bluuebunny/crossref_metadata_2025_split huggingface dataset:
IN DEFENSE OF THE WHAT‐IT‐IS‐LIKENESS OF EXPERIENCE
Authors: JANZEN GREG 
Published: September 2011

abstractIt is common parlance among philosophers who inquire into the nature of consciousness to speak of there being something it is like for the subject of a mental state to be in it. The popularity of the ‘what‐it‐is‐like’ phrase stems, in part, from the assumption that it enables us to distinguish, in an intuitive and illuminating way, between conscious and unconscious mental states: conscious mental states, unlike unconscious mental states, are such that there is something it is like for their subjects to be in them. The ‘what‐it‐is‐like’ phrase, however, has not gone unopposed; some very clever philosophers have vigorously disputed it. Peter Hacker, for example, argues that the phrase should be abandoned because it is ungrammatical, and Paul Snowdon argues that it should be abandoned because the propositions expressed by its usage are either trivial or false. This paper mounts a case for the claim that neither of these conclusions is warranted. Against Hacker, it is argued that the arguments he produces for the ungrammaticality of the phrase are unpersuasive; and, against Snowdon, it is argued that he fails to consider a plausible and independently motivated interpretation of the phrase and that on this interpretation, the propositions expressed by its usage are nontrivially true.
Understanding catastrophizing from a misdirected problem‐solving perspective
Authors: Flink Ida K. , Boersma Katja , MacDonald Shane , Linton Steven J. 
Published: September 2011

Objectives. The aim is to explore pain catastrophizing from a problem‐solving perspective. The links between catastrophizing, problem framing, and problem‐solving behaviour are examined through two possible models of mediation as inferred by two contemporary and complementary theoretical models, themisdirected problem solving model(Eccleston & Crombez, 2007) and thefear‐anxiety‐avoidance model(Asmundson, Norton, & Vlaeyen, 2004).Design. In this prospective study, a general population sample (n= 173) with perceived problems with spinal pain filled out questionnaires twice; catastrophizing and problem framing were assessed on the first occasion and health care seeking (as a proxy for medically oriented problem solving) was assessed 7 months later.Methods. Two different approaches were used to explore whether the data supported any of the proposed models of mediation. First, multiple regressions were used according to traditional recommendations for mediation analyses. Second, a bootstrapping method (n= 1000 bootstrap resamples) was used to explore the significance of the indirect effects in both possible models of mediation.Results. The results verified the concepts included in the misdirected problem solving model. However, the direction of the relations was more in line with the fear‐anxiety‐avoidance model. More specifically, the mediation analyses provided support for viewing catastrophizing as a mediator of the relation between biomedical problem framing and medically oriented problem‐solving behaviour.Conclusion. These findings provide support for viewing catastrophizing from a problem‐solving perspective and imply a need to examine and address problem framing and catastrophizing in back pain patients.
2H double- and zero-quantum filtered NMR spectroscopy for probing the environments of water in Nafion
Authors: Vanderveen Jesse R. , Blackburn Mark A. , Ooms Kristopher J. 
Published: September 2011

Multiple quantum 2H NMR spectroscopy is used to study the structure and dynamics of D2O in Nafion membranes as a function of membrane hydration. By employing both double- and zero-quantum filtered experiments, residual quadrupolar coupling constants and T2 relaxation values are obtained. The residual couplings vary from 240 to 20 Hz and the T2 values range from 20 to 180 ms, with the high hydration values having smaller couplings and longer T2 values. Analysis of the data using a water-exchange model suggests that the changes in parameters arise from a change in the fraction of time water spends in the anisotropic environments and not from changes in the order parameters that characterize the anisotropic sites. It has been found that a two-site model is needed to accurately fit the spectra above a hydration level of 10 D2O per sulfonate, with the second site having a negligible residual quadrupolar coupling. The data supports a model with two different hydration layers at high hydration and can be understood in terms of the recently proposed parallel-channel model for Nafion hydration.
Structural analysis of lanthanum-containing battery materials using 139La solid-state NMR
Authors: Spencer Leigh , Coomes Eric , Ye Eric , Terskikh Victor , Ramzy Adam , Thangadurai Venkataraman , Goward Gillian R. 
Published: September 2011

139La solid-state NMR spectra, acquired at 21.1 and 11.7 T, have been used to evaluate the structural properties of the lithium ion battery materials, La32Li16Fe6.4O67 and Li3xLa2/3–xTiO3. In particular, atomic-level disorder in the second coordination sphere environment of lanthanum in these materials has been indicated by the observation of a distribution in the asymmetry parameters and the quadrupolar coupling constants derived from experimental NMR spectra, and supported by theoretical calculations. For comparison, 139La NMR has been obtained for the two model compounds La2O3 and LaNbO4, in which there is no atomic-level disorder. Quadrupolar coupling constants in the range of 17 to 59 MHz have been measured, and these values are supported by previous work as well as theoretical predictions performed in CASTEP. It has been shown that 139La NMR is a useful tool for the structural analysis of lithium ion battery materials, and when combined with 7Li MAS NMR and powder X-ray diffraction, can be used to determine the structure of complex solid-state electrolyte and electrode materials.
Daily responses of mouflon (Ovis gmelini musimon ×Ovis sp.) activity to summer climatic conditions
Authors: Bourgoin G. , Garel M. , Blanchard P. , Dubray D. , Maillard D. , Gaillard J.-M. 
Published: September 2011

Investigating the factors shaping the activity of large herbivores is of prime importance because changes in their activity patterns may indicate physiological stress, which can affect reproduction and survival of individuals, and thereby population growth. Although climatic conditions are known to impact the activity patterns of large herbivores, few studies have investigated this relationship at a fine temporal scale. From a continuous monitoring of activity, we assessed the influence of temperature and wind on the summer activity of female mouflon ( Ovis gmelini musimon Pallas, 1811 × Ovis sp.) facing summer droughts. Females showed a marked bimodal activity pattern, with activity peaks occurring after dawn and before dusk. When temperature increased and wind speed decreased, the morning activity peak occurred earlier, while the evening activity peak was delayed. Hence, under stressing climatic conditions, female mouflon decreased their diurnal activity while increasing their nocturnal activity. However, this nocturnal increase did not prevent the activity rate over 24 h to decrease during hot nonwindy days compared with cool windy days. Although the occurrence of wind mitigated the negative influence of heat on the diurnal activity, wind had no effect at the daily scale. These findings emphasize the importance of working at different temporal scales when assessing the activity patterns of free-ranging vertebrates.
Climate limitations on the distribution and phenology of a large carpenter bee,Xylocopa virginica(Hymenoptera: Apidae)
Authors: Skandalis Dimitri A. , Richards Miriam H. , Sformo Todd S. , Tattersall Glenn J. 
Published: September 2011

We studied climatic correlates of the geographic range of a common large carpenter bee ( Xylocopa virginica (L., 1771)), which reaches farther north than any other Xylocopa in North America. Computational models of the species’ range predicted that summer and winter temperatures limit its northern extent, whereas summer precipitation limits its western extent. We empirically evaluated the climatic constraints imposed by different seasons by examining the winter low-temperature tolerance of X. virginica, and the timing of activity during spring and summer. The bee’s absolute low-temperature tolerance (supercooling point) did not differ between two populations at mid- and high latitudes, and was in excess of requirements of a mean winter minimum temperature. Absolute minimum temperature tolerances may not directly influence the range of X. virginica, whereas other measures of cold tolerance, like exposure duration, might be more relevant. Between years within a study population, spring emergence dates of bees were significantly predicted by spring temperatures and weather (April: 6–11 °C; May: 13–17 °C). Between populations across the bee’s geographic range, bees in warmer climates were observed as much as 2–3 months earlier in the year. This suggests that a major constraint on the bee’s range is the length of the active season, which may be too short for brood development at high latitudes.
A new way to estimate the age of bowhead whales (Balaena mysticetus) using ovarian corpora counts
Authors: George J.C. , Follmann E. , Zeh J. , Sousa M. , Tarpley R. , Suydam R. , Horstmann-Dehn L. 
Published: September 2011

We used lengths and reproductive data for bowhead whales ( Balaena mysticetus L., 1758) harvested by Alaskan Eskimos to estimate female reproductive parameters and age. Data from 117 females determined that 75 were sexually mature and 42 were immature. Estimated length at sexual maturity was 13.35 m. Counts of ovarian corpora were obtained from 50 mature females. Corpora and baleen data were used with aspartic acid racemization (AAR) data to obtain estimated age at sexual maturity (ASM) at ≈26 years. The number of corpora counted in both ovaries (or estimated when only one ovary was counted) was used with ASM and estimated ovulation rate (OR) to obtain corpora age estimates ranging from 26 to 149 years. A stone harpoon tip recovered from whale 92B2 was consistent with her corpora age of 133 years. The correlation between corpora and AAR age estimates was 0.77. Estimated standard errors of corpora ages tended to be somewhat higher than those for comparable AAR ages. A sample of potentially mature females examined for maturity and presence of a corpus luteum and (or) fetus provided an OR value of 0.332·year–1and an estimated pregnancy rate of 0.326·year–1, implying intervals between ovulations and pregnancies of 3.0 and 3.1 years.
Sperm depletion and a test of the phenotype-linked fertility hypothesis in Gray Treefrogs (Hyla versicolor)
Authors: Doyle Jacqueline M. 
Published: September 2011

The phenotype-linked fertility hypothesis (PLFH) predicts that ejaculate characteristics correlate with male phenotype, and that females may select for exaggerated phenotypes to guarantee high fertilization success. Female Gray Treefrogs ( Hyla versicolor LeConte, 1825) prefer males with long-duration calls and (or) calls produced at a fast rate. I tested the prediction that call duration or call rate were indicators of sperm number or viability. To assess whether female H. versicolor might benefit by identifying males with low sperm numbers, I examined the effect of mating history on sperm number and looked for evidence of sperm depletion. My study found no support for the PLFH in relation to call quality, as neither sperm number nor viability was related to call duration. I found that sperm stores are severely reduced after a single mating, and that sperm stores of males calling late in the season are often more similar to those of depleted males than unmated males. Thus, calling males may attempt to attract females without the sperm numbers necessary to fertilize the entire clutch. However, selection for females to identify males with high fertilization success may be low when all other factors that affect reproductive success (e.g., genetic benefits) are considered.
The Aurora Kinase Inhibitor CCT137690 Downregulates MYCN and SensitizesMYCN-Amplified NeuroblastomaIn Vivo
Authors: Faisal Amir , Vaughan Lynsey , Bavetsias Vassilios , Sun Chongbo , Atrash Butrus , Avery Sian , Jamin Yann , Robinson Simon P. , Workman Paul , Blagg Julian , Raynaud Florence I. , Eccles Suzanne A. , Chesler Louis , Linardopoulos Spiros 
Published: September 2011

AbstractAurora kinases regulate key stages of mitosis including centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. Aurora A and B kinase overexpression has also been associated with various human cancers, and as such, they have been extensively studied as novel antimitotic drug targets. Here, we characterize the Aurora kinase inhibitor CCT137690, a highly selective, orally bioavailable imidazo[4,5-b]pyridine derivative that inhibits Aurora A and B kinases with low nanomolar IC50 values in both biochemical and cellular assays and exhibits antiproliferative activity against a wide range of human solid tumor cell lines. CCT137690 efficiently inhibits histone H3 and transforming acidic coiled-coil 3 phosphorylation (Aurora B and Aurora A substrates, respectively) in HCT116 and HeLa cells. Continuous exposure of tumor cells to the inhibitor causes multipolar spindle formation, chromosome misalignment, polyploidy, and apoptosis. This is accompanied by p53/p21/BAX induction, thymidine kinase 1 downregulation, and PARP cleavage. Furthermore, CCT137690 treatment of MYCN-amplified neuroblastoma cell lines inhibits cell proliferation and decreases MYCN protein expression. Importantly, in a transgenic mouse model of neuroblastoma that overexpresses MYCN protein and is predisposed to spontaneous neuroblastoma formation, this compound significantly inhibits tumor growth. The potent preclinical activity of CCT137690 suggests that this inhibitor may benefit patients with MYCN-amplified neuroblastoma. Mol Cancer Ther; 10(11); 2115–23. ©2011 AACR.
Discovery and Evaluation of Inhibitors of Human Ceramidase
Authors: Draper Jeremiah M. , Xia Zuping , Smith Ryan A. , Zhuang Yan , Wang Wenxue , Smith Charles D. 
Published: September 2011

Abstract
The ceramide/sphingosine-1-phosphate (S1P) rheostat has been hypothesized to play a critical role in regulating tumor cell fate, with elevated levels of ceramide inducing death and elevated levels of S1P leading to survival and proliferation. Ceramidases are key enzymes that control this rheostat by hydrolyzing ceramide to produce sphingosine and may also confer resistance to drugs and radiation. Therefore, ceramidase inhibitors have excellent potential for development as new anticancer drugs. In this study, we identify a novel ceramidase inhibitor (Ceranib-1) by screening a small molecule library and describe the synthesis of a more potent analogue (Ceranib-2). In a cell-based assay, both compounds were found to inhibit cellular ceramidase activity toward an exogenous ceramide analogue, induce the accumulation of multiple ceramide species, decrease levels of sphingosine and S1P, inhibit the proliferation of cells alone and in combination with paclitaxel, and induce cell-cycle arrest and cell death. In vivo, Ceranib-2 was found to delay tumor growth in a syngeneic tumor model without hematologic suppression or overt signs of toxicity. These data support the selection of ceramidases as suitable targets for anticancer drug development and provide the first nonlipid inhibitors of human ceramidase activity. Mol Cancer Ther; 10(11); 2052–61. ©2011 AACR.
(3-Chloroacetyl)-indole, a Novel Allosteric AKT Inhibitor, Suppresses Colon Cancer Growth In Vitro and In Vivo
Authors: Kim Dong Joon , Reddy Kanamata , Kim Myoung Ok , Li Yan , Nadas Janos , Cho Yong-Yeon , Kim Jong-Eun , Shim Jung-Hyun , Song Nu Ry , Carper Andria , Lubet Ronald A. , Bode Ann M. , Dong Zigang 
Published: September 2011

Abstract
Indole-3-carbinol (I3C) is produced in Brassica vegetables such as broccoli and cabbage and has been shown to inhibit proliferation and induce apoptosis in various cancer cells, including breast, prostate, colon, and leukemia. However, only high doses of I3C were shown to inhibit cell proliferation (IC50 = 200–300 μmol/L). Our goal here was to develop a more potent antitumor agent by modifying the structure of I3C. We created I3C derivatives and found that (3-chloroacetyl)-indole (3CAI) more strongly inhibited colon cancer cell growth than I3C. In addition, by screening 85 kinases in a competitive kinase assay, we found that 3CAI was a specific AKT inhibitor. AKT is a serine/threonine kinase that plays a pivotal role in promoting transformation and chemoresistance by inducing proliferation and inhibiting apoptosis. Therefore, AKT is regarded as a critical target for cancer therapy. 3ICA, a derivative of I3C, is a potent and specific AKT inhibitor. This compound showed significant inhibition of AKT in an in vitro kinase assay and suppressed expression of AKT direct downstream targets such as mTOR and GSK3β as well as induced growth inhibition and apoptosis in colon cancer cells. In addition, oral administration of this potent AKT inhibitor suppressed cancer cell growth in an in vivo xenograft mouse model. Cancer Prev Res; 4(11); 1842–51. ©2011 AACR.
Deficient p27 Phosphorylation at Serine 10 Increases Macrophage Foam Cell Formation and Aggravates Atherosclerosis Through a Proliferation-Independent Mechanism
Authors: Fuster José J. , González-Navarro Herminia , Vinué Angela , Molina-Sànchez Pedro , Andrés-Manzano Maria J. , Nakayama Keiichi I. , Nakayama Keiko , Díez-Juan Antonio , Bernad Antonio , Rodríguez Cristina , Martínez-González José , Andrés Vicente 
Published: September 2011

Objective—

Genetic ablation of the growth suppressor p27
Kip1
(p27) in the mouse aggravates atherosclerosis coinciding with enhanced arterial cell proliferation. However, it is unknown whether molecular mechanisms that limit p27's protective function contribute to atherosclerosis development and whether p27 exerts proliferation-independent activities in the arterial wall. This study aims to provide insight into both questions by investigating the role in atherosclerosis of p27 phosphorylation at serine 10 (p27-phospho-Ser10), a major posttranslational modification of this protein.

Methods and Results—
Immunoblotting studies revealed a marked reduction in p27-phospho-Ser10 in atherosclerotic arteries from apolipoprotein E–null mice, and expression of the nonphosphorylatable mutant p27Ser10Ala, either global or restricted to bone marrow, accelerated atherosclerosis. p27Ser10Ala expression did not affect cell proliferation in early and advanced atheroma but activated RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) signaling and promoted macrophage foam cell formation in a ROCK-dependent manner. Supporting the clinical relevance of these findings, human atherosclerotic coronary arteries exhibited a prominent reduction in p27-phospho-Ser10 and increased ezrin/radixin/moesin protein phosphorylation, a marker of RhoA/ROCK activation.

Conclusion—
Scarce phosphorylation of p27 at Ser10 is a hallmark of human and mouse atherosclerosis and promotes disease progression in mice. This proatherogenic effect is mediated by a proliferation-independent mechanism that involves augmented foam cell formation owing to increased RhoA/ROCK activity. These findings unveil a new atheroprotective action of p27 and identify p27-phospho-Ser10 as an attractive target for the treatment of atherosclerosis.
MicroRNA-16 and MicroRNA-424 Regulate Cell-Autonomous Angiogenic Functions in Endothelial Cells via Targeting Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1
Authors: Chamorro-Jorganes Aránzazu , Araldi Elisa , Penalva Luiz O.F. , Sandhu Devraj , Fernández-Hernando Carlos , Suárez Yajaira 
Published: September 2011

Objective—
MicroRNAs play key roles in modulating a variety of cellular processes by posttranscriptional regulation of their target genes. Vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2), and fibroblast growth factor receptor-1 (FGFR1) were identified by bioinformatic approaches and subsequently validated as targets of microRNA (miR)-16 and miR-424 in endothelial cells (ECs).

Methods and Results—
Mimetics of these microRNAs reduced VEGF, VEGFR2, and FGFR1 expression, whereas specific antagonists enhanced their expression. Expression of mature miR-16 and miR-424 was upregulated on VEGF or basic fibroblast growth factor (bFGF) treatment. This upregulation was accompanied by a parallel increase in primary transcript (pri-miR)-16-1 and pri-miR-16-2 but not in pri-miR-424 levels, indicating a VEGF/bFGF-dependent transcriptional and posttranscriptional regulation of miR-16 and miR-424, respectively. Reduced expression of VEGFR2 and FGFR1 by miR-16 or miR-424 overexpression regulated VEGF and bFGF signaling through these receptors, thereby affecting the activity of downstream components of the pathways. Functionally, miR-16 or miR-424 overexpression reduced proliferation, migration, and cord formation of ECs in vitro, and lentiviral overexpression of miR-16 reduced the ability of ECs to form blood vessels in vivo.

Conclusion—
We conclude that these miRNAs fine-tune the expression of selected endothelial angiogenic mediators in response to these growth factors. Altogether, these findings suggest that miR-16 and miR-424 play important roles in regulating cell-intrinsic angiogenic activity of ECs.
Recent Patterns of Sex-Specific Midlife Stroke Hospitalization Rates in the United States
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce 
Published: September 2011

Background and Purpose—
Little is known about sex-specific stroke hospitalization rates among middle-aged individuals. This study assessed recent temporal trends in stroke hospitalizations among persons aged 35 to 64 years in the United States.

Methods—
The Nationwide Inpatient Sample was used to identify individuals with a primary or secondary discharge diagnosis of stroke between 1997 and 2006 (n=3 161 752). Age-adjusted sex-specific rates of ischemic and hemorrhagic stroke hospitalizations were assessed among individuals aged 35 to 64 years.

Results—

Over the study period, stroke hospitalization rates per 100 000 decreased by 10% from 66.7 to 60.3 (trend
P
<0.01) in men and 8% from 52.7 to 48.3 (trend
P
<0.001) in women. The 55- to 64-year age group drove reductions in hospitalization rates: slope (rate of change per year)=−12.3 for men and −8.9 for women (both
P
<0.001). Rates increased slightly in men and women aged 35 to 44 years and remained stable for persons aged 45 to 54 years. Stroke subtype analysis revealed that rates of ischemic stroke hospitalization increased and hemorrhagic stroke hospitalization remained stable among individuals aged 35 to 44 years. Rates of ischemic and hemorrhagic stroke hospitalizations remained stable among those aged 45 to 54 years and decreased among persons aged 55 to 64 years.

Conclusions—
From 1997 to 2006, ischemic and hemorrhagic stroke hospitalization rates declined among individuals aged 55 to 64 years and remained stable among persons aged 45 to 54 years; ischemic stroke hospitalization rates increased among individuals aged 35 to 44 years. Further studies are needed to assess and address increases in ischemic stroke hospitalizations among younger individuals.