bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concomitant inactivation of the p53‐ and pRB‐ functional pathways predicts resistance to DNA damaging drugs in breast cancer in vivo
Authors: Knappskog Stian , Berge Elisabet O. , Chrisanthar Ranjan , Geisler Stephanie , Staalesen Vidar , Leirvaag Beryl , Yndestad Synnøve , de Faveri Elise , Karlsen Bård O. , Wedge David C. , Akslen Lars A. , Lilleng Peer K. , Løkkevik Erik , Lundgren Steinar , Østenstad Bjørn , Risberg Terje , Mjaaland Ingvild , Aas Turid , Lønning Per E. 
Published: May 2015

Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance to DNA damaging drugs in breast cancer better than TP53 mutations alone. Further, we hypothesized that redundant pathway(s) may compensate for loss of p53‐pathway signaling and that these are inactivated as well in resistant tumour cells. Here, we assessed genetic alterations of the retinoblastoma gene (RB1) and its key regulators: Cyclin D and E as well as their inhibitors p16 and p27. In an exploratory cohort of 69 patients selected from two prospective studies treated with either doxorubicin monotherapy or 5‐FU and mitomycin for locally advanced breast cancers, we found defects in the pRB‐pathway to be associated with therapy resistance (p‐values ranging from 0.001 to 0.094, depending on the cut‐off value applied to p27 expression levels). Although statistically weaker, we observed confirmatory associations in a validation cohort from another prospective study (n = 107 patients treated with neoadjuvant epirubicin monotherapy; p‐values ranging from 7.0 × 10−4 to 0.001 in the combined data sets). Importantly, inactivation of the p53‐and the pRB‐pathways in concert predicted resistance to therapy more strongly than each of the two pathways assessed individually (exploratory cohort: p‐values ranging from 3.9 × 10−6 to 7.5 × 10−3 depending on cut‐off values applied to ATM and p27 mRNA expression levels). Again, similar findings were confirmed in the validation cohort, with p‐values ranging from 6.0 × 10−7 to 6.5 × 10−5 in the combined data sets. Our findings strongly indicate that concomitant inactivation of the p53‐ and pRB‐ pathways predict resistance towards anthracyclines and mitomycin in breast cancer in vivo.
Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8+ T cells
Authors: Martinet Valérie , Tonon Sandrine , Torres David , Azouz Abdulkader , Nguyen Muriel , Kohler Arnaud , Flamand Véronique , Mao Chai-An , Klein William H. , Leo Oberdan , Goriely Stanislas 
Published: May 2015

AbstractCD8+ T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8+ T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of ‘virtual memory’ CD8+ T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of ‘virtual memory’ CD8+ T cells in an Eomes-dependent fashion. We further show that the development of ‘innate thymic’ CD8+ T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8+ T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8+ T cells.
The spinning apparatus of webspinners – functional-morphology, morphometrics and spinning behaviour
Authors: Büsse Sebastian , Hörnschemeyer Thomas , Hohu Kyle , McMillan David , Edgerly Janice S. 
Published: May 2015

AbstractWebspinners (Insecta: Embioptera) have a distinctly unique behaviour with related morphological characteristics. Producing silk with the basitarsomeres of their forelegs plays a crucial role in the lives of these insects – providing shelter and protection. The correlation between body size, morphology and morphometrics of the spinning apparatus and the spinning behaviour of Embioptera was investigated for seven species using state-of-the-art methodology for behavioural as well as for morphological approaches. Independent contrast analysis revealed correlations between morphometric characters and body size. Larger webspinners in this study have glands with greater reservoir volume, but in proportionally smaller tarsi relative to body size than in the smaller species. Furthermore, we present a detailed description and review of the spinning apparatus in Embioptera in comparison to other arthropods and substantiate the possible homology of the embiopteran silk glands to class III dermal silk glands of insects.
BRET evidence that β2 adrenergic receptors do not oligomerize in cells
Authors: Lan Tien-Hung , Liu Qiuju , Li Chunman , Wu Guangyu , Steyaert Jan , Lambert Nevin A. 
Published: May 2015

AbstractBioluminescence resonance energy transfer (BRET) is often used to study association of membrane proteins and in particular oligomerization of G protein-coupled receptors (GPCRs). Oligomerization of class A GPCRs is controversial, in part because the methods used to study this question are not completely understood. Here we reconsider oligomerization of the class A β2 adrenergic receptor (β2AR) and reevaluate BRET titration as a method to study membrane protein association. Using inducible expression of the energy acceptor at multiple levels of donor expression we find that BRET between β2AR protomers is directly proportional to the density of the acceptor up to ~3,000 acceptors μm−2 and does not depend on the density of the donor or on the acceptor:donor (A:D) stoichiometry. In contrast, BRET between tightly-associating control proteins does not depend on the density of the acceptor, but does depend on the density of the donor and on the A:D ratio. We also find that the standard frameworks used to interpret BRET titration experiments rely on simplifying assumptions that are frequently invalid. These results suggest that β2ARs do not oligomerize in cells and demonstrate a reliable method of assessing membrane protein association with BRET.
Selectivity Mechanism of the Voltage-gated Proton Channel, HV1
Authors: Dudev Todor , Musset Boris , Morgan Deri , Cherny Vladimir V. , Smith Susan M. E. , Mazmanian Karine , DeCoursey Thomas E. , Lim Carmay 
Published: May 2015

AbstractVoltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp–Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O+ protonated the SF, breaking the Asp–Arg linkage and opening the conduction pathway, whereas Na+ or Cl– was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp–Lys SF behaved like the Asp–Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH0–H2O0–Arg+ interactions with hydronium but unfavorable Asp––X–/X+–Arg+ interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis and signaling.
CMOS BEOL‐embedded z‐axis accelerometer
Authors: Michalik P. , Sánchez‐Chiva J.M. , Fernández D. , Madrenas J. 
Published: May 2015

A first reported complementary metal‐oxide semiconductor (CMOS)‐integrated acceleration sensor obtained through isotropic inter‐metal dielectric (IMD) etching of a back‐end‐of‐line (BEOL) integrated circuit interconnection stack, without any additional substrate etching steps, is presented. The mechanical device composed of a CMOS‐process 8 μm‐thick metal‐via‐metal stack of 135 μm diameter and suspended 2.5 μm over a bottom fixed electrode, has a resonance frequency of 20 kHz, a sensing capacitance of 50 fF with sensitivity 14 aF/G and it is integrated on the same substrate with a simple low‐noise amplifier reaching 25 mG of RMS noise measured from 0.25 to 100 Hz bandwidth.
The treatment of tax as expropriation in International investor–state arbitration
Authors: Lazem Ali , Bantekas Ilias 
Published: May 2015

Abstract
Domestic tax measures are treated by investment tribunals as a fundamental attribute of sovereignty and constitute lex specialis in relation to the general rule on expropriation under customary international law. Although both direct and indirect expropriation are possible through the imposition of tax measures, in practice such findings are rare and further restricted by joint tax vetoes and tax exclusion clauses in international investment treaties and bilateral tax treaties. This inclination in favour of host states is further confirmed by the requirement that the conduct requirements for expropriation be satisfied, although the role of conduct requirements is to differentiate between lawful and unlawful expropriation. The lex specialis character of tax measures suggests, particularly as a result of cases such as Burlington, that investment tribunals are unlikely to lower the threshold of state liability for expropriation arising from tax measures and are in fact likely to view the substantial deprivation standard very strictly and in a manner that requires a total deprivation of property.
Propensity Score–matched Comparison of Postoperative Adverse Outcomes between Geriatric Patients Given a General or a Neuraxial Anesthetic for Hip Surgery
Authors: Chu Chin-Chen , Weng Shih-Feng , Chen Kuan-Ting , Chien Chih-Chiang , Shieh Ja-Ping , Chen Jen-Yin , Wang Jhi-Joung 
Published: May 2015

AbstractAbstract
Using Taiwan’s in-patient claims database, the effect of anesthetic technique on in-hospital outcomes was assessed. Neuraxial techniques were found to have lower rates of in-hospital adverse outcomes of several types including mortality, stroke, and others.

Background:
The effects of the mode of anesthesia on major adverse postoperative outcomes in geriatric patients are still inconclusive. The authors hypothesized that a neuraxial anesthetic (NA) rather than a general anesthetic (GA) would yield better in-hospital postoperative outcomes for geriatric patients undergoing hip surgery.

Methods:
The authors used data from Taiwan’s 1997–2011 in-patient claims database to evaluate the effect of anesthesia on in-hospital outcomes. The endpoints were mortality, stroke, transient ischemic stroke, myocardial infarction, respiratory failure, and renal failure. Of the 182,307 geriatric patients who had hip surgery, a GA was given to 53,425 (29.30%) and an NA to 128,882 (70.70%). To adjust for baseline differences and selection bias, patients were matched on propensity scores, which left 52,044 GA and 52,044 NA patients.

Results:
GA-group patients had a greater percentage and higher odds of adverse in-hospital outcomes than did NA-group patients: death (2.62 vs. 2.13%; odds ratio [OR], 1.24; 95% CI, 1.15 to 1.35; P < 0.001), stroke (1.61 vs. 1.38%; OR, 1.18, 95% CI, 1.07 to 1.31; P = 0.001), respiratory failure (1.67 vs. 0.63%; OR, 2.71; 95% CI, 2.38 to 3.01; P < 0.001), and intensive care unit admission (11.03 vs. 6.16%; OR, 1.95; 95% CI, 1.87 to 2.05; P < 0.001), analyzed using conditional logistic regression. Moreover, patients given a GA had longer hospital stays (10.77 ± 8.23 vs. 10.44 ± 6.67 days; 95% CI, 0.22 to 0.40; P < 0.001) and higher costs (New Taiwan Dollars [NT$] 86,606 ± NT$74,162 vs. NT$74,494 ± NT$45,264; 95% CI, 11,366 to 12,859; P < 0.001).

Conclusion:
For geriatric patients undergoing hip surgery, NA was associated with fewer odds of adverse outcomes than GA.
Dynamics and noise radiation of multiple bubbles in compressible fluid using boundary integral equation
Authors: Ye Xi , Sun Longquan , Pang Fuzhen 
Published: May 2015

Purpose
– The purpose of this paper is to research the interaction between multiple bubbles and their noise radiation considering the influence of compressibility. The influences of bubble spacing, initial inner pressure, buoyance and phase difference are presented with different bubbles arrangements.

Design/methodology/approach
– Based on wave equation, the new boundary integral equation considering the compressibility is given by the matching between prophase and anaphase approximation of bubble motion and solved with boundary element method. The time-domain characteristics of noise induced by multiple bubbles are obtained by the moving boundary Kirchhoff integral equation. With the surface discretization and coordinate transformation, the bubbles surface is treated as a moving deformable boundary and noise source, and the integral is implemented on the surface directly.

Findings
– Numerical results show the manner of jet generation will be affected by the phase difference between bubbles. With the increasing of phase difference, the directive property of noise becomes obvious. With the enlargement of initial inner pressure, the sound pressure will arise at the early stage of expanding, and the increasing of buoyance parameter will reduce the sound pressure after the generation of jet. Since the consideration of compressibility, the oscillation amplitude of bubbles will be weakened.

Originality/value
– The paper could provide the reference for the research about the dynamics and noise characteristics of multiple bubbles in compressible fluid. And the new method based on boundary integral equation to simulate the multiple bubbles motion and noise radiation is presented.
Heat transfer and fluid flow of a non-Newtonian nanofluid over an unsteady contracting cylinder employing Buongiorno’s model
Authors: Mahdy A. , Chamkha A 
Published: May 2015

Purpose
– The purpose of this paper is to discuss a combined similarity-numerical approach that is used to study the unsteady two-dimensional flow of a non-Newtonian nanofluid over a contracting cylinder using Buongiorno’s model and the Casson fluid model that is used to characterize the non-Newtonian fluid behavior.

Design/methodology/approach
– Similarity transformations are employed to transform the unsteady Navier-Stokes partial differential equations into a system of ordinary differential equations. The transformed equations are then solved numerically by means of the very robust symbolic computer algebra software MATLAB employing the routine bvpc45.

Findings
– The effect of increasing values of the Casson parameter is to suppress the velocity field (in absolute sense), the temperature and concentration decrease as Casson parameter increase. The heat and mass transfer rates decrease with the increase of unsteadiness parameters and Brownian motion parameter. In addition, they increase as the Casson parameter and the thermophoresis parameter increase.

Originality/value
– The problem is relatively original and represents a very important contribution to the field of non-Newtonian nanofluids.
Thermally stratified stagnation point flow of Casson fluid with slip conditions
Authors: Hayat Tasawar , Farooq Muhammad , Alsaedi A. 
Published: May 2015

Purpose
– The purpose of this paper is to focus on the stratified phenomenon through vertical stretching cylinder in the region of stagnation point with slip effects.

Design/methodology/approach
– Homotopy analysis method is used to find the series solutions of the governing equations.

Findings
– Velocity profile decreases with an increase in stratified parameters due to temperature and concentration. Velocity and thermal slips cause a reduction in the velocity profile. Thermally stratified and thermal slip parameters reduce the temperature field.

Originality/value
– The present analysis has not been existed in the literature yet.
On the Adomian decomposition method for solving the Stefan problem
Authors: Bougoffa Lazhar , Rach Randolph , Wazwaz Abdul-Majid , Duan Jun-Sheng 
Published: May 2015

Purpose
– The purpose of this paper is concerned with a reliable treatment of the classical Stephan problem. The Adomian decomposition method (ADM) is used to carry out the analysis, Moreover, the authors extend the work to examine the Stefan problem with variable latent heat. The study confirms the accuracy and efficiency of the employed method.

Design/methodology/approach
– The new technique, as presented in this paper in extending the applicability of the ADM, has been shown to be very efficient for solving the Stefan problem.

Findings
– The Stefan problem with variable latent heat was examined as well. The ADM was effectively used for analytic treatment of the Stefan problem with and without variable latent heat.

Originality/value
– The paper presents a new solution algorithm for the Stefan problem.
Approximate analytical solution for the one-dimensional nonlinear Boussinesq equation
Authors: Aminikhah Hossein 
Published: May 2015

Purpose– The purpose of this paper is to provide closed-form approximate solutions to the one-dimensional Boussinesq equation for a semi-infinite aquifer when the hydraulic head at the source is an arbitrary function of time. Combination of the Laplace transform and homotopy perturbation methods (LTHPM) are considered as an algorithm which converges rapidly to the exact solution of the nonlinear Boussinesq equation.Design/methodology/approach– The authors present the solution of nonlinear Boussinesq equation by combination of Laplace transform and new homotopy perturbation methods. An important property of the proposed method, which is clearly demonstrated in example, is that spectral accuracy is accessible in solving specific nonlinear nonlinear Boussinesq equation which has analytic solution functions.Findings– The authors proposed a combination of Laplace transform method and homotopy perturbation method to solve the one-dimensional Boussinesq equation. The results are found to be in excellent agreement. The results show that the LTNHPM is an effective mathematical tool which can play a very important role in nonlinear sciences.Originality/value– The authors provide closed-form approximate solutions to the one-dimensional Boussinesq equation for a semi-infinite aquifer when the hydraulic head at the source is an arbitrary function of time. In this work combination of Laplace transform and new homotopy perturbation methods (LTNHPM) are considered as an algorithm which converges rapidly to the exact solution of the nonlinear Boussinesq equation.
Is double fit a sufficient condition for SHRM success?
Authors: Garcia-Carbonell Natalia , Martin-Alcazar Fernando , Sanchez-Gardey Gonzalo 
Published: May 2015

Purpose– This paper aims to discuss the association between human resource management and performance from a process perspective, differentiating intended and implemented vertical and horizontal fit. Although researchers have examined deeply the relationship between these constructs, extant literature demonstrates inconclusive results. Previous studies have stressed the strategic importance of vertical and horizontal fit from a prescriptive view. Nevertheless, a deeper understanding, focused on management processes, is needed.Design/methodology/approach– This paper reviews and integrates two streams of strategic human resources management (SHRM) literature: the fit perspective, drawing on Martín-Alcázaret al.’s (2005) model, and the system strength approach, proposed by Bowen and Ostroff (2004).Findings– The conceptual analysis developed in this paper concludes that HRM system strength mediates the effects of an aligned strategy on performance. In this sense, the paper argues that success in implementation of the HRM strategy depends on employees’ perceptions about the system of policies and practices through which it is carried out. Additionally, organizational communication is considered as the mechanism to create a shared HRM meaning to translate to employees.Practical implications– Drawing on the theoretical discussions in the paper, the following implications for HRM practice are identified: the usefulness of the system strength construct as a tool to measure employees’ perceptions and anticipate potential problems at the implementation stage, the importance of organizational communication mechanisms, the relevance of formal and informal connections between HR managers and top executives and the need for specific training to promote HR managers’ communicational skills.Originality/value– This study examines the relationship between HRM and organizational performance by presenting a new model that integrates HRM strategy formulation and implementation, proposes employee perceptions concerning HRM are mediators of HRM strategy and firm performance, highlights the role of organizational communication in creating and managing shared HR messages and introduces system strength as an instrument to assess vertical and horizontal fit during implementation.
Leader roles, organization-based self-esteem, and employee outcomes
Authors: Norman Steven M. , Gardner Donald G. , Pierce Jon L. 
Published: May 2015

Purpose– The purpose of this paper is to examine the relationships between different managerial roles and organization-based self-esteem (OBSE), and employee job satisfaction, organization commitment, and turnover and absence intentions.Design/methodology/approach– Survey data were collected from 1,386 employees in a high technology industry. Employees described the roles their managers fulfilled, and then rated their own OBSE, satisfaction, commitment, and turnover and absence intent.Findings– Different managerial roles had different relationships with OBSE, which mediated the relationships between some of the management roles and employee outcomes.Research limitations/implications– This study used a cross-sectional design with single source data in a single industry. Future research should examine these relationships using longitudinal designs, multiple data sources, and a variety of industries.Practical implications– Managers should be aware that their behaviors affect employee self-esteem, which in turn has strong relationships with a variety of important outcomes. Managers should be trained to manifest behaviors that increase employee self-esteem.Originality/value– This is the first study to examine the effects of management roles on organization-based self-esteem, and ultimately employee satisfaction, commitment, and withdrawal intentions.