bluuebunny/crossref_metadata_2025 huggingface dataset:
A new era for castrate resistant prostate cancer: A treatment review and update
Authors: Fong Mei Ka , Hare Ryan , Jarkowski Anthony
Published: February 2012

Purpose: The purpose of this review article is to present the current treatment options for castrate resistant prostate cancer in addition to the recently approved agents and their role in treatment.

Summary: The biology of prostate cancer and the data supporting the use of traditional chemotherapeutic options in castrate resistant prostate cancer are reviewed. The newly approved agents, sipuleucel-T, cabazitaxel, and abiraterone, are presented as well. The studies that led to the approval of these three agents are discussed in this article as well as their current and potential roles in the treatment of castrate resistant prostate cancer.

Conclusion: New mechanisms, drugs, and clinically relevant molecular targets show survival advantage and are new options available for patients after traditional chemotherapy. The roles of these new agents have yet to be further clarified in future studies.
“Governments Have the Power”? Interpretations of Climate Change Responsibility and Solutions Among Canadian Environmentalists
Authors: Stoddart Mark C. J. , Tindall D. B. , Greenfield Kelly L.
Published: February 2012

The authors examine environmentalists’ attribution of responsibility for addressing climate change and their beliefs about solutions to this problem. Their analysis is based on responses to open-ended questions completed by 1,227 members of nine different environmental organizations. For these environmental movement participants, the federal government is seen as most responsible for addressing climate change. Government leadership is necessary because it has the power to set regulations and lead corporations and citizens toward pro-environmental behavior. However, a substantial number of participants also assert that “individuals are the driving force” in dealing with climate change. In this framework, individuals can take responsibility either through making lifestyle changes, or through applying pressure to government and businesses as citizens and consumers. Corporations are interpreted as unwilling to change on their own but must be coerced into becoming more environmentally sustainable by a strong state.
Transesophageal Echocardiography in Tetralogy of Fallot
Authors: Motta Pablo , Miller-Hance Wanda C.
Published: February 2012

Transesophageal echocardiography (TEE) plays an important role in the anatomical, functional, and hemodynamic assessment of patients with congenital heart disease (CHD). This imaging approach has been applied to both children and adults with a wide range of cardiovascular malformations. Extensive clinical experience documents significant contributions, particularly in the perioperative setting. In fact, in the current medical era, many consider this technology to be an essential adjunct to surgical and anesthetic management in CHD. This review focuses on the applications of TEE in patients with tetralogy of Fallot (TOF), the most common form of cyanotic heart disease. Emphasis is given to the perioperative use of this imaging modality and benefits derived during the prebypass and postbypass periods. Limitations and pitfalls relevant to the TEE assessment in patients with this anomaly are also addressed.
The Role of Free Radicals in Traumatic Brain Injury
Authors: O’Connell Karen M. , Littleton-Kearney Marguerite T.
Published: February 2012

Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.
Sliding friction and wear behavior of thermoplastic polyimide composites filled with differently surface-treated poly-p-phenylenebenzobisoxazole fibers
Authors: Yu Liang , Cheng Xianhua
Published: February 2012

Rare earth and coupling agent surface treatment methods were employed toward poly-p-phenylenebenzobisoxazole (PBO) fibers. X-ray photoelectron spectroscopy measurement was used to analyze the surface characteristics of untreated and treated PBO fibers. The friction and wear behavior of the thermoplastic polyimide (PI) composites filled with differently surface-treated PBO fibers, sliding against GCr15 steel under oil-lubricated condition, was investigated on a reciprocating ball-on-block UMT-2MT tribometer. Scanning electron microscope investigation of worn surface morphologies of PBO/PI composites showed that rare earth treatment was more effective than coupling agent treatment to improve the friction and wear behavior of PBO/PI composites under given load and reciprocating sliding frequency. The mechanism of the friction and wear behavior of PBO/PI composites was discussed.
Protective effect of an elastase inhibitor in a neuromyelitis optica-like disease driven by a peptide of myelin oligodendroglial glycoprotein
Authors: Herges Katja , de Jong Brigit A , Kolkowitz Ilan , Dunn Caitlin , Mandelbaum Gil , Ko Rose M , Maini Alexander , Han May H , Killestein Joep , Polman Chris , Goodyear Alexandra L , Dunn Jeffrey , Steinman Lawrence , Axtell Robert C
Published: February 2012

Background: The pathology of neuromyelitis optica (NMO), in contrast to multiple sclerosis, comprises granulocyte infiltrates along extensive lengths of spinal cord, as well as optic nerve. Furthermore, IFN-β treatment worsens NMO. We recently found that experimental autoimmune encephalomyelitis (EAE) induced with Th17 cells is exacerbated by IFN-β, in contrast to disease induced with Th1 where treatment attenuated symptoms.

Objective: This study demonstrates the similarities between NMO and Th17 EAE and how neutrophils mediate pathology in Th17 disease.

Methods: Levels of blood biomarkers in NMO were assessed by Luminex and ELISA. Effects of IFN-β on neutrophils were assessed by culture assays and immunofluorescence. EAE was induced by transfer of myelin-specific Th1 or Th17 cells and treated with Sivelestat sodium hydrate, a neutrophil elastase inhibitor.

Results: We show Th17 cytokines, granulocyte chemokines, type 1 interferon and neutrophil elastase are elevated in patients with definitive NMO. In culture, we find that IFN-β stimulates neutrophils to release neutrophil elastase. In Th17 EAE, we demonstrate neutrophilic infiltration in the optic nerve and spinal cord which was not present in Th1 EAE. Blockade of neutrophil elastase with Sivelestat had efficacy in Th17 EAE but not Th1 EAE.

Conclusions: The similarities between Th17 EAE and NMO indicate that this model represents several aspects of NMO. Neutrophils are critical in the pathologies of both Th17-EAE and NMO, and therefore blockade of neutrophil elastase is a promising target in treating NMO.
Datamoshing and the emergence of digital complexity from digital chaos
Authors: Brown William , Kutty Meetali
Published: February 2012

In this essay, we explore the aesthetic possibilities that are opened up by datamoshing, a practice whereby audiovisual artists actively downgrade the quality of digital images in order to render a more ‘raw’ aesthetic on screen. We follow this up by exploring the ways in which datamoshing as a practice (together with ‘glitch art’ more generally) highlights the decay that digital images undergo over time. Because it takes place through the deliberate compression of images, we here argue that the aforementioned loss of quality is an ‘artistic’ form of entropy, which leads us to the possibility for a theory of ‘digital chaos’. However, since the loss of data is reworked by artists in order to create new forms, we argue that this is a form of digital ‘emergence’ of ‘order out of chaos’, or ‘digital complexity’.
Experimental study of corrugated tubes under lateral loading
Authors: Eyvazian A , Akbarzadeh I , Shakeri M
Published: February 2012

Thin-walled tubes are widely used as energy absorbers in various vehicles and moving parts. The objective of this study is to investigate the energy absorption characteristics of tubes with corrugations in different geometries, under lateral loading. In order to produce corrugations, an innovative solution is introduced. Quasi-static tests were conducted to study the effect of changing the corrugation geometry (type and amplitude). The results show that tubes with corrugations have a higher mean crushing force which is directly proportional to the number of corrugations and their amplitudes. Moreover, it was observed that corrugated tubes can absorb approximately four times more energy than the tubes without corrugations in the same sizes and weights. Finally, it was found that corrugated tubes are more effective in lateral direction as energy absorbers, as they present suitable force–deflection responses.
A review of experimental studies on deposits in the combustion chambers of internal combustion engines
Authors: Shu Gequn , Dong Lihui , Liang Xingyu
Published: February 2012

This article reviews experimental studies on deposits in engine combustion chambers, with emphasis on deposit composition, damage to engines, formation mechanisms and study methods. The existence of combustion chamber deposits will definitely influence performance and emissions of engines, and is inevitable with the use of petroleum fuel and lubricating oil. These all make it necessary to study the formation, composition, structure and influential factors of deposits, which will provide the basis for reducing deposits in engines. Influential factors and methods of reducing deposit formation are also included. First, the deposit damage to engines is briefly introduced, with a focus mainly on the decline in engine performance and the deterioration of emissions, and the reasons for these phenomena are explained. Next, conclusions on deposit research approaches to their chemical composition and physical structure are drawn. Finally, with regards to deposit formation in gasoline and diesel engines, deposit composition and factors influencing deposit formation, such as engine type, fuel type, oil type, additives, exhaust gas recirculation, etc., are enumerated through experimental studies on engines. Studies on deposit formation with some newly developed types of fuel are also included. The mechanism of deposit formation under these different conditions is explained, and the methods for reducing deposit formation are summarized.
The Timescapes Archive: a stakeholder approach to archiving qualitative longitudinal data
Authors: Neale Bren , Bishop Libby
Published: February 2012

ESRC funding for the Timescapes initiative included provision for the creation of a specialist resource of Qualitative Longitudinal (QL) data for sharing and re-use. In this article we document the development of this resource, focusing on the strategic and practical dimensions of its growth. In the process we explore the importance of effective communication and negotiation in the development of stakeholder collaborations between researchers and archivists. We reveal the potential of the archive to operate at the intersection of primary and secondary research, acting as a useful repository for the data of primary researchers to aid temporal QL analysis, and bringing related datasets together for enhanced analysis by both primary and secondary users.
Impact of glycaemic control on the effect of direct renin inhibition in the AVOID study
Authors: Persson Frederik , Lewis Julia B , Lewis Edmund J , Rossing Peter , Hollenberg Norman K , Parving Hans-Henrik
Published: February 2012

Introduction: Hyperglycaemia induces development and progression of microvascular complications in diabetes. A direct link between high glucose levels and intrarenal renin–angiotensin activation has been demonstrated. This post-hoc analysis assessed the influence of baseline glycaemic control on the reduction of albuminuria with aliskiren or placebo added to losartan in the Aliskiren in the EValuation of PrOteinuria In Diabetes (AVOID) study.

Materials and methods: In AVOID, 599 patients with type 2 diabetes, hypertension and nephropathy received 6 months’ aliskiren or placebo added to losartan 100 mg and optimal antihypertensive therapy. Changes in urinary albumin creatinine ratio at end of study were assessed by tertiles of baseline HbA1c levels.

Results: Patients were divided into tertiles of HbA1c (<7.1%, 7.1 to <8.4% and ≥8.4%). There were no differences between tertiles, except patients in the highest tertile group more frequently used insulin. The antiproteinuric effect of aliskiren was consistent across tertiles, with the largest effect in the highest tertile (HbA1c ≥8.4%).

Conclusions: This post-hoc analysis of the AVOID study suggests that renin inhibition with aliskiren 300 mg once daily added to losartan 100 mg once daily plus optimal antihypertensive therapy provides reductions in urinary albumin creatinine ratio that are efficacious in all, but particularly in poorly controlled, diabetic patients.
Arteriovenous Loop Grafts for Free Tissue Transfer
Authors: Lind Benjamin , McCarthy Walter , Derman Gordon , Jacobs Chad
Published: February 2012

Arteriovenous (AV) loop grafts are a type of vascular conduit that can be used to support free tissue transfer. Wounds of various etiologies may require free tissue transfer, and the AV loop graft is a useful adjunct when adjacent blood supply is inadequate. Here we present 2 cases and review the technique and published literature.
Endovascular Treatment for Ischemic Stroke Induced by Vertebrobasilar Junction Artery Dissection
Authors: Liu Xun-Can , Shi Ming-Chao , Wang Shou-Chun
Published: February 2012

We reported 2 cases of vertebrobasilar junction artery dissection treated by different methods. Intra-artery thrombolysis was used to treat 1 patient, who died 53 hours after the procedure. The other case was treated by stenting for unaffected vertebral artery associated with a coil occlusion of affected vertebral artery, and the prognosis was good. These cases suggest that occlusion of proximal side of the vertebral artery affected by dissection and stenting for the junction between the other side of vertebral artery and the basilar artery may be a feasible method for vertebrobasilar junction artery dissection with or without thrombolysis.
Single-Access Laparoscopic “Lavage” for Purulent Diverticulitis in a 96-Year-Old Patient
Authors: Huscher Cristiano , Mingoli Andrea , Mereu Andrea , Sgarzini Giovanna
Published: February 2012

Introduction. Recently, laparoscopic lavage emerged as an effective alternative for patients with perforated diverticulitis with purulent peritonitis. Case Report. A 96-year-old woman, diagnosed with Hinchey 3 diverticulitis after a computed tomography scan, was operated on with a single-access “lavage” to reduce surgical trauma and to avoid stoma. Methods. The procedure was performed under general anesthesia. Tracheal intubation, nasogastric tube, and urethral catheterization were mandatory. The patient was in a modified Lloyd-Davis position, with the table tilted in Trendelenburg position, left side up. Surgeons were on the right side. Instrumentation. The procedure was performed using a surgical technique similar to standard laparoscopy with traditional laparoscopic instruments. Surgical Steps. The surgical procedure involved single-incision laparoscopic surgery (Covidien, Mansfield, MA) insertion, small bowel dissection, abscess opening, and peritoneal washing. Results. The procedure was completed in 75 minutes with an estimated blood loss of 120 mL. The patient was kept in the intensive care unit for 1 day. She was on postoperative analgesia for 2 days and was discharged from the hospital on postoperative day 5. The patient was able to drink on day 1 and eat on day 3 after flatus.
Assessment of Knee Implant Alignment Using Coordinate Measurement on Three-Dimensional Computed Tomography Reconstructions
Authors: Nowakowski Andrej M. , Müller-Gerbl Magdalena , Valderrabano Victor
Published: February 2012

The rapid development of navigation systems designed to improve implant alignment calls for precise methods to verify positioning. One new approach to assess knee implant alignment is coordinate measurement (CM) using reference objects on 3-dimensional reconstructions of computed tomographic (CT) image sequences. The objectives of this study were to determine whether implant alignment can be accurately and precisely examined with CT-based CM, and whether correct positioning of a transversal support implant can be attained using a specially developed aiming instrument. Average deviation of CT measurements from those made with a digital caliper remained within the caliper’s range of error. This level of accuracy was observer independent. CT-based CM can be used for accurate and precise alignment verification. As well, precise alignment of transversal support can be achieved during implantation with a conventional aiming device, assuming the bony landmarks are appropriately recognized.
Use of a Silicone Penrose Drain to Protect Incised Skin Edges During Thyroid Surgery
Authors: Lee Yong Sang , Kim Bup Woo , Chang Hang-Seok , Park Cheong Soo
Published: February 2012

Acceptable wound cosmesis is an important issue in thyroidectomy. We introduce a simple, economical and effective method of preventing traction and thermal damage to the incised skin edges during thyroidectomy.
The Effectiveness of Environmental Advertising in the Hotel Industry
Authors: Hu Hsin-Hui “Sunny”
Published: February 2012

Environmental advertising can create opportunities for a hospitality company to maximize messages and sponsorships. This research explores the independent and interactive influences of environmental claims and the emotional benefits on consumer response to hotels’ environmental advertising. This study further analyzes whether there are differences in responses to green advertisements between high-involved and low-involved consumers. The results indicate that a substantive claim would elicit much more positive responses from consumers than an associative claim, and a self-expressive benefit is generally more successful than a nature-related benefit in fostering positive responses. At the same time, a substantive claim was more persuasive when it was coupled with a self-expressive benefit, while an associative claim led to more positive reactions after exposure to a nature-related benefit. Finally, there is a difference in responses to hotels’ environmental ads between high- and low-involvement consumers. This article provides empirical information for hotel marketers contemplating the development and presentation of environmental advertising to improve their environmental brand image and increase consumer purchase intent.
Educational Supports for Students With Special Needs
Authors: Whipple Jennifer , VanWeelden Kimberly
Published: February 2012

Historically, music educators have expressed concerns about inadequate preparation to work with students with special needs, specifically desiring skills related to instruction adaptation. Research has indicated that educational supports (written words, color coding, icons, echoing, buddy system, and other visual aids) can be particularly successful for teaching students with special needs. To determine if preservice music teachers can employ these supports and determine which are most beneficial in various music settings, preservice music educators ( N = 47) completed a 5-week field experience in which they taught general music concepts to secondary students with special needs incorporating educational supports. Participants rated the educational supports of echoing and icons most important when leading various activities to teach concepts in general music and predicted that the educational supports of echoing and other visual aids would be most important when teaching in various ensembles settings. For implementing assessments, participants rated icons and small groups or stations most important. Implications for preservice and in-service teachers are discussed.
Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma
Authors: Kasamon Yvette L. , Jacene Heather A. , Gocke Christopher D. , Swinnen Lode J. , Gladstone Douglas E. , Perkins Brandy , Link Brian K. , Popplewell Leslie L. , Habermann Thomas M. , Herman Joseph M. , Matsui William H. , Jones Richard J. , Ambinder Richard F.
Published: February 2012

In classical Hodgkin lymphoma, circulating clonotypic malignant cells express CD20, which potentially explains the observed activity of rituximab. This multicenter phase 2 study investigated the combination of rituximab-ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage II-IV untreated classical Hodgkin lymphoma. A goal was to assess the behavior of circulating clonotypic B cells clinically. Of 49 evaluable patients, 69% had stage IIB-IV disease; 8% had CD20+ Hodgkin and Reed-Sternberg cells. Rituximab-ABVD was generally well tolerated. Delivered relative dose intensity was 94% for AVD and 79% for bleomycin. After 6 cycles, 81% of patients were in complete remission. Only 8% received radiation therapy. The actuarial 3-year event-free and overall survival rates were 83% and 98%, respectively. EBV copy number in plasma fell dramatically during cycle 1 in patients with EBV+ tumors. Persistence of detectable circulating clonotypic B cells was associated with a greater relapse frequency (P < .05). Rituximab-ABVD and clonotypic B cells warrant additional study in classical Hodgkin lymphoma. This trial was registered at www.clinicaltrials.gov as NCT00369681.
Assessing statistical significance in causal graphs
Authors: Chindelevitch Leonid , Loh Po-Ru , Enayetallah Ahmed , Berger Bonnie , Ziemek Daniel
Published: February 2012

Background

Causal graphs are an increasingly popular tool for the analysis of biological datasets. In particular, signed causal graphs--directed graphs whose edges additionally have a sign denoting upregulation or downregulation--can be used to model regulatory networks within a cell. Such models allow prediction of downstream effects of regulation of biological entities; conversely, they also enable inference of causative agents behind observed expression changes. However, due to their complex nature, signed causal graph models present special challenges with respect to assessing statistical significance. In this paper we frame and solve two fundamental computational problems that arise in practice when computing appropriate null distributions for hypothesis testing.

Results

First, we show how to compute a p-value for agreement between observed and model-predicted classifications of gene transcripts as upregulated, downregulated, or neither. Specifically, how likely are the classifications to agree to the same extent under the null distribution of the observed classification being randomized? This problem, which we call "Ternary Dot Product Distribution" owing to its mathematical form, can be viewed as a generalization of Fisher's exact test to ternary variables. We present two computationally efficient algorithms for computing the Ternary Dot Product Distribution and investigate its combinatorial structure analytically and numerically to establish computational complexity bounds.

Second, we develop an algorithm for efficiently performing random sampling of causal graphs. This enables p-value computation under a different, equally important null distribution obtained by randomizing the graph topology but keeping fixed its basic structure: connectedness and the positive and negative in- and out-degrees of each vertex. We provide an algorithm for sampling a graph from this distribution uniformly at random. We also highlight theoretical challenges unique to signed causal graphs; previous work on graph randomization has studied undirected graphs and directed but unsigned graphs.

Conclusion

We present algorithmic solutions to two statistical significance questions necessary to apply the causal graph methodology, a powerful tool for biological network analysis. The algorithms we present are both fast and provably correct. Our work may be of independent interest in non-biological contexts as well, as it generalizes mathematical results that have been studied extensively in other fields.
Travel risk behaviours and uptake of pre-travel health preventions by university students in Australia
Authors: Heywood Anita E , Zhang Meng , MacIntyre C Raina , Seale Holly
Published: February 2012

Background

Forward planning and preventative measures before travelling can significantly reduce the risk of many vaccine preventable travel-related infectious diseases. Higher education students may be at an increased risk of importing infectious disease as many undertake multiple visits to regions with higher infectious disease endemicity. Little is known about the health behaviours of domestic or international university students, particularly students from low resource countries who travel to high-resource countries for education. This study aimed to assess travel-associated health risks and preventative behaviours in a sample of both domestic and international university students in Australia.

Methods

In 2010, a 28 item self-administered online survey was distributed to students enrolled at the University of New South Wales, Sydney, Australia. Multiple methods of distributing links to the online survey were utilised. The survey examined the international travel history, travel intentions, infection control behaviours and self-reported vaccination history.

Results

A total of 1663 respondents completed the online survey, 22.1% were international students and 83.9% were enrolled at an undergraduate level. Half had travelled internationally in the previous 12 months, with 69% of those travelling only once during that time with no difference in travel from Australia between domestic and international students (p = 0.8). Uptake of pre-travel health advice was low overall with 68% of respondents reporting they had not sought any advice from a health professional prior to their last international trip. Domestic students were more likely to report uptake of a range of preventative travel health measures compared to international students, including diarrhoeal medication, insect repellent, food avoidance and condoms (P < 0.0001). Overall, students reported low risk perception of travel threats and a low corresponding concern for these threats.

Conclusions

Our study highlights the need to educate students about the risk associated with travel and improve preventative health-seeking and uptake of precautionary health measures in this highly mobile young adult population. Although immunisation is not an entry requirement to study at Universities in Australia, large tertiary institutions provide an opportunity to engage with young adults on the importance of travel health and provision of vaccines required for travel, including missed childhood vaccines.
Bacterium-like particles as multi-epitope delivery platform for Plasmodium berghei circumsporozoite protein induce complete protection against malaria in mice
Authors: Nganou-Makamdop Krystelle , van Roosmalen Maarten L , Audouy Sandrine AL , van Gemert Geert-Jan , Leenhouts Kees , Hermsen Cornelus C , Sauerwein Robert W
Published: February 2012

Background

Virus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins. The present study reports the immunogenicity and protective efficacy of bacterium-like particles (BLPs) generated from Lactococcus lactis and loaded with Plasmodium berghei circumsporozoite protein (PbCSP) peptides.

Methods

A panel of BLP-PbCSP formulations differing in composition and quantity of B-cell, CD4+ and CD8+ T-cell epitopes of PbCSP were tested in BALB/c mice.

Results

BLP-PbCSP1 induced specific humoral responses but no IFN-γ ELISPOT response, protecting 30-40% of the immunized mice. BLP-PbCSP2, with reduced length of the non-immunogenic part of the T-cell-epitopes construct, increased induction of IFN-γ responses as well as protection up to 60-70%. Compared to controls, lower parasitaemia was observed in unprotected mice immunized with BLP-PbCSP1 or 2, suggestive for partial immunity. Finally, further increase of the number of B-cell epitopes and codon optimization (BLP-PbCSP4) induced the highest anti-CSP antibody levels and number of IFN-γ spots, resulting in sterile immunity in 100% of the immunized mice.

Conclusion

Presentation of Plasmodium-derived antigens using BLPs as a delivery system induced complete protection in a murine malaria model. Eventually, BLPs have the potential to be used as a novel versatile delivery platform in malaria vaccine development.
Relationships between serum HER2 ECD, TIMP-1 and clinical outcomes in Taiwanese breast cancer
Authors: Tsai Hsiu-Pei , Chen Shin-Cheh , Chien Huei-Tzu , Jan Yi-Yin , Chao Tzu-Chieh , Chen Miin-Fu , Hsieh Ling-Ling
Published: February 2012

Background

Serum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. A disintegrin and metalloproteinase-10, a sheddase of HER2/neu, can drive cancer progression and its activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). However, elevated TIMP-1 expression has been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum HER2 ECD, TIMP-1 and clinical outcomes.

Methods

One hundred and eighty-five female breast cancer patients, who received curative mastectomy without neo-adjuvant chemotherapy at Chang-Gung Memorial Hospital, were recruited with informed consent for this study. Pre-operative serum levels of HER2 ECD and TIMP-1 were measured using an enzyme-linked immunosorbent assay.

Results

Twenty-three cases (12.4%) were classified HER2 ECD positive. HER2 ECD positivity was significantly associated with age, lymph node involvement, histological grade, estrogen receptor status, progesterone receptor status, tissue HER2/neu overexpression, and disease-free survival (DFS). In an age, stage, ER and HER2/neu status matched subgroup (N = 41), the serum level of TIMP-1 was significantly associated with HER2 ECD positivity and DFS.

Conclusions

A high serum TIMP-1 was significantly associated with HER2 ECD positivity and a poorer DFS among Taiwanese primary breast cancer patients with HER2 overexpression.
Does partial expander deflation exacerbate the adverse effects of radiotherapy in two-stage breast reconstruction?
Authors: Celet Ozden Burcu , Guven Erdem , Aslay Isik , Kemikler Gonul , Olgac Vakur , Soluk Tekkesin Merva , Serarslan Bengul , Tumerdem Ulug Burcak , Bilgin Karabulut Aylin , Arinci Atilla , Emekli Ufuk
Published: February 2012

Background

The optimum protocol for expander volume adjustment with respect to the timing and application of radiotherapy remains controversial.

Methods

Eighteen New Zealand rabbits were divided into three groups. Metallic port integrated anatomic breast expanders of 250 cc were implanted on the back of each animal and controlled expansion was performed. Group I underwent radiotherapy with full expanders while in Group II, expanders were partially deflated immediately prior to radiotherapy. Control group did not receive radiotherapy.

The changes in blood flow at different volume adjustments were investigated in Group II by laser Doppler flowmetry. Variations in the histopathologic properties of the irradiated tissues including the skin, capsule and the pocket floor, were compared in the biopsy specimens taken from different locations in each group.

Results

A significant increase in skin blood flow was detected in Group II with partial expander deflation. Overall, histopathologic exam revealed aggravated findings of chronic radiodermatitis (epidermal atrophy, dermal inflammation and fibrosis, neovascularisation and vascular changes as well as increased capsule thickness) especially around the lower expander pole, in Group II.

Conclusions

Expander deflation immediately prior to radiotherapy, may augment the adverse effects, especially in the lower expander pole, possibly via enhanced radiosensitization due to a relative increase in the blood flow and tissue oxygenation.
Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis
Authors: Zickert Agneta , Palmblad Karin , Sundelin Birgitta , Chavan Sangeeta , Tracey Kevin J , Bruchfeld Annette , Gunnarsson Iva
Published: February 2012

Introduction

High mobility group box 1 protein (HMGB1) is a nuclear DNA binding protein acting as a pro-inflammatory mediator following extracellular release. HMGB1 has been increasingly recognized as a pathogenic mediator in several inflammatory diseases. Elevated serum levels of HMGB1 have been detected in autoimmune diseases including Systemic lupus erythematosus (SLE). However, the local expression of HMGB1 in active lupus nephritis (LN) is not known. Here we aimed to study both tissue expression and serum levels of HMGB1 in LN patients with active disease and after induction therapy.

Methods

Thirty-five patients with active LN were included. Renal biopsies were performed at baseline and after standard induction therapy; corticosteroids combined with immunosuppressive drugs. The biopsies were evaluated according to the World Health Organization (WHO) classification and renal disease activity was estimated using the British Isles lupus assessment group (BILAG) index. Serum levels of HMGB1 were analysed by western blot. HMGB1 expression in renal tissue was assessed by immunohistochemistry at baseline and follow-up biopsies in 25 patients.

Results

Baseline biopsies showed WHO class III, IV or V and all patients had high renal disease activity (BILAG A/B). Follow-up biopsies showed WHO I to II (n = 14), III (n = 6), IV (n = 3) or V (n = 12), and 15/35 patients were regarded as renal responders (BILAG C/D).

At baseline HMGB1 was significantly elevated in serum compared to healthy controls (P < 0.0001). In all patients, serum levels decreased only slightly; however, in patients with baseline WHO class IV a significant decrease was observed (P = 0.03). Immunostaining revealed a pronounced extranuclear HMGB1 expression predominantly outlining the glomerular endothelium and in the mesangium. There was no clear difference in HMGB1 expression comparing baseline and follow-up biopsies or any apparent association to histopathological classification or clinical outcome.

Conclusions

Renal tissue expression and serum levels of HMGB1 were increased in LN. The lack of decrease of HMGB1 in serum and tissue after immunosuppressive therapy in the current study may reflect persistent inflammatory activity. This study clearly indicates a role for HMGB1 in LN.
Autosomal monoallelic expression in the mouse
Authors: Zwemer Lillian M , Zak Alexander , Thompson Benjamin R , Kirby Andrew , Daly Mark J , Chess Andrew , Gimelbrant Alexander A
Published: February 2012

Background

Random monoallelic expression defines an unusual class of genes displaying random choice for expression between the maternal and paternal alleles. Once established, the allele-specific expression pattern is stably maintained and mitotically inherited. Examples of random monoallelic genes include those found on the X-chromosome and a subset of autosomal genes, which have been most extensively studied in humans. Here, we report a genome-wide analysis of random monoallelic expression in the mouse. We used high density mouse genome polymorphism mapping arrays to assess allele-specific expression in clonal cell lines derived from heterozygous mouse strains.

Results

Over 1,300 autosomal genes were assessed for allele-specific expression, and greater than 10% of them showed random monoallelic expression. When comparing mouse and human, the number of autosomal orthologs demonstrating random monoallelic expression in both organisms was greater than would be expected by chance. Random monoallelic expression on the mouse autosomes is broadly similar to that in human cells: it is widespread throughout the genome, lacks chromosome-wide coordination, and varies between cell types. However, for some mouse genes, there appears to be skewing, in some ways resembling skewed X-inactivation, wherein one allele is more frequently active.

Conclusions

These data suggest that autosomal random monoallelic expression was present at least as far back as the last common ancestor of rodents and primates. Random monoallelic expression can lead to phenotypic variation beyond the phenotypic variation dictated by genotypic variation. Thus, it is important to take into account random monoallelic expression when examining genotype-phenotype correlation.
Genome-wide analysis of the maternal-to-zygotic transition in Drosophila primordial germ cells
Authors: Siddiqui Najeeb U , Li Xiao , Luo Hua , Karaiskakis Angelo , Hou Huayun , Kislinger Thomas , Westwood J Timothy , Morris Quaid , Lipshitz Howard D
Published: February 2012

Background

During the maternal-to-zygotic transition (MZT) vast changes in the embryonic transcriptome are produced by a combination of two processes: elimination of maternally provided mRNAs and synthesis of new transcripts from the zygotic genome. Previous genome-wide analyses of the MZT have been restricted to whole embryos. Here we report the first such analysis for primordial germ cells (PGCs), the progenitors of the germ-line stem cells.

Results

We purified PGCs from Drosophila embryos, defined their proteome and transcriptome, and assessed the content, scale and dynamics of their MZT. Transcripts encoding proteins that implement particular types of biological functions group into nine distinct expression profiles, reflecting coordinate control at the transcriptional and posttranscriptional levels. mRNAs encoding germ-plasm components and cell-cell signaling molecules are rapidly degraded while new transcription produces mRNAs encoding the core transcriptional and protein synthetic machineries. The RNA-binding protein Smaug is essential for the PGC MZT, clearing transcripts encoding proteins that regulate stem cell behavior, transcriptional and posttranscriptional processes. Computational analyses suggest that Smaug and AU-rich element binding proteins function independently to control transcript elimination.

Conclusions

The scale of the MZT is similar in the soma and PGCs. However, the timing and content of their MZTs differ, reflecting the distinct developmental imperatives of these cell types. The PGC MZT is delayed relative to that in the soma, likely because relief of PGC-specific transcriptional silencing is required for zygotic genome activation as well as for efficient maternal transcript clearance.
Time-lapse gravity: A numerical demonstration using robust inversion and joint interpretation of 4D surface and borehole data
Authors: Krahenbuhl Richard A. , Li Yaoguo
Published: February 2012

There are a number of ongoing developments in the 4D gravity method for time-lapse production and sequestration problems. Complex model construction is an essential component for meaningful feasibility studies and data interpretation in 4D. In the case of oil reservoirs, for example, the 4D gravity method must deal with very small density contrasts at depth, and overly simplistic model representations of a field site may not properly guide monitoring efforts for effective reservoir management decisions. The tracking of injected fluid through inversion can be significantly improved with the joint interpretation of surface and borehole gravity data. This is particularly relevant for time-lapse gravity problems where subtle changes in density contrast at depth may not produce surface data that alone contain the necessary information to recover the boundaries of fluid movement. Complex model construction and robust inversion show that time-lapse gravity surveys may contribute to improved production efficiency and reservoir management in-between the more traditional, and expensive 4D seismic surveys. Results hint that the true value of time-lapse gravity as an additional tool for production efficiency and reservoir management may be greatly undervalued. Data simulated within current and ongoing sensor technologies, combined with advances in computing power and robust inversion, can extract much more meaningful information about fluid movement in reservoirs that are geometrically complex and relatively thin and deep. To illustrate these points, simulations are performed using a representation of the published Jotun Field in the Norwegian North Sea, a well-studied site demonstrating successful application of the time-lapse seismic method, and reconstructed for 4D gravity understanding.
A Facile and Continuous Fabrication of Polyimide Hollow Nanoparticles Using a Microfluidic System
Authors: Ishizaka Takayuki , Ishigaki Atsushi , Suzuki Akira , Suzuki Toshishige M , Kawanami Hajime
Published: February 2012

A facile and continuous synthesis method of polyimide hollow nanoparticles has been developed by microemulsion reprecipitation method using a microfluidic system within a short reaction time (10 s). The mean particle size and the coefficient of variation were 314 nm and 0.22, respectively. We also successfully demonstrated that the polyimide hollow nanoparticles can be used as a nanocontainer as well as nanoreactor by retracting a chemical dye such as Rhodamine 6G.
Dopamine Detection on Boron-doped Diamond Electrodes Using Fast Cyclic Voltammetry
Authors: Kato Taisuke , Fierro Stéphane , Watanabe Takeshi , Yoshimi Kenji , Einaga Yasuaki
Published: February 2012

A new method is proposed for the accurate and reproducible detection of dopamine using cyclic voltammetry on boron-doped diamond (BDD) electrode. It is shown that reproducible voltammograms can be obtained when applying a relatively high scan rate (100 V s−1) during the detection measurements. For lower scan rates (1 V s−1), it is proven that electrode fouling occurs due do the deposition of a polymer at the electrode surface arising from the oxidation of aminochrome. Cyclic voltammetry measurements of the [Fe(CN)6]3−/[Fe(CN)6]4− couple performed before and after dopamine detection on BDD and glassy carbon electrodes have shown that the electrochemical activity of the electrode decreases only at low scan rates for BDD dopamine (DA) detection, which leads to electrode poisoning whereas the activity remains unchanged for higher scan rates. However, on glassy carbon electrodes, the electrochemical activity of the material decreases after DA detection measurements independently of the scan rate applied. Therefore, this study shows that electrode fouling during the detection of dopamine by cyclic voltammetry can be avoided only when using BDD electrode but also only for high applied scan rates.
Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow
Authors: Moberly Steven P , Berwick Zachary C , Kohr Meredith , Svendsen Mark , Mather Kieren J , Tune Johnathan D
Published: February 2012

We examined the acute dose-dependent effects of intracoronary glucagon-like peptide (GLP)-1 (7-36) on coronary vascular tone, cardiac contractile function and metabolism in normal and ischemic myocardium. Experiments were conducted in open chest, anesthetized dogs at coronary perfusion pressures (CPP) of 100 and 40 mmHg before and during intracoronary GLP-1 (7-36) infusion (10 pmol/L to 1 nmol/L). Isometric tension studies were also conducted in isolated coronary arteries. Cardiac and coronary expression of GLP-1 receptors (GLP-1R) was assessed by Western blot and immunohistochemical analysis. GLP-1R was present in the myocardium and the coronary vasculature. The tension of intact and endothelium-denuded coronary artery rings was unaffected by GLP-1. At normal perfusion pressure (100 mmHg), intracoronary GLP-1 (7-36) (targeting plasma concentration 10 pmol/L to 1 nmol/L) did not affect blood pressure, coronary blood flow or myocardial oxygen consumption (MVO2); however, there were modest reductions in cardiac output and stroke volume. In untreated control hearts, reducing CPP to 40 mmHg produced marked reductions in coronary blood flow (0.50 ± 0.10 to 0.17 ± 0.03 mL/min/g; P < 0.001) and MVO2 (27 ± 2.3 to 15 ± 2.7 μL O2/min/g; P < 0.001). At CPP = 40 mmHg, GLP-1 had no effect on coronary blood flow, MVO2 or regional shortening, but dose-dependently increased myocardial glucose uptake from 0.11 ± 0.02 μmol/min/g at baseline to 0.17 ± 0.04 μmol/min/g at 1 nmol/L GLP-1 ( P < 0.001). These data indicate that acute, intracoronary administration of GLP-1 (7-36) preferentially augments glucose metabolism in ischemic myocardium, independent of effects on cardiac contractile function or coronary blood flow.
Customer Influence Value and Purchase Acceleration in New Product Diffusion
Authors: Ho Teck-Hua , Li Shan , Park So-Eun , Shen Zuo-Jun Max
Published: February 2012

When social influence plays a key role in the diffusion of new product, the value of a customer often goes beyond her own product purchase. We posit that a customer's value (CV) comes not only from her purchase value (PV) but also from her influence value (IV) (i.e., CV = PV + IV). Therefore, a customer's value can be far greater than her purchase value if she exerts a considerable influence on others. Building on a two-segment influential–imitator asymmetric influence model, we develop a model framework to derive closed-form expressions for PV, IV, and CV by customer segment as well as time of adoption, and we examine their comparative statics with respect to the diffusion parameters. A key parameter of our model framework is the social apportioning parameter, δ, which determines the credit a customer receives by influencing other potential adopters. We develop an endogenous method for determining δ as a function of the new product diffusion parameters. Our model framework allows us to investigate how a firm might accelerate product purchases by providing introductory discount offers to a targeted group of potential adopters at product launch. We find that purchase acceleration frequently leads to a significant increase in total customer value.