bluuebunny/crossref_metadata_2025 huggingface dataset:
The Resources of Ambiguity
Authors: Journet Debra
Published: September 2009

Richard Dawkins’s The Selfish Gene illustrates the power of ambiguity in scientific discourse. The rhetorical and epistemic resources that ambiguity provide are most apparent at the level of metaphor but are also central to the exigency for Dawkins’s argument and to the narrative form that the argument takes. Using ratios derived from Burke’s dramatistic pentad, I analyze how ambiguous language helped Dawkins to link different theoretical conceptions of the gene and consequently posit connections between genes and organisms that had not yet been empirically established. I thus demonstrate at a conceptual and textual level how ambiguity contributes to the construction of novel scientific arguments. For Dawkins, ambiguity provided a discursive space in which he could speculate on connections and developments for which he did not yet have evidence, data, or terminology. Despite his insistence that his use of figurative motive language was simply a ‘‘convenient shorthand’’ for more technical language, The Selfish Gene demonstrates the powerful epistemological and rhetorical role that ambiguous metaphors play in biological discourse.
The Ethic of Exigence
Authors: Ward Mark
Published: September 2009

Compared to ethics in technical writing, ethics in design has received less attention. This lack of attention grows more apparent as document design becomes ‘‘information design.’’ Since Katz discerned an ‘‘ethic of expediency’’ in Nazi technical writing, scholars have often framed technical communication ethics in categorical terms. Yet analyses of information design must consider why arrangements of text and graphics have symbolic potency for given cultures. An ‘‘ethic of exigence’’ can be seen in an example of Nazi information design, a 1935 racial-education poster that illustrates how designers and users co-constructed a communally validated meaning. This example supports the postmodern view that ethics must account for naturalized authority as well as individual actions.
Convergence in the Rhetorical Pattern of Directness and Indirectness in Chinese and U.S. Business Letters
Authors: Wang Junhua
Published: September 2009

This article examines rhetorical patterns in claim letters from two universities, one in China and one in the United States, to see whether these patterns are convergent. A genre-based textual analysis of the claim letters, written by two different cultural groups of participants, found that both groups of letters display a similar rhetorical preference for directness and indirectness. The author explores how local contextual factors have contributed to these groups of participants’ preference for similar rhetorical patterns and calls for the integration of contextual factors in intercultural rhetoric research, practice, and pedagogy.
Relaxation Theorem and Lower-Dimensional Models in Micropolar Elasticity
Authors: Velčić Igor , Tambača Josip
Published: September 2009

In this paper we prove the relaxation theorem in micropolar elasticity and use it, together with the semicontinuity theorem, to justify lower-dimensional models of rods (and plates) by means of Γ-convergence starting from general energy functionals. The internal energy density is assumed to be continuous and satisfies some growth and coercivity conditions. In particular, we apply these results to derive a rod model starting from quadratic isotropic energy density function of a cylindrical three-dimensional micropolar body.
Variational Formulation of Crack Problems in Three-dimensional Classical Elasticity
Authors: Atroshchenko E. , Potapenko S. , Chudinovich I. , Glinka G.
Published: September 2009

In this paper we consider a crack of arbitrary shape in a homogeneous elastic media in the absence of body forces, formulate variational Dirichlet and Neumann crack problems in a linear three-dimensional elasticity in Sobolev spaces and prove the existence and uniqueness of the corresponding (weak) solutions.
A Note on Limit Analysis
Authors: Segev Reuven , Falach Lior
Published: September 2009

We present a mathematical framework for the theory of limit analysis of rigid, perfectly plastic bodies where the equality of the static multiplier and kinematic multiplier for incompressible fields is formulated and proved in a compact form. Assuming that the failure criterion is a norm on the space of deviatoric stress fields, we use standard properties of linear operators on Banach spaces.
Blurred Constitutive Laws and Bipotential Convex Covers
Authors: de Saxcé Géry , Buliga Marius , Vallée Claude
Published: September 2009

In many practical situations, uncertainties affect the mechanical behavior that is given by a family of graphs instead of a single graph. In this paper, we show how the bipotential method is able to capture such blurred constitutive laws, using bipotential convex covers.
Finite Deformations and Motions of a Pre-stressed Incompressible Elastic Tube
Authors: Carroll M.M.
Published: September 2009

Rivlin’s exact solution for finite bending of a rectangular block of incompressible isotropic elastic material into a circular cylindrical sector is specialized to the case of complete bending, in which two ends of the block are brought together. These ends may be glued together to form a circular cylindrical tube without introducing any stress discontinuity. Several boundary value problems that admit exact solutions, radial inflation or compaction, eversion, steady rotation, radial oscillation, torsion, azimuthal shearing and telescopic shearing, for a natural (unstressed) tube admit similar exact solutions for the pre-stressed tube. Except for the last two shearing deformations, these solutions for both the natural tube and the pre-stressed tube are independent of the strain energy. The availability of similar exact solutions for a naturally circular tube and for a pre-stressed tube that was originally a rectangular block should provide useful information about the effects of pre-stress on non-linearly elastic response.
Disseminating Chronic Disease Prevention “to or With” Canadian Public Health Systems
Authors: Masuda Jeffrey R. , Robinson Kerry , Elliott Susan , Eyles John
Published: September 2009

This article follows a conceptual article published in this journal by Elliott et al. and provides an empirical evaluation of the Canadian Heart Health Initiative—Dissemination Phase. Between 1994 and 2005, seven provincial research teams of the Canadian Heart Health Initiative—Dissemination Phase undertook projects to disseminate and evaluate the uptake of evidence-based chronic disease prevention strategies in their respective health systems. In this study, the authors draw from document and stakeholder interview analyses to assess the influence of strategic decisions about dissemination objects, targets, activities, and relationships between knowledge producers and users on the outcomes of chronic disease prevention programming. The findings show that successful dissemination strategies are not necessarily contingent on a high level of fidelity across these dimensions but depend more on the extent to which they are responsive to contextual variables within highly dynamic health systems.
Promoting Elementary Physical Education: Results of a School-Based Evaluation Study
Authors: Boyle-Holmes Trina , Grost Lisa , Russell Lisa , Laris B.A. , Robin Leah , Haller Elizabeth , Potter Susan , Lee Sarah
Published: September 2009

Using a quasiexperimental design, the authors examine whether fourth- and fifth-grade students exposed to a developmental physical education (PE) curriculum, Michigan’s Exemplary Physical Education Curriculum (EPEC), demonstrated stronger motor skill—specific self-efficacy and perceptions of physical activity competence, physical activity levels, motor skills, and physical fitness than did students exposed to existing PE curricula. The authors conducted a multilevel regression analysis with data from 1,464 students in the fourth and fifth grades. Data were collected using a student survey, an activity checklist, and motor and fitness assessments. Compared to students receiving standard PE, students exposed to EPEC showed significantly stronger results in motor skills but not fitness outcomes. The authors found significant positive intervention effects on indicators of motor skill self-efficacy and physical activity levels among the fourth-grade cohort. EPEC was more effective than standard PE curricula at improving motor skill performance (fourth- and fifth-grade cohorts) and at increasing self-reported motor skill-specific self-efficacy and physical activity (fourth-grade cohort).
The Efficiency Loss of Capital Income Taxation under Imperfect Loss Offset Provisions
Authors: Ahsan Syed M. , Tsigaris Panagiotis
Published: September 2009

The importance of capital loss offset provisions in a world of risk is well documented in the tax literature. However, the potential deadweight losses owing to imperfect offset has not been fully explored. This article develops a framework, whereby that investigation can be carried out, and uses numerical simulations to investigate the size of potential losses. The results obtained show that welfare losses owing to the absence of offset provisions could be substantial. Under plausible assumptions about attitudes toward risk and time preference, and with a capital income tax rate of 35 percent, over forty-five cents per dollar of tax revenue raised may be dissipated. In contrast, full loss offset may reduce that loss to approximately twelve cents.
The Application Perspective: Seeking Productivity and Performance
Authors: Barkai David
Published: September 2009

In this note we propose two projects: (1) creating a hierarchical programming model from current models; and (2) extracting application primitives from the “13 dwarfs”. The first topic addresses the need for a unified and manageable framework for very large-scale concurrent execution. This is the productivity part: less complexity will drive better mapping of algorithms to architecture, which will also contribute to better performance. The second topic focuses mostly on the processor and the node with the aim of laying the groundwork for software and silicon optimized kernels. While it is understood that applications primitives are outside the scope of IESP, the motivation for introducing it here is that it is a companion issue and that increasing the efficiency of each processor provides high return for science, at all levels of system size.
Programming Models at Exascale: Adaptive Runtime Systems, Incomplete Simple Languages, and Interoperability
Authors: Kale Laxmikant
Published: September 2009

Applications running on exascale machines will be complex in many ways. They will involve dynamic and adaptive refinements, and will be composed of multiple, independently developed modules, often involving a multiphysics simulation. The programming models of this era must have several characteristics. First, they need to do away with the notion of processors, and automate resource management via adaptive runtime systems. Data structure-specific frameworks and domain-specific environments will be needed to further simplify programming. More importantly, parallel mini-languages need to be developed, such that each language captures only a restricted subset of possible parallel interactions, but allows for a simple expression of them. Coupled with interoperability and parallel composition, which must be supported in many ways, including message-driven runtime systems, this will create a productive ecosystem of parallel programming models for the exascale era.
Early Application Development/Tuning and Application Characterization/ Segmentation
Authors: Kale Laxmikant
Published: September 2009

This position paper makes two separate, only tangentially related points:

1. A research program is necessary to produce tools and techniques that allow application developers to develop and tune applications for future exascale machines, well before the machines are deployed.

2. In order to cope with, or facilitate, segmentation of exascale architectures, it is necessary to carry out an extensive study characterizing the needs and behaviors of applications that are expected to run on exascale machines.
Exercise Prescription for the Prevention and Management of Hypertension
Authors: Goodwin Kimberly A. , Headley Samuel A. E. , Pescatello Linda S.
Published: September 2009

Regular physical activity is known to reduce blood pressure in 75% of individuals with hypertension and is a key component of lifestyle therapy for the prevention and management of hypertension. However, the frequency, intensity, duration, and mode of activity play a role in the magnitude and duration of blood pressure reduction. Aerobic activity is the preferred type of activity to lower blood pressure. Acute, moderate-intensity aerobic activity (40%-60% VO2max ) can decrease blood pressure by 5 to 7 mm Hg for up to 22 hours postexercise, so participation in aerobic activity is recommended on most, if not all, days of the week. The recommended duration for aerobic activity is 30 to 60 minutes of continuous or intermittent activity. Resistance activity results in a 3-mm Hg decrease in blood pressure and should supplement the aerobic activity. Low- to moderate-intensity resistance training (30%-40% of a 1—repetition maximum [1RM] for upper body exercises and 50%-60% 1RM for lower body exercises) is recommended 2 to 3 d/wk. The volume of resistance training for blood pressure reduction is 1 to 3 sets of 10 to 15 repetitions for 8 to 10 exercises that target large muscle groups (thighs, hips, back, chest, arms, and abdominals). When prescribing physical activity for the prevention or management of hypertension, it is important to know that certain populations respond differently to activity and that certain medications can inhibit physical performance.
When It Comes to Managing Blood Pressure, Don’t Overlook the Importance of Salt
Authors: Gerweck Catherine , Curran Celentano Joanne
Published: September 2009

Controlling blood pressure is complex and influenced by a variety of physiologic, dietary, and environmental factors. Dietary salt, or more specifically sodium chloride (NaCl), is an important effector of blood pressure regulation. In our current food environment, we are ingesting an amount of salt that is far above recommendations. A major issue in salt consumption is that much of it is involuntary and attributed to the increase in the consumption of packaged, processed, and restaurant foods. Although there is still debate regarding the role of sodium in the development of hypertension for all individuals, reducing the use of salt is warranted to decrease the risk for cardiovascular disease and stroke. It is important for individuals to take personal action, but it is equally essential that the food industry reduce the salt content of food so that consumers can have more control over their health.
Sonographic Diagnosis of Caudal Regression Syndrome
Authors: Diawara Fousseyni , Camara Magan , Thera Moussa , Diallo Mahamadou , Traore Mamadou
Published: September 2009

Caudal regression syndrome is a partial or complete agenesis of the lumbosacral vertebrae. Other abnormalities may be associated, such as polyhydramnios, single umbilical artery, club feet, and renal, gastrointestinal, and genitourinary defects. This report of caudal regression syndrome is about a woman in her mid-20s who was first seen for a routine obstetrical sonogram in her second trimester. Her last menstrual period was unknown. She had no history of diabetes, and her glycemia was normal. Sonographic examination showed a 27-week singleton fetus with polyhydramnios, club feet, multicystic kidneys, sudden termination of the spine at the sacral level, short femurs, a single umbilical artery, and a cystic umbilical cord with excessive Wharton’s jelly. These findings confirmed the diagnosis of caudal regression syndrome. After counseling, the patient elected for termination of the pregnancy and delivered a female fetus with an imperforate anus at 800 grams in weight. Anteroposterior and lateral radiographs of the fetus confirmed the sacral agenesis.
The role of B cells in the pathogenesis of graft-versus-host disease
Authors: Shimabukuro-Vornhagen Alexander , Hallek Michael J. , Storb Rainer F. , von Bergwelt-Baildon Michael S.
Published: September 2009

Allogeneic hematopoietic stem cell transplantation is an established treatment modality for malignant and nonmalignant hematologic diseases. Acute and chronic graft-versus-host diseases (GVHDs) are a major cause of morbidity and mortality after allogeneic stem cell transplantation. T cells have been identified as key players in the graft-versus-host reaction and, therefore, most established drugs used against GVHD target T cells. Despite our knowledge on the pathogenesis of the GVH reaction, success of established therapies for prevention and treatment of GHVD is unsatisfactory. Recently, animal and human studies demonstrated that B cells are involved in the immunopathophysiology of acute and chronic GVHD. Early phase clinical trials of B-cell depletion with rituximab have shown beneficial effects on both acute and chronic GVHD. This review summarizes the current experimental and clinical evidence for the involvement of B cells in the pathogenesis of acute and chronic GVHD and discusses the clinical implications for the management of patients undergoing allogeneic stem cell transplantation.
miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221
Authors: Kotani Ai , Ha Daon , Hsieh James , Rao Prakash K. , Schotte Diana , den Boer Monique L. , Armstrong Scott A. , Lodish Harvey F.
Published: September 2009

MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.
Spatial gradients of blood vessels and hematopoietic stem and progenitor cells within the marrow cavities of the human skeleton
Authors: Bourke Vincent A. , Watchman Christopher J. , Reith John D. , Jorgensen Marda L. , Dieudonnè Arnaud , Bolch Wesley E.
Published: September 2009

This report evaluates the spatial profile of blood vessel fragments (BVFs) and CD34+ and CD117+ hematopoietic stem and progenitor cells (HSPCs) in human cancellous bone. Bone specimens were sectioned, immunostained (anti-CD34 and anti-CD117), and digitally imaged. Immunoreactive cells and vessels were then optically and morphometrically identified and labeled on the corresponding digital image. The distance of each BVF, or CD34+ or CD117+ HSPC to the nearest trabecular surface was measured and binned in 50-μm increments. The relative concentration of HSPCs and BVFs within cancellous marrow was observed to diminish with increasing distance in the marrow space. On average, 50% of the CD34+ HSPC population, 60% of the CD117+ HSPC population, and 72% of the BVFs were found within 100 μm of the bone surfaces. HSPCs were also found to exist in close proximity to BVFs, which supports the notion of a shared HSPC and vessel spatial niche.
Vaccine site inflammation potentiates idiotype DNA vaccine-induced therapeutic T cell–, and not B cell–, dependent antilymphoma immunity
Authors: Qin Hong , Cha Soung-chul , Neelapu Sattva S. , Lou Yanyan , Wei Jinsong , Liu Yong-Jun , Kwak Larry W.
Published: September 2009

Lymphoma idiotype protein vaccines have shown therapeutic potential in previous clinical studies, and results from a completed pivotal, phase 3 controlled trial are promising. However, streamlined production of these patient-specific vaccines is required for eventual clinical application. Here, we show that second-generation, chemokine-fused idiotype DNA vaccines, when combined with myotoxins that induced sterile inflammation with recruitment of antigen-presenting cells at vaccination sites, were exceptional in their ability to provoke memory antitumor immunity in mice, compared with several TLR agonists. The combined vaccination strategy elicited both antigen-specific T-cell responses and humoral immunity. Unexpectedly, vaccine-induced tumor protection was intact in B cell–deficient mice but was abrogated completely by T-cell depletion in vivo, suggesting T-cell dependence. Furthermore, the optimal effect of myotoxins was observed with fusion vaccines that specifically targeted antigen delivery to antigen-presenting cells and not with vaccines lacking a targeting moiety, suggesting that the rational vaccine design will require combination strategies with novel, proinflammatory agents and highly optimized molecular vaccine constructs. These studies also challenge the paradigm that antibody responses are the primary of idiotype-specific antitumor effects and support the optimization of idiotype vaccines designed to induce primarily T-cell immunity.
Uptake of CCR7 and acquisition of migratory properties by human KIR+ NK cells interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA-class I interaction
Authors: Marcenaro Emanuela , Cantoni Claudia , Pesce Silvia , Prato Carola , Pende Daniela , Agaugué Sophie , Moretta Lorenzo , Moretta Alessandro
Published: September 2009

C-C chemokine receptor type 7 (CCR7) is a chemokine receptor playing a pivotal role in the induction of human natural killer (NK)–cell migration to lymph nodes. We show that “licensed” peripheral blood killer immunoglobulin-like receptor–positive (KIR+) NK-cell populations, as well as KIR+ NK-cell clones, de novo express CCR7 upon coculture with mature dendritic cells (mDCs) or Epstein-Barr virus (EBV)–transformed lymphoblastoid cell lines. As a consequence, they become capable of migrating in response to the CCR7-specific chemokines C-C chemokine ligand (CCL)–19 and/or CCL21. The acquisition of CCR7 by NK cells requires direct cell-to-cell contact, is detectable within a few minutes, and is due to receptor uptake from CCR7+ cells. This mechanism is tightly regulated by KIR-mediated recognition of human leukocyte antigen (HLA) class I as well as by adhesion molecules including leukocyte function-associated antigen 1 (LFA-1) and CD2. Analysis of NK-cell clones revealed that alloreactive (KIR-ligand mismatched) but not autologous NK cells acquire CCR7. These data have important implications in haploidentical hematopoietic stem cell transplantation (HSCT), in which alloreactive NK cells may acquire the ability to migrate to secondary lymphoid compartments (SLCs), where they can kill recipient antigen-presenting cells (APCs) and T cells thus preventing graft-versus-host (and host-versus-graft) reactions.
Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma
Authors: Pu Yeong-Shiau , Huang Chao-Yuan , Kuo Yi-Zih , Kang Wang-Yi , Liu Guang-Yaw , Huang A-Mei , Yu Hong-Jeng , Lai Ming-Kuen , Huang Shu-Pin , Wu Wen-Jeng , Chiou Shean-Jaw , Hour Tzyh-Chyuan
Published: September 2009

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells × staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis.
Improving power in genetic-association studies via wavelet transformation
Authors: Jiang Renfang , Dong Jianping , Dai Yilin
Published: September 2009

Background

A key to increasing the power of multilocus association tests is to reduce the number of degrees of freedom by suppressing noise from data. One of the difficulties is to decide how much noise to suppress. An often overlooked problem is that commonly used association tests based on genotype data cannot utilize the genetic information contained in spatial ordering of SNPs (see proof in the Appendix), which may prevent them from achieving higher power.

Results

We develop a score test based on wavelet transform with empirical Bayesian thresholding. Extensive simulation studies are carried out under various LD structures as well as using HapMap data from many different chromosomes for both qualitative and quantitative traits. Simulation results show that the proposed test automatically adjusts the level of noise suppression according to LD structures, and it is able to consistently achieve higher or similar powers than many commonly used association tests including the principle component regression method (PCReg).

Conclusion

The wavelet-based score test automatically suppresses the right amount of noise and uses the information contained in spatial ordering of SNPs to achieve higher power.
Gene-based microsatellites for cassava (Manihot esculentaCrantz): prevalence, polymorphisms, and cross-taxa utility
Authors: Raji Adebola AJ , Anderson James V , Kolade Olufisayo A , Ugwu Chike D , Dixon Alfred GO , Ingelbrecht Ivan L
Published: September 2009

Background

Cassava (Manihot esculentaCrantz), a starchy root crop grown in tropical and subtropical climates, is the sixth most important crop in the world after wheat, rice, maize, potato and barley. The repertoire of simple sequence repeat (SSR) markers for cassava is limited and warrants a need for a larger number of polymorphic SSRs for germplasm characterization and breeding applications.

Results

A total of 846 putative microsatellites were identifiedin silicofrom an 8,577 cassava unigene set with an average density of one SSR every 7 kb. One hundred and ninety-two candidate SSRs were screened for polymorphism among a panel of cassava cultivars from Africa, Latin America and Asia, four wildManihotspecies as well as two other important taxa in the Euphorbiaceae, leafy spurge (Euphorbia esula) and castor bean (Ricinus communis). Of 168 markers with clean amplification products, 124 (73.8%) displayed polymorphism based on high resolution agarose gels. Of 85 EST-SSR markers screened, 80 (94.1%) amplified alleles from one or more wild species (M epruinosa, M glaziovii,M brachyandra,M tripartita) whereas 13 (15.3%) amplified alleles from castor bean and 9 (10.6%) amplified alleles from leafy spurge; hence nearly all markers were transferable to wild relatives ofM esculentawhile only a fraction was transferable to the more distantly related taxa. In a subset of 20 EST-SSRs assessed by fluorescence-based genotyping the number of alleles per locus ranged from 2 to 10 with an average of 4.55 per locus. These markers had a polymorphism information content (PIC) from 0.19 to 0.75 with an average value of 0.55 and showed genetic relationships consistent with existing information on these genotypes.

Conclusion

A set of 124 new, unique polymorphic EST-SSRs was developed and characterized which extends the repertoire of SSR markers for cultivated cassava and its wild relatives. The markers show high PIC values and therefore will be useful for cultivar identification, taxonomic studies, and genetic mapping. The study further shows that mining ESTs is a highly efficient strategy for polymorphism detection within the cultivated cassava gene pool.
Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family
Authors: Sanga Sandeep , Broom Bradley M , Cristini Vittorio , Edgerton Mary E
Published: September 2009

Background

Pathway discovery from gene expression data can provide important insight into the relationship between signaling networks and cancer biology. Oncogenic signaling pathways are commonly inferred by comparison with signatures derived from cell lines. We use the Molecular Apocrine subtype of breast cancer to demonstrate our ability to infer pathways directly from patients' gene expression data with pattern analysis algorithms.

Methods

We combine data from two studies that propose the existence of the Molecular Apocrine phenotype. We use quantile normalization and XPN to minimize institutional bias in the data. We use hierarchical clustering, principal components analysis, and comparison of gene signatures derived from Significance Analysis of Microarrays to establish the existence of the Molecular Apocrine subtype and the equivalence of its molecular phenotype across both institutions. Statistical significance was computed using the Fasano & Franceschini test for separation of principal components and the hypergeometric probability formula for significance of overlap in gene signatures. We perform pathway analysis using LeFEminer and Backward Chaining Rule Induction to identify a signaling network that differentiates the subset. We identify a larger cohort of samples in the public domain, and use Gene Shaving and Robust Bayesian Network Analysis to detect pathways that interact with the defining signal.

Results

We demonstrate that the two separately introduced ER- breast cancer subsets represent the same tumor type, called Molecular Apocrine breast cancer. LeFEminer and Backward Chaining Rule Induction support a role for AR signaling as a pathway that differentiates this subset from others. Gene Shaving and Robust Bayesian Network Analysis detect interactions between the AR pathway, EGFR trafficking signals, and ErbB2.

Conclusion

We propose criteria for meta-analysis that are able to demonstrate statistical significance in establishing molecular equivalence of subsets across institutions. Data mining strategies used here provide an alternative method to comparison with cell lines for discovering seminal pathways and interactions between signaling networks. Analysis of Molecular Apocrine breast cancer implies that therapies targeting AR might be hampered if interactions with ErbB family members are not addressed.
Decreased PPARγ Expression Compromises Perigonadal-Specific Fat Deposition and Insulin Sensitivity
Authors: Tsai Yau-Sheng , Tsai Pei-Jane , Jiang Man-Jin , Chou Ting-Yu , Pendse Avani , Kim Hyung-Suk , Maeda Nobuyo
Published: September 2009

Mutations and polymorphisms in PPARG have been linked to adiposity and partial lipodystrophy in humans. However, how disturbances in PPARG lead to depot-specific effects on adipose tissue, as shown by the characteristic aberrant fat distribution in patients, remains unclear. By manipulating the 3′-untranslated region of the Pparg gene, we have generated mice with peroxisome proliferator-activated receptor γ (PPARγ) gene expression ranging from 25% to 100% normal. Basal levels of PPARγ transcripts between 50% and approximately 100% had no significant effect on body weight, fat mass, and insulin sensitivity. In contrast, mice with 25% normal PPARγ expression exhibited reduced body weight and total fat mass, insulin resistance, and dyslipidemia. Interestingly, fat mass was selectively reduced in perigonadal depot without significant changes in inguinal and other depots. Expression of adipogenic factor CCAAT enhancer binding protein-α and some other metabolic genes containing peroxisome proliferator response element were reduced in a perigonadal depot-specific fashion. This was further associated with depot-specific reduction in the expression of adipokines, increased expression of TNFα, and increased ectopic lipid deposition in muscles. Together, these results underscore the differential sensitivity of the individual fat depots on PPARγ availability as an underlying mechanism of partial lipodystrophy.
Effects of physical interference on life history shifts in Daphnia pulex
Authors: Ban Syuhei , Tenma Hideaki , Mori Tsukasa , Nishimura Kinya
Published: September 2009

Daphnia pulex were reared in 50 ml flasks, each containing 1, 20 or 40 individuals, which were serially connected with a 20-μm mesh screens between, in order to examine the effect of physical interference due to crowding on shifts of life history traits throughout two consecutive generations. A flow-through system, designed to maintain a sufficient food supply and minimize the accumulation of metabolites, was used. To eliminate the effect of infochemicals from crowded animals, a single-individual treatment flask was connected to two crowded flasks. In the first generation, D. pulex reared under crowded conditions grew more slowly after day 4 when oogenesis normally starts, and produced less offspring after day 9,compared with an animal reared alone, even when supplied with sufficient food. Although second generation daphniids of each treatment matured faster than in the first generation, crowded females grew more slowly even after day 2 and produced less offspring than single females. Age to maturity was no different between treatments in both generations. Crowded females, therefore, matured to smaller sizes but produced larger neonates compared with single females. Weight-specific reproduction rates of the first clutch were not significantly different between the treatments. These results suggest that physical interference between neighboring individuals due to crowding negatively affects growth and reproduction in daphniids. Crowded daphniids may allocate more energy to reproduction in order to produce larger and more starvation-tolerant offspring in preparation for severe food shortages. Crowding also triggered ephippial egg production and reduced survival compared with the single-individual treatment.
Determination of material properties in the Chaboche unified viscoplasticity model
Authors: Gong Y P , Hyde C J , Sun W , Hyde T H
Published: September 2009

An experimental programme of cyclic mechanical testing of a 316 stainless steel, at temperatures up to 600°C, under isothermal conditions, for the identification of material constitutive constants, has been carried out using a thermo-mechanical fatigue (TMF) test machine with induction coil heating. The constitutive model adopted is a modified Chaboche unified viscoplasticity model, which can deal with both cyclic effects, such as combined isotropic and kinematic hardening, and rate-dependent effects, associated with viscoplasticity. The characterization of 316 stainless steel is presented and compared with results from cyclic isothermal tests. A least-squares optimization algorithm has been developed and implemented for determining the material constants in order to further improve the general fit of the model to experimental data, using the initially obtained material constants as the starting point in this optimization process. The model predictions using both the initial and optimized material constants are compared to experimental data.
Bayesian Simulation and Decision Analysis: An Expository Survey
Authors: Merrick Jason R. W.
Published: September 2009

The aim of this expository survey on Bayesian simulation is to stimulate more work in the area by decision analysts. We discuss the main areas of research performed thus far, including input analysis, propagation and estimation of output uncertainty, output analysis, making decisions with simulations, selecting the best simulated system, and applications of Bayesian simulation methods. Throughout, we offer avenues of future research in Bayesian simulation that may be of interest to decision analysts.
Swift and Smart: The Moderating Effects of Technological Capabilities on the Market Pioneering–Firm Survival Relationship
Authors: Franco April M. , Sarkar MB , Agarwal Rajshree , Echambadi Raj
Published: September 2009

We extend the concept of first-mover advantage to the context of high-technology industries with multiple product generations, and propose that the notion of first-mover advantage needs to be viewed not only through a dynamic lens, but also in conjunction with technological capability. Our main finding is that first-mover advantages are best understood in tandem with the firm's technological capabilities; early entry is beneficial only for pioneers that are technically strong. However, pioneers that are low on technological capabilities suffer from poor survival rates vis-à-vis market responders or nonentrants into new product generations.
Volatility Spreads and Expected Stock Returns
Authors: Bali Turan G. , Hovakimian Armen
Published: September 2009

This paper investigates whether realized and implied volatilities of individual stocks can predict the cross-sectional variation in expected returns. Although the levels of volatilities from the physical and risk-neutral distributions cannot predict future returns, there is a significant relation between volatility spreads and expected stock returns. Portfolio level analyses and firm-level cross-sectional regressions indicate a negative and significant relation between expected returns and the realized-implied volatility spread that can be viewed as a proxy for volatility risk. The results also provide evidence for a significantly positive link between expected returns and the call-put options' implied volatility spread that can be considered as a proxy for jump risk. The parameter estimates from the VAR-bivariate-GARCH model indicate significant information flow from individual equity options to individual stocks, implying informed trading in options by investors with private information.
Implications of Expected Changes in the Seller's Price in Name-Your-Own-Price Auctions
Authors: Fay Scott , Laran Juliano
Published: September 2009

The seller's threshold price in name-your-own-price auctions varies over time. However, consumers must bid without knowing when these variations occur because the threshold price is unobservable to them. This paper uses an analytical model and laboratory auctions to explore how the frequency of changes in the threshold price impacts consumer bidding behavior in name-your-own-price auctions. In particular, we consider how the frequency of these expected changes affects the optimal pattern of bid sequences (e.g., strictly increasing over time or following a nonmonotonic pattern). We find that when the probability of a price change is moderate, consumers may have an incentive to use nonmonotonic bidding patterns. Rather than steadily increasing their bids over time, consumers will, at some point in the bid sequence, decrease their bid. However, when the expected probability of a price change is very low or very high, consumers do not have an incentive to use nonmonotonic bidding patterns. Interestingly, impatient bidders are more likely to decrease their bids at some point in the bid sequence than patient bidders. Finally, we find that more frequent price changes may increase customer satisfaction.
The Shape and Term Structure of the Index Option Smirk: Why Multifactor Stochastic Volatility Models Work So Well
Authors: Christoffersen Peter , Heston Steven , Jacobs Kris
Published: September 2009

State-of-the-art stochastic volatility models generate a “volatility smirk” that explains why out-of-the-money index puts have high prices relative to the Black-Scholes benchmark. These models also adequately explain how the volatility smirk moves up and down in response to changes in risk. However, the data indicate that the slope and the level of the smirk fluctuate largely independently. Although single-factor stochastic volatility models can capture the slope of the smirk, they cannot explain such largely independent fluctuations in its level and slope over time. We propose to model these movements using a two-factor stochastic volatility model. Because the factors have distinct correlations with market returns, and because the weights of the factors vary over time, the model generates stochastic correlation between volatility and stock returns. Besides providing more flexible modeling of the time variation in the smirk, the model also provides more flexible modeling of the volatility term structure. Our empirical results indicate that the model improves on the benchmark Heston stochastic volatility model by 24% in-sample and 23% out-of-sample. The better fit results from improvements in the modeling of the term structure dimension as well as the moneyness dimension.
Composition of Electricity Generation Portfolios, Pivotal Dynamics, and Market Prices
Authors: Banal-Estañol Albert , Micola Augusto Rupérez
Published: September 2009

We use simulations to study how the diversification of electricity generation portfolios influences wholesale prices. We find that the relationship between technological diversification and market prices is mediated by the supply-to-demand ratio. In each demand case there is a threshold where pivotal dynamics change. Pivotal dynamics pre- and post-threshold are the cause of nonlinearities in the influence of diversification on market prices. The findings are robust to changes in the main market assumptions.
Valuing Modularity as a Real Option
Authors: Gamba Andrea , Fusari Nicola
Published: September 2009

We provide a general valuation approach for capital budgeting decisions involving the modularization in the design of a system. Within the framework developed by Baldwin and Clark (Baldwin, C. Y., K. B. Clark. 2000. Design Rules: The Power of Modularity. MIT Press, Cambridge, MA), we implement a valuation approach using a numerical procedure based on the least-squares Monte Carlo method proposed by Longstaff and Schwartz (Longstaff, F. A., E. S. Schwartz. 2001. Valuing American options by simulation: A simple least-squares approach. Rev. Financial Stud. 14(1) 113–147). The approach is accurate, general, and flexible.
Women, Gender, and Politics in the New Deal Government: Josephine Roche and the Federal Security Agency
Authors: Muncy Robyn
Published: September 2009

In 1939, newspapers predicted that U.S. President Franklin Delano Roosevelt would appoint Josephine Roche to head his new Federal Security Agency. But Roche did not get the job. This article asks why. It argues that gender played a role in her failure of appointment but that her political ideals and associations were more significant. Analysis of the episode illuminates and challenges the transnational practice of personalizing women's political conflict and suggests a new understanding of women's political networks. Instead of the self-contained and unified female network that historians have identified as so important to shaping the U.S. welfare state in the 1930s, Roche's networks were many and sometimes at odds. Indeed, to comprehend women's politics in 1930s America, postwar Europe, or contemporary Africa, we need to imagine women as full participants in multiple, loosely connected and intersecting political networks, not all of which were exclusively female.
Othello at the Market Theatre
Authors: Seeff Adele
Published: September 2009

This article discusses the cultural work performed by Janet Suzman's 1987 production of  Othello  at the Market Theatre in Johannesburg: the first production to breach South Africa's colour-bar in casting black South African actor John Kani in the title role. Through an incorporation of reviews, a close reading of the playtexts, performance and reception history, literary criticism, and an awareness of the South African political and cultural context, the study situates Suzman's production in its specific historical moment, as well as considering its broader history in order to determine what it is about the production that merits the labels of 'radical' and 'ground-breaking' affixed to it by critics. In doing so, it shifts the focus from the production's multiracial casting and onto its treatment of women within the context of racial politics, positioning the white Desdemona's desire for the black Othello - arguably also present in Shakespeare's text - as the truly radical aspect of Suzman's production, in which racial difference is presented as the source of sexual power: a concept which finds parallels in the exchanges between Iago and Emilia and Roderigo and Bianca. The discussion of this neglected aspect of Suzman's radical production emphasizes the impact of social change on any production as well as on the reception of a black actor performing Othello: a performance which, in the case of Suzman's production, invites audiences to recognise the patriarchal societal forces which construct racism and oppression.
Cold War in the Countryside: Conflict in Guerrero, Mexico
Authors: Blacker O'Neill
Published: September 2009

“Our struggle has its inspirational roots in [our] national history and reality: our flag . . . is the same raised by Hidalgo, Morelos and Guerrero, Juarez, Zapata and Villa.”

Genaro Vazquez Rojas, La Asociacion Civica Nacional Revolucionaria, 1968
The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver
Authors: Bock Karl Walter , Köhle Christoph
Published: September 2009

The mammalian Ah receptor (AhR) is a ligand-activated transcription factor with multiple functions in adaptive metabolism, development and dioxin toxicity in a variety of organs and cell systems. Phenotypes observed following sustained activation by dioxin or in AhR-null mice suggest organ-dependent physiological functions. These functions are probably deregulated following exposure to dioxin. We focus on skin and liver to facilitate discussion of mechanisms linking phenotypes and AhR-modulated genotypes. After a brief summary of currently discussed AhR ligand candidates, two groups of direct AhR target genes/proteins and associated functions are highlighted: (i) xenobiotic-metabolizing enzymes which are also involved in homeostasis of endogenous ligands and (ii) proteins controlling cell proliferation/apoptosis, differentiation and inflammation. Homeostatic feedback loops might not only include CYP1A1 but also Phase II enzymes such as UGT1A1 which controls the antioxidant AhR ligand bilirubin. The AhR is involved in extensive crosstalk with other transcription factors and multiple signaling pathways. Efforts elucidating the pathway toward identification of physiological functions of the AhR remain challenging and promising.