bluuebunny/crossref_metadata_2025 huggingface dataset:
The time perspective of the Alzheimer caregiver
Authors: Potgieter Johan C. , Heyns Pieter M. , Lens Willy
Published: September 2011

Purpose of the study: Caring for a spouse diagnosed with Alzheimer’s disease holds potentially severe negative consequences for the physical and psychological well-being of the caregiver. As it is known that the maintenance of a flexible time perspective holds benefits for individual health, the main purpose of this study was to identify and describe the changes in the time perspective of persons caring for a spouse diagnosed with Alzheimer’s disease.

Design and Methods: The SELE instrument was administered in order to shed light on the time perspective of a total of 40 participants. A criterion group design was used, and a mixed methods approach adopted during the collection and analysis of data.

Results: The results of this research project highlighted the existence of a number of important differences regarding the time perspective of caregivers and non-caregivers. The time perspective of caregivers was severely affected by the caregiving situation and the accompanying grieving process. This proved to be one potential avenue through which the caregiving situation has its negative effect on caregivers’ well-being.

Implications: Owing to the usually insufficient funding for the care of demented patients, research regarding the identification of potential cost-effective methods to enhance the resilience of caregivers is of the essence. Maintenance of a balanced time perspective might prove to be to the benefit of caregiver psychological well-being.
Art therapies and dementia care: A systematic review
Authors: Beard Renée L.
Published: September 2011

Despite steadfast interest in the use of arts therapies (ATs) with individuals who have dementia of the Alzheimer's type (DAT), a systematic review of the literature has not been conducted. This paper aims to critique this evidence base, including music, visual arts, drama, and dance/movement therapies between the years 1990 and 2010, and make suggestions on how it can be strengthened. The review addresses four questions: (1) What is the focus of the empirical base on using AT with persons who have DAT? (2) (How) have these studies been designed and evaluated? (3) What findings are reported? (4) What does this tell us about the potential of AT for enriching the lives of people with dementia? This analysis reveals that systematically designed, documented, and evaluated AT studies are scarce. Information on research design, operational concepts, measurement tools, and methods of evaluation/analysis are vague, if provided. Disagreement exists about the utilization of theoretical concepts and measurement/evaluation tools. The evidence base is further divided between studies focusing on the ‘product’ versus the ‘process’ of art. Shortcomings in dementia-specific research include a paucity of accounts from participants, failure to extend therapies to individuals in the early stages, a lack of application to those living at home, and often superficial attention to the meaningful aspects of doing art. Models investigating subjective well-being, or ‘enrichment,’ rather than objectively measured biomedical approaches privileging the management of deficits, would expand the evidence base and help ensure that those with dementia receive the services they want, since strictly allopathic methodologies will continue to fall short of adequately evaluating what are deeply idiosyncratic psychosocial issues.
Re-politicizing space through technical rules
Authors: Chiodelli Francesco
Published: September 2011

The paper focuses on the concept of technical rules (according to an Aristotelian interpretation, that is to say as propositions that express a necessity: if you want x, you must do y). The thesis argued is that this concept is helpful in coping with some of the problems of both teleological and deontological planning theories. In particular the concept is useful in emphasizing the role of technical knowledge in planning and in ‘solving the relationship’ between planning and politics in a way consistent with the characteristics of liberal and pluralist democracies.
Novel treatments for systemic lupus erythematosus
Authors: Xiong Wen , Lahita Robert G.
Published: September 2011

There are many new therapeutic directions for the disease systemic lupus erythematosus (SLE). Despite this, the US Food and Drug Administration (FDA) has approved only one biological agent and it involves B cells, now thought to play a significant role in the pathogenesis of SLE. The name of the drug is belimumab, which is an agent that removes the B-cell cytokine called B lymphocyte stimulation factor (BLyS). Rituximab did not achieve its primary endpoints, even though the consensus is that it may be effective in some forms of SLE including renal disease. The anticytokine therapies against interleukin (IL)-6, IL-10, IL-17 and tumor necrosis factor (TNF) are effective in their own ways and phase II and III trials are in progress. Of particular interest to immunologists are the anti-interferon alpha and gamma drugs, which show promise in the animal models. Modulation of costimulatory molecules; specifically, the anti CD40, CTLA-Ig and ICOS/B7RP blockade agents offer possibilities for the future using new pathways heretofore limited to rheumatoid arthritis. Finally, the use of tyrosine kinase inhibitors is another direction that has been successful in the inhibition of SLE in the murine model; early trials in human SLE have begun.
An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets
Authors: Nisar Shaista , Daly Martina E. , Federici Augusto B. , Artoni Andrea , Mumford Andrew D. , Watson Stephen P. , Mundell Stuart J.
Published: September 2011

The platelet P2Y12 purinoceptor (P2Y12R), which plays a crucial role in hemostasis, undergoes internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function. Here, we observe that P2Y12R function is compromised after deletion or mutation of the 4 amino acids at the extreme C-terminus of this receptor (ETPM), a putative postsynaptic density 95/disc large/zonula occludens-1 (PDZ)–binding motif. In cell line models, removal of this sequence or mutation of one of its core residues (P341A), attenuates receptor internalization and receptor recycling back to the membrane, thereby blocking receptor resensitization. The physiologic significance of these findings in the regulation of platelet function is shown by identification of a patient with a heterozygous mutation in the PDZ binding sequence of their P2Y12R (P341A) that is associated with reduced expression of the P2Y12R on the cell surface. Importantly, platelets from this subject showed significantly compromised P2Y12R recycling, emphasizing the importance of the extreme C-terminus of this receptor to ensure correct receptor traffic.
Wnt4 regulates thymic cellularity through the expansion of thymic epithelial cells and early thymic progenitors
Authors: Heinonen Krista M. , Ruiz Vanegas Juan , Brochu Sylvie , Shan Jingdong , Vainio Seppo J. , Perreault Claude
Published: September 2011

Thymus atrophy is the most common immunopathology in humans, and its occurrence is hastened by several factors that coalesce in patients receiving chemotherapy and most of all in recipients of hematopoietic cell transplantation. We have shown previously that posthematopoietic cell transplantation thymic function was improved by retroviral overexpression of Wnt4 in donor hematopoietic cells. Here, by using both conventional and conditional null mutant mice, we show that Wnt4 regulates steady-state thymic cellularity by a thymic epithelial cell (TEC)–dependent mechanism. The absence of Wnt4 suppressed fetal and postnatal thymic expansion and resulted in decreased TEC numbers, an alteration of the medullary-to-cortical TEC ratio, and a disproportionate loss of the most immature cKithi thymocyte precursors. Wnt4 also is implicated in the maintenance of adult thymopoiesis, although the impact of its deletion once thymic involution has been initiated is more subtle. Together, our results show that Wnt4 controls thymic size by modulating TEC expansion and the earliest, TEC-dependent steps of thymocyte development both in the fetal and postnatal thymus. Wnt4 and its downstream signaling pathways could thus represent interesting candidates to improve thymic output in subjects with thymic atrophy.
Lack of clarity in the definition of treatment-related mortality: pediatric acute leukemia and adult acute promyelocytic leukemia as examples
Authors: Ethier Marie-Chantal , Blanco Esther , Lehrnbecher Thomas , Sung Lillian
Published: September 2011

Treatment-related mortality (TRM) is important in acute lymphoblastic leukemia and acute myeloid leukemia (AML); however, little is known about how TRM is defined across trials. Two major problems are related to what constitutes treatment versus disease-related cause of death and to TRM attribution (for example, death because of infection or hemorrhage). To address the former, we conducted a systematic review of randomized therapeutic pediatric acute leukemia and adult/pediatric acute promyelocytic leukemia trials and any study type focused on TRM in pediatric acute leukemia. We described definitions used for TRM. Sixty-six studies were included. Few therapeutic pediatric acute lymphoblastic leukemia studies (2/32, 6.3%) provided definitions for TRM, whereas more therapeutic pediatric AML studies (6/9, 66.7%) provided definitions. There was great heterogeneity in TRM classification. The authors of most studies relied on deaths during induction or in remission to delineate whether a death was TRM. However, 44.4% of therapeutic AML studies used death within a specific time frame to delineate TRM. We suggest that a consistent approach to defining and determining attribution for TRM in acute leukemia is an important future goal. Harmonization of definitions across the age spectrum would allow comparisons between pediatric and adult studies.
Induction of erythropoiesis using human vascular networks genetically engineered for controlled erythropoietin release
Authors: Lin Ruei-Zeng , Dreyzin Alexandra , Aamodt Kristie , Li Dan , Jaminet Shou-Ching S. , Dudley Andrew C. , Melero-Martin Juan M.
Published: September 2011

For decades, autologous ex vivo gene therapy has been postulated as a potential alternative to parenteral administration of recombinant proteins. However, achieving effective cellular engraftment of previously retrieved patient cells is challenging. Recently, our ability to engineer vasculature in vivo has allowed for the introduction of instructions into tissues by genetically modifying the vascular cells that build these blood vessels. In the present study, we genetically engineered human blood–derived endothelial colony-forming cells (ECFCs) to express erythropoietin (EPO) under the control of a tetracycline-regulated system, and generated subcutaneous vascular networks capable of systemic EPO release in immunodeficient mice. These ECFC-lined vascular networks formed functional anastomoses with the mouse vasculature, allowing direct delivery of recombinant human EPO into the bloodstream. After activation of EPO expression, erythropoiesis was induced in both normal and anemic mice, a process that was completely reversible. This approach could relieve patients from frequent EPO injections, reducing the medical costs associated with the management of anemia. We propose this ECFC-based gene-delivery strategy as a viable alternative technology when routine administration of recombinant proteins is needed.
Attenuation of antigen-induced airway hyperresponsiveness and inflammation in CXCR3 knockout mice
Authors: Lin Yi , Yan Haibo , Xiao Yu , Piao Hongmei , Xiang Ruolan , Jiang Lei , Chen Huaxia , Huang Kewu , Guo Zijian , Zhou Wexun , Lu Bao , Gao Jinming
Published: September 2011

Background

CD8+ T cells participate in airway hyperresponsiveness (AHR) and allergic pulmonary inflammation that are characteristics of asthma. CXCL10 by binding to CXCR3 expressed preferentially on activated CD8+ T cells, attracts T cells homing to the lung. We studied the contribution and limitation of CXCR3 to AHR and airway inflammation induced by ovalbumin (OVA) using CXCR3 knockout (KO) mice.

Methods

Mice were sensitized and challenged with OVA. Lung histopathological changes, AHR, cellular composition and levels of inflammatory mediators in bronchoalveolar lavage (BAL) fluid, and lungs at mRNA and protein levels, were compared between CXCR3 KO mice and wild type (WT) mice.

Results

Compared with the WT controls, CXCR3 KO mice showed less OVA-induced infiltration of inflammatory cells around airways and vessels, and less mucus production. CXCR3 KO mice failed to develop significant AHR. They also demonstrated significantly fewer CD8+ T and CD4+ T cells in BAL fluid, lower levels of TNFα and IL-4 in lung tissue measured by real-time RT-PCR and in BAL fluid by ELISA, with significant elevation of IFNγ mRNA and protein expression levels.

Conclusions

We conclude that CXCR3 is crucial for AHR and airway inflammation by promoting recruitment of more CD8+ T cells, as well as CD4+ T cells, and initiating release of proinflammatory mediators following OVA sensitization and challenge. CXCR3 may represent a novel therapeutic target for asthma.
Amplified fragment length polymorphism of clinical and environmental Vibrio cholerae from a freshwater environment in a cholera-endemic area, India
Authors: Mishra Arti , Taneja Neelam , Sharma Ram K , Kumar Rahul , Sharma Naresh C , Sharma Meera
Published: September 2011

Background

The region around Chandigarh in India has witnessed a resurgence of cholera. However, isolation ofV. choleraeO1 from the environment is infrequent. Therefore, to study whether environmental nonO1-nonO139 isolates, which are native to the aquatic ecosystem, act as precursors for pathogenic O1 strains, their virulence potential and evolutionary relatedness was checked.

Methods

V. choleraewas isolated from clinical cases of cholera and from water and plankton samples collected from freshwater bodies and cholera-affected areas. PCR analysis for thectxA, ctxB, tcpA, toxTandtoxRgenes and AFLP with six primer combinations was performed on 52 isolates (13 clinical, 34 environmental and 5 reference strains).

Results

All clinical and 3 environmental isolates belonged to serogroup O1 and remaining 31 environmentalV. choleraewere nonO1-nonO139. Serogroup O1 isolates werectxA, tcpA(ElTor),ctxB(Classical),toxRandtoxTpositive. NonO1-nonO139 isolates possessedtoxR, but lackedctxAandctxB; only one isolate was positive fortoxTandtcpA. Using AFLP, 2.08% of theV. choleraegenome was interrogated. Dendrogram analysis showed one large heterogeneous clade (n = 41), with two compact and distinct subclades (1a and 1b), and six small mono-phyletic groups. AlthoughV. choleraeO1 isolates formed a distinct compact subclade, they were not clonal. A clinical O1 strain clustered with the nonO1-nonO139 isolates; one strain exhibited 70% similarity to the Classical control strain, and all O1 strains possessed an ElTor variant-specific fragment identified with primer ECMT. Few nonO1-nonO139 isolates from widely separated geographical locations intermingled together. Three environmental O1 isolates exhibited similar profiles to clinical O1 isolates.

Conclusion

In a unique study from freshwater environs of a cholera-endemic area in India over a narrow time frame, environmentalV. choleraepopulation was found to be highly heterogeneous, diverse and devoid of major virulence genes. O1 and nonO1-nonO139 isolates showed distinct lineages. Clinical isolates were not clonal but were closely related, indicating accumulation of genetic differences over a short time span. Though, environment plays an important role in the spread of cholera, the possibility of an origin of pathogenic O1 strains from environmental nonO1-nonO139 strains seems to be remote in our region.
Treatment incidence of and medical utilization for hospitalized subjects with pathologic fractures in Taiwan-Survey of the 2008 National Health Insurance data
Authors: Lee Yi-Hui , Hsu Yuan-Nian , Yu I-Liang , Phan Dinh-Van , Chou Pesus , Chan Chien-Lung , Yang Nan-Ping
Published: September 2011

Background

Almost all studies of pathologic fractures have been conducted based on patients with tumours and hospital-based data; however, in the present study, a nationwide epidemiological survey of pathologic fractures in Taiwan was performed and the medical utilization was calculated.

Methods

All claimants of Taiwan's National Health Insurance (NHI) Program in 2008 were included in the target population of this descriptive cross-sectional study. The registration and inpatient expenditure claims data by admission of all hospitalized subjects of the target population were examined and the concomitant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes were evaluated and classified into seven major categories of fracture.

Results

A total of 5,244 incident cases of pathologic fracture were identified from the 2008 hospitalized patient claims data. The incidence of pathologic fracture of the humerus, distal radius/ulna, vertebrae, femoral neck, other part of the femur, and tibia/fibula was 0.67, 0.08, 10.58, 1.11, 0.56, and 0.11 per 100,000 people, respectively, and patients with those fractures were hospitalized for 43.9 ± 42.9, 31.1 ± 32.9, 29. 4 ± 34.4, 43.3 ± 41.2, 42.4 ± 38.1, and 42.0 ± 32.8 days, respectively, incurring an average medical cost of US$11,049 ± 12,730, US$9,181 ± 12,115, US$6,250 ± 8,021, US$9,619 ± 8,906, US$10,646 ± 11,024, and US$9,403 ± 9,882, respectively. The percentage of patients undergoing bone surgery for pathologic fracture of the humerus, radius/ulna, vertebrae, femoral neck, other part of the femur, and tibia/fibula was 31.2%, 44.4%, 11.3%, 46.5%, 48.4%, and 52.5% respectively.

Conclusions

Comparing Taiwan to other countries, this study observed for Taiwan higher medical utilization and less-aggressive surgical intervention for patients hospitalized with pathologic fractures.
Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum isolates from Brazzaville, Republic of Congo
Authors: Mayengue Pembe Issamou , Ndounga Mathieu , Malonga Freddy Vladimir , Bitemo Michel , Ntoumi Francine
Published: September 2011

Background

The characterization of malaria parasite populations circulating in an area is part of site characterization, as a basis for evaluating the impact of malaria interventions on genetic diversity, parasite species, and multiplicity of infection. The present study was aimed at analysing genetic diversity of Plasmodium falciparum merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) and to determine the multiplicity of infection in clinical isolates collected from children living in the Southern district of Brazzaville in the Republic of Congo.

Methods

A total of 125 isolates from patients with uncomplicated malaria attending Terinkyo and Madibou health centres were collected between January and June 2005 while evaluating the therapeutic efficacy of amodiaquine-artesunate combination. DNA was extracted and msp-1 and msp-2 genes were genotyped using allele-specific nested-PCR.

Results

Out of 468 distinct fragments detected, 15 msp-1 and 20 msp-2 genotypes were identified. For the msp-1 gene, K1 family was the predominant allelic type carried alone or in association with RO33 and Mad20 types, whereas the 3D7 family was the most prevalent in the msp-2 gene. Overall, the mean multiplicity of infection was 2.2. Out of 125 samples, 104 (83%) harboured more than one parasite genotype. There was no statistical significant difference in the multiplicity of infection by either sex or age of patients. However, a statistically significant correlation was found between parasite densities and the number of genotypes.

Conclusion

Polymorphism in P. falciparum clinical isolates from Brazzaville was high and mainly of multiple clones. The basis for the positive association between parasite densities and multiplicity of infection is discussed.
Baseline results of the first malaria indicator survey in Iran at household level
Authors: Mohammadi Mahdi , Ansari-Moghaddam Alireza , Raiesi Ahmad , Rakhshani Fatemeh , Nikpour Fatemeh , Haghdost Aliakbar , Ranjbar Mansoor , Taghizadeh-Asl Rahim , Sakeni Mohammad , Safari Reza , Saffari Mehdi
Published: September 2011

Background

Malaria is one of the leading causes of sickness and death in the developing world, causing more than a million deaths and around 250 million new cases annually worldwide. The aim of this comprehensive survey was to provide information on malaria indicators at household level in high-risk malaria areas in Iran.

Methods

In a cluster randomized cross-sectional survey data were collected from 5,456 households in both rural and urban areas of 20 malaria-affected districts of Iran. All the fieldwork was done by trained interviewers and a validated questionnaire. The questionnaire comprised baseline characteristics of the study population, the knowledge of people about different aspects of malaria (such as clinical symptoms, transmission and prevention) and their practice to prevent illness (such as using mosquito nets, spraying houses). The data were analysed and descriptive statistics (i.e. frequencies, percentages) were used to summarize the results.

Results

The results of this survey showed that 20% (95% CI: 17.36 - 22.24) of households owned at least one mosquito net, whether treated or untreated. Consequently, the use of mosquito nets was considerably low among both children under age five [5.90% (95% CI: 5.14 - 6.66)] and pregnant women [5.70% (95% CI: 3.07 - 8.33)]. Moreover, less than 10% of households reported that the interior walls of their dwelling had been sprayed in the previous year [8.70% (95% CI: 6.09 - 11.31)]. Data also suggest that 63.8% of the participants recognized fever as a sign of malaria, 56.4% reported that mosquito bites cause malaria and about 35% of participants mentioned that the use of mosquito nets could prevent malaria.

Conclusion

Findings from this study indicate that low access to treated nets along with low understanding of the role of nets in malaria prevention are the main barriers to utilization of bed nets. Therefore, the use of insecticide-treated mosquito nets should be encouraged through health education on the importance of the use along with increasing access to it.
Analysis of the biofilm proteome of Xylella fastidiosa
Authors: Silva Mariana S , De Souza Alessandra A , Takita Marco A , Labate Carlos A , Machado Marcos A
Published: September 2011

Background

Xylella fastidiosa is limited to the xylem of the plant host and the foregut of insect vectors (sharpshooters). The mechanism of pathogenicity of this bacterium differs from other plant pathogens, since it does not present typical genes that confer specific interactions between plant and pathogens (avr and/or hrp). The bacterium is injected directly into the xylem vessels where it adheres and colonizes. The whole process leads to the formation of biofilms, which are considered the main mechanism of pathogenicity. Cells in biofilms are metabolically and phenotypically different from their planktonic condition. The mature biofilm stage (phase of higher cell density) presents high virulence and resistance to toxic substances such as antibiotics and detergents. Here we performed proteomic analysis of proteins expressed exclusively in the mature biofilm of X. fastidiosa strain 9a5c, in comparison to planktonic growth condition.

Results

We found a total of 456 proteins expressed in the biofilm condition, which correspond to approximately 10% of total protein in the genome. The biofilm showed 37% (or 144 proteins) different protein than we found in the planktonic growth condition. The large difference in protein pattern in the biofilm condition may be responsible for the physiological changes of the cells in the biofilm of X. fastidiosa. Mass spectrometry was used to identify these proteins, while real-time quantitative polymerase chain reaction monitored expression of genes encoding them. Most of proteins expressed in the mature biofilm growth were associated with metabolism, adhesion, pathogenicity and stress conditions. Even though the biofilm cells in this work were not submitted to any stress condition, some stress related proteins were expressed only in the biofilm condition, suggesting that the biofilm cells would constitutively express proteins in different adverse environments.

Conclusions

We observed overexpression of proteins related to quorum sensing, proving the existence of communication between cells, and thus the development of structuring the biofilm (mature biofilm) leading to obstruction of vessels and development of disease. This paper reports a first proteomic analysis of mature biofilm of X. fastidiosa, opening new perspectives for understanding the biochemistry of mature biofilm growth in a plant pathogen.
Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy
Authors: Jiang Haiyan , Fang Junxu , Wu Bo , Yin Guibin , Sun Lin , Qu Jia , Barger Steven W , Wu Shengzhou
Published: September 2011

Background

Recent data indicate that inflammatory mechanisms contribute to diabetic retinopathy (DR). We have determined that serine racemase (SR) expression is increased by inflammatory stimuli including liposaccharide (LPS), amyloid β-peptide (A-beta), and secreted amyloid precursor protein (sAPP); expression is decreased by the anti-inflammatory drug, dexamethasone. We tested possibility that SR and its product, D-serine, were altered in a rat model of DR.

Methods

Intraperitoneal injection of streptozotocin (STZ; 70 mg/kg body weight) to Sprague-Dawley rats produced type-I diabetic mellitus (fasting blood sugar higher than 300 mg/dL). At 3 and 5 months after STZ or saline injection, retinas from some rats were subjected to cryosectioning for immunofluorescent analysis of SR and TUNEL assay of apoptosis. Retinal homogenates were used to detect SR levels and Jun N-terminal kinase (JNK) activation by immunoblotting. Aqueous humor and retina were also collected to assay for neurotransmitters, including glutamate and D-serine, by reverse-phase HPLC.

Results

Compared to saline-injected rats, STZ-injected (diabetic) rats showed elevation of SR protein levels in retinal homogenates, attributed to the inner nuclear layer (INL) by immunofluorescence. Aqueous humor fluid from STZ-injected rats contained significantly higher levels of glutamate and D-serine compared to controls; by contrast, D-serine levels in retinas did not differ. Levels of activated JNK were elevated in diabetic retinas compared to controls.

Conclusions

Increased expression of SR in retina and higher levels of glutamate and D-serine in aqueous humor of STZ-treated rats may result from activation of the JNK pathway in diabetic sequelae. Our data suggest that the inflammatory conditions that prevail during DR result in elevation of D-serine, a neurotransmitter contributing to glutamate toxicity, potentially exacerbating the death of retinal ganglion cells in this condition.
HtrA chaperone activity contributes to host cell binding in Campylobacter jejuni
Authors: Bæk Kristoffer T , Vegge Christina S , Brøndsted Lone
Published: September 2011

Background

Acute gastroenteritis caused by the food-borne pathogen Campylobacter jejuni is associated with attachment of bacteria to the intestinal epithelium and subsequent invasion of epithelial cells. In C. jejuni, the periplasmic protein HtrA is required for efficient binding to epithelial cells. HtrA has both protease and chaperone activity, and is important for virulence of several bacterial pathogens.

Results

The aim of this study was to determine the role of the dual activities of HtrA in host cell interaction of C. jejuni by comparing an htrA mutant lacking protease activity, but retaining chaperone activity, with a ΔhtrA mutant and the wild type strain. Binding of C. jejuni to both epithelial cells and macrophages was facilitated mainly by HtrA chaperone activity that may be involved in folding of outer membrane adhesins. In contrast, HtrA protease activity played only a minor role in interaction with host cells.

Conclusion

We show that HtrA protease and chaperone activities contribute differently to C. jejuni's interaction with mammalian host cells, with the chaperone activity playing the major role in host cell binding.
A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis
Authors: Wang Dong-Yu , Done Susan J , McCready David R , Boerner Scott , Kulkarni Supriya , Leong Wey Liang
Published: September 2011

Introduction

When making treatment decisions, oncologists often stratify breast cancer (BC) into a low-risk group (low-grade estrogen receptor-positive (ER+)), an intermediate-risk group (high-grade ER+) and a high-risk group that includes Her2+ and triple-negative (TN) tumors (ER-/PR-/Her2-). None of the currently available gene signatures correlates to this clinical classification. In this study, we aimed to develop a test that is practical for oncologists and offers both molecular characterization of BC and improved prediction of prognosis and treatment response.

Methods

We investigated the molecular basis of such clinical practice by grouping Her2+ and TN BC together during clustering analyses of the genome-wide gene expression profiles of our training cohort, mostly derived from fine-needle aspiration biopsies (FNABs) of 149 consecutive evaluable BC. The analyses consistently divided these tumors into a three-cluster pattern, similarly to clinical risk stratification groups, that was reproducible in published microarray databases (n = 2,487) annotated with clinical outcomes. The clinicopathological parameters of each of these three molecular groups were also similar to clinical classification.

Results

The low-risk group had good outcomes and benefited from endocrine therapy. Both the intermediate- and high-risk groups had poor outcomes, and their BC was resistant to endocrine therapy. The latter group demonstrated the highest rate of complete pathological response to neoadjuvant chemotherapy; the highest activities in Myc, E2F1, Ras, β-catenin and IFN-γ pathways; and poor prognosis predicted by 14 independent prognostic signatures. On the basis of multivariate analysis, we found that this new gene signature, termed the "ClinicoMolecular Triad Classification" (CMTC), predicted recurrence and treatment response better than all pathological parameters and other prognostic signatures.

Conclusions

CMTC correlates well with current clinical classifications of BC and has the potential to be easily integrated into routine clinical practice. Using FNABs, CMTC can be determined at the time of diagnostic needle biopsies for tumors of all sizes. On the basis of using public databases as the validation cohort in our analyses, CMTC appeared to enable accurate treatment guidance, could be made available in preoperative settings and was applicable to all BC types independently of tumor size and receptor and nodal status. The unique oncogenic signaling pathway pattern of each CMTC group may provide guidance in the development of new treatment strategies. Further validation of CMTC requires prospective, randomized, controlled trials.
Libya: Dream versus Reality
Authors: Lewis William
Published: September 2011

Libya emerged under United Nations auspices as a stillborn, failed state dependent on Western subventions. The civil war in which it is embroiled in 2011 confirms its manifold failures, now attributable to Colonel Muammar Qadaffi. The West is ill-positioned to reengage in nation-building, given its past failures.
Role of Template Activating Factor-I as a chaperone in linker histone dynamics
Authors: Kato Kohsuke , Okuwaki Mitsuru , Nagata Kyosuke
Published: September 2011

Linker histone H1 is a fundamental chromosomal protein involved in the maintenance of higher-ordered chromatin organization. The exchange dynamics of histone H1 correlates well with chromatin plasticity. A variety of core histone chaperones involved in core histone dynamics has been identified, but the identity of the linker histone chaperone in the somatic cell nucleus has been a long-standing unanswered question. Here we show that Template Activating Factor-I (TAF-I, also known as protein SET) is involved in histone H1 dynamics as a linker histone chaperone. Among previously identified core histone chaperones and linker histone chaperone candidates, only TAF-I was found to be associated specifically with histone H1 in mammalian somatic cell nuclei. TAF-I showed linker histone chaperone activity in vitro. Fluorescence recovery after photobleaching analyses revealed that TAF-I is involved in the regulation of histone H1 dynamics in the nucleus. Therefore, we propose that TAF-I is a key molecule that regulates linker histone-mediated chromatin assembly and disassembly.
European Specialist Porphyria Laboratories: Diagnostic Strategies, Analytical Quality, Clinical Interpretation, and Reporting As Assessed by an External Quality Assurance Program
Authors: Aarsand Aasne K , Villanger Jørild H , Støle Egil , Deybach Jean-Charles , Marsden Joanne , To-Figueras Jordi , Badminton Mike , Elder George H , Sandberg Sverre
Published: September 2011

BACKGROUND

The porphyrias are a group of rare metabolic disorders whose diagnosis depends on identification of specific patterns of porphyrin precursor and porphyrin accumulation in urine, blood, and feces. Diagnostic tests for porphyria are performed by specialized laboratories in many countries. Data regarding the analytical and diagnostic performance of these laboratories are scarce.

METHODS

We distributed 5 sets of multispecimen samples from different porphyria patients accompanied by clinical case histories to 18–21 European specialist porphyria laboratories/centers as part of a European Porphyria Network organized external analytical and postanalytical quality assessment (EQA) program. The laboratories stated which analyses they would normally have performed given the case histories and reported results of all porphyria-related analyses available, interpretative comments, and diagnoses.

RESULTS

Reported diagnostic strategies initially showed considerable diversity, but the number of laboratories applying adequate diagnostic strategies increased during the study period. We found an average interlaboratory CV of 50% (range 12%–152%) for analytes in absolute concentrations. Result normalization by forming ratios to the upper reference limits did not reduce this variation. Sixty-five percent of reported results were within biological variation–based analytical quality specifications. Clinical interpretation of the obtained analytical results was accurate, and most laboratories established the correct diagnosis in all distributions.

CONCLUSIONS

Based on a case-based EQA scheme, variations were apparent in analytical and diagnostic performance between European specialist porphyria laboratories. Our findings reinforce the use of EQA schemes as an essential tool to assess both analytical and diagnostic processes and thereby to improve patient care in rare diseases.
Synthesis and chemistry of pyrazolines derived from diphenyldiazomethane
Authors: Louhichi Nesrine , Haouas Amel , Ben Hamadi Naoufel , Msaddek Moncef
Published: September 2011

The reaction of diphenyldiazomethane with N-substituted maleimides produces Δ1-pyrazolines. The photolysis of Δ1-pyrazolines leads to cyclopropanes.
Magnetic Particles Effects on Shear Performance in MR Fluid
Authors: Liu X. H. , Yao X. Y. , Li F. , Fu Z. M.
Published: September 2011

Magneto-rheological (MR) fluids, as smart fluids, are suspensions of micron-sized magnetic particles, such as iron particles or cobalt, in a silicone or hydraulic oil carrier fluid, which can change from the liquid state to a semi-solid state in several milliseconds in the external magnetic field. In this paper, the produced chain, which will give rise to the MR effect, is investigated by the magnetic force between two particles, the relationship between the produced shear torque, and magnetic particles are proposed. A set of testing systems, including the plate-on-plate MR fluid shearing test rig, is built to study the percentage of magnetic particles in MR fluid. The magnetic field in the gap, before and after the gap is added with MR fluid, is investigated by measuring and calculating. The results validate the effect of the content of magnetic particles in MR fluid on the shear performance.
Influence of Recovery Processes on Properties of Binders and Aggregates Recovered from Recycled Asphalt Pavement
Authors: Hossain Zahid , Solanki Pranshoo , Zaman Musharraf , Lewis Sharon , Hobson Kenneth
Published: September 2011

Usage of recycled asphalt pavement (RAP) in the construction of new pavements has increased in recent years due to the movement to conserve energy and raw materials, and reuse waste materials. To assess the effectiveness of RAP materials in new asphalt mixes, it is important to evaluate the properties of the recovered binders and aggregates. The widely used “Abson” method is employed in this study to recover asphalt binder from RAP. Also, the frequently used “NCAT ignition” method is used to extract aggregates. A laboratory study comprising two field RAP materials, two simulated RAP materials, and corresponding virgin materials was undertaken to assess possible influences of the aforementioned recovery processes. The performance grade (PG) of the recovered binders, and gradation, durability (LAAbrasion and Micro-Deval), specific gravity, sand equivalent, and insoluble residue of the extracted aggregates were evaluated as per the AASHTO and Oklahoma Dept. of Transportation (ODOT) standards. The test results showed that the Abson method notably influenced the critical PG temperatures of the recovered binder. It was also observed that some mechanical properties (durability and sand equivalent) of RAP aggregates were inconsistent with their virgin counterparts. Furthermore, field RAP aggregates showed significant variations in LA Abrasion loss and insoluble residue test results. The findings of this study are expected to be helpful in the evaluation of RAP for reuse in asphalt paving.
Fatty liver index in polycystic ovary syndrome
Authors: Lerchbaum Elisabeth , Gruber Hans-Jürgen , Schwetz Verena , Giuliani Albrecht , Möller Reinhard , Pieber Thomas R , Obermayer-Pietsch Barbara
Published: September 2011

Introduction

Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances and might be affected by hepatic steatosis. The fatty liver index (FLI) was developed as a simple and accurate predictor of hepatic steatosis. We aimed to analyze the association of FLI with endocrine and metabolic parameters in a cohort of PCOS and control women.

Methods

FLI was calculated using body mass index (BMI), waist circumference, triglycerides, and gamma-glutamyl transferase in 611 PCOS and 139 BMI-matched control women within the same age range. Elevated FLI was defined as >60. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed.

Results

PCOS women had significantly higher FLI levels than control women in age-adjusted analyses (11.4 (4.3–48.8) and 8.8 (3.9–35.0), respectively,P=0.001), whereas fibrosis indices were similar (aspartate amino transferase-to-platelet ratio index) or lower (FIB-4) respectively. In binary logistic regression analysis adjusted for age, odds ratio (OR) for elevated FLI was 2.52 (1.31–4.85),P=0.006, for PCOS women when compared with controls. PCOS women with high FLI levels had an adverse anthropometric, metabolic, and endocrine risk profile. The prevalence of elevated FLI was 88.7% in PCOS women with metabolic syndrome (MS) and 11.3% in PCOS women without MS (P<0.001). In control women, elevated FLI was present in 66.7% of women with MS and 30.8% of women without MS.

Conclusion

High FLI levels are a common finding in obese PCOS women and are closely linked to MS. FLI calculation might be a useful tool for identifying PCOS patients at high risk for metabolic and hepatic disturbances.
Evidence of oncogene-induced senescence in thyroid carcinogenesis
Authors: Vizioli Maria Grazia , Possik Patricia A , Tarantino Eva , Meissl Katrin , Borrello Maria Grazia , Miranda Claudia , Anania Maria Chiara , Pagliardini Sonia , Seregni Ettore , Pierotti Marco A , Pilotti Silvana , Peeper Daniel S , Greco Angela
Published: September 2011

Oncogene-induced senescence (OIS) is a growth arrest triggered by the enforced expression of cancer-promoting genes and acts as a barrier against malignant transformationin vivo. In this study, by a combination ofin vitroandin vivoapproaches, we investigate the role of OIS in tumours originating from the thyroid epithelium. We found that expression of different thyroid tumour-associated oncogenes in primary human thyrocytes triggers senescence, as demonstrated by the presence of OIS hallmarks: changes in cell morphology, accumulation of SA-β-Gal and senescence-associated heterochromatic foci, and upregulation of transcription of the cyclin-dependent kinase inhibitors p16INK4aand p21CIP1. Furthermore, immunohistochemical analysis of a panel of thyroid tumours characterised by different aggressiveness showed that the expression of OIS markers such as p16INK4a, p21CIP1and IGFBP7 is upregulated at early stages, and lost during thyroid tumour progression. Taken together, our results suggest a role of OIS in thyroid carcinogenesis.
Capacitance-Voltage Measurement of an Ambipolar Pentacene Field Effect Transistor in Operation by Using Displacement Current Measurement
Authors: Tanaka Yuya , Noguchi Yutaka , Ishii Hisao
Published: September 2011

The channel formation process of a pentacene ambipolar field-effect transistor was studied by displacement current measurement (DCM). We proposed a modified measurement circuit of DCM in order to investigate the channel formation at the organic/insulator interface under transistor operation. We observed an additional terrace structure between the depletion and accumulation states when the drain voltage is applied. The capacitance at the terrace structure corresponds well with that in pinch-off condition. DCM enables us to understand the operation mechanism of the organic FET in more detail.
Millisecond-annealing using flash lamps for improved performance of AZO layers
Authors: Gebel T. , Neubert M. , Endler R. , Weber J. , Vinnichenko M. , Kolitsch A. , Skorupa W. , Liepack H.
Published: September 2011

ZnO:Al films with a thickness of about 880nm were deposited by magnetron sputtering. The glass substrate was not heated neither before during nor after the deposition. Subsequently the deposited layers were treated by flash lamp annealing (FLA) at 1.3 ms. Using this method, the resistivity of the ZnO:Al films was decreased by a factor of two, down to 1.0 x 10-3 Ωcm. These results are in good agreement with results reported from rapid thermal processing or furnace annealing treatments. Despite the very short annealing time of only 1.3 ms not only the resistivity but also the transmittance in the UV and the blue range were considerably improved.
Influence of Deformation Rate on Overload Performance and Microstructure of Spot Welded Metastable Austenitic Stainless Steel
Authors: Liu Wei , Sun Chuanjing , Han Junlei , Li Qiang , Song Zhikun
Published: September 2011

Tensile-shear overload tests of spot welded cold-rolled 301LN plates deforming with slow and fast rates were carried out. The deformation behaviors of spot welds can be divided into two stages. Loading force with fast deformation rate increased more along with displacement in the first stage, while the force with slow rate increased more in the second stage. 21and 32(v.%) α´-martensite were introduced by failure deformation with fast and slow rates respectively. The hardness under the fracture surfaces was higher than HV400, which was more than two times of their original. The ultimate strengths and fracture energy absorptions of spot welds deforming with slow rate were higher than that with fast rate, especially for spot-welded thicker plates.
Introduction
Authors: Driscoll Christopher
Published: September 2011

At the 2010 annual meeting of the American Academy of Religion held in Atlanta, GA, a group of young scholars organized a wildcard session titled “What’s This ‘Religious’ in Hip Hop Culture?” The central questions under investigation by the panel were 1) what about hip hop culture is religious? and 2) how are issues of theory and method within African American religious studies challenged and/or rethought because of the recent turn to hip hop as both subject of study and cultural hermeneutic. Though some panelists challenged this “religious” in hip hop, all agreed that hip hop is of theoretical and methodological import for African American religious studies and religious studies in general. This collection of essays brings together in print many findings from that session and points out the implications of hip hop's influence on religious scholars' theoretical and methodological concerns.
Bishop Lamont and Hermeneutics of Play
Authors: Rolsky L.
Published: September 2011

This paper investigates the subject of hip-hop within the study of religion and the study of American religion and culture. In particular, the paper focuses on the corpus of California hip-hop artist Bishop Lamont in developing a "hermeneutics of play" through a combinative "lived religion" approach as a way of reading and reflecting on the larger religious significance of hip-hop in late 20th century America. As both a reading practice and a subject of study for both historians and religious studies scholars, hip-hop comes into view in this paper as an essential component in narrating an American religious history of the last three decades. Hip-hop and its study also reveals its own understandings of religion, America, and American religion as articulated through post-industrial and a variety of religious vocabularies that have been largely ignored by scholars of religion. In essence, this paper argues that by exploring the rhetorical, religious, and existential complexity found within hip-hop cultures, a more complex post-1965 American religious landscape emerges for both the historian and theorist of religion.
Treatment of biologically treated leachate by oxidation and coagulation
Authors: Zhang H. Y. , Zhao Y. C. , Qi J. Y.
Published: September 2011

This work aims to investigate removal efficiency of oxidation and coagulation/flocculation processes, to provide an effective method for the treatment of biologically pre-treated leachate. Leachate containing 985 mg L−1 COD was treated by using three treatment schemes, i.e. oxidation, coagulation/flocculation and the combined process of coagulation/flocculation followed by oxidation. The application of single oxidation resulted in the effective removal of COD and color up to 80.4 and 83.2%, respectively. However, residual COD values lower than 200 mg L−1 could only be achieved under intensive experimental conditions (high dosage of Ca(ClO)2 and prolonged oxidation time). Coagulation/flocculation yielded residual COD values higher than 200 mg L−1 even at the optimum coagulation conditions. The combined treatment by coagulation/flocculation followed by oxidation yielded final COD lower than 100 mg L−1 at the following conditions: pre-coagulation with 250 mg L−1 PFS (poly-ferric sulfate) and over 30-min post-oxidation, or pre-coagulation with 300 mg L−1 PFS and over 20-min post-oxidation. Hence, pre-coagulation with PFS followed by oxidation with Ca(ClO)2 was recommended for advanced treatment of biologically treated leachate.