bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fingerprint of Cell Metabolism in the Experimentally Observed Interstitial pH and pO2 in Solid Tumors
Authors: Molavian Hamid R. , Kohandel Mohammad , Milosevic Michael , Sivaloganathan Sivabal 
Published: November 2009

Abstract
Understanding cancer cell metabolism and targeting associated pathways is a field of increasing interest. Helmlinger and colleagues measured average pH and pO2 as functions of distance from a single blood vessel on the micrometer scale. We show that these results provide unique insight into cancer cell metabolism in vivo when combined with an appropriate mathematical model. We calculate pH as a function of distance from a single blood vessel and for a given metabolism while incorporating a single CO2 buffer with effective diffusion constants. By assuming that cancer cell metabolism is dominated by respiration with a smaller component of glycolysis in the normoxic state, by more balanced respiration and glycolysis in the hypoxic state, and by glycolysis alone in the anoxic state, we are able to semiquantitatively derive the experimental results of Helmlinger and colleagues. We also apply our model to glycolysis-impaired metabolism and show that the low pH and high pO2 observed in these tumors may be related to the substantial shift from a respiration-dominated metabolism to one in which glutaminolysis dominates. Based on this, we propose an in vivo experimental measurement of pH in a glycolysis-impaired tumor to validate the modeling results. [Cancer Res 2009;69(23):9141–7]
Human rRNA Gene Clusters Are Recombinational Hotspots in Cancer
Authors: Stults Dawn M. , Killen Michael W. , Williamson Erica P. , Hourigan Jon S. , Vargas H. David , Arnold Susanne M. , Moscow Jeffrey A. , Pierce Andrew J. 
Published: November 2009

Abstract
The gene that produces the precursor RNA transcript to the three largest structural rRNA molecules (rDNA) is present in multiple copies and organized into gene clusters. The 10 human rDNA clusters represent &lt;0.5% of the diploid human genome but are critically important for cellular viability. Individual genes within rDNA clusters possess very high levels of sequence identity with respect to each other and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. We recently developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. To prove that this dysregulated recombination is a potential driving force of genomic instability in human cancer, we assayed the rDNA for structural rearrangements in prospectively recruited adult patients with either lung or colorectal cancer, and pediatric patients with leukemia. We find that over half of the adult solid tumors show detectable rDNA rearrangements relative to either surrounding nontumor tissue or normal peripheral blood. In contrast, we find a greatly reduced frequency of rDNA alterations in pediatric leukemia. This finding makes rDNA restructuring one of the most common chromosomal alterations in adult solid tumors, illustrates the dynamic plasticity of the human genome, and may prove to have either prognostic or predictive value in disease progression. [Cancer Res 2009;69(23):9096–104]
Involvement of Mitochondrial DNA Sequence Variations and Respiratory Activity in Late Complications following Radiotherapy
Authors: Alsbeih Ghazi A. , Al-Harbi Najla M. , El-Sebaie Medhat M. , Al-Rajhi Nasser M. , Al-Hadyan Khaled S. , Abu-Amero Khaled K. 
Published: November 2009

Abstract
Purpose: Mitochondria and ionizing radiation overlap in a number of features; for instance, both generate harmful reactive oxygen species, and that radiation can induce cell death through the intermediary of mitochondria. Because a number of genetic variations in nuclear genes are frequently associated with response to cancer treatment, the aim of this case-control study was to test the hypothesis that mitochondrial DNA (mtDNA) genetic variations can contribute to patient-to-patient variability in normal tissue response to radiotherapy.
Experimental Design: Thirty-two nasopharyngeal carcinomas patients treated with definitive radiotherapy were included. The grade (G) of s.c. and deep tissue fibrosis was scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading system. Coding and RNA mtDNA (between 611 and 15,978 bp) were sequenced, and genetic variations were scored. Mitochondrial respiratory activity was measured by resazurin reduction assay.
Results: Data showed a significantly (P = 0.003) higher number of nonsynonymous genetic variations in the radiosensitive (G2-G3; 16 patients) as compared with the control (G0-G1; 16 patients) groups. The nonsynonymous A10398G variation in the ND3 gene was significantly associated with fibrotic reaction (P = 0.01). The radiosensitive patients had a 7-fold (95% confidence interval, 1.16-51.65) higher risk of developing moderate to severe fibrosis (G2-G3) following radiotherapy. This was significantly correlated with lower mitochondrial respiratory activity (P = 0.001).
Conclusion: Mitochondria contribute to radiation sensitivity, and genetic variations can be associated with late reactions to radiotherapy. Predictive markers of radiosensitivity should take into account mtDNA genetic variations in addition to variations in nuclear genes. (Clin Cancer Res 2009;15(23):7352–60)
Loss of HER2 Amplification Following Trastuzumab-Based Neoadjuvant Systemic Therapy and Survival Outcomes
Authors: Mittendorf Elizabeth A. , Wu Yun , Scaltriti Maurizio , Meric-Bernstam Funda , Hunt Kelly K. , Dawood Shaheenah , Esteva Francisco J. , Buzdar Aman U. , Chen Huiqin , Eksambi Sameena , Hortobagyi Gabriel N. , Baselga Jose , Gonzalez-Angulo Ana M. 
Published: November 2009

Abstract
Purpose: To evaluate HER2 status in residual tumor identified at the time of surgery in patients not achieving a pathologic complete response (pCR) and to determine the effect of alterations in HER2 status on recurrence-free survival (RFS).
Experimental Design: Clinicopathologic data for patients with HER2-overexpressing breast cancer receiving neoadjuvant therapy with a taxane, anthracycline, and concomitant trastuzumab between 2004 and 2007 were reviewed. Surgical specimens for patients achieving less than a pCR were assessed to determine if there was enough residual tissue to evaluate posttreatment HER2 status. RFS was determined using the Kaplan-Meier method and compared by the log-rank statistic.
Results: A pCR was achieved in 72 of the 142 (50.7%) patients. Residual tumor was sufficient to assess posttreatment HER2 status in 25 patients. Fluorescence in situ hybridization done on pretreatment specimens confirmed HER2 amplification before beginning therapy. Eight (32.0%) posttreatment tumors were found to be HER2-negative by fluorescence in situ hybridization. At a median follow-up of 37 months (range, 8-56 months), the RFS was significantly better for patients with tumors that retained HER2 amplification (87.5% versus 50%, P = 0.04).
Conclusion: High pCR rates are achieved in patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab in combination with anthracyclines and taxanes. One third of patients with significant residual disease loses HER2 amplification, and this change is associated with poor RFS. Residual tumor identified at the time of surgery should be reassessed for HER2 status, and novel adjuvant therapy strategies need to be studied in this population. (Clin Cancer Res 2009;15(23):7381–8)
Use of OralN-Acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress: Towards a Novel Paradigm for Melanoma Chemoprevention
Authors: Goodson Agnessa Gadeliya , Cotter Murray A. , Cassidy Pamela , Wade Mark , Florell Scott R. , Liu Tong , Boucher Kenneth M. , Grossman Douglas 
Published: November 2009

AbstractPurpose: Induction of oxidative stress has been implicated in UV-induced melanoma. We sought to determine whether the antioxidant N-acetylcysteine (NAC) could be safely administered to protect melanocytic nevi from the oxidative stress resulting from acute UV exposure.Experimental Design: Patients at increased risk for melanoma were recruited from a screening clinic. Induction and detection of oxidative stress (reactive oxygen species and glutathione depletion) was optimized in nevi following ex vivo UV irradiation. Nevi were removed from patients before, and following, oral ingestion of a single (1,200 mg) dose of NAC, and then these nevi were UV irradiated (4,000 J/m2).Results: Oxidative stress was induced in nevi 24 to 48 hours following ex vivo UV irradiation. A single oral dose of NAC was well tolerated in all patients (n = 72). Basal levels of reduced glutathione and the NAC metabolite cysteine were well correlated between similar-appearing nevi from the same patient and were significantly increased in nevi removed 3 hours after NAC ingestion compared with nevi removed before drug ingestion. In approximately half (9 of 19) of patients tested, UV-induced glutathione depletion was attenuated in the postdrug (compared with predrug) nevus.Conclusions: NAC can be safely administered to patients for the purpose of modulating UV-induced oxidative stress in nevi. This study suggests the feasibility of patients taking NAC prophylactically before acute UV exposure, to prevent pro-oncogenic oxidative stress in nevi and ultimately reduce long-term melanoma risk. (Clin Cancer Res 2009;15(23):7434–40)
The Blurring of Distinction: Performance and Jewish Identities in Late Nineteenth-Century Vienna
Authors: Hoedl Klaus 
Published: November 2009

In fin-de-siècle Vienna, Jews constituted about ten percent of the city’s population. They formed a visible community, and some of its members played a major role in Austrian political, cultural and scholarly life. Even if they faced myriad forms of discrimination, Viennese Jews socialized with non-Jews. Such interactions across ethnic and religious boundaries often blurred the lines that separated their respective cultural spheres.
These intimate ties between Jews and other inhabitants of the city raises the question about the circumscription of Jews and the determination of “things Jewish.” Is it possible to differentiate Jews from non-Jews without drawing upon some essentialized notion of Jewishness? What might be the best way to explore the relationship between Jews and society at large? Against the background of Viennese Jewish history, this article will explore how notions of performance might help to write Jewish history and to develop a de-essentialized concept of “things Jewish.”
Foreign vs. Local New Horizons, and Ancient Dilemmas and Strategies?
Authors: Touwaide Alain 
Published: November 2009

AbstractCapitalizing on the data presented in the three papers in this issue, the comments and conclusions here elaborate on the concept of transfer of knowledge in the field of materia medica and pharmacy. They evidence different mechanisms in three contexts, the Holy Roman Empire, the Western world and China, and trace the possible ancient roots of the phenomena under consideration. In so doing, they contextualize the processes under study in the three essays, and suggest also a possible new interpretation of the practice of science from the Late Middle Ages to the Scientific Revolution.
The Clinical and Psychometric Validation of a Questionnaire to Assess the Quality of Life of Adult Patients Treated With Long‐Term Parenteral Nutrition
Authors: Baxter Janet P. , Fayers Peter M. , McKinlay Alastair W. 
Published: November 2009

Background:Home parenteral nutrition (HPN) is an established treatment for the management of patients with chronic intestinal failure. No quality‐of‐life assessment tools have been developed and validated specifically for this patient population, and previous studies have used generic instruments or techniques not validated in HPN. The assessment of quality of life (QOL) should produce clinically relevant data reflecting patients' issues. The HPN‐QOL was designed to assess the QOL of HPN patients. The purpose of this study was to test the hypothesized scale structure of the questionnaire with regard to reliability and validity in a sample of patients.Methods:A provisional questionnaire was prepared following recognized guidelines and then subjected to field testing. The questionnaire was administered to 100 adult patients receiving HPN. Psychometric tests examined the reliability and validity of the questionnaire, and patients' debriefing comments were analyzed.Results:The provisional questionnaire was adapted using evidence from quantitative and qualitative analysis. Multitrait scaling analysis and face validity refined the questionnaire to 48 items. Compliance rates were high, and the questionnaire was well accepted.Conclusions:A method of objectively assessing the QOL of patients treated with HPN has been developed. The HPN‐QOL has been rigorously prepared and demonstrates psychometric and clinical validity to assess the QOL of long‐term HPN patients.
Induction of immune tolerance to FIX by intramuscular AAV gene transfer is independent of the activation status of dendritic cells
Authors: Bharadwaj Arpita S. , Kelly Meagan , Kim Dongsoo , Chao Hengjun 
Published: November 2009

AbstractThe nature of viral vectors is suggested to be a significant contributor to undesirable immune responses subsequent to gene transfer. Such viral vectors, recognized as danger signals by the host immune system, activate dendritic cells (DCs), causing unwanted antivector and/or transgene product immunity. We recently reported efficient induction of immune tolerance to coagulation factor IX (FIX) by direct intramuscular injection of adeno-associated virus (AAV)–FIX. AAV vectors are nonpathogenic and elicit minimal inflammatory response. We hypothesized that the nonpathogenic nature of AAV plays a critical role in induction of tolerance after AAV gene transfer. We observed inefficient recruitment and activation of DCs subsequent to intramuscular injection of AAV. To further validate our hypothesis, we examined immune responses to FIX after intramuscular injection of AAV with simultaneous activation of DCs. We were able to achieve phenotypic and functional activation of DCs after administration of lipopolysaccharide and anti-CD40 antibody. However, we observed efficient induction of FIX tolerance irrespective of DC activation in mice with different genetic and major histocompatibility complex backgrounds. Furthermore, activation of DCs did not exaggerate the immune response induced after intramuscular injection of AAV serotype 2 vector. Our results demonstrate that induction of FIX tolerance after AAV gene transfer is independent of DC activation status.
Different Forms of Glycine- and GABAA-Receptor Mediated Inhibitory Synaptic Transmission in Mouse Superficial and Deep Dorsal Horn Neurons
Authors: Anderson Wayne B , Graham Brett A , Beveridge Natalie J , Tooney Paul A , Brichta Alan M , Callister Robert J 
Published: November 2009

BackgroundNeurons in superficial (SDH) and deep (DDH) laminae of the spinal cord dorsal horn receive sensory information from skin, muscle, joints and viscera. In both regions, glycine-(GlyR) and GABAA-receptors (GABAARs) contribute to fast synaptic inhibition. For rat, several types of GABAAR coexist in the two regions and each receptor type provides different contributions to inhibitory tone. Recent work in mouse has discovered an additional type of GlyR, (containing alpha 3 subunits) in the SDH. The contribution of differing forms of the GlyR to sensory processing in SDH and DDH is not understood.Methods and ResultsHere we compare fast inhibitory synaptic transmission in mouse (P17-37) SDH and DDH using patch-clamp electrophysiology in transverse spinal cord slices (L3-L5 segments, 23°C). GlyR-mediated mIPSCs were detected in 74% (25/34) and 94% (25/27) of SDH and DDH neurons, respectively. In contrast, GABAAR-mediated mIPSCs were detected in virtually all neurons in both regions (93%, 14/15 and 100%, 18/18). Several Gly- and GABAAR properties also differed in SDH vs. DDH. GlyR-mediated mIPSC amplitude was smaller (37.1 ± 3.9 vs. 64.7 ± 5.0 pA; n = 25 each), decay time was slower (8.5 ± 0.8 vs. 5.5 ± 0.3 ms), and frequency was lower (0.15 ± 0.03 vs. 0.72 ± 0.13 Hz) in SDH vs. DDH neurons. In contrast, GABAAR-mediated mIPSCs had similar amplitudes (25.6 ± 2.4, n = 14 vs. 25. ± 2.0 pA, n = 18) and frequencies (0.21 ± 0.08 vs. 0.18 ± 0.04 Hz) in both regions; however, decay times were slower (23.0 ± 3.2 vs. 18.9 ± 1.8 ms) in SDH neurons. Mean single channel conductance underlying mIPSCs was identical for GlyRs (54.3 ± 1.6 pS, n = 11 vs. 55.7 ± 1.8, n = 8) and GABAARs (22.7 ± 1.7 pS, n = 10 vs. 22.4 ± 2.0 pS, n = 11) in both regions. We also tested whether the synthetic endocanabinoid, methandamide (methAEA), had direct effects on Gly- and GABAARs in each spinal cord region. MethAEA (5 μM) reduced GlyR-mediated mIPSC frequency in SDH and DDH, but did not affect other properties. Similar results were observed for GABAAR mediated mIPSCs, however, rise time was slowed by methAEA in SDH neurons.ConclusionTogether these data show that Gly- and GABAARs with clearly differing physiological properties and cannabinoid-sensitivity contribute to fast synaptic inhibition in mouse SDH and DDH.
A theoretical investigation of the development of physical activity habits in retirement
Authors: Beck Fay , Gillison Fiona , Standage Martyn 
Published: November 2009

Objectives. This study examined the impact of retirement on physical activity (PA) patterns. More specifically, the process of initiating and maintaining behaviour changes in PA were explored using a self‐determination theory perspective.Design. Semi‐structured interviews were conducted to explore the formation of lifestyle habits post‐retirement, and the role of PA within these. Interviews were analysed using thematic analysis and an informal comparison made between physically active and inactive retired adults.Methods. A total of 11 participants (7 female, 4 male; 6 physically active, 5 physically inactive) were recruited from churches and a local newspaper advertisement in South West England. On average, participants (M age=62.91 years; SD =2.3) had been retired 2 years and 8 months (SD =20.03).Results. Three main themes emerged from the interviews specific to retired adults; social factors, lifelong tendencies, and sense of purpose. All retired adults searched for purpose in their lives, and for physically active adults having an exercise schedule contributed to this on a daily basis. PA also represented a source of personal challenge, whereas physically inactive retirees sought meaning and challenge from non‐exercise domains. All participants were acutely aware of their mortality, but active participants felt that PA would increase their chances of enjoying a healthy retirement, rather than accepting a decline in physical function.Conclusions. The results highlighted how global aspirations for life after retirement can influence one's post‐retirement lifestyle. The implications for future research and potential health promotion approaches are discussed.
Heterogeneous Au and Rh catalysts for cycloisomerization reactions of γ-acetylenic carboxylic acids
Authors: Neaţu Florentina , Toullec Patrick Y. , Michelet Véronique , Pârvulescu Vasile I. 
Published: November 2009

Abstract
Au- and Rh-based heterogeneized catalytic systems have been prepared and analyzed. Their efficiency has been evaluated for the cycloisomerization of γ-acetylenic carboxylic acids leading to valuable γ-alkylidene γ-butyrolactones. Bulk AuO3 was found to be a valuable and easy-to-handle catalyst for selective transformations, whereas [C6mim][AuCl4] presented a high activity and Au/β-zeolite was recyclable.
De cónsul a ministro: Gilberto Crespo y Martínez en La Habana.
Authors: Muñoz Laura 
Published: November 2009

Este trabajo examina la labor del representante de México en Cuba en los primeros años del siglo XX. Sostiene que sus labores como cónsul interino y luego como cónsul general y más tarde enviado extraordinario correspondieron a dos etapas diferentes en la percepción mexicana respecto de esa Antilla. Además, que en cada una de esas etapas, en las que las condiciones en la región y en México fueron diferentes, la diplomacia mexicana tuvo que tomar en consideración la presencia de los Estados Unidos en la región del Golfo-Caribe. Dichas etapas evidencian cómo las percepciones reflejaron, a su vez, dos momentos con condiciones regionales y situaciones internas diversas, en las que la presencia e intereses norteamericanos tuvieron que ser contemplados en el diseño de la diplomacia que podía promover México.
This article studies the work of the Mexican agent in Cuba during the early twentieth century. It argues that his functions as temporary consul and later on as general consul and extraordinary envoy reflect two different stages in the Mexican perception of the Antillean Island. It also claims that in each one of these stages, when conditions both in the region and in Mexico were different, Mexican diplomacy had to ponder the presence of the United States in the Gulf-Caribbean region. These stages clearly express two different moments with regional conditions and internal situations in which American presence had to be considered in the design of Mexican diplomacy.
Darwin and Darwinism: The (Alleged) Social Implications of The Origin of Species
Authors: Orr H Allen 
Published: November 2009

Abstract
Most scientific theories, even revolutionary ones, change the practice of a particular science but have few consequences for culture or society at large. But Darwinism, it has often been said, is different in this respect. Since the publication of The Origin of Species, many have claimed that Darwinism has a number of profound social implications. Here, I briefly consider three of these: the economic, the political, and the religious. I suggest that, for the most part, these supposed implications have been misconstrued or exaggerated. Indeed, it is reasonably clear that the chain of implication sometimes primarily ran in the opposite direction—from, for instance, economics and political theory to Darwinism.
Oceanic, riverine, and genetic influences on spring chinook salmon migration timing
Authors: Anderson James J. , Beer W. Nicholas 
Published: November 2009

Migrating salmonids often return to their spawning habitats in overlapping timing patterns of multiple stocks (populations) collectively called a run that varies in its genetic makeup across and within years. Managers, tasked with developing harvest strategies on these runs, may have preseason estimates of total run size but little information on run timing. Without both it is difficult to assess a run's status in real time. Consequently, to avoid overharvest, managers tend to control the timing of harvest. However, this strategy may inadvertently affect the component stocks disproportionately and therefore the run's diversity. Thus, accurate estimates of run timing are needed to improve management.We developed a model that includes genetic and environmental factors to predict the mean run timing of chinook salmon (Oncorhynchus tshawytscha) at Bonneville Dam on the Columbia River, Oregon, USA. The model predicted mean run timing (P < 0.00001, r2 = 0.78) by characterizing genetic run timing components from the arrival timing of precocious males returning one year prior to the remainder of the adults and environmental influences of oceanic and riverine flows that impede or advance the run timing. Variations in the relative abundances of the populations in the run explain 62% of the interannual variation in mean run timing while the oceanic and riverine factors combined account for 15.5%. We suggest that when genetic run timing characteristics are preserved in species with multiple maturation strategies the information can be used to improve run time predictions and maintain genetic diversity of harvested species.