bluuebunny/crossref_metadata_2025 huggingface dataset:
On Directional Change and Anti-Windup Compensation in Multivariable Control Systems
Authors: Horla Dariusz
Published: July 2009

On Directional Change and Anti-Windup Compensation in Multivariable Control Systems

The paper presents a novel description of the interplay between the windup phenomenon and directional change in controls for multivariable systems (including plants with an uneven number of inputs and outputs), usually omitted in the literature. The paper also proposes a new classification of anti-windup compensators with respect to the method of generating the constrained control signal.
Automatic Risk Control Based on FSA Methodology Adaptation for Safety Assessment in Intelligent Buildings
Authors: Mikulik Jerzy , Zajdel Mirosław
Published: July 2009

Automatic Risk Control Based on FSA Methodology Adaptation for Safety Assessment in Intelligent Buildings

The main area which Formal Safety Assessment (FSA) methodology was created for is maritime safety. Its model presents quantitative risk estimation and takes detailed information about accident characteristics into account. Nowadays, it is broadly used in shipping navigation around the world. It has already been shown that FSA can be widely used for the assessment of pilotage safety. On the basis of analysis and conclusion on the FSA approach, this paper attempts to show that the adaptation of this method to another area—risk evaluating in operating conditions of buildings—is possible and effective. It aims at building a mathematical model based on fuzzy logic risk assessment with different habitat factors included. The adopted approach lets us describe various situations and conditions that occur in creating and exploiting of buildings, allowing for automatic control of the risk connected to them.
Computer-Aided Diagnosis Systems for Brain Diseases in Magnetic Resonance Images
Authors: Arimura Hidetaka , Magome Taiki , Yamashita Yasuo , Yamamoto Daisuke
Published: July 2009

This paper reviews the basics and recent researches of computer-aided diagnosis (CAD) systems for assisting neuroradiologists in detection of brain diseases, e.g., asymptomatic unruptured aneurysms, Alzheimer's disease, vascular dementia, and multiple sclerosis (MS), in magnetic resonance (MR) images. The CAD systems consist of image feature extraction based on image processing techniques and machine learning classifiers such as linear discriminant analysis, artificial neural networks, and support vector machines. We introduce useful examples of the CAD systems in the neuroradiology, and conclude with possibilities in the future of the CAD systems for brain diseases in MR images.
Shell architecture and its relation to shell occupation by the hermit crab Clibanarius antillensis under different wave action conditions
Authors: Argüelles Araceli , Álvarez Fernando , Alcaraz Guillermina
Published: July 2009

We studied the intertidal hermit crab Clibanarius antillensis at Montepio Beach, Veracruz, Mexico, to determine whether architecture and weight of occupied shells varied with the degree of exposure to wave action. Data on shell use were obtained from 30-m transects perpendicular to the shoreline. The gastropod shells species used by C. antillensis were classified into four groups according to their morphology: neritiform, conical, turriculate, and turbinate. Neither the size nor the weight of hermit crabs varied along transects. A pattern showing differential use of shell type according to water velocity was detected. Neritiform and turriculate shells were the least occupied, and their abundance decreased with increasing water velocities. Conical and turbinate shells were the most used and their presence increased with increasing water velocities. Turbinate and conical shells are heavier and have a higher weight/exposed-area ratio than neritiform and turriculate shells, so using them at higher energy sites seems to be more advantageous than using turriculate shells. The pattern that emerges is one in which C. antillensis occupy different shells along the intertidal transect, probably due to the advantages that different shells may bring, such as minimising drag and the risk of dislodgement.
Metric and nonmetric dental variation and the population structure of the Ainu
Authors: Hanihara Tsunehiko
Published: July 2009

Gene flow and genetic drift are important factors affecting geographic variations in human phenotypic traits. In the present study, the effects of gene flow from an outside source on the pattern of within‐ and among‐group variation of the Ainu from Sakhalin Island and three local groups of Hokkaido are examined by applying an R‐matrix approach to metric and nonmetric dental data. The comparative samples consist of their ancestral and neighboring populations, such as the Neolithic Jomon, the subsequent Epi‐Jomon/Satsumon, the Okhotsk culture people who migrated from Northeast Asia to the northeastern part of Hokkaido during a period 1600–900 years B.P., and modern non‐Ainu Japanese. The results obtained by using the census population sizes of the regional groups of the Ainu as an estimate of relative effective population size suggest the possibility of an admixture between the Okhotsk culture people and the indigenous inhabitants in Hokkaido, at least in the coastal region along the Sea of Okhotsk. Such gene flow from Northeast Asian continent may have exerted an effect on the genetic structure of the contemporary Ainu. The present findings indicate that the population structure, as represented by genetic drift and gene flow, tend to be obscured in the results obtained by standard statistical methods such as Mahalanobis' generalized distance and Smith's MMDs. The present extension of the R‐matrix approach to metric and nonmetric dental data provide results that can be interpreted in terms of a genetically, archaeologically, and prehistorically suggested pattern of gene flow and isolation. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.
Variation in GRIN2B contributes to weak performance in verbal short‐term memory in children with dyslexia
Authors: Ludwig Kerstin U. , Roeske Darina , Herms Stefan , Schumacher Johannes , Warnke Andreas , Plume Ellen , Neuhoff Nina , Bruder Jennifer , Remschmidt Helmut , Schulte‐Körne Gerd , Müller‐Myhsok Bertram , Nöthen Markus M. , Hoffmann Per
Published: July 2009

A multi‐marker haplotype within GRIN2B, a gene coding for a subunit of the ionotropic glutamate receptor, has recently been found to be associated with variation in human memory performance [de Quervain and Papassotiropoulos, 2006]. The gene locus is located within a region that has been linked to a phonological memory phenotype in a recent genome scan in families with dyslexia [Brkanac et al., 2008]. These findings may indicate the involvement of GRIN2B in memory‐related aspects of human cognition. Memory performance is one of the cognitive functions observed to be disordered in dyslexia patients. We therefore investigated whether genetic variation in GRIN2B contributes to specific quantitative measures in a German dyslexia sample by genotyping 66 SNPs in its entire genomic region. We found supportive evidence that markers in intron 3 are associated with short‐term memory in dyslexia, and were able to demonstrate that this effect is even stronger when only maternal transmission is considered. These results suggest that variation within GRIN2B may contribute to the genetic background of specific cognitive processes which are correlates of the dyslexia phenotype. © 2009 Wiley‐Liss, Inc.
D10S1423 identifies a susceptibility locus for Alzheimer's disease (AD7) in a prospective, longitudinal, double‐blind study of asymptomatic individuals: Results at 14 years
Authors: Zubenko George S. , Hughes Hugh B. , Zubenko Wendy N.
Published: July 2009

Typical forms of Alzheimer's disease (AD) appear to be influenced by multiple susceptibility loci. This report describes the prospective, longitudinal, double‐blind assessment of the age‐specific risk of AD encountered by 325 asymptomatic first‐degree relatives of AD probands who carried the D10S1423 (AD7) 234 bp allele, the APOE E4 allele, or both, after 14 years of systematic follow‐up. A total of 30 incident cases of AD were detected during the first 3752 subject‐years of surveillance. The effects of carrying either or both of the D10S1423 234 bp and APOE E4 alleles on the age‐specific risk of developing AD were determined using Kaplan–Meier survival analysis. The risk of developing AD was the greatest for individuals who carried both alleles (Mantel–Cox statistic = 16.46, df = 3, P = 0.0009; Breslow statistic = 13.38, df = 3, P = 0.004). Cox proportional hazards models were developed to estimate the risk ratios for each genotype, controlling for the potential effects of age at recruitment, sex, and years of education. Only individuals who carried both risk alleles exhibited a risk ratio that differed significantly from 1 (risk ratio = 7.5, P = 0.002, 95% CI = 2.1–27.0). Neither age at recruitment, sex, nor years of education made significant contributions to the model, although women tended to be at greater risk (P = 0.06). Recent evidence that D10S1423 resides within open reading frame C10orf112, whose predicted product resembles a low‐density lipoprotein receptor, suggests a molecular mechanism for this gene–gene interaction. © 2009 Wiley‐Liss, Inc.
The reveal: ABA ethics opinion highlights civil practice mediator confidentiality
Authors: Bleemer Russ
Published: July 2009

A new opinion by the ABA's Committee on Mediator Ethical Guidance investigates how mediators can introduce essential information to parties where the adversary would be prohibited from doing so.
Preparation and properties of Mahua oil‐based liquid crystalline pentalkyds
Authors: Tiwari Sangeeta , Tiwari Sandeep
Published: July 2009

Medium oil length Mahua oil‐based pentalkyds are prepared with varying degree of excess hydroxyl. These alkyds are subsequently converted into liquid crystalline form by copolymerizing with p‐hydroxy benzoic acid (p‐HBA). Esterification is facilitated by dicyclohexyl carbodiimide (DCC). Graft efficiencies of copolymers are calculated and reported. Characterization of grafted alkyds is carried out using IR, DSC, and polarizing microscope techniques. A sharp melting point indicates liquid crystalline characteristic of p‐HBA grafted alkyds. DSC and polarizing microscope study results further substantiated the observation. Mechanical film properties of LC resins viz., hardness, impact resistance, and adhesion are also reported and compared with the amorphous counterparts. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Algal biofuels: What is the real potential?
Authors: Darzins Al , Garofalo Raffaello
Published: July 2009

Algae are gaining increasing interest as a feedstock for sustainable biofuels production — but what are the real promises and challenges for production at commercial scale? BioFPR Managing Editor Mara Staffilani interviews Al Darzins, Group Manager and Principal Researcher at the National Renewable Energy Laboratory in the USA,and Raffaello Garofalo, Secretary General of the European Biodiesel Board (EBB). To listen to the full interview please go to: http://www.biofpr.com/podcasts
Sensitive determination of protein based on the fluorescence enhancement effect of terbium (III)–epinephrine–protein–sodium dodecylsulfate system
Authors: Guo Yumei , Yang Jinghe , Wu Xia , Mao Hongzhi
Published: July 2009

It was found that the fluorescence of Tb3+–epinephrine (E) complex can be enhanced by both bovine serum albumin (BSA) and sodium dodecylsulfate (SDS), and stabilized by ascorbic acid (AA). It is considered that the fluorescence enhancement of the Tb3+–E–BSA–AA–SDS system originates not only from the hydrophobic microenvironment provided by BSA–SDS, but also from the energy transfer from BSA to Tb3+ in this system. Therefore, a new fluorescence method for the determination of protein concentrations as low as 1.3 × 10−9 g mL−1 BSA is established using Tb3+–epinephrine complex as probe. The method has been applied for the determination of BSA and human serum albumin in actual samples, and the results obtained are satisfactory. Compared with other fluorescence methods, this method is simpler and more sensitive for the determination of protein. The mechanism of the fluorescence enhancement of the system is studied in detail. Copyright © 2009 John Wiley & Sons, Ltd.
Effects of summer training camp on serum opsonic activity and plasma cytokine levels in female long‐distance runners
Authors: Kumae Takashi , Ishii Takashi , Osanai Hirokazu , Ito Takashi
Published: July 2009

In a summer training camp, strenuous physical exercises are carried out to improve endurance ability. The effects of the training stress on the immune system have been studied extensively. However, less attention has been paid to non‐specific immunological changes. Serum opsonic activity (SOA) is a more direct and suitable indicator of non‐specific humoral immunity. In this study, we used the luminal‐dependent chemiluminescence (LmCL) to measure reactive oxygen species generation from pooled human neutrophils as an indicator of SOA. We also measured plasma myeloperoxidase (MPO) and plasma cytokine levels. Twenty‐two female college runners took part in this study after giving their written informed consent. There was no significant difference in the physical characteristics and serum enzyme levels. However, significant differences were observed in the changes of blood property and plasma cytokine levels. According to MPO levels, neutrophils in vivo may be deactivated during the camp. Positive correlations between fluctuations of pro‐ and anti‐inflammatory cytokine levels were observed in this study. According to the results of peak time and peak height of LmCL, SOA seems to increase at first qualitatively and then quantitatively during the summer camp. The increased SOA level may compensate for the decrease in neutrophil activity. Copyright © 2009 John Wiley & Sons, Ltd.
Long-term outcome in patients with adrenal metastases following resection of colorectal liver metastases
Authors: de Haas R J , Rahy Martin A C , Wicherts D A , Azoulay D , Castaing D , Adam R
Published: July 2009

Background

The prognostic significance of adrenal metastases (AMs) in patients with colorectal liver metastases (CLMs) remains unknown. The aim of this study was to determine the influence of AMs on long-term outcome and the role of adrenalectomy in patients with CLMs.

Methods

All patients resected for CLMs who developed AMs at a single institution between 1992 and 2006 were included in the study. Their long-term outcome was compared with that of all other patients resected for CLMs but without AMs.

Results

Hepatectomy was performed in 796 patients, of whom 14 (1·8 per cent) developed AMs, a median of 28 months after initial diagnosis of CLMs; the remaining 782 patients (98·2 per cent) had no AMs. All 14 patients had chemotherapy, and ten went on to adrenalectomy. Median survival after diagnosis of CLMs was 50 months in patients with AMs versus 68 months in those without (P = 0·020). After diagnosis of AMs, median survival was 23 months, whether or not adrenalectomy was performed.

Conclusion

The development of AMs after liver resection for colorectal cancer deposits carries a poor prognosis, and adrenalectomy is probably not warranted.
Systematic review of oxidative stress associated with pneumoperitoneum
Authors: Sammour T , Mittal A , Loveday B P T , Kahokehr A , Phillips A R J , Windsor J A , Hill A G
Published: July 2009

Background

There have been several reports of ischaemic complications after routine laparoscopy. The aim of this review was to investigate the relationship between this oxidative stress and pneumoperitoneum.

Methods

Medline, Medline in-process, The Cochrane Library, PubMed and EMBASE were searched for papers on oxidative stress and pneumoperitoneum, from 1947 to March 2008 with no language restriction or restriction on trial design. Papers that did not investigate pneumoperitoneum as a causative factor, or did not report outcome measures related to oxidative stress, were excluded.

Results

A total of 73 relevant papers were identified: 36 animal studies, 21 human clinical trials, nine case reports, five review articles and two comments. Pneumoperitoneum causes a reduction in splanchnic blood flow, resulting in biochemical evidence of oxidative stress in a pressure- and time-dependent manner. There is evidence that the use of carbon dioxide for insufflation is contributory. Several measures proposed to minimize the oxidative stress have shown promise in animal studies, but few have been evaluated in the clinical setting.

Conclusion

There is an increasing body of evidence, mainly from animal studies, that pneumoperitoneum decreases splanchnic perfusion with resulting oxidative stress. It is now appropriate to investigate the clinical significance of pneumoperitoneum-associated oxidative stress.
Circumferential suction-assisted lipectomy for lymphoedema after surgery for breast cancer
Authors: Damstra R J , Voesten H G J M , Klinkert P , Brorson H
Published: July 2009

Background

The incidence of arm lymphoedema after treatment for breast cancer ranges from 1 to 49 per cent. Although most women can be treated by non-operative means with satisfying results, end-stage lymphoedema is often non-responsive to compression, where hypertrophy of adipose tissue limits the outcome value of compression or massage.

Methods

This was a prospective study of 37 women with unilateral non-pitting lymphoedema. After initial conservative treatment for 2–4 days, circumferential suction-assisted lipectomy was used to remove excess volume. Limb compression was resumed after surgery with short-stretch bandages, followed by flat-knit compression garments.

Results

The mean preoperative excess arm volume was 1399 ml. The total aspirate volume was 2124 ml with 93 per cent aspirate adipose tissue content. After 12 months, the mean reduction in excess volume was 118 per cent. The percentage reduction in excess volume after 12 months was linearly related to the preoperative excess volume but showed no linear relationship with the duration of lymphoedema or surgeon experience.

Conclusion

Circumferential lipectomy combined with lifelong compression hose is an effective technique in end-stage lymphoedema after treatment for breast cancer.
Sympathetic nerve damage as a potential cause of lymphoedema after axillary dissection for breast cancer
Authors: Bennett Britton T M , Wallace S M L , Wilkinson I B , Mortimer P S , Peters A M , Purushotham A D
Published: July 2009

Background

The physiological disturbances leading to lymphoedema after breast cancer surgery are poorly understood. Damage to sympathetic nerves during axillary lymph node dissection (ALND), leading to increased capillary fluid filtration, was investigated as a possible contributory factor.

Methods

The integrity of the upper limb sympathetic nervous system was tested in 36 patients before, and 3 and 12 months after ALND. Forearm vascular resistance (FVR), calculated from forearm blood flow and mean systemic arterial pressure, was measured before and after exposure to lower-body negative pressure. Forearm venous compliance was measured using 99mTc-labelled autologous erythrocytes and radionuclide plethysmography before and after cold water immersion of the feet.

Results

There were clear changes in FVR and venous compliance in response to sympathetic stimulation but no differences attributable to surgery or between the nine patients who developed lymphoedema and the 27 who did not; nor were there differences between the two arms. There was a trend towards lower preoperative FVR in patients who developed lymphoedema.

Conclusion

Lymphoedema is not the result of sympathetic nerve damage sustained during ALND. Preoperative FVR may help predict who will get lymphoedema following this surgery.
Lasioglossins: Three Novel Antimicrobial Peptides from the Venom of the Eusocial Bee Lasioglossum laticeps (Hymenoptera: Halictidae)
Authors: Čeřovský Václav , Buděšínský Miloš , Hovorka Oldřich , Cvačka Josef , Voburka Zdeněk , Slaninová Jiřina , Borovičková Lenka , Fučík Vladimír , Bednárová Lucie , Votruba Ivan , Straka Jakub
Published: July 2009

Three novel structurally related pentadecapeptides, named lasioglossins, were isolated from the venom of the eusocial bee Lasioglossum laticeps. Their primary sequences were established as H‐Val‐Asn‐Trp‐Lys‐Lys‐Val‐Leu‐Gly‐Lys‐Ile‐Ile‐Lys‐Val‐Ala‐Lys‐NH2 (LL‐I), H‐Val‐Asn‐Trp‐Lys‐Lys‐Ile‐Leu‐Gly‐Lys‐Ile‐Ile‐Lys‐Val‐Ala‐Lys‐NH2 (LL‐II) and H‐Val‐Asn‐Trp‐Lys‐Lys‐Ile‐Leu‐Gly‐Lys‐Ile‐Ile‐Lys‐Val‐Val‐Lys‐NH2 (LL‐III). These lasioglossins exhibited potent antimicrobial activity against both Gram‐positive and Gram‐negative bacteria, low haemolytic and mast cell degranulation activity, and a potency to kill various cancer cells in vitro. The lasioglossin CD spectra were measured in the presence of trifluoroethanol and sodium dodecyl sulfate solution and indicated a high degree of α‐helical conformation. NMR spectroscopy, which was carried out in trifluoroethanol/water confirmed a curved α‐helical conformation with a concave hydrophobic and convex hydrophilic side. To understand the role of this bend on biological activity, we studied lasioglossin analogues in which the Gly in the centre of the molecule was replaced by other amino acid residues (Ala, Lys, Pro). The importance of the N‐terminal part of the molecule to the antimicrobial activity was revealed through truncation of five residues from both the N and C termini of the LL‐III peptide. C‐terminal deamidation of LL‐III resulted in a drop in antimicrobial activity, but esterification of the C terminus had no effect. Molecular modelling of LL‐III and the observed NOE contacts indicated the possible formation of a bifurcated H‐bond between hydrogen from the Lys15 CONH peptide bond and one H of the C‐terminal CONH2 to the Ile11 oxygen atom. Such interactions cannot form with C‐terminal esterification.
Modeling of Multi‐Tubular Reactors for Fischer‐Tropsch Synthesis
Authors: Jess A. , Kern C.
Published: July 2009

The results of the simulation of multi‐tubular Fischer‐Tropsch reactors based on a two‐dimensional pseudo‐homogeneous model are presented. The model takes into account the intrinsic kinetics of two commercial iron and cobalt catalysts, intraparticle mass transfer limitations, and the radial heat transfer within the fixed bed and to the cooling medium (boiling water). The effective rate with Co is slightly higher than with Fe. Hence, a temperature level can be used for Co that is 20 °C lower compared to Fe. The conversion and product selectivies are then almost the same and the reactor can be operated safely without a temperature runaway. The results of the simulations are consistent with literature data and show that there is still room for improvement of fixed bed FT reactors, e.g., by an enhanced heat transfer.
Numerical solutions of linear and nonlinear diffusion equations by a differential quadrature method (DQM)
Authors: Gürarslan Gürhan , Sari Murat
Published: July 2009

In this work, accurate solutions to linear and nonlinear diffusion equations were introduced. A polynomial‐based differential quadrature scheme in space and a strong stability preserving Runge–Kutta scheme in time have been combined for solving these equations. This scheme needs less storage space, as opposed to conventional numerical methods, and causes less accumulation of numerical errors. The results computed by this way have been compared with the exact solutions to show the accuracy of the method. The approximate solutions to the nonlinear equation have been computed without transforming the equation and without using the linearization. The present results are seen to be a very reliable alternative method to the existing techniques for the problems. In order to obtain physical models much closer to the nature, this procedure has a potential to be used to other nonlinear partial differential equations. Copyright © 2009 John Wiley & Sons, Ltd.
Improving energy efficiency of asymmetric chip multithreaded multiprocessors through reduced OS noise scheduling
Authors: Grant Ryan E. , Afsahi Ahmad
Published: July 2009

The performance of the emerging chip multithreaded symmetric multiprocessors (SMPs) is of great importance to the high performance computing community. However, the growing power consumption of such systems is of increasing concern, and techniques that can be used to increase the overall system power efficiency while sustaining the performance are very desirable. Operating system (OS) noise can have a dramatic effect on the system performance. Effectively handling the smaller OS tasks while simultaneously preserving application thread synchronicity leads to gains in the overall system efficiency. Recently, under a fixed power budget, asymmetric multiprocessors (AMP) have been proposed to improve the performance of multithreaded applications. An AMP in this context is a multiprocessor system in which its processors are not operating at the same frequency. This paper proposes two simple scheduling methods that reduce the impact of OS noise, while simultaneously taking advantage of an opportunity to increase the overall machine energy efficiency on AMP servers. Prototyping AMPs on a commercial 2‐way dual‐core Hyper‐Threaded (HT) Intel Xeon SMP server, using real power measurements across six SPEC OpenMP applications, indicates that the first proposed scheduler performs better on average for HT‐enabled systems, whereas the second scheduler is superior on average for HT‐disabled systems. Copyright © 2009 John Wiley & Sons, Ltd.
‘Do as we say but not as we do’: Organizational, professional and personal barriers to the receipt of support at work
Authors: Walsh Sue , Cormack Maggie
Published: July 2009

Given the existence of an established literature on the costs of burnout to the well‐being of the clinician and to the effectiveness of therapeutic interventions for the client, self‐care amounts to sensible preventative action on the part of the mental health worker. This study focuses on experiences of clinical psychologists working in the National Health Service (NHS) in Britain. A two‐stage qualitative study was designed which explored the attitudes and practices of this group of mental health workers towards the receipt of support at work. Analyses revealed that psychologists may be vulnerable to poor levels of self‐care because they perceive the expression of support needs as psychologically threatening.

Four themes emerged as significant factors in explaining the relationship between the receipt of support and psychological threat: Organizational devaluation of supportive work practices, ambivalent professional values, psychologists' own fears of being a client, and the perceived costs of the support process itself. An explanatory model describing the interrelationship between these factors is developed.
Short‐term interventions for morbid jealousy
Authors: de Silva P.
Published: July 2009

This paper discusses short‐term treatment for morbid jealousy. A brief account of the clinical presentation of morbid jealousy is given. Theoretical approaches to this phenomenon are summarized and commented on. Specific behavioural and cognitive techniques are described, and their rationale explained. Case examples are cited to illustrate the use of these techniques. Some general comments on the application of these techniques are also made.
Cognition, emotion and defence: Processes and mechanisms of change in a brief psychotherapy for depression
Authors: Hingley Susan M.
Published: July 2009

A brief psychodynamically oriented therapy with a female client was monitored using the Brief Symptom Inventory (BSI). The Object Relations Technique (ORT) and the Dysfunctional Attitudes Scale (DAS) were used pre and post therapy to reflect changes in variables of relevance to psychodynamic and cognitive perspectives of depression. The data indicated changes in depression, cognitions and defences, and are used to support a theoretical discussion of potential relationships between cognitive and psychodynamic formulations. Aspects of therapy process are discussed in terms of possible underlying mechanisms, examining the importance of different characteristics of therapy in promoting change. The potential contribution of psychodynamic mechanisms to a recent model from cognitive science is considered.
Evaluation of intensity‐based ratiometric FRET in image cytometry—Approaches and a software solution
Authors: Roszik János , Lisboa Duarte , Szöllősi János , Vereb György
Published: July 2009

The intensity‐based ratiometric FRET (fluorescence resonance energy transfer) method is a powerful technique for following molecular interactions in living cells. Since it is not based on irreversibly destroying the donor or the acceptor fluorophores, the time course of changes in FRET efficiency values can be monitored by this method. ImageJ, a sophisticated software tool for many types of image processing allows users to extend it with programs for various purposes. Implementing intensity‐based ratiometric FRET with ImageJ vastly enhances the applicability of the FRET method. We developed an efficient ImageJ plugin, RiFRET, which calculates FRET efficiency on a pixel‐by‐pixel basis from ratiometric FRET images. It allows the user to correct for channel cross‐talk (bleed‐through) and to calculate FRET from image stacks, i.e., from 3D data sets. Semiautomatic processing for larger datasets is also included in the program. Furthermore, several options for calibrating FRET efficiency calculations were tested and their applicability to various expression systems is discussed. Although the ratiometric FRET method is widely applied, our plugin is the first freely available software for evaluating such FRET data. The program is user friendly and provides reliable, standardized results. © 2009 International Society for Advancement of Cytometry
Rational optimization of tumor epitopes using in silico analysis‐assisted substitution of TCR contact residues
Authors: Shang Xiaoyun , Wang Li , Niu Wei , Meng Gang , Fu Xiaolan , Ni Bing , Lin Zhihua , Yang Zhao , Chen Xiaolin , Wu Yuzhang
Published: July 2009

Altered peptide ligands with increased affinity of the peptide–MHC complex for the TCR provide an alternative strategy to natural T‐cell epitopes for cancer immunotherapy, as they can recruit and stimulate stronger T‐cell repertoires. However, it remains unclear how alterations of the TCR contact residues improve the interaction between the peptide–MHC complex and the TCR molecule. In this study, we introduced a molecular simulation strategy to optimize a tumor immunodominant epitope NY–ESO‐1157–165 by the substitution of the potential TCR contact residues. We correlated molecule simulation with T‐cell activation capacity assay and detected the effect of modifications of TCR contact residues on T‐cell recognition. An agonist peptide W5F with substitution at Trp5 with Phe was identified and it exhibits a stronger ability to induce a cross‐reactive CTL response with the WT peptide. Additionally, the W5F‐induced CTL could be maintained with the WT peptide and possess higher capacity in lysing native NY–ESO‐1‐expressing tumor cells. These results provide important insights into the enhanced immunogenicity of epitopes through substitution at the TCR contact sites and revealed a novel molecular simulation approach for rational therapeutic peptide vaccine design.
Ligation of the OX40 co‐stimulatory receptor reverses self‐Ag and tumor‐induced CD8 T‐cell anergy in vivo
Authors: Redmond William L. , Gough Michael J. , Weinberg Andrew D.
Published: July 2009

Tumor‐specific CD8 T‐cell peripheral tolerance occurs through clonal deletion, suppression, and the induction of anergy and can limit the generation of anti‐tumor immunity. Several groups have demonstrated that prostate cancer can render tumor‐specific CD8 T cells anergic, suggesting reversing tumor‐induced anergy may greatly augment anti‐tumor immunity. Recent work has demonstrated that signaling through the OX40 (CD134) co‐stimulatory receptor, a member of the TNFR super‐family, can augment CD4 and CD8 T‐cell expansion, differentiation, and the generation of memory cells. However, whether OX40 ligation can reverse CD8 T‐cell anergy, and more specifically, tumor‐induced CD8 T‐cell anergy, remains unclear. In the current study, we demonstrate that OX40 ligation can reverse CD8 T‐cell anergy to a prostate‐specific self‐Ag in non‐tumor‐bearing hosts. Furthermore, OX40 engagement reversed tumor‐specific CD8 T‐cell anergy and restored the proliferative capacity of tumor‐reactive CD8 T cells, which attenuated tumor growth and enhanced the survival of tumor‐bearing hosts. These data demonstrate that OX40 ligation can rescue the function of anergic self‐ or tumor‐reactive CD8 T cells in vivo and suggests that OX40‐mediated therapy may provide a novel means of boosting anti‐tumor immunity by restoring the responsiveness of previously anergic tumor‐specific CD8 T cells.
Molecular Iodine Stabilization in an Extended N···I–I···N Assembly
Authors: Isaia Francesco , Aragoni M. Carla , Arca Massimiliano , Demartin Francesco , Devillanova Francesco A. , Ennas Guido , Garau Alessandra , Lippolis Vito , Mancini Annalisa , Verani Gaetano
Published: July 2009

The adduct [bis(quinoxaline)‐2,2′,3,3′‐disulfide·I2]∞ (Q2S2·I2)∞ (1) can be easily synthesised from the reaction of Q2S2 and I2 in CH2Cl2 or, in the absence of any solvent, through diffusion of I2 vapours at 60 °C. X‐ray diffraction analysis shows the presence of an extended N···I–I···N assembly in which each I2 molecule links a Q2S2 molecule at both ends through a nitrogen atom to form a polymeric species; the d(I–I) and d(N–I) bond lengths confirm a very weak nitrogen–iodine interaction at the base of the N···I–I···N assembly. DFT calculations provide optimised distances for the N···I and I–I bonds and explanation for the zigzag chain formation: the mPW1PW functional and the B3LYP hybrid functional with a variety of basis sets for the I atomic species [CRENBL, LANL2DZ, LANL2DZ(d,p), LANL08(d), SBKJC, SBKJC polarised‐LFK and Stuttgart RLC] have been tested. Compound 1 proved stable up to nearly 100 °C, and the stability is to be mainly attributed to the lattice energy of its polymeric structure then to donor–acceptor stabilisation. The facile insertion of molecular iodine into the Q2S2 network makes this compound an interesting iodine sponge, suitable for I2 storage; moreover, Q2S2 can easily collect and release I2(g) by a temperature‐controlled process (60 and 97 °C, respectively). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Cyclometallated [C,N,O] Complexes as Metalloligands: Synthesis and Structural Characterisation of New Di‐, Tri‐, Tetra‐ and Pentanuclear Heterometallic Complexes (Eur. J. Inorg. Chem. 21/2009)
Authors: Gómez‐Blanco Nina , Fernández Jesús J. , Fernández Alberto , Vázquez‐García Digna , López‐Torres Margarita , Vila José M.
Published: July 2009

The cover picture shows (left) the new heteropentametallic [{Pd[4‐[W(CO)5WNC5H4]C6H3C(H)=N{2′‐(O)‐5′‐tBuC6H3}]}2(μ‐PPh2(η5‐C5H4)Fe(η5‐C5H4)PPh2)] and heterodimetallic [Pd{4‐[RuCl2(CO)(PPh3)I2]NC5H3]C(H)=N[2′‐(O)‐5′‐tBuC6H3]}(PPh3)] cyclometallated complexes synthesized from [C,N,O] palladacycles, which behave as metalloligands by coordination through the pyridine nitrogen atom. The crystal structure (right) shows the precursor for the tungsten complex, which like its chromium and molybdenum analogues, requires UV radiation in the preparative process. Details are discussed in the article by J. J. Fernández, J. M. Vila et al. on p. 3071 ff.
A Novel Approach to the Practical Synthesis of Sulfides: An InBr3–Et3SiH Catalytic System Promoted the Direct Reductive Sulfidation of Acetals with Disulfides
Authors: Sakai Norio , Moritaka Kohei , Konakahara Takeo
Published: July 2009

We have demonstrated a facile and direct synthesis of sulfide derivatives using acetals and ketals, derived from aromatic/conjugated aldehydes and aromatic ketones, with disulfides and the InBr3–Et3SiH reducing system. We also succeeded in developing an unprecedented one‐pot preparation of an aliphatic sulfide from a disulfide and an aliphatic acetal. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Numerical approximation of viscous terms in finite volume models for shallow waters
Authors: Mohammadian A.
Published: July 2009

Two methods for the numerical treatment of viscous terms in shallow water equations are studied and computational details are given for structured grids. It is demonstrated that the first scheme, which is widely used, may lead to spurious oscillations arising from computational modes. In fact, the shortest resolvable waves of wave length 2Δx are invisible to this method. The second method, although more expensive, is free of computational modes and it presents a more accurate approximation of viscous terms. The dispersion relation of the second method is closer to the analytical case and it has a smaller truncation error, which is due to the fact that it uses a more localized control volume. Numerical experiments are also presented that support the study. Copyright © 2009 John Wiley & Sons, Ltd.
Comparing isotropic and anisotropic smoothing for voxel‐based DTI analyses: A simulation study
Authors: Van Hecke Wim , Leemans Alexander , De Backer Steve , Jeurissen Ben , Parizel Paul M. , Sijbers Jan
Published: July 2009

Voxel‐based analysis (VBA) methods are increasingly being used to compare diffusion tensor image (DTI) properties across different populations of subjects. Although VBA has many advantages, its results are highly dependent on several parameter settings, such as those from the coregistration technique applied to align the data, the smoothing kernel, the statistics, and the post‐hoc analyses. In particular, to increase the signal‐to‐noise ratio and to mitigate the adverse effect of residual image misalignments, DTI data are often smoothed before VBA with an isotropic Gaussian kernel with a full width half maximum up to 16 × 16 × 16 mm3. However, using isotropic smoothing kernels can significantly partial volume or voxel averaging artifacts, adversely affecting the true diffusion properties of the underlying fiber tissue. In this work, we compared VBA results between the isotropic and an anisotropic Gaussian filtering method using a simulated framework. Our results clearly demonstrate an increased sensitivity and specificity of detecting a predefined simulated pathology when the anisotropic smoothing kernel was used. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
Two novel NPM1 mutations in a therapy‐responder AML patient
Authors: Pianta Annalisa , Fabbro Dora , Damiani Daniela , Tiribelli Mario , Fanin Renato , Franzoni Alessandra , Romanello Milena , Tell Gianluca , Di Loreto Carla , Damante Giuseppe
Published: July 2009

Nucleophosmin 1 (NPM1) is an abundant phosphoprotein mainly located in the nucleolus but also shuttling between the nucleus and cytoplasm. NPM1 has been proposed to be involved in synthesis and processing of ribosomal RNA, regulation of chromatin structure and transport of rRNA and ribosomal proteins. NPM1 gene is considered to be implicated in human cancer as it is a frequent target of genetic alterations, primarily in haematopoietic neoplasms. We describe a case of a therapy‐responder acute myeloid leukaemia (AML) patient bearing two novel NPM1 mutations. Cells' transfection studies indicate that the presence of one of these mutations is associated to an abnormal nucleolar structure, suggesting that NPM1 may contribute to the control of nucleolar integrity. Copyright © 2009 John Wiley & Sons, Ltd.
Experimental and clinical characteristics in myelodysplastic syndrome patients with or without HLA‐DR15 allele
Authors: Xiao Li , Qiong Liao , Yan Zhang , Zheng Zhang , Luxi Song , Li Xu , Ying Tao , Yizhi Liu , Quan Pu
Published: July 2009

We studied the effects of the presence of the HLA‐DR15 allele on the experimental and clinical features of myelodysplastic syndrome (MDS) by assessing the clinical data of 136 patients with MDS. We observed that the frequency of HLA‐DR15 expression in MDS patients (38.7%) was significantly higher than that in the healthy controls (p < 0.01). We noted the following observations with regard to disease progression: None of the 46 HLA‐DR15 positive patients with international prognostic scoring system (IPSS) scores ≤1 developed acute myeloid leukaemia (AML) during the follow‐up period, while six of the 63 DR15‐negative patients with the same IPSS score developed AML within a shorter follow‐up period (p = 0.039). Furthermore, the incidence of poor chromosomal abnormalities, the percentage of patients with IPSS scores ≥1.5 and the presence of ≥5% blasts in the bone marrow in the DR15‐positive patients were lower than the corresponding findings in the DR15‐negative patients. In addition, we also recorded the following observations with regard to bone marrow (BM) failure: The bicytopenia/pancytopenia ratio in the DR15‐positive patients was higher than that in the DR15‐negative patients (92.4 vs. 78.3%; p = 0.029). The peripheral–neutrophil count and the platelet count in the DR15‐positive patients were lower than those in the DR15‐negative patients (p = 0.028 and p = 0.011, respectively). Moreover, hypocellularity was more easily detectable in the DR15‐positive patients (26.4 vs. 16.9%). In addition, the BM CD4+ lymphocyte count and the CD4/CD8 ratio in the DR15‐positive patients were higher than the corresponding values in the DR15‐negative patients (p < 0.05 for both). However, there were no significant differences between the polarization of T‐helper (Th) and T‐cytotoxic (Tc) cells and the cytokine levels in these two patient groups. We concluded that the presence of the HLA‐DR15 allele is indicative of a genetic susceptibility to MDS and, the presence of the HLA‐DR15 allele showed less association with disease progression and greater association with BM failure. Copyright © 2009 John Wiley & Sons, Ltd.
Inhibition of ovarian cancer cell proliferation by a cell cycle inhibitory peptide fused to a thermally responsive polypeptide carrier
Authors: Massodi Iqbal , Moktan Shama , Rawat Aruna , Bidwell Gene L. , Raucher Drazen
Published: July 2009

Current treatment of solid tumors is limited by normal tissue tolerance, resulting in a narrow therapeutic index. To increase drug specificity and efficacy and to reduce toxicity in normal tissues, we have developed a polypeptide carrier for a cell cycle inhibitory peptide, which has the potential to be thermally targeted to the tumor site. The design of this polypeptide is based on elastin‐like polypeptide (ELP). The coding sequence of ELP was modified by the addition of the cell penetrating peptide Bac‐7 at the N‐terminus and a 23 amino acid peptide derived from p21 at the C‐terminus (Bac‐ELP1‐p21). Bac‐ELP1‐p21 is soluble in aqueous solutions below physiological temperature (37°C) but aggregates when the temperature is raised above 39°C, making it a promising thermally responsive therapeutic carrier that may be actively targeted to solid tumors by application of focused hyperthermia. While Bac‐ELP1‐p21 at 37°C did not have any effect on SKOV‐3 cell proliferation, the use of hyperthermia increased the antiproliferative effect of Bac‐ELP1‐p21 compared with a thermally unresponsive control polypeptide. Bac‐ELP1‐p21 displayed both a cytoplasmic and nuclear distribution in the SKOV‐3 cells, with nuclear‐localized polypeptide enriched in the heated cells, as revealed by confocal microscopy. Using Western blotting, we show that Bac‐ELP1‐p21 caused a decrease in Rb phosphorylation levels in cells treated at 42°C. The polypeptide also induced caspase activation, PARP cleavage, and cell cycle arrest in S‐phase and G2/M‐phase. These studies indicate that ELP is a promising macromolecular carrier for the delivery of cell cycle inhibitory peptides to solid tumors.
Risk of testicular cancer according to birthplace and birth cohort in Denmark
Authors: Myrup Charlotte , Wohlfahrt Jan , Oudin Anna , Schnack Tine , Melbye Mads
Published: July 2009

Based on the intriguing finding of an east‐west gradient of testicular cancer risk in the Nordic countries with a low risk in Finland, intermediate in Sweden, and high risk in Denmark, it was suggested that national practices rather than individual behavior may be important in the etiology of this cancer. We investigated the risk of testicular cancer in all men born in Denmark, 1931–1969 according to birthplace. Testicular cancer information was derived from the Danish Cancer Registry and population data from Statistics Denmark. There was a several fold geographical variation in testicular cancer risk within Denmark. Among men born in the early period, 1931–39, the highest risk was primarily observed in the western part of Denmark whereas no such gradient was observed in more recent cohorts. The incidence of testicular cancer increased in all counties from the earliest to the latest birth cohort, but the increase was highest in the eastern parts of Denmark. The heterogeneity in risk according to place of birth within Denmark suggests that individual behavior plays an important role for the risk of testicular cancer. Based on the Danish data, the factor that may have caused the east‐west gradient in testicular cancer risk appears to have been more unevenly distributed in the early part of the past century compared to more recent times.
Detection of gastric carcinoma‐associated MG7‐Ag by serum immuno‐PCR assay in a high‐risk Chinese population, with implication for screening
Authors: Zhang Lian , Ren Jun , Pan Kaifeng , Ma Junling , Li Jiyou , Shen Lin , Zhang Xiaodong , Li Jie , Fan Daiming , Gail Mitchell , You Weicheng
Published: July 2009

To evaluate gastric carcinoma‐associated antigen, MG7‐Ag, for detection of gastric cancer in a high‐risk population, a population‐based screening of gastric cancer was conducted in Linqu County, Shandong Province, China. In 2002 and 2003, a total of 2,710 participants aged 35–65 years received an endoscopic examination with 5 biopsies taken from standard sites with pathological diagnosis, and serum samples were collected to detect MG7‐Ag by serum‐based Immunopolymerase chain reaction (PCR) assay. The sensitivity and specificity of MG7‐Ag Immuno‐PCR assay in detecting of gastric cancer were assessed. Of 2,710 participants, 148 (5.46%) were determined to be MG7‐Ag positive. The sensitivity of MG7‐Ag Immuno‐PCR assay for the detection of gastric cancer was 77.5% (31 of 40 gastric cancer cases), the specificity was 95.62% (2,553 of 2,670 nongastric cancer subjects) and the accuracy was 73.12%. A total of 24 gastric cancer cases were in Stage I or II, of which 17 (70.8%) were MG7‐Ag positive. However, the proportion of MG7‐Ag positivity in subjects with superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, indefinite dysplasia or dysplasia was ranged from 3.00% to 5.61% in comparison with 77.5% in those with gastric cancer. Our findings suggest that MG7‐Ag was a sensitive and specific serum biomarker and may have a potential for gastric cancer screening in the high‐risk population.