bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico panning for a non-competitive peptide inhibitor
Authors: Yagi Yukiko , Terada Kotaro , Noma Takahisa , Ikebukuro Kazunori , Sode Koji 
Published: January 2007

Abstract

Background
Peptide ligands have tremendous therapeutic potential as efficacious drugs. Currently, more than 40 peptides are available in the market for a drug. However, since costly and time-consuming synthesis procedures represent a problem for high-throughput screening, novel procedures to reduce the time and labor involved in screening peptide ligands are required. We propose the novel approach of 'in silico panning' which consists of a two-stage screening, involving affinity selection by docking simulation and evolution of the peptide ligand using genetic algorithms (GAs). In silico panning was successfully applied to the selection of peptide inhibitor for water-soluble quinoprotein glucose dehydrogenase (PQQGDH).

Results
The evolution of peptide ligands for a target enzyme was achieved by combining a docking simulation with evolution of the peptide ligand using genetic algorithms (GAs), which mimic Darwinian evolution. Designation of the target area as next to the substrate-binding site of the enzyme in the docking simulation enabled the selection of a non-competitive inhibitor. In all, four rounds of selection were carried out on the computer; the distribution of the docking energy decreased gradually for each generation and improvements in the docking energy were observed over the four rounds of selection. One of the top three selected peptides with the lowest docking energy, 'SERG' showed an inhibitory effect with K
i value of 20 μM. PQQGDH activity, in terms of the V
max value, was 3-fold lower than that of the wild-type enzyme in the presence of this peptide. The mechanism of the SERG blockage of the enzyme was identified as non-competitive inhibition. We confirmed the specific binding of the peptide, and its equilibrium dissociation constant (K
D) value was calculated as 60 μM by surface plasmon resonance (SPR) analysis.

Conclusion
We demonstrate an effective methodology of in silico panning for the selection of a non-competitive peptide inhibitor from small virtual peptide library. This study is the first to demonstrate the usefulness of in silico evolution using experimental data. Our study highlights the usefulness of this strategy for structure-based screening of enzyme inhibitors.
Wnt/β-catenin signaling is required for development of the exocrine pancreas
Authors: Wells James M , Esni Farzad , Boivin Gregory P , Aronow Bruce J , Stuart William , Combs Chelsea , Sklenka Angela , Leach Steven D , Lowy Andrew M 
Published: January 2007

AbstractBackgroundβ-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of β-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that β-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of β-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of β-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of β-catenin disrupts pancreatic development. APdx1-cremouse line was used to delete a floxedβ-cateninallele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis.ResultsPdx1-crefloxedβ-cateninanimals were viable but demonstrated small body size and shortened median survival. The pancreata from knockout mice were hypoplastic and histologically demonstrated a striking paucity of exocrine pancreas, acinar to duct metaplasia, but generally intact pancreatic islets containing all lineages of endocrine cells. In animals with extensive acinar hypoplasia, putative hepatocyte transdifferention was occasionally observed. Obvious and uniform pancreatic hypoplasia was observed by embryonic day E16.5. Transcriptional profiling ofPdx1-crefloxedβ-cateninembryonic pancreata at E14.5, before there was a morphological phenotype, revealed significant decreases in the β-catenin target geneN-myc, and the basic HLH transcription factorPTF1, and an increase of several pancreatic zymogens compared to control animals. By E16.5, there was a dramatic loss of exocrine markers and an increase inHoxb4, which is normally expressed anterior to the pancreas.ConclusionWe conclude that β-catenin expression is required for development of the exocrine pancreas, but is not required for development of the endocrine compartment. In contrast, β-catenin/Wnt signaling appears to be critical for proliferation of PTF1+ nascent acinar cells and may also function, in part, to maintain an undifferentiated state in exocrine/acinar cell precursors. Finally, β-catenin may be required to maintain positional identity of the pancreatic endoderm along the anterior-posterior axis. This data is consistent with the findings of frequentβ-cateninmutations in carcinomas of acinar cell lineage seen in humans.
Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway
Authors: Ishiura Yoshihisa , Fujimura Masaki , Nobata Kouichi , Oribe Yoshitaka , Abo Miki , Myou Shigeharu 
Published: January 2007

AbstractInflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold was significantly (p < 0.05) decreased after two weeks of treatment with beraprost [17.8 (GSEM 1.20) μM] compared with placebo [30.3 (GSEM 1.21) μM]. PGI2 increases cough reflex sensitivity of the asthmatic airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for patients with asthma, especially cough predominant asthma.
Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders
Authors: Huckans Marilyn S , Loftis Jennifer M , Blackwell Aaron D , Linke Alex , Hauser Peter 
Published: January 2007

Abstract

Background
Individuals with substance use disorders (SUDs) are at increased risk for hepatitis C viral infection (HCV), and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN) completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare Administration (VHA) between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN) or combination therapy (IFN and ribavirin) who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group) and patients without a history of SUD (SUD- Group).

Results
Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4 (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%) and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%).

Conclusion
Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.
A comparative study of the complications of surgical tracheostomy in morbidly obese critically ill patients
Authors: El Solh Ali A , Jaafar Wafaa 
Published: January 2007

Abstract
Introduction
There is little objective comparative information about the postoperative complications of tracheostomy in morbidly obese patients. The aim of this study was to determine the incidence and severity of complications associated with open tracheostomy in critically ill morbidly obese patients during hospitalization.

Methods
During a six year period, all consecutive morbidly obese patients (body mass index [BMI] of greater than or equal to 40 kg/m2) who underwent an elective open tracheostomy were compared to a control group (BMI of less than 40 kg/m2) of the same institution. Variables examined included age, gender, BMI, Charlson index, and reasons for tracheostomy. All postoperative tracheotomy-related complications that occurred during hospitalization, including death, were recorded.

Results
A tracheostomy was performed in 89 morbidly obese patients out of 427 critically ill patients. A total of 27 complications were recorded in 22 morbidly obese patients (25%) compared to 65 complications in 49 patients (14%) of the control group (p = 0.03). The majority of these complications were minor in origin. Overall, nine serious events were responsible for two deaths in the morbidly obese compared to seven cases and two deaths in the control group (p = 0.001). Life-threatening complications were attributed to tube obstruction and malpositioning of the tracheostomy after being dislodged. In multivariate analysis, morbid obesity (odds ratio 4.4, 95% confidence interval 2.1 to 11.7) was independently associated with increased risk of tracheostomy-related complications.

Conclusion
In the present series, morbid obesity is associated with increased frequency and life-threatening complications from conventional tracheostomy. Special techniques and operative policies must be applied to overcome loss of airway control.
Managing an effective treatment for neuroleptic malignant syndrome
Authors: Reulbach Udo , Dütsch Carmen , Biermann Teresa , Sperling Wolfgang , Thuerauf Norbert , Kornhuber Johannes , Bleich Stefan 
Published: January 2007

Abstract
Introduction
Neuroleptic malignant syndrome (NMS) is a rare, but sometimes fatal, adverse reaction to neuroleptics characterized principally by fever and rigor. The aim of this study was to prove the efficacy of different NMS treatment strategies, focusing on the efficacy of dantrolene.

Methods
Altogether, 271 case reports were included. These cases were categorized into four treatment groups and compared to each other according to effectiveness of therapy within 24 hours, mortality, complete time of remission in days, effectiveness due to increase of dosage, relapse on the basis of decrease of dosage, and improvement of symptoms.

Results
Between the four treatment groups, the complete time of remission was significantly different (analysis of variance, F = 4.02; degrees of freedom = 3; p = 0.008). In a logistic regression with adjustment for age, gender, and severity code, no significant predictor of the treatment for the complete time of remission (dichotomized by median) could be found. However, if the premedication was a monotherapy with neuroleptics, the complete time of remission was significantly shorter with dantrolene monotherapy (t = -2.97; p = 0.004).

Conclusion
The treatment of NMS with drugs that are combined with dantrolene is associated with a prolongation of clinical recovery. Furthermore, treatment of NMS with dantrolene as monotherapy seems to be associated with a higher overall mortality. Therefore, dantrolene does not seem to be the evidence-based treatment of choice in cases of NMS but might be useful if premedication consisted of a neuroleptic monotherapy.
Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection
Authors: Panelli Monica C , Stashower Mitchell E , Slade Herbert B , Smith Kina , Norwood Christopher , Abati Andrea , Fetsch Patricia , Filie Armando , Walters Shelley-Ann , Astry Calvin , Aricó Eleonora , Zhao Yingdong , Selleri Silvia , Wang Ena , Marincola Francesco M 
Published: January 2007

Abstract
Background
Imiquimod is a Toll-like receptor-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection.

Results
We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (n = 22) or vehicle cream (n = 14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hours for 4 or 8 days). RNA was amplified and hybridized to 17.5 K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 × 4 days regimen, associated with highest effectiveness, induced the most changes, with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-α involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity.

Conclusion
This study, based on a powerful and reproducible model of cancer eradication by innate immune mechanisms, provides the first insights in humans into the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction.
From Persistent Triplet Carbenes to Persistent High-Spin Polycarbenes
Authors: Itoh Tetsuji , Hirai Katsuyuki , Tomioka Hideo 
Published: January 2007

Abstract
Triplet carbenes are regarded as one of the most effective spin sources for organic ferromagnetic materials since the magnitude of the exchange coupling between the neighboring centers is large. However, those systems have two disadvantages that prevent their use as practical magnetic materials. First, a triplet carbene unit is highly unstable and lacks the stability for practical applications under ambient conditions. Second, diazo groups, which are precursors for triplet carbenes, are generally labile and, hence, cannot be used as building blocks to prepare a more complicated poly(diazo) compound. After great efforts to stabilize the triplet carbenes, we have succeeded in preparing fairly stable triplet carbenes that survive for days. We found that a diazo precursor for a persistent triplet carbene was also persistent and, hence, can be further modified into a more complicated diazo compound that can generate persistent high-spin polycarbenes. In this account, we would like to summarize our efforts along this line. We employed the following three approaches to prepare poly(diazo) compounds; (1) synthesis of dendritic molecules having peripheral diazo groups starting from diazo compounds, (2) preparation of a poly(phenylacetylene) with a diazo unit using Rh-complex-catalyzed polymerization of diazo compounds with p-ethynyl substituents, and (3) preparation of a polymer chain as a result of complexation of the pyridine ligand on diazo compounds with coordinatively unsaturated metal ions. We also characterized the magnetic properties of photoproducts obtained by photolysis of those poly(diazo) compounds. Although spin-states observed for those photoproducts were not so high, the results suggest that our approach using persistent triplet carbenes will eventually lead us to a persistent high-spin polycarbenes by taking advantage of the stability of our diazo compounds.
Interaction of a Coordinatively Unsaturated Transition-Metal Center with Small Molecules: DFT Studies on W(CO)5L (L = None, C2H4, and NH3)
Authors: Kawakami Kenta , Nakazawa Hirotaka , Kinoshita Toshimichi , Ishikawa Yo-ichi 
Published: January 2007

Abstract
DFT calculations were performed in order to investigate the interactions between coordinatively unsaturated sites on W(CO)5 and C2H4 as a typical π-acceptor and NH3 as a typical σ-donor. B3LYP-based DFT calculations with ECPs (LANL2DZ) on W and 6-311G(d,p) all-electron basis sets on H, C, N, and O reproduced the characteristic shifts in vibrational frequency of carbonyls that have been experimentally observed for the successive processes W(CO)6 (− CO) → W(CO)5 (+ L) → W(CO)5L (L = C2H4 and NH3). Based on the calculations, C2H4 coordinates to the coordinatively unsaturated site of W atom in a side-on fashion with a 23.1 kcal mol−1 bond dissociation enthalpy (BDE), where the center of the C=C double bond was 2.39 Å from W atom, and NH3 coordinates with a BDE of 31.9 kcal mol−1 and a distance of 2.37 Å. As well, the C=C bond length (1.38 Å) in C2H4 was found to be slightly longer than that of free C2H4 (1.33 Å).
V-Shaped Polyoxotungstoarsenates Incorporating a Prism-Like Hexa Transition-Metals Center: [M6(H2O)2(AsW9O34)2(AsW6O26)]17− (M2+ = Mn2+, Co2+, Zn2+)
Authors: Fukaya Keisuke , Yamase Toshihiro 
Published: January 2007

Abstract
Hexa transition-metals incorporated polyoxotungstoarsenates, [M6(H2O)2(AsW9O34)2(AsW6O26)]17− (M2+ = Mn2+, Co2+I, Zn2+), have been prepared at pH 7–8 and characterized by elemental analysis, electrochemistry, and X-ray crystallography: Na17[Mn6(H2O)2(AsW9O34)2(AsW6O26)]·41H2O (1), P21/c, a = 17.73(1) Å, b = 22.34(1) Å, c = 35.41(3) Å, β = 95.37(3)°, V = 13963(14) Å3, and Z = 4; Na17[Co6(H2O)2(AsW9O34)2(AsW6O26)]·41H2O (2), P21/c, a = 17.65(1) Å, b = 22.24(1) Å, c = 34.78(2) Å, β = 95.84(2)°, V = 13584(13) Å3, and Z = 4; Na17[Zn6(H2O)2(AsW9O34)2(AsW6O26)]·38H2O (3), P21/c, a = 17.6295(6) Å, b = 22.2992(7) Å, c = 34.927(1) Å, β = 95.695(2)°, V = 13662.8(7) Å3, and Z = 4. The anion of 1–3 consists of two B-α [{M(H2O)}M2(AsW9O34)]3− units joined by a B-type hexa-vacant [AsW6O26]11− fragment, corresponding to a removal of the edge-sharing W3O8 moiety from B-α [AsW9O34]9−, to form a C2v-symmetric V-shaped geometry. Two edge-sharing MO6-octahedral triads (with M···M distances 3.2–3.4 Å) are well-separated with M···M distances of 5.5–8.9 Å. Three successive electrochemically quasi-reversible two-electron MnII/MnIII waves were observed in the cyclic voltammogram of 1. M2+ ion with larger radius causes an elongation of the As···As distances. A single Na+ cation coordinated by three oxygen atoms (two belonging to B-α [AsW9O34]9− and one belonging to B-[AsW6O26]11−) in the crevice of the anion stabilizes the V-shaped structure.
Ion-Association Extraction of Nitrobenzoate Ions with Tetrabutylammonium Ion into Nonionic Surfactant Micelles as Studied by Capillary Zone Electrophoresis
Authors: Takayanagi Toshio , Motomizu Shoji 
Published: January 2007

Abstract
Ion-associates formed between tetrabutylammonium ion (TBA+) and substituted nitrobenzoate ions have been extracted into nonionic surfactant micelles in an aqueous solution. The micelle extraction property of the ion-associates was investigated through the changes in electrophoretic mobility in capillary zone electrophoresis, in which a nonionic surfactant, Brij 35 or Brij 58, was used as a micelle substrate. Prior to the extraction analysis, ion-association constants (Kass) between TBA+ and the benzoate ions as well as binding constants of the anions to the nonionic surfactant micelle (KB) were determined through the mobility change. Binding of the ion-associates from aqueous to the micelle phases was observed, when both TBA+ and the nonionic surfactant were present in the migrating solution. Micelle extraction constants for the ion-associates (Kex,m), were also determined by using the mobility change, and the values were compared with the ion-association solvent extraction constants between water and chloroform.
Synthesis and Characterization of a Novel Chiral Molecular-Based Ferrimagnet Prepared from a Chiral Nitronyl Nitroxide Radical and Manganese(II) Ion
Authors: Akita-Tanaka Motoko , Kumagai Hitoshi , Markosyan Ashot , Inoue Katsuya 
Published: January 2007

Abstract
A new chiral organic radical, 4,4,5,5-tetramethyl-2-{4-[(S)-2-methylbutoxy]phenyl}-3-oxido-4,5-dihydroimidazol-1-oxyl (1) and its MnII complex ([1·MnII(hfac)2]n (hfac = hexafluoroacetylacetonato)) were synthesized and characterized. From single crystal X-ray structure analysis, 1 and [1·MnII(hfac)2]n have a chiral space group (P212121), and [1·MnII(hfac)2]n has a one-dimensional helical structure. Magnetic susceptibility measurements of [1·MnII(hfac)2]n indicate that this heterospin system behaves as a ferrimagnet with very weak interchain ferromagnetic exchange interaction.
Preparation and Characterization of Nanomaterials of Tellurium, Bismuth, and Bismuth Telluride
Authors: Watanabe Norihisa , Toshima Naoki 
Published: January 2007

Abstract
In order to improve the processing and performance of tellurium (Te), bismuth (Bi), and bismuth telluride (dibismuth tritelluride, Bi2Te3), which are valuable thermoelectric materials that operate near room temperature in the bulk state, a nanometer scale synthetic method, in which the starting materials are reduced with NaBH4 in the presence of protecting agents in solution under mild conditions, was used. Te nanorods having an average diameter of 10 ± 3 nm (aspect ratio = 3.0) were prepared by reducing tellurium(IV) ethoxide in ethanol in the presence of poly(N-vinyl-2-pyrrolidone) (PVP) under nitrogen. Although Bi nanoparticles prepared from bismuth(III) chloride by this method have an average diameter of 29 ± 8 nm, PVP-protected Bi2Te3 nanoparticles have a really small average diameter (7 ± 5 nm) and they are probably the smallest Bi2Te3 particles ever reported. Heat treatment of PVP-protected Bi2Te3 nanoparticles in refluxing solvents was found to improve the stability.
Shape-Selective Alkylation of Biphenyl over H-[Al]-SSZ-24 Zeolites with AFI Topology
Authors: Ito Akira , Maekawa Hiroyoshi , Kawagoe Hiroaki , Komura Kenichi , Kubota Yoshihiro , Sugi Yoshihiro 
Published: January 2007

Abstract
H-[Al]-SSZ-24 zeolites with AFI topology were synthesized through the alumination of [B]-SSZ-24 zeolites, and applied for the alkylation of biphenyl (BP). H-[Al]-SSZ-24 zeolites have high activity for the isopropylation. The shape-selective formation of 4,4′-diisopropylbiphenyl (4,4′-DIPB) occurred at moderate temperature; however, the selectivity for 4,4′-DIPB decreased with an increase in the reaction temperature. Isomerization of 4,4′-DIPB occurred at higher temperatures over internal and external acid sites when there are enough acid sites inside the channels. The channels can discriminate 4,4′-DIPB from the other DIPB isomers in their transition states; however, they can not prevent the isomerization of 4,4′-DIPB at higher temperatures. The selectivity for the least bulky 4,4′-dialkylbiphenyl increased with the bulkiness of alkylating agents in the order: isopropylation &lt; s-butylation &lt; t-butylation. These results strongly support the shape-selective formation of the least bulky products inside the channels of H-[Al]-SSZ-24 zeolites.