bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival trends among 1,325 patients with chronic lymphocytic leukemia seen over the past 40 years in Israel
Authors: Shvidel Lev , Braester Andrei , Bairey Osnat , Rahimi‐Levene Naomi , Klepfish Abraham , Herishanu Yair , Shtalrid Mordechai , Polliack Aaron , Berrebi Alain ,   for the Israeli CLL Study Group
Published: August 2011

In the light of recent data showing survival improvement of patients with chronic lymphocytic leukemia (CLL), we investigated clinical characteristics and survival patterns of patients with CLL over the last 40 years in Israel. Demographic and clinical data collected in the database of the Israeli CLL Study Group were analyzed. Of the 1,325 patients, 221 were diagnosed during the time period 1968–1989, 456 during 1990–1999, and 639 during 2000–2010. There was shift toward older age (median, 71 vs. 68 vs. 66 years) and a higher proportion of patients at Binet stage A at diagnosis (77.6% vs. 66.7% vs. 60.3%) in the more recent time periods. Median survival for the entire cohort was 10.9 years; 12.2 years for patients diagnosed at Binet stage A, 8.5 years for stage B, and 6.4 years for stage C patients. Older age, high‐beta 2‐microglobulin level, and expression of ZAP‐70 predicted shorter survival. There were no apparent changes over time regarding gender, age or different clinical stages. Young patients with Binet stage A had lower life expectancy than the general population; but, in older ages, the survival rates were comparable. There were increased proportions of CLL patients diagnosed in early stages, and, at older age, during the last decades, however, survival rates according to sex, age, or stage remained stable. CLL continues to be an incurable disease affecting survival even in patients diagnosed at early stages. Survival benefit shown in recent trials using chemoimmunotherapy has still to be proven in wider general practice. Am. J. Hematol. 86:985–992, 2011. © 2011 Wiley‐Liss, Inc.
Host‐Enhanced π–π Interaction for Water‐Soluble Supramolecular Polymerization
Authors: Liu Yiliu , Liu Kai , Wang Zhiqiang , Zhang Xi
Published: August 2011

Host‐enhanced π–π interaction based on anthracene derivatives and cucurbit[8]uril can be used as the driving force for constructing water‐soluble supramolecular polymers. For this purpose, two anthracene moieties were encapsulated into one cucurbit[8]uril cavity, forming a ternary complex. After encapsulation in the host, the distance between the two anthracene moieties was shortened, and the π–π interaction between them was enhanced significantly. To realize supramolecular polymerization, a bifunctional monomer consisting of two anthracene moieties and a short linker in between was carefully designed. Cyclization was avoided in this way. Thus, host‐enhanced π–π interaction can function as a new driving force for supramolecular polymerization.
Five‐year quality of life results of the randomized clinical phase III (RADPLAT) trial, comparing concomitant intra‐arterial versus intravenous chemoradiotherapy in locally advanced head and neck cancer
Authors: Ackerstaff Annemieke H. , Rasch Coen R. N. , Balm Alfons J. M. , de Boer Jan Paul , Wiggenraad Ruud , Rietveld Derek H. F. , Gregor R. Theo , Kröger Robert , Hauptmann Michael , Vincent Andrew , Hilgers Frans J. M.
Published: August 2011

Background

The purpose of this investigation was to present 5‐years of quality‐of‐life (QOL) results of a multicenter randomized phase III trial, assessing intra‐arterial (IA) versus standard intravenous (IV) chemoradiation for inoperable stage IV head and neck cancer.

Methods

Evaluation of 71 patients through European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC QLQ‐C30) and Head and Neck Module (QLQ‐H&N35), and trial‐specific questionnaires. Treatment consisted of standard radiotherapy with 4 weekly IA or 3 weekly IV cisplatin infusions.

Results

No significant differences in treatment‐related QOL problems between 1 and 5 years posttreatment were observed, except for “dry mouth” (gradually improving; p = .004). Survivors have lower fatigue levels (p = .04), better voice (p = 0.3), and swallowing (p = .03) than patients who could not complete all subsequent follow‐up questionnaires.

Conclusions

Most treatment‐related QOL issues deteriorate during treatment, improve in the first year, and then remain stable, except xerostomia, improving up to the 5‐year assessment point. Survivors show more positive scores for fatigue, voice, and swallowing. QOL issues at 1 year, thus, for most already represent those after 5‐year follow‐up. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Cell biology of paget's disease
Authors: Reddy Sakamuri V. , Menaa Cheikh , Singer Frederick R. , Demulder Anne , Roodman G. David
Published: August 2011

Paget's disease is characterized by markedly increased osteoclast formation and bone resorption followed by excessive new bone formation. Osteoclasts in Paget's disease are increased both in number and size, contain paramyxoviral-like nuclear inclusions, and can have up to 100 nuclei per cell. Marrow culture studies have identified several abnormalities in osteoclast formation in Paget's disease. Osteoclast-like multinucleated cells formed more rapidly in marrow cultures from patients with Paget's disease, produced increased levels of inter-leukin-6 (IL-6), and expressed high levels of IL-6 receptors compared to normals. IL-6 levels were also increased in bone marrow and peripheral blood of patients with Paget's disease. In addition, osteoclast precursors from patients with Paget's disease are hyperresponsive to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and calcitonin. The increased sensitivity of osteoclast precursors to 1,25(OH)2D3 is mediated through the vitamin D receptor (VDR), since 24-hydroxylase activity is also up-regulated at concentrations of 1,25(OH)2D3 that are one log less than that needed to induce 24-hydroxylase activity in osteoclast precursors from normals. However, VDR numbers and affinity for 1,25(OH)2D3 do not differ in osteoclast precursors from Paget's patients compared to those from normals. Synergistic interactions between cytokines such as IL-6 and 1,25(OH)2D3 also cannot explain the enhanced sensitivity of osteoclast precursors from patients with Paget's disease to 1,25(OH)2D3. Interestingly, coculture studies of osteoclast precursors and cells from the marrow microenvironment of patients with Paget's disease and normals have demonstrated that the marrow microenvironment is more osteoclastogenic than normal. Thus, studies of the cell biology of osteoclasts in Paget's disease have demonstrated an increased rate of osteoclast formation and abnormalities in both osteoclast precursors and the marrow microenvironment Enhanced IL-6 production by osteoclasts in Paget's disease may further amplify the increased osteoclast formation already ongoing in the pagetic lesion, and may explain the increased bone turnover at uninvolved sites distant from the pagetic lesion.
Patterns of diagnosis of paget's disease in spain
Authors: Rapado A. , Jimenez J. , Morales A. , Carbonell J. , Pino J. Del
Published: August 2011

To evaluate the incidence of diagnosis of Paget's disease of bone in Spain, a retrospective study was performed from 1991–1997 in four Spanish centers to evaluate the number of diagnosed Paget's disease cases. Information about the age, gender, and year of admission and an estimation of the reference population with the number of discharges at the centers were registered for each calendar year. The relative diagnostic risk of Paget's disease was calculated, using 1991 as the reference by Poisson's regression models. The percentage of males among the diagnosed cases varied from 39% in 1992 to 62% in 1993 without significant difference between the different years (p = 031). The great majority of the cases were diagnosed between 50 and 89 years of age, from 89% in 1992 and 94% in 1993. During the first years the main part of the cases corresponded to persons younger than 69 years (57.5% in 1991, 50% in 1992, and 64.7% in 1993), but from 1994 the major percentage was found in individuals over 70 years of age (68.1% in 1994, 53.8% in 1995, 62.3% in 1996, and 58.1% in 1997) (p = 0.045). Once the results were adjusted by the diagnosis center, an increased diagnostic risk of Paget's disease relative to the year of diagnosis was seen. In 1996 the risk was 54% higher than in 1991. This tendency reached statistical significance (p for trend = 0.03). The results of this study demonstrate that there is an increasing diagnostic tendency of Paget's disease along the period of study due to different analyzed variables.
Application of the thin‐shell formulation to the numerical modeling of Stern layer in biomolecular electrostatics
Authors: Manzin Alessandra , Bottauscio Oriano , Ansalone Domenico Patrizio
Published: August 2011

In this article, the thin‐shell formulation is applied to efficiently modeling the Stern layer within computational algorithms oriented toward the boundary element solution of the linearized Poisson–Boltzmann equation. The attention is focused on the calculation of the electrostatic potential in proximity to a biomolecule immersed in an electrolyte medium. Following the proposed approach, the Stern layer is made to collapse to a zero‐thickness region (two‐dimensional surface) with interface conditions linking the electrostatic potential over the molecular and the bulk ion accessible surfaces. Advantages lie in the limitation of divergent integral problems and in the halving of the unknown number, with a significant impact on computational time and memory requirements when modeling large biomolecules. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Influence of growth rate on occurrences of pale muscle in broilers
Authors: Samuel Dora D , Billard Lynne , Pringle Dean , Wicker Louise
Published: August 2011

BACKGROUND: Pale broiler breast meat is a defect in commercial production operations. The incidence of pale broiler breast meat was examined in two commercial processing plants which had average growth rates of 59 g day−1 and 46 g day−1 and final average weights of 3.36 kg and 1.93 kg. Color measurements of dorsal and ventral surfaces and pH were completed to evaluate the impact of selection for growth on meat water‐holding capacity.

RESULTS: L* greater than 60 were observed in 57% of broilers selected for greater yield and 26% of slower growing broilers. Average L* between 10 growers was significantly different (P = 0.001). Pearson's correlation coefficients for pH and L* were − 0.51 and − 0.27 for the faster growing broilers and slower growing broilers, respectively. The Pearson correlation coefficients between water‐holding capacity and L* and pH was − 0.35 and 0.42, respectively. There was a higher correlation between production factors (age, weight and grower) and a* and b* than L* for ventral surface measurements.

CONCLUSION: Breasts from broilers selected for faster growth tend to have lighter color. Weak correlation with water‐holding capacity suggests that quality remains the same and light color is probably related to other factors. Copyright © 2011 Society of Chemical Industry
Evaluation of fecal DNA preservation techniques and effects of sample age and diet on genotyping success
Authors: Panasci Michael , Ballard Warren B. , Breck Stewart , Rodriguez David , Densmore Llewellyn D. , Wester David B. , Baker Robert J.
Published: August 2011

Optimal collection and preservation protocols for fecal DNA genotyping are not firmly established. We evaluated 3 factors that influence microsatellite genotyping success of fecal DNA extracted from coyote (Canis latrans) scats: 1) age of scat, 2) preservative, and 3) diet content. We quantified genotyping success by comparing rates of allelic dropout, false alleles, and failed amplifications among consensus genotypes. We used a panel of 6 microsatellite loci to genotype 20 scat samples, each of which was subjected to 3 age (1 day, 5 days, and 10 days post‐deposition) and 3 preservation (DET buffer, 95% ethanol [EtOH], and lysis buffer) treatments. Both sample age and storage buffer had a significant effect on success and reliability. Ethanol and DET buffer preserved fecal samples with similar efficiency, and both were superior to lysis buffer. Our analysis of DNA degradation rates revealed that samples collected as early as 5 days of age yielded DNA that was highly degraded relative to samples collected on day 1. We tested the influence of dietary remains on microsatellite genotyping by using scat samples consisting predominantly of insect prey (n = 5), mammalian prey (n = 9), or the remains of juniper (Juniperus spp.) berries (n = 6) and compared EtOH and DET buffer preservation efficacy. We observed a significant interaction effect between storage buffer and diet for the probability of a false allele in a polymerase chain reaction (PCR), suggesting that the optimal preservation technique depended on the food remains comprising the scat. Scats comprised of juniper berry remains were more reliably genotyped when preserved in DET than EtOH. Mammalian prey‐based scats were more reliable when stored in EtOH than DET buffer. Insect‐predominant scats were preserved in EtOH and DET buffer with similar efficiency. Although accurate and reliable results can be obtained from scats collected at ≥5 days of age, we suggest sampling design to include collection of scats <5 days of age to minimize field and laboratory expenses. We suggest EtOH preservation for scats of obligate carnivores and of facultative carnivores with a diet consisting primarily of mammals. We suggest DET buffer preservation for animals with a diet consisting of plant‐derived foods. Lysis buffer protocols that we employed should not be used for fecal DNA preservation. © 2011 The Wildlife Society.
Modeling perforation in glass fiber reinforced composites subjected to low velocity impact loading
Authors: Fan Jiying , Guan Zhongwei , Cantwell Wesley J.
Published: August 2011

In this article, experimental results are presented investigating the response of glass fiber composites subjected to low velocity impact loading. The resulting load‐displacement traces and deformation modes have been used to validate a number of numerical models. Here, finite element models have been developed to predict the impact behavior of the composite plates. Damage in the woven glass‐fiber reinforced composite plate was modeled using the Hashin failure criteria. The influence of target size, projectile size, projectile shape, and striking location on the impact response of the composites was investigated. In general, good agreement was obtained in terms of the load‐displacement traces and the failure modes in the composite plates. It has been shown that the perforation energy increases rapidly with target thickness, with the numerical results closely agreeing with the experimental data. Similarly, the energy required to perforate the composite targets increases with increasing projectile diameter, with the failure mechanisms being similar in all cases. Finally, increasing the bluntness of the impactor resulted in a significant increase in the energy to perforate these targets. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers
Adolescents’ over‐use of the cyber world – Internet addiction or identity exploration?
Authors: Israelashvili Moshe , Kim Taejin , Bukobza Gabriel
Published: August 2011

In this study, we tested the hypothesis that the Internet can serve as a valuable tool assisting adolescents in pursuing the developmentally‐related need for self concept clarity. Participants in the study were 278 adolescents (48.5% girls; 7th–9th graders) who completed questionnaires relating to their levels of Internet use, Internet addiction, ego development, self consciousness, self‐concept clarity, and personal demographic data. The study results support the general notion that adolescents’ level of self‐clarity is negatively related to Internet addiction and over‐use. Hence, it is suggested that future studies on adolescents’ Internet over‐use should use qualitative rather than quantitative conceptualization and measurements in order to properly explore such a behavior and its, either positive or negative, implications. A differentiation is proposed between over‐users, heavy users, and addicted users. Namely, over‐users and heavy users utilize the Internet for age‐related and modern‐life‐related purposes, and hence should not be labeled as addicted. Implications for the measurement, definition, and treatment of Internet over‐use are suggested.
Identification and recognition of depression in community care assessments: impact of a national policy in England
Authors: Clarkson Paul , Abendstern Michele , Sutcliffe Caroline , Hughes Jane , Challis David
Published: August 2011

Background: Depression continues to be under-recognized in older people. Most policies addressing this issue focus on the primary health care team. However, recognition may be improved by use of assessment tools and collaboration between secondary health and social care, particularly at the assessment stage. This study aimed to evaluate whether the Single Assessment Process (SAP), introduced in England from April 2004, promoting such processes, improved the identification and correct recognition of depression by enhancing the content of statutory community care assessments by social services care managers.

Methods: An observational study compared depression identification and its accuracy (“correct recognition”) in samples of older people before and after SAP introduction. Participants were interviewed using standardized measures including the Geriatric Depression Scale (GDS). Depression elicited from the GDS was compared with that recorded in community care assessments with calculation of inter-rater reliabilities (kappa statistic) pre- and post-SAP. Logistic regression examined the associations between the policy's introduction, potential confounding factors (depression, cognitive impairment, function, behavior and characteristics) and the identification and correct recognition of depression.

Results: Whilst the identification of depression was more likely after SAP, its correct recognition did not improve after the policy, with only slight agreement between GDS and community care assessments. The existence of depression and cognitive impairment made identification, but not correct recognition, more likely.

Conclusions: Correct recognition of depression was not improved in these statutory care assessments following the policy. Recognizing and thus responding to depression in a coordinated and appropriate way in the community requires further action.
Disparities in Counseling for Lifestyle Modification Among Obese Adults: Insights from the Dallas Heart Study
Authors: Powell‐Wiley Tiffany M. , Ayers Colby R. , Banks‐Richard Kamakki , Berry Jarett D. , Khera Amit , Lakoski Susan G. , McGuire Darren K. , de Lemos James A. , Das Sandeep R.
Published: August 2011

Clinician counseling is a catalyst for lifestyle modification in obesity. Unfortunately, clinicians do not appropriately counsel all obese patients about lifestyle modification. The extent of disparities in clinician counseling is not well understood. Obese participants (BMI ≥30 kg/m2, N = 2097) in the Dallas Heart Study (DHS), a probability‐based sample of Dallas County residents ages 18–65, were surveyed regarding health‐care utilization and lifestyle counseling over the year prior to DHS enrollment. Health‐care utilization and counseling were compared between obese participants across three categories based on the presence of 0, 1, or 2+ of the following cardiovascular (CV) risk factors: hypertension, hypercholesterolemia, or diabetes. Logistic regression modeling was used to determine likelihood of counseling in those with 0 vs. 1+ CV risk factors, stratified by race, adjusting for age, sex, insurance status, and education. Among obese subjects who sought medical care, those with 0 CV risk factors, compared to those with 1 or 2+ CV risk factors, were less likely to report counseling about losing weight (41% vs. 67% vs. 87%, P trend <0.001), dietary changes (44% vs. 71% vs. 85%, P trend <0.001), and physical activity (46% vs. 71% vs. 86%, P trend <0.001). Blacks and Hispanics without CV risk factors had a lower odds of receiving counseling than whites without risk factors on weight loss (adjusted odds ratio (OR), 95% confidence interval (CI) for nonwhites 0.19, [0.13–0.28], whites 0.48, [0.26–0.87]); dietary changes (nonwhites 0.19, [0.13–0.27], whites 0.37, [0.21–0.64]); and physical activity (nonwhites 0.22, [0.16–0.32], whites 0.32, [0.18–0.57]). Lifestyle counseling rates by clinicians are suboptimal among obese patients without CV risk factors, especially blacks and Hispanics. Systematic education about and application of lifestyle interventions could capitalize on opportunities for primary CV risk prevention.
Role of Thrombospondin‐2 in Murine Adipose Tissue Angiogenesis and Development
Authors: Van Hul Matthias , Frederix Liesbeth , Lijnen H. Roger
Published: August 2011

Expression of thrombospondin‐2 (TSP‐2), a matricellular protein with anti‐angiogenic properties, is modulated in developing adipose tissue. To investigate a potential functional role of TSP‐2 in adipose tissue angiogenesis and growth, TSP‐2 deficient (TSP‐2−/−) and wild‐type littermate (TSP‐2+/+) mice were kept on normal chow (standard fat diet (SFD)) or on high fat diet (HFD) for 15 weeks. TSP‐2−/− mice kept on HFD had a significantly lower total body weight throughout the experimental period. Subcutaneous (SC) and gonadal (GON) fat mass were, however, not different, and their composition in terms of size and density of adipocytes and blood vessels was also comparable in both genotypes. Macrophage infiltration in SC or GON adipose tissues was not affected by TSP‐2 deficiency. TSP‐2 deficiency had no effect on adipose tissue mRNA expression of gelatinase A (MMP‐2), whereas gelatinase B (MMP‐9) was downregulated in SC and GON adipose tissues of TSP‐2−/− mice on HFD. Glucose tolerance and insulin resistance tests were comparable for TSP‐2+/+ and TSP‐2−/− mice. TSP‐2 deficiency was not compensated by increased expression of TSP‐1 in the TSP‐2−/− mice. These data suggest that TSP‐2, despite its reported anti‐angiogenic properties, does not play an important functional role in adipose tissue related angiogenesis or associated fat development in mice.
Isolation and identification of a novel polysaccharide–peptide complex with antioxidant, anti-proliferative and hypoglycaemic activities from the abalone mushroom
Authors: Li Ning , Li Le , Fang Jin Cen , Wong Jack Ho , Ng Tzi Bun , Jiang Yun , Wang Chang Rong , Zhang Ni Ye , Wen Ting Yi , Qu Li Yuan , Lv Peng Yun , Zhao Ruili , Shi Bin , Wang Yin Ping , Wang Xiao Ying , Liu Fang
Published: August 2011

A novel antioxidant polysaccharide–peptide complex LB-1b from the fruiting bodies of the edible abalone mushroom (Pleurotus abalonus) was purified and identified. The structural characteristic of LB-1b was identified by FTIR (Fourier-transform IR), 13C NMR and 1H NMR spectroscopy. LB-1b is a polysaccharide–peptide complex that contains glucose, rhamnose, glucuronic acid and galactose in the molar ratio of 22.4:1:1.7:1.6 and the N-terminal sequence of its peptide moiety has also been determined. The N-terminal amino acid sequence of LB-1b, IPKERKEFQQAQHLK, showed some resemblance to antioxidant enzymes. LB-1b exhibited high antioxidant activity in erythrocyte haemolysis in vitro and the anti-proliferative activity towards hepatoma HepG2 cells and breast cancer MCF7 cells with an IC50 of 24 and 14 μM respectively. LB-1b also demonstrated hypoglycaemic activity in drug-induced diabetic mice and anti-HIV-1 RT (reverse transcriptase) with an IC50 value of 12.5 μM.
The threshold electric field of 180° domain switching in the misfit strain-external electric field phase diagram
Authors: Zhu Z. , Zheng X. J. , Jiang D. D. , Yang Z. C.
Published: August 2011

The single domain treatment on the selected single grain was performed by the negative DC bias in order to obtain the single-domain state, and the opposite color contrasts within the selected grain in piezoelectric phase images of Pb(Zr0.52Ti0.48)O3 ferroelectric thin film were observed by piezoelectric force microscopy. Based on nonlinear thermodynamic theory, the a1c– and r– phases with the negative P3 component are introduced to describe the electric-generated domain switching, and the external misfit strain-electric field phase diagram and the electric field-polarization components curve are simulated at the simplification of uniform stress/electric distribution for the single-domain state of a single grain. In phase diagram, the electric field at the misfit strain –0.002 evaluated by x ray diffraction is 139 kV/cm for the phase transition from a1c– phase to c+ phase, and it is corresponding to the threshold electric field for 180° domain switching observed by the piezoelectric phase images.
Hydrogenation-chain-opened conductive channels in zigzag graphene nanoribbons
Authors: Wu D. D. , Jiang F. , Yin G. , Chen H. , Liang Y. Y. , Mizuseki H. , Kawazoe Y.
Published: August 2011

We discover a method of opening the conductive channels of zigzag graphene nanoribbons (ZGNRs) by using hydrogenation chains to separate the nanoribbon into two strips with a ∼0.7 Å distance, although the overall hydrogenation on graphene transforms the highly conductive semimetal sheet into an insulator. Two edge-like states emerge around each hydrogenation chain. The conductance enhancement, made by the hydrogenation chain, is found in nanoribbons with 5 to 7 chains, e.g. 5ZGNRH, 6ZGNRH, 7ZGNRH, and 7ZGNR2H (7ZGNR with two hydrogenation chains). The ZGNRs with hydrogenation chains illustrate their potential in nanoelectronics and carbon electronics as electronic leads and nonlinear devices.
Interaction between hydrogen and the Fe-B pair in boron-doped p-type silicon
Authors: Tang C. K. , Vines L. , Svensson B. G. , Monakhov E. V.
Published: August 2011

The effect of hydrogen incorporation into iron-contaminated boron-doped Cz-Si has been investigated using deep level transient spectroscopy. In-diffusion of hydrogen by wet chemical etching followed by reverse bias annealing of Al, Schottky diodes result in the appearance of the defect level characteristic to interstitial iron (Fei), and the concentration of iron-boron pairs (Fe-B) decreases correspondingly. Quantitative observations from various defect concentration versus depth profiles imply strongly that H promotes dissociation of Fe-B releasing Fei whereas no detectable passivation of Fe-B or Fei by H occurs.
High frequency elastic losses in LaAlO3 and its importance for LaAlO3/SrTiO3 heterojunctions
Authors: Salje Ekhard K. H. , Carpenter Michael A.
Published: August 2011

Cooling heterojunctions on LaAlO3 substrates or thick layers of LaAlO3 on SrTiO3 substrates below 820 K lead to a ferroelastic phase transition Pm3−m→ R3−c in LaAlO3, with extensive twinning and elastic softening. Twin boundaries add to structural disorder near the heterojunction and generate partially localized carriers. Resonant Ultrasound Spectroscopy data relating to the elastic instability in LaAlO3 show that elastic Cole-Cole circles and the background autocorrelation function follow Vogel-Fulcher behaviour, with a Vogel-Fulcher temperature of 230 K. An extremely low activation energy, 0.02 eV, would promote the formation of highly structured, “glassy” LaAlO3 near the junction.
High-power rf oscillation induced in half-metallic Co2MnSi layer by spin-transfer torque
Authors: Okura R. , Sakuraba Y. , Seki T. , Izumi K. , Mizuguchi M. , Takanashi K.
Published: August 2011

The rf oscillation induced in a current-perpendicular-to-plane device with Co2MnSi (CMS) layers by spin-transfer torque was investigated to enhance the rf output power due to the large magnetoresistance (MR) ratio. A large MR ratio of 12.5% was obtained due to the large spin-polarization of CMS, and fundamental and second harmonic rf oscillations were clearly observed in the CMS layer. A high rf output power of 1.1 nW was achieved in spite of a small precession angle of 8.6°.
Nonrandom attrition of the naive CD8
+
T-cell pool with aging governed by T-cell receptor:pMHC interactions
Authors: Rudd Brian D. , Venturi Vanessa , Li Gang , Samadder Partha , Ertelt James M. , Way Sing Sing , Davenport Miles P. , Nikolich-Žugich Janko
Published: August 2011

Immunity against new infections declines in the last quartile of life, as do numbers of naive T cells. Peripheral maintenance of naive T cells over the lifespan is necessary because their production drastically declines by puberty, a result of thymic involution. We report that this maintenance is not random in advanced aging. As numbers and diversity of naive CD8
+
T cells declined with aging, surviving cells underwent faster rates of homeostatic proliferation, were selected for high T-cell receptor:pMHC avidity, and preferentially acquired “memory-like” phenotype. These high-avidity precursors preferentially responded to infection and exhibited strong antimicrobial function. Thus, T-cell receptor avidity for self-pMHC provides a proofreading mechanism to maintain some of the fittest T cells in the otherwise crumbling naive repertoire, providing a degree of compensation for numerical and diversity defects in old T cells.
The GNAT library for local and remote gene mention normalization
Authors: Hakenberg Jörg , Gerner Martin , Haeussler Maximilian , Solt Illés , Plake Conrad , Schroeder Michael , Gonzalez Graciela , Nenadic Goran , Bergman Casey M.
Published: August 2011

Summary: Identifying mentions of named entities, such as genes or diseases, and normalizing them to database identifiers have become an important step in many text and data mining pipelines. Despite this need, very few entity normalization systems are publicly available as source code or web services for biomedical text mining. Here we present the Gnat Java library for text retrieval, named entity recognition, and normalization of gene and protein mentions in biomedical text. The library can be used as a component to be integrated with other text-mining systems, as a framework to add user-specific extensions, and as an efficient stand-alone application for the identification of gene and protein names for data analysis. On the BioCreative III test data, the current version of Gnat achieves a Tap-20 score of 0.1987.

Availability: The library and web services are implemented in Java and the sources are available from http://gnat.sourceforge.net.

Contact:  jorg.hakenberg@roche.com
Disruption of repressive p130–DREAM complexes by human papillomavirus 16 E6/E7 oncoproteins is required for cell-cycle progression in cervical cancer cells
Authors: Nor Rashid Nurshamimi , Yusof Rohana , Watson Roger J.
Published: August 2011

Human papillomaviruses (HPVs) with tropism for mucosal epithelia are the major aetiological factors in cervical cancer. Most cancers are associated with so-called high-risk HPV types, in particular HPV16, and constitutive expression of the HPV16 E6 and E7 oncoproteins is critical for malignant transformation in infected keratinocytes. E6 and E7 bind to and inactivate the cellular tumour suppressors p53 and Rb, respectively, thus delaying differentiation and inducing proliferation in suprabasal keratinocytes to enable HPV replication. One member of the Rb family, p130, appears to be a particularly important target for E7 in promoting S-phase entry. Recent evidence indicates that p130 regulates cell-cycle progression as part of a large protein complex termed DREAM. The composition of DREAM is cell cycle-regulated, associating with E2F4 and p130 in G0/G1 and with the B-myb transcription factor in S/G2. In this study, we addressed whether p130–DREAM is disrupted in HPV16-transformed cervical cancer cells and whether this is a critical function for E6/E7. We found that p130–DREAM was greatly diminished in HPV16-transformed cervical carcinoma cells (CaSki and SiHa) compared with control cell lines; however, when E6/E7 expression was targeted by specific small hairpin RNAs, p130–DREAM was reformed and the cell cycle was arrested. We further demonstrated that the profound G1 arrest in E7-depleted CaSki cells was dependent on p130–DREAM reformation by also targeting the expression of the DREAM component Lin-54 and p130. The results show that continued HPV16 E6/E7 expression is necessary in cervical cancer cells to prevent cell-cycle arrest by a repressive p130–DREAM complex.
Genome-wide depletion of replication initiation events in highly transcribed regions
Authors: Martin Melvenia M. , Ryan Michael , Kim RyangGuk , Zakas Anna L. , Fu Haiqing , Lin Chii Mei , Reinhold William C. , Davis Sean R. , Bilke Sven , Liu Hongfang , Doroshow James H. , Reimers Mark A. , Valenzuela Manuel S. , Pommier Yves , Meltzer Paul S. , Aladjem Mirit I.
Published: August 2011

This report investigates the mechanisms by which mammalian cells coordinate DNA replication with transcription and chromatin assembly. In yeast, DNA replication initiates within nucleosome-free regions, but studies in mammalian cells have not revealed a similar relationship. Here, we have used genome-wide massively parallel sequencing to map replication initiation events, thereby creating a database of all replication initiation sites within nonrepetitive DNA in two human cell lines. Mining this database revealed that genomic regions transcribed at moderate levels were generally associated with high replication initiation frequency. In genomic regions with high rates of transcription, very few replication initiation events were detected. High-resolution mapping of replication initiation sites showed that replication initiation events were absent from transcription start sites but were highly enriched in adjacent, downstream sequences. Methylation of CpG sequences strongly affected the location of replication initiation events, whereas histone modifications had minimal effects. These observations suggest that high levels of transcription interfere with formation of pre-replication protein complexes. Data presented here identify replication initiation sites throughout the genome, providing a foundation for further analyses of DNA–replication dynamics and cell-cycle progression.
Factors associated with injection cessation, relapse and initiation in a community‐based cohort of injection drug users in Chennai, India
Authors: Mehta Shruti H. , Sudarshi Darshan , Srikrishnan Aylur K. , Celentano David D. , Vasudevan Canjeevaram K. , Anand Santhanam , Kumar Muniratnam Suresh , Latkin Carl , Solomon Suniti , Solomon Sunil S.
Published: August 2011

Aims  To characterize factors associated with injection cessation, relapse and initiation.

Design  The Madras Injection Drug User and AIDS Cohort Study (MIDACS) is a prospective cohort of injection drug users (IDUs) recruited in 2005–06 with semi‐annual follow‐up to 2009. Discrete‐time survival models were used to characterize predictors of time to first injection cessation and relapse.

Setting  Chennai, India.

Participants  A total of 855 IDUs who reported injecting in the 6 months prior to baseline and had >1 follow‐up visit.

Measurements  Cessation was defined as the first visit where no injection drug use was reported (prior 6 months) and relapse as the first visit where drug injection (prior 6 months) was reported after first cessation.

Findings  All participants were male; median age was 35 years. Over 3 years, 92.7% reported cessation [incidence rate (IR): 117 per 100 person‐years]. Factors associated positively with cessation included daily injection and incarceration and factors associated negatively with cessation included marriage, alcohol and homelessness. Of those who reported cessation, 23.6% relapsed (IR: 19.7 per 100 person‐years). Factors associated positively with relapse included any education, injection in the month prior to baseline, sex with a casual partner, non‐injection drug use, incarceration and homelessness. Alcohol was associated negatively with relapse. The primary reasons for cessation were medical conditions (37%) and family pressure (22%). The majority initiated with non‐injection drugs, transitioning to injection after a median 4 years.

Conclusions  Injection drug users in southern India demonstrate a high rate of injection cessation over 3 years, but relapse is not uncommon. Compensatory increases in alcohol use indicate that cessation of injection does not mean cessation of all substance use. Family pressure, concerns about general health, fear of human immunodeficiency virus infection and a history of non‐injection drug use are important correlates of cessation.
Non steroidal anti‐inflammatory drug use and levels of oestrogens and androgens in men
Authors: Gates Margaret A. , Araujo Andre B. , Hall Susan A. , Wittert Gary A. , McKinlay John B.
Published: August 2011

Objective  Studies suggest that regular use of nonsteroidal anti‐inflammatory drugs (NSAIDs) may lower oestrogen levels in women. However, no large, population‐based studies have assessed NSAID/hormone associations in men. Our objective was to examine the association between use of prescription and over‐the‐counter NSAIDs, and levels of oestrogens and androgens in men.

Design  The Boston Area Community Health Survey, an observational survey with initial data collection in 2002–2005.

Patients  A total of 1766 men who provided a blood sample and data on recent analgesic use.

Measurements  Adjusted geometric mean levels of androgens, oestrogens, SHBG, LH and FSH for each category of NSAID use and the per cent difference in hormone levels for users vs nonusers.

Results  There was no significant association between prescription/over‐the‐counter NSAID use and any hormone examined after adjustment for potential confounders. For example, geometric mean testosterone levels were 13·8, 13·6 and 14·2 nm in nonusers, prescription users and over‐the‐counter NSAID users, respectively; the corresponding levels for estradiol were 80·3, 70·4 and 79·9 pm. In stratified analyses, however, prescription NSAID use was associated with lower testosterone, estradiol and estrone levels in obese men and lower testosterone and dehydroepiandrosterone sulphate levels in inactive men.

Conclusions  While overall these data do not provide strong support for an association between NSAID use and hormone levels in men, prescription NSAIDs may decrease levels of certain oestrogens and androgens in obese and inactive men.
Benefits associated with a broad selection of dosage strengths for recombinant factor VIII products
Authors: EPSTEIN J. , XIONG Y. , LUO M. , LI‐McLEOD J.
Published: August 2011

Summary.  Factor VIII (FVIII) concentrates for haemophilia A patients are dosed according to body weight. This results in a continuous range of prescribed doses, which challenges pharmacies to find dosage strengths closest to the prescribed dose while utilizing the least number of vials. This study was conducted to determine whether a broader selection of FVIII dosage strengths results in improved dispensing accuracy and an increased number of single‐vial users. This research retrospectively analyzed a US pharmacy database of prescriptions filled in 2008. Recombinant FVIII (rFVIII) therapies were classified by the range of dosage strengths offered in 2008: Group 1 had three dosage strengths; Group 2 had four dosage strengths; and Group 3 had six dosage strengths. A total of 76 584 dispensed doses of rFVIII for 1 244 patients were included in this analysis. Dispensing accuracy (calculated as both the absolute and relative difference between dispensed and prescribed dose) was significantly better for Group 3 (23.2 IU, 1.2%) than Groups 1 (33.5 IU, 1.6%) and 2 (50.2 IU, 2.4%) (both P < 0.01). In addition, the average number of unique actual rFVIII potencies dispensed per month was highly correlated (−0.977) with dispensing accuracy for each dosage strength group. Among Groups 1, 2 and 3, 23.0%, 44.9% and 73.4% of patients, respectively, had at least one single vial option dispensed (P < 0.0001). A broader selection of rFVIII dosage strengths and more actual rFVIII potencies were associated with improved dispensing accuracy and more single‐vial users. This may translate into less waste, cost savings, increased convenience and improved adherence to physician‐prescribed regimens.
Are expression and localization of tight and adherens junction proteins in testes of adult boar affected by foetal and neonatal exposure to flutamide?
Authors: Hejmej A. , Kopera I. , Kotula‐Balak M. , Lydka M. , Lenartowicz M. , Bilinska B.
Published: August 2011

Several recent studies have indicated that androgen disruption induced by the administration of anti‐androgen flutamide during critical developmental stages results in various reproductive abnormalities, mainly in rodents. However, scarce data are available regarding the alterations caused by this toxicant on cell–cell adhesion molecules. Of note, there is no report on the expression and regulation of tight and adherens junction proteins in the boar. Therefore, the purpose of this study was to analyse whether foetal and neonatal exposure to flutamide affects the expression and distribution of ZO‐1, occludin, β‐catenin, and N‐cadherin in testes of adult pigs. Moreover, to evaluate whether androgen signal was altered in the boar, testicular levels of testosterone and oestradiol and the expression of androgen receptor were examined. Flutamide (50 mg/kg bw) was injected into pregnant gilts during gestational days 20–28 and 80–88 (GD20, GD80), and into male piglets on postnatal days 2–10 (PD2). In the testes of all flutamide‐exposed boars, expressions of ZO‐1, N‐cadherin and β‐catenin were significantly decreased at mRNA and protein level, whereas expression of occludin was unchanged when compared with the controls. In addition, in severely damaged seminiferous tubules of PD2 pigs, mislocalization of ZO‐1, N‐cadherin and β‐catenin was observed. Changes in junction protein expressions were accompanied by disturbed intratesticular androgen–oestrogen balance, although androgen receptor expression was not altered. Taken together, these results demonstrate that blockade of androgen action by flutamide during both gestational and neonatal periods affects the expression of ZO‐1, N‐cadherin and β‐catenin in adult pig testes. Of concern, neonatal window seems to be most critical for the organization of BTB and consequently for normal spermatogenesis in the boar. It is likely that altered expression of junction proteins is related to insufficient testosterone production and/or excessive oestradiol synthesis, which may result from impaired Leydig cell function.
Sacred spaces in public places: religious and spiritual plurality in health care
Authors: Reimer‐Kirkham Sheryl , Sharma Sonya , Pesut Barb , Sawatzky Richard , Meyerhoff Heather , Cochrane Marie
Published: August 2011

REIMER‐KIRKHAM S, SHARMA S, PESUT B, SAWATZKY R, MEYERHOFF H and COCHRANE M. Nursing Inquiry 2012; 19: 202–212  Sacred spaces in public places: religious and spiritual plurality in health care

Several intriguing developments mark the role and expression of religion and spirituality in society in recent years. In what were deemed secular societies, flows of increased sacralization (variously referred to as ‘new’, ‘alternative’, ‘emergent’ and ‘progressive’ spiritualities) and resurgent globalizing religions (sometimes with fundamentalist expressions) are resulting in unprecedented plurality. These shifts are occurring in conjunction with increasing ethnic diversity associated with global migration, as well as other axes of difference within contemporary society. Democratic secular nations such as Canada are challenged to achieve social cohesion in the face of growing religious, spiritual and ethnic diversity. These challenges are evident in the high‐paced, demanding arena of Health care. Here, religious and spiritual plurality enter in, sometimes resulting in conflict between medical services and patients’ beliefs, other times provoking uncertainties on the part of healthcare professionals about what to do with their own religiously or spiritually grounded values and beliefs. In this paper, we present selected findings from a 3‐year study that examined the negotiation of religious and spiritual pluralism in Health care. Our focus is on the themes of ‘sacred’ and ‘place’, exploring how the sacred – that which is attributed as special and set apart as it pertains to the divine, transcendence, God or higher power – takes form in social and material spaces in hospitals.
Micro‐indentation fracture from flat‐ended cylindrical indenter
Authors: XIE Y. J. , HU X. Z. , CHEN J. , LEE K.Y.
Published: August 2011

Unlike a Hertzian ring crack induced by a spherical indenter in absence of a singular stress field, a ring crack generated by a rigid flat cylindrical indenter can be explicitly linked to a K‐dominant singular stress field at the perimeter of the flat indenter. This means microcrack initiation induced by a flat indenter and relevant properties such as the critical indentation load and fracture toughness can be formulated explicitly using the fracture mechanics approach. It is shown in this paper that the indentation stress intensity factor, , for such a stress field is similar to that of a mode I crack. Based on the energy‐releasing rate and the Griffith's theorem, a flat indentation cracking model has been proposed; the critical load and critical cracking angle for crack initiation are derived. A new concept of fracture toughness for negative mode I singular stress field,, has been defined and a relationship between and the traditional KIC has been derived. The experimental investigation validates the existence of such , from which the KIC value of the glass had been determined to be 0.772 ± 0.003 MPa m1/2, agreeing well with the literature data. This analysis for indentation fracture or crack initiation due to surface contact of a flat indenter is particularly useful in determining KIC of brittle materials with dimensions in micro/nanoscales, e.g. thin films and other microstructures as flat micro/nano‐indenters are available and can be used on various nano‐indentation machines.
The Staphylococcus aureus CsoR regulates both chromosomal and plasmid‐encoded copper resistance mechanisms
Authors: Baker Jonathan , Sengupta Mrittika , Jayaswal Radheshyan K. , Morrissey Julie A.
Published: August 2011

Copper is an essential metal which is used as a cofactor in several enzymes and is required for numerous essential biochemical reactions. However, free copper ions can be toxic to cellular systems if the intracellular concentration is not tightly regulated. In this study we show that Staphylococcus aureus copper resistance is not the same in every staphylococcal isolate, but in fact varies considerably between clinical strains. Hyper‐copper‐resistance was shown to be due to the carriage of an additional plasmid‐encoded copper homeostasis mechanism, copBmco. This plasmid can be transferred into the copper‐sensitive S. aureus Newman to confer a hyper‐copper‐resistant phenotype, showing that copper resistance has the potential to spread to other S. aureus strains. This is the first time that plasmid‐encoded copper resistance has been reported and shown to be transferable between pathogenic bacteria isolated from humans. A homologue of the Bacillus subtilis and Mycobacterium tuberculosis CsoR regulators was identified in S. aureus. The S. aureus csoR gene is conserved in all sequenced S. aureus genomes and was found to be copper‐induced and transcribed along with two downstream genes: a putative copper chaperone (csoZ) and a hypothetical gene. Mutational and complementation studies showed that unlike other homologues, the S. aureus CsoR negatively regulates both chromosomal and plasmid‐encoded copper homeostasis mechanisms in response to excess‐copper conditions.