approaches. Although these methods are typically applied to large collections of equilibrated structures of protein‐ligand complexes sampled during molecular dynamics in water, the possibility to reliably estimate ligand affinity using a single energy‐minimized structure and implicit solvation models has not been explored in sufficient detail. Herein, we thoroughly investigate this hypothesis by comparing different methods for the generation of protein‐ligand complexes and diverse methods for free energy prediction for their ability to correlate with experimental values. The methods were tested on a series of structurally diverse inhibitors of Plasmodium falciparum DHFR with known binding mode and measured affinities. The results showed that correlations between MM‐PBSA or MM‐GBSA binding free energies with experimental affinities were in most cases excellent. Importantly, we found that correlations obtained with the use of a single protein‐ligand minimized structure and with implicit solvation models were similar to those obtained after averaging over multiple MD snapshots with explicit water molecules, with consequent save of computing time without loss of accuracy. When applied to a virtual screening experiment, such an approach proved to discriminate between true binders and decoy molecules and yielded significantly better enrichment curves. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
On the methane adsorption capacity of activated carbons: in search of a correlation with adsorbent properties
Authors: Contreras M. , Lagos G. , Escalona N. , Soto‐Garrido G. , Radovic L.R. , Garcia R. 
Published: June 2009

AbstractBACKGROUND: There exists now a widely held view that the methane storage capacity on an activated carbon is not related to any of the routinely determined properties of the adsorbent, such as surface area or micropore volume. This has been confirmed and a correlation pursued with other physical and/or chemical properties of both commercially available carbons and those prepared in the laboratory. Textural characteristics (from nitrogen adsorption isotherms at 77 K) considered were BET‐equivalent specific surface area, DR micropore volume and Horvath–Kawazoe micropore size distribution. Chemical properties were evaluated using Fourier transform infrared (FTIR) spectroscopy, thermal programmed decomposition (TPD) and Boehm titrations. Both kinetic and equilibrium methane adsorption experiments were performed at 273 and 298 K and up to 3.5 MPa.RESULTS: Using phosphoric acid to activate peach stones together with additional thermal treatment enabled the production of activated carbons with 137 v/v methane adsorption capacity at 298 K.CONCLUSIONS: The presence of acidic surface functional groups has a detrimental influence on methane uptake, due to the chemical inertness of the adsorbate and/or to pore blockage of the adsorbent. Basic surface functional groups (pyrone), together with a desirable pore size distribution centered at ca 0.8 nm, are thought to be responsible for improved methane adsorption capacity on such activated carbons. Copyright © 2009 Society of Chemical Industry
Pre‐, intra‐, and postoperative sonography of the abdominal wall in patients with incisional hernias repaired via a three‐layered operative suture method
Authors: den Hartog Dennis , Dur Alfons H. M. , Kamphuis Alfons G. A. , Tuinebreijer Wim E. , Hermans John J. , Kreis Robert W. 
Published: June 2009

AbstractWe illustrate the various sonographic (US) appearances of the abdominal wall following this type of repair, including partial and complete recurrences. Correlation is made with CT imaging. The three‐layered anatomical reconstruction of an incisional hernia is described. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
A simple method for multiday imaging of slice cultures
Authors: Seidl Armin H. , Rubel Edwin W 
Published: June 2009

AbstractThe organotypic slice culture (Stoppini et al. A simple method for organotypic cultures of nervous tissue. 1991;37:173‐182) has become the method of choice to answer a variety of questions in neuroscience. For many experiments, however, it would be beneficial to image or manipulate a slice culture repeatedly, for example, over the course of many days. We prepared organotypic slice cultures of the auditory brainstem of P3 and P4 mice and kept them in vitro for up to 4 weeks. Single cells in the auditory brainstem were transfected with plasmids expressing fluorescent proteins by way of electroporation (Haas et al. Single‐cell electroporation for gene transfer in vivo. 2001;29:583‐591). The culture was then placed in a chamber perfused with oxygenated ACSF and the labeled cell imaged with an inverted wide‐field microscope repeatedly for multiple days, recording several time‐points per day, before returning the slice to the incubator. We describe a simple method to image a slice culture preparation during the course of multiple days and over many continuous hours, without noticeable damage to the tissue or photobleaching. Our method uses a simple, inexpensive custom‐built insulator constructed around the microscope to maintain controlled temperature and uses a perfusion chamber as used for in vitro slice recordings. Microsc. Res. Tech., 2009. © 2009 Wiley‐Liss, Inc.
Changes in MAPK pathway in neonatal and adult testis following fetal estrogen exposure and effects on rat testicular cells
Authors: Thuillier Raphael , Manku Gurpreet , Wang Yan , Culty Martine 
Published: June 2009

AbstractConcerns have been raised about the possible role of the phytoestrogen genistein and the xenoestrogen Bisphenol A (BPA) as endocrine disruptors. In the present study, we examined the effects of fetal exposure to genistein and BPA on the Mitogen‐activated protein kinase (MAPK) pathway and on testicular cell populations in neonatal and adult rat testes. At postnatal day (PND) 3, genistein (0.1–10 mg/kg/day) and BPA (1–200 mg/kg/day) induced Raf1 and Erk1/2 mRNA and protein increases in testes, mainly in Sertoli cells. No changes were seen for Mek1. At PND60, Erk1/2 protein expression remained robust in Sertoli cells and in some spermatogonia. Raf1 was predominant in Leydig cells while Mek1 was expressed strongly in spermatogonia, and they were both expressed in pachytene spermatocytes. No consistent change was seen in these proteins at PND60. Transient effects were observed on germ cell populations, while the only remaining effect on adult testicular cells was an increase in Leydig cell number. Rats exposed in utero to the two compounds did not present significant changes in circulating testosterone levels, suggesting normally functioning adult Leydig cells. Furthermore, Sertoli cell numbers were not affected by exposure to genistein and BPA. Finally, around 10% of genistein and BPA exposed rats were sterile, whereas all control rats were fertile. These data suggest that fetal exposure to genistein and BPA exerts transient effects in rat testes and that the changes observed at PND3 did not correlate with relevant changes in germ cell populations, Leydig cell function, or fertility in the adult. Microsc. Res. Tech., 2009. © 2009 Wiley‐Liss, Inc.
Facile and selective solvent‐free synthesis of 2‐isoxazolines under microwave irradiation
Authors: Mouradzadegun Arash , Dianat Shima 
Published: June 2009

Abstract
magnified imageTriarylpyrylium perchlorates are readily and selectively converted into corresponding 2‐isoxazolines in good yield and short reaction time using solventless conditions. J. Heterocyclic Chem., (2009).
Junjappa‐Ila annulation: α‐Oxoketene dithioacetal mediated synthesis of substituted benzotriazoles
Authors: Shetty Nitinkumar S. , Lamani Ravi S. , Panchamukhi Shridhar I. , Khazi Imtiyaz Ahmed M. 
Published: June 2009

Abstractmagnified image2‐(1‐Benzyl‐1H–1,2,3‐triazole‐4‐yl)‐3‐methylsulfanyl‐5‐oxo‐5‐substituted‐pent‐2‐enenitrile3a,3b,3c,3d,3ewere obtained in good yields by condensation of (1‐benzyl‐1H‐1,2,3‐triazole‐4‐yl)acetonitrile1with various α‐oxoketene dithioacetals2a,2b,2c,2d,2ein the presence of sodium hydride. The intermediates3a,3b,3c,3d,3eunderwent facile acid‐induced cyclization in the presence of PTSA to afford the corresponding benzotriazoles4a,4b,4c,4d,4ein moderate yields. J. Heterocyclic Chem., (2009).
Chemically modified porous silicon for laser desorption/ionization mass spectrometry of ionic dyes
Authors: Shmigol I. V. , Alekseev S. A. , Lavrynenko O. Yu. , Vasylieva N. S. , Zaitsev V. N. , Barbier D. , Pokrovsky V. A. 
Published: June 2009

AbstractDesorption/ionization on silicon (DIOS) mass spectra of model ionic dyes methylene blue (MB+Cl−) and methyl orange (Na+MO−) were studied using p+ type‐derived porous silicon (PS) free layers. As‐prepared PS (PS‐H), the PS thermally oxidized at 300 °C (PS‐OX), PS with chemically grafted cation‐exchanging alkylsulfonic acid (PS‐SO3H) and anion‐exchanging propyl‐octadecyldimethylammonium chloride (PS‐ODMA+Cl−) groups was tested as ionization platforms. Two mechanisms of the methylene blue desorption/ionization were found: (1) the formation of [MB + H]+• ion due to the reduction/protonation of MB+, which is predominant for PS‐H and PS‐OX platforms and (2) direct thermal desorption of the MB+ cation, prevailing for PS‐SO3H. The fragmentation of the cation is significantly suppressed in the latter case. The samples of PS‐SO3H and PS‐ODMA+ Cl− efficiently adsorb the dyes of the opposite charge from their solutions via the ion‐exchange. Consequent DIOS MS studies allow to detect only low fragmented ions (MB+ and MO−, respectively), demonstrating the potential of the ion‐exchange adsorption combined with DIOS MS for the analysis of ionic organic compounds in solutions. Copyright © 2009 John Wiley & Sons, Ltd.
Proteasome inhibition modulates kinase activation in neural cells: Relevence to ubiquitination, ribosomes, and survival
Authors: Zhang Le , Ebenezer Philip J. , Dasuri Kalavathi , Bruce‐Keller Annadora J. , Liu Ying , Keller Jeffrey N. 
Published: June 2009

AbstractIn this study we examined whether established signal transduction cascades, p44/42 mitogen‐activated protein kinase (ERK1/2) and Jun N‐terminal kinases (JNK) pathways, are altered in N2a neural cells in response to proteasome inhibition. Additionally, we sought to elucidate the relative contribution of these signal transduction pathways to the multiple downstream effects of proteasome inhibition. Our data indicate that ERK1/2 and JNK are activated in response to proteasome inhibition. Washout of proteasome inhibitor (MG132) results in an enhancement of ERK1/2 activation and amelioration of JNK activation. Treatment with an established MAPK inhibitor resulted in an increase in proteasome inhibitor toxicity, and incubation with JNK inhibitor was observed to attenuate proteasome inhibitor toxicity significantly. Subsequent studies demonstrated that inhibition of ERK1/2 and JNK activity does not alter the gross increase in ubiquitinated protein following proteasome inhibitor administration. Similarly, ERK1/2 and JNK activity do not appear to play a role in the disruption of polysomes following proteasome inhibitor administration in neural cells. Together these data indicate that ERK1/2 and JNK activation may play differential roles in modulating neurochemical disturbances and neurotoxicity induced by proteasome inhibition. © 2009 Wiley‐Liss, Inc.
Environmental enrichment stimulates progenitor cell proliferation in the amygdala
Authors: Okuda Hiroaki , Tatsumi Kouko , Makinodan Manabu , Yamauchi Takahira , Kishimoto Toshifumi , Wanaka Akio 
Published: June 2009

AbstractEnriched environments enhance hippocampal neurogenesis, synaptic efficacy, and learning and memory functions. Recent studies have demonstrated that enriched environments can restore learning behavior and long‐term memory after significant brain atrophy and neural loss. Emotional and anxiety‐related behaviors were also improved by enriched stimuli, but the effect of enriched environments on the amygdala, one of the major emotion‐related structures in the central nervous system, remains largely unknown. In this study, we have focused on the effects of an enriched environment on cell proliferation and differentiation in the murine amygdala. The enriched environment increased bromodeoxyuridine (BrdU)‐positive (newborn) cell numbers in the amygdala, almost all of which, immediately after a 1‐week period of enrichment, expressed the oligodendrocyte progenitor marker Olig2. Furthermore, enriched stimuli significantly suppressed cell death in the amygdala. Some of the BrdU‐positive cells in mice exposed to the enriched environment, but none in animals housed in the standard environment, later differentiated into astrocytes. Our findings, taken together with previous behavioral studies, suggest that progenitor proliferation and differentiation in the amygdala may contribute to the beneficial aspects of environmental enrichment such as anxiolytic effects. © 2009 Wiley‐Liss, Inc.
Sodium channelopathy induced by mild axonal trauma worsens outcome after a repeat injury
Authors: Yuen Tracy J. , Browne Kevin D. , Iwata Akira , Smith Douglas H. 
Published: June 2009

AbstractThere is great concern that one mild traumatic brain injury (mTBI) predisposes individuals to an exacerbated response with a subsequent mTBI. Although no mechanism has been identified, mounting evidence suggests traumatic axonal injury (TAI) plays a role in this process. By using a cell culture system, a threshold of mild TAI was found where dynamic stretch of cortical axons at strains lower than 5% induced no overt pathological changes. However, the axons were found to display an increased expression of sodium channels (NaChs) by 24 hr. After a second, identical mild injury, pathologic increases in [Ca2+]i were observed, leading to axon degeneration. The central role of NaChs in this response was demonstrated by blocking NaChs with tetrodotoxin prior to the second injury, which completely abolished postinjury increases in [Ca2+]i. These data suggest that mild TAI induces a form of sodium channelopathy on axons that greatly exaggerates the pathophysiologic response to subsequent mild injuries. © 2009 Wiley‐Liss, Inc.
Deficits in peroneal latency and electromechanical delay in patients with functional ankle instability
Authors: Hopkins J. Ty , Brown Tyler N. , Christensen Logan , Palmieri‐Smith Riann M. 
Published: June 2009

AbstractThe purpose of this study was to compare alterations in peroneal latency and electromechanical delay (EMD) following an inversion perturbation during walking in patients with functional ankle instability (FAI) and with a matched control group. Peroneal latency and EMD were measured from 21 patients with unilateral FAI and 21 controls. Latencies were collected during a random inversion perturbation while walking. EMD measures were collected during stance using a percutaneous stimulus. Two‐way ANOVAs were used to detect differences between leg (affected, unaffected) and group (FAI, Control). Functionally unstable ankles displayed delayed peroneus longus (PL) latencies and EMD when compared to the unaffected leg and a matched control group. Peroneal latency and EMD deficits could contribute to recurrence of ankle injury in FAI subjects. How these deficits are associated with the chronic symptoms associated with FAI remains unclear, but gamma activation and subsequent muscle spindle sensitivity likely play a role. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1541–1546, 2009
Sensitive determination of 1‐ and 2‐naphthol in human plasma by HPLC‐fluorescence detection with 4‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)benzoyl chloride as a labeling reagent
Authors: Ohyama Kaname , Kishikawa Naoya , Matayoshi Kenji , Adutwum Lawrence Asamoah , Wada Mitsuhiro , Nakashima Kenichiro , Kuroda Naotaka 
Published: June 2009

AbstractA sensitive HPLC‐fluorescence (FL) method with FL‐labeling reagent for simultaneous determination of 1‐ and 2‐naphthol was developed. The FL‐labeling reaction of naphthols with 4‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)benzoyl chloride (DIB‐Cl) was completed in 20 min at 40°C. The separation of DIB derivatives was achieved with an ODS column and isocratic elution. The LODs of 1‐ and 2‐naphthol were 16 fmol and 14 fmol/injection, respectively, which were 5‐fold and 14‐fold lower than those obtained by HPLC‐FL method using the native FL of naphthols. The DIB‐naphthol derivatives were stable for at least 24 h even when they were placed at room temperature. The proposed method was applied to the measurement of 1‐ and 2‐naphthol in human plasma with sufficient accuracy (90.8–109%) and precision (< 6.3%).
Simultaneous analysis of morphine‐related compounds in plasma using mixed‐mode solid phase extraction and UltraPerformance liquid chromatography–mass spectrometry
Authors: Fountain Kenneth J. , Yin Zhe , Diehl Diane M. 
Published: June 2009

AbstractA bioanalytical method using mixed‐mode solid phase extraction and UltraPerformance liquid chromatography‐tandem mass spectrometry (UPLC–MS/MS) was developed for the analysis of morphine, morphine‐3β‐glucuronide, morphine‐6β‐glucuronide, 6‐acetylmorphine, morphineN‐oxide, and 10‐hydroxymorphine in porcine plasma. All six compounds, along with four deuterated internal standards, were simultaneously extracted using mixed‐mode strong cation exchange SPE in a 96‐well μElution plate format. Due to analyte instability, a neutralizing solvent was used during the elution step to minimize degradation of 6‐acetylmorphine. Separation was subsequently performed in 8 minutes on a 2.1×100 mm, 1.8 μm C18column designed for retention of extremely polar compounds using a formic acid and methanol gradient. Analytes were detected by positive electrospray ionization in multiple reaction monitoring mode using a fast‐scanning triple quadrupole mass spectrometer. Recovery was 73–123% depending on the analyte, and inter‐day variability was less than 6%. Linearity was determined in porcine plasma by spiking the analytes prior to SPE. Correlation coefficients were ⪈ 0.998, and% deviation from the actual concentrations was less than 15%. The lower limit of quantitation (LLOQ) for all compounds was between 0.1 and 0.25 ng/mL.
Development of a GC×GC–TOFMS method using SPME to determine volatile compounds in cacao beans
Authors: Humston Elizabeth M. , Zhang Yan , Brabeck Gregory F. , McShea Andrew , Synovec Robert E. 
Published: June 2009

AbstractA method to analyze volatile compounds from cacao beans has been developed and evaluated. The method utilizes solid phase micro extraction (SPME) sampling followed by comprehensive 2‐D (GC×GC) coupled with TOFMS. For the SPME procedure, a polydimethyl siloxane/divinyl benzene (PDMS/DVB) fiber was implemented. Cacao beans from four geographical origins were studied under two storage conditions, either dry or high moisture. A given cacao bean sample was sealed in a SPME vial and heated for 15 min. Extraction temperatures of 45, 60, 80, and 100°C were analyzed and an optimal extraction temperature of 60°C was determined. Many peaks were found to change as a function of storage conditions with Fisher Ratio analysis. Four representative compounds were identified and quantified (on a relative basis): acetic acid, nonanal, tetramethyl pyrazine, and trimethyl pyrazine. Acetic acid and nonanal were elevated in samples without evident mold on the bean surface, while the two pyrazines were elevated when mold was evident on the bean surface. The results for these comparisons, indicate that metabolism at the bean surface plays a role in the concentration of analytes, and can be readily determined using this analytical technology and methodology.
Analytical and statistical approaches to metabolomics research
Authors: Issaq Haleem J. , Van Que N. , Waybright Timothy J. , Muschik Gary M. , Veenstra Timothy D. 
Published: June 2009

AbstractMetabolomics, the global profiling of metabolites in different living systems, has experienced a rekindling of interest partially due to the improved detection capabilities of the instrumental techniques currently being used in this area of biomedical research. The analytical methods of choice for the analysis of metabolites in search of disease biomarkers in biological specimens, and for the study of various low molecular weight metabolic pathways include NMR spectroscopy, GC/MS, CE/MS, and HPLC/MS. Global metabolite analysis and profiling of two different sets of data results in a plethora of data that is difficult to manage or interpret manually because of their subtle differences. Multivariate statistical methods and pattern‐recognition programs were developed to handle the acquired data and to search for the discriminating features between data acquired from two sample sets, healthy and diseased. Metabolomics have been used in toxicology, plant physiology, and biomedical research. In this paper, we discuss various aspects of metabolomic research including sample collection, handling, storage, requirements for sample analysis, peak alignment, data interpretation using statistical approaches, metabolite identification, and finally recommendations for successful analysis.