bluuebunny/crossref_metadata_2025 huggingface dataset:
OPTIMAL CONSUMPTION AND INVESTMENT IN INCOMPLETE MARKETS WITH GENERAL CONSTRAINTS
Authors: CHERIDITO PATRICK , HU YING
Published: August 2011

We study an optimal consumption and investment problem in a possibly incomplete market with general, not necessarily convex, stochastic constraints. We provide explicit solutions for investors with exponential, logarithmic as well as power utility and show that they are unique if the constraints are convex. Our approach is based on martingale methods that rely on results on the existence and uniqueness of solutions to BSDEs with drivers of quadratic growth.
Recent methods for software effort estimation by analogy
Authors: Gupta Syona , Sikka Geeta , Verma Harsh
Published: August 2011

Fairly accurate cost and effort predictions of software projects have always been a challenging goal for both, industry as well as academia. Most approaches for effort estimation are either algorithmic or analogy based. The most well-known algorithmic models are COCOMO 81 [1] and Function Points [2]. Estimation by analogy, on the other hand, is essentially a form of case based reasoning. Fuzzy logic, Grey System Theory, Machine Learning techniques such as Genetic Algorithms, Support vector Machines, etc. have been used to optimize the prediction by analogy method. We study these analogy based approaches to software effort estimation and compare some of these techniques on the basis of widely used measures of accuracy.
ICT and social entrepreneurship
Authors: Fraizer Lani , Madjidi Farzin
Published: August 2011

Social entrepreneurs are impassioned leaders who strive to find systemic solutions for matters affecting human welfare such as poverty, unemployment, and poor access to quality healthcare. Their social-value creating work is defined as social entrepreneurship. The purpose of this paper is to lay the groundwork for a larger discussion on (1) the role of ICT as vehicles for change and reform in the social sector, with emphasis on social entrepreneurship; and (2), the opportunities that social entrepreneurship paves for the future ICT workforce. This paper, through a qualitative methodology, reports on the findings from semi-structured interviews of Ashoka Fellows across the United States. Findings on five critical insights on the role of technology in implementation of social solutions are reported, and their implications for the development of next generations entering the ICT professions are discussed.
Circadian intervention of obesity development via resting-stage feeding manipulation or oxytocin treatment
Authors: Zhang Guo , Cai Dongsheng
Published: August 2011

The obesity pandemic can be viewed as a result of an imbalanced reaction to changing environmental factors. Recent research has linked circadian arrhythmicity to obesity and related diseases; however, the underlying mechanisms are still unclear. In this study, we found that high-fat diet (HFD) feeding strikingly promoted daytime rather than nighttime caloric intake in mice, leading to feeding circadian arrhythmicity. Using scheduled feeding with a defined amount of daily HFD intake, we found that an increase in the ratio of daytime to nighttime feeding promoted weight gain, whereas a decrease of this ratio rebalanced energy expenditure to counteract obesity. In identifying the underlying mechanism, we found that hypothalamic release of anorexigenic neuropeptide oxytocin displayed a diurnal rhythm of daytime rise and nighttime decline, which negatively correlated with the diurnal feeding activities of normal chow-fed mice. In contrast, chronic HFD feeding abrogated oxytocin diurnal rhythmicity, primarily by suppressing daytime oxytocin rise. Using pharmacological experiments with hypothalamic injection of oxytocin or oxytocin antagonist, we showed that daytime manipulation of oxytocin can change feeding circadian patterns to reprogram energy expenditure, leading to attenuation or induction of obesity independently of 24-h caloric intake. Also importantly, we found that peripheral injection of oxytocin activated hypothalamic oxytocin neurons to release oxytocin, and exerted metabolic effects similar to central oxytocin injection, thus offering a practical clinical avenue to use oxytocin in obesity control. In conclusion, resting-stage oxytocin release and feeding activity represent a critical circadian mechanism and therapeutic target for obesity.
Chronic reduction of insulin receptors in the ventromedial hypothalamus produces glucose intolerance and islet dysfunction in the absence of weight gain
Authors: Paranjape Sachin A. , Chan Owen , Zhu Wanling , Horblitt Adam M. , Grillo Claudia A. , Wilson Steven , Reagan Lawrence , Sherwin Robert S.
Published: August 2011

Insulin is believed to regulate glucose homeostasis mainly via direct effects on the liver, muscle, and adipose tissues. The contribution of insulin's central nervous system effects to disorders of glucose metabolism has received less attention. To evaluate whether postnatal reduction of insulin receptors (IRs) within the ventromedial hypothalamus (VMH), a brain region critical for glucose sensing, contributes to disorders of peripheral glucose metabolism, we microinjected a lentiviral vector expressing an antisense sequence to knockdown IRs or a control lentiviral vector into the VMH of nonobese nondiabetic rats. After 3–4 mo, we assessed 1) glucose tolerance, 2) hepatic insulin sensitivity, and 3) insulin and glucagon secretion, using the glucose clamp technique. Knockdown of IRs locally in the VMH caused glucose intolerance without altering body weight. Increments of plasma insulin during a euglycemic clamp study failed to suppress endogenous glucose production and produced a paradoxical rise in plasma glucagon in the VMH-IR knockdown rats. Unexpectedly, these animals also displayed a 40% reduction ( P < 0.05) in insulin secretion in response to an identical hyperglycemic stimulus (∼220 mg/dl). Our data demonstrate that chronic suppression of VMH-IR gene expression is sufficient to impair glucose metabolism as well as α-cell and β-cell function in nondiabetic, nonobese rats. These data suggest that insulin resistance within the VMH may be a significant contributor to the development of type 2 diabetes.
Solvability of a Class of Generalized Neumann Boundary Value Problems for Second‐Order Nonlinear Difference Equations
Authors: Xia Jianye , Liu Yuji
Published: August 2011

This paper is motivated by Rachnkovab and Tisdell (2006) and Anderson et al. (2007). New sufficient conditions for the existence of at least one solution of the generalized Neumann boundary value problems for second order nonlinear difference equations ∇Δx(k) = f(k, x(k), x(k + 1)), k ∈ [1, n − 1], x(0) = ax(1), x(n) = bx(n − 1), are established.
Powder Characterization and Electrochemical Properties of LiNi0.5Mn1.5O4Cathode Materials Produced by Large Spray Pyrolysis Using Flame Combustion
Authors: Akao Shinsuke , Yamada Motofumi , Kodera Takayuki , Myoujin Kenichi , Ogihara Takashi
Published: August 2011

LiNi0.5Mn1.5O4cathode materials were produced by spray pyrolysis apparatus using the flame combustion. SEM revealed that as-prepared powders had spherical morphology with porous microstructure which had an average diameter of about 2 μm with broad size distribution. After the calcination, LiNi0.5Mn1.5O4powders with polygonal morphology and narrow particle size distribution were obtained. XRD showed that LiNi0.5Mn1.5O4was well crystallized after the calcination at 900°C. Rechargeable measurement of LiNi0.5Mn1.5O4cathode showed that the long plateau was observed at 4.7 V in discharge curve of LiNi0.5Mn1.5O4cathode and its discharge capacity was 145 mAh/g at 1 C. The capacity retention of LiNi0.5Mn1.5O4cathode were 95% at 1 C after 100 cycles. The discharge capacity and capacity retention of LiNi0.5Mn1.5O4cathode were 125 mAh/g and 88% at 20 C. LiNi0.5Mn1.5O4cathode exhibited also stable cycle performance at 50C.
Multiple Transverse Colonic Perforations Associated with Slow-Release Nonsteroidal Anti-Inflammatory Drugs and Corticosteroids: A Case Report
Authors: Shioya Nobuki , Shibata Shigehiro , Kojika Masahiro , Endo Shigeatsu
Published: August 2011

The patient was a 36-year-old woman with sarcoidosis and Sjogren's syndrome, and had been prescribed slow-release diclofenac sodium and prednisolone for the treatment of pain associated with uveitis and erythema nodosum. She was admitted to our emergency center with abdominal pain and distention. A chest X-ray showed free air under the diaphragm on both sides, and an emergency laparotomy was performed for suspected panperitonitis associated with intestinal perforation. Laparotomy revealed several perforations on the antimesenteric aspect of the transverse colon. The resected specimen showed 11 punched-out ulcerations, many of which were up to 10 mm in diameter. The microscopic findings were non-specific, with leukocytic infiltration around the perforations. She showed good postoperative recovery, as evaluated on day 42. The present case highlights the need for exercising caution while prescribing slow-release nonsteroidal anti-inflammatory drugs with corticosteroids to patients with autoimmune diseases, as such treatment may exacerbate intestinal epithelial abnormalities.
Effects of Glial Cell Line-derived Neurotrophic Factor on Dental Pulp Cells
Authors: Gale Z. , Cooper P.R. , Scheven B.A.A.
Published: August 2011

This study investigated the effects of glial cell line-derived neurotrophic factor (GDNF) on dental pulp cells (DPCs). Cultures of DPCs expressed GDNF as well as its receptors, GFRα1 and RET. Addition of recombinant GDNF to cultures in serum-containing medium did not significantly affect DPC growth; however, GDNF dose-dependently increased viable cell number under serum-free culture conditions. Live/dead, lactate dehydrogenase (LDH), and caspases-3/-7 assays demonstrated that cell death occurred under serum-free conditions, and that GDNF significantly reduced the number of dead cells by inhibiting apoptotic cell death. GDNF also stimulated cell proliferation in serum-free conditions, as assessed by the BrdU incorporation assay. The effect of GDNF was abolished in the presence of inhibitors to GFRα1 and RET suggesting receptor-mediated events. This study also demonstrated that GDNF counteracted TNFα-induced DPC cytotoxicity, suggesting that GDNF may be cytoprotective under disease conditions. In conclusion, our findings indicate that GDNF promotes cell survival and proliferation of DPCs and suggest that GDNF may play a multifunctional role in the regulation of dental pulp homeostasis.
Pathologic Lesions Caused by Coinfection of Mycoplasma gallisepticum and H3N8 Low Pathogenic Avian Influenza Virus in Chickens
Authors: Stipkovits L. , Glavits R. , Palfi V. , Beres A. , Egyed L. , Denes B. , Somogyi M. , Szathmary S.
Published: August 2011

Chickens were infected under experimental conditions with Mycoplasma gallisepticum and low pathogenic avian influenza (LPAI) strain A/mallard/Hungary/19616/07 (H3N8). Two groups of chickens were aerosol challenged with M. gallisepticum strain 1226. Seven days later, one of these groups and one mycoplasma-free group was challenged with LPAI H3N8 virus; one group without challenge remained as negative control. Eight days later, the birds were euthanized and examined for gross pathologic and histologic lesions. The body weight was measured, and the presence of antimycoplasma and antiviral antibodies was tested before the mycoplasma challenge, before the virus challenge, and at the end of the study to confirm both infections. Chickens in the mycoplasma-infected group developed antibodies against M. gallisepticum but not against the influenza virus. Chickens of the group infected with the influenza virus became serologically positive only against the virus, while the birds in the coinfected group developed antibodies against both agents. The LPAI H3N8 virus strain did not cause decrease in body weight and clinical signs, and macroscopic pathological lesions were not present in the chickens. The M. gallisepticum infection caused respiratory signs, airsacculitis, and peritonitis characteristic of mycoplasma infection. However, the clinical signs and pathologic lesions and the reduction in weight gain were much more significant in the group challenged with both M. gallisepticum and LPAI H3N8 virus than in the group challenged with M. gallisepticum alone.
Cocultures of Adult and Juvenile Chondrocytes Compared With Adult and Juvenile Chondral Fragments
Authors: Bonasia Davide Edoardo , Martin James A. , Marmotti Antongiulio , Amendola Richard L. , Buckwalter Joseph A. , Rossi Roberto , Blonna Davide , Adkisson Huston Davis , Amendola Annunziato
Published: August 2011

Background: The use of allogenic juvenile chondrocytes or autologous chondral fragments has shown promising laboratory results for the repair of chondral lesions.

Hypothesis: Juvenile chondrocytes would not affect matrix production when mixed with adult chondrocytes or cartilage fragments.

Study Design: Controlled laboratory study.

Methods: Cartilage sources consisted of 3 adult and 3 juvenile (human) donors. In part 1, per each donor, juvenile chondrocytes were mixed with adult chondrocytes in 5 different proportions: 100%, 50%, 25%, 12.5%, and 0%. Three-dimensional cultures in low-melt agarose were performed. At 6 weeks, biochemical and histologic analyses were performed. In part 2, isolated adult, isolated juvenile, and mixed 3-dimensional cultures (1:1) were performed with chondral fragments (<1 mm), both with low-melt agarose and a hyaluronic acid scaffold. At 2 and 6 weeks, cultures were evaluated with biochemical and histologic analyses.

Results: Part 1: Biochemical and histologic analyses showed that isolated juvenile cultures performed significantly better than mixed and isolated adult cultures. No significant differences were noted between mixed cultures (1:1) and isolated adult cultures. Part 2: Biochemical and histologic results at 6 weeks showed that mixed cartilage fragment cultures performed better than isolated adult cultures in terms of proteoglycans/DNA ratio ( P = .014), percentage of safranin O–positive cells ( P = .012), Bern score ( P = .001), and collagen type II. No statistically significant difference was noted between juvenile and mixed cultures.

Conclusion: Extracellular matrix production of juvenile chondrocytes is inhibited by adult chondrocytes. The addition of juvenile cartilage fragments to adult fragments improves matrix production, with a positive interaction between the 2 sources.

Clinical Relevance: Even if the underlying mechanisms are still unknown, this study describes the behavior of juvenile/adult cocultures using both chondrocytes and cartilage fragments, with potential for new research and clinical applications.
Finding Levels of Abstraction in Speech Production
Authors: Buchwald Adam , Miozzo Michele
Published: August 2011

A widely held view in linguistics and psycholinguistics is that there are distinct levels of processing for context-independent and context-specific representations of sound structure. Recently, this view has been disputed, in part because of the absence of clear evidence that there are abstract mental representations of discrete sound-structure units. Here, we present novel evidence that separate context-independent and context-specific representations of sound structure are supported by distinct brain mechanisms that can be selectively impaired in individuals with acquired brain deficits. Acoustic data from /s/-deletion errors of 2 aphasic speakers suggest both a phonological level of processing at which sound representations (e.g., /p/) do not specify context-specific detail (e.g., aspirated or unaspirated) and a distinct level at which context-specific information is represented. These data help constrain accounts of sound-structure processing in word production and crucially support the claim that context-independent linguistic information affects language production.
Social support and health in patients with systemic lupus erythematosus: A literature review
Authors: Mazzoni D , Cicognani E
Published: August 2011

In the last decades, with the improvement of life expectancies for systemic lupus erythematosus (SLE) patients, the relationship between social support and health in this population has received a considerable amount of attention in behavioural medicine and health psychology. This paper is the first to review research studies which specifically investigated perceived social support in relation to SLE patients’ health outcomes (quality of life, disease activity and damage). Starting with a descriptive approach to social support perceived by patients with SLE, the research evidence on the impact of social support on health is presented. These studies demonstrate that the consideration of social support is critical in predicting disease activity, damage and quality of life (both physical and psychological components) although the precise ways in which social support contributes to health are not yet completely understood. Discussing the results, the authors offer some suggestions which could guide further research in this field. Finally, clinical and non-clinical implications of the findings are discussed.
Terminalia arjuna Enhances Baroreflex Sensitivity and Myocardial Function in Isoproterenol-Induced Chronic Heart Failure Rats
Authors: Parveen Adila , Babbar Rashmi , Agarwal Sarita , Kotwani Anita , Fahim Mohammad
Published: August 2011

Chronic heart failure (CHF) is characterized by left ventricular (LV) dysfunction along with impaired autonomic control functions. Herbal drugs are increasingly being used in the treatment of cardiovascular disorders. The present study was designed to examine the protective effect of Terminalia arjuna ( T arjuna) bark extract on LV and baroreflex function in CHF and to elucidate the possible mechanistic clues in its cardioprotective action. The baroreflex was evaluated by measuring the changes in heart rate (HR) with changes in arterial blood pressure induced by bolus injections of phenylephrine (vasoconstrictor) and sodium nitroprusside (vasodilator). T arjuna bark extract and fluvastatin were tested/administered therapeutically and prophylactically in isoproterenol-induced rat model of CHF. Fifteen days after isoproterenol administration, rats exhibited cardiac dysfunction, hypertrophy, and LV remodeling along with reduced baroreflex sensitivity. Prophylactic and therapeutic treatment with T arjuna improved cardiac functions and baroreflex sensitivity. It also attenuated hypertrophy and fibrosis of the LV. Fluvastatin treatment exerted a similar protective effect against myocardial remodeling and heart failure. Further, T arjuna and fluvastatin significantly reduced oxidative stress and inflammatory cytokine level in CHF rats. In conclusion, T arjuna exerts beneficial effect on LV functions, myocardial remodeling, and autonomic control in CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.
Factor structure of Guy’s Neurological Disability Scale in a sample of Dutch patients with multiple sclerosis
Authors: Mokkink LB , Knol DL , Uitdehaag BMJ
Published: August 2011

Background: Guy’s Neurological Disability Scale (GNDS) is designed to assess disability (i.e. activity limitations) in patients with multiple sclerosis. It contains 12 functional domains, each indicating a level of disability. Four domain scores and a total score can be calculated.

Objective: The aim of this study was to evaluate the structural validity of the GNDS in a Dutch population who were definitely diagnosed as having multiple sclerosis.

Methods: Data of 974 patients were available. The structural validity of the GNDS was evaluated by confirmatory item factor analysis (CIFA). Two first-order models and two bifactor models were investigated.

Results: The best fitted model was a bifactor model with a general factor underlying all items, and 10 items loading on 3 group factors. Cronbach’s alpha on the general factor (0.78) and on the group factor spinal-plus (0.74) were satisfying. Cronbach’s alpha on the group factors mental (0.56) and bulbar (0.48) were low. Reliability based on CIFA was 0.85.

Conclusion: Results showed a clear factor structure of the GNDS. It justifies the use of the total score of the GNDS. In addition, three sub-scale scores could be used.
Welcome back? Frequent attenders to a pediatric primary care center
Authors: Klein Melissa , Vaughn Lisa M , Baker Raymond C , Taylor Trisha
Published: August 2011

This study examines frequent attenders of a pediatric primary care clinic at a large urban children’s hospital — who they are and their reasons for frequent attendance to the clinic. The literature suggests that some visits by frequent attenders may not be medically necessary, and these additional appointments may impair others’ access to medical care within the same system. The key to eliminating excessive primary care visits is to determine if it is a problem in the primary care practice (quantify the problem), explore the reasons for the visits (from the patients’ perspective), and then provide educational interventions that address the various causes for the extra visits and encourage the use of available resources, either ancillary services in the practice itself or resources and agencies available in the community (e.g. social service, legal aid).
Activation Encounters: Dilemmas of Accountability in Constructing Clients as ‘Knowledgeable’
Authors: Solberg Janne
Published: August 2011

In activation encounters such as vocational rehabilitation, clients are expected to take an active part in the process of making individual plans and counsellors regularly elicit suggested solutions from clients themselves. This article addresses how such questions nevertheless constitute expectations of clients to be ‘knowledgeable’, which might be problematic for clients without plans or ideas to report in these interactions. Using ethnomethodological conversation analysis, the author closely examines extracts of four interactions between clients and counsellors, focusing on counsellors’ ways of framing or ‘recipient designing’ clients as ‘knowledgeable’ as well as clients’ efforts to align to the counsellor’s suggested identities in their responses. In spite of the normative pressure of the professionals’ questions, this analysis finds that clients are not completely locked into ascribed identities, but rather are capable of managing issues of accountability in situ: although they have no plans or ideas to provide for their future, they manage to give relevant accounts for not fulfilling professionals’ expectations.
Enhanced detection through low-order stochastic modeling for guided-wave structural health monitoring
Authors: Flynn Eric B , Todd Michael D , Croxford Anthony J , Drinkwater Bruce W , Wilcox Paul D
Published: August 2011

Guided wave structural health monitoring offers the potential for efficient defect detection and localization on large plate-like structures. The aim of this article is to demonstrate that the performance of guided wave structural health monitoring on complex structures can be quantified, predicted, and enhanced through basic stochastic modeling and application of a likelihood-based detector. These are necessary steps in enabling such structural heath monitoring techniques to be used more robustly on safety-critical structures. Extensive ensembles of measurements were taken using a sparse array of transducers on an aluminum plate with geometric complexities (stiffeners), before and after introducing several sizes of damage at several locations, and in the presence of large noise processes. This enabled a full statistical treatment of performance evaluation using a modification of the standard receiver operating characteristic curve. The incorporation of stochastic modeling produced on average a 44% reduction in missed detections among the damage modes tested, with up to a 95% reduction in some cases.
Development of method for in-service crack detection based on distributed fiber optic sensors
Authors: Glisic Branko , Inaudi Daniele
Published: August 2011

Many bridges worldwide are approaching the end of their lifespan and it is necessary to assess their health condition in order to mitigate risks, prevent disasters, and plan maintenance activities in an optimized manner. Fracture critical bridges are of particular interest since they have only little or no load path redundancy. Structural health monitoring (SHM) has recently emerged as a branch of engineering, which aim is to improve the assessment of structural condition. Distributed optical fiber sensing technology has opened new possibilities in SHM. A distributed deformation sensor (sensing cable) is sensitive at each point of its length to strain changes and cracks. Such a sensor practically monitors a one-dimensional strain field and can be installed over all the length of the monitored structural members, thereby providing with integrity monitoring, i.e. direct detection and characterization (including recognition, localization, and quantification or rating) of local strain changes generated by damage. Integrity monitoring principles are developed and presented in this article. A large scale laboratory test and a real on-site application are briefly presented.
Studies on compression properties of polyester needle-punched nonwoven fabrics under dry and wet conditions
Authors: Debnath Sanjoy , Madhusoothanan M
Published: August 2011

In this article, the effects of fabric weight, fiber cross-sectional shapes (round, hollow, and trilobal), and presence of reinforcing material on the compression properties (initial thickness, percentage compression, percentage thickness loss, and percentage compression resilience) under dry and wet conditions of polyester needle-punched industrial nonwoven fabrics are presented. It has been found that initial thickness of the fabric decreases under wet condition for both with and without reinforcing materials. The percentage thickness loss values are higher under wet condition in case of samples with reinforcing material compared to samples without reinforcing material. In the presence of reinforcing material, the trilobal cross-sectional fabric samples show the highest increase in thickness loss under wet condition followed by round and hollow cross-sectional polyester needle-punched nonwoven samples. Compression resilience is the highest in case of round cross-sectional fabric without reinforcing material under wet condition than fabric with reinforcing material. The initial thickness increases, and percentage compression and thickness loss decrease with the increase in fabric weight irrespective of fiber cross-sectional shapes both in dry and wet conditions. The initial thickness, percentage compression, and percentage compression resilience of the fabric decrease but percentage thickness loss increases under wet condition compared to the dry condition irrespective of the fiber cross-sectional shape. Compared to other cross-sectioned polyester samples, the hollow cross-section samples undergo very less consolidation under wet condition due to their consolidated structure. There is a drastic drop in compression resilience and increase in thickness loss under wet condition than in dry state irrespective of the fiber cross-sectional shape.
How I treat hemophagocytic lymphohistiocytosis
Authors: Jordan Michael B. , Allen Carl E. , Weitzman Sheila , Filipovich Alexandra H. , McClain Kenneth L.
Published: August 2011

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation, occurring as either a familial disorder or a sporadic condition, in association with a variety of triggers. This immune dysregulatory disorder is prominently associated with cytopenias and a unique combination of clinical signs and symptoms of extreme inflammation. Prompt initiation of immunochemotherapy is essential for survival, but timely diagnosis may be challenging because of the rarity of HLH, its variable presentation, and the time required to perform diagnostic testing. Therapy is complicated by dynamic clinical course, high risk of treatment-related morbidity, and disease recurrence. Here, we review the clinical manifestations and patterns of HLH and describe our approach to the diagnosis and therapy for this elusive and potentially lethal condition.
RNase H-dependent PCR (rhPCR): improved specificity and single nucleotide polymorphism detection using blocked cleavable primers
Authors: Dobosy Joseph R , Rose Scott D , Beltz Kristin R , Rupp Susan M , Powers Kristy M , Behlke Mark A , Walder Joseph A
Published: August 2011

Background

The polymerase chain reaction (PCR) is commonly used to detect the presence of nucleic acid sequences both in research and diagnostic settings. While high specificity is often achieved, biological requirements sometimes necessitate that primers are placed in suboptimal locations which lead to problems with the formation of primer dimers and/or misamplification of homologous sequences.

Results

Pyrococcus abyssi (P.a.) RNase H2 was used to enable PCR to be performed using blocked primers containing a single ribonucleotide residue which are activated via cleavage by the enzyme (rhPCR). Cleavage occurs 5'-to the RNA base following primer hybridization to the target DNA. The requirement of the primer to first hybridize with the target sequence to gain activity eliminates the formation of primer-dimers and greatly reduces misamplification of closely related sequences. Mismatches near the scissile linkage decrease the efficiency of cleavage by RNase H2, further increasing the specificity of the assay. When applied to the detection of single nucleotide polymorphisms (SNPs), rhPCR was found to be far more sensitive than standard allele-specific PCR. In general, the best discrimination occurs when the mismatch is placed at the RNA:DNA base pair.

Conclusion

rhPCR eliminates the formation of primer dimers and markedly improves the specificity of PCR with respect to off-target amplification. These advantages of the assay should find utility in challenging qPCR applications such as genotyping, high level multiplex assays and rare allele detection.
Lobular neoplasia: frequency and association with other breast lesions
Authors: Gomes Douglas S , Balabram Débora , Porto Simone S , Gobbi Helenice
Published: August 2011

Background

Using new molecular biology techniques, recent studies have implicated a common evolutionary pathway between lobular neoplasia, lobular carcinomas, and columnar cell lesions. Our aims were to assess the frequency of lobular neoplasia in a series of breast biopsies that were performed and examined in the same institution and to analyze the association between subtypes of lobular neoplasia and benign and malignant breast lesions.

Methods

Cases were selected after reviewing archived pathological reports in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais (1999-2008). Cases of lobular neoplasia were reviewed and classified as atypical lobular hyperplasia, ductal involvement by cells of atypical lobular hyperplasia, lobular carcinoma in situ, and pleomorphic lobular carcinoma in situ. Coexistence of lobular neoplasia with other breast lesions, including columnar cell lesions, invasive ductal carcinoma and invasive lobular carcinoma, was evaluated. The association between lobular neoplasia and breast lesions was analyzed by Fisher's exact test and chi-square test for linear trend.

Results

We analyzed 5650 breast specimens, selecting 135 breast specimens (2.4%) that had a diagnosis of lobular neoplasia, corresponding to 106 patients. Hematoxylin and eosin-stained slides were available for 84 cases, 5 of which were excluded because they contained only "indeterminate" in situ lesions. Of the 79 remaining cases, columnar cell lesions were present in 78.5%, primarily with columnar cell changes without atypia (67.7%). Invasive carcinoma was present in 45.6% of cases of lobular neoplasia--a similar frequency (47.2%) as invasive ductal carcinoma and invasive lobular carcinoma. We noted a significant linear trend (p < 0.03) of a higher frequency of invasive carcinomas that were concomitant with lobular carcinoma in situ compared with atypical lobular hyperplasia. Invasive lobular carcinomas were associated with lobular carcinoma in situ in 33% of cases, compared with 2.8% of atypical lobular hyperplasia cases.

Conclusions

Our findings confirm a frequent association between lobular neoplasia and columnar cell lesions, the majority of which lacked atypia. We also observed a greater frequency of invasive carcinoma, more commonly invasive lobular carcinoma, associated with more developed forms of lobular neoplasia (lobular carcinoma in situ).

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1354154297558319.
The HIV/AIDS epidemic in sub‐Saharan Africa: thinking ahead on programmatic tasks and related operational research
Authors: Zachariah Rony , Van Damme Wim , Arendt Vic , Schmit Jean Claude , Harries Anthony D
Published: August 2011

Until now, we have all been desperately trying to run behind the HIV/AIDS epidemic and catch up with it, but despite all our efforts, the epidemic remains well ahead of us. In 2010, the antiretroviral treatment (ART) gap was about 60%, AIDS‐related deaths were almost two million a year, and on top of these figures, for every one person started on ART, there were two new HIV infections. What is needed to change this situation is to think ahead of the epidemic in terms of the programmatic tasks we will be faced with and try to act boldly in trying to implement those tasks. From a programmatic perspective, we: a) highlight what needs to fundamentally change in our thinking and overall approach to the epidemic; and b) outline a number of key task areas for implementation and related operational research.
Waist circumference and insulin resistance: a community based cross sectional study on reproductive aged Iranian women
Authors: Zadeh-Vakili Azita , Tehrani Fahimeh Ramezani , Hosseinpanah Farhad
Published: August 2011

Background

Although the positive relationship between insulin resistance (IR) and central obesity is well known, the direct relationship between waist circumference and IR is not clear yet and there is no consensus regarding the cut off value for waist circumference as a surrogate index for central obesity. The present study was aimed to determine the optimal cut-off value of waist circumference (WC) for predicting IR in reproductive aged Iranian women.

Methods

Using the stratified, multistage probability cluster sampling method 1036 women were randomly selected from among reproductive aged women of different geographic regions of Iran. Following implementation of exclusion criteria, complete data for 907 women remained for analysis. Insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR) and its cut off value was defined as the 95th percentile of HOMA-IR value for 129 subjects, without any metabolic abnormality. The optimal cut-off of WC in relation to HOMA-IR was calculated based on the receiver operating characteristics (ROC) curve analysis using the Youden index and the area under curve (AUC).

Results

The mean age of the total sample of 907 subjects was 34.4 ± 7.6 years (range, 18 - 45 years). After adjustment for age the odds ratios (OR) of elevated HOMA-IR were progressively higher with increasing levels of waist circumference; the age adjusted OR of IR for women with WC > 95 cm in comparison to those subjects with WC < 80 cm, was 9.5 (95% CI 5.6-16.1). The optimal cutoff value for WC predicting IR was 88.5 cm; with a sensitivity and specificity of 71% and 64%, respectively.

Conclusions

Waist circumference is directly related to insulin resistance and the optimal cut-off value for waist circumference reflecting insulin resistance is considered to be 88.5 cm for reproductive aged Iranian women.
Resolution on multiples: Interpreters' perceptions, decision making, and multiple attenuation
Authors: Hunt Lee , Reynolds Scott , Hadley Mark , Hadley Scott , Zheng Ye , Perz Mike
Published: August 2011

We investigated our ability to remove a specific short-period multiple from the Nisku and Blueridge formations in West Central Alberta, Canada. This problem is commercial in nature, and has persisted because it was believed that the multiple had too little moveout to be removed, rendering interpretation of the thin Blueridge zone impossible. Associated with this issue was the belief that the modern high-resolution Radon transforms do not materially affect the stack response of real data in this area despite their excellent performance on synthetics and on other data in the literature. Serious technical work seldom affords a discussion of “beliefs”, but this work is concerned with the decision-making of the interpreter. We show that in order to address a specific, real, short-period multiple problem, the interpreter was required to challenge previously held technical assumptions. This required the interpreter to consider the nature of the multiple itself, the nature and limitations of the multiple suppression technology used, and to objectively measure the level of success in suppressing the multiple.
Earthquake-Induced Structural and Nonstructural Damage in Hospitals
Authors: Achour Nebil , Miyajima Masakatsu , Kitaura Masaru , Price Andrew
Published: August 2011

The Sichuan (China) and L'Aquila (Italy) earthquakes have again highlighted the question of our preparedness for natural hazards. Within a few seconds, an earthquake can demolish many buildings, destroy infrastructure, and kill and injure thousands of people. In order to reduce the impact of earthquakes on human life and to prepare hospitals to cope with future disasters, this paper discusses earthquake-related damage to healthcare facilities. It investigates the damage to 34 healthcare facilities in seven countries caused by nine earthquakes between 1994 and 2004, in order to determine common and specific issues. The investigation shows that structural and architectural damage tended to be different and specific to the situation, while utility supplies and equipment damage were similar in most cases and some common trends emerged.
Representation of Bidirectional Ground Motions for Design Spectra in Building Codes
Authors: Stewart Jonathan P. , Abrahamson Norman A. , Atkinson Gail M. , Baker Jack W. , Boore David M. , Bozorgnia Yousef , Campbell Kenneth W. , Comartin Craig D. , Idriss I. M. , Lew Marshall , Mehrain Michael , Moehle Jack P. , Naeim Farzad , Sabol Thomas A.
Published: August 2011

The 2009 NEHRP Provisions modified the definition of horizontal ground motion from the geometric mean of spectral accelerations for two components to the peak response of a single lumped mass oscillator regardless of direction. These maximum-direction (MD) ground motions operate under the assumption that the dynamic properties of the structure (e.g., stiffness, strength) are identical in all directions. This assumption may be true for some in-plan symmetric structures, however, the response of most structures is dominated by modes of vibration along specific axes (e.g., longitudinal and transverse axes in a building), and often the dynamic properties (especially stiffness) along those axes are distinct. In order to achieve structural designs consistent with the collapse risk level given in the NEHRP documents, we argue that design spectra should be compatible with expected levels of ground motion along those principal response axes. The use of MD ground motions effectively assumes that the azimuth of maximum ground motion coincides with the directions of principal structural response. Because this is unlikely, design ground motions have lower probability of occurrence than intended, with significant societal costs. We recommend adjustments to make design ground motions compatible with target risk levels.
IL-1β Stimulates Activin βA mRNA Expression in Human Skin Fibroblasts Through the MAPK Pathways, the Nuclear Factor-κB Pathway, and Prostaglandin E2
Authors: Arai Koji Y. , Ono Mariko , Kudo Chikako , Fujioka Atsuko , Okamura Ryoko , Nomura Yoshihiro , Nishiyama Toshio
Published: August 2011

During mouse skin wound healing, mRNAs encoding IL-1, activins, and TGF-βs significantly increased. To elucidate involvement of IL-1 in the regulation of activins and related factors in the wounded skin, human foreskin fibroblasts were stimulated with IL-1β, and levels of mRNAs encoding activins, TGF-βs, and follistatin family proteins were examined by quantitative real-time PCR. IL-1β increased activin βA (INHBA) and follistatin (FST) mRNA expression within 6 h. A p38 MAPK inhibitor, SB202190, a MAPK/ERK kinase inhibitor, U0126, and an nuclear factor κB pathway inhibitor, SC-514, significantly suppressed the IL-1β-stimulated INHBA and FST mRNA expression. A prostaglandin-endoperoxide synthase inhibitor indomethacin, a potent inhibitor of prostaglandin E2 (PGE2) synthesis, also significantly suppressed the IL-1β-stimulated INHBA but not FST mRNA expression. Furthermore, stimulation of fibroblasts with PGE2 significantly increased INHBA mRNA. The PGE2-induced INHBA mRNA expression was significantly suppressed by U0126 and a protein kinase C inhibitor, Gö 6983. Although IL-1β stimulated FST mRNA in an acute phase, long-term exposure of fibroblasts to IL-1β revealed time-dependent stimulatory and inhibitory effects of IL-1β on FST mRNA expression. On the other hand, coculture with keratinocytes significantly increased INHBA mRNA expression in dermal equivalents. In summary, the present study indicates that the p38 MAPK, the MAPK/ERK kinase, the nuclear factor κB pathway, and PGE2 mediate the effects of IL-1β on INHBA mRNA expression. Furthermore, it is indicated that keratinocyte-derived factor of factors stimulate INHBA mRNA expression during wound healing.
Norepinephrine Causes a Biphasic Change in Mammalian Pinealocye Membrane Potential: Role of α1B-Adrenoreceptors, Phospholipase C, and Ca2+
Authors: Zemkova Hana , Stojilkovic Stanko S. , Klein David C.
Published: August 2011

Perforated patch clamp recording was used to study the control of membrane potential (Vm) and spontaneous electrical activity in the rat pinealocyte by norepinephrine. Norepinephrine did not alter spiking frequency. However, it was found to act through α1B-adrenoreceptors in a concentration-dependent manner (0.1–10 μm) to produce a biphasic change in Vm. The initial response was a hyperpolarization (∼13 mV from a resting potential of −46 mV) due to a transient (∼5 sec) outward K+ current (∼50 pA). This current appears to be triggered by Ca2+ released from intracellular stores, based on the observation that it was also seen in cells bathed in Ca2+-deficient medium. In addition, pharmacological studies indicate that this current was dependent on phospholipase C (PLC) activation and was in part mediated by bicuculline methiodide and apamin-sensitive Ca2+-controlled K+ channels. The initial transient hyperpolarization was followed by a sustained depolarization (∼4 mV) due to an inward current (∼10 pA). This response was dependent on PLC-dependent activation of Na+/Ca2+ influx but did not involve nifedipine-sensitive voltage-gated Ca2+ channels. Together, these results indicate for the first time that activation of α1B-adrenoreceptors initiates a PLC-dependent biphasic change in pinealocyte Vm characterized by an initial transient hyperpolarization mediated by a mixture of Ca2+-activated K+ channels followed by a sustained depolarization mediated by a Ca2+-conducting nonselective cation channel. These observations indicate that both continuous elevation of intracellular Ca2+ and sustained depolarization at approximately −40 mV are associated with and are likely to be required for activation of the pinealocyte.
Effects of altered ambient pressure on the volume and distribution of gas within the swimbladder of the adult zebrafish,Danio rerio
Authors: Stoyek Matthew R. , Smith Frank M. , Croll Roger P.
Published: August 2011

Many teleosts use gas-filled swimbladders to control buoyancy and influence three-dimensional orientation (pitch and roll). However, swimbladder volume, and its contributions to these functions, varies with depth-related pressure according to Boyle's law. Moreover, the swimbladder volume at a given depth also depends on the compliance of the swimbladder wall, but this latter factor has been investigated in only a limited number of species. In this study, changes in the volume of the zebrafish swimbladder were observed both in vitro and in situ in pressure chambers that allowed simulations of movements within the water column to and from depths of >300 cm. Results show the anterior chamber to be highly compliant, varying ±38% from its initial volume over the range of simulated depths. This large volume change was accomplished, at least in part, by a series of regular corrugations running along the ventral aspect of the chamber wall and another set of pleats radiating from around the communicating duct in the caudal aspect of the chamber wall. The posterior chamber, in contrast, was found to be minimally compliant, varying only a fraction of a percent from its initial volume over the same pressure range. The different volumetric responses of the chambers caused a significant shift in the distribution of gas within the swimbladder system, but only resulted in a change in the whole-body pitch angle of ±2 deg over the range of pressures tested. Together, our findings provide new insights into the control of buoyancy and trim within teleosts and suggest novel mechanisms that may contribute to swimbladder performance.
Northern elephant seals adjust gliding and stroking patterns with changes in buoyancy: validation of at-sea metrics of body density
Authors: Aoki Kagari , Watanabe Yuuki Y. , Crocker Daniel E. , Robinson Patrick W. , Biuw Martin , Costa Daniel P. , Miyazaki Nobuyuki , Fedak Mike A. , Miller Patrick J. O.
Published: August 2011

Many diving animals undergo substantial changes in their body density that are the result of changes in lipid content over their annual fasting cycle. Because the size of the lipid stores reflects an integration of foraging effort (energy expenditure) and foraging success (energy assimilation), measuring body density is a good way to track net resource acquisition of free-ranging animals while at sea. Here, we experimentally altered the body density and mass of three free-ranging elephant seals by remotely detaching weights and floats while monitoring their swimming speed, depth and three-axis acceleration with a high-resolution data logger. Cross-validation of three methods for estimating body density from hydrodynamic gliding performance of freely diving animals showed strong positive correlation with body density estimates obtained from isotope dilution body composition analysis over density ranges of 1015 to 1060 kg m–3. All three hydrodynamic models were within 1% of, but slightly greater than, body density measurements determined by isotope dilution, and therefore have the potential to track changes in body condition of a wide range of freely diving animals. Gliding during ascent and descent clearly increased and stroke rate decreased when buoyancy manipulations aided the direction of vertical transit, but ascent and descent speed were largely unchanged. The seals adjusted stroking intensity to maintain swim speed within a narrow range, despite changes in buoyancy. During active swimming, all three seals increased the amplitude of lateral body accelerations and two of the seals altered stroke frequency in response to the need to produce thrust required to overcome combined drag and buoyancy forces.