bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actual Isothermal Effects of Water‐Filtered Infrared A‐Irradiation
Authors: Höhn Annika , Hartmann Petra , Gebhart Veronika , Sonntag Johanna , Grune Tilman , Jung Tobias 
Published: February 2015

AbstractIn this study, the athermal effects of water‐filtered infrared A (wIRA)‐irradiation (780–1400 nm) on human dermal fibroblasts were investigated. For this purpose, cells were exposed to wIRA‐irradiation (178 mW cm−2 for 1 h), while a sophisticated experimental setup prevented warming of the samples exceeding 0.1°C. The investigated parameters were the formation of reactive oxygen species (ROS), mitochondrial membrane potential and superoxide release, protein oxidation, proliferation rate, as well as intracellular Ca2+‐release in single cells, most of them quantified via fluorescence microscopy and fluorimetric techniques. The existence of actual athermal wIRA‐effects is still intensively discussed, since their detection requires a careful experimental setup and both efficient and powerful temperature regulation of the exposed samples. Here, we can definitively show that some of the supposed athermal wIRA‐effects may be rather artifacts, since wIRA did not reveal any impact on the above mentioned parameters—as long as the temperature of the exposed cells was carefully maintained. Though, we were able to identify an athermal DNA‐protective wIRA‐effect, since the induced DNA damage (quantified via 8‐Oxo‐G‐formation) was significantly decreased after a subsequent UVB‐exposure. These results suggest that many of the supposed athermal wIRA‐effects can be induced by pure warming of the samples, independent from any wIRA‐irradiation.
Blunting of Exercise-Induced Salivary Testosterone in Elite-Level Triathletes With a 10-Day Training Camp
Authors: Hough John , Robertson Caroline , Gleeson Michael 
Published: February 2015

Purpose:
This study examined the influence of 10 days of intensified training on salivary cortisol and testosterone responses to 30-min, high-intensity cycling (55/80) in a group of male elite triathletes.

Methods:
Seven elite male triathletes (age 19 ± 1 y, V̇O2max 67.6 ± 4.5 mL · kg–1 · min–1) completed the study. Swim distances increased by 45%. Running and cycling training hours increased by 25% and 229%, respectively. REST-Q questionnaires assessed mood status before, during, and after the training period. Unstimulated saliva samples were collected before, after, and 30 min after a continuous, high-intensity exercise test. Salivary cortisol and testosterone concentrations were assessed.

Results:
Compared with pretraining, blunted exercise-induced salivary testosterone responses to the posttraining 55/80 were found (P = .004). The absolute response of salivary testosterone concentrations to the 55/80 decreased pretraining to posttraining from 114% to 85%. No changes were found in exercise-induced salivary cortisol concentration responses to the 55/80. REST-Q scores indicated no changes in the participants’ psychological stress–recovery levels over the training camp.

Conclusions:
The blunted exercise-induced salivary testosterone is likely due to decreased testicular testosterone production and/or secretion, possibly attributable to hypothalamic dysfunction or reduced testicular blood flow. REST-Q scores suggest that the triathletes coped well with training-load elevations, which could account for the finding of no change in the exercise-induced salivary cortisol concentration. Overall, these findings suggest that the 55/80 can detect altered exercise-induced salivary testosterone concentrations in an elite athletic population due to increased training stress. However, this alteration occurs independently of a perceived elevation of training stress.
Incorrect Arrangement of the Bamboo Tablets in the Shangshu: A Falsifiable Hypothesis?
Authors: Takashima Ken-ichi 
Published: February 2015

The problem of cuojian 錯簡 “incorrect ordering of bamboo tablets” is not a new scholarly issue in the field of studies involving jiandu 簡牘 (writings on bamboo tablets). As early as Song times (960-1279), scholars began to notice that the received version of the Shangshu 尚書 was suspected to have had the problem of omitting or missing some characters in the bamboo tablets, referred to as tuojian 脫簡 in the Kanggao 康誥 chapter of the Shangshu. In Qing times (1644-1911) a counter-view was presented; namely, the song tuojian hypothesis in the Kanggao chapter was not really correct, but it was how the text was arranged that led to some discontinuity in the beginning portion of the said chapter.This paper provides two specific examples of what may have been the result of a cuojian in the Yaodian 堯典 chapter. It investigates such a possibility in terms of (A) context, (B) lexical features, (C) syntax and semantics, and (D) colometry or isocolometry.
Trajectory Analysis of the Mechanism for Westward Propagation of Rossby Waves
Authors: Schneider Edwin K. 
Published: February 2015

Abstract
An analysis of Rossby wave dynamics in two and three dimensions is carried from the point of view of a reference frame propagating with the zonal phase speed of the wave. Since trajectories and streamlines coincide in this reference frame, the mechanism for (westward) propagation of free waves has a different interpretation than in a reference frame fixed to the ground. In the wave reference frame, propagating free-wave solutions are possible only when parcels approach from the west. When parcels approach from the east, potential vorticity cannot be conserved along trajectories.
Cost‐effectiveness of steroid (methylprednisolone) injections versus anaesthetic alone for the treatment of Morton's neuroma: economic evaluation alongside a randomised controlled trial (MortISE trial)
Authors: Edwards Rhiannon Tudor , Yeo Seow Tien , Russell Daphne , Thomson Colin E , Beggs Ian , Gibson J N Alastair , McMillan Diane , Martin Denis J , Russell Ian T 
Published: February 2015

AbstractBackgroundMorton's neuroma is a common foot condition affecting health‐related quality of life. Though its management frequently includes steroid injections, evidence of cost‐effectiveness is sparse. So, we aimed to evaluate whether steroid injection is cost‐effective in treating Morton's neuroma compared with anaesthetic injection alone.MethodsWe undertook incremental cost‐effectiveness and cost‐utility analyses from the perspective of the National Health Service, alongside a patient‐blinded pragmatic randomised trial in hospital‐based orthopaedic outpatient clinics in Edinburgh, UK. Of the original randomised sample of 131 participants with Morton's neuroma (including 67 controls), economic analysis focused on 109 (including 55 controls). Both groups received injections guided by ultrasound. We estimated the incremental cost per point improvement in the area under the curve of the Foot Health Thermometer (FHT‐AUC) until three months after injection. We also conducted cost‐utility analyses using European Quality of life‐5 Dimensions–3 Levels (EQ‐5D‐3L), enhanced by the Foot Health Thermometer (FHT), to estimate utility and thus quality‐adjusted life years (QALYs).ResultsThe unit cost of an ultrasound‐guided steroid injection was £149. Over the three months of follow‐up, the mean cost of National Health Service resources was £280 for intervention participants and £202 for control participants – a difference of £79 [bootstrapped 95% confidence interval (CI): £18 to £152]. The corresponding estimated incremental cost‐effectiveness ratio was £32 per point improvement in the FHT‐AUC (bootstrapped 95% CI: £7 to £100). If decision makers value improvement of one point at £100 (the upper limit of this CI), there is 97.5% probability that steroid injection is cost‐effective. As EQ‐5D‐3L seems unresponsive to changes in foot health, we based secondary cost‐utility analysis on the FHT‐enhanced EQ‐5D. This estimated the corresponding incremental cost‐effectiveness ratio as £6,400 per QALY. Over the recommended UK threshold, ranging from £20,000 to £30,000 per QALY, there is 80%‐85% probability that steroid injection is cost‐effective.ConclusionsSteroid injections are effective and cost‐effective in relieving foot pain measured by the FHT for three months. However, cost‐utility analysis was initially inconclusive because the EQ‐5D‐3L is less responsive than the FHT to changes in foot health. By using the FHT to enhance the EQ‐5D, we inferred that injections yield good value in cost per QALY.Trial registrationCurrent Controlled Trials ISRCTN13668166
In silico discovery and validation of potent small-molecule inhibitors targeting the activation function 2 site of human oestrogen receptor α
Authors: Singh Kriti , Munuganti Ravi Shashi Nayana , Leblanc Eric , Lin Yu Lun , Leung Euphemia , Lallous Nada , Butler Miriam , Cherkasov Artem , Rennie Paul S 
Published: February 2015

Abstract
Introduction
Current approaches to inhibit oestrogen receptor-alpha (ERα) are focused on targeting its hormone-binding pocket and have limitations. Thus, we propose that inhibitors that bind to a coactivator-binding pocket on ERα, called activation function 2 (AF2), might overcome some of these limitations.

Methods
In silico virtual screening was used to identify small-molecule ERα AF2 inhibitors. These compounds were screened for inhibition of ERα transcriptional activity using stably transfected T47D-KBluc cell line. A direct physical interaction between the AF2 binders and the ERα protein was measured using biolayer interferometry (BLI) and an ERα coactivator displacement assay. Cell viability was assessed by MTS assay in ERα-positive MCF7 cells, tamoxifen-resistant (TamR) cell lines TamR3 and TamR6, and ERα-negative MDA-MB-453 and HeLa cell lines. In addition, ERα inhibition in TamR cells and the effect of compounds on mRNA and protein expression of oestrogen-dependent genes, pS2, cathepsin D and cell division cycle 2 (CDC2) were determined.

Results
Fifteen inhibitors from two chemical classes, derivatives of pyrazolidine-3,5-dione and carbohydrazide, were identified. In a series of in vitro assays, VPC-16230 of the carbohydrazide chemical class emerged as a lead ERα AF2 inhibitor that significantly downregulated ERα transcriptional activity (half-maximal inhibitory concentration = 5.81 μM). By directly binding to the ERα protein, as confirmed by BLI, VPC-16230 effectively displaced coactivator peptides from the AF2 pocket, confirming its site-specific action. VPC-16230 selectively suppressed the growth of ERα-positive breast cancer cells. Furthermore, it significantly inhibited ERα mediated transcription in TamR cells. More importantly, it reduced mRNA and protein levels of pS2, cathepsin D and CDC2, validating its ER-directed activity.

Conclusion
We identified VPC-16230 as an ERα AF2-specific inhibitor that demonstrated promising antiproliferative effects in breast cancer cell lines, including TamR cells. VPC-16230 reduced the expression of ERα-inducible genes, including CDC2, which is involved in cell division. We anticipate that the application of ERα AF2 inhibitors will provide a novel approach that can act as a complementary therapeutic to treat ERα-positive, tamoxifen-resistant and metastatic breast cancers.
Combined histone deacetylase inhibition and tamoxifen induces apoptosis in tamoxifen-resistant breast cancer models, by reversing Bcl-2 overexpression
Authors: Raha Paromita , Thomas Scott , Thurn K Ted , Park Jeenah , Munster Pamela N 
Published: February 2015

Abstract
Introduction
The emergence of hormone therapy resistance, despite continued expression of the estrogen receptor (ER), is a major challenge to curing breast cancer. Recent clinical studies suggest that epigenetic modulation by histone deacetylase (HDAC) inhibitors reverses hormone therapy resistance. However, little is known about epigenetic modulation of the ER during acquired hormone resistance. Our recent phase II study demonstrated that HDAC inhibitors re-sensitize hormone therapy-resistant tumors to the anti-estrogen tamoxifen. In this study, we sought to understand the mechanism behind the efficacy of this combination.

Methods
We generated cell lines resistant to tamoxifen, named TAMRM and TAMRT, by continuous exposure of ER-positive MCF7 and T47D cells, respectively to 4-hydroxy tamoxifen for over 12 months. HDAC inhibition, along with pharmacological and genetic manipulation of key survival pathways, including ER and Bcl-2, were used to characterize these resistant models.

Results
The TAMRM cells displayed decreased sensitivity to tamoxifen, fulvestrant and estrogen deprivation. Consistent with previous models, ER expression was retained and the gene harbored no mutations. Compared to parental MCF7 cells, ER expression in TAMRM was elevated, while progesterone receptor (PGR) was lost. Sensitivity of ER to ligands was greatly reduced and classic ER response genes were suppressed. This model conveyed tamoxifen resistance through transcriptional upregulation of Bcl-2 and c-Myc, and downregulation of the cell cycle checkpoint protein p21, manifesting in accelerated growth and reduced cell death. Similar to TAMRM cells, the TAMRT cell line exhibited substantially decreased tamoxifen sensitivity, increased ER and Bcl-2 expression and significantly reduced PGR expression. Treatment with HDAC inhibitors reversed the altered transcriptional events and reestablished the sensitivity of the ER to tamoxifen resulting in substantial Bcl-2 downregulation, growth arrest and apoptosis. Selective inhibition of Bcl-2 mirrored these effects in presence of an HDAC inhibitor.

Conclusions
Our model implicates elevated ER and Bcl-2 as key drivers of anti-estrogen resistance, which can be reversed by epigenetic modulation through HDAC inhibition.
Genetic depletion and pharmacological targeting of αv integrin in breast cancer cells impairs metastasis in zebrafish and mouse xenograft models
Authors: Li Yihao , Drabsch Yvette , Pujuguet Philippe , Ren Jiang , van Laar Theo , Zhang Long , van Dam Hans , Clément-Lacroix Philippe , ten Dijke Peter 
Published: February 2015

Abstract
Introduction
Increased expression of αv integrins is frequently associated with tumor cell adhesion, migration, invasion and metastasis, and correlates with poor prognosis in breast cancer. However, the mechanism by which αv integrins can enhance breast cancer progression is still largely unclear. The effects of therapeutic targeting of αv integrins in breast cancer also have yet to be investigated.

Methods
We knocked down αv integrin in MDA-MB-231 and MCF10A-M4 breast cancer cells, or treated these cells with the αv antagonist GLPG0187. The effects of αv integrin depletion on mesenchymal markers, transforming growth factor-β (TGF-β)/Smad signaling and TGF-β-induced target gene expression were analyzed in MDA-MB-231 cells by RNA analysis or Western blotting. The function of αv integrin on breast cancer cell migration was investigated by transwell assay in vitro, and its effect on breast cancer progression was assessed by both zebrafish and mouse xenografts in vivo. In the mouse model, GLPG0187 was administered separately, or in combination with the standard-of-care anti-resorptive agent zoledronate and the chemotherapeutic drug paclitaxel, to study the effects of combinational treatments on breast cancer metastasis.

Results
Genetic interference and pharmacological targeting of αv integrin with GLPG0187 in different breast cancer cell lines inhibited invasion and metastasis in the zebrafish or mouse xenograft model. Depletion of αv integrin in MDA-MB-231 cells inhibited the expression of mesenchymal markers and the TGF-β/Smad response. TGF-β induced αv integrin mRNA expression and αv integrin was required for TGF-β-induced breast cancer cell migration. Moreover, treatment of MDA-MB-231 cells with non-peptide RGD antagonist GLPG0187 decreased TGF-β signaling. In the mouse xenografts GLPG0187 inhibited the progression of bone metastasis. Maximum efficacy of inhibition of bone metastasis was achieved when GLPG0187 was combined with the standard-of-care metastatic breast cancer treatments.

Conclusion
These findings show that αv integrin is required for efficient TGF-β/Smad signaling and TGF-β-induced breast cancer cell migration, and for maintaining a mesenchymal phenotype of the breast cancer cells. Our results also provide evidence that targeting αv integrin could be an effective therapeutic approach for treatment of breast cancer tumors and/or metastases that overexpress αv integrin.
Increased 30-day and 1-year mortality rates and lower coronary revascularisation rates following acute myocardial infarction in patients with autoimmune rheumatic disease
Authors: Van Doornum Sharon , Bohensky Megan , Tacey Mark A , Brand Caroline A , Sundararajan Vijaya , Wicks Ian P 
Published: February 2015

Abstract
Introduction
It is now well-recognised that patients with autoimmune rheumatic disease (AIRD) have a predisposition to cardiovascular disease that results in increased morbidity and mortality. Following myocardial infarction (MI), patients with rheumatoid arthritis have been shown to have an increased case fatality rate; however, this has not been demonstrated in other forms of AIRD. The aim of this study was to compare case fatality rates following a first MI in patients with AIRD versus the general population. The secondary aim was to compare revascularisation treatment following MI in patients with AIRD versus the general population.

Methods
A retrospective cohort study using two population-based linked databases was undertaken. Cases of first MI from July 2001 to June 2007 were identified based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification, codes. Thirty-day and one-year mortality rates were calculated (all-cause and cardiovascular causes of death). Logistic regression models were fitted to calculate the odds of mortality by AIRD status with adjustment for relevant characteristics.

Results
There were 79,390 individuals with a first MI, of whom 1,409 (1.8%) had AIRD. After adjusting for relevant covariates, the odds ratio (OR) for 30-day cardiovascular mortality in patients with AIRD was 1.44 (95% confidence interval (CI): 1.25 to 1.66), and the OR for 12-month cardiovascular mortality was 1.71 (95% CI: 1.51 to 1.94). The 90-day adjusted odds of percutaneous transluminal coronary angioplasty and coronary artery bypass graft were significantly lower in the AIRD group compared with controls (OR: 0.81, 95% CI: 0.70 to 0.94, and OR: 0.52, 95% CI: 0.39 to 0.69, respectively).

Conclusions
We identified a higher risk-adjusted mortality rate for the majority of patients with AIRD at 30 days and 12 months after first MI. We also identified lower post-MI revascularisation rates in the AIRD group, suggesting there may be current gaps in cardiovascular treatment for patients with AIRD.
In praise of discrepancy? Art and ideology revisited
Authors: Bosteels Bruno 
Published: February 2015

Abstract
This article traces a brief genealogy of the move from totality to discrepancy as a major shift in the understanding of ideology and its critique as it supposedly takes place in art. Drawing on the work of Jorge Luis Borges, a model is developed for the study of 'theoretical ideology', as distinct both from the 'political ideology' of the author and from the 'aesthetic ideology' of his work. Borges's texts on the paradox of Achilles and the tortoise, in particular, are read as signposts on the path that leads from Lukács to Adorno and from Sartre to Lacan or Miller.
Fuzzy-EKF Controller for Intelligent Wheelchair Navigation
Authors: Njah Malek , Jallouli Mohamed 
Published: February 2015

AbstractThe electric wheelchair gives more autonomy and facilitates movement for handicapped persons in the home or in a hospital. Among the problems faced by these persons are collision with obstacles, the doorway, the navigation in a hallway, and reaching the desired place. These problems are due to the difficult manipulation of an electric wheelchair, especially for persons with severe disabilities. Hence, we tried to add more functionality to the standard wheelchair in order to increase movement range, security, environment access, and comfort. In this context, we have developed an automatic control method for indoor navigation. The proposed control system is mounted on the electric wheelchair for the handicapped, developed in the research laboratory CEMLab (Control and Energy Management Laboratory-Tunisia). The proposed method is based on two fuzzy controllers that ensure target achievement and obstacle avoidance. Furthermore, an extended Kalman filter was used to provide precise measurements and more effective data fusion localization. In this paper, we present the simulation and experimental results of the wheelchair navigation system.
The Possibility of Micro-fission Chain-reactions and their Application to the Controlled Release of Thermonuclear Energy
Authors: Winterberg F. 
Published: February 2015

It had been shown 1,
2 recently that it may be possible to reach densities up to 103 g/cm3 by imploding a solid hydrogen pellet with the aid of a symmetric arrangement of multiple laser beams irradiating the pellet simultaneously from all sides. The purpose of this proposed scheme was to reduce the energy input requirements for the controlled release of thermonuclear energy delivered by laser ignited T - D micro-explosion systems.
It is shown in this paper that by applying the foregoing concept of high density compression to a pellet consisting of fissionable material such as U235, Pu239, or U223, the critical mass for the initiation of a fission chain reaction in these materials can be reduced by many orders of magnitude raising the possibility of micro-fission-explosions with laser energy inputs for compression within the expected reach of laser technology. Alternatively, the pellet compression may be also achieved by the employment of intense relativistic electron beams. In addition, by surrounding the fis­sionable pellet with a layer of dense T - D material to be compressed together with the pellet, the minimum pellet size can be furthermore reduced by neutron reflection from the high neutron albedo T - D shell. For fissionable pellets without a reflector the critical mass can be as small as ∼ 0.3 g requiring a laser energy input for compression of several megajoule. For a pellet surrounded by a T - D reflector the critical mass can be reducel down to ∼10-3g with a laser energy input for compression of several 105 joule.
In addition to the neutron albedo effect of the T - D shell there is a bootstrap mechanism where­by the T - D mantle achieves thermonuclear temperatures resulting in the emission of thermo­nuclear reaction neutrons into the fissionable pellet causing more fission reactions and thereby raising the temperature of the pellet. This then in turn will lead to an additional heating of the T - D blanket resulting in an increased flux of thermonuclear neutrons raising the fission rate even further. Because of the greatly increased material density, a fission chain reaction initiated in it will grow in proportion much faster than in uncompressed fissionable material as it is being used in conventional fission bombs.
The system described may have important usefulness as a small fission power plant especially for space propulsion applications but also for a more effective burn in a thermonuclear micro-bomb reactor as a fission supported fusion reaction.
Interdiffusion of Silver Ions in Molten Thallous Nitrate
Authors: Behn Anders , Sjöblom Carl-Axel 
Published: February 2015

The interdiffusion coefficient of silver ions in molten thallous nitrate has been determined with the gravimetric technique. The observed data can be "least-squares" fitted into an Arrhenius equation
D12 = 1.07 × 10-3 exp-(4130 ± 400)/R T
where D12 is expressed in cm2s-1, R in calories equivalent-1, and T in degrees K. Friction coefficients rAgTl calculated according to the Klemm 1 model indicate association between the cations, as has been indicated in mixtures of silver nitrate with heavy alkali nitrates also.