bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Inhibition of the Epidermal Growth Factor Receptor Pathway with Cetuximab and Erlotinib: A Phase I Study in Patients with Advanced Solid Malignancies
Authors: Guarino Michael J. , Schneider Charles J. , Hosford Martha A. , Brahmer Julie R. , Rudin Charles M. , Finckenstein Friedrich Graf , Philip-Norton Robyn E. , Lu Haolan , Weber Martin R. , Ettinger David S.
Published: February 2009

Purpose.

To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies.

Patients and Methods.

Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m2 i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity.

Results.

Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1–31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1–25.1 weeks).

Conclusion.

Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m2 i.v. weekly for cetuximab and 150 mg daily orally for erlotinib.
Oligodendrogliomas: Molecular Biology and Treatment
Authors: Bromberg Jacolien E. C. , van den Bent Martin J.
Published: February 2009

Learning Objectives

Evaluate the current challenges in the histological diagnosis of oligodendroglial tumors and apply best practices to optimize patient outcomes. Analyze the molecular alterations in different subsets of tumors with oligodendroglial morphology. Formulate treatment options for your patients with newly diagnosed and recurrent oligodendroglial tumors.

This article is available for continuing medical education credit at CME.TheOncologist.com.
Paleoecology of the early Eocene Willwood mammal fauna from the central Bighorn Basin, Wyoming
Authors: Chew Amy E.
Published: February 2009

The mammal fauna of the Willwood Formation, central Bighorn Basin, Wyoming, is ideal for paleoecological analysis because it is extensive, well studied, and continuously distributed over sediments representing the first 3 Myr of the early Eocene. The geology of the Bighorn Basin is also well known, providing a precise temporal framework and climatic context for the Willwood mammals. Previous analysis identified three “biohorizons,” based on simple counts of the first and last appearances of species. This study uses species diversity and appearance rates calculated from more extensive collections to approximate the ecological dynamic of the ancient fauna and assess whether the biohorizons were significant turnover events related to recently described climatic variation. Diversity and appearance data collected for this project are extensively corrected for uneven sampling, which varies by two orders of magnitude. Observed, standardized appearance and diversity estimates are subsequently compared with predicted background frequencies to identify significant variation. Important coincident shifts in the biotic parameters demonstrate that ecological change was concentrated in two discrete intervals ≤300 Kyr each that correspond with two of the original biohorizons. The intervals coincide with the onset and reversal of an episode of climate cooling identified directly from Bighorn Basin floras and sediments. Ecological changes inferred from the diversity and turnover patterns at and following the two biohorizons suggest short- and long-term faunal response to shifts in mean annual temperature on the order of 5–8°C.
The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer
Authors: Lanari Claudia , Lamb Caroline A , Fabris Victoria T , Helguero Luisa A , Soldati Rocío , Bottino María Cecilia , Giulianelli Sebastián , Cerliani Juan Pablo , Wargon Victoria , Molinolo Alfredo
Published: February 2009

More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). By contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent (HD), metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependence, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discuss the relevance of this model in comparison with other presently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.
The Use of Exercise-Related Mental Imagery by Middle-Aged Adults
Authors: Kim Bang Hyun , Giacobbi Peter R.
Published: February 2009

Exercise imagery is an emerging topic in health and exercise psychology research. Previous studies have found that exercise imagery may have cognitive and motivational effects on exercise behaviors. However, the research in exercise imagery has focused primarily on college students and the use of qualitative methods. Therefore, this study expanded previous research by using qualitative methods with middle-aged adults. Specifically, 30 middle-aged adults from 35 to 65 (M=48.13, SD=8.33) that included 11 males and 19 females were interviewed to examine when, where, what (content), and why (function) they used imagery focused on their exercise behaviors. By using grounded theory procedures, results revealed seven higher order themes: exercise technique images, appearance images, health outcome images, plan/strategy images, stress level/emotion images, confidence enhancing images, and energy/drive images. These results were consistent with previous research and theoretical frameworks in imagery. Certain quotes were chosen from the interviews to highlight each higher order theme. Some additional findings were the importance of health imagery, the thoughts of past images of self and comparing to present, making plans/strategies to motivate oneself to exercise, and the relationship between the content and functions of exercise imagery. Overall, this study represented a descriptive basis for research in exercise imagery by using grounded theory analysis and the development of a conceptual framework.
All in the Family: Mental Health Spillover Effects between Working Spouses
Authors: Fletcher Jason
Published: February 2009

It is well documented that mental health outcomes are correlated between spouses. There are several alternative hypotheses for this correlation, including both causal and non-causal pathways. In this paper, I use an instrumental variables/fixed effects approach to examine whether there is evidence that an individual's mental health status spills over on his or her spouse's mental health status. Results from the IV-FE specifications that use spousal job problems as an instrument are large in magnitude. In particular, spousal mental health status is estimated to have a greater influence on an individual's mental health status than his or her own mental health endowment and is similar in magnitude with his or her own physical health status. Although not conclusive, these findings suggest that within-family spillovers of mental illness could be economically important and that policies that reduce mental health problems for individuals likely have unmeasured benefits for their family members.
Legislative Conduct in Response to Executive Initiative: Unity among Political Blocs in Chile
Authors: Toro Sergio Y.
Published: February 2009

This paper seeks to investigate the behavior presented by the chamber of deputies, with regards to the bills which were presented by the executive power during the 20022006 legislative term. The author demonstrates that one of the most relevant reasons that the government of Ricardo Lagos was able to successfully pass the bills it favored, was the high unity of the governmental party and the heterogeneous action of the opposition bloc. Thus, through the use of Roll Call Vote analysis, this article assigns each of the parties and coalitions a percentage point relative to its degree of approval to the Executive's initiatives. This method indicates that the "Renovacion Nacional" was a pivotal party, which fluctuated between supporting the ruling party and maintaining its stance as an opposition party.
Fatal Cases of Staphylococcus Aureus Pleural Empyema in Infants
Authors: Rougemont Anne-Laure , Buteau Chantal , Ovetchkine Philippe , Bergeron Cybèle , Fournet Jean-Christophe , Soglio Dorothée Bouron-Dal
Published: February 2009

Community-associated infections and especially pleural empyema due to Staphylococcus aureus are increasing worldwide. The virulence of staphylococcal strains is notably determined by different toxin expressing–genes, such as the Panton-Valentine leukocidin (PVL) gene found in S. aureus isolates obtained from pediatric necrotizing pneumonia samples. We describe 2 similar cases of infants with severe respiratory distress and death after an upper respiratory tract infection, having occurred in the same urban area during the same winter time. Necropsies performed between November 2006 and March 2007 revealed bronchopneumonia and an important pleural empyema, justifying the review of clinical charts and laboratory exams. A methicillin-sensitive S. aureus (MSSA) isolate carrying the PVL gene was identified in both cases. We have subsequently cared for an additional case in the same time interval with sudden death and similar pathological findings. No positive microbiological results were obtained, a negative finding possibly related to a 5-day antibiotics regimen. This report describes the pathological features of these cases and stresses the need to recognize PVL-positive S. aureus infections in young children. Finally, we believe that all lethal infections due to PVL-positive S. aureus, independently of the methicillin resistance profile, deserve a mandatory report to the provincial public health authorities.
PbS nanostructures synthesized via surfactant assisted mechanochemical route
Authors: Baláž Peter , Pourghahramani Parviz , Dutková Erika , Fabián Martin , Kováč Jaroslav , Šatka Alexander
Published: February 2009

PbS nanocrystals using surfactant assisted mechanochemical route has been successfully prepared. The methods of XRD, SEM, surface area and particle size measurements were used for nanocrystals characterization. The XRD patterns confirmed the presence of galena PbS (JCPDS 5–592) whatever treatment conditions were applied. The strong observable peaks indicate the highly crystalline nature in formation of PbS nanostructures where preferential crystal growth in the (200) direction after chelating agent (EDTANa2•2H2O) addition has been observed. The mean volume weighted crystallite size 4.9 nm and 35 nm has been calculated from XRD data using Williamson-Hall method for PbS synthesized without and/or with chelating agent, respectively corresponding with surface weighted crystallites sizes of 2.9 and 18.8 nm. The sample prepared without surfactant yields the smaller crystallites and the higher microstrain compared with surfactant assisted synthesis. The obtained results illustrate a possibility to manipulate crystal morphology by combining effect of milling and surfactant application.
Research in the Midst of Organized School Reform: Versions of Teacher Community in Tension
Authors: Craig Cheryl J.
Published: February 2009

Arising from a longitudinal study examining the influence of school reform on teachers’ knowledge communities and communities of knowing, this narrative inquiry traces the development of a workshop approach to reading and writing, principally through the introduction of a staff developer, to the school’s professional knowledge landscape and to the literacy teachers’ curriculum making over a 3-year period. While some of the school administrators perceived the trainer as building professional learning community through sharing knowledge, skills, and dispositions, the majority of the teachers, and some of the other administrators, appeared to view the staff developer, herself a teacher, as being in collusion with the principal (and vice versa) and as crossing the line concerning what teachers and their communities of knowing are able to tolerate. Different stories produced different visions of community, and a number of issues related to teacher development emerged. Disconnects among theory, practice, and policy surfaced.
Retirement Patterns and the Shortage of Anesthesiologists in Quebec and British Columbia
Authors: Tessler Michael J. , Shrier Ian , Steele Russell J.
Published: February 2009

We describe the practice profile of Quebec and British Columbia (BC) specialist anesthesiologists. All provincial health-care billings from Quebec and BC were obtained for the period from 1 January 1993 to 31 December 2002. We categorized the specialist anesthesiologists into one of three age categories (<51, 51–64, and 65+) and assigned a case complexity value (low, moderate, high) to every procedure billed. Anesthesiologists who continued working after age 65 provided anesthesia to fewer patients and for less complex surgery than those in the younger age groups. The end-of-career package introduced in Quebec in 1995 led to an overall reduction in the number of cared-for patients. Predictions of manpower shortages in anesthesia must be province specific and may fail to account for government policies or changes in practice. Consequently they are likely underestimates.
Synthesis, characterization and effect of microstructure on slurry erosion resistance of cast Fe-TiC composites
Authors: Manoj MK , Galgali RK , Nath SK , Ray S
Published: February 2009

Fe-TiC composites containing varying amounts of TiC particles have been synthesized by casting route. This is achieved by carbothermic reduction of ilmenite ore along with varying amount of steel scrap in a plasma reactor in one step. Three composites containing TiC particles varying from 4 to 9% have been prepared. Microstructures of composites show TiC particles in the matrix of transformed ledeburite (pearlite and cementite). Distribution of TiC particles has been found to be satisfactorily uniform and size varies from 2 to 3 microns. Composite having 9 vol% has shown non-uniform distribution of TiC particles and size variation from 2 to 8 microns. In 9% TiC composites, graphite flakes have also been found. It has also been observed that composite having TiC content greater than 9 % becomes very difficult to cast because of higher viscosity of the melt during pouring. These composites have been characterized by hardness measurement, optical microscopy, FESEM, and XRD. Hardness of these composites has been found to depend on vol.% of TiC and on the nature of the matrix. Slurry erosion test has shown higher erosion resistance in castings with lesser porosity, optimum vol% of TiC, and in the matrix of transformed ledeburite. Presence of graphite in the matrix lowers slurry erosion resistance of the cast composite. Keywords: Fe-TiC composite, Carbothermic reduction, Graphite, Slurry wear. Â Â  doi:10.3329/jname.v5i1.1825 Journal of Naval Architecture and Marine Engineering Vol. 5, No.Â 1 (June, 2008) 19-26.
Performance of Three Reflectance Calibration Methods for Airborne Hyperspectral Spectrometer Data
Authors: Miura Tomoaki , Huete Alfredo R.
Published: February 2009

In this study, the performances and accuracies of three methods for converting airborne hyperspectral spectrometer data to reflectance factors were characterized and compared. The “reflectance mode (RM)” method, which calibrates a spectrometer against a white reference panel prior to mounting on an aircraft, resulted in spectral reflectance retrievals that were biased and distorted. The magnitudes of these bias errors and distortions varied significantly, depending on time of day and length of the flight campaign. The “linear-interpolation (LI)” method, which converts airborne spectrometer data by taking a ratio of linearly-interpolated reference values from the preflight and postflight reference panel readings, resulted in precise, but inaccurate reflectance retrievals. These reflectance spectra were not distorted, but were subject to bias errors of varying magnitudes dependent on the flight duration length. The “continuous panel (CP)” method uses a multi-band radiometer to obtain continuous measurements over a reference panel throughout the flight campaign, in order to adjust the magnitudes of the linear-interpolated reference values from the preflight and post-flight reference panel readings. Airborne hyperspectral reflectance retrievals obtained using this method were found to be the most accurate and reliable reflectance calibration method. The performances of the CP method in retrieving accurate reflectance factors were consistent throughout time of day and for various flight durations. Based on the dataset analyzed in this study, the uncertainty of the CP method has been estimated to be 0.0025 ± 0.0005 reflectance units for the wavelength regions not affected by atmospheric absorptions. The RM method can produce reasonable results only for a very short-term flight (e.g., < 15 minutes) conducted around a local solar noon. The flight duration should be kept shorter than 30 minutes for the LI method to produce results with reasonable accuracies. An important advantage of the CP method is that the method can be used for long-duration flight campaigns (e.g., 1-2 hours). Although this study focused on reflectance calibration of airborne spectrometer data, the methods evaluated in this study and the results obtained are directly applicable to ground spectrometer measurements.
Familial placement and relations of Rehmannia and Triaenophora (Scrophulariaceae s.l.) inferred from five gene regions
Authors: Xia Zhi , Wang Yin‐Zheng , Smith James F.
Published: February 2009

Accurate classification systems based on evolution are imperative for biological investigations. The recent explosion of molecular phylogenetics has resulted in a much improved classification of angiosperms. More than five phylogenetic lineages have been recognized from Scrophulariaceae sensu lato since the family was determined to be polyphyletic; however, questions remain about the genera that have not been assigned to one of the segregate families of Scrophulariaceae s.l. Rehmannia Liboschitz and Triaenophora Solereder are such genera with uncertain familial placement. There also is debate whether Triaenophora should be segregated from Rehmannia. To evaluate the phylogenetic relations between Rehmannia and Triaenophora, to find their closest relatives, and to verify their familial placement, we conducted phylogenetic analyses of the sequences of one nuclear DNA (ITS) region and four chloroplast DNA gene regions (trnL‐F, rps16, rbcL, and rps2) individually and combined. The analyses showed that Rehmannia and Triaenophora are each strongly supported as monophyletic and together are sister to Orobanchaceae. This relation was corroborated by phytochemical and morphological data. Based on these data, we suggest that Rehmannia and Triaenophora represent the second nonparasitic branch sister to the remainder of Orobanchaceae (including Lindenbergia).
Is Oligomeris (Resedaceae) indigenous to North America? Molecular evidence for a natural colonization from the Old World
Authors: Martín‐Bravo Santiago , Vargas Pablo , Luceño Modesto
Published: February 2009

Oligomeris linifolia constitutes one of the few examples of intercontinental disjunctions at the species level between the arid regions of the Old World and SW North America. The status of the American populations has been obscure, with some authors considering the populations to be introduced, whereas others believe them to be native. To clarify these conflicting opinions, we performed phylogeographic analyses using nuclear ribosomal ITS and plastid trnL‐F and rps16 sequences to infer the origin of the disjunct American populations. Two independent molecular clock approaches based on ITS and cpDNA sequences (rbcL, matK, trnL‐F) were used to estimate a divergence time of O. linifolia. Low levels of sequence divergence and estimates of relatively recent splits of Oligomeris lineages disagree with the vicariance hypotheses traditionally suggested to account for New–Old World disjunctions. In addition, significant genetic differentiation of American populations does not indicate a recent anthropogenic introduction. Morphological uniformity and the sharing of haplotypes between disjunct populations, together with the molecular clock results, suggest that a long‐distance dispersal event from the Old Word to SW North America may have taken place during the Quaternary, in spite of limited dispersal mechanisms in Oligomeris.
Association studies and gene expression analyses of the DISC1‐interacting molecules, pericentrin 2 (PCNT2) and DISC1‐binding zinc finger protein (DBZ), with schizophrenia and with bipolar disorder
Authors: Anitha Ayyappan , Nakamura Kazuhiko , Yamada Kazuo , Iwayama Yoshimi , Toyota Tomoko , Takei Nori , Iwata Yasuhide , Suzuki Katsuaki , Sekine Yoshimoto , Matsuzaki Hideo , Kawai Masayoshi , Thanseem Ismail , Miyoshi Ko , Katayama Taiichi , Matsuzaki Shinsuke , Baba Kousuke , Honda Akiko , Hattori Tsuyoshi , Shimizu Shoko , Kumamoto Natsuko , Kikuchi Mitsuru , Tohyama Masaya , Yoshikawa Takeo , Mori Norio
Published: February 2009

Disrupted‐in‐Schizophrenia 1 (DISC1) and its molecular cascade have been implicated in the pathophysiology of major psychoses. Previously, we identified pericentrin 2 (PCNT2) and DISC1‐binding zinc finger protein (DBZ) as binding partners of DISC1; further, we observed elevated expression of PCNT2 in the postmortem brains and in the lymphocytes of bipolar disorder patients, compared to controls. Here, we examined the association of PCNT2 with schizophrenia in a case–control study of Japanese cohorts. We also examined the association of DBZ with schizophrenia and with bipolar disorder, and compared the mRNA levels of DBZ in the postmortem brains of schizophrenia, bipolar and control samples. DNA from 180 schizophrenia patients 201 controls were used for the association study of PCNT2 and DBZ with schizophrenia. Association of DBZ with bipolar disorder was examined in DNA from 238 bipolar patients and 240 age‐ and gender‐matched controls. We observed significant allelic and genotypic associations of the PCNT2 SNPs, rs2249057, rs2268524, and rs2073380 (Ser/Arg) with schizophrenia; the association of rs2249057 (P = 0.002) withstand multiple testing correction. Several two SNP‐ and three SNP‐haplotypes showed significant associations; the associations of haplotypes involving rs2249057 withstand multiple testing correction. No associations were observed for DBZ with schizophrenia or with bipolar disorder; further, there was no significant difference between the DBZ mRNA levels of control, schizophrenia and bipolar postmortem brains. We suggest a possible role of PCNT2 in the pathogenesis of schizophrenia. Abnormalities of PCNT2, the centrosomal protein essential for microtubule organization, may be suggested to lead to neurodevelopmental abnormalities. © 2009 Wiley‐Liss, Inc.
Self‐Assembly of Fivefold‐Symmetric Molecules on a Threefold‐Symmetric Surface
Authors: Guillermet Olivier , Niemi Eeva , Nagarajan Samuthira , Bouju Xavier , Martrou David , Gourdon André , Gauthier Sébastien
Published: February 2009

Buckybowls: Mithilfe von Rastertunnelmikroskopie und Strukturberechnungen wurde die Adsorption von Penta‐tert‐butylcorannulen (mit fünfzähliger Symmetrie) auf einer Cu(111)‐Oberfläche (mit dreizähliger Symmetrie) untersucht. Abhilfe wegen der nicht passenden Symmetrien schafft die Bildung von Untereinheiten aus drei Molekülen mit dreizähliger Symmetrie, die zusammen mit Einzelmolekülen die Ebene nahezu perfekt bedecken (siehe Bild).

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Erdbautechnische Untersuchungen zur Qualitätssicherung der 1000 km langen Hochgeschwindigkeitsstrecke Wuhan–Guangzhou
Authors: Tang Xiaoguang , Hu Yifeng
Published: February 2009

Zur Qualitätssicherung des Erdbaus für die 1000km lange Hochgeschwindigkeitsstrecke Wuhan–Guangzhou (WGPDL) in China wurden umfangreiche erdbautechnische Untersuchungen durchgeführt. Dabei wurden sowohl die Chinesischen Vorschriften als auch die deutschen Standards bzw. Erfahrungen für den Erdbau der HGS herangezogen. In dieser Veröffentlichung werden exemplarisch die Ergebnisse der Eignungsuntersuchungen für ein natürliches Schüttmaterial hinsichtlich der Dauerhaftigkeit unter vorgesehenen Einwirkungen vorgestellt. Danach werden die Ergebnisse der vergleichenden Labor‐ und Felduntersuchungen von vier ausgewählten Schüttmaterialien für die Prüfparameter der Dichte und Tragfähigkeit beschrieben. Mit den Erkenntnissen aus diesen Untersuchungen wurde eine wesentliche Basis für die Qualitätssicherung des Erdbaus in WGPDL geschaffen (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Modeling a granule‐based anaerobic ammonium oxidizing (ANAMMOX) process
Authors: Ni Bing‐Jie , Chen You‐Peng , Liu Shao‐Yang , Fang Fang , Xie Wen‐Ming , Yu Han‐Qing
Published: February 2009

A mathematical model was developed to describe the anaerobic ammonium oxidation (ANAMMOX) process in a granular upflow anaerobic sludge blanket (UASB) reactor. ANAMMOX granules were cultivated in the UASB reactor by seeding aerobic granules. The granule‐based reactor had a great N‐loading resistant capacity. The model simulation results on the 1‐year reactor performance matched the experimental data well. The yield coefficient for the growth and the decay rate coefficient of the ANAMMOX granules were estimated to be 0.164 g COD g−1 N and 0.00016 h−1, respectively. With this model, the effects of process parameters on the reactor performance were evaluated. Results showed that the optimum granule diameter for the maximum N‐removal should be between 1.0 and 1.3 mm and that the optimum N loading rate should be 0.8 kg N m−3 d−1. In addition, the substrate micro‐profiles in the ANAMMOX granules were measured with a microelectrode to explore the diffusion dynamics within the granules, and the measured profiles matched the predicted results well. Biotechnol. Bioeng. 2009;103: 490–499. © 2009 Wiley Periodicals, Inc.
Refolding of lactate dehydrogenase by zeolite beta
Authors: Togashi Hideaki , Nara Takayuki , Sekikawa Chisato , Kawakami Masayuki , Yaginuma Nakatsugu , Tsunoda Tatsuo , Sakaguchi Kengo , Mizukami Fujio
Published: February 2009

We used zeolite beta as an adsorbing matrix to refold recombinant lactate dehydrogenase (LDH) protein collected as an insoluble aggregate from a bacterial expression system. The adsorption isotherm revealed that 1 g of zeolite adsorbed 200 mg of denatured LDH solubilized with a buffer containing 6 M of guanidine hydrochloride. The pH of the buffer had little effect on the adsorption, but this property was abolished by preincubation of the zeolite with polyethylene glycol (PEG) in a weight ratio of 1:10. These data suggest that the adsorption of LDH depends on the hydrophobicity of the zeolite surface, and that the adsorption of PEG to zeolite is sufficient to release LDH from its surface. LDH was thus released by refolding buffer containing PEG and arginine, and soluble LDH was obtained in its active enzymatic form. The addition of arginine dramatically increased the yield of LDH in a dose‐dependent manner. The overall refolding efficiency was optimized to 35%. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Can shear stress direct stem cell fate?
Authors: Stolberg Sarah , McCloskey Kara E.
Published: February 2009

Mechanical forces are important signals in the development and function of the heart and lung, growth of skin and muscle, and maintenance of cartilage and bone. The specific mechanical force “shear stress” has been implicated as playing a critical role in the physiological responses of blood vessels through endothelial cell signaling. More recently, studies have shown that shear stress can induce differentiation of stem cells toward both endothelial and bone‐producing cell phenotypes. This review will highlight current data supporting the role of shear stress in stem cell fate and will propose potential mechanisms and signaling cascades for transducing shear stress into a biological signal. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Observing Proteins as Single Molecules Encapsulated in Surface‐Tethered Polymeric Nanocontainers
Authors: Rosenkranz Tobias , Katranidis Alexandros , Atta Diaa , Gregor Ingo , Enderlein Jörg , Grzelakowski Mariusz , Rigler Per , Meier Wolfgang , Fitter Jörg
Published: February 2009

Protein unfolding inside immobilized polymerosomes: One of the most interesting properties of polymeric vesicles is their remarkable stability against extreme temperatures and osmotic stress, and their longevity even under harsh environmental conditions. We have demonstrated, in an application on protein folding, that surface‐tethered polymerosomes are suitable for performing time‐resolved single molecule studies with encapsulated proteins, as illustrated here.

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Immobilizing biomolecules provides the advantage of observing them individually for extended time periods, which is impossible to accomplish for freely diffusing molecules in solution. In order to immobilize individual protein molecules, we encapsulated them in polymeric vesicles made of amphiphilic triblock copolymers and tethered the vesicles to a cover slide surface. A major goal of this study is to investigate polymeric vesicles with respect to their suitability for protein‐folding studies. The fact that polymeric vesicles possess an extreme stability under various chemical conditions is supported by our observation that harsh unfolding conditions do not perturb the structural integrity of the vesicles. Moreover, polymerosomes prove to be permeable to GdnHCl and, thereby, ideally suited for unfolding and refolding studies with encapsulated proteins. We demonstrate this with encapsulated phosphoglycerate kinase, which was fluorescently labeled with Atto655, a dye that exhibits pronounced photoinduced electron transfer (PET) to a nearby tryptophan residue in the native state. Under unfolding conditions, PET was reduced, and we monitored alternating unfolding and refolding conditions for individual encapsulated proteins.
Beyond Molecular Beacons: Optical Sensors Based on the Binding‐Induced Folding of Proteins and Polypeptides
Authors: Oh Kenneth J. , Cash Kevin J. , Plaxco Kevin W.
Published: February 2009

A beacon in the night! The binding‐induced folding of otherwise unfolded biopolymers may prove a generic signal‐transduction mechanism for protein‐ and polypeptide‐based biosensors. An example of such a biosensor is illustrated here.

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Many polypeptides and small proteins can be readily engineered such that they only fold upon binding a specific target ligand. This approach couples target recognition with a considerable change in polymer structure and dynamics. Recent years have seen the development of a number of biosensors that couple these large changes to readily measurable optical (fluorescent) outputs. These sensors afford the detection of a wide variety of macromolecular targets including proteins, polypeptides, and nucleic acids. Here we describe the design of such biosensors, from the first iterations as protein engineering experiments, to the development of biosensors targeting a range of protein and nucleic acid targets.
Insight Into the Defects of Cage‐Type Silica Mesoporous Crystals with Fd$\bar 3$m Symmetry: TEM Observations and a New Proposal of “Polyhedron Packing” for the Crystals
Authors: Han Lu , Sakamoto Yasuhiro , Che Shunai , Terasaki Osamu
Published: February 2009

The many faces of crystals: Silica mesoporous crystals were synthesized by using a co‐structure directing method. Structural defects in the crystals with Fd$\bar 3$m symmetry—described as tetrahedrally close‐packed and consisting of 512 and 51264 polyhedra—were found (see figure). These defects were explained through the use of simulated TEM images. The defect formation is also discussed.

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Silica mesoporous crystals were synthesized by using a gemini cationic surfactant (C18‐3‐1) as the directing agent, carboxyethylsilanetriol sodium salt as the co‐structure directing agent (CSDA), and varying amounts of HCl. By using transmission electron microscopy (TEM) we observed 1) a structural change from the close‐packed structures of spherical micelles—face‐centered cubic (Fm$\bar 3$m) and hexagonal close‐packed (P63/mmc)—to Fd$\bar 3$m structures with an increase of HCl and 2) a few structural defects in the crystals with Fd$\bar 3$m symmetry. The structure of a crystal with Fd$\bar 3$m symmetry is described as one of the tetrahedrally close‐packed (tcp) structures consisting of 512 and 51264 polyhedra. The observed TEM images of the structural defects were explained well through use of simulated TEM images by introducing new 13–15 polyhedra comprising 51262, 51263, 4151062, 425865, and 4151064, which have been observed in bubbles by Matzke. The mesostructural changes and defect formation are discussed in terms of the hardness of micelles composed of surfactant/CSDA/silica species that have formed through a change of the interaction between the surfactant and CSDA, which causes the micelles to change from a regime of close‐packing to one of minimum‐area packing.
TiO2‐Modified Macroporous Silica Foams for Advanced Enrichment of Multi‐Phosphorylated Peptides
Authors: Wan Jingjing , Qian Kun , Qiao Liang , Wang Yunhua , Kong Jilie , Yang Pengyuan , Liu Baohong , Yu Chengzhong
Published: February 2009

Enriching peptides: Novel TiO2‐modified macroporous materials (Ti‐MOSF, see figure) have been synthesized with high surface area, large pore volume, and functional surfaces that are rich in coordinatively unsaturated TiIV species, which can be applied in the specific extraction of phosphopeptides and which show a preferential capture of multi‐phosphorylated peptides with low detection limits and high selectivity.

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Stoichiometric Valence and Structural Valence—Two Different Sides of the Same Coin: “Bonding Power”
Authors: Liebau Friedrich , Wang Xiqu , Liebau Waltrude
Published: February 2009

Two valencies instead of one!Stoichiometric valence and structural valence are two distinct properties of atoms. The former,stoichV, is derived from the composition of a compound and has integer values; the latter,structV, depends on the structure of a compound and has non‐integer values. The scheme shows a representation of valence states of antimony and oxidation of SbIIIto SbV, as a function of the eccentricity parameterΦi.

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Recent studies use the term valence to describe two distinct aspects of the phenomenon bonding power of an atom. Measured in valence units, one valence term, the classical chemical valence, has integer values and is derived solely from the composition of a compound. The second one, used mainly by solid‐state physicists and crystallographers, has non‐integer values. It is determined from structure data, which are derived from diffraction experiments, spectroscopy, or quantum‐chemical calculations. To distinguish clearly between these two types of valencies, the descriptive termsstoichiometric valenceandstructural valenceand the respective symbolsstoichVandstructVshould be used. For the majority of crystalline structures, values ofstoichVandstructV, both measured in valence units, differ by less than 5 %. However, for p‐block atoms with one lone electron pair, differences betweenstoichVandstructVof up to 30 % have been reported.
Topology of Electron Charge Density for Chemical Bonds from Valence Bond Theory: A Probe of Bonding Types
Authors: Zhang Lixian , Ying Fuming , Wu Wei , Hiberty Philippe C. , Shaik Sason
Published: February 2009

Covalent, ionic, or something new?A new interpretation of the topology of the electron density at the bond critical point is proposed to characterize covalent, ionic, and charge‐shift bonding from the density point of view (see figure). The topological properties of the density representation confirm the reality of charge‐shift bonds, in which the covalent contribution is weak or repulsive, and most of the bonding is due to the covalent–ionic resonance energy.

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To characterize the nature of bonding we derive the topological properties of the electron charge density of a variety of bonds based on ab initio valence bond methods. The electron density and its associated Laplacian are partitioned into covalent, ionic, and resonance components in the valence bond spirit. The analysis provides a density‐based signature of bonding types and reveals, along with the classical covalent and ionic bonds, the existence of two‐electron bonds in which most of the bonding arises from the covalent–ionic resonance energy, so‐called charge‐shift bonds. As expected, the covalent component of the Laplacian at the bond critical point is found to be largely negative for classical covalent bonds. In contrast, for charge‐shift bonds, the covalent part of the Laplacian is small or positive, in agreement with the weakly attractive or repulsive character of the covalent interaction in these bonds. On the other hand, the resonance component of the Laplacian is always negative or nearly zero, and it increases in absolute value with the charge‐shift character of the bond, in agreement with the decrease of kinetic energy associated with covalent–ionic mixing. A new interpretation of the topology of the total density at the bond critical point is proposed to characterize covalent, ionic, and charge‐shift bonding from the density point of view.
Mechanism of Pd(OAc)2/Pyridine Catalyst Reoxidation by O2: Influence of Labile Monodentate Ligands and Identification of a Biomimetic Mechanism for O2 Activation
Authors: Popp Brian V. , Stahl Shannon S.
Published: February 2009

Aerobic oxidation: Mechanisms of aerobic oxidation of the PdII(OAc)2/pyridine catalyst system were evaluated by using density functional theory methods. The results reveal that labile monodentate ligands, such as pyridine, favor a catalyst reoxidation pathway that proceeds via Pd0, rather than direct reaction of O2 with a PdII–hydride intermediate (see scheme).

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The mechanism of catalyst oxidation by O2 in Pd‐catalyzed aerobic oxidation reactions has been the subject of considerable debate, particularly with respect to the reactivity of PdII–hydride species. Here, we describe the use of unrestricted DFT computational methods to investigate the mechanism of catalyst reoxidation with the Pd(OAc)2/pyridine catalyst system, one of the most widely used catalysts. These studies probe four different pathways for the formation of a PdII–hydroperoxide species from the reaction of O2 from the corresponding PdII–hydride [(py)nPdII(H)OAc]: 1) a homolytic pathway involving hydrogen‐atom abstraction by O2; 2) AcOH reductive elimination to yield a Pd0 species that subsequently reacts with O2; 3) migratory insertion of O2 into a PdH bond; and 4) oxidative addition of O2 to PdII to yield a PdIV(η2‐peroxo) species. In contrast to previous studies of reactions between O2 and Pd–hydride species, the reductive‐elimination pathway (mechanism 2) is significantly more favorable than any of the other pathways. This outcome is traced to the presence of labile ligands (pyridine) that can readily dissociate from Pd to enable the hydride and acetate ligands to occupy cis‐coordination sites. These results strongly support the involvement of Pd0 as an intermediate in the catalytic cycle. Investigations of the mechanism of the reaction of O2 with the Pd0 intermediate revealed a novel, previously unrecognized mechanism that yields a Pd–OOH product without proceeding through the intermediacy of a PdII(η2‐peroxo) species. This mechanism resembles pathways commonly observed in biological O2 activation and suggests that noble‐metal and biological oxidation mechanisms may be more similar than previously appreciated.
Mesoporous Nanofibers from Dual Structure‐Directing Agents in AAO: Mesostructural Control and their Catalytic Applications
Authors: Lee Kyung Jin , Min Sa Hoon , Jang Jyongsik
Published: February 2009

Control yourself! The mesoporous silica nanofibers (MSNFs) from dual structure‐directing agents were fabricated inside the pores of porous alumina (AAO, see figure) by using vapor phase synthesis. The pore structures could be controlled to form a range of structures from mesocellular foams to cylindrical mesopores with long‐range order by adding cationic cosurfactants.

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Transportprozesse von Schüttungen aus Biomasse und Pyrolysaten im Drehrohr
Authors: Gómez A. , Klose W.
Published: February 2009

Die Transportprozesse und die Verweilzeit von Schüttungen aus Biomasse und Pyrolysaten werden im einbautenlosen Drehrohr durch die Bestimmung der charakteristischen Winkel der Schüttungen untersucht. Zusätzlich werden die Einflüsse der Anwendung eines Wehres am Austritt des Reaktors auf die Transportprozesse und Verweilzeit ausgewertet. Die Nutzung von Wehren ermöglicht für die gleichen Prozessbedingungen die Zunahme des Füllungsgrades im Reaktor. Alle Versuche erfolgen bei Raumtemperatur.
Use of graded exercise testing in assessing the hypertensive patient
Authors: Millar‐Craig M. W. , Balasubramanian V. , Mann S. , Raftery E. B.
Published: February 2009

Twenty‐five patients with suspected hypertension were studied using the “Oxford” continuous intra‐arterial blood pressure recording technique. Each patient carried out graded exercise on a bicycle ergometer, using a standard protocol, and then underwent a fully ambulatory 24‐h outpatient blood pressure recording. Using computer analysis, ambulatory blood pressure in each patient was characterised by measuring the mean daytime systolic and diastolic pressures. Exercise was found to be associated with a characteristic increase in systolic and diastolic blood pressure. Submaximal and maximal exercise blood pressures were shown to correlate strongly with ambulatory blood pressure. A much weaker correlation was found between clinic and ambulatory blood pressure. These findings suggest that the blood pressure response to exercise may be a better indicator of elevated blood pressure than a casual clinic blood pressure in individual borderline subjects.
Severe mitral stenosis secondary to massive calcification of the mitral annulus with unusual echocardiographic manifestations
Authors: Ramirez J. , Flowers N. C.
Published: February 2009

In mitral annular calcifications, hemodynamic documentation of a significant diastolic gradient across the mitral valve has been rarely demonstrated, and then only with the associated finding of a small left ventricular cavity with hypertrophic left ventricular wall. We present a patient with severe mitral annular calcification, with a significant diastolic gradient and unusual echocardiographic manifestations which include a densely calcified mitral valve annulus with anterior mitral valve leaflets consistent with what is seen in patients with mitral stenosis. When recordings were made immediately below the mitral valve annulus at the free edge of the mitral valve, its leaflets were seen departing in opposite directions, certainly not suggestive of outflow obstruction of the left atrium. Although in previous studies it has been suggested that mitral stenosis does not exist in the presence of mitral annulus calcification, our present report indicates that significant diastolic gradients can be found in patients with mitral annular calcifications. Because of the predominance of this condition in the elderly population, it is suggested that a more aggressive approach be taken in those patients in whom it is warranted by clinical circumstance.
Long‐term results of coronary artery bypass surgery for unstable angina: incidence of mortality, myocardial infarction, and angina resumption
Authors: Davidson D. M. , Lamb I. , Schroeder J. S.
Published: February 2009

To determine if routine treadmill testing would be helpful in identifying patients at high risk for subsequent events, the first 81 patients to undergo coronary artery bypass0 surgery for unstable angina pectoris at Stanford University Medical Center were reevaluated at four intervals after surgery. Evaluations, including assessment of angina pectoris and a treadmill test, were done at mean times of 18,40, and 72 months after surgery. At a mean time of 90 months postoperatively, angina status was determined in survivors. The prevalence of angina rose from 19% during the first year to 53% during the fourth and fifth postoperative years. Cardiac deaths and myocardial infarctions were frequent during the first postoperative year, and were more frequent in patients with three‐vessel disease and those with one or more severely narrowed coronary arteries which were not bypassed. Cardiac events were rare between 12 and 36 months after operation; clinical and treadmill variables did not predict these events. During the fourth and subsequent postoperative years, the incidence of cardiac events increased. While the presence of stable angina pectoris was the clinical variable most useful prognostically, treadmill testing added additional independent prognostic information (p<0.0001). During the intervals between visits 1 and 2, and visits 2 and 3, cardiac events were ten times more frequent in persons with a maximal heart rate of 130 beats/min or less on the treadmill at 18 and 40 months.

We conclude that the prevalence of angina increased steadily during the first 5 postoperative years. Myocardial infarction and cardiac death rates were high during the first postoperative year, low during the second and third postoperative years, and then began to rise thereafter. The early events were more frequent in persons with three‐vessel disease and one or more severely narrowed coronary arteries which were unbypassed. The late events were more frequent in persons with a maximal heart rate of 130 beats/min or less on treadmill exercise testing. No other clinical or treadmill variables added additional independent prognostic information.