Minus Side Research Articles

Validation of AISI Design of Cold-Formed Steel Beams Using Non-Linear Finite Element Analysis

In the local building industry of Pakistan, pre-engineered steel building manufacturers mainly employ their own self-developed software and Excel sheets. These systems are based on empirical formulas mentioned in the AISI manual. Under this scenario, a need was found to validate AISI flow charts using commercial software like CUFSM 5.04 and ABAQUS R2019x. This study presents a validation of the CUFSM software and the American Iron and Steel Institute (AISI) Direct Strength Method (DSM) results of channel section flexural members using the non-linear finite element method employing ABAQUS. In this study, eight standard cold-formed channel-section (C-section) steel members were modeled and analyzed using ABAQUS to simulate realistic behavior under four-point loading conditions. The non-linear finite element models incorporated material and geometric non-linearities to capture the actual response of the steel elements. The results obtained from ABAQUS were compared with those predicted by the CUFSM and DSM, focusing on critical parameters such as nominal strength, buckling modes, and deformation patterns. During this study, it was observed that out of the selected sections, the AISI charts predict conservative and even unsafe flexural capacities in some of the cases concerning other methods, with a maximum difference of 14.03%. The differences obtained using DSM and ABAQUS when compared with the results of the AISI charts varies on both the plus and minus sides. This study will not only affect the industry in terms of innovative designs for efficient structures but also the community in regards to low-budget construction.

A Eulerian Monte Carlo method for the numerical solution of the multivariate population balance equation

Statistical descriptions of particulate phases and granular media based on the notion of a property distribution are particularly advantageous for dense, many-particle dispersions since they support the direct evaluation of Eulerian property statistics, permit a kinematically simple treatment of particle collisions and feature a model complexity that is independent of the number of physical particles. On the minus side, the property distribution is governed by a high-dimensional population balance equation (PBE) whose moment reduction is accompanied by a challenging closure problem and engenders intricate dynamical nonlinearities. Circumventing both the curse of dimensionality and the moment closure problem, we present a Eulerian Monte Carlo (EMC) solution method that harnesses a representation of the property distribution in terms of an ensemble of property samples and is based on a statistical enforcement of the spatially and temporally discretized PBE. After application of a kinetic finite volume scheme, the PBE is subjected to a fractional steps decomposition that separates spatial transport from transport in property space. Conceptually, spatial transport is emulated by assembling the ensemble in one spatial grid cell from samples drawn from the ensembles in neighbouring cells at the previous time point. In this regard, we propose a two-level sampling scheme that is sensitive to large-scale features of the marginal velocity distribution and effectively reduces the instantaneous sampling error. The property transport step, by contrast, is based on the method of characteristics and involves the propagation of individual samples as property characteristics in time. While the sampling error afflicting the property statistics needs to be controlled using a top-level time or ensemble averaging, the EMC method remains well-conditioned for an arbitrary number of samples, is easy to implement and involves a computational expense that scales only linearly with the number of particle properties. Based on two benchmark examples, we analyze the spatial and statistical convergence properties of the EMC method and demonstrate its capacity to capture multiple crossings of particle trajectories. A third example involves the two-way coupled transport of size-polydispersed inertial particles in an inhomogeneous flow field.

A Comparison of Low-Temperature Deposition for SiO2 in PECVD Using SiH4 and TEOS

We have developed a method for depositing SiO2 as an insulating layer at temperatures below 100°C using PECVD. This method has potential applications in the development of flexible displays and organic transistors. We have previously reported on TSV via-hole formation by the Bosch process and TEOS-SiO2 deposition on sidewall by PECVD at 150°C [1]. In this study, we performed PECVD using a power supply frequency of 400 kHz. The deposition temperature was set at 100°C. We compared the deposition rates and the film stress of SiO2 films deposited using SiH4 and TEOS at different RF power densities.Figure 1 shows the relationship between 400 kHz power and the deposition rates. In this power density range, the deposition rate of SiH4 was almost constant at approximately 52 nm/min regardless of power density. On the other hand, the rate using TEOS tended to decrease as the power density increased above 0.28 W/cm2.Figure 2 shows the film stress of each film immediately after deposition and after few days of atmospheric exposure. The minus side of the stress indicates compressive stress. The stress of SiH4 was -50 to -70 MPa immediately after deposition; however, after few days of atmospheric exposure, the stress shifted by approximately -50 MPa at all power densities. On the other hand, in the case of TEOS, the stress did not change at approximately -120 MPa at a power density of 0.18 W/cm2 or higher immediately after deposition; however, after few days of exposure, the amount of change to the compressive stress side became smaller as the power density increased. It has been reported that the change in stress to the compressive side is influenced by moisture in the atmosphere [2]. The small change in stress is considered to mean that the film is denser, and that moisture is less likely to enter the film. The deposition rate is considered to decrease during the process of film densification.In summary, it is thought that by increasing the power density with TEOS-SiO2, a dense film is formed even at a low temperature of 100°C.

A Stochastic Frontier Analysis of the Human Capital Effects on the Manufacturing Industries’ Technical Efficiency in the United States

This study seeks to establish substantive empirical evidence on the role of college and non-college labour in productivity through technical efficiency in the manufacturing sector in the U.S. economy. This investigation fits a Cobb-Douglas stochastic frontier function with inefficiency effects to a set of panel data for 15 manufacturing industries over the period from 1998 to 2019. The contribution of this paper lies in the application of the stochastic frontier analysis following the approach of Caudill et al. (1995) by estimating and testing stochastic frontier production functions, assuming the presence of heteroscedasticity in the one-sided error term (inefficiency), which provides robust estimates of the technical efficiency measures. This paper also contributes to the literature in the sense that it follows the Hadri (1999) approach and its extension for panel data, Hadri et al. (2003), assuming the existence of heteroscedasticity in both error terms (the one-sided inefficiency term and the two-sided symmetric random noise). The rationale for the double heteroscedasticity estimation is that it results in more accurate measures of the effects of the technical efficiency determinants. Therefore, it adds another layer of confidence in the economic analysis of the impact of human capital components on the manufacturing sector efficiency and by extension, its productivity. The stochastic frontier results show the effects of highly educated workers and low educated workers – proxied by college and non-college labour – on technical inefficiency. This is where the maximum likelihood estimates suggest that the increase in the percentage of the hours worked by college workers tends to contribute positively to technological efficiency in the U.S. manufacturing industries. While on the minus side, it can be noted that the rise in the share of the hours worked by non-college persons seems to have negative impact on efficiency in these industries. JEL Codes: J24, D24, C23, C24, Q12 Keywords: human capital, technical efficiency, stochastic frontier production, double heteroscedasticity, panel data

Digital competence of teachers and students in Yakutia: problems and prospects of e-learning during the pandemic

Under self-isolation and quarantine measures during the COVID-19 pandemic in 2020, distance learning is urgent at every educational level. These events affected the digital competence of teachers and students of pedagogical specialties who teach students and schoolchildren. The article analyzes the digital competencies required for a modern teacher to successfully implement students’ educational needs when using distance educational technologies and e-learning. The research objective is to increase the level of digital competence by assessing this level and identifying problems in the e-learning usage. The study was carried out through a questionnaire developed by the National Agency for Financial Research (NAFR) analytical center Russian Teachers’ Digital Literacy, allowing identification of the main competencies required for a modern teacher, such as work in distance learning environments, knowledge of the basics of cloud technologies, and the ability to organize online and offline interaction, using various services. According to the calculation of Kendall’s concordance coefficient, a ranking of the plus and minus sides identified in the organization of remote interaction among teachers and students of the Republic of Sakha (Yakutia) during the pandemic was made. The study outcomes allowed increasing the efficiency of work with students and teachers and organizing refresher courses and support in the e-learning implementation

Determinants for α4β2 vs. α3β4 Subtype Selectivity of Pyrrolidine-Based nAChRs Ligands: A Computational Perspective with Focus on Recent cryo-EM Receptor Structures.

The selectivity of α4β2 nAChR agonists over the α3β4 nicotinic receptor subtype, predominant in ganglia, primarily conditions their therapeutic range and it is still a complex and challenging issue for medicinal chemists and pharmacologists. Here, we investigate the determinants for such subtype selectivity in a series of more than forty α4β2 ligands we have previously reported, docking them into the structures of the two human subtypes, recently determined by cryo-electron microscopy. They are all pyrrolidine based analogues of the well-known α4β2 agonist N-methylprolinol pyridyl ether A-84543 and differ in the flexibility and pattern substitution of their aromatic portion. Indeed, the direct or water mediated interaction with hydrophilic residues of the relatively narrower β2 minus side through the elements decorating the aromatic ring and the stabilization of the latter by facing to the not conserved β2-Phe119 result as key distinctive features for the α4β2 affinity. Consistently, these compounds show, despite the structural similarity, very different α4β2 vs. α3β4 selectivities, from modest to very high, which relate to rigidity/extensibility degree of the portion containing the aromatic ring and to substitutions at the latter. Furthermore, the structural rationalization of the rat vs. human differences of α4β2 vs. α3β4 selectivity ratios is here proposed.

Revealing New Candidate Genes for Teat Number Relevant Traits in Duroc Pigs Using Genome-Wide Association Studies.

Simple SummaryNumber of teats is very important for lactating sows. We conducted genome-wide association studies (GWAS) and estimated the genetic parameters for traits related to teat number. Results showed that there were nine and 22 SNPs exceeding genome-wide significance and suggestive significance levels, respectively. Eighteen genes annotated near them were concentrated on chromosomes 7 and 10. Among them, three new candidate genes were located on the genomic regions around the significant SNPs. Our findings provide new insight into investigating the complex genetic mechanism of traits related to teat number in pigs.The number of teats is related to the nursing ability of sows. In the present study, we conducted genome-wide association studies (GWAS) for traits related to teat number in Duroc pig population. Two mixed models, one for counted and another for binary phenotypic traits, were employed to analyze seven traits: the right (RTN), left (LTN), and total (TTN) teat numbers; maximum teat number on a side (MAX); left minus right side teat number (LR); the absolute value of LR (ALR); and the presence of symmetry between left and right teat numbers (SLR). We identified 11, 1, 4, 13, and 9 significant SNPs associated with traits RTN, LTN, MAX, TTN, and SLR, respectively. One significant SNP (MARC0038565) was found to be simultaneous associated with RTN, LTN, MAX and TTN. Two annotated genes (VRTN and SYNDIG1L) were located in genomic region around this SNP. Three significant SNPs were shown to be associated with TTN, RTN and MAX traits. Seven significant SNPs were simultaneously detected in two traits of TTN and RTN. Other two SNPs were only identified in TTN. These 13 SNPs were clustered in the genomic region between 96.10—98.09 Mb on chromosome 7. Moreover, nine significant SNPs were shown to be significantly associated with SLR. In total, four and 22 SNPs surpassed genome-wide significance and suggestive significance levels, respectively. Among candidate genes annotated, eight genes have documented association with the teat number relevant traits. Out of them, DPF3 genes on Sus scrofa chromosome (SSC) 7 and the NRP1 gene on SSC 10 were new candidate genes identified in this study. Our findings demonstrate the genetic mechanism of teat number relevant traits and provide a reference to further improve reproductive performances in practical pig breeding programs.

Role of Tryptophan 38 in Loading Substrate Chain into the Active-site Tunnel of Cellobiohydrolase I from Trichoderma reesei.

Cellobiohydrolase I from Trichoderma reesei ( Tr Cel7A) is one of the best-studied cellulases, exhibiting high activity towards crystalline cellulose. Tryptophan residues at subsites -7 and -4 (Trp40 and Trp38 respectively) are located at the entrance and middle of the tunnel-like active site of Tr Cel7A, and are conserved among the GH family 7 cellobiohydrolases. Trp40 of Tr Cel7A is important for the recruitment of cellulose chain ends on the substrate surface, but the role of Trp38 is less clear. Comparison of the effects of W38A and W40A mutations on the binding energies of sugar units at the two subsites indicated that the contribution of Trp38 to the binding was greater than that of Trp40. In addition, the smooth gradient of binding energy was broken in W38A mutant. To clarify the importance of Trp38, the activities of Tr Cel7A WT and W38A towards crystalline cellulose and amorphous cellulose were compared. W38A was more active than WT towards amorphous cellulose, whereas its activity towards crystalline cellulose was only one-tenth of that of WT. To quantify the effect of mutation at subsite -4, we measured kinetic parameters of Tr Cel7A WT, W40A and W38A towards cello-oligosaccharides. All combinations of enzymes and substrates showed substrate inhibition, and comparison of the inhibition constants showed that the Trp38 residue increases the velocity of substrate intake ( k on for forming productive complex) from the minus side of the subsites. These results indicate a key role of Trp38 residue in processively loading the reducing-end of cellulose chain into the catalytic tunnel.

Effect of Production Technology of Hydrin T6000 Elastomers on Their Properties and Structure

The influence of the technology for producing elastomer materials based on epichlorohydrin rubber of Hydrin T6000 brand on physical-mechanical properties, structure formation, and frost resistance is studied. Differences in the properties of vulcanizates are revealed due to the formation of various sulfide bonds in a vulcanization network with different densities. The use of rubber swelling technology in a plasticizer leads to a screening effect, which reduces the interaction of the filler with the polymer. On the plus side, this effect improves low-temperature properties, and on the minus side, deteriorates physical-mechanical properties of the material.

Problematika Pembelajaran Berbasis Online pada Lembaga Pendidikan Nonformal Era Pandemi Covid-19 (Studi Kasus di Madrasah Diniyah Manbaul Huda)

Implementation of education in the Covid-19 era still has to pay attention to the needs of children, including in formal educational institutions such as madrasah diniyah. Of course the learning that is carried out is in the corridor of health protocols and the use of online or online systems. Obstacles and obstacles are certainly the minus side of online system learning. This paper seeks to examine in detail the problems of online-based learning in non-formal educational institutions. The focus of the discussion is aimed at the problematic aspects and efforts to solve them at Madrasah Diniyah Manbaul Huda. This research uses a descriptive qualitative approach, with interview techniques. Furthermore, the data were analyzed using data reduction techniques, data display and drawing conclusions. The results of this study indicate that (1) the internet network, the cost of internet data packages, and the limited number of family smartphones are the problems of learning the online system at Madrasah Diniyah Manbaul Huda; (2) Some of the efforts that the teacher can make are preparing online learning, preparing a new schedule and socializing that the teaching and learning process will be through online learning.

The general anesthetic etomidate and fenamate mefenamic acid oppositely affect GABAAR and GlyR: a structural explanation.

GABA and glycine act as inhibitory neurotransmitters in the CNS. Inhibitory neurotransmission is mediated via activation of ionotropic GABAA and glycine receptors. We used a modeling approach to explain the opposite effects of the general anesthetic etomidate (ETM) and fenamate mefenamic acid (MFA) on GABA- and glycine-activated currents recorded in isolated cerebellar Purkinje cells and hippocampal pyramidal neurons, respectively. These drugs potentiated GABAARs but blocked GlyRs. We built a homology model of α1β GlyR based on the cryo-EM structure of open α1 GlyR, used the α1β3γ2 GABAAR structure from the PDB, and applied Monte-Carlo energy minimization to optimize models of receptors and ligand-receptor complexes. In silico docking suggests that ETM/MFA bind at the transmembrane β( +)/α( -) intersubunit interface in GABAAR. Our models predict that the bulky side chain of the highly conserved Arg19' residue at the plus interface side wedges the interface and maintains the conducting receptor state. We hypothesized that MFA/ETM binding at the β( +)/α( -) interface leads to prolongation of receptor life-time in the open state. Having analyzed different GABAAR and GlyR structures available in the PDB, we found that mutual arrangement of the Arg19' and Gln-26' side chains at the plus and minus interface sides, respectively, plays an important role when the receptor switches from the open to closed state. We show that this process is accompanied by narrowing of the intersubunit interfaces, leading to extrusion of the Arg19' side chain from the interface. Our models allow us to explain the lack of GlyR potentiation in our electrophysiological experiments.

EVOLUTION OF ELECTORAL LAW AND ITS BASIC PRINCIPLES IN THE REPUBLIC OF CHILE

In the paper legislation of Chile that is concerned with election law, its history and modern state is analyzed, evaluation of plus and minus sides of this state legislative provisions is given.

John Henry Newman's Spiritual Theology: "Reflections" on Keith Beaumont's Dieu Intérieur

John Henry Newman's Spiritual Theology:"Reflections" on Keith Beaumont's Dieu Intérieur John T. Ford (bio) The technology of the twenty-first century has made eReaders a remarkable convenience that can store hundreds of eBooks in a handy device the size of a slim printed volume. Nonetheless, many people, myself included, still prefer the pleasure of print-publications. This preference is partially due to my long-standing habit of jotting personal reflections and references in the margins of books while I am reading—in effect, attempting to dialogue with the author. On the plus side, this habit has the advantage of affording a quick retrieval of the salient features of every chapter; on the minus side, it has the disadvantage of drastically diminishing a book's re-sale value. In any case, this incorrigible habit is especially useful when reading books in another language, where marginal notes can be helpful both in identifying key ideas and in adding references in English. This quasi-compulsive habit is the origin of the following "reflections" about Keith Beaumont's Dieu Intérieur, a mega-volume, which seems destined to be the gold-standard for future treatments of John Henry Newman's spiritual theology.1 There is, of course, no substitute for reading a book in its original language. The Italian expression—traduttore, traditore (translator, traitor)—succinctly captures the inevitable liabilities of translations. At worst, translators betray—usually inadvertently but sometimes intentionally—an author's meaning. At best, translators can hardly be restrained from inserting a bit of themselves into their translations. However, the following "reflections" are not translations, but an expansion of this reader's margin-notes on the dozen chapters of Beaumont's magnificent book. Hopefully these reflections will provide others with a sampler of Newman's "spiritual theology." [End Page 56] Admittedly, these reflections amplify the original by adding comments and providing some references to relevant works in English. Hopefully, these reflections may prompt some readers to read the French original—a highly rewarding experience eminently worth the time and effort. But for those who do not read French, hopefully these reflections will provide a glimpse into the richness of Newman's spirituality and prompt their own spiritual reflections. theology and spirituality Many people have recognized Newman's stature as a theologian, including Popes Paul VI, John Paul II, and Benedict XVI. Indeed, there are ample grounds for hoping that Newman will not only be canonized but also be declared a "doctor of the Church," a title his theological writings certainly merit.2 First and foremost, Newman's An Essay on the Development of Christian Doctrine (1845) was a seminal work that effectively changed the historical and theological understanding of dogma. Second, his An Essay in Aid of a Grammar of Assent (1870) was a perceptive analysis of the human dimensions of faith that anticipated the pervasive secularism of today's technological world. While these are the two most widely read of Newman's theological writings, other significant contributions include his theological anthropology as presented in his Lectures on the Doctrine of Justification (1838) and his ecclesiology as presented in his Lectures on the Prophetical Office of the Church (1837), a work which was subsequently augmented by his "Preface to the Third Edition" (1878), as well as by his A Letter to the Duke of Norfolk (1875). In terms of quantity, quality, and enduring influence, these writings are a remarkable theological achievement well deserving the designation of "Doctor." Yet, some may be puzzled that Newman repeatedly denied that he was a theologian. His denial was apparently prompted by several factors.3 First, he was an autodidact in theology. During his Oxford years, there were no established Anglican theological schools where he could study.4 Instead, he attended theological lectures, read a plethora of Anglican theologians, and adopted a variety of theological insights—which, like an artist constructing a mosaic, he eventually amalgamated into his own original and creative theological view. [End Page 57] As a Roman Catholic, Newman read not only the leading theologians of his day but also dutifully examined scholastic and post-Tridentine theological treatises. Although he possessed more-than-passing familiarity with the Roman Catholic...

Comparison of numerical models for Acoustic Emission propagation

Acoustic Emissions (AE) are at the basis of extremely accurate and reliable monitoring systems. Within the SmartBench project, data regarding structural health of components are gathered in a database in order to make safety integrated, operative and smart. An accurate modelling of wave propagation is a necessary requirement for a proper design of sensor networks as well as for data interpretation. Numerical simulations of the transient behavior of structural systems are well-established in this field but, on the minus side, they are very expensive in terms of computational time and resources. This paper reports different instances of AE propagation through metallic media. Bulk waves and guided waves are both investigated by means of 2D and 3D models and resorting to different software. Obtained results are cross-checked and computational times are compared as well. As a last point, High Performance Computing is applied to the case of waves simulation in order to get a significant reduction of the required computational time.

\u03b1 subunits in GABAA receptors are dispensable for GABA and diazepam action

The major isoform of the GABAA receptor is α1β2γ2. The binding sites for the agonist GABA are located at the β2+/α1− subunit interfaces and the modulatory site for benzodiazepines at α1+/γ2−. In the absence of α1 subunits, a receptor was formed that was gated by GABA and modulated by diazepam similarly. This indicates that alternative subunits can take over the role of the α1 subunits. Point mutations were introduced in β2 or γ2 subunits at positions homologous to α1− benzodiazepine binding and GABA binding positions, respectively. From this mutation work we conclude that the site for GABA is located at a β2+/β2− subunit interface and that the diazepam site is located at the β2+/γ2− subunit interface. Computational docking leads to a structural hypothesis attributing this non-canonical interaction to a binding mode nearly identical with the one at the α1+/γ2− interface. Thus, the β2 subunit can take over the role of the α1 subunit for the formation of both sites, its minus side for the GABA binding site and its plus side for the diazepam binding site.

Stress-Sensitive Permeability: Application to Fault Integrity During Gas Production

The objective is to propose a simple theoretical approach and the associated numerical algorithm to capture the permeability evolution within a fractured region in response to a stress perturbation. The stress range of interest is typical of a reversible deformation such that the fractures have varying apertures but constant lengths and densities. It is the permeability evolution from a negligible value characteristic of flows on geological times to values more relevant for gas production which is important for the structural integrity of the fractured region. A simple 1D application related to the sealing capacity of a fault bounding a producing gas reservoir is proposed to illustrate the theory. The stress change on the two sides of the faults is obtained with a 2D finite-element simulation based on the theory of poro-elasticity and considering the fault as a material discontinuity. The 1D flow simulation is done in a second step, and the flux is assumed to occur through the fault thickness from the non-depleted (minus side) to the depleted (plus side) regions. It is shown how the depletion results in the fractures opening in the fault damaged zone close to the minus side and the fracture closure next to the plus side. This evolution could be non-monotonic in time because of the development and the thinning of a boundary layer in the fluid pressure at the plus side. The simulations end once a Coulomb criterion is reached, typically at the minus side of the fault. The presence of a low-permeability core in the fault center does not change these conclusions although a positive effective normal stress is detected in the damaged zone on the minus side of the core prior to the Coulomb criterion activation.

An opioid minus major side effects

When given to rats, a new opioid relieves their pain but doesn’t cause the negative side effects typically associated with this class of analgesic, such as addiction, respiratory depression, and constipation (Science 2017, DOI: 10.1126/science.aai8636). “These things are big problems when we treat patients for long periods of time with opioids,” says Christoph Stein, a professor of anesthesiology and critical care medicine at the Free University of Berlin, who led the research. Stein’s group has spent more than 25 years studying opioid receptors on neurons outside the brain and spinal cord. These receptors, he says, become more active at sites of injury or inflammation. Knowing that pH is lower at such sites and that therefore more protons are floating around, Stein teamed up with Marcus Weber at Zuse Institute Berlin to computationally model what the extra protons might be doing to the binding behavior of opioids. They found that the

Leaf phenotypic variation and developmental instability in relation to different light regimes

For pioneer plants, shaded habitats represent a stressful condition, where sunlight exposure is below the optimum level and so leaves expand in order to intercept a greater amount of light. We investigated changes in both phenotypic variation and stress of Bauhinia brevipes in sunny and shaded microhabitats. Leaf area was used as a measure of phenotypic variation, whereas leaf asymmetry (difference between right and left sides of leaves), was used as a measure of stress. We hypothesized an increase in leaf area and stress in shaded locations, which might indicate that B. brevipes was compensating for low light absorption, and elevated levels of stress, respectively. Plants in the sun fitted a fluctuating asymmetry pattern (normal distribution of right minus left sides), while shaded plants were clearly antisymmetric (bimodal distribution of leaf side differences). Leaf asymmetry and area were 5% and 26.8% higher in plants in the shade compared to plants in the sun, respectively. These results were expected since B. brevipes is found predominantly in open areas; so sunlight exposure is important for its development. The presence of antisymmetry is rare in studies of developmental instability, and here it might indicate higher stress compared to plants with fluctuating asymmetry.

Mutagenesis and computational docking studies support the existence of a histamine binding site at the extracellular β3+β3− interface of homooligomeric β3 GABAA receptors

Histamine is an important neurotransmitter that exerts its physiological actions through H1-4 metabotropic receptors in mammals. It also directly activates ionotropic GABAA receptor (GABAAR) β3 homooligomers and potentiates GABA responses in αβ heterooligomers in vitro, but the respective histamine binding sites in GABAARs are unknown. We hypothesized that histamine binds at the extracellular β+β− interface at a position homologous to the GABA binding site of heterooligomeric GABAARs. To test this, we individually mutated several residues at the putative ligand binding minus side of a rat GABAAR β3 wild type subunit and of a β3 subunit that was made insensitive to trace Zn2+ inhibition [β3(H267A); called Zβ3]. Zβ3, Zβ3(Y62L), Zβ3(Q64A), Zβ3(Q64E), α1Zβ3, or α1Zβ3(Y62L) receptors were studied in HEK293T cells using whole cell voltage clamp recording. β3, β3(Y62C), β3(Q64C), β3(N41C), β3(D43C), β3(A45C) or β3(M115C) receptors were examined in Xenopus oocytes using two-electrode voltage clamp. Histamine directly activated Zβ3 and β3 homooligomers and potentiated GABA actions in α1Zβ3 heterooligomers. Receptors containing Zβ3(Y62L), β3(Y62C) and β3(D43C) showed markedly reduced histamine potency, but homo- and heterooligomers with Zβ3(Q64E) exhibited increased potency. The GABAAR αβ(γ) competitive antagonist bicuculline elicited sub-maximal agonist currents through Zβ3 homooligomers, the potency of which was strongly decreased by Zβ3(Y62L). Mutations β3(N41C), β3(A45C) and β3(M115C) disturbed receptor expression or assembly. Computational docking into the crystal structure of homooligomeric β3 receptors resulted in a histamine pose highly consistent with the experimental findings, suggesting that histamine activates β3 receptors via a site homologous to the GABA site in αβγ receptors.

Review of Thomas Christensen,The Work of Music Theory(Ashgate, 2014)

[1] Thomas Christensen's The Work of Music Theory is a recent addition to Ashgate's new Contemporary Thinkers on Critical Musicology series, in which each title, in the words of the publisher, brings together "a selection of previously published and some unpublished essays by leading authorities in the field of musicology." The author chooses what essays to include, and then writes an introduction that puts them into context. Unless the volume includes previously unpublished work, this introduction is the only new material in the book. Ashgate simply photographs and compiles all the essays, without resetting them or allowing any changes. It then adds the title, introduction, and index, and puts a generic black cover on the whole. The series began with the publication of Gary Tomlinson's Music and Historical Critique in 2007, and has continued with collections of the work of Simon Frith, Nicholas Cook, Susan McClary, Richard Leppert, Lawrence Kramer, James Hepokoski, Richard Middleton, Scott Burnham, Derek B. Scott, Tia DeNora, Lucy Green, Robert Morgan, and Annegret Fauser, as well as Christensen.(1) With Kramer, Leppert, McClary, and Tomlinson, the list clearly recognizes the cutting-edge American musicology of the 1990s. But it also includes a number of British scholars who have worked primarily, or at least occasionally, in popular music; a music educator (Green); and, happily, a robust selection of writers whose work across their careers has straddled the disciplines of music theory and music history (Christensen, Cook, Burnham, Hepokoski, and Morgan).[2] The series, of course, has predictable plusses and minuses. On the plus side, it is indeed illuminating to have in a single volume a large body of work from some of the scholars who have definitively shaped their disciplines for the past twenty-five to thirty years--especially when they have (as is the case with most of the writers here) ranged across an impressive expanse of repertoires, issues, and points of view. There's much to be gained from reading their volumes straight through: doing so gives a sense of a scholarly voice, and of a scholarly corpus, that one does not get so easily from reading an author's essays piecemeal over a long period of time. And Ashgate rightly advertises the fact that virtually all of the volumes include important but hard-to-find essays published in obscure venues (festschrifts, foreign-language journals, etc.), and occasionally even essays not previously published at all, so the books make available much material that would be difficult or impossible to gain access to otherwise. In addition, since the essays are printed in facsimile from the original source, readers can see each original publication and cite exact page numbers from that original version, as well as those of the Ashgate volume. On the minus side, though, Ashgate is being a bit disingenuous (to say the least) in the way it promotes and sells the series. The labor-saving means of production for the books assures not only that 1) in a given volume the fonts and the general appearance of the different essays will vary, sometimes dramatically--not a critical problem, necessarily, but an odd one; 2) authors cannot correct errors, add citations of other important work that has appeared since the original publication, or alter their points of view, even many years later; and 3) the publisher realizes significant savings by cutting production costs to the bone--a point not insignificant to us as consumers, and not insignificant even to libraries, since the volumes all cost around $200 (Christensen's is listed at a regular price of $225, or $202.50 if purchased from the Ashgate website).[3] All fifteen essays in Christensen's collection have been published before--a fact that immediately raises two questions about the series. First, why, in this age of the internet, would a publisher produce such books at all, since for the most part they recycle older and often readily available content, and thus would seem to involve risky financial ventures? …