bluuebunny/crossref_metadata_2025 huggingface dataset:
Silencing of high‐mobility group box 2 (HMGB2) modulates cisplatin and 5‐fluorouracil sensitivity in head and neck squamous cell carcinoma
Authors: Syed Nazia , Chavan Sandip , Sahasrabuddhe Nandini A. , Renuse Santosh , Sathe Gajanan , Nanjappa Vishalakshi , Radhakrishnan Aneesha , Raja Remya , Pinto Sneha M. , Srinivasan Anand , Prasad T. S. Keshava , Srikumar Kotteazeth , Gowda Harsha , Santosh Vani , Sidransky David , Califano Joseph A. , Pandey Akhilesh , Chatterjee Aditi
Published: October 2014

Dysregulation of protein expression is associated with most diseases including cancer. MS‐based proteomic analysis is widely employed as a tool to study protein dysregulation in cancers. Proteins that are differentially expressed in head and neck squamous cell carcinoma (HNSCC) cell lines compared to the normal oral cell line could serve as biomarkers for patient stratification. To understand the proteomic complexity in HNSCC, we carried out iTRAQ‐based MS analysis on a panel of HNSCC cell lines in addition to a normal oral keratinocyte cell line. LC‐MS/MS analysis of total proteome of the HNSCC cell lines led to the identification of 3263 proteins, of which 185 proteins were overexpressed and 190 proteins were downregulated more than twofold in at least two of the three HNSCC cell lines studied. Among the overexpressed proteins, 23 proteins were related to DNA replication and repair. These included high‐mobility group box 2 (HMGB2) protein, which was overexpressed in all three HNSCC lines studied. Overexpression of HMGB2 has been reported in various cancers, yet its role in HNSCC remains unclear. Immunohistochemical labeling of HMGB2 in a panel of HNSCC tumors using tissue microarrays revealed overexpression in 77% (54 of 70) of tumors. The HMGB proteins are known to bind to DNA structure resulting from cisplatin‐DNA adducts and affect the chemosensitivity of cells. We observed that siRNA‐mediated silencing of HMGB2 increased the sensitivity of the HNSCC cell lines to cisplatin and 5‐FU. We hypothesize that targeting HMGB2 could enhance the efficacy of existing chemotherapeutic regimens for treatment of HNSCC. All MS data have been deposited in the ProteomeXchange with identifier PXD000737 (http://proteomecentral.proteomexchange.org/dataset/PXD000737).
Psychosocial telephone interventions for patients with cancer and survivors: a systematic review
Authors: Okuyama Sonia , Jones Whitney , Ricklefs Christine , Tran Zung Vu
Published: October 2014

Objective

Over one third of patients with cancer experience elevated psychosocial distress. As screening for distress becomes more common, the number of patients referred for psychosocial care will increase. Psychosocial telephone interventions are recommended as a convenient and exportable alternative to in‐person interventions addressing psychosocial distress. This study reviews the efficacy of randomized controlled trials (RCTs) of psychosocial telephone interventions for patients with cancer.

Methods

We conducted a systematic review of peer‐reviewed RCTs evaluating telephone interventions in adult patients with cancer across the survivorship continuum.

Results

Through a database search, 480 articles were identified. After manual review, 13 were included, with 7 additional studies identified by back citation, totaling 20 studies. Participants were largely Caucasian, highly educated, with mean age ranging from 49 to 75 years. Most participants were patients with breast cancer (n = 13 studies). Sample sizes were generally small, with most patients recruited from large medical centers. Only one screened for psychosocial need. Interventions varied greatly in length and intensity. Eight studies reported significant effects post‐intervention in the hypothesized direction on at least one psychosocial outcome measure. Of these eight studies, four included more than one follow‐up assessment; of these, only one reported significant effects at last follow‐up. No clear commonalities were found among studies reporting significant effects.

Conclusions

Methodological concerns and lack of consistency in adherence to CONSORT reporting guidelines were identified. This body of research would benefit from well‐designed, theory‐based RCTs adequately powered to provide more definitive evidence for intervention efficacy. This will probably require multi‐institutional collaborations, guided by intervention and research methodology best practices. Copyright © 2014 John Wiley & Sons, Ltd.
Structure of the lysine specific protease Kgp from Porphyromonas gingivalis, a target for improved oral health
Authors: Gorman Michael A. , Seers Christine A. , Michell Belinda J. , Feil Susanne C. , Huq N. Laila , Cross Keith J. , Reynolds Eric C. , Parker Michael W.
Published: October 2014

The oral pathogen Porphyromonas gingivalis is a keystone pathogen in the development of chronic periodontitis. Gingipains, the principle virulence factors of P. gingivalis are multidomain, cell‐surface proteins containing a cysteine protease domain. The lysine specific gingipain, Kgp, is a critical virulence factor of P. gingivalis. We have determined the X‐ray crystal structure of the lysine‐specific protease domain of Kgp to 1.6 Å resolution. The structure provides insights into the mechanism of substrate specificity and catalysis.
Solution NMR characterization of WTCXCL8 monomer and dimer binding to CXCR1 N‐terminal domain
Authors: Joseph Prem Raj B. , Rajarathnam Krishna
Published: October 2014

Chemokine CXCL8 and its receptor CXCR1 are key mediators in combating infection and have also been implicated in the pathophysiology of various diseases including chronic obstructive pulmonary disease (COPD) and cancer. CXCL8 exists as monomers and dimers but monomer alone binds CXCR1 with high affinity. CXCL8 function involves binding two distinct CXCR1 sites – the N‐terminal domain (Site‐I) and the extracellular/transmembrane domain (Site‐II). Therefore, higher monomer affinity could be due to stronger binding at Site‐I or Site‐II or both. We have now characterized the binding of a human CXCR1 N‐terminal domain peptide (hCXCR1Ndp) to WT CXCL8 under conditions where it exists as both monomers and dimers. We show that the WT monomer binds the CXCR1 N‐domain with much higher affinity and that binding is coupled to dimer dissociation. We also characterized the binding of two CXCL8 monomer variants and a trapped dimer to two different hCXCR1Ndp constructs, and observe that the monomer binds with ∼10‐ to 100‐fold higher affinity than the dimer. Our studies also show that the binding constants of monomer and dimer to the receptor peptides, and the dimer dissociation constant, can vary significantly as a function of pH and buffer, and so the ability to observe WT monomer peaks is critically dependent on NMR experimental conditions. We conclude that the monomer is the high affinity CXCR1 agonist, that Site‐I interactions play a dominant role in determining monomer vs. dimer affinity, and that the dimer plays an indirect role in regulating monomer function.
Irreversible electroporation: Just another form of thermal therapy?
Authors: van Gemert Martin J. C. , Wagstaff Peter G. K. , de Bruin Daniel M. , van Leeuwen Ton G. , van der Wal Allard C. , Heger Michal , van der Geld Cees W. M.
Published: October 2014

BACKGROUND

Irreversible electroporation (IRE) is (virtually) always called non‐thermal despite many reports showing that significant Joule heating occurs. Our first aim is to validate with mathematical simulations that IRE as currently practiced has a non‐negligible thermal response. Our second aim is to present a method that allows simple temperature estimation to aid IRE treatment planning.

METHODS

We derived an approximate analytical solution of the bio‐heat equation for multiple 2‐needle IRE pulses in an electrically conducting medium, with and without a blood vessel, and incorporated published observations that an electric pulse increases the medium's electric conductance.

RESULTS

IRE simulation in prostate‐resembling tissue shows thermal lesions with 67–92°C temperatures, which match the positions of the coagulative necrotic lesions seen in an experimental study. Simulation of IRE around a blood vessel when blood flow removes the heated blood between pulses confirms clinical observations that the perivascular tissue is thermally injured without affecting vascular patency.

CONCLUSIONS

The demonstration that significant Joule heating surrounds current multiple‐pulsed IRE practice may contribute to future in‐depth discussions on this thermal issue. This is an important subject because it has long been under‐exposed in literature. Its awareness pleads for preventing IRE from calling “non‐thermal” in future publications, in order to provide IRE‐users with the most accurate information possible. The prospect of thermal treatment planning as outlined in this paper likely aids to the important further successful dissemination of IRE in interventional medicine. Prostate 75:332–335, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc.
Efficacy studies of an antibody‐drug conjugate PSMA‐ADC in patient‐derived prostate cancer xenografts
Authors: DiPippo Vincent A. , Olson William C. , Nguyen Holly M. , Brown Lisha G. , Vessella Robert L. , Corey Eva
Published: October 2014

BACKGROUND

It is timely and important to develop new treatment modalities for advanced prostate cancer, because even the newly FDA approved treatments, despite providing significant survival benefits, do not constitute cure of this disease. Antibody drug conjugates (ADCs) represent a promising approach to cancer therapy. Prostate‐specific membrane antigen (PSMA) is expressed in advanced prostate cancer and targeting this protein is used for imaging of advanced prostate cancer as well as development of targeting strategies. The objective of our studies was to evaluate the efficacy of PSMA ADC against a series of patient‐derived prostate cancer xenografts (LuCaP 58, LuCaP 77, LuCaP 96CR, and LuCaP 105) with different characteristics, including varying levels of PSMA expression and responses to androgen suppression.

METHODS

Mice bearing subcutaneous LuCaP prostate cancer‐derived xenografts received PSMA antibody monomethyl auristatin E (MMAE) drug conjugate (PSMA ADC) in which the antibody and MMAE are linked via a protease‐cleavable linker. PSMA ADC dose ranged from 1 to 6 mg/kg. Unmodified PSMA mAb + free MMAE at the amount equivalent to those contained in 6 mg/kg PSMA ADC was used as control. All treatments were administered once a week via tail‐vein injections and repeated four times once a week and tumor responses were monitored for 10 weeks. IHC analyses were performed to determine PSMA and AR expression and effects on proliferation.

RESULTS

Treatment responses varied widely across the tumor models, from complete tumor regressions in LuCaP 96CR to largely unimpeded tumor progression of LuCaP 58, which had the lowest baseline level of PSMA expression. Intermediate antitumor effects were seen for LuCaP 77 and LuCaP 105 tumors, despite their having similar basal expression of PSMA as LuCaP 96CR. Interestingly, we detected substantial differences in responses even within the same model, indicating that PSMA expression is not the only factor involved in treatment outcomes.

CONCLUSIONS

Our results show high efficacy of PSMA ADC in advanced prostate cancer but also considerable variability in effects despite PSMA expression. Further studies to identify tumor characteristics that are predictive of treatment response are ongoing. Prostate 75:303–313, 2015. © 2014 Wiley Periodicals, Inc.
Can erbium dopant occupy both cation sites in cubic barium titanate via a mechanism different than self‐compensation?
Authors: Zulueta Y. A. , Guerrero F. , Leyet Y. , Anglada‐Rivera J. , González‐Romero R. L. , Meléndez Juan J.
Published: October 2014

The defect energetics for several dopant incorporation modes and the dielectric–electric properties in Er‐doped BaTiO3 were studied by numerical simulations and the dielectric modulus formalism. Two “mixed” incorporation modes, both compatible with the existence of oxygen vacancies, are proposed. Simulation results for the solution energies show that, despite self‐compensation is the most favourable mode, the mixed modes exhibit quite similar energies and, therefore, could be active under some conditions. The incorporation of Er3+ into the BaTiO3 lattice decreases the dc conductivities with respect to the undoped case at high temperatures. Molecular Dynamics calculations and experimental measurements about conducting properties of Er‐doped BaTiO3 allow one to calculate activation energies for ionic conductivity, which agree with data for oxygen migration. Experimental and Molecular Dynamics data are then correlated with the possible defect configurations.

Scheme of the defect clusters corresponding to the proposed mixed incorporation mechanisms: (a) “Ti‐vac” and (b) “Ba‐vac”. Green, grey, blue, and red balls correspond, respectively, to Ba2+, Ti4+, Er3+, and O2− ions.
Band‐gap and phonon distribution in alkali halides
Authors: Messaoudi I. S. , Zaoui A. , Ferhat M.
Published: October 2014

A systematic first‐principles study is performed to calculate the structural, electronic, dynamical, and thermodynamic properties of alkali halides NaF, NaCl, NaBr, and NaI by means of both full‐potential linear augmented plane‐wave, and plane wave pseudopotential methods. The obtained structural parameters agree favourably with experimental findings. The calculated band gaps are underestimated by GGA functional compared to experiment. The gap values are improved from the modified Becke–Johnson exchange potential, which gives band gaps in perfect agreement with the measured values. In addition, linear‐response approach to the density functional theory is used to derive several quantities such as the Born effective charges, high‐frequency dielectric constant, phonon band structure, and phonon density of states. The dynamical properties of Na‐based alkali halides are also analysed and discussed. Finally the temperature dependence of various quantities such as the mean‐squared displacement, and the heat capacity are computed using the quasi‐harmonic approximation.
A mass restoration scheme for limited‐area models with semi‐Lagrangian advection
Authors: Aranami Kohei , Davies Terry , Wood Nigel
Published: October 2014

A method for imposing mass conservation in limited‐area models (LAMs) with non‐conservative semi‐Lagrangian advection is proposed. The key feature of the scheme is to estimate the budget of the total mass through the lateral boundaries by splitting the original field into interior and exterior areas and to advect them individually. Idealized and real test cases show the reduction in error of the total mass, especially in the case when a monotonicity filter is applied.
Computation of the real structured singular value via pole migration
Authors: Iordanov P. , Halton M.
Published: October 2014

The paper introduces a new computationally efficient algorithm to determine a lower bound on the real structured singular value μ. The algorithm is based on a pole migration approach where an optimization solver is used to compute a lower bound on real μ independent of a frequency sweep. A distinguishing feature of this algorithm from other frequency independent one‐shot tests is that multiple localized optima (if they exist) are identified and returned from the search. This is achieved by using a number of alternative methods to generate different initial conditions from which the optimization solver can initiate its search from. The pole migration algorithm presented has also been extended to determine lower bounds for complex parametric uncertainties as well as full complex blocks. However, the results presented are for strictly real and repeated parametric uncertainty problems as this class of problem is the focus of this paper and are in general the most difficult to solve. Copyright © 2014 John Wiley & Sons, Ltd.
Seeing the Case Clearly: File‐Work, Material Mediation, and Visualizing Practices in a Dutch Criminal Court
Authors: van Oorschot Irene
Published: October 2014

In Dutch criminal courts, judges and their assisting clerks spend significant amounts of time doing file‐work in preparation for the court hearing: a practice they often call “visualizing the case.” This practice is distributed over clerks and judges and materially mediated: the legal case file enters into face‐to‐file interaction as both a text and a material object. This article aims to unpack what techniques clerks and judges draw on in order to come to “see the case clearly,” while at the same time it elaborates on the renegotiations of these largely paper‐based practices when court workers are confronted with the digitization of case files.
Wind field simulation and wind‐induced responses of large wind turbine tower‐blade coupled structure
Authors: Ke S T , Ge Y J , Wang T G , Cao J F , Tamura Y
Published: October 2014

Herein, by a case study on a 5‐MW wind turbine system developed by Nanjing University of Aeronautics and Astronautics, the wind field simulation and wind‐induced vibration characteristics of wind turbine tower‐blade coupled systems is analyzed. First, the blade‐nacelle‐tower‐basis integrated finite element model with centrifugal forces induced by rotational blades is established. Then, based on a harmony superposition method and the modified blade element‐momentum theory, the fluctuating wind field of tower‐blade coupled systems is simulated, which considers wind shear effect, tower shadow effect, rotational effect, blade‐tower dynamic and model interaction effects. Finally, the wind‐induced dynamic responses and wind vibration coefficients of the wind turbine tower‐blade coupled structure are discussed through the ‘consistent coupled method’ previously proposed by us. The results indicate that the wind‐induced responses of a large wind turbine tower‐blade coupled structure present complicated modal responses and multimode coupling effect. Additionally, the rotational effect would amplify aerodynamic loads on blades with high frequency, wind‐induced dynamic responses and wind vibration coefficients of wind turbine tower. The centrifugal force effect could also amplify natural vibration frequency of the tower‐blade coupled system and reduce the wind‐induced dynamic responses and wind vibration coefficients of wind turbine tower. The research could contribute to wind‐resistant design of structure for a large‐scale wind turbine tower‐blade system. Copyright © 2014 John Wiley & Sons, Ltd.
Rotor position estimation method of IPMSM using HF signal injection and sliding‐mode controller
Authors: Yoon Tae‐Min , Lee June‐Seok , Lee Kyo‐Beum
Published: October 2014

This paper presents a simplified algorithm for the estimation of rotor position. A high‐frequency (HF) sinusoidal voltage is injected into the stator of a motor. An interior permanent magnet synchronous motor (IPMSM) has spatial saliency because the d‐ and q‐axis inductances are different from each other. The injected HF voltage is influenced by this saliency. Therefore, the rotor position is included in the stator current of the motor. The proposed method uses different synchronous reference frame transformations (SFTs) to extract the rotor position error between the estimated value and actual value. Also, a sliding‐mode controller is used for robustness against parameter variation and external disturbance. The experimental results confirm the effectiveness of the proposed method by showing waveforms of the rotor speed and position with load conditions. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Effective frequency range of ladder network realization for complex permeability of magnetic sheets
Authors: Shindo Yuji , Noro Osamu
Published: October 2014

By using Cauer realization, the complex permeability of magnetic sheets is realized by a finite‐order ladder network. The effective frequency range of this ladder network is derived by using the corner frequency of the network. It is shown that Cauer realization can cover a wide frequency range with a very small number of circuit components. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
An efficient search algorithm for ACELP algebraic codebook
Authors: Yeh Cheng‐Yu
Published: October 2014

In a bid to enhance the search performance, this paper presents an improved version of reduced candidate mechanism (RCM), an algebraic codebook search conducted on an algebraic code‐excited linear‐prediction (ACELP) speech coder. This improvement is made on the basis of two findings in our prior work. The first finding is that a pulse with a high contribution in the associated track is more likely to serve as the optimal pulse in the optimal codevector; the second is that the speech quality can be well maintained at a search accuracy above 50% approximately. Subsequently, a new finding in this study is that there is a 0.8321 probability that the No. 1 ranked pulse in a global sorting by pulse contribution is indeed one of the optimal pulses. Hence, the No. 1 pulse in the global sorting is labeled as one of the optimal pulses, following which a sequence of search tasks is fulfilled through RCM. This proposed complexity reduction algorithm, implemented on a G.729A speech codec, takes as few as eight searches, a search load amounting to 2.5% of G.729A, 12.5% of global pulse replacement method (iteration = 2), 16.7% of iteration‐free pulse replacement method, and 50% of RCM (N = 2). This proposal is thus found to successfully reduce the required computational complexity to a great extent as intended. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Electronic circuit using magnetic tunnel junctions with normal and inverse magnetoresistive effects
Authors: Isogami Shinji , Owada Takuya
Published: October 2014

CoFeB/MgO/CoFeB‐based magnetic tunnel junctions (CoFeB‐MTJs) with the tunneling magnetoresistance (TMR) ratio of 181% and Fe4N/MgO/CoFe‐based MTJs (Fe4N‐MTJs) with −66% TMR ratio were fabricated using a magnetron sputtering system. In this letter, we report the layout of an electronic circuit comprising both MTJs. Two independent external magnetic fields were applied to the MTJs, which worked as binary inputs as in present logic gates. The demonstrations reveal that the circuits behave like a three‐way switching device with NOR logic operation. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
A multistage multiobjective substation siting and sizing model based on operator–repair genetic algorithm
Authors: Jiao Runhai , Yang Zhen , Shi Ruifeng , Lin Biying
Published: October 2014

The establishment of a multistage multiobjective substation siting and sizing planning model, taking into account various constraints such as load flow constraint, maximum capacity constraint, and maximum power supply radius constraint makes possible substation planning between multiple years to be adjusted to achieve an optimal overall plan. Through multiple optimization objectives, it is possible to prevent the plan from becoming useless because of excessive changes in power supply affiliation during the multistage optimization process. To find the optimal solution for the model, a repair operator is proposed and used with an improved multiobjective genetic algorithm to repair the decision variables for each chromosome corresponding to one stage so as to satisfy the constraints while ensuring that population diversity evolves heuristically to the optimal solution. Moreover, a tournament selection operator based on crowding distance is adopted, which can prevent the algorithm from premature convergence and make populations trend to the Pareto frontier. Experimental results show that the proposed model and algorithm can efficiently solve the issue of rolling planning between multiple target years and achieve a joint optimal planning. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
An impedance measurement of a small‐capacitance circuit using transient responses for lightning surge analysis
Authors: Permata Diah , Nagaoka Naoto
Published: October 2014

A method to measure a small capacitance with its loss resistance using a set of transient current waveforms is proposed in this paper. The parameters are obtained from the time constants in the time domain. The method has high resistance to extraneous noise, because a time‐to‐frequency transformation, which is sensitive to noise, is not required. The transient current waveforms are obtained by a voltage or current source, a current transformer, and a waveform recorder. The measured capacitance by the proposed method is not affected by the capacitance of the voltage probe, because it is obtained without any voltage information. The sheath surge impedance of the current injection cable, which is indispensable for the transient measurement, is corrected. The application of the method has the advantage in that it allows the modeling of a fast transient of a power apparatus, comparing it with the steady‐state measurement using an impedance measuring instrument. The proposed method is applied to create an equivalent circuit between electrodes implanted into a piece of wood, and its reliability is confirmed by comparison between the measured and calculated results. Stray capacitances of a miniature circuit breaker are also measured, and the results show that the proposed method is applicable to equipment in power systems. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Processing of preribosomal RNA in Saccharomyces cerevisiae
Authors: Fernández‐Pevida Antonio , Kressler Dieter , de la Cruz Jesús
Published: October 2014

Most, if not all RNAs, are transcribed as precursors that require processing to gain functionality. Ribosomal RNAs (rRNA) from all organisms undergo both exo‐ and endonucleolytic processing. Also, in all organisms, rRNA processing occurs inside large preribosomal particles and is coupled to nucleotide modification, folding of the precursor rRNA (pre‐rRNA), and assembly of the ribosomal proteins (r‐proteins). In this review, we focus on the processing pathway of pre‐rRNAs of cytoplasmic ribosomes in the yeast Saccharomyces cerevisiae, without doubt, the organism where this pathway is best characterized. We summarize the current understanding of the rRNA maturation process, particularly focusing on the pre‐rRNA processing sites, the enzymes responsible for the cleavage or trimming reactions and the different mechanisms that monitor and regulate the pathway. Strikingly, the overall order of the various processing steps is reasonably well conserved in eukaryotes, perhaps reflecting common principles for orchestrating the concomitant events of pre‐rRNA processing and ribosome assembly. WIREs RNA 2015, 6:191–209. doi: 10.1002/wrna.1267

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes

Translation > Ribosome Biogenesis

RNA Processing > rRNA Processing
Ilf3 and NF90 functions in RNA biology
Authors: Castella Sandrine , Bernard Rozenn , Corno Mélanie , Fradin Aurélie , Larcher Jean‐Christophe
Published: October 2014

Double‐stranded RNA‐binding proteins (DRBPs) are known to regulate many processes of RNA metabolism due, among others, to the presence of double‐stranded RNA (dsRNA)‐binding motifs (dsRBMs). Among these DRBPs, Interleukin enhancer‐binding factor 3 (Ilf3) and Nuclear Factor 90 (NF90) are two ubiquitous proteins generated by mutually exclusive and alternative splicings of the Ilf3 gene. They share common N‐terminal and central sequences but display specific C‐terminal regions. They present a large heterogeneity generated by several post‐transcriptional and post‐translational modifications involved in their subcellular localization and biological functions. While Ilf3 and NF90 were first identified as activators of gene expression, they are also implicated in cellular processes unrelated to RNA metabolism such as regulation of the cell cycle or of enzymatic activites. The implication of Ilf3 and NF90 in RNA biology will be discussed with a focus on eukaryote transcription and translation regulation, on viral replication and translation as well as on noncoding RNA field. WIREs RNA 2015, 6:243–256. doi: 10.1002/wrna.1270

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
On minimizers of interaction functionals with competing attractive and repulsive potentials
Authors: Fetecau Razvan C. , Topaloglu Ihsan , Choksi Rustum
Published: October 2014

We consider a family of interaction functionals consisting of power-law potentials with attractive and repulsive parts and use the concentration compactness principle to establish the existence of global minimizers. We consider various minimization classes, depending on the signs of the repulsive and attractive power exponents of the potential. In the special case of quadratic attraction and Newtonian repulsion we characterize in detail the ground state.
Sites and functional consequence of VDAC–alkylphenol anesthetic interactions
Authors: Weiser Brian P. , Bu Weiming , Wong David , Eckenhoff Roderic G.
Published: October 2014

General anesthetics have previously been shown to bind mitochondrial VDAC. Here, using a photoactive analog of the anesthetic propofol, we determined that alkylphenol anesthetics bind to Gly56 and Val184 on rat VDAC1. By reconstituting rat VDAC into planar bilayers, we determined that propofol potentiates VDAC gating with asymmetry at the voltage polarities; in contrast, propofol does not affect the conductance of open VDAC. Additional experiments showed that propofol also does not affect gramicidin A properties that are sensitive to lipid bilayer mechanics. Together, this suggests propofol affects VDAC function through direct protein binding, likely at the lipid‐exposed channel surface, and that gating can be modulated by ligand binding to the distal ends of VDAC β‐strands where Gly56 and Val184 are located.
Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus
Authors: Maejima Yuko , Sakuma Kazuya , Santoso Putra , Gantulga Darambazar , Katsurada Kenichi , Ueta Yoichi , Hiraoka Yuichi , Nishimori Katsuhiko , Tanaka Shigeyasu , Shimomura Kenju , Yada Toshihiko
Published: October 2014

Intracerebroventricular injection of oxytocin (Oxt), a neuropeptide produced in hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), melanocortin‐dependently suppresses feeding. However, the underlying neuronal pathway is unclear. This study aimed to determine whether Oxt regulates propiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of the hypothalamus. Intra‐ARC injection of Oxt decreased food intake. Oxt increased cytosolic Ca2+ in POMC neurons isolated from ARC. ARC POMC neurons expressed Oxt receptors and were contacted by Oxt terminals. Retrograde tracer study revealed the projection of PVN and SON Oxt neurons to ARC. These results demonstrate the novel oxytocinergic signaling from PVN/SON to ARC POMC, possibly regulating feeding.
Expanding the SRI domain family: A common scaffold for binding the phosphorylated C‐terminal domain of RNA polymerase II
Authors: Rebehmed Joseph , Revy Patrick , Faure Guilhem , de Villartay Jean-Pierre , Callebaut Isabelle
Published: October 2014

The SRI domain is a small three‐helix domain originally discovered near the C‐terminus of both histone methyltransferase SETD2 and helicase RECQL5. The SRI domain binds to the C‐terminal repeat domain of the largest subunit of RNA polymerase II, allowing SETD2 and RECQL5 to regulate various mechanisms associated with RNA transcription. Using original tools to detect common patterns in distantly related sequences, we have identified SRI domains in several additional proteins, most of which are involved in RNA metabolism. Combining sequence analysis with structural prediction, we show that this domain family is more diverse than previously thought and we predict critical structural and functional features.
The role of social comparison for maximizers and satisficers: Wanting the best or wanting to be the best?
Authors: Weaver Kimberlee , Daniloski Kim , Schwarz Norbert , Cottone Keenan
Published: October 2014

Consumers chose between options that paired either an objectively inferior good with high relative standing (Your laptop is rated 60/100 in quality; others' laptops are rated 50/100) or an objectively superior good with low relative standing (Your laptop is rated 80/100 in quality; others' laptops are rated 95/100). Decision makers who try to make the “best” decision, known as maximizers (Schwartz et al., 2002), pursued relative standing more than decision makers who are satisfied with outcomes that are “good enough” (known as satisficers). That is, maximizers were more likely than satisficers to choose objectively inferior products when they were associated with higher relative standing. Subsequent analyses investigating decisions across time showed that maximizers' interest in relative standing persisted even when the nature of the tradeoff was made overt, suggesting it is a conscious aspect of the maximizer identity. Overall, results suggest that the maximizer self concept is more complex than has been previously assumed—they are focused on relative outcomes in addition to absolute outcomes.
Wahrgenommene Verfügbarkeit und Alkoholkonsum Jugendlicher im Längsschnitt
Authors: Suchert Vivien , Hanewinkel Reiner , Morgenstern Matthis
Published: October 2014

Zielsetzung: Untersuchung des Einflusses der wahrgenommenen Verfügbarkeit von Alkohol auf die Initiierung des Rauschtrinkens im Kindes- und Jugendalter Methodik: Es handelt sich um eine längsschnittliche Beobachtungsstudie mit drei Erhebungszeitpunkten über einen Zeitraum von 30 Monaten. Die Daten wurden an 1167 Schüler/innen mittels Fragebögen erhoben. Ergebnisse: Die Wahrscheinlichkeit für die Initiierung des Rauschtrinkens im Beobachtungszeitraum war bei Kindern und Jugendliche, die die Verfügbarkeit von Bier/Wein als hoch einschätzten, im Vergleich zu denen, die sie für gering erachteten, mit einem Chancenverhältnis (Adjustiertes Odds Ratio: AOR) von 1,54 (95 % Konfidenzintervall (KI): 1,14 – 2,09; p = 0,005) signifikant erhöht. Auch die wahrgenommene Verfügbarkeit von Spirituosen stellte sich als signifikanter Prädiktor heraus (AOR = 1,59; 95 % KI: 1,10 – 2,32; p = 0,014). Hier ergab sich weiterhin ein signifikanter Interaktionseffekt mit dem Alter der Kinder und Jugendlichen (AOR = 3,01; 95 % KI: 1,35 – 6,74; p = 0,007). Ein signifikanter Einfluss der wahrgenommenen Verfügbarkeit von Spirituosen konnte lediglich bei älteren Jugendlichen gefunden werden. Schlussfolgerungen: Neben politischen Maßnahmen zur Regulation der objektiven Verfügbarkeit von Alkohol (Mindestbezugsalter, Öffnungszeiten und Dichte von Verkaufsstellen) erscheint im Hinblick auf die subjektive Verfügbarkeit auch die Berücksichtigung des unmittelbaren sozialen Umfeldes für präventive Maßnahmen von Bedeutung zu sein.
Sensibilisierung der Fachpersonen des externen Versorgungssystems für glücksspielsuchtspezifische Probleme
Authors: Lischer Suzanne , Häfeli Jörg , Villiger Simone
Published: October 2014

Fragestellung: Nur ein kleiner Teil der Personen mit einem problematischen Glücksspielverhalten wendet sich an eine spezialisierte Beratungsstelle. Es kann jedoch davon ausgegangen werden, dass ein Teil der betroffenen Personen Unterstützung von Fachpersonen ausserhalb der Suchthilfe in Anspruch nimmt. Voraussetzung, dass die Fachpersonen eine Glücksspielsucht frühzeitig erkennen, ist jedoch, dass sie in Bezug auf die Glücksspielproblematik sensibilisiert sind. Deshalb interessiert, inwieweit Fachpersonen des externen Versorgungssystems für die Thematik der Glücksspielsucht sensibilisiert sind. Methodik: Es wurde eine Online-Befragung mit Personen des externen Versorgungssystems durchgeführt. Ergebnisse: Das Phänomen der glücksspielsuchtspezifischen Problematik nimmt im beruflichen Alltag der Fachpersonen aus dem externen Versorgungssystem eine kleine Rolle ein. Es besteht jedoch der Bedarf nach Sensibilisierungsmassnahmen. Schlussfolgerungen: Das externe Versorgungssystem ist eine wichtige Ressource in der Versorgungslandschaft von Personen mit glücksspielsuchtspezifischen Problemen. Um dieses Potential nutzen zu können, braucht es Schulungsmassnahmen mit Fokus auf die Früherkennung von glücksspielsuchtbezogenen Problemen sowie ein Schnittstellenmanagement zu den Suchtfachstellen.
Evaluation des Alkoholpräventionsprogramms „Lieber schlau als blau – für Jugendliche“: Ergebnisse einer kontrollierten Studie
Authors: Lindenmeyer Johannes , Hanewinkel Reiner , Morgenstern Matthis
Published: October 2014

Hintergrund: „Lieber schlau als blau“ wurde als Alkohol-Präventions-Programm für Schulen entwickelt. Im Mittelpunkt steht ein Trinkexperiment, in dem Jugendliche unter sicheren Rahmenbedingungen eine vorab vereinbarte Alkoholmenge konsumieren. In drei anschließenden Unterrichtseinheiten werden die persönlichen Ergebnisse im Trinkexperiment mithilfe von Gruppenübungen systematisch erörtert. Die Teilnehmer/innen entwickeln auf dieser Grundlage eigene Normen hinsichtlich ihres künftigen Umgangs mit Alkohol. Methode: Kontrollierte Studie an Schüler/innen der 9. und 10. Klasse (n = 725). Unterschiede im Trinkverhalten zwischen Interventions- und Kontrollgruppe wurden drei und sechs Monate nach Durchführung des Trainings mittels multivariater logistischer und linearer Multilevel-Regressionsanalysen geprüft. Ergebnisse: Es zeigte sich in der Interventions- im Vergleich zur Kontrollgruppe ein höherer Anteil von Schüler/innen ohne Binge Drinking in den letzten 90 Tagen, wobei der Unterschied zur 6 Monatskatamnese signifkant war (OR = 2,20; p = 0,043). Außerdem zeigte sich in der Interventionsgruppe zu beiden Katamnesezeitpunkten ein höherer Anteil von Nichttrinkern in den letzten 90 Tagen mit signifikantem Unterschied bei der 6-Monatskatamnese (OR 3.45; p = 0,002). Schlussfolgerung: Die Ergebnisse deuten darauf hin, dass das Präventionsprogramm „Lieber schlau als blau“ bedeutsame Veränderungen des Alkoholkonsums von Jugendlichen bewirken kann.
Hungarian Validation of the Penn State Worry Questionnaire	(PSWQ)
Authors: Pajkossy Péter , Simor Péter , Szendi István , Racsmány Mihály
Published: October 2014

Abstract. The Hungarian version of the Penn State Worry Questionnaire (PSWQ) was validated in two studies, using five different samples. Study 1 tested the factor structure and internal consistency of the PSWQ in two undergraduate student samples, comparing the psychometric properties of the paper-pencil and the online versions of the scale. Study 2 assessed construct validity in two undergraduate student samples and in a sample of patients diagnosed with Generalized Anxiety Disorder (GAD) and matched control participants. Our results suggest that the Hungarian PSWQ demonstrates good psychometric properties. We found no difference between the online and the paper-pencil versions of the scale. A factor structure with one general worry factor and two method factors representing wording effects showed the best fit to the data.
Substance and Artifact in Interest Self-Reports
Authors: Nelling Annika , Kandler Christian , Riemann Rainer
Published: October 2014

Abstract. Although self-reports are often distorted by response biases, nearly all knowledge about interests rely on self-reports. This multiple-rater twin study investigated the degree to which interest self-reports reflect substance. Specifically, we examined whether genetic variance in interest self-reports reflect substance in terms of genetically based motivational attributes or artifact in terms of genetically influenced self-rater biases. We compared normative and ipsatized self- and peer reports on interests from 844 individuals (incl. 225 monozygotic and 113 dizygotic twin pairs) regarding psychometric qualities and further regarding the estimates of genetic and environmental components in self-other agreement and self-rater specificity. Ipsatized interest scores showed lower internal consistency but higher consensus and self-other agreement. Self-other agreement showed a large genetic component, whereas variance specific to self-reports was not significantly attributable to genetic influences. The results provide strong support that genetic variance in interest self-reports reflect substance rather than artifact.
Impact of Verb Tense on Response to the Four-Dimensional Symptom	Questionnaire (4DSQ)
Authors: Terluin Berend , Marchand Miquelle A. G. , de Vet Henrica C. W. , Brouwers Evelien P. M.
Published: October 2014

Abstract. The verb tense of a questionnaire hypothetically might influence the way people respond to its items. We examined the effects of the verb tense on the response to the Four-Dimensional Symptom Questionnaire (4DSQ) in a population-based sample (N = 4,959; present tense N = 605; past tense N = 4,354). We determined whether the verb tense impacted the overall response rate, the scale structure, differential item functioning, reliability, proportions of respondents scoring above a range of cut-offs, and mean scale scores. The verb tense did not influence response rate, scale structure, item functioning, and reliability. The present tense increased the number of respondents scoring above very low cut-offs for distress and somatization. The effect on mean scale scores was limited and of little clinical importance.
Item Response Model Investigation of the (German) Interpersonal Reactivity Index Empathy Questionnaire
Authors: Koller Ingrid , Lamm Claus
Published: October 2014

Abstract. The interpersonal reactivity index (IRI) is a widely used personality questionnaire for measuring empathy. We investigated the psychometric properties of the German version using the partial credit model. If this model fits the data, the raw-scores are fair measures of the latent construct. Only in such a case, further analyses based on the raw-scores are accurate and valid. The results showed model fit only for the subscale empathic concern. The subscales perspective taking and fantasy consisted of two theoretically explainable sub-dimensions. For the subscale personal distress, no model fit could be achieved. Our study provides important information on the psychometric qualities of the IRI that has been repeatedly used to assess, for example, group differences. It demonstrates that these analyses were not warranted by the psychometric quality of the questionnaire. Our results provide direct suggestions (e.g., theoretically explainable sub-dimensions) for further developments of the IRI to overcome this limitation.
Deviatoric stress-induced phase transitions in diamantane
Authors: Yang Fan , Lin Yu , Dahl Jeremy E. P. , Carlson Robert M. K. , Mao Wendy L.
Published: October 2014

The high-pressure behavior of diamantane was investigated using angle-dispersive synchrotron x-ray diffraction (XRD) and Raman spectroscopy in diamond anvil cells. Our experiments revealed that the structural transitions in diamantane were extremely sensitive to deviatoric stress. Under non-hydrostatic conditions, diamantane underwent a cubic (space group Pa3) to a monoclinic phase transition at below 0.15 GPa, the lowest pressure we were able to measure. Upon further compression to 3.5 GPa, this monoclinic phase transformed into another high-pressure monoclinic phase which persisted to 32 GPa, the highest pressure studied in our experiments. However, under more hydrostatic conditions using silicone oil as a pressure medium, the transition pressure to the first high-pressure monoclinic phase was elevated to 7–10 GPa, which coincided with the hydrostatic limit of silicone oil. In another experiment using helium as a pressure medium, no phase transitions were observed to the highest pressure we reached (13 GPa). In addition, large hysteresis and sluggish transition kinetics were observed upon decompression. Over the pressure range where phase transitions were confirmed by XRD, only continuous changes in the Raman spectra were observed. This suggests that these phase transitions are associated with unit cell distortions and modifications in molecular packing rather than the formation of new carbon-carbon bonds under pressure.
Cholesterol enhances surface water diffusion of phospholipid bilayers
Authors: Cheng Chi-Yuan , Olijve Luuk L. C. , Kausik Ravinath , Han Songi
Published: October 2014

Elucidating the physical effect of cholesterol (Chol) on biological membranes is necessary towards rationalizing their structural and functional role in cell membranes. One of the debated questions is the role of hydration water in Chol-embedding lipid membranes, for which only little direct experimental data are available. Here, we study the hydration dynamics in a series of Chol-rich and depleted bilayer systems using an approach termed 1H Overhauser dynamic nuclear polarization (ODNP) NMR relaxometry that enables the sensitive and selective determination of water diffusion within 5–10 Å of a nitroxide-based spin label, positioned off the surface of the polar headgroups or within the nonpolar core of lipid membranes. The Chol-rich membrane systems were prepared from mixtures of Chol, dipalmitoyl phosphatidylcholine and/or dioctadecyl phosphatidylcholine lipid that are known to form liquid-ordered, raft-like, domains. Our data reveal that the translational diffusion of local water on the surface and within the hydrocarbon volume of the bilayer is significantly altered, but in opposite directions: accelerated on the membrane surface and dramatically slowed in the bilayer interior with increasing Chol content. Electron paramagnetic resonance (EPR) lineshape analysis shows looser packing of lipid headgroups and concurrently tighter packing in the bilayer core with increasing Chol content, with the effects peaking at lipid compositions reported to form lipid rafts. The complementary capability of ODNP and EPR to site-specifically probe the hydration dynamics and lipid ordering in lipid membrane systems extends the current understanding of how Chol may regulate biological processes. One possible role of Chol is the facilitation of interactions between biological constituents and the lipid membrane through the weakening or disruption of strong hydrogen-bond networks of the surface hydration layers that otherwise exert stronger repulsive forces, as reflected in faster surface water diffusivity. Another is the concurrent tightening of lipid packing that reduces passive, possibly unwanted, diffusion of ions and water across the bilayer.
Pump-probe measurements of the thermal conductivity tensor for materials lacking in-plane symmetry
Authors: Feser Joseph P. , Liu Jun , Cahill David G.
Published: October 2014

We previously demonstrated an extension of time-domain thermoreflectance (TDTR) which utilizes offset pump and probe laser locations to measure in-plane thermal transport properties of multilayers. However, the technique was limited to systems of transversely isotropic materials studied using axisymmetric laser intensities. Here, we extend the mathematics so that data reduction can be performed on non-transversely isotropic systems. An analytic solution of the diffusion equation for an N-layer system is given, where each layer has a homogenous but otherwise arbitrary thermal conductivity tensor and the illuminating spots have arbitrary intensity profiles. As a demonstration, we use both TDTR and time-resolved magneto-optic Kerr effect measurements to obtain thermal conductivity tensor elements of <110> α-SiO2. We show that the out-of-phase beam offset sweep has full-width half-maxima that contains nearly independent sensitivity to the in-plane thermal conductivity corresponding to the scanning direction. Also, we demonstrate a Nb-V alloy as a low thermal conductivity TDTR transducer layer that helps improve the accuracy of in-plane measurements.