bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of protein–protein interactions: The discovery of druglike β‐catenin inhibitors by combining virtual and biophysical screening
Authors: Trosset Jean‐Yves , Dalvit Claudio , Knapp Stefan , Fasolini Marina , Veronesi Marina , Mantegani Sergio , Gianellini Laura M. , Catana Cornel , Sundström Michael , Stouten Pieter F.W. , Moll Jürgen K. 
Published: March 2006

AbstractThe interaction between β‐catenin and Tcf family members is crucial for the Wnt signal transduction pathway, which is commonly mutated in cancer. This interaction extends over a very large surface area (4800 Å2), and inhibiting such interactions using low molecular weight inhibitors is a challenge. However, protein surfaces frequently contain “hot spots,” small patches that are the main mediators of binding affinity. By making tight interactions with a hot spot, a small molecule can compete with a protein. The Tcf3/Tcf4‐binding surface on β‐catenin contains a well‐defined hot spot around residues K435 and R469. A 17,700 compounds subset of the Pharmacia corporate collection was docked to this hot spot with the QXP program; 22 of the best scoring compounds were put into a biophysical (NMR and ITC) screening funnel, where specific binding to β‐catenin, competition with Tcf4 and finally binding constants were determined. This process led to the discovery of three druglike, low molecular weight Tcf4‐competitive compounds with the tightest binder having a KD of 450 nM. Our approach can be used in several situations (e.g., when selecting compounds from external collections, when no biochemical functional assay is available, or when no HTS is envisioned), and it may be generally applicable to the identification of inhibitors of protein–protein interactions. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Molecular dynamics study of a calmodulin‐like protein with an IQ peptide: Spontaneous refolding of the protein around the peptide
Authors: Ganoth Assaf , Nachliel Esther , Friedman Ran , Gutman Menachem 
Published: March 2006

AbstractThe Calmodulin (CaM) is a small (16.7 kDa), highly acidic protein that is crucial to all eukaryotes by serving as a prototypical calcium sensor. In the present study, we investigated, through molecular dynamics simulations, the dynamics of a complex between the Mlc1p protein, which is a CaM‐like protein, and the IQ4 peptide. This protein‐peptide interaction is of high importance because IQ motifs are widely distributed among different kinds of CaM‐binding proteins. The Mlc1p‐IQ4 complex, which had been resolved by crystallography to 2.1 Å, confers to a Ca+2‐independent stable structure. During the simulations, the complex undergoes a complicated modulation process, which involves bending of the angles between the α‐helices of the protein, breaking of the α‐helical structure of the IQ4 peptide into two sections, and formation of new contact points between the protein and the peptide. The dynamics of the process consist of fast sub picosecond events and much slower ones that take a few nanoseconds to completion. Our study expands the information embedded in the crystal structure of the Mlc1p‐IQ4 complex by describing its dynamic behavior as it evolves from the crystal structure to a form stable in solution. The article shows that careful application of molecular dynamics simulations can be used for extending the structural information presented by the crystal structure, thereby revealing the dynamic configuration of the protein in its physiological environment. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Comparing programs for rigid‐body multiple structural superposition of proteins
Authors: Hill Anthony D. , Reilly Peter J. 
Published: March 2006

AbstractDifferent programs and methods were employed to superimpose protein structures, using members of four very different protein families as test subjects, and the results of these efforts were compared. Algorithms based on human identification of key amino acid residues on which to base the superpositions were nearly always more successful than programs that used automated techniques to identify key residues. Among those programs automatically identifying key residues, MASS could not superimpose all members of some families, but was very efficient with other families. MODELLER, MultiProt, and STAMP had varying levels of success. A genetic algorithm program written for this project did not improve superpositions when results from neighbor‐joining and pseudostar algorithms were used as its starting cases, but it always improved superpositions obained by MODELLER and STAMP. A program entitled PyMSS is presented that includes three superposition algorithms featuring human interaction. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Protonation of metal‐bound α‐hydroxycarboxylate ligand and implication for the role of homocitrate in nitrogenase: Computational study of the oxy‐bidentate chelate ring opening
Authors: Cao Zexing , Jin Xi , Zhou Zhaohui , Zhang Qianer 
Published: March 2006

AbstractProtonation of the metal‐bound oxy‐bidentate ligand in the model complexes of [(HS)3(NH3)M(OCH2COO)]q (M = Mo, Fe, V, Co; q = −2, −1) in the gas phase and in solutions of water and acetonitrile has been explored by the density functional approach. Calculations show that protonation of the carboxyl oxygen can open the α‐hydroxycarboxylate chelate ring ligated to a transition‐metal center under specific oxidation and spin states. The feasibility of the chelate ring opening by protonation depends on the electronic nature of the metal site in tune with conversion of a six‐coordinate with a five‐coordinate metal atom. Such selective dissociation of the metal‐bound chelate ligand manipulates the availability of an empty site at the metal center and significantly affects reactivity of the metal‐mediated chemical processes. Protonation changes the stability of species with different spin multiplicities and impels spin transition at the metal center in dissociation of the oxy‐bidentate ligand. Solvent environments of water and acetonitrile play an important role in stabilizing the negatively charged species. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
A graphical method to construct a phylogenetic tree
Authors: Wang Weiping , Liao Bo , Wang Tianming , Zhu Wen 
Published: March 2006

AbstractA 3D graphical representation of DNA sequences, which has no circuit or degeneracy, is derived for mathematical denotation of DNA sequence. Based on this graphical representation, we propose a new sequence distance measure. We make use of the corresponding similarity matrix to construct a phylogenic tree by virtue of the fuzzy theory. The examination of phylogenic tree belong to eight species illustrates the utility of our approach. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Auxiliary functions for molecular integrals with Slater‐type orbitals. I. Translation methods
Authors: Fernández J. J. , López R. , Ema I. , Ramírez G. , Fernández Rico J. 
Published: March 2006

AbstractMany types of molecular integrals involving Slater functions can be expressed, with the ζ‐function method in terms of sets of one‐dimensional auxiliary integrals whose integrands contain two‐range functions. After reviewing the properties of these functions (including recurrence relations, derivatives, integral representations, and series expansions), we carry out a detailed study of the auxiliary integrals aimed to facilitate both the formal and computational applications of the ζ‐function method. The usefulness of this study in formal applications is illustrated with an example. The high performance in numerical applications is proved by the development of a very efficient program for the calculation of two‐center integrals with Slater functions corresponding to electrostatic potential, electric field, and electric field gradient. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Multi‐channel coupling effects for electronic excitations leading to the b3∑, a3∑, and c3∏u states of H2
Authors: Taveira A. M. A. , Brescansin L. M. , Machado A. M. , Lee M.‐T. 
Published: March 2006

AbstractIn this work we use the unitarized distorted wave method to study the effect of multi‐channel coupling on the calculated electronic excitation cross sections in H2. Specifically, such an effect for electronic excitations leading to the excited states b3∑, a3∑, and c3∏u for incident energies varying from 15 to 60 eV is studied. Our results have shown that converged cross sections can be obtained with the inclusion of only triplet intermediate states, except for energies near the excitation thresholds, where the inclusion of singlet intermediate states is important. Also, convergence improves with increasing energies for all excitations considered. Comparison of our calculated cross sections with available experimental and other theoretical results is encouraging. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
The initial oxidation of magnesium: an in situ study with XPS, HERDA and ellipsometry
Authors: Kurth M. , Graat P. C. J. , Carstanjen H. D. , Mittemeijer E. J. 
Published: March 2006

AbstractThe initial oxidation of magnesium at oxygen partial pressures between 1.3 × 10−8 and 1.3 × 10−5 Pa and at temperatures ranging from 273 to 550 K has been investigated in situ with X‐ray photoelectron spectroscopy (XPS), ellipsometry and high resolution elastic recoil detection analysis (HERDA). Quantitative analysis of the XPS spectra showed a clear oxygen deficiency with respect to MgO for the initial oxide. HERDA measurements confirmed this relatively low oxygen content in the thin oxide layers formed. Ellipsometry measurements showed that the electronic structure of the initially formed oxide differs significantly from that of bulk MgO. The band gap values at room temperature for the oxide layers investigated are clearly smaller than the value for bulk MgO. Copyright © 2006 John Wiley & Sons, Ltd.
Measurements of ion‐induced ferroelectric emission and surface charge dynamics on LiTaO3(0001) by time‐of‐flight scattering and recoiling spectrometry (TOF‐SARS)
Authors: Lui K. M. , Leang P. S. , Kam Y. K. , Lau W. M. 
Published: March 2006

AbstractWe have derived a special surface analysis method for studying surface charge dynamics on ferroelectrics from time‐of‐flight ion scattering and recoiling spectrometry (TOF‐SARS). In this method, shifts of the TOF‐SARS peaks of a ferroelectric crystal are measured as a function of sample temperature, and these spectral data are used to deduce changes in electrical potential on the sample surface. These changes are then converted to information on surface charge dynamics. In addition, the method is also applicable in extracting data regarding ion‐induced ferroelectric electron emission (FEE) from the TOF‐SARS spectra. In this work, we have tested the method with LiTaO3(0001) crystals having the nominal stoichiometry and single domain properties. Our results show that for temperature changes from 25 to ∼100 °C, the excess amount of surface charge induced by pyroelectricity, ion irradiation, and ion‐induced electron emission is drained mainly by surface conductivity. For temperature changes above 100 °C, the bulk ionic conductivity becomes an important charge drainage channel. Our measurements give an activation energy of 0.75 eV for the thermally activated ionic conductivity, and the result agrees well with the literature value previously obtained by d.c. conductivity measurements. Copyright © 2006 John Wiley & Sons, Ltd.
Study of hydration layers near a hydrophilic surface in water through AFM imaging
Authors: Peng Changsheng , Song Shaoxian , Fort Tomlinson 
Published: March 2006

AbstractIn this work, a hydrophilic silica plate exposed in air, and immersed in an aqueous solution was studied through atomic force microscopy (AFM) imaging in contact‐ and tapping‐mode operations. It was experimentally found that the tapping‐mode AFM images of the silica surface were different when it was immersed in an aqueous solution from those when it was exposed in air. The former showed fewer topographic features. However, the contact‐mode AFM images of the silica surface were almost uninfluenced by the medium in which the surface was placed. This phenomenon might be attributed to the existence of hydration layers near the silica surface in the aqueous solution. The layers are like a large sheet on the surface that hides the details, so that an AFM tip in the tapping mode can read only the hydration layer and therefore image only the rough outline of the surface. This result might suggest the existence of hydration layers near a hydrophilic surface immersed in water. Copyright © 2006 John Wiley & Sons, Ltd.
Impact of Overweight and Pneumoperitoneum on Hemodynamics and Oxygenation during Prolonged Laparoscopic Surgery
Authors: Meininger Dirk , Zwissler Bernhard , Byhahn Christian , Probst Michael , Westphal Klaus , Bremerich Dorothee H. 
Published: March 2006

AbstractBackgroundAnesthesia adversely affects respiratory function and hemodynamics in obese patients. Although many studies have been performed in morbidly obese patients, data are limited concerning overweight patients [BMI 25–29.9 kg m−2]. The aim of this study was to evaluate the effects of prolonged pneumoperitoneum in Trendelenburg position on hemodynamics and gas exchange in normal and overweight patients.MethodsWe studied 15 overweight and 15 non‐obese [BMI 18.5–24.9 kg m−2] patients who underwent totally endoscopic robot‐assisted radical prostatectomy under general anesthesia with an inspired oxygen fraction of 0.5. A standardized anesthetic regimen was used, and patients were examined at standard times: after induction of anesthesia and Trendelenburg posture, every 30 minutes after establishing pneumoperitoneum, and after the release of the pneumoperitoneum with the patient still in Trendelenburg position.ResultsAfter induction of anesthesia and Trendelenburg positioning arterial oxygen pressure [PaO2] and alveolar‐arterial difference in oxygen tension [AaDO2] differed significantly between both groups with lower PaO2 [235 ± 27 versus 164 ± 51 mmHg] and higher AaDO2 [149 ± 48 versus 76 ± 28 mmHg] values in overweight patients. During pneumoperitoneum, PaO2 transient increased above baseline values in overweight patients, whereas AaDO2 decreased. Hemodynamic parameters [HR, MAP, and CVP] did not differ significantly between groups.ConclusionsArterial oxygenation and AaDO2 are significantly impaired in overweight patients under general anesthesia in Trendelenburg posture. In overweight patients pneumoperitoneum transient reduced the impairment of arterial oxygenation and lead to a decrease in AaDO2. Hemodynamic parameters were not affected by body weight.
Which Octogenarians Do Poorly After Major Open Abdominal Surgery in Our Asian Population?
Authors: Tan Kok‐Yang , Chen Chung‐Ming , Ng Chin , Tan Su‐Ming , Tay Khoon‐Hean 
Published: March 2006

AbstractBackgroundAs the elderly population grows and surgeons are faced with more octogenarians, there is a need to know how our Asian patients fair after major surgery.MethodsA retrospective review of 125 octogenarians who underwent major abdominal surgery between January 1997 and September 2003 was performed. Preoperative condition was assessed using a weighted index of comorbidity used in Charlson Comorbidity Index and classification of patients according to the American Society of Anaesthesiologists (ASA). Outcome was measured as to whether complications developed, 30‐day mortality and whether there was return to premorbid function.ResultsThe patients had a mean age of 84.6 years (range: 80–106). Nearly half (48.8%, n = 61) the cases were emergency cases. The median index of comorbidity was 3, and 29.6% of patients were classified either ASA III or IV. The operations were mostly stomach, small bowel or large bowel resection. Multivariate analysis revealed that emergency operations were associated with significantly increased odds of morbidity. The overall 30‐day mortality was 5.6%, being only 4.7% for elective cases, despite high morbidity rates. ASA classification, comorbidity index >5, development of acute coronary syndrome and anastomotic leakage were found on multivariate analysis to significantly increase the odds of mortality. For elective cases, 82.8% of patients were able to return to their premorbid functional status. Development of complications and comorbidity index >5 were found to predict failure of its occurrence. Low serum albumin and haemoglobin and renal impairment were also predictors of adverse outcome.ConclusionsEfforts to improve outcome in geriatric surgery patients should emphasize a shift of attitude towards elective surgery rather than doing emergency operations when complications occur and also target the optimization of predictors of adverse outcome. Octogenarians should not be denied elective surgery.
Posttraumatic Thromboprophylaxis Revisited: An Argument Against the Current Methods of DVT and PE Prophylaxis after Injury
Authors: Velmahos George C. 
Published: March 2006

AbstractBackgroundThromboprophylaxis after injury is a controversial issue. Practices and outcomes vary widely.MethodsReview of selected trauma literature on venous thromboprophylaxis after injury.ResultsMultiple trauma articles suggest that the efficacy of different methods of thromboprophylaxis is unproven. Most of the practices on this issue are extrapolated from studies which were performed in non‐trauma patients and therefore, may not be applicable in the unique trauma population.ConclusionsIn the absence of undisputable evidence, none of the current methods of venous thromboprophylaxis after injury should be considered as standard of care. There is a need to discover new methods of thromboprophylaxis for the Trauma patient.
Surgery for “Body Packers” — A 15‐year Experience
Authors: Silverberg Daniel , Menes Tehillah , Kim Unsup 
Published: March 2006

AbstractBackground“Body packing” of illegal drugs has increased in the last decades, and with it our experience in treating these patients, yet no clear guidelines for surgical treatment are available. We examined the characteristics and outcomes of patients who required surgical intervention.Study designCharts of all patients who underwent surgery at our institution for ingested drug packets between January 1990 and January 2005 were reviewed. Patients were identified by a pre‐existing list of names collected prospectively and by admission codes. Reviewed parameters included presentation, method of diagnosis, indication for surgery, procedure, and patient outcome.ResultsTwenty‐five patients were identified, for whom charts were available for review. Main indications for surgery were drug toxicity and small bowel obstruction. Most packets were retrieved using a combination of milking and multiple enterotomies. A high rate (40%) of postoperative wound infection was found. The incidence of wound infection correlated significantly with the number of enterotomies.ConclusionSurgical intervention for body packing remains the treatment for a minority of these patients. Patients should be placed in lithotomy to facilitate the exposure of the entire gastrointestinal tract, and to allow milking of the packets and their possible retrieval through the anus. The number of enterotomies should be minimized in order to reduce the risk of wound infection. If multiple enterotomies are used, the surgeon should consider leaving the wound open for delayed closure.
Peritoneal Cytology Does Not Increase the Prognostic Information Provided by TNM in Gastric Cancer
Authors: de Manzoni G. , Verlato G. , Leo A. Di , Tomezzoli A. , Pedrazzani C. , Pasini F. , Piubello Q. , Cordiano C. 
Published: March 2006

AbstractBackgroundThis study aimed at verifying whether peritoneal cytology could improve the prognostic information provided by TNM staging in gastric cancer patients.MethodThe presence of free peritoneal tumor cells was investigated in 168 patients who underwent curative resection for gastric cancer from January 1992 to July 2002 in Verona, Italy. The influence of peritoneal cytology on survival was evaluated by a Cox regression model, controlling for potential confounders.ResultsTwenty‐three patients (14%) had positive peritoneal cytology. Patients with positive lavage were more likely to present serosal infiltration (100 vs. 46%) and nodal metastases (91 vs. 67%; P < 0.001). Positive lavage was associated with a very poor prognosis: 3‐year survival was only 9% (95% CI 2–27%) when peritoneal cancer cells had been detected, whereas survival reached 50% (95% CI 42–59%) in patients with a negative cytology. In multivariate survival analysis, peritoneal cytology was an independent predictor of mortality when controlling for sex, age, site, histology, and nodal metastases, but not when adjusting also for depth of tumor invasion (RR of positive versus negative = 1.2, 95% CI 0.7–2.0). Similarly, the influence of peritoneal cytology on survival was no longer significant when univariate analysis was restricted to T3/T4 patients (RR = 1.5, 0.9–2.5).ConclusionsPositive peritoneal cytology was a marker of poor prognosis in gastric cancer patients. Nevertheless, peritoneal lavage did not increase the prognostic information already provided by the TNM staging system in this Italian series.
Factors Predicting Long‐term Responses to Splenctomy in Patients with Idiopathic Thrombocytopenic Purpura
Authors: Ojima Hitoshi , Kato Toshihide , Araki Kenichirou , Okamura Kaori , Manda Ryokuhei , Hirayama Isao , Hosouchi Yasuo , Nishida Yasuji , Kuwano Hiroyuki 
Published: March 2006

AbstractBackgroundIdiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder for which appropriate diagnostic treatments are uncertain. The response to splenectomy varies from 60% to 90%, and the remaining patients relapse and require further treatment. Therefore, it is important to predict the outcome of splenectomy before and after surgery. The objective of this study was to evaluate the efficacy of splenectomy in patients diagnosed with ITP.Materials and MethodsFrom 1988 to 2004, we splenectomized 32 patients with ITP; 17 underwent laparoscopic splenectomy (LS) and 15 underwent conventional open splenectomy (OS). For analysis, patients were separated retrospectively into two groups: the “responding group,” those who showed good outcomes with splenectomy, and the “non‐responding group,” those who did not show good outcomes with splenectomy. Blood samples were examined before and immediately after surgery (day 0) and on postoperative days (POD) 1, 3, 5, and 7.ResultsThe median follow‐up was 8.3 years (range: 1–16 years). The overall 5‐ and 10‐year survival rates after splenectomy were 96.9% (one death). The responding group included 24 patients (75%), and the non‐responding group included 7 (21.9%). Platelet counts in the responding group increased gradually until POD 7, and although platelet counts in the non‐responding group were almost constant until POD 5, they subsequently decreased until POD 7. Average platelet counts in the responding and non‐responding groups were 269 and 124 × 109/l on POD 7, respectively (P < 0.05). The pre‐ to post‐surgery ratio of platelet counts were almost the same as the result of the actual data. Platelet counts during the long‐term follow‐up for the responding and non‐responding groups were related to those noted on discharge.ConclusionsA high platelet count on POD 7 was associated with a good response to splenectomy, but age at surgery, the time interval between diagnosis and splenectomy, and prior responses to corticosteroid were not. We suggest that long‐term outcomes of splenectomy can easily be predicted by platelet counts on POD 7.