bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic Formulations—Photopatterning of Luminescent Conjugated Polymers
Authors: Solomeshch O. , Medvedev V. , Mackie P. R. , Cupertino D. , Razin A. , Tessler N.
Published: September 2006

The versatility of light‐emitting conjugated polymers in terms of optoelectronic properties is enormous, but tailoring of other essential properties has been relatively limited. In other fields such a problem would be rectified using material formulations. However, the need to maintain high optoelectronic compatibility between components has hampered such development. In this paper, careful design of electronically compatible materials is demonstrated. Additive molecules that are compatible with a family of luminescent polymers are presented, and their performance in a light‐emitting diode configuration is demonstrated. This formulation is aimed to adjust the glass‐transition temperature, maintain/improve film‐forming ability, and introduce a crosslinking functionality. It is found that, by using electronic formulations, a robust procedure is obtained that could be used to produce waveguide lasers or full‐color displays. The patterning ability is shown via the construction of a single pixel that is half green and half orange.
High‐Rate LiFePO4 Electrode Material Synthesized by a Novel Route from FePO4 · 4H2O
Authors: Wang Y. , Wang J. , Yang J. , Nuli Y.
Published: September 2006

A LiFePO4 material with ordered olivine structure is synthesized from amorphous FePO4 · 4H2O through a solid–liquid phase reaction using (NH4)2SO3 as the reducing agent, followed by thermal conversion of the intermediate NH4FePO4 in the presence of LiCOOCH3 · 2H2O. Simultaneous thermogravimetric–differential thermal analysis indicates that the crystallization temperature of LiFePO4 is about 437 °C. Ellipsoidal particle morphology of the resulting LiFePO4 powder with a particle size mainly in the range 100–300 nm is observed by using scanning electron microscopy and transmission electron microscopy. As an electrode material for rechargeable lithium batteries, the LiFePO4 sample delivers a discharge capacity of 167 mA h g–1 at a constant current of 17 mA g–1 (0.1 C rate; throughout this study n C rate means that rated capacity of LiFePO4 (170 mA h g–1) is charged or discharged completely in 1/n hours), approaching the theoretical value of 170 mA h g–1. Moreover, the electrode shows excellent high‐rate charge and discharge capability and high electrochemical reversibility. No capacity loss can be observed up to 50 cycles under 5 C and 10 C rate conditions. With a conventional charge mode, that is, 5 C rate charging to 4.2 V and then keeping this voltage until the charge current is decreased to 0.1 C rate, a discharge capacity of ca. 134 mA h g–1 and cycling efficiency of 99.2–99.6 % can be obtained at 5 C rate.
Acquired von Willebrand syndrome: Diagnostic problems and therapeutic options
Authors: Eikenboom Jeroen C.J. , Tjernberg Pernilla , Van Marion Vincent , Heering Karel J.
Published: September 2006

We present a case of acquired von Willebrand syndrome (AVWS) due to a monoclonal gammopathy of undetermined significance. Initially this case was diagnosed as congenital von Willebrand disease (VWD); however, re‐examination of the medical history rendered a congenital bleeding disorder unlikely. A normal plasma von Willebrand factor (VWF) propeptide level and a very short half‐life of VWF after a test infusion with factor VIII/VWF concentrate confirmed the diagnosis AVWS. Two major surgical procedures were successfully managed using high‐dose intravenous immunoglobulin. The differential diagnosis with congenital VWD and the diagnostic and therapeutic approaches of AVWS are discussed. We conclude that the diagnosis of AVWS relies primarily on clinical suspicion and a careful bleeding history. A correct diagnosis is essential for optimal perioperative management and treatment of bleeding episodes. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Platelet functional implications of glycoprotein Ibα polymorphisms in African Americans
Authors: Williams Marlene S. , Ng'alla Ladina S. , Vaidya Dhananjay
Published: September 2006

The platelet glycoprotein Ibα is crucial in the binding of platelets to Von Willebrand Factor within areas of high stress. A single nucleotide polymorphism of GP Ibα gives rise to the Koa (HPA‐2b) and the ‐5C Kozak polymorphism. The presence of these polymorphisms has been associated with an increased risk for atherothrombotic disease. The Koa polymorphism has been shown to have a higher prevalence in African Americans compared to American Caucasians. However, very little is known regarding any functional consequences of these platelet polymorphisms in African Americans. We assessed the prevalence of the Ko and ‐5C Kozak polymorphisms in a population of both African American and American Caucasian patients with and without CAD and determined whether there were platelet functional consequences in both groups. We studied 99 patients of which 22 were African American and 77 were American Caucasian. Aggregations were performed and shear induced platelet plug formation was tested using a platelet function analyzer. The HPA‐2b allele was significantly higher in African Americans when compared to Caucasians (P = 0.001). Genotype frequencies of the ‐5C Kozak polymorphism were not significantly different between the two groups. We found no differences in platelet aggregation in African Americans who were either heterozygous or homozygous for the HPA‐2b allele or the ‐5C Kozak allele when compared to American Caucasians of the same category. We found no significant differences in PFA‐100 testing. We conclude from our study that these polymorphisms do not lead to altered platelet function in African Americans. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Hypocupremia associated with prior vitamin B12 deficiency
Authors: Prodan Calin I. , Bottomley Sylvia S. , Vincent Andrea S. , Cowan Linda D. , Holland Neil R. , Lind Stuart E.
Published: September 2006

Clinical similarities between vitamin B12 and copper deficiencies prompted us to investigate if hypocupremia is present in patients receiving vitamin B12 supplementation. Our pilot study results indicate that a significant number of elderly patients with prior diagnosis of vitamin B12 deficiency have also undiagnosed hypocupremia. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Zur Unmöglichkeit der Geruchsvorhersage
Authors: Sell C. S.
Published: September 2006

Seit mehr als einem Jahrhundert sind Chemiker bestrebt, mehr über die faszinierende und rätselhafte Beziehung zwischen der Molekülstruktur und dem Geruch herauszufinden. Trotz intensiver Forschung zu Struktur‐Geruchs‐Beziehungen bleibt die Vorhersage des Geruchs einer neuen Verbindung aber eine statistische Übung, und Modelle können bestenfalls Aussagen über die Wahrscheinlichkeit von Art, Schwellenwert und Intensität eines Geruchs treffen. Überraschungen sind auf diesem Gebiet alltäglich, und der Zufall bleibt ein wichtiger Faktor bei der Entdeckung neuer Duftstoffe. Neuere Erkenntnisse zum Mechanismus der Geruchswahrnehmung bieten eine Erklärung hierfür und lassen darauf schließen, dass sich unsere Fähigkeit zur Vorhersage der Geruchseigenschaften von Verbindungen in naher Zukunft nicht wesentlich verbessern wird.
p53—A Natural Cancer Killer: Structural Insights and Therapeutic Concepts
Authors: Römer Lin , Klein Christian , Dehner Alexander , Kessler Horst , Buchner Johannes
Published: September 2006

Every single day, the DNA of each cell in the human body is mutated thousands of times, even in absence of oncogenes or extreme radiation. Many of these mutations could lead to cancer and, finally, death. To fight this, multicellular organisms have evolved an efficient control system with the tumor‐suppressor protein p53 as the central element. An intact p53 network ensures that DNA damage is detected early on. The importance of p53 for preventing cancer is highlighted by the fact that p53 is inactivated in more than 50 % of all human tumors. Thus, for good reason, p53 is one of the most intensively studied proteins. Despite the great effort that has been made to characterize this protein, the complex function and the structural properties of p53 are still only partially known. This review highlights basic concepts and recent progress in understanding the structure and regulation of p53, focusing on emerging new mechanistic and therapeutic concepts.
Sustaining water resources in South East England
Authors: Rodda John C.
Published: September 2006

The South East of England is one of the driest regions of the UK and it is also one of the most densely populated. As a consequence the available water resource per head of population is about half of the figure used by the World Bank to indicate that a country is suffering water stress. The South East Plan, prepared by the South East England Regional Assembly, proposes to increase the population of the region by about 1 million by 2026. This paper considers the ability of the Region's water resources to cope with this growth. Copyright © 2006 Royal Meteorological Society
Krank durch Stress: Molekulare Wirkmechanismen und Folgen für die Gesundheit
Authors: Rensing Ludger
Published: September 2006

Psychosozialer Stress hat deutliche Wirkungen auf das Immunsystem: kurzer kontrollierbarer Stress beeinflusst eine Reihe von Immunfunktionen positiv, während traumatische Erfahrungen, chronischer Stress oder Depressionen viele Immunfunktionen hemmen. Übermittelt werden die Stresswirkungen über das neuroendokrine System. Das neuroendokrine System wirkt auf die Produktion von Cytokinen in den Immunzellen über diverse Rezeptoren und Proteinkinasen und deren Einfluss auf die Aktivität von verschiedenen Transkriptionsfaktoren, insbesondere auf die des nuclear factor kappaB (NFκB). Stressbelastungen sind oft an chronischen Entzündungen in verschiedenen Geweben beteiligt. Dagegen werden zurzeit Medikamente entwickelt, die in die molekularen Mechanismen der Entzündungsprozesse eingreifen.
Spinnennetz nur einmal erfunden
Authors: Brennicke Axel
Published: September 2006

Heutzutage nutzen Spinnen zwei unterschiedliche Methoden, um ihre Netze klebrig zu machen. Wissenschaftler waren lange im Zweifel, ob Spinnennetze einmal oder mehrmals erfunden wurden. Neue Befunde belegen jetzt, dass in der Evolutionsgeschichte die Idee für das Netz weltweit nur einmal auftauchte und seit mehr als 100 Millionen Jahren erfolgreich eingesetzt wird.
Darwinfinken – die Evolution geht weiter
Authors: Wendler Silke
Published: September 2006

Galapagosfinken gelten seit der Zeit von Charles Darwin als Paradebeispiel für die Evolution durch Selektion. Kürzlich veröffentlichte Beobachtungen über den Mittleren Grundfink (Geospiza fortis) zeigen eine Veränderung der Schnabelgröße, die durch Nahrungskonkurrenz mit dem Großen Grundfink (Geospiza magnirostris) hervorgerufen wurde. Verblüfft hat bei diesen Beobachtungen die Geschwindigkeit, mit denen sich diese Veränderung durchgesetzt hat.
Current role of radiofrequency ablation for the treatment of colorectal liver metastases
Authors: McKay A , Dixon E , Taylor M
Published: September 2006

Background and method

This paper reviews the current status of radiofrequency ablation in the treatment of colorectal liver metastases. Relevant studies with at least ten patients that reported rates of complete tumour ablation, local recurrence, or survival from 1 to 5 years after treatment were included in the review.

Results and conclusion

Only six studies that reported at least 3-year survival were identified, with results ranging from 37 to 58 per cent. Some of these figures are promising, given that the patients were considered to have unresectable disease. However, available evidence is limited and hepatic resection remains the standard of care when feasible; radiofrequency ablation cannot be considered an equivalent. Radiofrequency ablation does, however, appear to have a role in treating unresectable disease, and may also be used in conjunction with resection to extend its limits.
Diversity‐Oriented Approach to Biologically Relevant Molecular Frameworks Starting with β‐Naphthol and Using the Claisen Rearrangement and Olefin Metathesis as Key Steps
Authors: Kotha Sambasivarao , Mandal Kalyaneswar , Tiwari Arti , Mobin Shaikh M.
Published: September 2006

A diversity‐oriented approach for the synthesis of various structurally different molecular frameworks from readily accessible and common precursors is described. A Claisen rearrangement followed by ring‐closing metathesis or ethylene‐promoted ring‐closing enyne metathesis has been utilized as the key synthetic transformation to generate naphthoxepine derivatives. The ring‐closing metathesis approach has also been used to generate spirocyclic compounds and the pleiadene framework.
Linear systems analysis of the ciliary steering behavior associated with negative‐phototaxis in Chlamydomonas reinhardtii
Authors: Josef Keith , Saranak Jureepan , Foster Kenneth W.
Published: September 2006

In response to light stimulation Chlamydomonas reinhardtii changes the beating frequency, beating pattern, and beating synchrony of the trans and cis cilia to steer the freely‐swimming cell relative to light sources. To understand the cell steering behavior the impulse responses of the beating frequency and stroke velocity of each cilium have been obtained with high temporal resolution on cells held with a micropipette. Interestingly the response of each cilium is quite different. The trans cilium responds with less delay than the cis cilium for both beating frequency and stroke velocity. For light stimulation at 2 Hz, the critical cell‐rotation frequency, both responses of the trans and cis cilia are about 180° out of phase. The trans‐cilium beating frequency response peaks at a stimulus frequency of 5–6 Hz, higher than the cis at 1–2 Hz. The stroke velocities of the trans and cis cilia have the same stimulus‐frequency response (˜2 Hz), but the trans cilium has a shorter delay than the cis. The times to maximum response are much shorter than the time for a rotation of the cell. The use of two different approaches that enable the trans cilium to respond ahead of the cis for both the beating frequency and stroke velocity responses suggests the importance of both responses to phototaxis. Internal cell processing responsible for the time course of the responses is proposed. Cell Motil. Cytoskeleton 2006. © 2006 Wiley‐Liss, Inc.
Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion
Authors: Benlloch Susana , Galbis‐Caravajal Jose Marcelo , Martín Concepcion , Sanchez‐Paya Jose , Rodríguez‐Paniagua Jose Manuel , Romero Santiago , Mafe Juan Jose , Massutí Bartomeu
Published: September 2006

BACKGROUND.

The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid.

METHODS.

The authors used methylation‐specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death‐associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor β (RARβ), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients).

RESULTS.

Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001).

CONCLUSIONS.

Cell‐free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests. Cancer 2006. © 2006 American Cancer Society.
Analysis of differential BRAFV600E mutational status in multifocal papillary thyroid carcinoma
Authors: Park So Yeon , Park Young Joo , Lee Yu Jin , Lee Hyun Sook , Choi Sung Hee , Choe Gheeyoung , Jang Hak‐Chul , Park Seong Hoe , Park Do Joon , Cho Bo Youn
Published: September 2006

BACKGROUND.

Papillary thyroid cancers often occur as multiple foci. Multifocal cancers have been considered to have a poor prognosis because they are thought to be the consequence of intrathyroidal spread of the papillary cancer. However, to the authors' knowledge there has been little investigation into whether multifocal thyroid papillary carcinomas arise from the intrathyroidal spread of a single carcinoma or from independent primary tumors. To answer this question, the BRAFV600E mutational status of individual tumor foci was examined. This approach was justified because in the Korean population a high proportion (65%) of papillary carcinomas harbor the BRAF mutation.

METHODS.

DNA was isolated from paraffin‐embedded tissue samples of multifocal papillary thyroid carcinoma and the BRAF exon 15 was amplified by the polymerase chain reaction (PCR). The PCR product was digested with restriction endonuclease TspRI to test for the presence of the BRAFV600E (T1799A) mutation.

RESULTS.

In all, 140 cancers from 61 patients diagnosed with multifocal papillary carcinoma were examined. The BRAF mutation was found in all the individual cancers in 29 (47.5%) of the patients (all‐positive group) and the mutation was absent in all the individual cancers in 8 (13.1%) patients (all‐negative group). However, in 24 (39.3%) patients, some of the individual cancers contained the BRAF mutation, whereas others did not (mixed group).

CONCLUSIONS.

At least 39.3% of the multifocal papillary cancers in the Korean population that were examined could be attributed to independently arising papillary cancers rather than to intrathyroidal spread of single cancers. Cancer 2006. © 2006 American Cancer Society.
Expression of inhibitor of apoptosis proteins in B‐cell non‐Hodgkin and Hodgkin lymphomas
Authors: Akyurek Nalan , Ren Yongsheng , Rassidakis Georgios Z. , Schlette Ellen J. , Medeiros L. Jeffrey
Published: September 2006

BACKGROUND.

Inhibitor of apoptosis proteins (IAPs) inhibit apoptosis by binding specific caspases, and possibly by other mechanisms. Eight IAPs have been identified in humans, of which cIAP1, cIAP2, and XIAP are well known. IAPs are being investigated as potential treatment targets in cancer patients.

METHODS.

cIAP1, cIAP2, and XIAP were assessed in lymphoma cell lines, 240 B‐cell non‐Hodgkin lymphoma (NHL) tumors, and 40 Hodgkin lymphoma (HL) tumors.

RESULTS.

All IAPs were expressed in most NHL and all HL cell lines. In NHL tumors, cIAP1 was expressed in 174 (73%), cIAP2 in 115 (48%), and XIAP in 37 (15%). cIAP1 was positive in all precursor B‐cell lymphoblastic lymphoma/leukemia (LBL) and nodal marginal zone B‐cell lymphoma (MZL), over 90% of follicular lymphoma and diffuse large B‐cell lymphoma (DLBCL), and approximately 50% to 60% of myeloma, Burkitt lymphoma (BL), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM), small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL), extranodal marginal zone B‐cell lymphoma of mucosa associated lymphoid tissue (MALT‐lymphoma), splenic MZL, and mantle cell lymphoma. cIAP2 was positive in all MALT‐lymphoma, over 90% of precursor B‐cell LBL (94%), most BL (75%), LPL/WM (71%), and SLL/CLL (67%), and approximately 40% to 60% of follicular lymphoma, myeloma, and DLBCL. XIAP was positive most cases of precursor B‐cell LBL (57%) and approximately 30% to 40% of nodal MZL, BL, and DLBCL. In HL tumors, cIAP1 was positive in 30 (75%), cIAP2 in 27 (68%), and XIAP in 23 (58%), and did not correlate with histologic type.

CONCLUSIONS.

Differential expression of IAPs in B‐cell lymphomas suggests differences in pathogenesis that may have implications for novel treatment strategies targeting IAPs. Cancer 2006. © 2006 American Cancer Society.
Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma
Authors: Suppiah Revathi , Shaheen Philip E. , Elson Paul , Misbah Seema A. , Wood Laura , Motzer Robert J. , Negrier Slyvie , Andresen Steven W. , Bukowski Ronald M.
Published: September 2006

BACKGROUND.

It has been suggested that thrombocytosis, as defined by a platelet count >400,000/μL, is a negative predictor for survival among patients with metastatic renal cell carcinoma. However, this has not been a uniform finding.

METHODS.

To address this issue, retrospective analysis of 700 previously untreated patients entering on institution review board‐approved phase 1, 2, or 3 clinical trials in the United States and Europe was conducted between 1982 and 2002.

RESULTS.

Thrombocytosis was present at study entry in 25% of patients. Median baseline platelet count was 304,000/μL (range, 86–1,420,000/μL). Eighty‐seven percent of patients died with a median survival of 13.0 months. Median follow‐up for patients not known to have died was 2.4 years. On univariate analysis, patients with elevated platelet counts had significantly shorter survival than patients with normal platelet counts; median survivals of 8.4 and 14.6 months, respectively, P < .001. However, platelet count was associated with several clinical and biochemical factors, including gender, age, performance status, time from diagnosis to study entry, prior radiotherapy or nephrectomy, presence of liver metastasis, number of metastatic sites, amount of hemoglobin, white blood cell count, amount of lactate dehydrogenase, and amount of serum alkaline phosphatase. Several of these factors have previously been reported as prognostic indicators for survival, and, therefore, multivariable analyses were conducted to determine whether thrombocytosis is an independent predictor of survival. After adjusting for multiple factors, thrombocytosis continued to impact negatively on survival, P < .001.

CONCLUSIONS.

Thrombocytosis was found to be an independent prognostic factor for survival in patients with metastatic renal cell carcinoma. Cancer 2006. © 2006 American Cancer Society.
Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain
Authors: Krown Susan E. , Niedzwiecki Donna , Hwu Wen‐Jen , Hodgson Lydia , Houghton Alan N. , Haluska Frank G. ,   for the Cancer and Leukemia Group B
Published: September 2006

BACKGROUND.

Preliminary studies suggesting that extended‐dose temozolomide with thalidomide is safe and active in patients with metastatic melanoma have led to frequent use of this oral regimen. To confirm these observations the combination was tested in a multicenter Phase II trial in patients with melanoma brain metastases.

METHODS.

Eligible patients had melanoma brain metastases, with or without systemic metastases. The primary endpoint was response rate in brain metastases. Patients received temozolomide at a dose of 75 mg/m2/day for 6 weeks with a 2‐week rest between cycles, and thalidomide (escalated to 400 mg/day for patients age <70 years or to 200 mg/day for patients age ≥70 years). A 2‐stage design required ≥3 responses in the first 21 patients before enrolling 29 additional patients in the second stage.

RESULTS.

Sixteen eligible patients were enrolled. No objective responses were observed. The median survival was 23.9 weeks. Seven patients withdrew because of tumor progression; 7 were removed during Cycle 1 because of adverse events, including allergic reaction (1 patient), severe fatigue (1 patient), sudden death (1 patient), and thromboembolic events (pulmonary embolism in 3 patients and deep vein thrombosis in 1 patient); 2 patients withdrew when the study was suspended and subsequently closed. No associations could be established between baseline characteristics and toxicity.

CONCLUSIONS.

The proportion of patients with lethal or potentially life‐threatening adverse events was high (0.31, 95% confidence interval, 0.11–0.59), and the absence of objective responses made it unlikely that further accrual would demonstrate the efficacy of the regimen. These observations provide little support for the use of this combination for melanoma brain metastases unless safe and effective methods to prevent thrombosis are developed. Cancer 2006. © 2006 American Cancer Society.
Rank‐based ant colony algorithms for truss weight minimization with discrete variables
Authors: Capriles Priscila V. S. Z. , Fonseca Leonardo G. , Barbosa Helio J. C. , Lemonge Afonso C. C.
Published: September 2006

One variant of the ant colony optimization (ACO) metaheuristic, known as rank‐based ant system (RBAS), is proposed for weight minimization of structures involving discrete design variables. Stress and displacements constraints are handled using a penalty technique, and the structural analysis is performed by the finite element method.

Results obtained for several discrete weight minimization problems show that the RBAS algorithm implemented is effective and competitive when compared with results found by genetic algorithms and another RBAS variant. Copyright © 2006 John Wiley & Sons, Ltd.
The radial integration method applied to dynamic problems of anisotropic plates
Authors: Albuquerque E. L. , Sollero P. , Portilho de Paiva W.
Published: September 2006

In this paper, the radial integration method is applied to transform domain integrals into boundary integrals in a boundary element formulation for anisotropic plate bending problems. The inertial term is approximated with the use of radial basis functions, as in the dual reciprocity boundary element method. The transformation of domain integrals into boundary integrals is based on pure mathematical treatments. Numerical results are presented to verify the validity of this method for static and dynamic problems and a comparison with the dual reciprocity boundary element method is carried out. Although the proposed method is more time‐consuming, it presents some advantages over the dual reciprocity boundary element method as accuracy and the absence of particular solutions in the formulation. Copyright © 2006 John Wiley & Sons, Ltd.
Peptide‐doxorubicin conjugates specifically degraded by matrix metalloproteinases expressed from tumor
Authors: Lee Gee Young , Song Ji‐hye , Kim Sang Yoon , Park Kyeongsoon , Byun Youngro
Published: September 2006

Specific peptide‐doxorubicin conjugates were developed for targeting matrix metalloproteinases (MMPs) expressed from tumors. The peptide‐doxorubicin conjugates were designed to be cleaved by MMP‐2 and MMP‐9 in order that doxorubicin or the active form that acts as an anticancer agent was released free from the peptide fragment at the tumor site. Three types of peptide‐doxorubicin conjugates were synthesized using the peptides: GPLG (Gly‐Pro‐Leu‐Gly), GPLGV (Gly‐Pro‐Leu‐Gly‐Val), and GPLGPAG (Gly‐Pro‐Leu‐Gly‐Pro‐Ala‐Gly). The synthesized peptide‐doxorubicin conjugates were characterized for their degradation behavior and bioactivity in vitro, and their antitumoral activity was assessed using the Lewis lung carcinoma (LLC) model, which expresses MMP‐2 and MMP‐9. After incubation with active MMP‐2 for 24 h, GPLG‐doxorubicin was barely degraded, whereas GPLGV‐doxorubicin and GPLGPAG‐doxorubicin were considerably degraded by active MMP‐2. Consequently, all peptide‐doxorubicin conjugates had significantly low cytotoxicity compared to doxorubicin, but tumor growth suppression was exhibited only by GPLGV‐doxorubicin and GPLGPAG‐doxorubicin. The tumor growth suppression by the two conjugates was higher compared to control, although it did not exceed the suppression level shown by doxorubicin. The low toxicity exhibited by peptide‐doxorubicin conjugates resulted in only slight body weight loss in mice, whereas doxorubicin greatly reduced body weight and induced severe side effects. Therefore, we propose MMPs‐specific peptide‐doxorubicin conjugates in targeting anti‐cancer drug delivery that could reduce systemic toxicities. Drug Dev. Res. 67:438–447, 2006. © 2006 Wiley‐Liss, Inc.
A reporter gene cellular model for evaluating induction of CYP3A4 by new chemical entities
Authors: Enoru‐Eta Julius , Yengi Lilian G. , Kao John , Scatina JoAnn
Published: September 2006

A cell‐based reporter gene assay to study CYP3A4 induction was developed in the present study. The pregnane X receptor (PXR) gene or variant (PXR2) was cloned into the pSG5 vector and cotransfected into HepG2 cells, with a construct, pGL3‐3A4‐Luc, containing the promoter/enhancer region of the CYP3A4 gene. The two systems were validated using rifampicin (RIF). The variant, PXR2, did not mediate induction of CYP3A4 by rifampicin (10 µM) whereas PXR showed dose‐dependent induction of CYP3A4, with a fold change of 40–60, compared to the vehicle control, 0.1% dimethylsulfoxide (DMSO). Further validation of the PXR/3A4 system was performed using other inducers of CYP3A4, after which CYP3A4 inducibility by a Wyeth compound, Tanaproget (TNPR), and the synthetic steroid, 3‐ketodesogestrel (3‐KDG), were assessed. At the highest concentrations tested, troleandomycin (TROL) and phenobarbital (PB) induced CYP3A4 by 15–25‐fold, while carbamazepine (CMZ), dexamethasone (DEX), and erythromycin (ERY) produced fold induction of <3. Pregnenolone 16‐α carbonitrile (PCN), a rat‐specific CYP3A inducer, did not induce CYP3A4. TNPR did not induce CYP3A4 at concentrations up to 10 µM while 3‐KDG produced a concentration‐dependent induction, with a fold change of 14 at 20 µM. These data show that the variant PXR2 is not activated by rifampicin. The PXR/3A4 system described can be used to study CYP3A4 induction and provides a robust, specific, and reproducible in vitro system that can be used to assess CYP3A4 inducibility by compounds in the drug development process. Drug Dev. Res. 67:470–475, 2006. © 2006 Wiley‐Liss, Inc.
Transmembrane TNF protects mutant mice against intracellular bacterial infections, chronic inflammation and autoimmunity
Authors: Alexopoulou Lena , Kranidioti Ksanthi , Xanthoulea Sofia , Denis Maria , Kotanidou Anastasia , Douni Eleni , Blackshear Perry J. , Kontoyiannis Dimitris L. , Kollias George
Published: September 2006

Using targeted mutagenesis in mice, we have blocked shedding of endogenous murine TNF by deleting its cleavage site. Mutant mice produce physiologically regulated levels of transmembrane TNF (tmTNF), which suffice to support thymocyte proliferation but cannot substitute for the hepatotoxic activities of wild‐type TNF following LPS/D‐galactosamine challengein vivoand are not sufficient to support secondary lymphoid organ structure and function. Notably, however, tmTNF is capable of exerting anti‐Listerial host defenses while remaining inadequate to mediate arthritogenic functions, as tested in the tristetraprolin‐deficient model of TNF‐dependent arthritis. Most interestingly, in the EAE model of autoimmune demyelination, tmTNF suppresses disease onset and progression and retains the autoimmune suppressive properties of wild‐type TNF. Together, these results indicate that tmTNF preserves a subset of the beneficial activities of TNF while lacking detrimental effects. These data support the hypothesis that selective targeting of soluble TNF may offer several advantages over complete blockade of TNF in the treatment of chronic inflammation and autoimmunity.
Imputation methods to improve inference in SNP association studies
Authors: Dai James Y. , Ruczinski Ingo , LeBlanc Michael , Kooperberg Charles
Published: September 2006

Missing single nucleotide polymorphisms (SNPs) are quite common in genetic association studies. Subjects with missing SNPs are often discarded in analyses, which may seriously undermine the inference of SNP‐disease association. In this article, we develop two haplotype‐based imputation approaches and one tree‐based imputation approach for association studies. The emphasis is to evaluate the impact of imputation on parameter estimation, compared to the standard practice of ignoring missing data. Haplotype‐based approaches build on haplotype reconstruction by the expectation‐maximization (EM) algorithm or a weighted EM (WEM) algorithm, depending on whether case‐control status is taken into account. The tree‐based approach uses a Gibbs sampler to iteratively sample from a full conditional distribution, which is obtained from the classification and regression tree (CART) algorithm. We employ a standard multiple imputation procedure to account for the uncertainty of imputation. We apply the methods to simulated data as well as a case‐control study on developmental dyslexia. Our results suggest that imputation generally improves efficiency over the standard practice of ignoring missing data. The tree‐based approach performs comparably well as haplotype‐based approaches, but the former has a computational advantage. The WEM approach yields the smallest bias at a price of increased variance. Genet. Epidemiol. © 2006 Wiley‐Liss, Inc.
The 2‐dimensional rigidity of certain families of graphs
Authors: Jackson Bill , Servatius Brigitte , Servatius Herman
Published: September 2006

Laman's characterization of minimally rigid 2‐dimensional generic frameworks gives a matroid structure on the edge set of the underlying graph, as was first pointed out and exploited by L. Lovász and Y. Yemini. Global rigidity has only recently been characterized by a combination of two results due to T. Jordán and the first named author, and R. Connelly, respectively. We use these characterizations to investigate how graph theoretic properties such as transitivity, connectivity and regularity influence (2‐dimensional generic) rigidity and global rigidity and apply some of these results to reveal rigidity properties of random graphs. In particular, we characterize the globally rigid vertex transitive graphs, and show that a random d‐regular graph is asymptotically almost surely globally rigid for all d ≥ 4. © 2006 Wiley Periodicals, Inc. J Graph Theory 54: 154–166, 2007
Effect of the type and concentration of lubricating additives on the antiwear and extreme pressure properties and rolling fatigue life of a four‐ball tribosystem
Authors: Tuszyński Waldemar , Piekoszewski Witold
Published: September 2006

Tests were performed on two different four‐ball testers. The first was used to determine antiwear (AW) and extreme pressure (EP) properties at sliding friction. The second was used to assess the surface fatigue (pitting) life at rolling movement. Lubricating oils of various chemical compositions were tested. A base mineral oil was blended with two different commercial packages of lubricating additives of AW and EP types. The AW additives contained ZDDP and were blended with the base oil at 0.2 and 3wt %. The EP additives were organic compounds of sulphur and phosphorus, blended with the base oil at 1 and 10wt %. It is shown that AW additives not only improve AW and EP properties but also — at 0.2% — are beneficial for the fatigue life. An increase in the concentration of AW additives leads to an improvement of AW and EP properties but — for one of the packages — reduces the fatigue life. EP additives — at 1% concentration — significantly improve EP properties, and to a lesser extent AW properties. Such a concentration of EP additives has no influence on the fatigue life. An increase in the concentration of EP additives leads to a further improvement of EP and AW properties. However, this is accompanied by a considerable decrease in the fatigue life. By using a scanning electron microscope and energy dispersive spectrometer for analysis of the worn surface, mechanisms of action of various lubricating additives under different friction conditions were identified. Copyright © 2006 John Wiley & Sons, Ltd.
Tetrabenazine for hyperglycemic‐induced hemichorea–hemiballismus
Authors: Sitburana Oraporn , Ondo William G.
Published: September 2006

We reported a 74‐year‐old woman with new‐onset diabetes mellitus who presented with the sudden onset of mild left hemiparesis and marked left hemichorea–hemiballismus. Brain CT scan and MRI showed T1W, T2W, and DWI lesions in the right putamen and caudate, which have been previously reported in cases of hyperglycemic‐induced hemichorea–hemiballismus (HIHH). The patient dramatically responded to tetrabenazine within a day. Subsequent dose reductions lead to a reemergence of symptoms. Tetrabenazine improves a variety of hyperkinetic movement disorders but, to our knowledge, its use has never been reported for HIHH. © 2006 Movement Disorder Society
Fully balanced steady‐state 3D‐spin‐echo (bSSSE) imaging at 3 Tesla
Authors: Krug R. , Han E.T. , Banerjee S. , Majumdar S.
Published: September 2006

In this work a 3D fully balanced steady‐state spin‐echo sequence (bSSSE) was designed and implemented on a 3‐Tesla whole‐body MR scanner. In contrast to previously introduced nonbalanced SSSE (nbSSSE) sequences, bSSSE features fully rewound imaging gradients. Additionally, all phase encodings and the readout prephasing are performed after the refocusing pulse. Its performance was compared with previously used gradient‐echo (GE) and nbSSSE sequences. The signal response of each sequence was simulated by numerical solution of the Bloch equation. All sequences were then optimized based on these simulations for high‐resolution (HR) imaging of tissues with short relaxation times and applied to in vivo HR‐MRI of trabecular bone. bSSSE outperformed nbSSSE sequences in terms of SNR and SNR efficiency. Measurements of structural bone parameters revealed thinner trabeculae and a lower bone/bone‐marrow fraction for the bSSSE sequence compared to the nbSSSE sequence. By applying a parallel imaging technique based on generalized autocalibrating partially parallel acquisition (GRAPPA) with a reduction factor of 2, we were able to maintain a clinically feasible scan time using bSSSE. Comparisons of structural bone parameters revealed a difference of less than 3% for all structural parameters between parallel and conventional imaging. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Early proactive management improves upper urinary tract function and reduces the need for surgery in patients with myelomeningocele
Authors: Kessler Thomas M. , Lackner Jakob , Kiss Gustav , Rehder Peter , Madersbacher Helmut
Published: September 2006

Aims

To investigate whether upper urinary tract function and the need for surgery in patients with myelomeningocele depends on the timing of initiating neurourological management.

Patients and Methods

One hundred thirty‐three patients with myelomeningocele were included in our retrospective study. The patients were divided based on age at the initial evaluation into three categories: from day of birth to age 2 (group 1, n = 67), from age 3 to age 10 (group 2, n = 44), and after age 10 (group 3, n = 22). Upper urinary tract function and the need for surgery with the intention to preserve or normalize the upper urinary tract function were compared between the three groups.

Results

Mean follow‐up was 11, 10, and 9 years in group 1, 2, and 3, respectively. The upper urinary tract function was normal in 91%, 80%, and 82% at the initial evaluation (P = 0.194) and in 99%, 86%, and 86% at the last follow‐up (P = 0.012) in group 1, 2, and 3, respectively. Following failure of conservative therapy only, the proportions of patients undergoing surgical interventions with the intention to preserve or normalize the upper urinary tract function was significantly (P = 0.0002) different among the three groups: 15%, 34%, and 59%, respectively.

Conclusions

Early proactive management improves upper urinary tract function and reduces the need for surgery in patients with myelomeningocele in the long‐term. Therefore, initiation of proactive neurourological management as early as possible, ideally from the day of birth, is strongly recommended. Neurourol. Urodynam. 25:758–762, 2006. © 2006 Wiley‐Liss, Inc.
Stereospecific living radical polymerization for simultaneous control of molecular weight and tacticity
Authors: Kamigaito Masami , Satoh Kotaro
Published: September 2006

The simultaneous control of the molecular weights and the tacticity was attained even during radical polymerization by the judicious combinations of the living/controlled radical polymerizations based on the fast interconversion between the dormant and active species, and the stereospecific radical polymerizations mediated by the added Lewis acids or polar solvents via the coordination to the monomer/polymer terminal substituents. This can be useful for various monomers including not only conjugated monomers, such as acrylamides and methacrylates, but also nonconjugated ones such as vinyl acetate and N‐vinylpyrrolidone. Stereoblock polymers were easily obtained by the addition of the Lewis acids or by change of the solvents during the living radical polymerizations. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6147–6158, 2006
A run‐to‐run framework for prandial insulin dosing: handling real‐life uncertainty
Authors: Palerm C. C. , Zisser H. , Jovanovič L. , Doyle F. J.
Published: September 2006

Individuals with type 1 diabetes require frequent adjustment of their insulin dose to maintain as near to normal glycaemia as possible. This process is not only burdensome but also, for many, difficult to achieve. As a result, control algorithms to facilitate insulin dosage have been proposed, but have not been completely successful in normalizing glycaemia. Here we present a novel run‐to‐run control algorithm to adjust the meal‐related insulin dose using only post‐prandial blood glucose measurements. For each meal independently, the insulin dose is adjusted based on the performance measure for the same meal the previous day. A robustness analysis is performed which considers the sources of uncertainty typically encountered in clinical use. This shows that the system remains stable even with large uncertainty. Copyright © 2006 John Wiley & Sons, Ltd.
On performing concepts during science lectures
Authors: Pozzer‐Ardenghi Lilian , Roth Wolff‐Michael
Published: September 2006

When lecturing, teachers make use of both verbal and nonverbal communication. What is called teaching, therefore, involves not only the words and sentences a teacher utters and writes on the board during a lesson, but also all the hands/arms gestures, body movements, and facial expressions a teacher performs in the classroom. All of these communicative modalities constitute resources that are made available to students for making sense of and learning from lectures. Yet in the literature on teaching science, these other means of communication are little investigated and understood—and, correspondingly, they are undertheorized. The purpose of this position paper is to argue for a different view of concepts in lectures: they are performed simultaneously drawing on and producing multiple resources that are different expressions of the same holistic meaning unit. To support our point, we provide examples from a database of 26 lectures in a 12th‐grade biology class, where the human body was the main topic of study. We analyze how different types of resources—including verbal and nonverbal discourse and various material artifacts—interact during lectures. We provide evidence for the unified production of these various sense‐making resources during teaching to constitute a meaning unit, and we emphasize particularly the use of gestures and body orientations inside this meaning unit. We suggest that proper analyses of meaning units need to take into account not only language and diagrams but also a lecturer's pointing and depicting gestures, body positions, and the relationships between these different modalities. Scientific knowledge (conceptions) exists in the concurrent display of all sense‐making resources, which we, following Vygotsky, understand as forming a unit (identity) of nonidentical entities. © 2006 Wiley Periodicals, Inc. Sci Ed 91:96–114, 2007
Teachers' scientific epistemological views: The coherence with instruction and students' views***
Authors: Tsai Chin‐Chung
Published: September 2006

Research about the relationship between teachers' scientific epistemological views (SEVs) and science instruction is often an important issue for many science educators. This study, by collecting research data from four Taiwanese science teachers, their students, and classroom observations, was carried out to examine the coherences between teachers' SEVs and their (1) teaching beliefs, (2) instructional practices, (3) students' SEVs, and (4) students' perceptions toward actual science learning environments. The findings suggested adequate coherences between teachers' SEVs and their teaching beliefs as well as instructional practices. The teachers with relatively positivist‐aligned SEVs tended to draw attention to students' science scores in tests and allocate more instructional time on teacher‐directed lectures, tutorial problem practices, or in‐class examinations, implying a more passive or rote perspective about learning science. In contrast, teachers with constructivist‐oriented SEVs tended to focus on student understanding and application of scientific concepts and they adopted more time on student inquiry activities or interactive discussion. These findings are quite consistent with the results about the coherence between teachers' SEVs and students' perceptions toward science learning environments, suggesting that the constructivist‐oriented SEVs appeared to foster the creation of more constructivist‐oriented science learning environments. Finally, although this study provided some evidence that teachers' SEVs were likely related to their students' SEVs, the teachers' SEVs and those of their students were not obviously coherent. © 2006 Wiley Periodicals, Inc. Sci Ed 91:222–243, 2007
Two familial cases of high blood galactose of unknown aetiology
Authors: Brunetti‐Pierri Nicola , Opekun Antone R. , Craigen William J.
Published: September 2006

We report two male siblings presenting as newborns with increased blood galactose, urinary excretion of galactitol, and normal galactose 1‐phosphate on a breast milk diet. A lactose‐free diet led to normalization of all metabolites, while reintroduction of galactose in the diet resulted in an accumulation of metabolites. Potential causes of galactosaemia include: (1) activities of three enzymes of galactose metabolism: galactokinase (GALK), galactose‐1‐phosphate uridyltransferase (GALT), and uridine diphosphate galactose 4'‐epimerase (GALE), (2) portosystemic shunting, (3) Fanconi‐Bickel syndrome, (4) tyrosinaemia. Each was excluded with appropriate tests. These two familial cases may represent a novel autosomal or X‐linked recessive disorder of galactose metabolism, possibly due to a novel defect in the transport of galactose across the plasma membrane.
Expression and regulation of Spätzle‐processing enzyme in Drosophila
Authors: Mulinari Shai , Häcker Udo , Castillejo-López Casimiro
Published: September 2006

The Drosophila melanogaster Toll receptor controls embryonic dorsal‐ventral axis formation and is crucial for the innate immune response. In both cases, Toll is activated by the enzymatically cleaved form of its ligand Spätzle (Spz). During axis formation, Spz is cleaved by the maternally provided serine protease Easter while the Spätzle‐processing enzyme (SPE) activates Spz after infection. We confirm the role of SPE in immunity and show that it is a zygotic gene specifically expressed in immune tissues implying that the dual activation of Spz is achieved by differential spatiotemporal expression of two similar but distinct serine proteases.