bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypophosphatasia: Nonlethal disease despite skeletal presentation in utero (17 new cases and literature review)
Authors: Wenkert Deborah , McAlister William H , Coburn Stephen P , Zerega Janice A , Ryan Lawrence M , Ericson Karen L , Hersh Joseph H , Mumm Steven , Whyte Michael P
Published: June 2011

Hypophosphatasia (HPP) is caused by deactivating mutation(s) within the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Patients manifest rickets or osteomalacia and dental disease ranging from absence of skeletal mineralization in utero to only loss of adult dentition. Until recently, HPP skeletal disease in utero was thought to always predict a lethal outcome. However, several reports beginning in 1999 emphasized a benign prenatal form of HPP (BP-HPP) where skeletal disease detected in utero had a mild postnatal course. Here we describe prenatal and postnatal findings of 17 additional BP-HPP patients among our 178 pediatric HPP patients. Their findings are compared with those of their siblings with HPP, carrier parents, and others with identical TNSALP mutations. New information concerning 7 previously published BP-HPP patients accompanies a review of the HPP literature. Among our 17 BP-HPP patients, prenatal ultrasound showed normal chest or abdominal circumferences where recorded. Sometimes, poor skeletal mineralization, fetal crowding, and third-trimester improvement were observed. Postnatally, extremity bowing further improved (13 patients). BP-HPP severity postnatally spanned the “infantile” to “odonto” HPP phenotypes, resembling our patients who harbored identical TNSALP mutation(s). Eight had autosomal dominant (AD) and 9 had autosomal recessive (AR) BP-HPP. Fourteen of our 15 mothers were HPP carriers or affected. Of the 41 cumulative BP-HPP patients (24 literature cases meriting a BP-HPP diagnosis since 1996 plus our 17 patients), 63% had AR BP-HPP. Maternally transmitted HPP involved 11 of the 13 total AD BP-HPP probands (p = 0.01), supporting a maternal in utero effect on the baby. Fetal crowding, normal fetal mineralization and chest size, and TNSALP heterozygosity seem to identify BP-HPP. However, bowed fetal long bones with AR HPP, specific TNSALP mutations, or poor skeletal mineralization before the third trimester do not reliably diagnose HPP lethality. © 2011 American Society for Bone and Mineral Research
DockoMatic: Automated peptide analog creation for high throughput virtual screening
Authors: Jacob Reed B. , Bullock Casey W. , Andersen Tim , McDougal Owen M.
Published: June 2011

The purpose of this manuscript is threefold: (1) to describe an update to DockoMatic that allows the user to generate cyclic peptide analog structure files based on protein database (pdb) files, (2) to test the accuracy of the peptide analog structure generation utility, and (3) to evaluate the high throughput capacity of DockoMatic. The DockoMatic graphical user interface interfaces with the software program Treepack to create user defined peptide analogs. To validate this approach, DockoMatic produced cyclic peptide analogs were tested for three‐dimensional structure consistency and binding affinity against four experimentally determined peptide structure files available in the Research Collaboratory for Structural Bioinformatics database. The peptides used to evaluate this new functionality were alpha‐conotoxins ImI, PnIA, and their published analogs. Peptide analogs were generated by DockoMatic and tested for their ability to bind to X‐ray crystal structure models of the acetylcholine binding protein originating from Aplysia californica. The results, consisting of more than 300 simulations, demonstrate that DockoMatic predicts the binding energy of peptide structures to within 3.5 kcal mol−1, and the orientation of bound ligand compares to within 1.8 Å root mean square deviation for ligand structures as compared to experimental data. Evaluation of high throughput virtual screening capacity demonstrated that Dockomatic can collect, evaluate, and summarize the output of 10,000 AutoDock jobs in less than 2 hours of computational time, while 100,000 jobs requires approximately 15 hours and 1,000,000 jobs is estimated to take up to a week. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Speaking freely: my experiences in individual psychotherapies, group therapies, and growth groups
Authors: Curtis Rebecca Coleman
Published: June 2011

This article traces the author's experiences in sensitivity, Tavistock, and psychotherapy groups, an experience in individual psychotherapy, and two experiences in psychoanalysis. Group work was very helpful in learning how the author came across to others in general and in improving the author's ways of being helpful to others. Although the experience was valuable, difficulties emerged in the first psychoanalysis, largely because of the psychoanalyst's belief that psychoanalysis was the best form of treatment for everyone. Desiring a variety of approaches, the author undertook a second analysis with more of an integrative and intuitive therapist, which worked better for her. Lasting lessons are shared from this series of personal therapy experiences. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–12, 2011.
Behavior of 3(2‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones and 3(3‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones as alkylating agents: A comparative study
Authors: Abou Elmagd Wael S. I.
Published: June 2011

3(2‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones and 3(3‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones were prepared as a mixture of (E) and (Z) stereoisomers by condensing pyridine‐2‐carboxaldehyde and pyridine‐3‐carboxaldehyde with 3‐aroylpropionic acids. The reaction of the furanones 6 and 7 with anhydrous aluminium chloride in benzene led to the formation of 4,4‐diaryl‐1‐(2‐pyridinyl)but‐1,3‐diene (8) and 4,4‐diaryl‐1‐(3‐pyridinyl)but‐1,3‐diene (9) as mixtures of geometrical (E,E‐ and E,Z‐) stereoisomers via an intermolecular alkylation mode. When the reaction was carried out in tetrachloroethane as a solvent, the reaction of 6 gave 5‐arylquinoline‐7‐carboxylic acid via intramolecular alkylation mode. This may be considered as a novel method for the synthesis of quinoline derivatives. J. Heterocyclic Chem., (2011).
On the evolution of arterial vascular patterns of tetrapods
Authors: Farmer C.G.
Published: June 2011

The factors that explain the diverse arrangement of the major arteries of tetrapods are not known. Here, I aim to illuminate some of the underpinnings of these patterns. I review the variation in the sauropsid left, right, and dorsal aortae regarding the origin of the gastrointestinal blood vessels and the relative diameters of left and right aortae where they join together to form the dorsal aorta. I focus on these features because the quality of blood that flows through these aortae can vary depending on the state of cardiac shunting and the size of the vessel can provide insight into the quantity of blood borne by the vessels. I then place the information in a phyletic, historical, and ecological context. The plesiomorphic pattern is for the gastrointestinal vessels to arise as segmental arteries from the dorsal aorta, which is formed from the confluence of left and right aortae with similar diameters. The pattern is well conserved with only two major variations. First, in several clades of reptiles (testudines, crocodilians, lizards of the generaVaranusandHydrosaurus) a substantial portion of the gastrointestinal arteries arises from the left aorta, leaving the diameter of the left aorta smaller than the right at their confluence. I hypothesize that this vascular arrangement facilitates growth by allowing more alkaline blood to flow to the somatic (body wall) and appendicular circulations, which may promote bone deposition and inhibit resorption, whereas hypercapnic, acidic blood flows to the digestive viscera, which may provide CO2as a substrate for the synthesis of gastric acid, bicarbonate, fatty acids, glutamine, purine rings, as well as glucose from lactate. Second, in some snakes and lizards with snake‐like body forms, such as Amphisbaenidae, the diameters of left and right aortae are asymmetrical at their confluence with the left aorta exceeding the right, but in members of the amphibian order Gymnophiona the right generally exceeds the left. This condition is associated with asymmetrical development of the lungs. J. Morphol. 2011. © 2011 Wiley‐Liss, Inc.
Trends of Convective Available Potential Energy over the Indian region and its effect on rainfall
Authors: Murugavel P. , Pawar S. D. , Gopalakrishnan V.
Published: June 2011

Many studies in recent times have suggested that long‐term changes in Convective Available Potential Energy (CAPE) are associated with the changes in convective activity and atmospheric energy budget and, hence, the changes in CAPE could be used as a potential indicator of climate change. Here, we analyse daily radiosonde data of 32 stations over the Indian region from 1984 to 2008 (25 years), to study the climatology and long‐term changes in CAPE, lower troposphere moisture content and upper tropospheric temperature. Using gridded daily rainfall data over this region, the relationship between average CAPE and average rainfall as well as the trends in CAPE and its effect on rainfall pattern are also examined during different seasons of this region. All the coastal and island stations, as well as some stations in the foothills of the Himalayas, show higher values of CAPE compared to other inland stations. This study clearly demonstrates that CAPE values have been systematically increasing over most parts of the Indian region during last 25 years. The increase in CAPE is found to be due to increase in low‐level moisture content and decrease in upper level temperature over the last 25 years. The seasonal variations show that the CAPE is higher during the monsoon compared to pre‐monsoon or post‐monsoon seasons and it suggests that thermodynamic conditions favourable for high CAPE together with large‐scale dynamics are necessary for organized monsoon convections over this region. In comparison with a large increase in the all‐India average of CAPE during monsoon season, which is about 38 J Kg−1 year−1, the all‐India summer monsoon rainfall increases about 1.3 mm year−1. The systematic increasing trend in CAPE may be compensating for weakening of monsoon circulation and, thus, maintaining the monsoon rainfall over the Indian region. Copyright © 2011 Royal Meteorological Society
Multiple drought indices for agricultural drought risk assessment on the Canadian prairies
Authors: Sun Liu , Mitchell Scott W. , Davidson Andrew
Published: July 2011

A multi‐index drought (MID) model was developed to combine the strengths of various drought indices for agricultural drought risk assessment on the Canadian prairies, as related to spring wheat crop yield. The model automatically selects and combines optimum drought indices derived from the preceding and current months as they become available to better match the conditions (both spatially and temporally) where they work well. The cross‐validation results showed that (1) the prediction accuracy of the MID model is better than (or occasionally equal to) using any single drought index for all modelling stages, (2) drought indices derived from the recharge period are useful for early drought risk detection, (3) model prediction accuracy improved as the growing season progressed with the most accurate assessments at the beginning of August, and (4) the model performed best in the more arid locations in the southern prairies, which tend to have a more variable precipitation regime. The model assessment results provide the spatial intensity distribution of possible drought progression and recession before and during the growing season, and can be used with complementary information in agricultural drought risk management and mitigation strategies. Copyright © 2011 Royal Meteorological Society
Association between measures of trochlear morphology and structural features of patellofemoral joint osteoarthritis on MRI: The MOST study
Authors: Stefanik Joshua J. , Roemer Frank W. , Zumwalt Ann C. , Zhu Yanyan , Gross K. Douglas , Lynch John A. , Frey‐Law Laura A. , Lewis Cora E. , Guermazi Ali , Powers Christopher M. , Felson David T.
Published: June 2011

The sulcus angle has been widely used in the literature as a measure of trochlear morphology. Recently, lateral trochlear inclination and trochlear angle have been reported as alternatives. The purpose of this study was to determine the association between measures of trochlear morphology and patellofemoral joint (PFJ) cartilage damage and bone marrow lesions (BMLs). Nine hundred seven knees were selected from the Multicenter Osteoarthritis Study, a cohort study of persons aged 50–79 years with or at risk for knee OA. Trochlear morphology was measured using lateral trochlear inclination, trochlear angle, and sulcus angle on axial MRI images; cartilage damage and BMLs were graded on MRI. We determined the association between quartiles of each trochlear morphology variable with the presence or absence of cartilage damage and BMLs in the PFJ using logistic regression. The strongest associations were seen with lateral trochlear inclination and lateral PFJ cartilage damage and BMLs, with knees in the lowest quartile (flattened lateral trochlea) having more than two times the odds of lateral cartilage damage and BMLs compared to those in the highest quartile (p < 0.0001). Lateral trochlear inclination may be the best method for assessment of trochlear morphology as it was strongly association with structural damage in the PFJ. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:1–8, 2012
Revision of the Shoulder Normalization tests is required to include rhomboid major and teres major
Authors: Ginn K.A. , Halaki M. , Cathers I.
Published: June 2011

The four “Shoulder Normalization Tests” were found previously to be a parsimonious set of isometric tests that produce maximal voluntary isometric contractions (MVIC) in the supraspinatus, infraspinatus, subscapularis, trapezius, serratus anterior, deltoid, latissimus dorsi, and pectoralis major [Boettcher et al. (2008). J Orthop Res 26:1591–1597]. However, these tests have not been validated for rhomboid major and teres major. In the current study, these Shoulder Normalization Tests were evaluated and compared to three other tests that could possibly elicit maximum activity in rhomboid major and teres major: abduction/extension in 90° abduction; adduction at 90° abduction; and extension in 30° abduction. No statistical difference was found in the mean activation of rhomboid major and teres major in these additional MVIC tests compared to the Shoulder Normalization Tests. However, the extension MVIC test produced maxima for at least 50% of subjects in rhomboid major, teres major, and latissimus dorsi. We concluded that the original Shoulder Normalization Tests should be expanded to include the extension MVIC test. The EMG normalization reference value for any of the above muscles would be the maximum EMG level generated across these Revised Shoulder Normalization Tests. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1846–1849, 2011
Migration responses of outer and inner meniscus cells to applied direct current electric fields
Authors: Gunja Najmuddin J. , Dujari Divya , Chen Andrew , Luengo Alba , Fong Jason V. , Hung Clark T.
Published: June 2011

Injuries to the inner regions of the knee meniscus do not heal and can result in degenerative changes to the articular surface, ultimately leading to osteoarthritis. A possible stimulus to enhance meniscus healing is to use electric fields that induce galvanotaxis. In this study, a novel characterization of the effects of direct current electric fields on migration characteristics of meniscus cells was performed. Primary and passaged inner and outer meniscus cells were exposed to varying electric field strengths from 0 to 6 V/cm. Cell migration was tracked using time lapse digital photography, and cell displacement and cathodal direct velocity were quantified. Cytoskeletal staining was performed to examine actin distribution and nuclear content. Cell adhesion strength was quantified as a function of wall shear stress. Meniscus cells exhibited cathodal migration and cell elongation perpendicular to the applied electric field accompanied by actin reorganization. Outer meniscus cells migrated quicker and exhibited lower adhesion strengths when compared to inner meniscus cells. Passaged cells exhibited higher migration characteristics when compared to primary cells. Overall, this study demonstrated that electric fields can significantly enhance and direct meniscus cell migration and suggests the potential for their incorporation in strategies of meniscus repair and tissue engineering. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:103–111, 2012
Raman spectroscopy in the diagnosis of the wall painting History of Concepción, Chile
Authors: Aguayo T. , Clavijo E. , Eisner F. , Ossa‐Izquierdo C. , Campos‐Vallette M. M.
Published: June 2011

Pigments and fresco‐related materials from the wall painting Historia de Concepción by Gregorio De La Fuente in Concepción, Chile were identified by Raman microscopy. The pigments were compared with those obtained from the artist's studio, and results allowed inference about subsequent interventions. Materials coming from processes such as salt efflorescence were also studied. The results contribute to the diagnosis of the current conservation state of the wall painting for its future restoration. Copyright © 2011 John Wiley & Sons, Ltd.
Identification of Acetobacter strains from Thai fermented rice products based on the 16S rRNA gene sequence and 16S–23S rRNA gene internal transcribed spacer restriction analyses
Authors: Tanasupawat Somboon , Kommanee Jintana , Yukphan Pattaraporn , Nakagawa Yasuyoshi , Yamada Yuzo
Published: June 2011

BACKGROUND: Fermented rice flour (khao‐khab, a non‐glutinous rice) and related products are Thai traditional products. The types of acetic acid bacteria (AAB) microflora in khao‐khab have not been reported. In this study, Acetobacter strains were isolated and identified based on the phenotypic and chemotaxonomic characteristics and molecular aspects.

RESULTS: Twenty‐five acetic acid bacteria isolated from fermented rice products and a starter for sweetened rice in Thailand by an enrichment culture approach, were assigned to the genus Acetobacter by phenotypic and chemotaxonomic characterisations. On the basis of the 16S rRNA gene sequence and 16S–23S rRNA gene ITS restriction analyses, 25 isolates were divided into six groups and identified at the specific level: (1) Group 1 included five isolates, which were identified as A. indonesiensis; (2) Group 2 included two isolates, which were identified as A. lovaniensis; (3) Group 3 included one isolate, which was identified as A. orientalis; (4) Group 4 included eleven isolates, which were identified as A. pasteurianus; (5) Group 5 included three isolates, which were identified as A. syzygii and (6) Group 6 included three isolates, which were unidentified and considered to constitute a new species.

CONCLUSION: Results revealed that various Acetobacter species were distributed in Thai fermented rice flour and related products. A novel Acetobacter species was isolated from the product. Copyright © 2011 Society of Chemical Industry
Salt‐induced modulation in inorganic nutrients, antioxidant enzymes, proline content and seed oil composition in safflower (Carthamus tinctorius L.)
Authors: Siddiqi Ejaz Hussain , Ashraf Muhammad , Al‐Qurainy Fahad , Akram Nudrat Aisha
Published: June 2011

BACKGROUND: Safflower (Carthamus tinctorius L.) has gained considerable ground as a potential oil‐seed crop. However, its yield and oil production are adversely affected under saline conditions. The present study was conducted to appraise the influence of salt (NaCl) stress on yield, accumulation of different inorganic elements, free proline and activities of some key antioxidant enzymes in plant tissues as well as seed oil components in safflower. Two safflower accessions differing in salt tolerance (Safflower‐33 (salt sensitive) and Safflower‐39 (salt tolerant)) were grown under saline (150 mmol L−1) conditions and salt‐induced changes in the earlier‐mentioned physiological attributes were determined.

RESULTS: Salt stress enhanced leaf and root Na+, Cl− and proline accumulation and activities of leaf superoxide dismutase, catalase and peroxidase, while it decreased K+, Ca2+ and K+/Ca2+ and Ca2+/Na+ ratios and seed yield, 100‐seed weight, number of seeds, as well as capitula, seed oil contents and oil palmitic acid. No significant effect of salt stress was observed on seed oil α‐tocopherols, stearic acid, oleic acid or linoleic acid contents. Of the two safflower lines, salt‐sensitive Safflower‐33 was higher in leaf and root Na+ and Cl−, while Safflower‐39 was higher in leaf and root K+, K+/Ca2+ and Ca2+/Na+ and seed yield, 100‐seed weight, catalase activity, seed oil contents, seed oil α‐tocopherol and palmitic acid. Other attributes remained almost unaffected in both accessions.

CONCLUSION: Overall, high salt tolerance of Safflower‐39 could be attributed to Na+ and Cl− exclusion, high accumulation of K+ and free proline, enhanced CAT activity, seed oil α‐tocopherols and palmitic acid contents. Copyright © 2011 Society of Chemical Industry
Epigallocatechin‐3‐gallate induces growth inhibition and apoptosis of human anaplastic thyroid carcinoma cells through suppression of EGFR/ERK pathway and cyclin B1/CDK1 complex
Authors: Lim Young Chang , Cha Yun Yi
Published: July 2011

Background

Anaplastic thyroid carcinoma (ATC) is one of the most lethal cancers because of its aggressiveness and the lack of efficacious therapy. Epigallocatechin‐3‐gallate (EGCG), a major catechin in green tea, was shown to possess remarkable therapeutic potential against various types of human cancer cells in in vitro and in vivo models. The aim of this study was to investigate the effect of EGCG on the proliferation and apoptosis of ARO cells—human ATC cells.

Study design

Experimental study.

Methods

Human ATC cell line, ARO, was treated with EGCG. Cell viability was assessed by MTT assay. Inhibition of EGFR/MAPK pathway and cell cycle‐related proteins by EGCG were measured by Western blot analysis. In addition, cell cycle analysis was measured by flow cytometry.

Results

EGCG treatment inhibited the growth of ARO cells in a dose‐dependent manner. Furthermore, EGCG suppressed phosphorylation of EGFR, ERK1/2, JNK, and p38. These changes were associated with increased p21 and reduced cyclin B1/CDK1 expression. In addition, EGCG treatment increased the accumulation of sub‐G1 cell, activated caspase‐3 and cleaved PARP.

Conclusions

Taken together, EGCG inhibits cell proliferation and induces apoptosis via suppression of the EGFR/ERK pathway and cyclin B1/CDK1 complex in ATC cells.

J. Surg. Oncol. 2011; 104:776–780. © 2011 Wiley Periodicals, Inc.
Adjuvant Imatinib treatment after R0 resection for patients with high‐risk gastrointestinal stromal tumors: A median follow‐up of 44 months
Authors: Jiang Wei‐Zhong , Guan Guo‐Xian , Lu Hui‐Shan , Yang Ying‐Hong , Kang De‐Yong , Huang He‐Guang
Published: June 2011

Background

The optimal duration of Imatinib adjuvant treatment for patients with high‐risk gastrointestinal stromal tumors (GISTs) is uncertain.

Patients and Methods

A total of 90 patients with high‐risk GISTs after curative resection were recruited into this non‐randomized case–control study, including 35 having Imatinib adjuvant therapy and 55 having follow‐up alone. The recurrence‐free survival (RFS) was compared.

Results

After a median follow‐up of 44.0 months, a significantly reduced recurrence rate was observed in the treatment group than the control group (17.1% vs. 78.2%, P = 0.000). One‐year, 2‐year, and 3‐year RFS rates were 100% vs. 70.9%, 88.0% vs. 37.8%, and 88.0% vs. 27.5%, respectively; with a significant advantage for Imatinib adjuvant therapy versus the surgery only (P = 0.000, HR 0.122, 95% CI 0.041–0.363). Continuation Imatinib treatment further improved RFS by comparison with the interruption treatment (both 2‐year and 3‐year RFS were 95.8% vs. 63.6%, P = 0.011, HR 0.103, 95% CI 0.012–0.883). There were no serious adverse events in the adjuvant therapy group.

Conclusions

Imatinib Adjuvant therapy could significantly prolong the RFS of patients with high‐risk GISTs. Extended Imatinib adjuvant treatment strategy may further reduce the risk of relapse with a low drug resistance rate and toxicity profile. J. Surg. Oncol. 2011; 104:760–764. © 2011 Wiley Periodicals, Inc.
Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: A systematic review of survival, mortality, and morbidity
Authors: Gill Richdeep S. , Al‐Adra David P. , Nagendran Jeevan , Campbell Sandy , Shi Xinzhe , Haase Erika , Schiller Daniel
Published: June 2011

Gastric cancer with peritoneal carcinomatosis has an extremely poor prognosis, which may be improved with cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC). We systematically reviewed the literature regarding the efficacy of CRS + HIPEC in these patients. Electronic databases were searched from 2000 to 2010. Following CRS + HIPEC, overall median survival was 7.9 months and improved to 15 months for patients with completeness of cytoreduction scores of 0/1, however with a 30‐day mortality rate of 4.8%. J. Surg. Oncol. 2011; 104:692–698. © 2011 Wiley Periodicals, Inc.
Sulfonated cyclofructan 6 based stationary phase for hydrophilic interaction chromatography
Authors: Padivitage Nilusha L. T. , Armstrong Daniel W.
Published: June 2011

A stationary phase composed of silica‐bonded sulfonated cyclofructan 6 (SCF6) was synthesized and evaluated for hydrophilic interaction chromatography (HILIC). The separation of a large variety of polar compounds was evaluated on different versions of the stationary phase and compared with the same separations obtained with commercially available HILIC columns. The new columns successfully separate polar and hydrophilic compounds including β blockers, xanthines, salicylic acid related compounds, nucleic acid bases, nucleosides, maltooligosaccharides, water soluble vitamins and amino acids. The separation conditions were optimized by changing the composition and the pH of the mobile phase. The dependence of analyte retention on temperature was studied using van't Hoff plots. The newly synthesized stationary phase showed broad applicability for HILIC mode separations.
Retention of β blockers on native titania stationary phase
Authors: El Debs Racha , Abi Jaoudé Maguy , Morin Nicolas , Miege Cécile , Randon Jérôme
Published: July 2011

In recent years, metal oxides such as titania have been commercially available as chromatographic beds that can potentially be used to achieve novel separations of polar compounds. For example β blockers, which are more often encountered in environmental sciences, have a wide range of polarity, and their basic character leads to difficult sample treatment and separation on conventional silica‐based sorbents. The contribution of titania to the selective analysis of nine β blockers was evaluated in terms of retention mechanisms observed in hydrophilic interaction LC using acetonitrile/water mobile phases with various additives. The mobile phase additives enabled to control the β blocker charge as well as the titania surface charge. Depending on their respective ionic state, various retention mechanisms were identified at low water contents (<40%), including mainly adsorption mixed with hydrophilic interaction LC partition, ion exchange and ion exclusion. An unexpected retention was also observed for high water content and high pH, changing the selectivity of the support.
Phosphoprotein electrophoresis in the presence of Fe(III) ions
Authors: Kučerová Zdenka , Muselová Hana , Přikryl Petr , Tichá Marie
Published: July 2011

Preparation of affinity polyacrylamide gels containing immobilized Fe(III) ions for the separation of proteins exhibiting metal ion binding properties is described. The presented method enables uniform distribution of immobilized metal ions in the affinity part of the polyacrylamide separating gel. Affinity gels prepared by this way are suitable to follow the effect of different concentrations of metal ions immobilized in polyacrylamide gel on a protein electrophoretic behavior. Polyacrylamide gels containing immobilized Fe(III) ions were used to study the electrophoretic behavior of two model proteins differing in their phosphate group content: chicken ovalbumin and bovine α‐casein. For the electrophoretic separation, both the native and the denaturating conditions were used.
Nonlinear optics in spheres: from second harmonic scattering to quasi‐phase matched generation in whispering gallery modes
Authors: Kozyreff G. , Dominguez‐Juarez J.L. , Martorell J.
Published: July 2011

Over the last fifteen years, a series of theoretical and experimental investigations have demonstrated the usefulness of circular geometries to tailor second‐order nonlinear optical effects. However, until recently, such effects have remained rather weak, calling for their enhancement. In parallel, developments in the field of high quality factor spherical or ring resonators have shown that many different types of light‐matter interactions can be dramatically amplified when light is coupled in the whispering gallery modes of such resonators. In high‐quality spherical micro‐resonators, close to one million interactions can occur between a nonlinear molecule and a circulating light pulse. Recent research on nonlinear optics in spherical geometry is reviewed, from micrometer‐size spheres to whispering gallery mode resonators.
Linear Polyethyleneimine: Optimized Synthesis and Characterization – On the Way to “Pharmagrade” Batches
Authors: Tauhardt Lutz , Kempe Kristian , Knop Katrin , Altuntaş Esra , Jäger Michael , Schubert Stephanie , Fischer Dagmar , Schubert Ulrich S.
Published: June 2011

The synthesis of linear polyethyleneimine (LPEI) by acidic hydrolysis of poly(2‐ethyl‐2‐oxazoline) is studied and optimized to reach the highest degree of hydrolysis within the shortest time range using a microwave synthesizer. In addition, the purification procedure is significantly improved; the fast batch processing combined with an excellent control of the actual heating time represents a well‐suited alternative to the conventional synthesis on the way to “pharmagrade” PEI. The developed protocol for the preparation of methyl and proton‐initiated LPEIs shows a high reproducibility, and the identity and purity of the LPEIs is proven by means of 1H NMR and IR spectroscopy as well as MALDI‐TOF‐ and ESI‐Q‐TOF‐MS.

magnified image
A Fully Polymeric Mouldable Microfluidic Device. Part 2: Designing the Process
Authors: Neerincx Peter E. , Hellenbrand Swen J. M. , Meijer Han E. H.
Published: July 2011

Details of the mould design are explained and optimized as needed to produce the system on the two‐component injection moulding machine available in this laboratory. A number of adjustments were required in order to reduce the pressures needed to fill all parts without the danger of exceeding the maximum clamping force. For these hierarchical, subsequent optimization steps, a commercial analysis package was used. After the first successful production runs, the two major functional components of the device were tested: the splitting serpentine channels were fed with two fluids, one containing a fluorescent dye, and down‐flow analysis results showed that laminar mixing indeed proceeds efficiently. The peristaltic pumps, consisting of three air‐pressure actuated membranes, were also tested, and found to have a maximum operating frequency of 5 Hz. Above this critical frequency, the membranes do not sufficiently close on their hubs and begin trembling and vibrating in the pulsating flow. Using a mild vacuum to support the membrane motion shifts the critical frequency to 15 Hz. The volume displacement per stroke is in the order of 7 µL, yielding a maximum flux of ca. 100 µL · s−1.

magnified image
Integration of Ligand‐ and Target‐Based Virtual Screening for the Discovery of Cruzain Inhibitors
Authors: Wiggers H. J. , Rocha J. R. , Cheleski J. , Montanari C. A.
Published: June 2011

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand‐Based Virtual Screening (LBVS) and Target‐Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled‐rank‐by‐number, rank‐by‐rank and rank‐by‐vote, with the most thriving the scaled‐rank‐by‐number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand‐based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.
MPO Inhibitors Selected by Virtual Screening
Authors: Malvezzi Alberto , Queiroz Raphael F , de Rezende Leandro , Augusto Ohara , Amaral Antonia T.‐do
Published: June 2011

The hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure‐based drug design (SBDD) and ligand‐based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical‐chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC50 values ranging from 1.0 to 2.8 µM. MPO inactivation by the most effective compound was shown to be irreversible. Overall, our results show that SBDD and LBDD may be useful for the rational development of new MPO inhibitors.
Trans‐resveratrol simultaneously increases cytoplasmic Ca2+ levels and nitric oxide release in human endothelial cells
Authors: Elíes Jacobo , Cuíñas Andrea , García‐Morales Verónica , Orallo Francisco , Campos‐Toimil Manuel
Published: June 2011

Scope: The aim of this study was to investigate whether the dietary polyphenol trans‐resveratrol (t‐Resv) increases [Ca2+]c in endothelial cells, leading to a simultaneous augmentation of nitric oxide (NO) biosynthesis.

Methods and results: We have separately and simultaneously measured [Ca2+]c and NO in human endothelial cells using the Ca2+ indicator fura‐2 and the NO‐sensitive fluorescent probe 4,5‐diaminofluorescein. In ∼30% of cells, t‐Resv (30 μM) induced an increase in [Ca2+]c with a transient as well as sustained component and a simultaneous increase in NO biosynthesis. This effect was reduced by non‐selective Ca2+ channel blockers, inhibition of intracellular Ca2+ release, inhibition of endothelial nitric oxide synthase (eNOS) and, to a lesser extent, inhibition of extracellular signal‐regulated kinase 1/2 (ERK 1/2) or 5′ adenosine monophosphate‐activated protein kinase (AMPK). t‐Resv did not modify in vitro eNOS activity, suggesting that the observed stimulation of NO generation proceeds via mobilisation of Ca2+ and not through direct effects on eNOS.

Conclusion: We therefore show, for the first time, that t‐Resv induces a concentration‐dependent, simultaneous increase in [Ca2+]c and NO biosynthesis that could be linked to its endothelium‐dependent vasorelaxant effect. Under the assumption that t‐Resv exhibits similar behaviour in human blood vessels in vivo, the pharmacological properties described here may contribute to the beneficial cardiovascular effects of this polyphenol by improving endothelial function.
Ultrashort echo time imaging using pointwise encoding time reduction with radial acquisition (PETRA)
Authors: Grodzki David M. , Jakob Peter M. , Heismann Bjoern
Published: June 2011

Sequences with ultrashort echo times enable new applications of MRI, including bone, tendon, ligament, and dental imaging. In this article, a sequence is presented that achieves the shortest possible encoding time for each k‐space point, limited by pulse length, hardware switching times, and gradient performance of the scanner. In pointwise encoding time reduction with radial acquisition (PETRA), outer k‐space is filled with radial half‐projections, whereas the centre is measured single pointwise on a Cartesian trajectory. This hybrid sequence combines the features of single point imaging with radial projection imaging. No hardware changes are required. Using this method, 3D images with an isotropic resolution of 1 mm can be obtained in less than 3 minutes. The differences between PETRA and the ultrashort echo time (UTE) sequence are evaluated by simulation and phantom measurements. Advantages of pointwise encoding time reduction with radial acquisition are shown for tissue with a T2 below 1 ms. The signal to noise ratio and Contrast‐to‐noise ratio (CNR) performance, as well as possible limitations of the approach, are investigated. In‐vivo head, knee, ankle, and wrist examples are presented to prove the feasibility of the sequence. In summary, fast imaging with ultrashort echo time is enabled by PETRA and may help to establish new routine clinical applications of ultrashort echo time sequences. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Accelerated water–fat imaging using restricted subspace field map estimation and compressed sensing
Authors: Sharma Samir D. , Hu Houchun H. , Nayak Krishna S.
Published: June 2011

Water–fat separation techniques play an important role in a variety of clinical and research applications. In particular, multiecho separation methods remain a topic of great interest due to their ability to resolve water and fat images in the presence of B0‐field inhomogeneity. However, these methods are inherently slow as they require multiple measurements. An accelerated technique with reduced k‐space sampling is desirable to decrease the scan time. This work presents a new method for water–fat separation from accelerated multiecho acquisitions. The proposed approach does not require the region‐growing or region‐merging schemes that are typically used for field map estimation. Instead, the water, fat, and field map signals are estimated directly from the undersampled k‐space measurements. In this work, up to 2.5×‐acceleration is demonstrated in a water–fat phantom, ankle, knee, and liver. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Komplexität ohne Kompliziertheit
Authors: Jung Udo
Published: July 2011

Sind globale Megatrends ein Erfolgsfaktor oder eine Worthülse? Beeinflussen sie die Wachstums‐ und Wertschaffungschancen chemischer Unternehmen unterschiedlich, oder sind sie wenig differenzierend, da ja fast alle davon profitieren? Europäische Chemieunternehmen sollten den Trends folgen, ihre Gravitätszentren verschieben und die Fähigkeit nutzen, komplexe Geschäfte unkompliziert zu steuern.
Elektronisches Journal an der Uni
Authors: Kotaskova Michaela , Tserovski Lyudmil
Published: July 2011

Ein Programm dokumentiert Projekte, ein anderes verwaltet Chemikalien. So bleiben dem Arbeitskreis Fotos jeder Versuchsanlage erhalten und Bestellungen laufen automatisch.
Transient partial response to sorafenib treatment in an adolescent patient with MEN2B Syndrome and end‐stage medullary thyroid carcinoma
Authors: Aller Steven , Popescu Andrada , Rao Sudha , Morgan Elaine , Gosiengfiao Yasmin
Published: June 2011

Metastatic medullary thyroid carcinoma (MTC) is an aggressive malignancy with an extremely poor prognosis. Currently no effective conventional systemic therapies exist to treat pediatric MTC. We describe an adolescent female with newly diagnosed MEN2B syndrome who presented with advanced stage metastatic MTC and demonstrated a partial transient response to sorafenib monotherapy. This clinical result supports further research into the use of sorafenib in the treatment of pediatric MTC. Pediatr Blood Cancer 2012; 58: 98–100. © 2011 Wiley Periodicals, Inc.
Neuropsychological outcomes of standard risk and high risk patients treated for acute lymphoblastic leukemia on Dana‐Farber ALL consortium protocol 95‐01 at 5 years post‐diagnosis
Authors: Waber Deborah P. , Queally Jennifer Turek , Catania Lori , Robaey Philippe , Romero Ivonne , Adams Heather , Alyman Cheryl , Jandet‐Brunet Christine , Sallan Stephen E. , Silverman Lewis B.
Published: June 2011

Background

Children treated for acute lymphoblastic leukemia (ALL) as High Risk (HR) patients may be more vulnerable to neurocognitive late effects because of the greater intensity of their therapy. We compared neuropsychological outcomes in children treated for Standard Risk (SR) or HR ALL on Dana‐Farber Cancer Institute (DFCI) Consortium ALL Protocol 95‐01. We also evaluated their performance relative to normative expectations.

Procedure

Between 1996 and 2000, 498 children with newly diagnosed ALL were treated on Protocol 95‐01, 298 of whom were eligible for neuropsychological follow‐up. A feature of this protocol was modification of risk group criteria to treat more children as SR rather than HR patients, intended to minimize toxicities. Testing was completed at a median of 5.3 years post‐diagnosis for 211 patients (70.8%; ages 6–25 years; 45.5% male; 40% HR), all of whom were in continuous complete remission.

Results

Test scores for both groups were generally at or above normative expectation, with the exception of verbal working memory, processing complex visual information, and parent ratings of metacognitive skills. After adjusting for covariates, the SR group performed better on measures of IQ and academic achievement, working memory and visual learning. Effect sizes, however, were only in the small to moderate range.

Conclusions

HR patients exhibited neuropsychological deficits relative to SR patients, though the differences were modest in degree. Modification of the risk group criteria to treat more children on the SR protocol therefore likely afforded some benefit in terms of neurocognitive late effects. Pediatr Blood Cancer 2012; 58: 758–765. © 2011 Wiley Periodicals, Inc.
Genetic screening in a university clinic: impact of primary language
Authors: Hawk Angela F. , Pastore Lisa , Saller Devereux N.
Published: June 2011

Objective

To contrast Spanish‐speaking (S) with English‐speaking (E) obstetric patients regarding utilization of genetic screening, motivation for undergoing/declining screening, pregnancy‐related anxiety, knowledge about genetic conditions, and printed information as an adjunct to counseling.

Method

Paper surveys were given to patients (n = 121) in an academic OB/GYN clinic or placed in charts (n = 271) over a 4‐week period. Comparisons were evaluated with Chi‐square and Fisher's exact tests.

Results

Completed surveys were returned from 245 gravidas (response rate 63%, S 48%, and E 67%). Uptake of genetic screening was similar between the groups (S 69% vs E 57%, p = 0.13). No significant differences were noted in patients' motivation regarding screening, source of screening information, or self‐assessed pregnancy‐related anxiety. Familiarity of genetic disorders other than Down syndrome differed between the S and E groups (p < 0.003). Perceived positive utility of printed information differed significantly when groups were analyzed by language (S 85% vs E 47%, p < 0.001) and by uptake of screening(screened 62% vs not screened 44%, p = 0.006).

Conclusion

A majority of study participants (n = 147, 60%) chose genetic screening; uptake and motivation were similar across language groups. Familiarity with genetic conditions was deficient and screening terminology confusing regardless of primary language. The perceived positive utility of printed information (S > E) highlights the importance of clear and early counseling. Copyright © 2011 John Wiley & Sons, Ltd.
Prenatal brain imaging in congenital toxoplasmosis
Authors: Malinger G. , Werner H. , Rodriguez Leonel J. C. , Rebolledo M. , Duque M. , Mizyrycki S. , Lerman‐Sagie T. , Herrera M.
Published: June 2011

Objective

To describe brain imaging findings and outcomes in fetuses with confirmed congenital toxoplasmosis (CTX).

Methods

Physicians from Prenatal Diagnosis Units in ten Latin American countries were contacted and asked to provide data on fetuses with ultrasound findings suggestive of intrauterine infection and a positive diagnosis of CTX. The imaging studies were reviewed, and findings were described and tabulated.

Results

Intracranial findings suggestive of CTX were identified in eight patients at a median gestational age of 31.5 weeks (range, 24.4–34 weeks). Ventriculomegaly was found in seven patients [severe (3), mild (4)]. Multiple echogenic nodular foci consistent with calcifications were found in seven patients [brain parenchyma (7), periventricular zone (3) and caudothalamic zone (3)]. Diffuse periventricular echogenicity or cysts were seen in three and callosal dysgenesis in one. All six survivors have choroidoretinitis and intracranial calcifications, four suffer from developmental delay and three of these four children also suffer from seizures and blindness. Postnatal hydrocephaly was found in five children.

Conclusions

Ventriculomegaly associated with multiple echo‐dense nodules is characteristic of severe fetal toxoplasmosis and carries a poor prognosis. When the ventricles have normal size or are only mildly dilated, the nodules restricted to the parenchyma development may be normal. Copyright © 2011 John Wiley & Sons, Ltd.