nils-herrmann/clean_scirepeval huggingface dataset:
Electrophysiological characterization of a novel Kv channel blocker N, N′-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide found in virtual screening

N,N′-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide (OMBSA) is a hit compound with potent voltage-gated K+ (Kv) channel-blocking activities that was found while searching the MDL Available Chemicals Directory with a virtual screening approach. In the present study, the blocking actions of OMBSA on Kv channels and relevant mechanisms were characterized.Whole-cell voltage-clamp recording was made in acutely dissociated hippocampal CA1 pyramidal neurons of newborn rats.Superfusion of OMBSA reversibly inhibited both the delayed rectifier (IK) and fast transient K+ currents (IA) with IC50 values of 2.1±1.1 μmol/L and 27.8±1.5 μmol/L, respectively. The inhibition was voltage independent. OMBSA markedly accelerated the decay time course of IK, without a significant effect on that of IA. OMBSA did not change the activation, steady-state inactivation of IK, and its recovery from inactivation, but the compound caused a significant hyperpolarizing shift of the voltage dependence of the steady-state inactivation of IA and slowed down its recovery from inactivation. Intracellular dialysis of OMBSA had no effect on both IK and IA.Conclusion:The results demonstrate that OMBSA blocks both IK and IA through binding to the outer mouth of the channel pore, as predicted by the molecular docking model used in the virtual screening. In addition, the compound differentially moderates the inactivation kinetics of the K+ channels through allosteric mechanisms.

Field of study: Biology, Chemistry, Medicine
Multigrid methods: development of fast solvers

Numerical and programming aspects are discussed of multigrid algorithms for the solution of discretized linear elliptic equations. The aim is to obtain software that is perceived and can be used just like any standard subroutine for solving systems of linear equations. The user has to specify only the matrix and the right-hand-side, and remains unaware of the underlying multigrid method. We find that a large class of equations can be solved efficiently in this way. The equation may be non-self-adjoint, and its coefficients are arbitrary. Special attention is given to the treatment of the convection-diffusion equation at high Peclet number. Details are given of an available portable FORTRAN code, which vectorizes satisfactorily on vector machines. CP time statistics are given for a CYBER-205.

Field of study: Mathematics
Cetacean habitat modelling to inform conservation management, marine spatial planning, and as a basis for anthropogenic threat mitigation in Indonesia

Indonesia harbours a high diversity of cetaceans, yet effective conservation is hampered by a lack of knowledge about cetacean spatial distribution and habitat preferences. This study aimed to address this knowledge gap at an adequate resolution to support national cetacean conservation and management planning. Maximum Entropy (Maxent) modelling was used to map the distribution of 15 selected cetacean species in seven areas within Indonesian waters using recent cetacean presence datasets as well as environmental predictors (topographic and oceanographic variables). We then combined the individual species suitable habitat maps and overlaid them with provincial marine spatial planning (MSP) jurisdictions, marine protected areas (MPAs), oil and gas contract areas, and marine traffic density. Our results reflect a great heterogeneity in distribution among species and within species among different locations. This heterogeneity reflects an interrelated influence of topographic variables and oceanographic processes on the distribution of cetacean species. Bathymetry, distance to- coast and the −200m isobaths, and chlorophyll-a concentration and sea surface temperature were important variables influencing distribution of most species in many regions. Areas rich in species were mainly related to coastal areas or insular-reef complexity, representing high productivity and upwelling-modified waters. Although some important suitable habitats currently fall within MPAs, other areas are not and overlap with oil and gas exploration activities and marine traffic, indicating potentially high risk areas for cetaceans. The results of this study can support national cetacean conservation and management planning, and be used to reduce or avoid adverse anthropogenic threats. We advise to consider currently unprotected suitable cetacean habitats in MPA and MSP development.

Field of study: Environmental science
“Are you human beings?” Order and knowledge construction through questioning in primary classroom interaction

This article examines how question-answer sequences are constructed in primary school instructional activities. The interaction between teacher and students in two 3rd-year groups is analyzed using a conversation-analytic approach. Four questioning patterns – yes-no, alternative, wh-questions , and a non-interrogative format very frequently used in this setting which I call the Eliciting Completion Device (ECD) – teachers use to address the class as a whole are examined in relation to their sequential uptakes: in-unison answers and bids to answer. The analysis shows that students recognize the conventions of question construction as methodical practices used by teachers to convey expectations as to whether the answer is accessible to students. Choral responses are produced when the question is constructed as eliciting information which is obviously known to students, while bids to answer are deployed when the answer is less transparent. The findings reveal that the practices used to construct collectively assembled knowledge are closely connected to the organization of the classroom social order.

Field of study: Education, Linguistics
Interleukin-6 and tumour necrosis factor-α differentially regulate lincRNA transcripts in cells of the innate immune system in vivo in human subjects with rheumatoid arthritis.

lincRNAs recently have been discovered as evolutionary conserved transcripts of non-coding DNA sequences and have been implicated in the regulation of cellular differentiation. In humans, molecular studies have suggested a functional role for lincRNAs in cancer development. The aim of the present study was to examine whether these novel molecules are specifically regulated by different cytokines in cells of the innate immune system in humans in vivo and whether lincRNAs thereby might be involved in the pathophysiology of rheumatoid arthritis (RA). Therefore, CD14(+) monocytes were isolated from RA patients before and after anti-IL-6R (tocilizumab) or anti-TNF-α (adalimumab) therapy and lincRNA transcription was analysed by a microarray based experiment. As expected, we found lincRNAs to be present in CD14(+) monocytes of RA patients. However, of the total number of 7.419 lincRNAs examined in this study only a very small number was significantly regulated by either IL-6 or TNF-α (85 lincRNAs, corresponding to 1.1%). The numbers of lincRNAs regulated was higher due to TNF-α compared to IL-6. Interestingly, none of the identified lincRNAs was influenced by both, IL-6 and TNF-α, suggesting the regulation of lincRNA transcription to be highly specific for distinct cytokines. Taken together, our results suggest (1) that lincRNAs are novel intracellular molecular effectors of specific cytokines in cells of the innate immune system in humans in vivo and (2) that lincRNAs might be involved in the molecular pathophysiology of RA.

Field of study: Medicine
Differential autoshaping to common and distinctive elements of positive and negative discriminative stimuli.

The learning by hungry pigeons of a discrimination between two successively presented compound visual stimuli was investigated using a two-key autoshaping procedure. Common and distinctive stimulus elements were simultaneously presented on separate keys and either followed by food delivery, S+, or not, S-. The subjects acquired both between-trial and within-trial discriminations. On S+ trials, pigeons pecked the distinctive stimulus more than the common stimulus; before responding ceased on S- trials, they pecked the common stimulus more than the distinctive one. Mastery of the within-display discrimination during S+ trials preceded mastery of the between-trials discrimination. These findings extend the Jenkins-Sainsbury analysis of discriminations based upon a single distinguishing feature to discriminations in which common and distinctive elements are associated with both the positive and negative discriminative stimuli. The similarity of these findings to other effects found in autoshaping-approach to signals that forecast reinforcement and withdrawal from signals that forecast nonreinforcement-is also discussed.

Field of study: Biology, Psychology
Stellar population of the irregular galaxy IC 10

Based on our observations with the 6-m BTA telescope at the Special Astrophysical Observatory, the Russian Academy of Sciences, and archival Hubble Space Telescope images, we have performed stellar photometry for several regions of the irregular galaxy IC 10, a member of the Local Group. Distance moduli with a median value of m − M = 24.47, D = 780 ± 40 kpc, have been obtained by the TRGB method for several regions of IC 10. We have revealed 57 star clusters with various masses and ages within the fields used. Comparison of the Hertzsprung-Russell diagrams for star clusters in IC 10 with theoretical isochrones has shown that this galaxy has an enhanced metallicity, which probably explains the high ratio of the numbers of carbon and nitrogen Wolf-Rayet stars (WC/WN). The size of the galaxy’s thick disk along its minor axis is 10′.5 and a more extended halo is observed outside this disk.

Field of study: Physics
Multiplex PCR rapid detection for pathogenic bacteria in milk powder

To establish a multiplex PCR method for the simultaneous detection of pathogenic bacteria such as Enterobacter sakazakii,Staphylococcus aureus and Bacillus cereus in milk powder,three pairs of oligonucleotide primers were designed according to Enterobacter sakazakii ompA gene,Staphylococcus aureus nuc gene and Bacillus cereus hblA gene.They were used to amplify the special DNA sequences by multiplex PCR and the reaction conditions were optimized.The results showed that the multiplex PCR assay amplified three specific target channels of 514 bp,156 bp and 235 bp.Without bacterial enrichment,the sensitivities of the multiplex PCR for Enterobacter sakazakii,Staphylococcus aureus and Bacillus cereus were 103 cfu/mL,and the detection limits of the multiplex PCR for Enterobacter sakazakii,Staphylococcus aureus and Bacillus cereus in milk powder were 104 cfu/g.This multiplex PCR method was accurate,fast and effective and provided a new approach for detecting Enterobacter sakazakii,Staphylococcus aureus,and Bacillus cereus in milk powder.

Field of study: Agricultural and Food sciences
Searching for a common currency: critical appraisal of the scientific basis underlying European harmonization of the measurement of health related quality of life (EuroQol)

The EuroQol has recently been proposed as a measure of health-related quality of life based on individuals' valuations of health states. The derived values would be used in assessing cost-effectiveness and establishing priorities across a wide range of health-care activities. In this paper we identify some of the limitations of the EuroQol in its role as a particular method for deriving the more generic QALYs. More specifically we explore the implications of using the EuroQol as a measure of individuals' and communities' valuation of health outcomes. We show that the EuroQol suffers from several major limitations and thus cannot be relied upon to provide a valid measure to be used in economic appraisals or studies concerned with establishing priorities as proposed by its proponents. An alternative approach is identified and discussed.

Field of study: Medicine, Political science
NMR and molecular dynamics studies of tachykinins: conformation of the C-terminal pentapeptide of substance P(SP7-11).

Substance P belongs to the tachykinin family of neuropeptides which exhibit diverse pharmacological activity. The conformation of Phe1-Phe2-Gly3-Leu4-Met5-NH2 the C-terminal pentapeptide of substance P (SP7-11) has been studied by NMR and molecular dynamics (MD) methods. NMR studies were carried out both in DMSO-d6 and 95% H2O. Based on the observed chemical shifts, 3JNH alpha coupling constants, temperature coefficients of chemical shifts of NH resonances and the pattern of inter- and intraresidue NOE's, a predominantly extended backbone conformation has been deduced for the peptide in both DMSO and H2O. MD calculations carried out in vacuo indicate that the global minimum energy conformation of the molecule is folded with an intramolecular hydrogen bond between the protonated N-terminal and the C-terminal CONH2 group. The simulation shows that beta-turns are energetically unfavourable, while alpha-helices are seen to be unstable for the peptide. gamma-Bends at either Gly3 or Leu4 are the most preferred ones. Simulations carried out in DMSO as well as in water show a preference for a nearly extended conformation.

Field of study: Biology, Chemistry, Physics
Blocking Wnt5a signaling decreases CD36 expression and foam cell formation in atherosclerosis.

Wnt5a is a highly studied member of the Wnt family and recently has been implicated in the pathogenesis of atherosclerosis, but its precise role is unknown. Foam cell development is a critical process to atherosclerotic plaque formation. In the present study, we investigated the role of noncanonical Wnt5a signaling in the development of foam cells.



Human carotid atherosclerotic tissue and THP-1-derived macrophages were used to investigate the contribution of Wnt5a signaling in the formation of foam cells. Immunohistochemistry was used to evaluate protein expression of scavenger receptors and noncanonical Wnt5a receptors [frizzled 5 (Fz5) and receptor tyrosine kinase-like orphan receptor 2 (Ror2)] in human atherosclerotic macrophages/foam cells. Changes in protein expression in response to Wnt5a stimulation/inhibition were determined by Western blot, and lipid accumulation was evaluated by fluorescent lipid droplet staining.



Wnt5a (P<.05), Fz5 (P<.01), and Ror2 (P<.01) were significantly expressed in advanced atherosclerotic lesions compared to less advanced lesions (N=10). Wnt5a, Fz5, and Ror2 were expressed in macrophages/foam cells within the plaque. In vitro studies revealed that Wnt5a significantly increased the expression of the lipid uptake receptor CD36 (P<.05) but not the lipid efflux receptor ATP-binding cassette transporter (P>.05). rWnt5a also significantly increased lipid accumulation in THP-1 macrophages (P<.05). Furthermore, inhibition of Wnt5a signaling with Box5 prevented lipid accumulation (P<.01) and prevented CD36 up-regulation (P<.01).



These results suggest a direct role for Wnt5a signaling in the pathogenesis of atherosclerosis, specifically the accumulation of lipid in macrophages and the formation of foam cells.

Field of study: Biology, Medicine
Electronic Structure of Single-Crystalline MgxAl1−xB2 Probed by X-ray Diffraction Multipole Refinements and Polarization-Dependent X-ray Absorption Spectroscopy

X-ray diffraction multipole refinements of single-crystalline MgxAl1−xB2 and polarization-dependent near-edge x-ray absorption fine structure at the B 1s edge reveal a strongly anisotropic electronic structure. Comparing the data for superconducting compounds (x = 0.8, 1.0) with those for the non-superconductor (x = 0) gives direct evidence for a rearrangement of the hybridizations of the boron pz bonds and underline the importance of holes in the σ-bonded covalent sp2 states for the superconducting properties of the diborides. The data indicate that Mg is approximately divalent in MgB2 and suggest predominantly ionic bonds between the Mg ions and the two-dimensional covalent B rings. For AlB2 (x = 0), on the other hand, about 1.5 electrons per Al atom are transferred to the B sheets while the residual 1.5 electrons remain at the Al site which suggests significant covalent bonding between the Al ions and the B sheets. This finding together with the static electron deformation density points to almost equi...

Field of study: Physics
Regulation of FGF10 Signaling in Development and Disease

Fibroblast Growth Factor 10 (FGF10) is a multifunctional mesenchymal-epithelial signaling growth factor, which is essential for multi-organ development and tissue homeostasis in adults. Furthermore, FGF10 deregulation has been associated with human genetic disorders and certain forms of cancer. Upon binding to FGF receptors with heparan sulfate as co-factor, FGF10 activates several intracellular signaling cascades, resulting in cell proliferation, differentiation, and invasion. FGF10 activity is modulated not only by heparan sulfate proteoglycans in the extracellular matrix, but also by hormones and other soluble factors. Despite more than 20 years of research on FGF10 functions, context-dependent regulation of FGF10 signaling specificity remains poorly understood. Emerging modes of FGF10 signaling regulation will be described, focusing on the role of FGF10 trafficking and sub-cellular localization, heparan sulfate proteoglycans, and miRNAs. Systems biology approaches based on quantitative proteomics will be considered for globally investigating FGF10 signaling specificity. Finally, current gaps in our understanding of FGF10 functions, such as the relative contribution of receptor isoforms to signaling activation, will be discussed in the context of genetic disorders and tumorigenesis.

Field of study: Biology
A new paradigm of chosen ciphertext secure public key encryption scheme

For all current adaptive chosen ciphertext(CCA) secure public key encryption schemes in standard model there are two operations in the decryption algorithm, “validity check” and decryption. The decryption algorithm returns the corresponding plaintext if the ciphertext is valid otherwise it returns a rejection symbol ⊥. We call this paradigm “invalid ciphertext rejection”. However the “validity check” is not necessary for an encryption scheme. Also in this case the adversary will get the information that the ciphertext is ”invalid” which he may not know before the decryption query. We propose a new paradigm for constructing CCA secure public key encryption schemes which combines “validity check” and decryption together. The decryption algorithm will execute the same operation regardless of the ciphertext’s validity. We call this new paradigm “uniform decryption”. Compared with the ”invalid ciphertext rejection” paradigm, the decryption oracle of schemes in the new paradigm will reveal less information. The attacker even can not get whether the queried ciphertext is “valid” or not. Moreover the combination of “validity check” and the decryption will yield more efficient schemes. Using the new paradigm we construct an efficient public key encryption scheme. Our scheme is more efficient than CS98 in both computation and bandwidth. Compered with KD04 and HK07 the new scheme is more efficient in bandwidth and the same efficient in computation. The new scheme is as efficient as Kiltz07 both in computation and bandwidth. However the new scheme is CCA secure based on DDH assumption which is more flexible than GHDH assumption that Kiltz07 based on. Kurosawa and Desmedt proposed an efficient hybrid scheme named as KD04[14]. Although the key encapsulation part of KD04(KD04-KEM) is not CCA secure [20], the whole scheme can be proved to be CCA secure. We show that if the key derivation function(KDF) of KD04-KEM is a non-malleable hash function it will be a CCA secure KEM in the new paradigm.

Field of study: Computer science, Mathematics
Discrete weierstrass transform in discrete hermitian clifford analysis

The classical Weierstrass transform is an isometric operator mapping elements of the weighted L 2 − space L 2 ( R , exp ( − x 2 / 2 ) ) to the Fock space. It has numereous applications in physics and applied mathematics. In this paper, we define an analogue version of this transform in discrete Hermitian Clifford analysis, where functions are defined on a grid rather than the continuous space. This new transform is based on the classical definition, in combination with a discrete version of the Gaussian function and discrete counterparts of the classical Hermite polynomials. Furthermore, a discrete Weierstrass space with appropriate inner product is constructed, for which the discrete Hermite polynomials form a basis. In this setting, we also investigate the behaviour of the discrete delta functions and check if they are elements of this newly defined Weierstrass space.

Field of study: Mathematics
A New Approach in Surface Modification and Surface Hardening of Aluminum Alloys Using Friction Stir Process: Cu-Reinforced AA5083

In the current study, a new approach for surface modification and surface hardening of aluminum alloys is developed. The method is based on the logic of in-situ reinforcing FSP strategies. The novelty of the proposed process is the application of a bulk reinforcing metallic material instead of metallic powders. The FSP was carried out on aluminum alloy AA5083—thick plates. A thin sheet of pure copper (cross-section 4 × 0.8 mm2) was placed in a machined groove on the upper surface of the aluminum plate, and both materials were FSPed together. Samples with one, two and three FSP passes were manufactured respectively. Results indicate that the copper thin sheet was successfully integrated in the AA5083 stir zone. By increasing the FSP passes, almost all copper was integrated in the stir zone, mainly in the form of coper-based micron-sized intermetallic particles, and secondly, by copper diffusion in the AA5083 matrix. Due to the presence of complex intermetallic compounds created by the high heat input and intense plastic deformation, the hardness inside the stir-zone was found highly increased from 77 to 138 HV.

Field of study: Materials science
A non-ideal second order thermal model with effects of losses for simulating Beta-type Stirling refrigerating machine

A key issue in the optimal designing of a Stirling machine is to develop a precise thermodynamic numerical model that could predict the performances and provide means for further optimization. In this paper, a non-ideal second-order numerical model called modified simple analysis model has been presented for the Stirling cycle refrigerating machine. The model incorporates effects of shuttle heat loss to the expansion space and mass leakage to the crankcase in the differential equations of pressure change, rate of change of mass of gas in compression and expansion spaces, and mass flow rates across these working spaces. The model was simulated using MATLAB code for Beta configuration FEMTO 60 Stirling engine operating as a refrigerator and validated with an experiment. The validation of the numerical model with experimental work showed that the results of the simulation are consistent with the results of the experiment. Hence, the numerical model could be used to design a Stirling cycle refrigerating machine for moderate temperature applications with reasonable accuracy especially if optimization is performed further. The effects of incorporating shuttle heat loss in the differential equations on the temperature of working gas and the overall performance of the Stirling refrigerator have been analyzed. Lastly, parametric investigations have also been performed to evaluate the effect of operating parameters (temperature, pressure, and frequency) on the performances of the refrigerating machine. Better performance could be achieved at relatively lower frequency or higher pressure.

Field of study: Engineering