cssi/SciSciGPT-SciSciNet huggingface dataset:
Single amino acid residue determinants of non-peptide antagonist binding to the corticotropin-releasing factor1 (CRF1) receptor.

The molecular interactions between non-peptide antagonists and the corticotropin-releasing factor type 1 (CRF1) receptor are poorly understood. A CRF1 receptor mutation has been identified that reduces binding affinity of the non-peptide antagonist NBI 27914 (M276I in transmembrane domain 5). We have investigated the mechanism of the mutation's effect using a combination of peptide and non-peptide ligands and receptor mutations. The M276I mutation reduced binding affinity of standard non-peptide antagonists 5–75-fold while having no effect on peptide ligand binding. We hypothesized that the side chain of isoleucine, β-branched and so rotationally constrained when within an α-helix, introduces a barrier to non-peptide antagonist binding. In agreement with this hypothesis, mutation of M276 to the rotationally constrained valine produced similar reductions of affinity as M276I mutation, whereas mutation to leucine (with an unbranched β-carbon) minimally affected non-peptide antagonist affinity. Mutation to alanine did not appreciably affect non-peptide antagonist affinity, implying the methionine side chain does not contribute directly to binding. Three observations suggested M276I/V mutations interfere with binding of the heterocyclic core of the compounds: (1) all compounds affected by M276I/V mutations possess a planar heterocyclic core. (2) None of the M276 mutations affected binding of an acylic compound. (3) The mutations differentially affected affinity of two compounds that differ only by core methylation. These findings imply that non-peptide antagonists, and specifically the heterocyclic core of such molecules, bind in the vicinity of M276 of the CRF1 receptor. M276 mutations did not affect peptide ligand binding and this residue is distant from determinants of peptide binding (predominantly in the extracellular regions), providing molecular evidence for non-overlapping (allosteric) binding sites for peptide and non-peptide ligands within the CRF1 receptor.
Referral hiring and ethnically homogeneous jobs: How prevalent is the connection and for whom?

Abstract Research on organizations and labor markets has rekindled interest in the role of insider referrals in matching workers to jobs, emphasizing the contribution this process makes to the reproduction of ethnic segregation in local labor markets. My objective in this study was to provide a systematic examination of ethnic/immigrant variation in these processes using unique data from the Multi-City Study of Urban Inequality. Three key findings emerged. First, evidence showed that insider referrals account for nearly all ethnic/immigrant variation in informal job matching. Second, Latinos, especially newly arrived immigrants, are more likely than native-born Whites to enter jobs through insider referrals. Third, the correlation between insider referrals and ethnically homogeneous jobs is positive and significant only for native-born Blacks. These findings support the proposition that insider referrals are critical for understanding immigrant employment opportunities but also imply that Blacks are uniquely reliant on insider referrals to enter and thus sustain ethnically homogeneous jobs.
Quality of life pilot intervention for breast cancer patients: use of social cognitive theory.

Objective: The purpose of this article is to evaluate an 8-week pilot intervention based on Social Cognitive Theory to improve quality of life for women with breast cancer.Methods: A total of 32 breast cancer patients were randomized to either the intervention or standard care. Outcome variables included quality of life, mood, self-efficacy, outcome expectations, and self-regulation.Results: Effect sizes were calculated to examine the impact of the intervention, with moderate to large effect sizes found for several subscales of the outcome expectations variable: learning about cancer and treatment (d = 0.85), having a positive attitude (d = 0.54), talking about cancer (d = 1.02), engaging in relaxation (d = 0.62), and setting goals (d = 1.58).Significance of results: A nonparametric sign test was conducted, indicating that women in the intervention condition either improved more or showed less decline than the women in standard care, p = .034, two-tailed. Implications and suggestions for the content and delivery of future psychosocial interventions with cancer patients are reviewed.
Development of a Portable Raman Spectrometer for Medical Diagnostics

This paper describes a self-contained, portable Raman instrument that has been developed for biomedical analyses. The instrument consists of a 785-nm diode laser for excitation, an acousto-optic tunable filter (AOTF) for wavelength discrimination, and an avalanche photodiode for detection. The primary component of this system is the AOTF and it has been selected based on its spectral range along with its high resolution, approximately 7.5 cm-1. Software has been developed in-house in the programming language of C for controlling the instrument (i.e., the AOTF frequency, the signal acquisition, etc.). Evaluation of this instrument has been performed by analyzing several standard samples and comparing their spectra to spectra acquired using a conventional laboratory system. In addition to system evaluation, this paper will also discuss potential applications of this instrument to multiplexed genechip types of analyses.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
An electromyography in spastic diplegia

To evaluate the pathologic state accurately and objectively, fifteen patients with spastic diplegia were examined with surface electromyography (EMG) of the rectus femoris, medial hamstring, anterior tibial and gastrocnemius muscles. Seven showed disturbed reciprocal innervation (disturbed group) and 8 showed reciprocal innervation (non disturbed group). The disturbance of reciprocal innervation on EMG showed a positive correlation with delay in onset of crawling by 10 months (p
Spatial hierarchy in Arctic sea ice dynamics

We define a new classification for Arctic sea ice dynamics based on a spatial and temporal scale:floe, multifloe, aggregate, coherent, sub-basin and seasonal. The classification is supported by remotesensing and in situ observations of ice motions at scales of 1–700 km, as found in the existing scientificliterature. The first significant change in sea ice behavior appears as an “emergent” property of the seaice at the transition from the multifloe scale (2–10 km/<1 d) to the aggregate scale (10–75 km/1–3 d).This emergent behavior establishes a statistical mechanical length where sea ice can be considered aplastic continuum. A second important, or coherent scale occurs at 75–300 km and 3–7 d, where thespatial/temporal processes of sea ice dynamics best match the scales of the wind forcing, i.e., winds ofthis duration and fetch are necessary to fully load the internal stress field. At scales smaller than thecoherent scale, the spatial dimension is important because the sea ice motions on the coherent scaleprovide non-local forcing to the aggregate scale. At dimensions larger than the coherent scale, includingthe sub-basin and seasonal scales, spatial and temporal averaging occurs, which smooths discontinuities.To understand and model sea ice dynamics at each of these scales requires an understanding of thedetail at the next smallest level. Proper understanding and representation of sea ice dynamics at allscales is critical to devising a sound strategy for data assimilation into sea ice models. DOI: 10.1034/j.1600-0870.2003.00012.x
CT pulmonary angiography was not inferior to ventilation-perfusion lung scanning for ruling out pulmonary embolism.

Source Citation Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized...
The Game of Electoral Fraud and the Ousting of Authoritarian Rule

How can autocrats be restrained from rigging elections when they hold a huge military advantage over their opponents? This article suggests that even when opposition parties have no military capacity to win a revolt, opposition unity and a consequent threat of massive civil disobedience can compel autocrats to hold clean elections and leave office by triggering splits within the state apparatus and the defection of the armed forces. Opposition unity can be elite-driven, when parties unite prior to elections to endorse a common presidential candidate, or voter-driven, when elites stand divided at the polls and voters spontaneously rebel against fraud. Moreover, the article identifies some conditions under which autocrats will tie their hands willingly not to commit fraud by delegating power to an independent electoral commission. The article develops these ideas through a formal game and the discussion of various case studies. M ost autocracies today hold multiparty elections. What accounts for ruling parties’ decision to commit fraud or respect the election results, and why would rulers ever tie their hands by delegating the organization of elections to independent electoral bodies? What explains that opponents protest against fraud or tacitly acquiesce to electoral tyranny? Why and when is the opposition expected to challenge clean elections? This article answers these fundamental questions by presenting a theory of the dynamics of electoral fraud and postelection opposition protest against it. The article simultaneously seeks to contribute to the study of democratization and to shed light on the politics of what some scholars call “electoral authoritarian�
Comparison of nonequilibrium viscous-shock-layer solutions with shuttle heating measurement

A three-dimensional viscous-shock-layer code has been modified and used to compute the nonequilibrium flowfield over the windward surface of the Space Shuttle Orbiter for re-entry conditions between 75 and 60 km. Centerline heating predictions obtained with the modified code using a recent expression for oxygen recombination at the Shuttle surface were found to be in good agreement with flight data from STS-2 and STS-3. The centerline predictions also show a roughly 30% decrease in heat transfer in comparison with previous results and are now in agreement with two-dimensional viscous-shock-layer results. Comparisons of heating predictions on the off-centerline windward surface were in good agreement with the data flight, and the calculated results followed measured trends in the crossflow heating distributions.
BAKING PERFORMANCE AND CONSUMER ACCEPTABILITY OF RAW AND EXTRUDED COWPEA FLOUR BREADS

Cowpea flour was used to partially replace wheat flour in yeast bread, using automatic household-type bread machines for mixing, proofing and baking. Loaves containing 15 or 30% extruded cowpea flour weighed more (683.4 g) than loaves from other treatments (641.1-652.6 g). The 100% wheat had the highest loaf volume (2.58 L) and the 30% extruded cowpea the lowest (1.64 L). Cowpea flour breads contained more protein (13.9-15.4%) than the 100% wheat (4.1% fat, 12.5% protein). Bread made with 15% extruded cowpea flour was not different (P < 0.05) from the all-wheat control in sensory quality and acceptability. Hedonic ratings for the control and 15% extruded cowpea flour ranged from 6.6 (like slightly) to 7.4 (like moderately) for all sensory attributes. The least liked samples contained either 30% raw or 30% extruded cowpea flour, receiving ratings for all attributes ranging from 4.8 (disliked slightly) to 6.2 (liked slightly). Overall, 15% extruded cowpea flour demonstrated successful bread making performance without compromising sensory quality.
Tutorial on Gravitational Pendulum Theory Applied to Seismic Sensing of Translation and Rotation

Following a treatment of the simple pendulum provided in Appendix [A][1], a rigorous derivation is given first for the response of an idealized rigid compound pendulum to external accelerations distributed through a broad range of frequencies. It is afterward shown that the same pendulum can be an effective sensor of rotation, if the axis is positioned close to the center of mass. [1]: #app-1
Identification of a Candidate Streptococcus pneumoniae Core Genome and Regions of Diversity Correlated with Invasive Pneumococcal Disease

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and gram-positive sepsis. While multiple virulence determinants have been identified, the combination of features that determines the propensity of an isolate to cause invasive pneumococcal disease (IPD) remains unknown. In this study, we determined the genetic composition of 42 invasive and 30 noninvasive clinical isolates of serotypes 6A, 6B, and 14 by comparative genomic hybridization. Comparison of the present/absent gene matrix (i.e., comparative genomic analysis [CGA]) identified a candidate core genome consisting of 1,553 genes (73% of the TIGR4 genome), 154 genes whose presence correlated with the ability to cause IPD, and 176 genes whose presence correlated with the noninvasive phenotype. Genes identified by CGA were cross-referenced with the published signature-tagged mutagenesis studies, which served to identify core and IPD-correlated genes required for in vivo passage. Among these, two pathogenicity islands, region of diversity 8a (RD8a), which encodes a neuraminidase and V-type sodium synthase, and RD10, which encodes PsrP, a protein homologous to the platelet adhesin GspB in Streptococcus gordonii, were identified. Mice infected with a PsrP mutant were delayed in the development of bacteremia and demonstrated reduced mortality versus wild-type-infected controls. Finally, the presence of seven RDs was determined to correlate with the noninvasive phenotype, a finding that suggests some RDs may contribute to asymptomatic colonization. In conclusion, RDs are unequally distributed between invasive and noninvasive isolates, RD8a and RD10 are correlated with the propensity of an isolate to cause IPD, and PsrP is required for full virulence in mice.
Inference for influence over multiple degrees of separation on a social network

States and behaviors of different individuals are expected to be correlated across a social network. Christakis and Fowler have proposed a 'three degrees of influence rule' to characterize the extent of such dependence. In this paper, we discuss three distinct interpretations of such a rule, one involving only associations (which is the interpretation for which Christakis and Fowler give evidence), one involving actual causation, generally referred to as contagion or social influence, and one involving direct effects. We discuss analytic procedures appropriate for assessing evidence for each possible interpretation and the increasingly difficult methodological challenges present in each interpretation.
Diffusion tensor imaging in the assessment of ossification of the posterior longitudinal ligament: a report on preliminary results in 3 cases and review of the literature

Cervical spondylotic myelopathy due to ossification of the posterior longitudinal ligament (OPLL) is a common neurosurgical disease that carries high morbidity. OPLL and other degenerative processes cause narrowing of the central canal, with subsequent spinal cord injury. Repeated minor trauma and vascular aberrations have been purported to underlie cervical spondylotic myelopathy, although the exact pathophysiological mechanism is unclear. Regardless, detection of early axonal damage may allow more timely surgical intervention and prediction of functional outcome. Diffusion tensor (DT) imaging of the cervical spine is a novel technique with improved sensitivity compared with conventional anatomical MR imaging that is currently available on most clinical scanners. This review describes the theoretical basis, application, and analysis of DT imaging as it pertains to neurosurgery. Particular emphasis is placed on OPLL.
Outcomes with prolonged clopidogrel therapy after coronary stenting in patients with chronic kidney disease

Objectives Patients with chronic kidney disease (CKD) are at high risk of death or myocardial infarction (MI) after percutaneous coronary interventions (PCI). We assessed whether prolonged dual antiplatelet therapy beyond the recommended 12 months may prevent adverse outcomes in patients with CKD receiving drug-eluting stents (DES) or bare-metal stents (BMS). Methods We studied all Veterans receiving PCI with BMS or first-generation DES in the Veterans Affairs (VA) Healthcare System between 2002 and 2006, classified by CKD (estimated glomerular filtration rate Results Of 23 042 eligible subjects receiving PCI, 4880 (21%) had CKD. Compared with normal renal function, patients with CKD had higher risks of death or MI 1–4 years after DES (21% vs 12%, HR=1.75; 95% CI 1.51 to 2.04) or BMS (28% vs 15%, HR=2.10; 95% CI 1.90 to 2.32). In patients with CKD receiving DES, clopidogrel use of more than 12 months after PCI was associated with lower risks of death or MI (18% vs 24%, HR=0.74; 95% CI 0.58 to 0.95), and death (15% vs 23%, HR=0.61; 95% CI 0.47 to 0.80), but had no effect on repeat revascularisation 1–4 years after PCI. Conclusions In patients with CKD, prolonging clopidogrel beyond 12 months after PCI may decrease the risk of death or MI only in patients receiving first-generation DES. These results support a patient-tailored approach to prolonging clopidogrel after PCI.
THE DISTRIBUTION OF DNA AMONG DIVIDING MITOCHONDRIA OF TETRAHYMENA PYRIFORMIS

A squash technique was developed for log phase Tetrahymena pyriformis which permitted the resolution of over 100 individual mitochondria from a single cell. Mitochondria incorporated thymidine at all stages of the cell cycle, even when nuclear DNA synthesis was not occurring. During the stage of macronuclear DNA synthesis, however, there was a significant increase in the extent of mitochondrial labeling. Low radioautograph background suggests that mitochondrial DNA is synthesized at the mitochondria themselves. All mitochondria incorporated thymidine-3H within one population-doubling time. Grain counts also showed that the amount of mitochondrial label was retained for four generations and that this label remained randomly distributed among all mitochondria during this time. The results are not consistent with any theory of de-novo or "microbody" origin of mitochondria, but do support the hypothesis that mitochondria are produced by the growth and division of preexisting mitochondria. The stability of the mitochondrial DNA and its distribution among daughter mitochondria satisfy two prerequisites for a genetic material. The possibility is discussed that some of the genetic information for the mitochondrion is contained in the DNA associated with this organelle.
Randomized Clinical Trial of Therapeutic Exercise in Subacute Stroke

Background and Purpose— Rehabilitation care after stroke is highly variable and increasingly shorter in duration. The effect of therapeutic exercise on impairments and functional limitations after stroke is not clear. The objective of this study was to determine whether a structured, progressive, physiologically based exercise program for subacute stroke produces gains greater than those attributable to spontaneous recovery and usual care. Methods— This randomized, controlled, single-blind clinical trial was conducted in a metropolitan area and 17 participating healthcare institutions. We included persons with stroke who were living in the community. One hundred patients (mean age, 70 years; mean Orpington score, 3.4) consented and were randomized from a screened sample of 582. Ninety-two subjects completed the trial. Intervention was a structured, progressive, physiologically based, therapist-supervised, in-home program of thirty-six 90-minute sessions over 12 weeks targeting flexibility, strength, balan...
Chemistry with spatial control using particles and streams

Spatial control of chemical reactions, with micro- and nanometer scale resolution, has important consequences for one pot synthesis, engineering complex reactions, developmental biology, cellular biochemistry and emergent behavior. We review synthetic methods to engineer this spatial control using chemical diffusion from spherical particles, shells and polyhedra. We discuss systems that enable both isotropic and anisotropic chemical release from isolated and arrayed particles to create inhomogeneous and spatially patterned chemical fields. In addition to such finite chemical sources, we also discuss spatial control enabled with laminar flow in 2D and 3D microfluidic networks. Throughout the paper, we highlight applications of spatially controlled chemistry in chemical kinetics, reaction-diffusion systems, chemotaxis and morphogenesis.
Atomistic insights into human Cys-loop receptors by solution NMR

Abstract Cys-loop receptors are pentameric ligand-gated ion channels (pLGICs) mediating fast neurotransmission in the central and peripheral nervous systems. They are important targets for many currently used clinical drugs, such as general anesthetics, and for allosteric modulators with potential therapeutic applications. Here, we provide an overview of advances in the use of solution NMR in structural and dynamic characterization of ion channels, particularly human Cys-loop receptors. We present challenges to overcome and realistic solutions for achieving high-resolution structural information for this family of receptors. We discuss how subtle structural differences among homologous channels define unique channel pharmacological properties and advocate the necessity to determine high-resolution structures for individual receptor subtypes. Finally, we describe drug binding to the TMDs of Cys-loop receptors identified by solution NMR and the associated dynamics changes relevant to channel functions. This article is part of a Special Issue entitled: NMR Spectroscopy for Atomistic Views of Biomembranes and Cell Surfaces. Guest Editors: Lynette Cegelski and David P. Weliky.
Race, Crime, and the Micro‐Ecology of Deadly Force

Limitations in data and research on the use of firearms by police officers in the United States preclude sound understanding of the determinants of deadly force in police work. The current study addresses these limitations with detailed case attributes and a microspatial analysis of police shootings in St. Louis, MO, between 2003 and 2012. The results indicate that neither the racial composition of neighborhoods nor their level of economic disadvantage directly increase the frequency of police shootings, whereas levels of violent crime dobut only to a point. Police shootings are less frequent in areas with the highest levels of criminal violence than in those with midlevels of violence. We offer a provisional interpretation of these results and call for replications in other settings. Policy ImplicationsNationwide replications of the current research will require the establishment of a national database of police shootings. Informative assessments of a single agency's policies and practices require comparative information from other agencies. We recommend specific data elements to be included in such an information system that would shed further empirical light on the interconnections among race, crime, and police use of deadly force. The database also would contribute to the development of evidence-based policies and procedures on deadly forcean urgent public priority in light of recent controversial police shootings across the United States. Language: en
Assessment of Family History Information in Case-Control Cancer Studies

Evidence for the genetic basis of cancer has increased in recent years, and thus, assessing familial aggregation may play an important role in epidemiologic studies. To assess the degree to which family history variables are collected in cancer case-control studies, the authors conducted a literature review of studies published in six journals during 1982-1984. Only 25% of these included a family history component. The authors review some of the literature in favor of inclusion of family information and argue for its routine collection in cancer case-control studies.
Brain Cortical Thickness Differences in Adolescent Females with Substance Use Disorders.

Some youths develop multiple substance use disorders early in adolescence and have severe, persistent courses. Such youths often exhibit impulsivity, risk-taking, and problems of inhibition. However, relatively little is known about the possible brain bases of these behavioral traits, especially among females. Methods We recruited right-handed female patients, 14–19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses. Results A priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size). Conclusions Adolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies.
The relationship between synapsis, recombination nodules and chiasmata in tomato translocation heterozygotes

The relationship between synapsis, recombination nodules and chiasmata in tomato translocation heterozygotes
Management by Objectives for the Academic Medical Center

Management by Objectives (MBO) is results-oriented, participatory management, which is appropriate for the current era of keen competition for resources. MBO was installed in the author’s institution in clinical laboratory divisions meeting prerequisites and fit the system to the local management environment. The results were decidedly positive. Benefits included improved communication, organizational clarity, planning for deadlines, motivation of participants, work load distribution, and productivity. Projects were easier to visualize, track, and coordinate. A natural review cycle of three to four months evolved, with general review twice a year. MBO worked best with one- to two-year-long projects involving problem solving and innovation. The author expects maturity of his MBO application within three years. He recommends MBO for other academic medical center laboratories, provided executive management commits the necessary time and resources to install MBO carefully as a relatively loose, locally administered form of management philosophy, rather than management technology.
A Surrogate-based Adjustment Factor Approach to Multi-Fidelity Design Optimization

The conceptual and preliminary design stages of aircraft design have traditionally been two separate, time intensive design phases. However, the concept of dialable/multi-fidelity design is one in which the gap between these two phases, conceptual and preliminary design, is bridged by introducing physics into the design process at an earlier stage than traditionally possible. This introduction of physics at an earlier stage eliminates the need for separate conceptual and preliminary design phases and consequently reduces total design time. The concept of multi-fidelity design does however pose certain obstacles such as determining how and when to “dial” or switch between different fidelity models. This paper explores the ability to apply an adjustment factor to the response of the low-fidelity model so as to “correct” the low-fidelity model. In doing so, the “corrected low-fidelity” model becomes more representative of the high-fidelity model. This process is employed within a Trust Region Model Management optimization routine. A surrogate model is constructed on the calculated adjustment factors available at high-fidelity simulation points with corresponding low-fidelity simulations. This surrogate serves the purpose of determining an adjustment factor given any design point (thus a function of design variables) that is then utilized in correcting the low-fidelity simulation at a corresponding design point. It is shown that optimization on the high-fidelity as well as corrected low-fidelity models converge to the same local optimum. Employing the proposed multi-fidelity methodology results in converging to the high-fidelity optimum in an order of magnitude fewer highfidelity function evaluations. This paper outlines the Trust Region Model Management optimization,surrogate modeling, and adjustment factor procedures. These procedures are then demonstrated on two different demonstration optimization problems. The first of these demonstration problems is a purely academic test case while the second consists of optimizing a geometrically nonlinear, tapered, cantilever beam.
Thermodynamics of multicomponent olivines and the solution properties of (Ni,Mg,Fe)2SiO4 and (Ca,Mg,Fe)2SiO4 olivine—Reply

Fleet (2000) criticizes several aspects of the thermodynamic model for (Ni,Mg,Fe)2SiO4-bearing olivine from Hirschmann (1991) and its subsequent recalibration in my Ph.D. thesis (Hirschmann 1992). He also justifies the thermodynamic methods used by Fleet (1989) to extract activity coefficients of NiSi0.5O2 in olivine. I am pleased that somebody has taken the time to read parts of my Ph.D. thesis and will take this opportunity to reply to Fleet’s comments on some of my early work and elaborate on the problems with Fleet (1989). Fleet (2000) finds fault with three aspects of the thermodynamic model for (Ni,Mg,Fe)2SiO4 olivine from Hirschmann (1991 Hirschmann (1992). He criticizes the formulation of the model, but his contentions reflect misapprehensions regarding thermodynamic models that account for long-range ordering. He questions the quality of the ordering data used to calibrate the model, but does not acknowledge available data that corroborate the site occupancy measurements. He also disparages the accuracy of the predicted activity-composition relations, but fails to account for experimental uncertainties and discounts considerable evidence for agreement between the model and experimental constraints on NiSi0.5O2 olivine activities. Fleet (2000) also defends the activity coefficients for NiSi0.5O2 extracted in the thermodynamic analysis of Fleet (1989). He suggests that there is a posteriori evidence that silica activity was nearly constant in a suite of experiments that were not designed to buffer silica but, as detailed below, there is good reason to suspect significant silica activity variation in these experiments. He reiterates evidence presented in Fleet (1989) suggesting that the oxysulfide liquids in the experiments of interest are reasonable approximations of FeS-NiS binary solutions. However, these liquids are unlikely to be close to monosulfide composition because their reported compositions are critically …
Exploring paradoxical functional facilitation with TMS.

Publisher Summary This chapter describes experiments conducted in cats to underscore the local and distant effects exerted by repetitive transcranial magnetic stimulation (TMS). The better understanding of the modulatory effects of repetitive transcranial magnetic stimulation (rTMS) can then lead to the experimental testing of specific hypotheses relating to the paradoxical effects of TMS-induced “virtual lesions.” The chapter describes studies on attention and motor performance that highlight the potential of TMS as a tool to reveal functional facilitations and ultimately offer the possibility to use such an approach for therapeutic purposes. The chapter presents the results that underscore the potential of TMS as a tool to probe the paradoxical functional facilitations that may occur following lesions to a particular node of a complex and distributed neural network. Work in cats has shown the robust metabolic effects of rTMS on local and distant cortical and subcortical sites.
Thermostatistics of a damped bimodal particle.

We study the thermostatistics of a damped bimodal particle, i.e., a particle of mass m subject to a work reservoir that is analytically represented by the telegraph noise. Because of the colored nature of the noise, it does not fit the Levy-Ito class of stochastic processes, making this system an instance of a nonequilibrium system in contact with a non-Gaussian external reservoir. We obtain the statistical description of the position and velocity, namely in the stationary state, as well as the (time-dependent) statistics of the energy fluxes in the system considering no constraints on the telegraph noise features. With that result we are able to give an account of the statistical properties of the large deviations of the injected and dissipated power that can change from sub-Gaussianity to super-Gaussianity depending on the color of the noise. By properly defining an effective temperature for this system, T, we are capable of obtaining an equivalent entropy production-exchange rate equal to the ratio between the dissipation of the medium, γ, and the mass of the particle, m, a relation that concurs with the case of a standard thermal reservoir at temperature, T=T.
Party ideology and popular politics at the accession of George III: From Old Corps to Rockinghamite whigs: the emergence of a party

I will attend to measures not men, but wish to see those measures conducted by [the] Butes and Grenville connection, rather than by Rockinghams, etc. I have reason to think the former wishes to extirpate party distinctions, as I know the latter wants to establish ‘em. (Sir Armine Wodehouse to Lord Townshend, 9 August 1767. Norfolk RO Townshend Mss.) Two closely related problems dominated the thinking of the Newcastle and Rockingham whigs after the political disasters of 1762. The first of these was the question of the fate of the whig party. Because the Rockinghams saw the battle between government and opposition as a struggle between tory and whig, it was not difficult for them to agree with others in opposition who urged that ttee whig party ought to be united against the threat of a (putative) new toryism. This, after all, was merely the application, in opposition, of a tried and well-worn tactic which the whig alliance had used when it had dominated officeholding. But, throughout the first decade of George III's reign, there was very considerable disagreement amongst those who selfconsciously opposed the ‘new toryism’, about both the ideological complexion of the whig party and the composition of its leadership. Tensions that had usually, though by no means invariably, remained covert before 1761 were now, in the adverse circumstance of opposition, made quite explicit.
Storytelling, Sincerity, and Islamic Televangelism in Egypt

In 2001, the first episode of what was to become a hit show — Kalam min al-Qalb (Words from the Heart) — aired on a privately owned Egyptian satellite channel. Amr Khaled, at the time a relatively unknown da’iyia (‘caller to Islam’, pl. duah) who was also a practising accountant, was the host of the show. Interweaving Qur’anic stories of the prophets with the personal stories of ordinary Muslims struggling to be more pious, the show inaugurated what has since become an extraordinarily popular genre of Islamic television programming. Indeed, Amr Khaled’s fame soared as the show attracted an increasingly vocal viewership. Thousands of young people began attending his Friday mosque sermons in one of Cairo’s new satellite suburbs and his website received more than 3 million hits per month, making it one of the most visited sites in the nation by the end of 2001. As 2002 drew to a close, however, the Mubarak regime banned Khaled from preaching in public, leading the da’iyia to leave the country.1
Cell Surface Protein Detection to Assess Receptor Internalization

The migration of membrane receptors upon exposure to different stimulants/inhibitors is of great importance. Among others, the internalization of membrane receptors affects their accessibility to ligands and cell responsiveness to environmental cues. Experimentally, receptor internalization can be used as a measure of their activation. In our studies, we employed this approach to explore cross-talk between a seven transmembrane domain receptor for neuropeptide Y (NPY), Y5R, and a tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF), TrkB. To this end, we measured the internalization of Y5R upon stimulation with the TrkB ligand, BDNF. Upon treatment with BDNF, the cells were exposed to a membrane impermeable, biotinylation reagent that selectively labels surface proteins. Subsequently, the biotinylated membrane proteins were affinity-purified on columns with avidin resins and analyzed by Western blot. Differences in the fraction of receptors present on the cell surface of control and ligand-treated cells served as a measure of their internalization and response to particular stimuli.
Testicular Cancer in a Russell-Silver Dwarf

A case of Russell-Silver dwarfism is described in which surgically corrected inguinal cryptorchidism was followed by advanced embryonal carcinoma. This case is noteworthy because 42 per cent of male Russell-Silver dwarfs have cryptorchidism, yet testicular malignancy in this syndrome has not been reported previously. Risk factors for the development of testicular cancer in this case include cryptorchidism, inguinal hernia and testicular atrophy. Optimal management of testicular abnormalities in the Russell-Silver dwarf is discussed.
An extended surface target for high-frequency multibeam echo sounder calibration.

An extended calibration target has been developed for calibrating the intensity output of a multibeam echo sounder (MBES). The target was constructed of chain links arranged similar to a curtain, providing an extended surface target with a mean scattering strength of −17.8 dB at 200 kHz. The target was used to calibrate a 200 kHz MBES, and the MBES was subsequently used to collect seafloor backscatter over sand and gravel seafloors. Field results were compared with calibrated split-beam echo sounder measurements at an incidence angle of 45°. The results suggest that the chain target is a viable MBES calibration tool.
An intramolecular para-phenolic allylation free radical cyclization strategy for the synthesis of alkaloids and terpenes with spiro[4.5]decane architectures

Abstract A Tsuji-Trost variant of the Winstein-Masamune reaction has been investigated for the synthesis of the AC spirocyclic ring system 9 bearing a quaternary carbon found in the fawcettimine type Lycopodium alkaloids magellanine 1 and lycojaponicumin B 2 and cyclopiane diterpenes such as conidiogenone 3. Annulation of the B ring for the synthesis of tricyclic ABC cores was demonstrated utilizing a 5-exo-trig free radical cyclization of a primary carbon radical onto a cyclohexadienone generated with tri-n-butylgermanium hydride (9 → 11).
A Probabilistic New Model Compounding a Dynamic Trial Process and a Repeat-Buying Process

A new product model is developed which assumes that the introduction of a new brand affects brand choice in the product class but not the primary demand, i.e., the timing of the purchases of the product class. Each individual is characterized by a trial probability, a repeat purchase probability, and his particular unchanged rate of purchase of the product class. All three parameters are allowed to vary across consumers. A dynamic model of availability of the new brand is also postulated, since a new brand usually does not reach intensive distribution coverage immediately. The analytical expressions for the first purchase function and the total sales function are derived. Two sales patterns emerge, with or without a peak, depending upon the values of the parameters of the model. A deeper understanding of the early part of the life cycle of new products could result from this model. It may also lead to improved forecasting of new product sales, since the model could result in better understanding of how a peak can arise, when it may occur, and what its magnitude may be relative to the long term equilibrium sales level of the new brand.
Variable-Reluctance Stepping Motor Performance Capabilities for Point-To-Point Positional Control

Abstract The question considered in this paper is the ultimate performance limitations of variable-reluctance stepping motors. It has been shown previously that solving the problem of matching a stepping motor to a load reveals two key parameters needed to characterize its performance for point-to-point positional control. These parameters are the work per step and the upper limit on stepping frequency when the motor runs free of its load. These parameters apply when certain operating conditions, termed “Class I operation,” are satisfied. The electromagnetically limited performance capability of two types of stepping motors is examined in terms of the above two parameters. The types considered are machines with armature motion parallel to the air gap and those with armature motion normal to the air gap. Expressions are derived that relate the key performance parameters to the physical dimensions of the machines and to basic properties of materials. It is concluded that the machines with motion normal to the air gap potentially offer superior performance to those with parallel motion, at least over size ranges of greatest interest. However, the full realization of this superior performance will not be possible until the mechanical problem of converting small linear displacements into shaft rotation is solved in an efficient manner.
Abstract 1019:In vivoCRISPR screening identifies Ptpn2 as a target for cancer immunotherapy

Despite the dramatic clinical success of cancer immunotherapy with PD-1 checkpoint blockade, most patients don’t experience sustained clinical benefit, suggesting that additional therapeutic strategies are needed. Functional genomic screens in cancer cells to discover new therapeutic targets are usually carried out in vitro where interaction with the immune system is absent. Here we report a pooled, loss-of-function genetic screening approach using CRISPR/Cas9 genome editing that is conducted in vivo in mouse transplantable tumors treated with vaccination and PD-1 checkpoint blockade. We tested 2,400 genes expressed by melanoma cells for those that synergize with or cause resistance to checkpoint blockade, and recovered the known immune evasion molecules, PD-L1 and CD47. Loss of function of multiple genes required to sense interferon-y caused resistance to immunotherapy. Deletion of Ptpn2, a pleotropic protein tyrosine phosphatase improved response to immunotherapy. In vivo, Ptpn2 deficient tumors showed increased infiltration of activated CD8+T cells. In vitro, Ptpn2 loss by tumor cells increased antigen presentation to T cells. Biochemical, transcriptional and genetic epistasis experiments demonstrated that loss of function of Ptpn2 sensitizes tumors to immunotherapy by enhancing interferon-y-mediated effects on the tumor cell. Thus, augmenting interferon-y signaling in tumor cells could increase the efficacy of immunotherapy. More generally, in vivo genetic screens in tumor models can identify new immunotherapy targets and rationally prioritize combination therapies. Citation Format: Robert T. Manguso, Hans W. Pope, Margaret D. Zimmer, Flavian D. Brown, Kathleen B. Yates, Brian C. Miller, Natalie B. Collins, Kevin Bi, Martin W. Lafleur, Vikram R. Juneja, Sarah A. Weiss, David E. Fisher, David E. Root, Arlene H. Sharpe, John G. Doench, W Nicholas Haining. In vivo CRISPR screening identifies Ptpn2 as a target for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1019. doi:10.1158/1538-7445.AM2017-1019
Combinatorial multinomial generators for colorings of 4D-hypercubes and their applications

Combinatorial enumeration of colorings of vertices, edges, faces and cells of 4D-hypercubes are considered for all irreducible representations of the 4D-hyperoctahedral group. We have developed computer codes that enumerate colorings of such hypercubes up to 25 dimensions and up to 10 different colors, only limitation being the combinatorial explosion. Tables are obtained for all irreducible representations and colorings for a four-dimensional hypercube with four-colorings. Several applications to spectroscopy, molecular dynamics, boolean algebra, DNA with unnatural pairs, parallel computing and rovibronic states and nuclear spin statistics of non-rigid molecular tetramers such as (H2O)4, (D2O)4, (Cl2O)4, etc., are pointed out.
Bioorthogonal click chemistry for fluorescence imaging of choline phospholipids in plants

Phospholipids are important structural and signaling molecules in plant membranes. Some fluorescent dyes can stain general lipids of membranes, but labeling and visualization of specific lipid classes have yet to be developed for most components of the membrane. New techniques for visualizing membrane lipids are needed to further delineate their dynamic structural and signaling roles in plant cells. In this study we examined whether propargylcholine, a bioortholog of choline, can be used to label the major membrane lipid, phosphatidylcholine, and other choline phospholipids in plants. We established that propargylcholine is readily taken up by roots, and that its incorporation is not detrimental to plant growth. After plant tissue is harvested and fixed, a click-chemistry reaction covalently links the alkyne group of propargylcholine to a fluorescently-tagged azide, resulting in specific labeling of choline phospholipids. Uptake of propargylcholine, followed by click chemistry with fluorescein or Alexa Fluor 594 azide was used to visualize choline phospholipids in cells of root, leaf, stem, silique and seed tissues from Arabidopsis thaliana. Co-localization with various subcellular markers indicated coinciding fluorescent signals in cell membranes, such as the tonoplast and the ER. Among different cell types in the leaf epidermis, guard cells displayed strong labeling. Mass spectrometry-based lipidomic analysis of the various plant tissues revealed that incorporation of propargylcholine was strongest in roots with approximately 50% of total choline phospholipids being labeled, but it was also incorporated in the other tissues including seeds. Phospholipid profiling confirmed that, in each tissue analyzed, incorporation of the bioortholog had little impact on the pool of choline plus choline-like phospholipids or other lipid species. We developed and validated a click-chemistry based method for fluorescence imaging of choline phospholipids using a bioortholog of choline, propargylcholine, in various cell-types and tissues from Arabidopsis. This click-chemistry method provides a direct way to metabolically tag and visualize specific lipid molecules in plant cells. This work paves the way for future studies addressing in situ localization of specific lipids in plants.