bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasion thresholds and the evolution of nonequilibrium virulence
Authors: Bull James J. , Ebert Dieter 
Published: January 2008

AbstractThe enterprise of virulence management attempts to predict how social practices and other factors affect the evolution of parasite virulence. These predictions are often based on parasite optima or evolutionary equilibria derived from models of host‐parasite dynamics. Yet even when such models accurately capture the parasite optima, newly invading parasites will typically not be at their optima. Here we show that parasite invasion of a host population can occur despite highly nonoptimal virulence. Fitness improvements soon after invasion may proceed through many steps with wide changes in virulence, because fitness depends on transmission as well as virulence, and transmission improvements can overwhelm nonoptimal virulence. This process is highly sensitive to mutation supply and the strength of selection. Importantly, the same invasion principle applies to the evolution of established parasites, whenever mutants arise that overcome host immunity/resistance. A host population may consequently experience repeated invasions of new parasite variants and possible large shifts in virulence as it evolves in an arms race with the parasite. An experimental study of phage lysis time and examples of mammalian viruses matching some of these characteristics are reviewed.
Adaptation, extinction and global change
Authors: Bell Graham , Collins Sinéad 
Published: January 2008

AbstractWe discuss three interlinked issues: the natural pace of environmental change and adaptation, the likelihood that a population will adapt to a potentially lethal change, and adaptation to elevated CO2, the prime mover of global change.1. Environmental variability is governed by power laws showing that ln difference in conditions increases with ln elapsed time at a rate of 0.3–0.4. This leads to strong but fluctuating selection in many natural populations.2. The effect of repeated adverse change on mean fitness depends on its frequency rather than its severity. If the depression of mean fitness leads to population decline, however, severe stress may cause extinction. Evolutionary rescue from extinction requires abundant genetic variation or a high mutation supply rate, and thus a large population size. Although natural populations can sustain quite intense selection, they often fail to adapt to anthropogenic stresses such as pollution and acidification and instead become extinct.3. Experimental selection lines of algae show no specific adaptation to elevated CO2, but instead lose their carbon‐concentrating mechanism through mutational degradation. This is likely to reduce the effectiveness of the oceanic carbon pump. Elevated CO2is also likely to lead to changes in phytoplankton community composition, although it is not yet clear what these will be.We emphasize the importance of experimental evolution in understanding and predicting the biological response to global change. This will be one of the main tasks of evolutionary biologists in the coming decade.
Why is HIV not vector‐borne?
Authors: Day Troy , Mideo Nicole , Alizon Samuel 
Published: January 2008

AbstractMany pathogens of humans are blood borne, including HIV, Malaria, Hepatitis B and C, West Nile virus, Dengue, and other viral hemorrhagic fevers. Although several of these pathogens are transmitted by blood‐feeding arthropods, HIV is not. A number of properties of HIV and its life cycle have been identified as proximate explanations for the absence of arthropod transmission, but little consideration has been given to why HIV has not evolved this form of transmission. We consider the empirical evidence for arthropod transmission, and suggest that mechanical transmission has not evolved in HIV because such strains would induce a faster onset of AIDS during infection, which would thereby limit their ability to spread. On the other hand, it is not as clear why biological transmission has not occurred. Available data suggests that a lack of appropriate genetic variation in HIV is one explanation, but it is also possible that a conflict between natural selection occurring within and between infected individuals has prevented its evolution instead. We discuss the potential significance of these ideas, and argue that taking such an evolutionary perspective broadens our understanding of infectious diseases and the potential consequences of public health interventions.
Oestrogen receptors α and β show different associations to clinicopathological parameters and their co-expression might predict a better response to endocrine treatment in breast cancer
Authors: Borgquist S , Holm C , Stendahl M , Anagnostaki L , Landberg G , Jirström K 
Published: January 2008

Aims:The majority of all breast cancers are hormone responsive, traditionally defined by the expression of oestrogen receptor (ER) α and/or progesterone receptors. In contrast to ERα, the clinical significance of the relatively recently identified ERβ is still unclear. This study aimed to define the relationship between ERβ and clinicopathological parameters in a mixed cohort of breast cancer and, furthermore, to investigate the impact of ERβ expression on disease outcome.Methods:The immunohistochemical expression of ERα and ERβ was analysed in tissue microarrays containing a total number of 512 tumours with all incident breast cancers diagnosed at the Malmö University Hospital between 1988 and 1992.Results:78% of the tumours were ERα positive and 50% were ERβ positive. ERβ correlated positively with ERα (p = 0.001). In contrast to ERα, ERβ was not associated with any important clinicopathological variables. Furthermore, no overall prognostic significance could be demonstrated for ERβ. In the ERα-positive subgroup, however, a low expression of ERβ correlated with a decreased disease-free survival in patients receiving endocrine treatment (p = 0.003).Conclusions:Although interrelated, ERα and ERβ seem to be differentially associated to clinicopathological parameters, and this would support the fact that they might have different functions in vivo. Furthermore, ERβ might be a predictive marker of response to endocrine therapy, although this needs to be confirmed in additional studies, preferably randomised trials.
Modelling the clogging of coarse gravel and tire shreds in column tests
Authors: Rowe R. Kerry , Babcock Dan 
Published: January 2008

A combination of data from laboratory tests and modelling is reported for both coarse gravel (19–38 mm) and two types of tire shred permeated with municipal solid waste leachate. It is suggested that the dispersivity of both the coarse gravel (initially about 4 mm) and tire shreds (initially about 45 mm) increases as the porosity of the drainage media is reduced because of clogging. The detachment of biofilm caused by growth and shear is examined and both are found to influence clogging. The average grain size estimated based on the measured surface area of the particles within a unit volume is shown to provide a good prediction of the rate of clogging for gravel and a conservative prediction for tire shreds. The size and density of suspended solids in leachate is found to significantly influence clogging rates. It is shown that Monod kinetic constants deduced for gravel at 27 °C give a good prediction of clogging for two different types of tire shred at the same temperature. Calibrated parameters used with the BioClog model are shown to give good fits to the porosity of both gravel and tire shred drainage material in laboratory column tests over time periods of up to 2 years.
Liquefaction assessment by the unit energy concept through centrifuge and torsional shear tests
Authors: Dief Hesham M. , Figueroa J. Ludwig 
Published: January 2008

The fundamentals of the energy concept to assess the liquefaction potential of cohesionless soils have been formulated in recent years. To examine the validity of this procedure, a series of centrifuge liquefaction tests were carried out using the same soils that were tested previously as part of extensive research conducted on the subject at Case Western Reserve University. A total of 30 liquefaction tests at accelerations of 50g and 60g were conducted on scaled pore fluid saturated models, prepared in a laminar box, representing a prototype soil deposit. The influence of relative density and effective confining pressure, as well as the effect of different grain size distribution on the energy per unit volume required for liquefaction, is studied. Generalized relationships were obtained by performing regression analyses between the energy per unit volume at the onset of liquefaction and liquefaction affecting parameters. These equations are compared with similar ones that were developed previously using torsional shear tests. A rational procedure to determine site response to earthquake loading and liquefaction susceptibility of a soil deposit is verified.
PREDICTIONS FROM NON-TRIVIAL QUARK-LEPTON COMPLEMENTARITY
Authors: PICARIELLO MARCO , CHAUHAN BHAG C. , PULIDO JOÃO , TORRENTE-LUJAN EMILIO 
Published: January 2008

The complementarity between the quark and lepton mixing matrices is shown to provide robust predictions. We obtain these predictions by first showing that the matrix VM, product of the quark (CKM) and lepton (PMNS) mixing matrices, may have a zero (1,3) entry which is favored by experimental data. We obtain that any theoretical model with a vanishing (1,3) entry of VM that is in agreement with quark data, solar, and atmospheric mixing angle leads to [Formula: see text]. This value is consistent with the present 90% CL experimental upper limit. We also investigate the prediction on the lepton phases. We show that the actual evidence, under the only assumption that the correlation matrix VM product of CKM and PMNS has a zero in the entry (1, 3), gives us a prediction for the three CP-violating invariants J, S1, and S2. A better determination of the lepton mixing angles will give stronger prediction for the CP-violating invariants in the lepton sector. These will be tested in the next generation experiments. Finally we compute the effect of non diagonal neutrino mass in li → ljγ in SUSY theories with non trivial Quark-Lepton complementarity and a flavor symmetry. The Quark-Lepton complementarity and the flavor symmetry strongly constrain the theory and we obtain a clear prediction for the contribution to μ → eγ and the τ decays τ → eγ and τ → μγ. If the Dirac neutrino Yukawa couplings are degenerate but the low energy neutrino masses are not degenerate, then the lepton decays are related among them by the VM entries. On the other hand, if the Dirac neutrino Yukawa couplings are hierarchical or the low energy neutrino masses are degenerate, then the prediction for the lepton decays comes from the CKM hierarchy.
Sodium Thiosulfate Administered Six Hours after Cisplatin Does Not Compromise Antineuroblastoma Activity
Authors: Harned Theresa M. , Kalous Ondrej , Neuwelt Alexander , Loera Jason , Ji Lingyun , Iovine Peter , Sposto Richard , Neuwelt Edward A. , Reynolds C. Patrick 
Published: January 2008

AbstractPurpose: We determined if the potentially otoprotective agent sodium thiosulfate (STS) could be given 6 h after cisplatin without diminishing the antineuroblastoma activity of cisplatin in human neuroblastoma cell lines in vitro (including cisplatin-resistant cell lines) and in neuroblastoma xenografts in vivo.Experimental Design: We determined the antineuroblastoma activity of cisplatin with or without the addition of STS at 0 or 6 h after cisplatin in six neuroblastoma cell lines, both in standard cell culture conditions (20% O2) and in physiologic hypoxia (2% O2). Drug cytotoxicity was measured using the DIMSCAN fluorescence/digital imaging microscopy assay. In vivo studies of cisplatin combined with STS used a human neuroblastoma subcutaneous xenograft model (SMS-SAN) in athymic nu/nu mice.Results: A significant protection against cisplatin cytotoxicity was seen when the neuroblastoma cells were exposed to cisplatin directly combined with STS. However, when cisplatin was given first and STS exposure occurred 6 h later, no effect on cisplatin cytotoxicity was observed. In a subcutaneous neuroblastoma xenograft model in nu/nu mice, mice receiving cisplatin alone or cisplatin + STS at 6 h had significantly better progression-free survival rates (P &lt; 0.03) compared with controls or mice treated with cisplatin + STS concurrently. There was no statistically significant difference in outcomes between mice treated with cisplatin alone and the group treated with cisplatin followed by STS 6 h later (P = 0.9).Conclusion: These preclinical data suggest that the use of STS 6 h after cisplatin for otoprotection is unlikely to compromise the antineuroblastoma activity of cisplatin.
Role of IG20 Splice Variants in TRAIL Resistance
Authors: Prabhakar Bellur S. , Mulherkar Nirupama , Prasad Kanteti V. 
Published: January 2008

AbstractTumor necrosis factor receptor–related apoptosis-inducing ligand (TRAIL) can induce apoptosis primarily in cancer cells with little or no effect on normal cells; therefore, it has the potential for use in cancer therapy. TRAIL binding to death receptors DR4 and DR5 triggers the death-inducing signal complex formation and activation of procaspase-8, which in turn activates caspase-3, leading to cell death. Like FasL, TRAIL can trigger type 1 (caspase-8 → caspase-3) or type 2 (caspase-8 → Bid cleavage → capsase-9 → caspase-3) apoptotic pathways depending on the cell type. Some cancers are resistant to TRAIL treatment because most molecules in the TRAIL signaling pathway, including FLIPs and IAPs, can contribute to resistance. In addition, we have identified an essential role for splice variants of the IG20 gene in TRAIL resistance.
MicroRNAs as Prognostic Indicators and Therapeutic Targets: Potential Effect on Breast Cancer Management
Authors: Lowery Aoife J. , Miller Nicola , McNeill Roisin E. , Kerin Michael J. 
Published: January 2008

AbstractThe discovery of microRNAs (miRNA) as novel modulators of gene expression has resulted in a rapidly expanding repertoire of molecules in this family, as reflected in the concomitant expansion of scientific literature. MiRNAs are a category of naturally occurring RNA molecules that play important regulatory roles in plants and animals by targeting mRNAs for cleavage or translational repression. Characteristically, miRNAs are noncoding, single-stranded short (18-22 nucleotides) RNAs, features which possibly explain why they had not been intensively investigated until recently. Accumulating experimental evidence indicates that miRNAs play a pivotal role in many cellular functions via the regulation of gene expression. Furthermore, their dysregulation and/or mutation has been shown in carcinogenesis. We provide a brief review of miRNA biogenesis and discuss the technical challenges of modifying experimental techniques to facilitate the identification and characterization of these small RNAs. MiRNA function and their involvement in malignancy, particularly their putative role as oncogenes or tumor suppressors is also discussed, with a specific emphasis on breast cancer. Finally, we comment on the potential role of miRNAs in breast cancer management, particularly in improving current prognostic tools and achieving the goal of individualized cancer treatment.
Clinical Validation of a Customized Multiple Signature Microarray for Breast Cancer
Authors: Tan Benita K.T. , Tan Lay Keng , Yu Kun , Tan Puay Hoon , Lee Ming , Sii Lang Hiong , Wong Chow Yin , Ho Gay Hui , Yeo Allen W.Y. , Chow Pierce K.H. , Koong Heng Nung , Yong Wei Sean , Lim Dennis T.H. , Ooi London L.P.J. , Soo Khee Chee , Tan Patrick 
Published: January 2008

Abstract
Purpose: Current histopathologic systems for classifying breast tumors require evaluation of multiple variables and are often associated with significant interobserver variability. Recent studies suggest that gene expression profiles may represent a promising alternative for clinical cancer classification. Here, we investigated the use of a customized microarray as a potential tool for clinical practice.
Experimental Design: We fabricated custom 188-gene microarrays containing expression signatures for three breast cancer molecular subtypes [luminal/estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2), and “basaloid”], the Nottingham prognostic index (NPI-ES), and low histologic grade (TuM1). The reliability of these multiple-signature arrays (MSA) was tested in a prospective cohort of 165 patients with primary breast cancer.
Results: The MSA-ER signature exhibited a high concordance of 90% with ER immunohistochemistry reported on diagnosis (P &lt; 0.001). This remained unchanged at 89% (P &lt; 0.001) when the immunohistochemistry was repeated using current laboratory standards. Expression of the HER2 signature showed a good correlation of 76% with HER2 fluorescence in situ hybridization (FISH; ratio ≥2.2; P &lt; 0.001), which further improved to 89% when the ratio cutoff was raised to ≥5. A proportion of low-level FISH-amplified samples (ratio, 2.2-5) behaved comparably to FISH-negative samples by HER2 signature expression, HER2 quantitative reverse transcription-PCR, and HER2 immunohistochemistry. Luminal/ER+ tumors with high NPI-ES expression were associated with high NPI scores (P = 0.001), and luminal/ER+ TuM1-expressing tumors were significantly correlated with low histologic grade (P = 0.002) and improved survival outcome in an interim analysis (hazard ratio, 0.2; P = 0.019).
Conclusion: The consistency of the MSA platform in an independent patient population suggests that custom microarrays could potentially function as an adjunct to standard immunohistochemistry and FISH in clinical practice.
Ductal Carcinoma In situ and the Emergence of Diversity during Breast Cancer Evolution
Authors: Allred D. Craig , Wu Yun , Mao Sufeng , Nagtegaal Iris D. , Lee Sangjun , Perou Charles M. , Mohsin Syed K. , O'Connell Peter , Tsimelzon Anna , Medina Dan 
Published: January 2008

Abstract
Purpose: Human invasive breast cancers (IBC) show enormous histologic and biological diversity. This study comprehensively evaluated diversity in ductal carcinoma in situ (DCIS), the immediate precursors of IBCs.
Experimental Design: The extent of diversity for conventional histologic grade and standard prognostic biomarkers assessed by immunohistochemistry was evaluated in a series of pure DCIS (n = 200) compared with a contemporaneous series of IBCs (n = 200). A subset of the DCIS (n = 25) was evaluated by DNA microarrays for the presence of luminal, basal, and erbB2 intrinsic subtypes. The extent of diversity within individual cases of DCIS (n = 120) was determined by assessing multiple regions independently for histologic (nuclear) grade and several biomarkers by immunohistochemistry, which approximate microarrays in determining intrinsic subtypes.
Results: DCIS showed a broad distribution of conventional histologic grades and standard biomarkers ranging from well to poorly differentiated, nearly identical to IBCs. Microarrays showed the same intrinsic subtypes in DCIS as in IBCs. However, higher resolution analysis showed that multiple histologic grades, biomarker phenotypes, and intrinsic subtypes often coexist within the same DCIS, and these diverse regions probably compete for dominance. Diversity within cases of DCIS was highly correlated with mutated p53 (P = 0.0007).
Conclusions: These results support the hypothesis that poorly differentiated DCIS gradually evolve from well-differentiated DCIS by randomly acquiring genetic defects resulting in increasingly abnormal cellular features. This diversity is amplified by defects resulting in genetic instability (e.g., p53 mutation), and the alterations are propagated to IBC in a manner independent of progression to invasion.
Large Deletions of the PRKAR1A Gene in Carney Complex
Authors: Horvath Anelia , Bossis Ioannis , Giatzakis Christoforos , Levine Elizabeth , Weinberg Frank , Meoli Elise , Robinson-White Audrey , Siegel Jennifer , Soni Payal , Groussin Lionel , Matyakhina Ludmila , Verma Somya , Remmers Elaine , Nesterova Maria , Carney J. Aidan , Bertherat Jérôme , Stratakis Constantine A. 
Published: January 2008

Abstract
Purpose: Since the identification of PRKAR1A mutations in Carney complex, substitutions and small insertions/deletions have been found in ∼70% of the patients. To date, no germ-line PRKAR1A deletion and/or insertion exceeded a few base pairs (up to 15). Although a few families map to chromosome 2, it is possible that current sequencing techniques do not detect larger gene changes in PRKAR1A–mutation-negative individuals with Carney complex.
Experimental Design: To screen for gross alterations of the PRKAR1A gene, we applied Southern hybridization analysis on 36 unrelated Carney complex patients who did not have small intragenic mutations or large aberrations in PRKAR1A, including the probands from two kindreds mapping to chromosome 2.
Results: We found large PRKAR1A deletions in the germ-line of two patients with Carney complex, both sporadic cases; no changes were identified in the remaining patients, including the two chromosome-2-mapping families. In the first patient, the deletion is expected to lead to decreased PRKAR1A mRNA levels but no other effects on the protein; the molecular phenotype is predicted to be PRKAR1A haploinsufficiency, consistent with the majority of PRKAR1A mutations causing Carney complex. In the second patient, the deletion led to in-frame elimination of exon 3 and the expression of a shorter protein, lacking the primary site for interaction with the catalytic protein kinase A subunit. In vitro transfection studies of the mutant PRKAR1A showed impaired ability to bind cyclic AMP and activation of the protein kinase A enzyme. The patient bearing this mutation had a more-severe-than-average Carney complex phenotype that included the relatively rare psammomatous melanotic schwannoma.
Conclusions: Large PRKAR1A deletions may be responsible for Carney complex in patients that do not have PRKAR1A gene defects identifiable by sequencing. Preliminary data indicate that these patients may have a different phenotype especially if their defect results in an expressed, abnormal version of the PRKAR1A protein.
Plasma Stromal Cell–Derived Factor-1: Host Derived Marker Predictive of Distant Metastasis in Breast Cancer
Authors: Hassan Saima , Baccarelli Andrea , Salvucci Ombretta , Basik Mark 
Published: January 2008

Abstract
Purpose: Homing of breast cancer cells to metastatic sites may be regulated by the production of stromal cell–derived factor (SDF)-1 by specific target organs, which attracts CXCR4-expressing breast cancer cells. We investigated the value of SDF-1 as a predictive blood marker of distant metastasis in breast cancer, together with a common polymorphism of SDF-1, SDF-1-3′A.
Experimental Design: Plasma samples were collected prospectively for 270 consecutive primary breast cancer patients with a median follow-up of 3.3 years. Plasma SDF-1 levels were measured using an ELISA, and the polymorphism was identified via PCR-RFLP analysis.
Results: Plasma SDF-1 levels were divided into two groups, low and high, based on the median SDF-1 value of 2,661 pg/mL. Patients with low SDF-1 showed an increased risk of developing distant metastasis (relative risk, 1.94; P = 0.02) and poorer breast cancer–specific survival [adjusted hazard ratio (AHR), 3.92; P = 0.007]. Patients with both low plasma SDF-1 levels and the SDF-1-3′A polymorphism showed a poorer breast cancer–specific survival (AHR, 3.98; P = 0.001) and distant disease-free survival (AHR, 2.88; P = 0.003). In a separate cohort of 22 breast cancer patients, we found no significant difference in SDF-1 levels before and posttumor resection.
Conclusion: We found that low plasma SDF-1 is an independent host-derived predictive marker of distant metastasis in breast cancer. The prognostic value of the combination of a low plasma SDF-1 level and the SDF-1-3′A polymorphism identifies a cohort of patients with an intrinsic susceptibility for poorer survival.