bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of gefitinib versus erlotinib in patients with nonsmall cell lung cancer who failed previous chemotherapy
Authors: Kim Seung Tae , Lee Jeeyun , Kim Jeong‐hoon , Won Young‐Woong , Sun Jong‐Mu , Yun Jina , Park Yeon Hee , Ahn Jin Seok , Park Keunchil , Ahn Myung‐Ju
Published: April 2010

BACKGROUND:

Gefitinib and erlotinib are commonly used for salvage therapy in patients with nonsmall cell lung cancer (NSCLC) who have progressed on prior therapies. Although both agents have similar structure and have demonstrated efficacy in NSCLC, gefitinib and erlotinib have not been directly compared in terms of efficacy and other clinical outcomes in patients with NSCLC who have failed prior chemotherapy. This prompted us to analyze the clinical outcomes between gefitinib‐treated and erlotinib‐treated patients with metastatic or recurrent NSCLC.

METHODS:

A total of 467 patients with metastatic or recurrent NSCLC who had progressed on prior therapies and received gefitinib or erlotinib therapy between January 2006 and December 2008 were retrospectively reviewed. By using a matched‐pair case‐control study design, 171 pairs of gefitinib‐treated and erlotinib‐treated patients were matched according to sex, Eastern Cooperative Oncology Group (ECOG) performance status, histologic type, and smoking history.

RESULTS:

The median age of all patients was 58 years (range, 20‐85 years), and the median ECOG performance status was 1 (range, 0‐3). Of 342 patients, 294 (86%) received an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor as second‐line or third‐line therapy, whereas the remaining 14% had received >2 prior chemotherapy regimens before starting EGFR TK inhibitor therapy. The confirmed overall response rate was 35.1%, and the disease control rate was 64%. With 13.2 months of follow‐up, the median overall survival (OS) for the total 342 patients was 12.4 months (95% confidence interval [95% CI], 10.66‐14.14 months), and the median progression‐free survival (PFS) was 3.2 months (95% CI, 2.65‐3.75 months). The overall response rates and disease control rates in the gefitinib‐treated and erlotinib‐treated groups were 38% versus 32.2% (P = .273) and 63.2% versus 64.9%, respectively (P = .677). There was no statistically significant difference noted with regard to OS (median, 12.6 vs 12.1 months; P = 0.99) and PFS (median, 4.6 vs 2.7 months; P = .06) between the gefitinib‐treated and erlotinib‐treated groups.

CONCLUSIONS:

This retrospective analysis shows that gefitinib and erlotinib appear to have similar antitumor activity in terms of response rate and OS in pretreated patients with metastatic or recurrent NSCLC. Further prospective studies are warranted to elucidate any potential differences in toxicity and in dose intensity between gefitinib‐ and erlotinib‐treated patients. Cancer 2010. © 2010 American Cancer Society.
Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2‐positive breast cancer
Authors: Dominici Laura S. , Negron Gonzalez Viviana M. , Buzdar Aman U. , Lucci Anthony , Mittendorf Elizabeth A. , Le‐Petross Huong T. , Babiera Gildy V. , Meric‐Bernstam Funda , Hunt Kelly K. , Kuerer Henry M.
Published: April 2010

BACKGROUND:

The axillary pathologic complete response rate (pCR) and the effect of axillary pCR on disease‐free survival (DFS) was determined in patients with HER2‐positive breast cancer and biopsy‐proven axillary lymph node metastases who were receiving concurrent trastuzumab and neoadjuvant chemotherapy. The use of neoadjuvant chemotherapy is reported to result in pCR in the breast and axilla in up to 25% of patients. Patients achieving a pCR have improved DFS and overall survival. To the authors' knowledge, the rate of eradication of biopsy‐proven axillary lymph node metastases with trastuzumab‐containing neoadjuvant chemotherapy regimens has not been previously reported.

METHODS:

Records were reviewed of 109 consecutive patients with HER2‐positive breast cancer and axillary metastases confirmed by ultrasound‐guided fine‐needle aspiration biopsy who received trastuzumab‐containing neoadjuvant chemotherapy followed by breast surgery with complete axillary lymph node dissection. Survival was evaluated by the Kaplan‐Meier method. Clinicopathologic factors and DFS were compared between patients with and without axillary pCR.

RESULTS:

Eighty‐one patients (74%) achieved a pCR in the axilla. Axillary pCR was not associated with age, estrogen receptor status, grade, tumor size, initial N classification, or median number of lymph nodes removed. More patients with an axillary pCR also achieved a pCR in the breast (78% vs 25%; P < .001). At a median follow‐up of 29.1 months, DFS was significantly greater in the axillary pCR group (P = .02).

CONCLUSIONS:

Trastuzumab‐containing neoadjuvant chemotherapy appears to be effective in eradicating axillary lymph node metastases in the majority of patients treated. Patients who achieve an axillary pCR are reported to have improved DFS. The success of pCR with concurrent trastuzumab and chemotherapy in eradicating lymph node metastases has implications for surgical management of the axilla in these patients. Cancer 2010. © 2010 American Cancer Society.
CA 125 and the detection of recurrent ovarian cancer
Authors: Bast Robert C.
Published: April 2010

Rising cancer antigen 125 (CA125) levels have been used to detect recurrence of ovarian cancer. A recent study questions the value of this practice, but the clinical trial has significant limitations and discounts the value of early detection to permit treatment of recurrence with novel and conventional agents.
Optimizing utilization of resource pools in web application servers
Authors: Totok Alexander , Karamcheti Vijay
Published: April 2010

Among the web application server resources, the most critical for their performance are those that are held exclusively by a service request for the duration of its execution (or some significant part of it). Such exclusively held server resources become performance bottleneck points, with failures to obtain such a resource constituting a major portion of request rejections under server overload conditions. In this paper, we propose a methodology that computes the optimal pool sizes for two such critical resources: web server threads and database connections. Our methodology uses information about incoming request flow and about fine‐grained server resource utilization by service requests of different types, obtained through offline and online request profiling. In our methodology, we advocate (and show its benefits) the use of a database connection pooling mechanism that caches database connections for the duration of a service request execution (so‐called request‐wide database connection caching). We evaluate our methodology by testing it on the TPC‐W web application. Our method is able to accurately compute the optimal number of server threads and database connections, and the value of sustainable request throughput computed by the method always lies within a 5% margin of the actual value determined experimentally. Copyright © 2010 John Wiley & Sons, Ltd.
Nanowires Formed by the Co‐Assembly of a Negatively Charged Low‐Molecular Weight Gelator and a Zwitterionic Polythiophene
Authors: Li Feng , Palaniswamy Ganesan , de Jong Menno R. , Åslund Andreas , Konradsson Peter , Marcelis Antonius T. M. , Sudhölter Ernst J. R. , Stuart Martien A. Cohen , Leermakers Frans A. M.
Published: April 2010

Conjugated organic nanowires have been prepared by co‐assembling a carboxylate containing low‐molecular weight gelator (LMWG) and an amino acid substituted polythiophene derivative (PTT). Upon introducing the zwitterionic polyelectrolyte PTT to a basic molecular solution of the organogelator, the negative charges on the LMWG are compensated by the positive charges of the PTT. As a result, nanowires form through co‐assembly. These nanowires are visualized by both transmission electron microscopy (TEM) and atomic force microscopy (AFM). Depending on the concentration and ratio of the components these nanowires can be micrometers long. These measurements further suggest that the aggregates adopt a helical conformation. The morphology of these nanowires are studied with fluorescent confocal laser scanning microscopy (CLSM). The interactions between LMWG and PTT are characterized by steady‐state and time‐resolved fluorescence spectroscopy studies. The steady‐state spectra indicate that the backbone of the PTT adopts a more planar and more aggregated conformation when interacting with LMWG. The time‐ resolved fluorescence decay studies confirm this interpretation.
Impact of Amino Acid Substitutions near the Catalytic Site on the Spectral Properties of an O2‐Tolerant Membrane‐Bound [NiFe] Hydrogenase
Authors: Saggu Miguel , Ludwig Marcus , Friedrich Bärbel , Hildebrandt Peter , Bittl Robert , Lendzian Friedhelm , Lenz Oliver , Zebger Ingo
Published: April 2010

[NiFe] hydrogenases are widespread among microorganisms and catalyze the reversible cleavage of molecular hydrogen. However, only a few bacteria, such as Ralstonia eutropha H16 (Re), synthesize [NiFe] hydrogenases that perform H2 cycling in the presence of O2. These enzymes are of special interest for biotechnological applications. To gain further insight into the mechanism(s) responsible for the remarkable O2 tolerance, we employ FTIR and EPR spectroscopy to study mutant variants of the membrane‐bound hydrogenase (MBH) of Re‐carrying substitutions of a particular cysteine residue in the vicinity of the [NiFe] active site that is characteristic of O2‐tolerant membrane‐bound [NiFe] hydrogenases. We demonstrate that these MBH variants, despite minor changes in the electronic structure and in the interaction behavior with the embedding protein matrix, display all relevant catalytic and noncatalytic states of the wild‐type enzyme, as long as they are still located in the cytoplasmic membrane. Notably, in the oxidized Nir‐B state and the fully reduced forms, the CO stretching frequency increases with increasing polarity of the respective amino acid residue at the specific position of the cysteine residue. We purified the MBH mutant protein with a cysteine‐to‐alanine exchange to apparent homogeneity as dimeric enzyme after detergent solubilization from the membrane. This purified version displays increased oxygen sensitivity, which is reflected by detection of the oxygen‐inhibited Niu‐A state, an irreversible inactive redox state, and the light‐induced Nia‐L state even at room temperature.
Π‐Stacking Functionalization of Carbon Nanotubes through Micelle Swelling
Authors: Roquelet Cyrielle , Lauret Jean‐Sébastien , Alain‐Rizzo Valérie , Voisin Christophe , Fleurier Romain , Delarue Morgan , Garrot Damien , Loiseau Annick , Roussignol Philippe , Delaire Jacques A. , Deleporte Emmanuelle
Published: April 2010

We report on a new, original and efficient method for π‐stacking functionalization of single‐wall carbon nanotubes. This method is applied to the synthesis of a high‐yield light‐harvesting system combining single‐wall carbon nanotubes and porphyrin molecules. We developed a micelle‐swelling technique that leads to controlled and stable complexes presenting an efficient energy transfer. We demonstrate the key role of the organic solvent in the functionalization mechanism. By swelling the micelles, the solvent helps the non‐water‐soluble porphyrins to reach the micelle core and allows a strong enhancement of the interaction between porphyrins and nanotubes. This technique opens new avenues for the functionalization of carbon nanostructures.
Evaluating transformative practice in the U.S. Postal Service REDRESS program
Authors: Nabatchi Tina , Bingham Lisa Blomgren , Moon Yuseok
Published: April 2010

Interest in transformative mediation is growing, yet there are few tools with which to assess mediators' use of the transformative model. This study presents a novel way of examining transformative mediation in practice. It triangulates data from training and screening processes and surveys of both mediators and participants to determine whether mediators in the U.S. Postal Service REDRESS program were correctly using transformative mediation. The results indicate that during the period of the study REDRESS mediators were in fact engaged in transformative practice. Such triangulation of data may be a useful approach to assessing transformative practice in other organizations.
Performance analysis of a cell‐based call admission control scheme for QoS support in multimedia wireless networks
Authors: Nasser Nidal , Guizani Sghaier
Published: April 2010

Next generation wireless communication systems, including 3G and 4G technologies, are envisaged to support more mobile users and a variety of high‐bandwidth multimedia services. Different multimedia services have diverse bandwidth and quality of service (QoS) requirements from their users that need to be guaranteed by wireless cellular systems. Furthermore, these systems will use micro/pico cellular architecture to provide a higher capacity. As a result of the smaller coverage area of this architecture, handoff events will occur at a much higher rate compared with the present macrocellular systems. In this paper, a multiple‐threshold bandwidth reservation scheme combined with a call admission control algorithm is proposed and analyzed. The objective of our work is to achieve better QoS provisioning for mobile users while achieving efficient utilization of the available limited bandwidth. The proposed scheme is modeled as M/M/C/C queueing system and the performance measures, call blocking probability (CBP), and call dropping probability (CDP) are computed. The performance of our scheme is compared with the Complete Sharing (CS) policy. Simulation results show that our scheme surpasses the CS policy in terms of CBP, CDP, and bandwidth utilization. Copyright © 2010 John Wiley & Sons, Ltd.
Defining age limits of the sensitive period for attachment learning in rat pups
Authors: Upton Karen J. , Sullivan Regina M.
Published: April 2010

Enhanced odor preference learning and attenuated fear learning characterizes rat pups' attachment learning Sensitive Period for learning the maternal odor. This period terminates at 10 days old (PN10) with increasing endogenous levels of the stress hormone, corticosterone. Increasing Sensitive Period pups' corticosterone prematurely terminates the Sensitive Period, while decreasing corticosterone in older pups delays Sensitive Period termination. Here we extend these findings and define the age range corticosterone alters learning and question whether corticosterone permanently terminates the Sensitive Period. Pups were odor‐0.5 mA shock conditioned with either corticosterone increased (PN5–6; 4 mg/kg vs. saline) or decreased (PN15–16; naturally by maternal presence or corticosterone synthesis blocker, Metyrapone). Finally, PN7–8 pups were conditioned with corticosterone and reconditioned without corticosterone to assess whether the Sensitive Period was permanently terminated. Results indicate developmental limits for corticosterone regulation of pup learning are PN6 through PN15. Furthermore, inducing precocious corticosterone induced fear learning was not permanent, since reconditioning without corticosterone enabled odor preference learning. Results suggest pups are protected from learning aversions to maternal odor until approaching weaning. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 453–460, 2010.
Bimodal septal and cortical triggering and complex propagation patterns of spontaneous waves of activity in the developing mouse cerebral cortex
Authors: Conhaim Jay , Cedarbaum Emily R. , Barahimi Mitra , Moore Jennifer G. , Becker Matthew I. , Gleiss Helge , Kohl Christine , Moody William J.
Published: April 2010

Spontaneous waves of activity that propagate across large structures during specific developmental stages play central roles in CNS development. To understand the genesis and functions of these waves, it is critical to understand the spatial and temporal patterns of their propagation. We recently reported that spontaneous waves in the neonatal cerebral cortex originate from a ventrolateral pacemaker region. We have now analyzed a large number of spontaneous waves using calcium imaging over the entire area of coronal slices from E18‐P1 mouse brains. In all waves, the first cortical region active is this ventrolateral pacemaker. In half of the waves, however, the cortical pacemaker activity is itself triggered by preceding activity in the septal nuclei. Most waves are restricted to the septum and/or ventral cortex, with only some invading the dorsal cortex or the contralateral hemisphere. Waves fail to propagate at very stereotyped locations at the boundary between ventral and dorsal cortex and at the dorsal midline. Waves that cross these boundaries pause at these same locations. Waves at these stages are blocked by both picrotoxin and CNQX, indicating that both GABAA and AMPA receptors are involved in spontaneous activity. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 679–692, 2010
On the Tautomerism of Secondary Phosphane Oxides
Authors: Christiansen Andrea , Li Chuanzhao , Garland Marc , Selent Detlef , Ludwig Ralf , Spannenberg Anke , Baumann Wolfgang , Franke Robert , Börner Armin
Published: April 2010

The tautomeric behaviour of five secondary phosphane oxides (SPOs) with different electronic properties has been investigated by NMR and IR spectroscopy, density functional theory calculations and X‐ray structural analysis. Proof is given that only with strong electron‐withdrawing groups on the phosphorus atom can the relevant trivalent phosphinous acid be observed in the equilibrium, whereas in the case of electron‐rich phosphane oxides the pentavalent species dominates. For a detailed analysis of the IR spectra, the deconvolution programme BTEM has been successfully applied.
An Enzymatic Toolbox for the Kinetic Resolution of 2‐(Pyridin‐x‐yl)but‐3‐yn‐2‐ols and Tertiary Cyanohydrins
Authors: Nguyen Giang‐Son , Kourist Robert , Paravidino Monica , Hummel Anke , Rehdorf Jessica , Orru Romano V. A. , Hanefeld Ulf , Bornscheuer Uwe T.
Published: April 2010

The kinetic resolution of a series of acetates of tertiary alcohols bearing a nitrogen substituent has been studied by using several recombinant carboxyl esterases and variants thereof expressed in E. coli. Most of the enzymes were active in the conversion of these tertiary alcohols and excellent enantioselectivities were achieved in the synthesis of three 2‐(pyridin‐x‐yl)but‐3‐yn‐2‐ols with the nitrogen atom in the pyridine ring in the 2′‐, 3′‐, and 4′‐positions. The resolution of tertiary cyanohydrins proved to be more difficult as the enantioselectivity of the enzymes was generally lower. Nevertheless, (S)‐1‐cyano‐2,2,2‐trifluoro‐1‐phenylethyl acetate was obtained with 99 % ee. The results show that the limited substrate range of the individual enzymes in the synthesis of a series of tertiary alcohols can be efficiently overcome by using a combination of different enzymes.
CE‐MS characterization of negatively charged α‐, β‐ and γ‐CD derivatives and their application to the separation of dipeptide and tripeptide enantiomers by CE
Authors: Sungthong Bunleu , Iványi Róbert , Bunz Svenja‐Catharina , Neusüß Christian , Scriba Gerhard K. E.
Published: April 2010

Sulfated, sulfopropyl and carboxymethyl α‐, β‐ and γ‐CDs were characterized by CE‐ESI‐MS using an acidic BGE with anodic MS detection and a basic BGE with cathodic MS detection. Isomers of the sulfated CDs comigrated in both systems. The acidic BGE with anodic MS detection resulted in slightly better separation of the isomers of the sulfopropyl CDs, which were separated according to the number of substituents. In the case of carboxymethyl CDs, isomers with an identical number of substituents but with a different substitution pattern with regard to substitution of the primary and secondary hydroxyl groups of the CDs could be separated using the basic BGE. The separation of the LL and DD enantiomers of dipeptides and tripeptides using the CDs was studied with regard to the amino acid sequence and the nature of the CDs. Standardized conditions with regard to buffer pH, CD concentration and voltage were applied. The peptides were analyzed at pH 2.5 as positively charged compounds and at pH 5.3 as neutral zwitterions. The β‐CD derivatives were more effective chiral selectors for the investigated peptides followed by the α‐CD derivatives. The γ‐CDs were the least effective selectors. The enantiomer migration order depended on both the CD and the amino acid sequence of the peptides. For several combinations, pH‐dependent reversal of the enantiomer migration order was also observed.
Search for optimum conditions of Paulownia autohydrolysis process and influence in pulping process
Authors: García Juan C. , Zamudio Minerva A.M. , Pérez Antonio , López Francisco , Colodette Jorge L.
Published: April 2010

In this study, we evaluated the potential of a species trihybrid Paulownia fortunei, tormentosa, and elongata as an industrial crop in terms of its contents in holocellulose, lignin, xylo‐oligomers, monomers, and other glucan and its use for making cellulose pulp. Well‐optimized biomass autohydrolysis processes yield valuable liquid and solid phases that can be used to produce liquid fuels and cellulosic pulp. The process was modeled to optimize the extraction of xylo‐oligomers and xylose in the liquid phase while preserving the integrity of cellulose fibers. The optimum processing conditions (viz. temperatures of 180–195°C and operating times of 0–15 min) provided an acceptable solid phase yield (70%), while maintaining a high xylose and xylo‐oligomer contents in the liquid phase. Soda—anthraquinone pulping of solid fraction provide 60.6% pulp yield at Kappa number 33 and a viscosity of 787 cm3/g. The autohydrolyzed chips required 16.6% less alkali than the regular chips to achieve Kappa number 33. © 2010 American Institute of Chemical Engineers Environ Prog, 2011
Numerical prediction of isothermally reacting mixing layer using vortex‐in‐cell and filtered density function
Authors: Siklawi C. , Milane R. E.
Published: April 2010

A large eddy simulation based on the filtered vorticity transport equation and the filtered density function (FDF) transport equation developed in an earlier study is extended to predict a chemically reacting flow with no heat release. The filtered vorticity transport equation is solved using the vortex‐in‐cell scheme in conjunction with the dynamic eddy viscosity subgrid‐scale models. The transport equation for FDF is solved using the Lagrangian Monte‐Carlo method. The methodology is tested on a chemically reacting spatially growing mixing layer with no heat release. The effects of Damköhler number (Da) on the concentration structure of the reacting mixing layer, the mean reactant and product concentrations and on the reactant FDF are investigated. It is shown that mixing has a greater effect on scalar field within the vortex structure as compared with the braid regions. Also for high Da, the reaction zones are mainly limited to the thin reacting interfacial zones, i.e. the contact zone between the reactants, whereas for low Da, the reacting zones are spread as reacting pockets within the vortex structure. The effects of Da on mean reactant and product concentrations, root‐mean‐square concentration fluctuations and probability density are discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Jubiläum multimediale
Authors: Finetti Marco
Published: April 2010

Soundcollage, Märchenbuch und eine fulminante Dankesrede: Die 25. Verleihung des renommiertesten deutschen Forschungspreises war voller besonderer Momente
Qualität statt Quantität
Authors: Kleiner Matthias
Published: April 2010

Die Publikationsflut schadet der Wissenschaft. Die DFG antwortet nun auf ihre Weise: Unsere verbindlichen Regeln für Literaturangaben in Förderanträgen und Abschlussberichten sind ein Paradigmenwechsel
Immer noch gut für Überraschungen
Authors: Martin Lutz
Published: April 2010

Mehr als sieben Jahrzehnte ruhten die Grabungen am Tell Halaf. Vor kurzem haben deutsche und syrische Archäologen die Arbeit wieder aufgenommen – und gewinnen erneut vielfältige Einblicke in die altorientalische Siedlungsgeschichte
Microwave‐assisted synthesis of novel 4‐N,N‐dimethylamino‐ and 4‐cycloamino‐ substituted 1,2,4‐triazole‐3‐thiones
Authors: Gobis Katarzyna , Foks Henryk
Published: April 2010

4‐N,N‐Dimethylamino‐ and 4‐cycloamino‐5‐phenyl‐1,2,4‐triazole‐3‐thiones 1–13 have been synthesized from benzhydrazides and substituted methyl dithiocarbazates under various conditions including short microwave irradiations. The last method seemed faster than the classical refluxing one. The influence of base and solvent types on the reaction direction has been also examined. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:188–195, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20594
GRP78 as potential predictor for breast cancer response to adjuvant taxane therapy
Authors: Lee Eunjung , Nichols Peter , Groshen Susan , Spicer Darcy , Lee Amy S.
Published: April 2010

Few predictive markers exist for response to adjuvant chemotherapy in breast cancer. The 78‐kDa glucose‐regulated protein (GRP78) is a potent antiapoptotic factor, conferring drug resistance. Recently, we reported that high GRP78 expression in breast cancer specimens predicts a shorter recurrence‐free survival in patients who received doxorubicin‐based adjuvant chemotherapy. Interestingly, the opposite effect was observed in 25 patients who additionally received a taxane. To confirm this potentially paradigm shifting finding, we investigated whether GRP78 is associated with recurrence‐free survival in an independent cohort of taxane‐treated breast cancer patients. Immunohistochemical staining of GRP78 was performed on archival paraffin‐embedded formalin‐fixed tumor specimens obtained from 48 female breast cancer patients before chemotherapy treatment. These patients received doxorubicin and cyclophosphamide, followed by paclitaxel or docetaxel on a clinical trial. GRP78 expression level was evaluated by a pathologist, masked to all clinical and outcome data. Association between GRP78 expression and recurrence‐free survival was evaluated. GRP78 positivity predicts a better recurrence‐free survival, independent of other prognostic factors [hazard ratio (HR) for moderate positivity: 0.40 (95% confidence interval (CI): 0.087–1.83); HR for strong positivity: 0.16 (95% CI: 0.018–1.50); ptrend = 0.053]. In a pooled analysis with the previous 25 patients, almost identical HRs were obtained with ptrend = 0.024. This provides further evidence that GRP78 is a potential independent predictor for response to taxane‐based adjuvant chemotherapy in breast cancer.
Alpha‐fetoprotein: A new member of intracellular signal molecules in regulation of the PI3K/AKT signaling in human hepatoma cell lines
Authors: Li Mengsen , Li Hui , Li Chaoying , Wang Shanshan , Jiang Wei , Liu Zhongmin , Zhou Sheng , Liu Xinhua , McNutt Michael A. , Li Gang
Published: April 2010

Despite its well‐defined role as a serum growth factor during fetal liver development and hepatic oncogenesis, the biological significance of cytoplasmic alpha‐fetoprotein (AFP) remains incompletely understood. Here, we provide evidence to illustrate that cytoplasmic AFP may function as a regulator in the phosphatidylinositol 3‐kinase (PI3K)/AKT pathway in human hepatocellular carcinoma cells. The results demonstrated colocalization and interaction of AFP and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in the cytoplasm of AFP‐producing Bel 7402 and HepG2 cells, with an interaction distance of 12.6 ± 2.7 Å as determined with the fluorescence resonance energy transfer technique. Knockdown of AFP mRNA or inhibition of AFP expression by all trans‐retinoic acid resulted in enhancement of the PTEN level with a synchronous decrease in phosphorylated AKT. Transfection of the afp gene into HLE cells (originally AFP negative) led to a significant activation of AKT signaling. The inhibition of PI3K signaling by LY 294002 was simultaneously reversed by transfection, accompanied by diminution of all trans‐retinoic acid‐induced upregulation of PTEN and enhancement of cell growth. In conclusion, these results demonstrate that cytoplasmic AFP is involved in regulation of hepatocellular growth and tumorigenesis.
Diagnostic evaluation of apoptosis inhibitory gene and tissue inhibitor matrix metalloproteinase‐2 in patients with bladder cancer
Authors: Eissa Sanaa , Shabayek Marwa I. , Ismail Manal F. , El‐Allawy Raouf M. , Hamdy Mohamed A.
Published: April 2010

Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low‐grade tumors. This study validates easier and less time‐consuming techniques for the estimation of survivin and TIMP‐2 in urine of bladder cancer patients to evaluate them in comparison with cytology. This study includes malignant (bladder cancer patients, n = 42), benign (patients with bilharzial cystitis, n = 22) and healthy (n = 21) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary survivin by qualitative RT‐nested PCR and TIMP‐2 by ELISA. Significantly higher positivity rates of urinary survivin and TIMP‐2 were observed in the malignant group compared with benign and healthy groups. On associating the two urinary markers with different clinicopathological factors, only TIMP‐2 exerted significantly higher positivity rate in invasive stage (100%) than superficial stage (82.3%). Survivin showed 78.6% sensitivity, 95.3% specificity, 94.3% PPV, 82% NPV, and 87% accuracy. When combined with urine cytology, the sensitivity increased to 83.3%. While on applying the cutoff value of urinary TIMP‐2 (≤639.5 pg/mg protein), it showed 93% sensitivity, 83.7% specificity, 85% PPV, 92.3% NPV, and 88.2% accuracy. When combined with urine cytology, the TIMP‐2 sensitivity remained 93%. On combining cytology with both urinary survivin and TIMP‐2, the highest sensitivity was reached (98%). Survivin and TIMP‐2 can be considered as potentially useful urine markers in early detection of bladder cancer. © 2010 IUBMB IUBMB Life, 62(5): 394–399, 2010
Thromboelastographic study of biomaterials
Authors: Peng Henry T.
Published: April 2010

Thromboelastography (TEG) is drawing more attention for clinical andin vitrostudies of blood coagulation. It can be applied to evaluate the effects of both blood‐soluble and insoluble biomaterials on whole blood coagulation from the beginning of coagulation through clot formation to the ending with fibrinolysis. TEG may also identify the relative contributions of various clotting factors, such as fibrinogen and platelets, to the overall coagulation process based on profiles of its variables using whole and partial blood components. A comprehensive review has been conducted on its applications for the assessment of a wide range of blood‐contacting biomaterials ranging from polymers to ceramics and biomedical devices involved in many applications. The methodology is different in terms of instrumentation, the methods to activate blood coagulation, the type of blood (citrated versus fresh blood), and study settings (in vitro,in vivo, and clinical trials). The author's own work and future directions are discussed as well. TEG should be considered as one of the most useful tools for evaluatingin vitroandin vivoblood–biomaterial interactions for different applications. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
An in vitro investigation of the mechanical–chemical and biological properties of calcium phosphate/calcium silicate/bismutite cement for dental pulp capping
Authors: Shen Qingyi , Sun Jiao , Wu Jie , Liu Changsheng , Chen Fangping
Published: April 2010

The properties of new calcium phosphate/calcium silicate/bismutite (CPCSBi) cement were compared with those of calcium hydroxide (CH) and Dycal cements in dental pulp‐capping applications. CPCSBi is composed of hydroxyapatite, tetracalcium phosphate, bismutite, and calcium silicate, which was analyzed by SEM, FTIR, and XRD. The results of ion release from CPCSBi showed that the concentrations of Bi3+, Ca2+, PO42−, and Si4+ increased with time in deionized water solutions. The setting time of CPCSBi and Dycal was 13 min 50 s and 2 min 25 s, respectively. There were no statistical differences in compressive strength and solubility between CPCSBi and Dycal (p > 0.05). The pH of CPCSBi (10.9) was lower than that of CH (11.6) and Dycal (12.5) after immersion for 24 h. Only slight cytotoxicity appeared for CPCSBi, whereas both CH and Dycal produced moderate discoloration and lysis. In antimicrobial tests against Sm, Av, La, and Sa, the antimicrobial potency of the CPCSBi was approximately 5–10 times greater than that of Dycal and CH groups. The dissoluble dentin matrix components (DDMCs) extracted from CPCSBi exposed to dentin powder demonstrated increased expression of dentin sialophosphoprotein (DSPP) and soteocalcin (OCN) dramatically in human pulp cells by RT‐PCR. These results suggest that CPCSBi will be a good candidate for use as a dental pulp‐capping agent in future. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Bioactivity and architecture of Candida albicans biofilms developed on poly(methyl methacrylate) resin surface
Authors: da Silva Wander José , Seneviratne Jayampath , Samaranayake Lakshman Perera , Del Bel Cury Altair Antoninha
Published: April 2010

The aim of this study was to evaluate the bioactivity and architecture of Candida albicans biofilms developed on the surface of poly(methyl methacrylate) (PMMA) resin. To do this, surface roughness (SR) and surface free energy of PMMA specimens were measured. Next, the biofilms of two different C. albicans strains (ATCC 90028 and SC5314) were allowed to develop on the PMMA surface and evaluated at 24, 48, and 72 h after adhesion. The bioactivity of the biofilms was measured by the XTT reduction assay. Biofilm topography was evaluated by scanning electron microscopy. Confocal microscopy was used to evaluate the architectural properties of bio‐volume, average thickness, biofilm roughness, surface area/volume ratio and the proportion of live/dead cells in the different biofilm development stages. SR and SFE had no influence on biofilm development. Each strain exhibited a different biofilm activity (P < 0.001). Confocal images showed different architectures for the different biofilm development stages. We conclude that the main differences detected in biofilm bioactivity and architecture were related to the characteristics of each C. albicans strain and to biofilm development time. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Enzymatic hydrolysis of sugarcane bagasse for bioethanol production: determining optimal enzyme loading using neural networks
Authors: Rivera Elmer Ccopa , Rabelo Sarita Cândida , dos Reis Garcia Daniella , Filho Rubens Maciel , da Costa Aline Carvalho
Published: April 2010

BACKGROUND:The efficient production of a fermentable hydrolyzate is an immensely important requirement in the utilization of lignocellulosic biomass as a feedstock in bioethanol production processes. The identification of the optimal enzyme loading is of particular importance to maximize the amount of glucose produced from lignocellulosic materials while maintaining low costs. This requirement can only be achieved by incorporating reliable methodologies to properly address the optimization problem.

RESULTS:In this work, a data‐driven technique based on artificial neural networks and design of experiments have been integrated in order to identify the optimal enzyme combination. The enzymatic hydrolysis of sugarcane bagasse was used as a case study. This technique was used to build up a model of the combined effects of cellulase (FPU/L) and β‐glucosidase (CBU/L) loads on glucose yield (%) after enzymatic hydrolysis. The optimal glucose yield, above 99%, was achieved with cellulase and β‐glucosidase concentrations in the ranges of 460.0 to 580.0 FPU L−1(15.3–19.3 FPU g−1bagasse) and 750.0 to 1140.0 CBU L−1(2–38 CBU g−1bagasse), respectively.

CONCLUSIONS:The dynamic model developed can be used not only to the prediction of glucose concentration profiles for different enzymatic loadings, but also to obtain the optimum enzymes loading that leads to high glucose yield. It can promote both a successful hydrolysis process control and a more effective employment of enzymes. Copyright © 2010 Society of Chemical Industry
Trauma exposure in childhood impairs the ability to recall specific autobiographical memories in late adolescence
Authors: Brennen Tim , Hasanović Mevludin , Zotović Marija , Blix Ines , Solheim Skar Ane‐Marthe , Prelić Nera Kravić , Mehmedović Indira , Pajević Izet , Popović Nemanja , Gavrilov‐Jerković Vesna
Published: April 2010

J. M. G. Williams (1996) predicted that exposure to potentially traumatizing events at an early age would give rise to overgeneral recall from autobiographical memory, i.e., recall of general rather than specific events, and that in adolescence this tendency would be uncorrelated with psychopathological symptoms, e.g., depression. This was supported by two studies where war‐exposed Bosnian adolescents produced significantly fewer specific autobiographical memories than a Norwegian control group, as did bombing‐exposed Serbian adolescents compared to nontrauma‐exposed Serbians. No significant correlations were found between autobiographical memory specificity and measures of depression, anxiety, dissociation or impact of trauma, which is consistent with Williams' idea that an overgeneral memory retrieval strategy is at first protective, and a risk factor for depression only upon reaching adulthood.
Liver Grafts Contain a Unique Subset of Natural Killer Cells That Are Transferred Into the Recipient After Liver Transplantation
Authors: Moroso Viviana , Metselaar Herold J. , Mancham Shanta , Tilanus Hugo W. , Eissens Diana , van der Meer Arnold , van der Laan Luc J. W. , Kuipers Ernst J. , Joosten Irma , Kwekkeboom Jaap
Published: April 2010

In contrast to other solid organ transplantations, liver grafts have tolerogenic properties. Animal models indicate that donor leukocytes transferred into the recipient after liver transplantation (LTX) play a relevant role in this tolerogenic phenomenon. However, the specific donor cell types involved in modulation of the recipient alloresponse are not yet defined. We hypothesized that this unique property of liver grafts may be related to their high content of organ-specific natural killer (NK) and CD56+ T cells. Here, we show that a high proportion of hepatic NK cells that detach from human liver grafts during pretransplant perfusion belong to the CD56bright subset, and are in an activated state (CD69+). Liver NK cells contained perforin and granzymes, exerted stronger cytotoxicity against K562 target cells when compared with blood NK cells, and secreted interferon-γ, but no interleukin-10 or T helper 2 cytokines, upon stimulation with monokines. Interestingly, whereas the CD56bright subset is classically considered as noncytolytic, liver CD56bright NK cells showed a high content of cytolytic molecules and degranulated in response to K562 cells. After LTX, but not after renal transplantation, significant numbers of donor CD56dim NK and CD56+ T cells were detected in the recipient circulation for approximately 2 weeks. In conclusion, during clinical LTX, activated and highly cytotoxic NK cells of donor origin are transferred into the recipient, and a subset of them mixes with the recirculating recipient NK cell pool. The unique properties of the transferred hepatic NK cells may enable them to play a role in regulating the immunological response of the recipient against the graft and therefore contribute to liver tolerogenicity. Liver Transpl 16:895–908, 2010. © 2010 AASLD.
Development of Electrospun Three‐arm Star Poly(ε‐caprolactone) Meshes for Tissue Engineering Applications
Authors: Puppi Dario , Detta Nicola , Piras Anna Maria , Chiellini Federica , Clarke David A. , Reilly Gwendolen C. , Chiellini Emo
Published: April 2010

We have developed three‐dimensional electrospun microfibrous meshes of a novel star branched three‐arm poly(ε‐caprolactone) (*PCL) as potential scaffolds for tissue engineering applications. The processing conditions required to obtain uniform fibers were optimized by studying their influence on fiber morphology and size. Polymer molecular weight and solution feed rate influenced both the mesh microstructure and the tensile properties of the developed mats. Electrospun samples were also tested for their mechanical properties in wet conditions, showing higher yield strength and strain in comparison to that observed in dry conditions. Cell culture experiments employing MC3T3‐E1 osteoblast like cells showed good cell viability adhesion and collagen production on the *PCL scaffolds.

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Fluorinated Polymer Nanoparticles as a Novel 19F MRI Contrast Agent Prepared by Dendrimer‐Initiated Living Radical Polymerization
Authors: Ogawa Michihiro , Nitahara Satoshi , Aoki Hiroyuki , Ito Shinzaburo , Narazaki Michiko , Matsuda Tetsuya
Published: April 2010

Novel fluorinated polymer nanoparticles (PNPs) for 19F MRI were prepared by living radical polymerization initiated by a dendrimer. The dendritic macroinitiator with Br substituents was synthesized from hydroxy‐group‐terminated G2 polyamidoamine dendrimers. The arborescent fluorinated polymers of 2,2,3,3‐tetrafluoropropyl methacrylate and 2,2,2‐trifluoroethyl methacrylate were characterized in molecular weight, the number of arms, the degree of polymerization per arm, and the diameter as a whole. The PNP diameter was precisely controlled by the molecular weight in the range of 3–25 nm. In addition, the fluorinated PNP gave a narrow resonance by 19F NMR spectroscopy. These results indicate that the fluorinated PNP can be used as a new type of 19F MRI agent.

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Dramatic Improvements in Mechanical Properties of Poly(L‐lactide)/Silica Nanocomposites by Addition of Hyperbranched Poly(ester amide)
Authors: Wen Xin , Lin Ying , Han Changyu , Han Lijing , Li Yuesheng , Dong Lisong
Published: April 2010

Biodegradable hyperbranched poly(ester amide) (HBP) was used as a compatibilizer to modify PLA/SiO2 nanocomposites for the first time. The ternary composites displayed dramatically improved mechanical properties including excellent toughness and fairly high stiffness. TEM images revealed that an encapsulation structure was formed by HBP surrounding SiO2 nanoparticles, and their surfaces became flocculent due to the migration process of silica. The linear viscoelastic behavior of the nanocomposites measured by parallel plate rheometer indicated that strong interface adhesion existed between PLA matrix and silica nanofiller after incorporating of HBP. The compatibilization effect of HBP and the enhanced mobility of nanoparticles contributed to the improved mechanical properties.

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Do hypermobile subjects without pain have alteration to the feedback mechanisms controlling the shoulder girdle?
Authors: Jeremiah H.M. , Alexander C.M.
Published: April 2010

Objectives: It has been reported that hypermobile subjects have proprioceptive deficits. However, it remains unclear whether pain‐free subjects with hypermobility also have deficits.

Methods: Ten subjects with hypermobility and nine without hypermobility were recruited following ethical approval and informed consent. Shoulder mobility, joint position sense (JPS) and a reflex of trapezius evoked from arm afferents were compared.

Results: There was greater shoulder mobility in the hypermobile group (p = 0.004). There were no differences in shoulder JPS between the groups (p = 0.27), although, the hypermobile group displayed a larger degree of variability (p = 0.014). Finally, there were no differences in the latency of upper and lower trapezius reflexes evoked from arm afferents (p = 0.86 and 0.98, respectively).

Conclusions: In a group of people with hypermobility without shoulder problems, there was no difference in either shoulder JPS or reflex latency when compared with a non‐ hypermobile group. The relevance of pain to proprioceptive deficits is discussed. © 2010 John Wiley & Sons, Ltd.
Dental health at the transition from the Late Antique to the early Medieval period on Croatia's eastern Adriatic coast
Authors: Šlaus Mario , Bedić Željka , Rajić Šikanjić Petra , Vodanović Marin , Domić Kunić Alka
Published: April 2010

Dento‐alveolar pathologies: caries, ante mortem tooth loss, abscesses, calculus, alveolar resorption and tooth wear were analysed in two composite skeletal series from Croatia's eastern Adriatic coast (Dalmatia). The first consists of 103 skeletons from seven Late Antique (3rd–6th century AD) sites, the second of 151 skeletons from three Early Medieval (7th–11th centuries AD) sites. As recent bioarhaeological studies (Šlaus,2008) showed a significant increase of disease loads and trauma frequencies in Dalmatia during the Early Medieval period, the aim of this study was to investigate whether dental health was equally adversely affected by the Late Antique/Early Medieval transition. The results of our analyses show that the frequencies of carious lesions, ante mortem tooth loss, abscesses and alveolar resorption increased significantly during the Early Medieval period, as did the degree of heavy occlusal wear on posterior teeth. These data suggest a change in alimentary habits, with a significantly higher dependence on carbohydrates and a greater reliance on hard, fibrous foods requiring vigorous mastication in the Early Medieval diet. The combination of higher calculus and lower caries rates in the Late Antique series similarly suggests more protein in the Late Antique diet and is, therefore, also consistent with the hypothesised change in alimentary habits. In general (the two exceptions are male caries and female alveolar resorption frequencies) lesion frequencies increased uniformly in both sexes suggesting that the deterioration of dental health during the Early Medieval period equally affected males and females. Cumulatively, the collected data suggest that the political, social, economic and religious changes that characterised the Late Antique/Early Medieval transition in Dalmatia resulted in a clear discontinuity, not only from the cultural, but also from the biological point of view with an evident deterioration of oral health during the Early Medieval period. Copyright © 2010 John Wiley & Sons, Ltd.
Early vaginal bleeding has no impact on markers used in first trimester aneuploidy screening
Authors: Spencer K. , Spencer C. E. , Stamatopoulou A. , Staboulidou I. , Nicolaides K. H.
Published: April 2010

Objective

To assess the impact of early vaginal bleeding on the levels of markers used in first trimester screening for aneuploidy.

Methods

A retrospective analysis was carried out on the free beta human chorionic gonadotrophin (β‐hCG) and pregnancy associated plasma protein‐A (PAPP‐A) levels and nuchal translucency thickness in 49 653 women with a normal singleton fetus who had first trimester combined screening for Down Syndrome in three centres. Median MoMs and the distribution of log MoMs of the two markers were compared in two groups—7470 women who self‐reported vaginal bleeding and 42 183 women who reported no vaginal bleeding at any stage prior to the screening test.

Results

The overall median MoM free β‐hCG and that in the bleeding and non‐bleeding group were 0.9854, 1.0012 and 0.9832, and for PAPP‐A were 1.0407, 1.0413 and 1.037. There was no significant difference between the bleeding and non‐bleeding group by median test (p = 0.080) or by t‐test comparing log MoMs (p = 0.1305) for free β‐hCG and for PAPP‐A with median test (p = 0.5071) or by t‐test comparing log MoMs (p = 0.1740). For delta nuchal translucency (NT) there was also no significant difference between the bleeding and non‐bleeding group (p = 0.055).

Conclusion

Vaginal bleeding has little or no impact on first trimester marker levels and no correction is necessary. Copyright © 2010 John Wiley & Sons, Ltd.