bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitrocytotoxicity of dental alloys and cpTi obtained by casting
Authors: Faria Adriana C. L. , Rosa Adalberto L. , Rodrigues Renata C. S. , Ribeiro Ricardo F.
Published: December 2007

Background: This study aimed to compare the cytotoxicity of base‐metal dental alloys and to evaluate if the casting method could influence their cytotoxicity. Methods: Disks of base‐metal dental alloys were cast by two methods: plasma, under argon atmosphere, injected by vacuum‐pressure; and oxygen‐gas flame, injected by centrifugation, except Ti‐6Al‐4V and commercially pure titanium (cpTi), cast only by plasma. SCC9 cells were cultured in culture media D‐MEM/Ham's F12 supplemented, at 37°C in a humidified atmosphere of 5% carbon dioxide and 95% air, on the previously prepared disks. At subconfluence in wells without disks (control), cell number and viability were evaluated. Results: In plasma method, cpTi and Ti‐6Al‐4V were similar to control and presented higher number of cells than all other alloys, followed by Ni‐Cr. In oxygen‐gas flame method, all alloys presented fewer cells than control. Ni‐Cr presented more cells than any other alloy, followed by Co‐Cr‐Mo‐W which presented more cells than Ni‐Cr‐Ti, Co‐Cr‐Mo, and Ni‐Cr‐Be. There were no significant differences between casting methods related to cell number. Cell viability was not affected by either chemical composition or casting methods. Conclusion: cpTi and Ti‐6Al‐4V were not cytotoxic while Ni‐Cr‐Be was the most cytotoxic among tested alloys. The casting method did not affect cytotoxicity of the alloys. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
In vitro biostability evaluation of polyurethane composites in acidic, basic, oxidative, and neutral solutions
Authors: Lyu SuPing , Schley James , Loy Brian , Luo Lian , Hobot Chris , Sparer Randall , Untereker Darrel , Krzeszak Jason
Published: December 2007

New and improved properties can often be achieved by compounding two or more different but compatible materials. But, can failure possibility also be increased by such a compounding strategy? In this article, we compared the in vitro biostability of composites with that of the pure polymer. We tested three model composites in oxidative, acidic, basic, and neutral solutions. We found that oxidation degradation was much more profound in the composites than in the corresponding pure polymer. This degradation seemed to be an intrinsic property of composite materials. We also observed the well documented interfacial debonding between filler and matrix and its effects on the mechanical reinforcement of the hydrated composites. The improvements in acid and base resistance were also observed. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Tissue‐engineered blood vessels with endothelial nitric oxide synthase activity
Authors: Lim Sang Hyun , Cho Seung‐Woo , Park Jong‐Chul , Jeon Oju , Lim Jae Min , Kim Sang‐Soo , Kim Byung‐Soo
Published: December 2007

Nondegradable synthetic polymer vascular grafts used in cardiovascular surgery have shown serious shortcomings, including thrombosis, calcification, infection, and lack of growth potential. Tissue engineering of vascular grafts with autologous stem cells and biodegradable polymeric materials could solve these problems. The present study is aimed to develop a tissue‐engineered vascular graft (TEVG) with functional endothelium using autologous bone marrow‐derived cells (BMCs) and a hybrid biodegradable polymer scaffold. Hybrid biodegradable polymer scaffolds were fabricated from poly(lactide‐co‐ε‐caprolactone) (PLCL) copolymer reinforced with poly(glycolic acid) (PGA) fibers. Canine bone marrow mononuclear cells were induced in vitro to differentiate into vascular smooth muscle cells and endothelial cells. TEVGs (internal diameter: 10 mm, length: 40 mm) were fabricated by seeding vascular cells differentiated from BMCs onto PGA/PLCL scaffolds and implanted into the abdominal aorta of bone marrow donor dogs (n = 7). Eight weeks after implantation of the TEVGs, the vascular grafts remained patent. Histological and immunohistochemical analyses of the vascular grafts retrieved at 8 weeks revealed the regeneration of endothelium and smooth muscle and the presence of collagen. Western blot analysis showed that endothelial nitric oxide synthase (eNOS) was expressed in TEVGs comparable to native abdominal aortas. This study demonstrates that vascular grafts with significant eNOS activity can be tissue‐engineered with autologous BMCs and hybrid biodegradable polymer scaffolds. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
The role of Doppler sonography in predicting severity of acute pancreatitis
Authors: Topal Naile Bolca , Kaya Ekrem , Ercan Ilker , Pourbagher Mir Ali , Topal Ugur
Published: December 2007

Purpose

To investigate the role of Doppler sonography (DUS) examination of major abdominal arteries in predicting severity of acute pancreatitis (AP).

Methods

Twenty‐nine patients diagnosed with AP and 14 controls were blindly and prospectively evaluated with Doppler sonography. Disease severity was defined clinically according to acute physiology and chronic health evaluation (APACHE II) score and was classified as severe for APACHE II score ≥8. DUS examination included the measurement of peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistance index (RI) of the celiac artery (CA) and superior mesenteric artery (SMA). Statistical analysis included Mann‐Whitney U test, Student t test, and receiver operating characteristic curve analysis.

Results

Twelve patients had severe AP and 17 had mild AP. PSV, EDV, and PI of the CA and RI of the SMA were higher in the severe AP group than in the mild AP and control groups (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity were 100% and 94%, respectively, for a 87 cm/second CA PSV cutoff value, 75% and 100%, respectively, for a 22 cm/second CA EDV cutoff value, 92% and 82%, respectively, for a 1.29 CA PI cutoff value, and 100% and 100%, respectively, for a 0.86 SMA RI cutoff value.

Conclusion

DUS can be useful in predicting the severity of AP in the early period of admission phase of the disease. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
Newly‐developed Sendai virus vector for retinal gene transfer: reduction of innate immune response via deletion of all envelope‐related genes
Authors: Murakami Yusuke , Ikeda Yasuhiro , Yonemitsu Yoshikazu , Tanaka Sakura , Kondo Haruhiko , Okano Shinji , Kohno Ri‐ichiro , Miyazaki Masanori , Inoue Makoto , Hasegawa Mamoru , Ishibashi Tatsuro , Sueishi Katsuo
Published: December 2007

Background

Recombinant Sendai virus vectors (rSeV) constitute a new class of cytoplasmic RNA vectors that have shown efficient gene transfer in various organs, including retinal tissue; however, the related immune responses remain to be overcome in view of clinical applications. We recently developed a novel rSeV from which all envelope‐related genes were deleted (rSeV/dFdMdHN) and, in the present study, assess host immune responses following retinal gene transfer.

Methods

rSeV/dFdMdHN or conventional F‐gene deleted rSeV (rSeV/dF) was injected into subretinal space of adult Wistar rats or C57BL/6 mice. The transgene expression and histopathological findings were assessed at various time points. Immunological assessments, including the expression of proinflammatory cytokines, natural killer (NK)‐cell activity, as well as SeV‐specific cytotoxic T lymphocytes (CTLs) and antibodies, were performed following vector injection.

Results

rSeV/dFdMdHN showed high gene transfer efficiency into the retinal pigment epithelium at an equivalent level to that seen with rSeV/dF. In the early phase, the upregulation of proinflammatory cytokines, local inflammatory cell infiltration and tissue damage that were all prominently seen in rSeV/dF injection were dramatically diminished using rSeV/dFdMdHN. NK cell activity was also decreased, indicating a reduction of the innate immune response. In the later phase, on the other hand, CTL activity and anti‐SeV antibodies were similarly induced, even using rSeV/dFdMdHN, and resulted in transient transgene expression in both vector types.

Conclusions

Deletion of envelope‐related genes of rSeV dramatically reduces the vector‐induced retinal damage and may extend the utility for ocular gene transfer; however, further studies regulating the acquired immune response are required to achieve long‐term transgene expression of rSeV. Copyright © 2007 John Wiley & Sons, Ltd.
Modeling the neurovascular niche: Murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn
Authors: Li Qi , Michaud Michael , Stewart William , Schwartz Michael , Madri Joseph A.
Published: December 2007

Preterm birth results in significant cognitive and motor disabilities, but recent evidence suggests that there is variable recovery over time. One possibility that may explain this variable recovery entails variable neurogenic responses in the subventricular zone (SVZ) following the period of chronic hypoxia experienced by these neonates. In this report, we have characterized the responses to chronic hypoxia of two mouse strains that represent a wide range of susceptibility to chronic hypoxia. We determined that C57BL/6 pups and neural progenitor cells (NPCs) derived from them exhibit a blunted response to hypoxic insult compared with CD‐1 pups and NPCs. Specifically, C57BL/6 pups and NPCs exhibited blunted in vivo and in vitro proliferative and increased apoptotic responses to hypoxic insult. Additionally, C57BL/6 NPCs exhibited lower baseline levels and hypoxia‐induced levels of selected transcription factors, growth factors, and receptors (including HIF‐1α, PHD2, BDNF, VEGF, SDF‐1, TrkB, Nrp‐1, CXCR4, and NO) that determine, in part, the responsiveness to chronic hypoxic insult compared with CD‐1 pups and NPCs, providing insight into this important and timely problem in perinatology. © 2007 Wiley‐Liss, Inc.
The challenges of developing commercial activity in new university business schools: alternative approaches
Authors: Prince Christopher , Beaver Graham
Published: December 2007

This original research examines the nature and development of commercial activity in new (post‐1992) university business schools. The picture that emerges is one of a complex market that is local and regional in nature, and where the ability of individual schools to compete in a range of commercial submarkets is constrained by their resources and capabilities, as well as by market opportunities in the region.

The research highlights that although most schools are seeking to grow commercial activity, it is likely to be a slow process, based for the most part on incremental and organic growth. While commercial activity is a small and marginal source of revenue generation, it is unlikely that school and university systems, processes and structures will be developed to support commercial activity in ways that will allow it to grow substantially.

Copyright © 2007 John Wiley & Sons, Ltd.
Managing organizational knowledge: developing a strategy for a professional services company
Authors: Skok Walter , Goldstein Brian
Published: December 2007

The aim of this paper is to identify the benefits of an improved Knowledge Management (KM) strategy for a small/medium‐sized professional services firm. The research examined how the three epistemological views (cognitivistic, connectionistic and autopoietic) influenced the management and use of organizational knowledge via the company intranet.

The Intranet Evaluation Model (Skok and Kalmanovitch, 2005) was selected to evaluate the company's KM strategy and was extended to emphasize group, cultural and external aspects. Knowledge Evaluation Maps were used to present findings in a revealing graphical display. The results indicated that the company's KM strategy should focus on the high‐value tacit knowledge of experts, develop the intranet in a connectionistic form, build upon existing knowledge activities and initiate more group activities. A knowledge steward should be appointed to motivate management and staff, and to overcome possible barriers to management buy‐in and a knowledge silo culture.

Furthermore, it was found that for small/medium‐sized professional service firms, knowledge can be used as the enabler of competitive advantage but that the epistemologies within the firm should be considered when evaluating a KM strategy.

Copyright © 2007 John Wiley & Sons, Ltd.
Shock‐tube and modeling study of acetaldehyde pyrolysis and oxidation
Authors: Yasunaga Kenji , Kubo Satoshi , Hoshikawa Hiroki , Kamesawa Takashi , Hidaka Yoshiaki
Published: December 2007

Pyrolysis and oxidation of acetaldehyde were studied behind reflected shock waves in the temperature range 1000–1700 K at total pressures between 1.2 and 2.8 atm. The study was carried out using the following methods, (1) time‐resolved IR‐laser absorption at 3.39 μm for acetaldehyde decay and CH‐compound formation rates, (2) time‐resolved UV absorption at 200 nm for CH2CO and C2H4 product formation rates, (3) time‐resolved UV absorption at 216 nm for CH3 formation rates, (4) time‐resolved UV absorption at 306.7 nm for OH radical formation rate, (5) time‐resolved IR emission at 4.24 μm for the CO2 formation rate, (6) time‐resolved IR emission at 4.68 μm for the CO and CH2CO formation rate, and (7) a single‐pulse technique for product yields. From a computer‐simulation study, a 178‐reaction mechanism that could satisfactorily model all of our data was constructed using new reactions, CH3CHO (+M) → CH4 + CO (+M), CH3CHO (+M) → CH2CO + H2(+M), H + CH3CHO → CH2CHO + H2, CH3 + CH3CHO → CH2CHO + CH4, O2 + CH3CHO → CH2CHO + HO2, O + CH3CHO → CH2CHO + OH, OH + CH3CHO → CH2CHO + H2O, HO2 + CH3CHO → CH2CHO + H2O2, having assumed or evaluated rate constants. The submechanisms of methane, ethylene, ethane, formaldehyde, and ketene were found to play an important role in acetaldehyde oxidation. © 2007 Wiley Periodicals, Inc. 40: 73–102, 2008
Preparation and thermal decomposition reaction kinetics of a dysprosium(III) p‐chlorobenzoate 1,10‐phenanthroline complex
Authors: Zhang Jian Jun , Xu Su Ling , Ren Ning , Zhang Hai Yan , Tian Liang
Published: December 2007

The title complex [Dy(p‐ClBA)3Phen]2·2H2O was synthesized, where p‐ClBA is p‐chlorobenzoate and Phen is 1,10‐phenanthroline. The complex was characterized by various techniques including elemental analysis, IR, XRD, and molar conductance. The thermal decomposition of the complex was studied under the nonisothermal condition by TG‐DTG and IR techniques. The kinetic parameters of dehydration process were obtained from the analysis of DSC curves of the complex by the NL‐DIF and Popescu methods, respectively. © 2007 Wiley Periodicals, Inc. 40: 66–72, 2008
A dynamic objective–subjective structure for forest management focusing on environmental issues
Authors: Henig M. I. , Weintraub A.
Published: December 2007

In this paper a decision‐making process is applied to a Chilean forestry firm that must deal with a host of environmental variables as well as profit making. At the core of this process is a ‘dynamic objective–subjective structure’ founded on the approach that decision making is about comprehending the preferences of the various parties involved and expanding the set of alternatives open to the decision makers. This is in contrast to many models that aim at finding the ‘best alternative’ and to decision analysis approaches that focus on presenting preferences via value functions. The paper describes in chronological order, following the sessions of a decision‐making process, how the various components of the structure emerged. In doing so it demonstrates how the process led to an understanding of the real effects of dealing with the environment and how comprehending the preferences led to the introduction of new decision variables. Copyright © 2007 John Wiley & Sons, Ltd.
A multicriteria decision framework for measuring banks' soundness around the world
Authors: Gaganis Chrysovalantis , Pasiouras Fotios , Zopounidis Constantin
Published: December 2007

In this paper, we use a sample of 894 banks from 79 countries to develop a multicriteria decision aid model, for the classification of banks into three groups on the basis of their soundness. The model is developed with the UTilités Additives DIScriminantes (UTADIS) method, through a 10‐fold cross‐validation procedure using six financial and four non‐financial variables. The ratings of Fitch form the basis for assigning banks into the three groups. The results indicate that the asset quality (as measured by loan loss provisions), capitalization, and the market where banks operate are the most important criteria (in terms of weights) in classifying the banks. Profitability and efficiency in expenses management are also important attributes, whereas size and listing in a stock exchange are the least important ones. UTADIS achieves higher classification accuracies than discriminant analysis and ordinary logistic regression which are used for benchmarking purposes. Copyright © 2007 John Wiley & Sons, Ltd.
A prospective study of delusional misidentification syndromes in Parkinson's disease with dementia
Authors: Pagonabarraga Javier , Llebaria Gisela , García‐Sánchez Carmen , Pascual‐Sedano Berta , Gironell Alexandre , Kulisevsky Jaime
Published: December 2007

Delusional misidentification syndromes (DMS) are a group of neuropsychiatric disorders due to disturbances in familiarity. DMS in organic diseases have been related to deficits in executive, memory, and visuospatial function. DMS are frequently reported in dementia with Lewy bodies (DLB). The presence of DMS in Parkinson's disease with dementia (PDD), which shares similar clinical and neuropsychological features with DLB, has not been studied. We describe the frequency and clinical features of DMS in a cohort of PDD patients, and we compare the neuropsychological profile between PDD patients with and without DMS. Prospective study of 30 PDD patients recruited from an outpatient setting, who received a structured behavioral interview assessing DMS and hallucinations, and a neuropsychological battery assessing executive function, memory, language, and visuospatial abilities. DMS were found in 16.7% of PDD patients. All DMS subjects also exhibited hallucinations that were significantly more severe than in PDD without DMS. DMS were responsive to neuroleptic drugs. PDD subjects with DMS presented a different neuropsychological profile than PDD subjects without DMS, with more severe memory and language deficits, but similar levels of executive and visuospatial impairment. DMS is a neuropsychiatric feature associated with PDD. Greater impairment in language and memory in PDD with DMS suggests a prominent role of the temporal cortex in the genesis of DMS in PDD. © 2007 Movement Disorder Society
Impaired intracortical inhibition in the primary somatosensory cortex in focal hand dystonia
Authors: Tamura Yohei , Matsuhashi Masao , Lin Peter , Ou Bai , Vorbach Sherry , Kakigi Ryusuke , Hallett Mark
Published: December 2007

Somesthetic temporal discrimination (STD) is impaired in focal hand dystonia (FHD). We explored the electrophysiological correlate of the STD deficit to assess whether this is due to dysfunction of temporal inhibition in the somatosensory inhibitory pathway or due to dysfunction in structures responsible for nonmodality‐specific timing integration. Eleven FHD patients and 11 healthy volunteers were studied. STD threshold was investigated as the time interval required for perceiving a pair of stimuli as two separate stimuli in time. We also examined the somatosensory‐evoked potential (SEP) in a paired‐pulse paradigm. We compared STD threshold and recovery function of SEP between the groups. STD thresholds were significantly greater in FHD than in healthy volunteers. The amount of P27 suppression in the 5 ms‐ISI condition was significantly less in FHD. It was also found that the STD threshold and P27 suppression were significantly correlated: the greater the STD threshold, the less the P27 suppression. Significantly less suppression of P27 with a lack of significant change in N20 indicates that the impairment of somatosensory information processing in the time domain is due to dysfunction within the primary somatosensory cortex, suggesting that that the STD deficit in FHD is more attributable to dysfunction in the somatosensory pathway. © 2007 Movement Disorder Society
Microanatomy and surgical relevance of the olfactory cistern
Authors: Wang Shou‐Sen , Zheng He‐Ping , Zhang Xiang , Zhang Fa‐Hui , Jing Jun‐Jie , Wang Ru‐Mi
Published: December 2007

All surgical approaches to the anterior skull base involve the olfactory cistern and have the risk of damaging the olfactory nerve. The purpose of this study was to describe the microanatomical features of the olfactory cistern and discuss its surgical relevance. In this study, the olfactory cisterns of 15 formalin‐fixed adult cadaveric heads were dissected using a surgical microscope. The results showed that the olfactory cistern was situated in the superficial part of the olfactory sulcus, which separated the gyrus retus from the orbital gyrus. In coronal section, the cistern was triangular in shape; its anterior part enveloped the olfactory bulbs and was high and broad; its posterior part was medial‐superior to internal carotid artery and was also much broader. There were one or several openings in the inferior wall of the posterior part in 53.4% of the cisterns. The olfactory cistern communicated with the surrounding subarachnoind cisterns through these openings. The middle part of the olfactory cistern gradually narrowed down posteriorly. Most cisterns were spacious with a few fibrous trabeculas and bands between the olfactory nerves and cistern walls. However 23% of the cisterns were narrow with the cistern walls tightly encasing the olfactory nerve. There were two or three of arterial loops in each olfactory sulcus, from which long, fine olfactory arteries originated. The olfactory arteries coursed along the olfactory nerve and gave off many terminal branches to provide the main blood supply to the olfactory nerve in most cisterns, but the blood supply was in segmental style in a few cisterns. Moreover, the veins of the cistern appeared to be more segmental than the olfactory arteries in most cisterns. These results suggested that most olfactory cisterns are spacious with relatively independent blood supply, and it is reasonable to separate the olfactory tract with its independent blood supply from the frontal lobe by 1–2 cm in the subfrontal approach, the pterional approach, or anterior interhemispheric approach. However, in the minority of cases, separation of the olfactory tract is not safe because of the anterior origin of the olfactory arteries or segmental blood supply. It is difficult to separate the olfactory nerve without any damage to the olfactory nerve, even with very skilled hands. © 2007 Wiley‐Liss, Inc. Microsurgery, 2008.
Obtaining smooth mesh transitions using vertex optimization
Authors: Brewer M.
Published: December 2007

Mesh optimization has proven to be an effective way to improve mesh quality for arbitrary Lagrangian Eulerian (ALE) simulations. To date, however, most of the focus has been on improving the geometric shape of individual elements, and these methods often do not result in smooth transitions in element size or aspect ratio across groups of elements. We present an extension to the mean ratio optimization that addresses this problem and yields smooth transitions within regions and across regions in the ALE simulation. While this method is presented in the context of ALE simulations, it is applicable to a wider set of applications that require mesh improvement, including the mesh generation process. Published in 2007 by John Wiley & Sons, Ltd.
Patient groups
Authors: Knight Alison
Published: December 2007

Epilepsy Action is the largest member‐led epilepsy organisation in the UK.The charitable association was founded in 1950 to improve the lives of people with epilepsy.As a campaigning charity,EpilepsyAction regularly speaks out on behalf of people with epilepsy on issues such as consistency of supply of medication,better health care,and a wider understanding of epilepsy among teachers, employers and the Government. Here, Alison Knight outlines the main aims and some of the current work of the organisation. Copyright © 2007 Wiley Interface Ltd
Dyspnea experience and management strategies in patients with lung cancer
Authors: Henoch Ingela , Bergman Bengt , Danielson Ella
Published: December 2007

Objective: The aim of this paper was to describe lung cancer patients' experience of dyspnea and their strategies for managing the dyspnea.

Methods: Semi‐structured interviews with two main questions about dyspnea experiences and management were conducted with 20 patients with lung cancer, not amenable to curative treatment, who had completed life prolonging treatments. Data analysis was made with a descriptive, qualitative content analysis.

Results: The two questions resulted in two domains with 7 categories and subcategories. The experience of dyspnea included four categories: ‘Triggering factors’ included circumstances contributing to dyspnea, which comprised physical, psychosocial and environmental triggers. Bodily manifestations were considered to be the core of the experience. ‘Immediate reactions’ concerned physical and psychological impact. The long‐term reactions included limitations, increased dependence and existential impact concerning hope, hopelessness and thoughts of death. The experience of managing dyspnea included three categories: ‘Bodily strategies’, ‘psychological strategies’ and ‘medical strategies’.

Conclusion: Dyspnea experience is a complex experience which influences the life of the patients both with immediate reactions and long‐term reactions concerning physical, emotional and existential issues in life and patients address this experience with managing strategies in order to take control of their situation, although they do not seem to be able to meet the existential distress they experience. Copyright © 2007 John Wiley & Sons, Ltd.
The association of prostate stem cell antigen (PSCA) mRNA expression and subsequent prostate cancer risk in men with benign prostatic hyperplasia following transurethral resection of the prostate
Authors: Zhigang Zhao , Wenlu Shen
Published: December 2007

BACKGROUND

Prior data showed prostate stem cell antigen (PSCA) mRNA expression in benign prostatic hyperplasia (BPH) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression in resected BPH samples was associated with the subsequent presence of cancer following transurethral resection of the prostate (TURP).

METHODS

PSCA in situ hybridization was performed on the TURP‐resected tissues from 288 patients, who were histopathologically confirmed BPH without cancer. All these patients were continuously followed for 9–70 months postoperatively. Univariate and multivariate cox regression analyses were used to evaluate the predictive performance of PSCA mRNA for subsequent cancer onset following TURP.

RESULTS

PSCA mRNA was detected in 93/288 (32.3%) of the resected BPH specimens, with a mean positive‐labeling cells of 23.8%, in which 22 patients (23.7%) were identified as having PCa on follow‐up. Of 195 patients with negative expression for PSCA mRNA 2 (1.0%) were subsequently found with PCa. PSCA mRNA expression levels were directly proportional to higher Gleason score and clinical T stage. Univariate and multivariate cox regression analyses demonstrated that only PSCA mRNA expression was predictive of the subsequent cancer development after TURP, however, PSA velocity was an univariately significant but not multivariately significant predictor.

CONCLUSIONS

This prospective study identifies PSCA mRNA in BPH as a significant predictor of cancer development after TURP, suggesting that PSCA may be used to identify patients who are at high risk for subsequent cancer onset following TURP for BPH and the PSCA test may be useful when applied for repeat biopsies. Prostate 68: 190–199, 2008. © 2007 Wiley‐Liss, Inc.
Proteasome inhibition blocks caspase‐8 degradation and sensitizes prostate cancer cells to death receptor‐mediated apoptosis
Authors: Thorpe Jeffery A. , Christian Perry A. , Schwarze Steven R.
Published: December 2007

BACKGROUND

Proteasome inhibition through the administration of Velcade is a viable chemotherapeutic strategy that is approved to treat multiple myeloma and is being evaluated for efficacy against prostate cancer. Currently, the apoptotic pathways that contribute to this anticancer response are poorly understood. Our goal is to test the extent to which proteasome inhibition modulates apoptosis through death receptor pathways.

METHODS

Several prostate cancer cell lines and primary prostate epithelial cells (PrECs) were used as models. The death receptor pathway was activated by the expression of Fas ligand (FasL) or addition of TNF‐related apoptosis‐inducing ligand (TRAIL) in the presence or absence of proteasome inhibitors. The apoptotic response was quantified by annexin V, TUNEL and nuclear condensation assays. Western blot analysis was conducted to quantify protein levels and enzyme assays were used to measure caspase activity.

RESULTS

Proteasome inhibition markedly sensitized prostate cancer cells to apoptosis initiated by Fas ligand (FasL) or TRAIL. In the presence of either death ligand, procaspase‐8 processing occurred, but led to minimal amounts of active caspase‐8. The addition of Velcade, however, led to robust active caspase‐8 protein abundance and activity. In the presence of Velcade the caspase‐8 p18 subunit half‐life increased from 22 min to over 2 hr.

CONCLUSIONS

These findings demonstrate that proteasome inhibition can sensitize cells to apoptosis elicited by tumor necrosis factor ligands and retarding caspase‐8 degradation provides one explanation for this activity. This study suggests that the clinical efficacy of Velcade may result, at least in part, from the activity of death ligands. Prostate 68: 200–209, 2008. © 2007 Wiley‐Liss, Inc.
Remote homology detection of integral membrane proteins using conserved sequence features
Authors: Bernsel Andreas , Viklund Håkan , Elofsson Arne
Published: December 2007

Compared with globular proteins, transmembrane proteins are surrounded by a more intricate environment and, consequently, amino acid composition varies between the different compartments. Existing algorithms for homology detection are generally developed with globular proteins in mind and may not be optimal to detect distant homology between transmembrane proteins. Here, we introduce a new profile–profile based alignment method for remote homology detection of transmembrane proteins in a hidden Markov model framework that takes advantage of the sequence constraints placed by the hydrophobic interior of the membrane. We expect that, for distant membrane protein homologs, even if the sequences have diverged too far to be recognized, the hydrophobicity pattern and the transmembrane topology are better conserved. By using this information in parallel with sequence information, we show that both sensitivity and specificity can be substantially improved for remote homology detection in two independent test sets. In addition, we show that alignment quality can be improved for the most distant homologs in a public dataset of membrane protein structures. Applying the method to the Pfam domain database, we are able to suggest new putative evolutionary relationships for a few relatively uncharacterized protein domain families, of which several are confirmed by other methods. The method is called Searcher for Homology Relationships of Integral Membrane Proteins (SHRIMP) and is available for download at http://www.sbc.su.se/shrimp/. Proteins 2008. © 2007 Wiley‐Liss, Inc.
The investigation of interactions of κ‐Hefutoxin1 with the voltage‐gated potassium channels: A computational simulation
Authors: Zarrabi M. , Naderi‐Manesh H.
Published: December 2007

κ‐Hefutoxin1 is a K+ channel‐blocking toxin from the scorpion Heterometrus fluvipes. It is a 22‐residue protein that adapts a novel fold of two parallel helices linked by two disulfide bridges without β‐sheets. Recognition of interactions of κ‐Hefutoxin1 with the voltage‐gated potassium channels, Kv1.1, Kv1.2, and Kv1.3, was studied by 3D‐Dock software package. All structures of κ‐Hefutoxin1 were considered during the simulations, which indicated that even small changes in the structure of κ‐Hefutoxin1 considerably affected both the recognition and the binding between κ‐Hefutoxin1 and the Kv1 channels. κ‐Hefutoxin1 is located around the extracellular part of the Kv1 channels, making contacts with its helices. Lys 19, Tyr 5, Arg 6, Trp 9, or Arg 10 in the toxin and residues Asp 402, His 404, Thr 407,Gly 401, and Asp 386 in each subunit of the Kv potassium channel are the key residues for the toxin‐channel recognition. Moreover, the simulation result demonstrates that the hydrophobic interactions are important in interaction of negatively charged toxins with potassium channels. The results of our docking/molecular dynamics simulations indicate that our 3D model structure of the κ‐Hefutoxin1‐complex is both reasonable and acceptable and could be helpful for smarter drug design and the blocking agents of Kv1 channels. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Probing electrostatic interactions and ligand binding in aspartyl‐tRNA synthetase through site‐directed mutagenesis and computer simulations
Authors: Thompson Damien , Lazennec Christine , Plateau Pierre , Simonson Thomas
Published: December 2007

Faithful genetic code translation requires that each aminoacyl‐tRNA synthetase recognise its cognate amino acid ligand specifically. Aspartyl‐tRNA synthetase (AspRS) distinguishes between its negatively‐charged Asp substrate and two competitors, neutral Asn and di‐negative succinate, using a complex network of electrostatic interactions. Here, we used molecular dynamics simulations and site‐directed mutagenesis experiments to probe these interactions further. We attempt to decrease the Asp/Asn binding free energy difference via single, double and triple mutations that reduce the net positive charge in the active site of Escherichia coli AspRS. Earlier, Glutamine 199 was changed to a negatively‐charged glutamate, giving a computed reduction in Asp affinity in good agreement with experiment. Here, Lysine 198 was changed to a neutral leucine; then, Lys198 and Gln199 were mutated simultaneously. Both mutants are predicted to have reduced Asp binding and improved Asn binding, but the changes are insufficient to overcome the initial, high specificity of the native enzyme, which retains a preference for Asp. Probing the aminoacyl‐adenylation reaction through pyrophosphate exchange experiments, we found no detectable activity for the mutant enzymes, indicating weaker Asp binding and/or poorer transition state stabilization. The simulations show that the mutations' effect is partly offset by proton uptake by a nearby histidine. Therefore, we performed additional simulations where the nearby Histidines 448 and 449 were mutated to neutral or negative residues: (Lys198Leu, His448Gln, His449Gln), and (Lys198Leu, His448Glu, His449Gln). This led to unexpected conformational changes and loss of active site preorganization, suggesting that the AspRS active site has a limited structural tolerance for electrostatic modifications. The data give insights into the complex electrostatic network in the AspRS active site and illustrate the difficulty in engineering charged‐to‐neutral changes of the preferred ligand. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Cysteine 10 is critical for the activity of Ochrobactrum anthropi glutathione transferase and its mutation to alanine causes the preferential binding of glutathione to the H‐site
Authors: Allocati Nerino , Federici Luca , Masulli Michele , Favaloro Bartolo , Di Ilio Carmine
Published: December 2007

The role of the evolutionarily conserved residue Cys10 in Ochrobactrum anthropi glutathione transferase (OaGST) has been examined by replacing it with an alanine. A double mutant C10A/S11A was also prepared. The effect of the replacements on the coniugating and thiotransferase activities, and on the thermal and chemical stability of the enzyme was analyzed. Our data support the view that in OaGST, in contrast with other beta class GSTs that display significant differences in the glutathione‐binding site, Cys10 is a key residue for glutathione coniugating activity. Furthermore, analysis of the OaGST‐Cys10Ala structure, crystallized in the presence of glutathione, reveals that this mutation causes a switch between the high‐affinity G‐site and a low‐affinity H‐site where hydrophobic cosubstrates bind and where we observe the presence of an unexpected glutathione. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Computational prediction of the binding site of proteinase 3 to the plasma membrane
Authors: Hajjar Eric , Mihajlovic Maja , Witko‐Sarsat Véronique , Lazaridis Themis , Reuter Nathalie
Published: December 2007

Proteinase 3 (PR3) is a neutrophil‐derived serine proteinase localized within cytoplasmic granules which can be released upon activation. PR3 is exposed at the neutrophil plasma membrane where it can mediate proinflammatory effects. Moreover, PR3 membrane expression is of special relevance in patients with Wegener's granulomatosis, a systemic vasculitis presenting anticytoplasmic neutrophil autoantibodies (ANCA) against PR3, which can bind to PR3 expressed at the surface of neutrophils and amplify their activation state. Therefore, it is of special relevance to unravel the molecular mechanisms governing its association with the membrane to be able to modulate it. To this end, we performed molecular dynamics (MD) simulations of PR3 with the implicit membrane model IMM1‐GC to identify its interfacial binding site (IBS). Both the energies and structures resulting from the MD suggest that PR3 associates strongly with anionic membranes. We observe a unique IBS consisting of five basic (R177, R186A, R186B, K187, R222) and six hydrophobic (F165, F166, F224, L223, F184, W218) amino acids. The basic residues provide the driving force to orient PR3 at the membrane surface, so that the hydrophobic residues can anchor into the hydrocarbon region. Energy decomposition and in silico mutations show that only a few residues account for the membrane association. Similar calculations with HNE suggest a different membrane‐binding mechanism. Our results agree with previous experimental observations and this work predicts, for the first time, the structural determinants of the binding of PR3 to membranes. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Solvent‐exposed residues located in the β‐sheet modulate the stability of the tetramerization domain of p53—A structural and combinatorial approach
Authors: Mora Puig , Carbajo Rodrigo J. , Pineda‐Lucena Antonio , Sánchez del Pino Manuel M. , Pérez‐Payá Enrique
Published: December 2007

The role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent‐exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent‐exposed residues (Tyr327, Thr329, and Gln331) located in theβ‐sheet of the tetramerization domain of the tumor suppressor p53 (p53TD). A conformationally defined peptide library was designed where these three positions were randomized. The library was screened for tetramer stability. A set of p53TD mutants containing putative stabilizing or destabilizing residue combinations was synthesized for a thermodynamic characterization. Unfolding experiments showed a wide range of stabilities, with Tm values between 27 and 83°C. Wild type p53TD and some highly destabilized and stabilized mutants were further characterized. Thermodynamic and biophysical data indicated that these proteins were folded tetramers, with the same overall structure, in equilibrium with unfolded monomers. An NMR study confirmed that the main structural features of p53TD are conserved in all the mutants analyzed. The thermodynamic stability of the different p53TD mutants showed a strong correlation with parameters that favor formation and stabilization of the β‐sheet. We propose that stabilization through hydrophobic interactions of key secondary structure elements might be the underlying mechanism for the strong influence of solvent‐exposed residues in the stability of p53TD. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Overexpression, physicochemical characterization, and modeling of a hyperthermophilic pyrococcus furiosus type 2 IPP isomerase
Authors: Dutoit Raphaël , de Ruyck Jérôme , Durisotti Virginie , Legrain Christianne , Jacobs Eric , Wouters Johan
Published: December 2007

In the first step of this study, type 2 isopentenyl diphosphate isomerase (IDI2) from Pyrococcus furiosus (pf‐IDI2), a hyperthermophilic microorganism, was cloned and overexpressed in E. coli. After purification, hyperthermophilic behavior of this protein was approached by means of enzymatic assays and thermal denaturation studies. Compared with the mesophilic Streptococcus pneumoniae IDI2, which unfolds and looses activity above 50°C, pf‐IDI2 is still folded and active at 80°C. Molecular modeling was applied, in a parallel step, to understand the molecular basis of thermal stability. Comparison of IDI2 from S. pneumoniae, T. thermophilus, and P. furiosus suggested that additional charged residues present in the hyperthermophilic enzyme might contribute to its higher thermal stability. This could increase the number of salt bridges between monomers of IDI2 in P. furiosus enzyme and, hence, decrease flexibility of loops or N‐terminal segment, thereby enhancing its thermal stability. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Tandem use of X‐ray crystallography and mass spectrometry to obtain ab initio the complete and exact amino acids sequence of HPBP, a human 38‐kDa apolipoprotein
Authors: Diemer Hélène , Elias Mikael , Renault Frédérique , Rochu Daniel , Contreras‐Martel Carlos , Schaeffer Christine , Van Dorsselaer Alain , Chabriere Eric
Published: December 2007

The Human Phosphate Binding Protein (HPBP) is a serendipitously discovered apolipoprotein from human plasma that binds phosphate. Amino acid sequence relates HPBP to an intriguing protein family that seems ubiquitous in eukaryotes. These proteins, named DING according to the sequence of their four conserved N‐terminal residues, are systematically absent from eukaryotic genome databases. As a consequence, HPBP amino acids sequence had to be first assigned from the electronic density map. Then, an original approach combining X‐ray crystallography and mass spectrometry provides the complete and a priori exact sequence of the 38‐kDa HPBP. This first complete sequence of a eukaryotic DING protein will be helpful to study HPBP and the entire DING protein family. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Protein classification with imbalanced data
Authors: Zhao Xing‐Ming , Li Xin , Chen Luonan , Aihara Kazuyuki
Published: December 2007

Generally, protein classification is a multi‐class classification problem and can be reduced to a set of binary classification problems, where one classifier is designed for each class. The proteins in one class are seen as positive examples while those outside the class are seen as negative examples. However, the imbalanced problem will arise in this case because the number of proteins in one class is usually much smaller than that of the proteins outside the class. As a result, the imbalanced data cause classifiers to tend to overfit and to perform poorly in particular on the minority class.

This article presents a new technique for protein classification with imbalanced data. First, we propose a new algorithm to overcome the imbalanced problem in protein classification with a new sampling technique and a committee of classifiers. Then, classifiers trained in different feature spaces are combined together to further improve the accuracy of protein classification. The numerical experiments on benchmark datasets show promising results, which confirms the effectiveness of the proposed method in terms of accuracy. The Matlab code and supplementary materials are available at http://eserver2.sat.iis.u‐tokyo.ac.jp/∼xmzhao/proteins.html. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Effective training programs using instructional systems design and e‐learning
Authors: Myers Philip M. , Watson Brent , Watson Molly
Published: December 2007

In an ever changing business environment, enterprise‐wide and plant site‐based training initiatives take on added importance. There are training requirements to address process safety management (PSM), risk management, security, and EHS needs and regulations, as well as training programs to address related internal company and business focused directives and initiatives. These ever‐changing topics and increasing requirements present ample challenges to companies attempting to provide quality training to their workforce for performance improvement. Much has been written regarding the promise of e‐learning technologies in meeting these needs. However, technology itself will not solve training challenges. Training programs built using a formal, structured approach such as instructional systems design (ISD) ensures that a highly effective, quality training program is built and consistently delivered. ISD utilizes the following sequential steps: analysis, design, development, implementation, and evaluation. Use of ISD assures that the proper target audience and specific instructional needs are identified, instructional objectives are established, an appropriate instructional strategy is selected, and the evaluation strategy is devised and implemented. This article outlines use of ISD to create and deliver highly effective training programs, and includes a review of new training technologies. © 2007 American Institute of Chemical Engineers Process Saf Prog 2008
The role of peptides in blood‐brain barrier nanotechnology
Authors: Teixidó Meritxell , Giralt Ernest
Published: December 2007

The blood‐brain barrier (BBB) regulates the passage of molecules between the bloodstream and the brain. Overcoming the difficulty of delivery drugs to specific areas of the brain is a major challenge. The BBB exerts a neuroprotective function as it hinders the delivery of diagnostic and therapeutic agents to the brain. Here, we provide an overview of the way in which peptides and nanotechnology are being exploited in tandem to address this problem. Peptides can be used as specialised coatings able to transport nanoparticles with specific properties, such as targeting. The nanoparticle can also carry a peptide drug. Furthermore, peptides can be used in less conventional approaches such as all‐peptide nanoparticles. In summary, the combined use of peptides and nanotechnology offers tremendous hope in the treatment of brain disorders. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.