cssi/SciSciGPT-SciSciNet huggingface dataset:
SMA-3 Smad Has Specific and Critical Functions in DBL-1/SMA-6 TGFβ-Related Signaling

Abstract A TGFβ signal transduction cascade controls body size and male tail morphogenesis in the nematode Caenorhabditis elegans. We have analyzed the function of the sma-3 Smad gene, one of three Smad genes that function in this pathway. Null mutations in sma-3 are at least as severe as null mutations in the ligand and type I receptor genes, dbl-1 and sma-6, indicating that the other Smads do not function in the absence of SMA-3. Furthermore, null mutations in sma-3 do not cause defects in egg laying or in regulation of the developmentally arrested dauer larva stage, indicating no overlapping function with another C. elegans TGFβ signaling pathway. The sma-3 gene is widely expressed at all developmental stages in hermaphrodites and males. The molecular lesions associated with eight sma-3 alleles of varying severity have been determined. The missense mutations cluster in two previously identified regions important for Smad function.
Sociosexuality and face perception: Unrestricted sexual orientation facilitates sensitivity to female facial cues

Across two studies, sexually unrestricted men and women showed heightened sensitivity to female facial symmetry (a signal of genetic fitness) and female sexual receptivity (happy facial expressions). In Study 1, individuals assessed the attractiveness of male and female targets of varying facial symmetry. Sexually unrestricted men and women, compared to their sexually restricted counterparts, showed a stronger symmetry advantage in attractiveness ratings for female targets, an indication of greater sensitivity to facial symmetry. Study 2 asked participants to discriminate between genuine (Duchenne) and deceptive smiles on both male and female faces. Results indicated that sexually unrestricted men and women, compared to sexually restricted individuals, were better able to discriminate between these actual and deceptive signals of receptivity for female targets. Neither study found any relationship between sociosexual orientation and the perception of male targets. These results suggest that sexually unrestricted individuals are attuned to reproductively-relevant cues in female faces.
Stochastic Seismic Ground Motion Modelling With Imperfectly Stratified Earth Medium

Abstract Earthquake wave propagation in an imperfectly stratified linear elastic earth medium, generated by a buried seismic dislocation source, is investigated. Using a first order perturbation approach, it is shown that the total wave field may be obtained as a superposition of a mean wave field and a scattered wave field. Both the mean and the scattered wave fields exist in the same perfectly stratified earth medium, without the presence of the irregular interface. The mean wave field is associated with a buried seismic dislocation source, while the scattered wave field is associated with a set of fictitious discontinuity sources distributed on the fictitious mean interface, which has the same effect as the interface irregularities and can be obtained in terms of the mean wave field. The response in the mean wave field can be obtained using the finite integral transform approach. The response in the scattered wave field may be constructed by the fundamental solution with a sinusoidal interface, which may be obtained using the same approach as the mean wave field. With knowledge of the fundamental solution and its corresponding properties, the statistical properties of the ground motion with an imperfectly stratified earth medium may be evaluated. Finally, a numerical example is carried out for illustration purposes.
On the Foundations of Reliability

Under the framework of a stochastic point process of failures, this paper discusses basic ways to characterize reliability. The distinction between the failure rate of a process, useful for repairable systems, and the failure rate of a distribution, useful for nonrepairable systems, is drawn. The paper then concentrates on modeling the wearout characteristics of repairable system reliability. Neither the homogeneous Poisson nor the renewal processes will suffice for this purpose. The nonhomogeneous Poisson process is appealing as a general wearout model, but it too has nonintuitive features; for example, the distribution of first failure determines the entire process. This leads us to search for other alternatives and to consider the reliability characteristics of general point processes of failures. Results pertaining to the appealing alternative of superimposed processes are reviewed.
The adenosine triphosphate content of the unfertilized and fertilized eggs of Asterias forbesii and Strongylocentrotus dröbachiensis

Abstract 1. 1. An isobutyl alcohol extraction method for the determination of inorganic phosphate in the presence of agents or complex colloidal substances interfering with color production is described. The method is particularly adapted to measuring inorganic phosphate in the presence of easily hydrolyzable phosphate compounds. 2. 2. Barium fractionation revealed that adenosine pyrophosphate accounts for all the organic phosphate in the barium-insoluble fraction of unfertilized eggs. In two experiments on Asterias eggs , and in all experiments on Strongylocentrotus eggs only adenosine triphosphate (ATP) was found. In one experiment on Asterias eggs only adenosine diphosphate (ADP) was found, and in another both ATP and ADP were found. 3. 3. Using Kalckar's method of differential spectrophotometry, the quantity of ATP found in the eggs of Asterias forbesii was 1.20–1.45 mg. ATP/ml. of eggs. Adenosine monophosphate (AMP) and ADP could not be detected in the unfertilized egg (first and second polar body stage) nor in the fertilized egg at various stages of the first cleavage cycle. The absolute quantity of ATP does not vary in the above stages.
Maternal Emotion-related Socialization and Preschoolers' Developing Emotion Self-awareness

Preschoolers’ ability to demonstrate awareness of their own emotion is an important socio-emotional competence which has received increasing attention in the developmental literature. The present study examined emotion self-awareness of happiness, sadness, and anger in response to a delay of gratification task in 78 preschool children. Maternal emotion-related socialization behaviors (ERSBs) including reported emotional expressivity, responses to her child’s emotions, and observed emotion talk, were examined as predictors of children’s emotion self-awareness skill one year later. Results show that, after controlling for receptive language ability, supportive ERSBs were predictive of high self-awareness of happiness whereas non-supportive ERSBs were predictive of low self-awareness of sadness. The results demonstrate that the concordance between observed and self-reported emotion serves as a useful index of children’s awareness of their emotional experience.
Corticothalamic Inhibition in the Thalamic Reticular Nucleus

Mutual inhibition between the GABAergic cells of the thalamic reticular nucleus (RTN) is important in regulating oscillations in the thalamocortical network, promoting those in the spindle range of...
Procedures for Revising Management Judgments Forecasts

Forecast improvement is often approached by attempting to find the “best” model for a given situation. Less attention has been paid to the possibility of examining past prediction errors for patterns that may suggest forecast adjustments for the future. This empirical study involves one firm’s management judgment forecasts for product sales and the attempts made to improve their accuracy by removing certain types of bias. In three of the five series examined, error reduction averaging close to thirty percent occurs as a result of the adjustment procedure. The other two series proved to be relatively free from bias and were therefore not in need of the correction method described.
MyD88- and TRIF-Independent Induction of Type I Interferon Drives Naive B Cell Accumulation but Not Loss of Lymph Node Architecture in Lyme Disease

Rapidly after infection, live Borrelia burgdorferi, the causative agent of Lyme disease, is found within lymph nodes, causing rapid and strong tissue enlargement, a loss of demarcation between B cell follicles and T cell zones, and an unusually large accumulation of B cells. We sought to explore the mechanisms underlying these changes, as lymph tissue disruption could be detrimental for the development of robust Borrelia-specific immunity. A time course study demonstrated that the loss of the normal lymph node structure was a distinct process that preceded the strong increases in B cells at the site. The selective increases in B cell frequencies were due not to proliferation but rather to cytokine-mediated repositioning of B cells to the lymph nodes, as shown with various gene-targeted and bone marrow irradiation chimeras. These studies demonstrated that B. burgdorferi infection induced type I interferon receptor (IFNR) signaling in lymph nodes in a MyD88- and TRIF-independent manner and that type I IFNR indirect signaling was required for the excessive increases of naive B cells at those sites. It did not, however, drive the observed histopathological changes, which occurred independently also from major shifts in the lymphocyte-homing chemokines, CXCL12, CXCL13, and CCL19/21, as shown by quantitative reverse transcription-PCR (qRT-PCR), flow cytometry, and transwell migration experiments. Thus, B. burgdorferi infection drives the production of type I IFN in lymph nodes and in so doing strongly alters the cellular composition of the lymph nodes, with potential detrimental effects for the development of robust Borrelia-specific immunity.
A semianalytic meshless approach to the Fokker-Planck equation with application to hybrid systems

A semianalytic partition of unity finite element method (PUFEM) is presented to solve the transient Fokker-Planck equation (FPE) for high-dimensional nonlinear dynamical systems. Meshless spatial discretization of the PUFEM is employed to develop linear ordinary differential equations for the time varying coefficients of the local shape functions. It is shown that a similarity transformation to the modal coordinates brings out numerous spurious modes in the eigenspace of the discretized FPE operator. The identification and elimination of these modes leads to an analytical solution of the ODEs for the coefficients of the shape functions developed by the spatial discretization. Furthermore, the retention of only a few admissible modes leads to a significant order-reduction in the transient problem. Equation-error bounds for the approximation are presented and it is shown that the equation-error at the initial time resulting from the retained set of admissible modes is an upper bound for all subsequent times. Results are presented for a two-dimensional nonlinear stochastic oscillator. Some initial ideas are presented for the application of this approach to determining the probabilistic behavior of stochastic hybrid dynamical systems with Markovian switching.
Layer Number Determination and Thickness-Dependent Properties of Graphene Grown on SiC

The electronic properties of few-layer graphene grown on the carbon face of silicon carbide (SiC) are found to be strongly dependent on the number of layers. The carrier mobility is larger in thicker graphene because substrate-related scattering is reduced in the higher layers. The carrier density dependence of the mobility is qualitatively different in thin and thick graphene, with the transition occurring at about 2 layers. The mobility increases with carrier density in thick graphene, similar to multilayer graphene exfoliated from natural graphite, suggesting that the individual layers are still electrically coupled in spite of reports recording non-Bernal stacking order in C-face grown graphene. The Hall coefficient peak value is reduced in thick graphene due to the increased density of states. A reliable and rapid characterization tool for the layer number is, therefore, highly desirable. To date, atomic force microscopy height determination and Raman scattering are typically used since the optical contrast of graphene on SiC is weak. However, both methods suffer from low throughput. We show that the scanning electron microscopy (SEM) contrast can give similar results with much higher throughput.
Space Frames: The Space Within—A Guided Tour:

New configurations as well as new applications are constantly discovered for space structures. There is every indication that this trend will continue for a very long time.This paper describes four configurations developed in the last ten years to provide architects with a framework for the accommodation of any building program.These configurations have their origin in a multi-layer, three-way space frame. They are, however, very different from each other. Although these have been the subjects of separate publications, they are discussed here together for the first time.The author feels that the discussion of topological aspects of space frames which relate to architectural considerations will make a positive contribution towards a more generalized use of space structures.
Borrelia burgdorferi stimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis

Joint fluid in patients with Lyme arthritis often contains high levels of CCL4 and CCL2, which are chemoattractants for monocytes and some T cells, and CXCL9 and CXCL10, which are chemoattractants for CD4+ and CD8+ T effector cells. These chemokines are produced primarily by cells of monocyte lineage in TH1-type immune responses. Our goal was to begin to learn how infection with Borrelia burgdorferi leads to the secretion of these chemokines, using patient cell samples. We hypothesized that B. burgdorferi stimulates chemokine secretion from monocytes/macrophages in multiple ways, thereby linking innate and adaptive immune responses. Peripheral blood mononuclear cells (PBMC) from 24 Lyme arthritis patients were stimulated with B. burgdorferi, interferon (IFN)-γ, or both, and the levels of CCL4, CCL2, CXCL9 and CXCL10 were measured in culture supernatants. CD14+ monocytes/macrophages from PBMC and synovial fluid mononuclear cells (SFMC) were stimulated in the same way, using available samples. CXCR3, the receptor for CXCL9 and CXCL10, and CCR5, the receptor for CCL4, were assessed on T cells from PBMC and SFMC. In patients with Lyme arthritis, B. burgdorferi but not IFN-γ induced PBMC to secrete CCL4 and CCL2, and B. burgdorferi and IFN-γ each stimulated the production of CXCL9 and CXCL10. However, with the CD14+ cell fraction, B. burgdorferi alone stimulated the secretion of CCL4; B. burgdorferi and IFN-γ together induced CCL2 secretion, and IFN-γ alone stimulated the secretion of CXCL9 and CXCL10. The percentage of T cells expressing CXCR3 or CCR5 was significantly greater in SFMC than PBMC, confirming that TH1 effector cells were recruited to inflamed joints. However, when stimulated with B. burgdorferi or IFN-γ, SFMC and PBMC responded similarly. B. burgdorferi stimulates PBMC or CD14+ monocytes/macrophages directly to secrete CCL4, but spirochetal stimulation of other intermediate cells, which are present in PBMC, is required to induce CD14+ cells to secrete CCL2, CXCL9 and CXCL10. We conclude that B. burgdorferi stimulates monocytes/macrophages directly and indirectly to guide innate and adaptive immune responses in patients with Lyme arthritis.
Multiplex Quantitative Real-Time Reverse Transcriptase PCR for F+-Specific RNA Coliphages: a Method for Use in Microbial Source Tracking

It is well documented that microbial contamination of coastal waters poses a significant risk to human health through recreational exposure and consumption of shellfish. Identifying the source of microbial contamination (microbial source tracking) plays a dominant role in enabling effective management and remediation strategies. One method used to determine the source of the contamination is quantification of the ratio of the four subgroups of F-specific RNA coliphages (family Leviviridae) in impacted water samples. Because of typically low concentrations in the environment, enrichment assays are performed prior to detection, even though differential replication rates have been reported. These assays are also compromised by differential loss of phage infectivity among subgroups after release into the environment, thus obscuring the initial ratio. Here, a culture-independent multiplex real-time reverse transcriptase-PCR (RT-PCR) protocol for the simultaneous quantification of all four subgroups of F-specific RNA coliphages using novel primer sets and molecular beacons is presented. This assay is extremely sensitive, achieving detection with as few as 10 copies of isolated coliphage RNA, and is linear for a minimum of six orders of magnitude. During survival experiments, the real-time RT-PCR technique was able to quantify coliphages in seawater when culture-based double agar layer assay failed. While infectivity was lost at different rates at the subgroup level, decay constants in seawater, calculated using the real-time RT-PCR estimates, did not vary among subgroups. The accurate determination of the in situ concentration of F-specific RNA coliphages using this method will facilitate more effective remediation strategies for impacted environments. Microbial contamination of lakes, rivers, estuarine, and coastal waters poses a major risk to human health through consumption of organisms that inhabit these environments as well as through recreational exposure. Identifying the source of microbial contamination (microbial source tracking) plays a dominant role in the types of actual risk and enabling effective management and remediation strategies. In their current form, monitoring programs and identification protocols for deter
A National Longitudinal Study of the Association Between Hours of TV Viewing and the Trajectory of BMI Growth Among US Children

Objectives To assess the association between hours of TV viewing and the trajectory of BMI growth from Kindergarten to Grade 5 among a national longitudinal cohort of 7,334 US children. Methods Multilevel growth curve modeling was used to estimate children’s BMI growth trajectories as a function of hours of TV viewing over time while controlling for gender, race/ethnicity, SES, birth weight, and baseline age. Results Hours of TV viewing were significantly positively associated with the acceleration of BMI growth from Kindergarten to Grade 5. Conclusions Hours spent watching TV may be contributing to the recent dramatic increase in the prevalence of overweight and obesity among children.
Distributed Neural Information Processing in the Vestibulo-Ocular System

A new distributed neural information-processing model is proposed to explain the response characteristics of the vestibulo-ocular system and to reflect more accurately the latest anatomical and neurophysiological data on the vestibular afferent fibers and vestibular nuclei. In this model, head motion is sensed topographically by hair cells in the semicircular canals. Hair cell signals are then processed by multiple synapses in the primary afferent neurons which exhibit a continuum of varying dynamics. The model is an application of the concept of "multilayered" neural networks to the description of findings in the bullfrog vestibular nerve, and allows us to formulate mathematically the behavior of an assembly of neurons whose physiological characteristics vary according to their anatomical properties.
Canons, Careers, and Campfollowers: Randall and the Historiography of Philosophy

Randall should be celebrated simply for the several ways in which he succeeded in shaking and displacing this "German" model of the history of philosophy, although there is, of course, much more to his work. I propose both to investigate some of these ways and to raise the question whether there might be some traces of the model still to be found in Randall's own work. Randall's objections to the German model in the passage just quoted seem to be two. First, it sees the development of philosophy as relatively unilinear, following a single pattern that neglects the many rough edges, the roads not taken and the thought that was so influential in its own time, but is now neglected. Second, it tends to construct that pattern in terms of a culminating point, which is simply the philosophical present understood in a certain way. It is not that Randall objects to mobilizing the sources of the past in order to make sense of the present but that he believes, quite sensibly, that we will succeed better at such a use of history if we acknowledge more explicitly to ourselves and others just what it is that we are doing. In a recent essay "The Historiography of Philosophy: Four Genres,"
Transcriptional Profiling of the Immune Response to Marburg Virus Infection

ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the immune cells circulating in the blood of infected primates respond following exposure to Marburg virus. Our results show that there are three discernible stages of response to infection that correlate with presymptomatic, early, and late symptomatic stages of infection, a response format similar to that seen following challenge with other hemorrhagic fever viruses. In contrast to the ability of the virus to block innate immune signaling in vitro , the earliest and most sustained response is an interferon-like response. Our analysis also identifies a number of cytokines that are transcriptionally upregulated during late stages of infection and suggest that there is a Th2-skewed response to infection. When correlated with companion data describing the animal model from which our samples were collected, our results suggest that the innate immune response may contribute to overall pathogenesis.
Analysis of Genetic and Non-Genetic Factors Influencing Timing and Time Perception.

Performance on different psychophysical tasks measuring the sense of time indicates a large amount of individual variation in the accuracy and precision of timing in the hundredths of milliseconds-to-minutes range. Quantifying factors with an influence on timing is essential to isolating a biological (genetic) contribution to the perception and estimation of time. In the largest timing study to date, 647 participants completed a duration-discrimination task in the sub-second range and a time-production task in the supra-second range. We confirm the stability of a participant’s time sense across multiple sessions and substantiate a modest sex difference on time production. Moreover, we demonstrate a strong correlation between performance on a standardized cognitive battery and performance in both duration-discrimination and time-production tasks; we further show that performance is uncorrelated with age after controlling for general intelligence. Additionally, we find an effect of ethnicity on time sense, with African Americans and possibly Hispanics in our cohort differing in accuracy and precision from other ethnic groups. Finally, a preliminary genome-wide association and exome chip study was performed on 148 of the participants, ruling out the possibility for a single common variant or groups of low-frequency coding variants within a single gene to explain more than ~18% of the variation in the sense of time.
PUB1 is a major nuclear and cytoplasmic polyadenylated RNA-binding protein in Saccharomyces cerevisiae

Abstract Proteins that directly associate with nuclear polyadenylated RNAs, or heterogeneous nuclear RNA-binding proteins (hnRNPs), and those that associate with cytoplasmic mRNAs, or mRNA-binding proteins (mRNPs), play important roles in regulating gene expression at the posttranscriptional level. Previous work with a variety of eukaryotic cells has demonstrated that hnRNPs are localized predominantly within the nucleus whereas mRNPs are cytoplasmic. While studying proteins associated with polyadenylated RNAs in Saccharomyces cerevisiae, we discovered an abundant polyuridylate-binding protein, PUB1, which appears to be both an hnRNP and an mRNP. PUB1 and PAB1, the polyadenylate tail-binding protein, are the two major proteins cross-linked by UV light to polyadenylated RNAs in vivo. The deduced primary structure of PUB1 indicates that it is a member of the ribonucleoprotein consensus sequence family of RNA-binding proteins and is structurally related to the human hnRNP M proteins. Even though the PUB1 protein is a major cellular polyadenylated RNA-binding protein, it is nonessential for cell growth. Indirect cellular immunofluorescence combined with digital image processing allowed a detailed comparison of the intracellular distributions of PUB1 and PAB1. While PAB1 is predominantly, and relatively uniformly, distributed within the cytoplasm, PUB1 is localized in a nonuniform pattern throughout both the nucleus and the cytoplasm. The cytoplasmic distribution of PUB1 is considerably more discontinuous than that of PAB1. Furthermore, sucrose gradient sedimentation analysis demonstrates that PAB1 cofractionates with polyribosomes whereas PUB1 does not. These results suggest that PUB1 is both an hnRNP and an mRNP and that it may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm.
Child, Family, and School Characteristics Related to English Proficiency Development Among Low-Income, Dual Language Learners

Little is known about 2nd language development among young, low-income, language-minority children. This article examined the longitudinal English development of low-income, dual language learners (DLLs) in Miami (n = 18,532) from kindergarten through 5th grade. Growth curve modeling indicated that social skills, good behavior, Spanish (L1) competence in preschool, having a mother born in the United States, and attending larger schools with fewer DLLs were associated with higher initial levels of English proficiency in kindergarten and/or steeper growth over time. Survival analyses indicated that it took about 2 years for half of the sample to become proficient in English according to the school district's criterion. Higher initial proficiency in kindergarten, not receiving free/reduced lunch, not being Hispanic or Black, strong cognitive, language, and socioemotional skills at age 4, and maternal education were associated with faster attainment of English proficiency. It is important for teachers, parents, researchers, and policy makers to understand that DLL students come from diverse backgrounds and that poverty and other factors influence the speed of English language development for DLLs.
Parity-Time Symmetry in Acoustics: Theory, Devices, and Potential Applications

Parity-time (PT) symmetric systems based on balanced distributions of gain and loss have attracted significant attention in wave physics, enabling the possibility of compensating material losses in photonic systems, and of inducing exceptional scattering phenomena, offering new possibilities for wave manipulation. A successful transition of these theoretical concepts to devices and practical applications requires a sufficient level of control over the frequency dispersion of the involved gain and loss elements, in order to engineer a PT-symmetric system that is stable and practical. Here, we show that such a degree of control can be achieved for acoustic waves, and obtain stable PT-symmetric acoustic systems that can manipulate sound in unprecedented ways. We describe the theory, design and potentials of PT-based negative refraction and phase compensation devices in free-space, induced by a pair of PT-symmetric acoustic metasurfaces engineered from active electro-acoustic resonators. Our study proves that acoustic systems represent an ideal platform to apply the unique scattering phenomena associated with PT-symmetric systems operated at exceptional points. We envision applications in acoustic imaging, furtive sensing, and noise control, and extension of these concepts to electromagnetics, optics, and nanophotonic systems.
Libertarian personal responsibility On the ethics, practice, and American politics of personal responsibility

While libertarians (by most accounts) affirm personal responsibility as a central moral and political value, libertarian theorists write relatively little about the theory and practice of this valu...
A technique for selectable band imaging in the ultraviolet and optical

We present a design concept that provides selectable band imaging in the optical and ultraviolet. The bandpass is created through reconstructive spectroscopy, utilizing crossed gratings, and creates an image, not a spectrum. The bandpass depends upon the field of view, the object location within that field, and the illuminated area of the second grating. All three factors are in principle selectable in real time, so that an instrument utilizing this technique is extremely flexible in its application. The technique utilizes no transmitting optics, and therefore is usable down to the limits of normal incidence reflectivity (~ 40 nm).
Tibet on Fire: Buddhism, Protest, and the Rhetoric of Self-Immolation

Between February 2009 and September 2015 more than 140 Tibetans voluntarily set themselves on fire, as documented by the International Campaign for Tibet. Tibet on Fire constitutes John Whalen-Brid...
The flagellar master operon flhDC is a pleiotropic regulator involved in motility and virulence of the fish pathogen Yersinia ruckeri

Aims To investigate the function of the master flagellar operon flhDC in the fish pathogen Yersinia ruckeri and compare the effect of a constructed flhD mutation to a naturally occurring fliR mutation causing loss-of-motility in emergent biotype 2 (BT2) strains. Methods and Results Yersinia ruckeri flhD and fliR mutants were constructed in a motile strain. Both mutations caused loss-of-motility, ablation of flagellin synthesis and phospholipase secretion, similar to naturally occurring BT2 strains. Transcriptome analysis confirmed flhDC regulation of flagellar, chemotaxis and phospholipase loci as well as other genes of diverse function. The flhD mutation confers a competitive advantage within the fish host when compared with its parent strain, while this advantage was not seen with the naturally occurring fliR mutation. Conclusions An intact flhD is necessary for expression of the flagellar secretion system as well as other diverse loci, consistent with a role for flhD as a pleiotropic regulator. The maintenance of the flhD locus in Y. ruckeri strains suggests its importance for aspects of Y. ruckeri biology other than virulence, since the flhD mutation conferred a competitive advantage during experimental challenge of rainbow trout. Significance and Impact of the Study Yersinia ruckeri is the causative agent of enteric red mouth disease, an invasive septicaemia that affects farmed salmonid fish species. Disease outbreaks can cause severe economic losses in aquaculture. BT2 variants, which have independently emerged worldwide, are an increasing threat to farmed fish production. Knowledge of mechanisms involved in virulence, conserved functions and gene regulation among strains may be exploited for the development of novel disease control strategies to prevent pathogen growth or virulence phenotypes within aquaculture.
Retrospective Waveform Analysis of Transcranial Motor Evoked Potentials (MEP) to Identify Early Predictors of Impending Motor Deficits in Spinal Surgeries.

ABSTRACTPurpose: Although there are guidelines analyzing transcranial motor evoked potentials (MEP) waveform criteria, they vary widely and are not applied universally during intraoperative neurophysiologic monitoring (IONM). The objective is to generate hypotheses to identify early and reliable MEP waveform characteristics prior to complete loss of MEP to predict impending motor spinal cord injuries during spinal surgeries. The ultimate goal is to enhance real-time feedback to prevent injury or detect reversible spinal cord damage.Methods: Fifteen true positive cases of persistent intraoperative MEP loss and new postoperative motor deficits were retrospectively identified from 2011 to 2013. Waveform characteristics of latency, amplitude, duration, phases, and area-under-the-curve (AUC) were measured, and an intraoperative spinal cord index (ISCI) was calculated for 5 traces prior to complete MEP loss. ISCI = [amplitude x duration x (phases+1) x AUC]/latency.Results: Out of 22 muscles in 15 cases, latency...
The CEP19-RABL2 GTPase Complex Binds IFT-B to Initiate Intraflagellar Transport at the Ciliary Base

Highly conserved intraflagellar transport (IFT) protein complexes direct both the assembly of primary cilia and the trafficking of signaling molecules. IFT complexes initially accumulate at the base of the cilium and periodically enter the cilium, suggesting an as-yet-unidentified mechanism that triggers ciliary entry of IFT complexes. Using affinity-purification and mass spectrometry of interactors of the centrosomal and ciliopathy protein, CEP19, we identify CEP350, FOP, and the RABL2B GTPase as proteins organizing the first known mechanism directing ciliary entry of IFT complexes. We discover that CEP19 is recruited to the ciliary base by the centriolar CEP350/FOP complex and then specifically captures GTP-bound RABL2B, which is activated via its intrinsic nucleotide exchange. Activated RABL2B then captures and releases its single effector, the intraflagellar transport B holocomplex, from the large pool of pre-docked IFT-B complexes, and thus initiates ciliary entry of IFT.
Ror2-mediated alternative Wnt signaling regulates cell fate and adhesion during mammary tumor progression

Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo. We further discovered an antagonistic role for Ror2 in regulating canonical Wnt/β-catenin activity in vivo, where lentiviral shRNA depletion of Ror2 expression augmented canonical Wnt/β-catenin signaling activity across multiple basal-like models. Depletion of Ror2 expression yielded distinct phenotypic outcomes and divergent alterations in gene expression programs among different tumors, despite all sharing basal-like features. Notably, we uncovered cell state plasticity and adhesion dynamics regulated by Ror2, which influenced Ras Homology Family Member A (RhoA) and Rho-Associated Coiled-Coil Kinase 1 (ROCK1) activity downstream of Dishevelled-2 (Dvl2). Collectively, these studies illustrate the integration and collaboration of Wnt pathways in basal-like breast cancer, where Ror2 provides a spatiotemporal function to regulate the balance of Wnt signaling and cellular heterogeneity during tumor progression.
Attainment of ‘5-2-1-0’ obesity recommendations in preschool-aged children

Obesity prevention guidelines recommend children eat ≥ 5 servings of fruits and vegetables, view ≤ 2 h of screen time, participate in 1 h of physical activity, and consume 0 sugar-sweetened beverages daily, commonly known as '5-2-1-0'. We sought to determine: the extent to which preschool-aged children attending child care meet these guidelines, predictors of attainment, and associations of attainment with weight status. We analyzed in 2016, 24-hour dietary, physical activity, and screen time data collected in 2009-10 from 398 preschool-aged children in 30 child-care centers in Cincinnati, OH. Dietary intake, screen time and body-mass index (BMI) were obtained by research staff during child care and from parents when at home. Accelerometers measured physical activity. Mixed-effects models and generalized estimating equations were used to determine associations between '5-2-1-0' recommendations, demographic variables, and BMI z-scores. Average child age was 4.3 ± 0.7 years; 26% had a BMI ≥ 85th percentile. Seventeen percent of children with complete dietary data (n = 307) consumed ≥ 5 servings of fruits and vegetables and 50% consumed 0 sugar-sweetened beverages. < 1% with complete physical activity data (n = 386) met the activity recommendation; 81% of children (n = 379) had ≤ 2 h of screen time. Only 1 child met all of the '5-2-1-0' recommendations. There were no consistent demographic predictors of attaining individual recommendations. An additional hour of screen time was associated with a 0.11 (SD 0.06) increase in BMI z-score. Our data suggests there is ample room to increase fruit and vegetable intake and physical activity in preschool-aged children.
Environmental Occurrence of Selenium

Selenium is very widely distributed in the earth’s crust, but is rarely present in any material in concentrations exceeding 500 (xg/g. The amount of selenium in any soil is dependent upon a number of factors: first, the presence or absence of selenium in the parent material of the soil; second, the possible removal of selenium by leaching during soil formation; and third, processes subsequent to soil formation added selenium or removed it. Figure 6-1 shows a simplified geochemical cycle of selenium, from molten rocks to igneous rocks or to the atmosphere, which can be converted to sediments, or to the hydrosphere, which can be taken up by plants and soils. From plants and soils selenium can enter the food chain of humans and animals.
Functional TRPM and TRPV Channel Subtypes are expressed in Rat Intralobar Pulmonary Arteries and Aorta

Transient receptor potential melastatin-like (TRPM) and vanilloid-related (TRPV) channels are non-selectively cation channels pertinent to diverse physiological functions. Multiple TRPM (1–8) and T...
Presidential Communication About Marginalized Groups: Applying a New Analytic Framework in the Context of the LGBT Community

Scholars have long observed that presidential communication about a marginalized group can help shape that group's reality. Yet most analyses of such communication focus on a relatively small number of texts, making it difficult to identify important changes over time and analyze factors that might explain those changes. The present study proposes an analytic framework that specifies 4 measurable parameters of presidential communication about marginalized groups, as well as 4 explanatory factors. We use this framework to analyze the census of presidents' formal communications about the LGBT community. Results highlight presidents' limited communicative engagement with the LGBT community and the roles that political party, rhetorical context, public opinion, and sociocultural touchstones play in explaining presidential communication about this important group.
Autosomal-recessive cerebellar ataxias

Abstract The autosomal-recessive cerebellar ataxias comprise more than half of the known genetic forms of ataxia and represent an extensive group of clinically heterogeneous disorders that can occur at any age but whose onset is typically prior to adulthood. In addition to ataxia, patients often present with polyneuropathy and clinical symptoms outside the nervous system. The most common of these diseases is Friedreich ataxia, caused by mutation of the frataxin gene, but recent advances in genetic analysis have greatly broadened the ever-expanding number of causative genes to over 50. In this review, the clinical neurogenetics of the recessive cerebellar ataxias will be discussed, including updates on recently identified novel ataxia genes, advancements in unraveling disease-specific molecular pathogenesis leading to ataxia, potential treatments under development, technologic improvements in diagnostic testing such as clinical exome sequencing, and what the future holds for clinicians and geneticists.
Activation of Akt by SC79 decreased cerebral infarct in early cerebral ischemia-reperfusion despite increased BBB disruption.

Activation of Akt has been suggested to produce neuronal protection in cerebral ischemia. Decreasing blood-brain barrier (BBB) disruption has been associated with a better neuronal outcome in cerebral ischemia. We hypothesized that activation of Akt would decrease BBB disruption and contribute to decreasing the size of infarct in the early stage of cerebral ischemia-reperfusion within the therapeutic window. Transient middle cerebral artery occlusion (MCAO) was performed in rats under isoflurane anesthesia with controlled ventilation. Rats were treated with SC79 (a selective Akt activator which is cell and BBB permeable) 0.05 mg/kg × 3 i.p. or vehicle i.p. perioperatively. After one hour of MCAO and two hours of reperfusion, the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid (14C-AIB, molecular weight 104 Da) and the volume of 3H-dextran (molecular weight 70,000 Da) distribution were determined to measure the degree of BBB disruption. At the same time point, the size of infarction was determined using tetrazolium staining. In an additional group of rats, a higher dose of SC79 (0.5 mg/kg × 3) was administered to determine the size of infarct. Administration of SC79 increased the Ki in the ischemic-reperfused cortex (IR-C, +32%, p < 0.05) as well as in the contralateral cortex (CC, +35%, p < 0.05) when compared with the untreated animals with MCAO/reperfusion. The volume of dextran distribution was not significantly changed by SC79. SC79 treatment significantly produced a decrease in the percentage of cortical infarct out of total cortical area (12.7 ± 1.7% vs 6.9 ± 0.9%, p < 0.001). Increasing the dose of SC79 by ten times did not significantly affect the size of cortical infarct. Contrary to our hypothesis, our data demonstrated that SC79 decreased the size of the infarct in the ischemic-reperfused cortex despite an increase in BBB disruption. Our data suggest the importance of activation of Akt for neuronal survival in the early stage of cerebral ischemia-reperfusion within the therapeutic window and that the mechanism of neuroprotection may not be related to the BBB effects of SC79.
Electrochemical and interfacial behavior of all solid state batteries using Li10SnP2S12 solid electrolyte

Abstract Thio-Lithium Superionic Conductor (Thio-LISICON) Li10GeP2S12 equivalent Li10SnP2S12 (LSPS) is comparable in ionic conductivity yet with a lower cost as an electrolyte for all solid-state batteries (ASSBs). ASSBs with LSPS solid electrolyte (SE), lithium-indium alloy anode, and LiCoO2 (LCO) cathode were successfully fabricated and their electrochemical performance at 60 °C was examined. Atomic layer deposition of Li3NbO4 on LCO was conducted to improve the interfacial stability. The Li3NbO4 coating effectively improves the cycle stability of the ASSB. Electrochemical impedance spectroscopy tests indicate a rapid growth of charge transfer resistance upon cycling for the cell with the uncoated LCO, primarily due to the surface instability and build-up of a space charge layer. However, the ASSBs with Li3NbO4 coated LCO show a more stable interface with a negligible impedance increase upon cycling, attributable to the buffering and passivating roles of the Li3NbO4 coating. The interfacial microstructure was analyzed to elucidate at the underlying reasons for the impedance increase and the pivotal role of the Li3NbO4 coating.
Mechanisms of Yeast Genetics

Saccharomyces cerewisiae is a lower eukaryote ideal for many current biological studies. It shares certain properties with higher eukaryotes: a nucleus containing multiple chromosomes packed in chromatin structures, and specialized organelles such as vacuoles and mitochondria. In addition, the organization of yeast structural genes is similar to that of higher eukaryotic cells: most functionally related genes are scattered on different chromosomes rather than linked together in operons (21). Yet, while yeast are more complex than bacteria, they still share many of the technical advantages which permitted rapid progress in the genetic and biochemical studies of prokaryotic organisms. Some of the properties which make yeast particularly amenable to study are their short generation time, the existence of both stable haploids and diploids, and the ease of replica plating and mutant isolation. Furthermore, the sophisticated classical genetics of yeast allows one to fully exploit recent technological advances in genetic engineering.
Does Patient Experience Predict 30-Day Readmission? A Patient-Level Analysis of HCAHPS Data.

BACKGROUND Hospital-level studies have found an inverse relationship between patient experience and readmissions. However, based on typical survey response time, it is unclear if patients are able to respond to surveys before they get readmitted and whether being readmitted might be a driver of poor experience scores (reverse causation). OBJECTIVE Using patient-level Hospital Consumer Assessment of Healthcare Providers and Systems (HCHAPS) and Press Ganey data to examine the relationship between readmissions and experience scores and to distinguish between patients who responded before or after a subsequent readmission. DESIGN Retrospective analysis of 10-year HCAHPS data. SETTING Single tertiary care academic hospital. PARTICIPANTS Patients readmitted within 30 days of an index hospitalization who received an HCAHPS survey linked to index admission comprised the exposure group. This group was divided into those who responded prior to readmission and those who responded after readmission. Nonreadmitted patients comprised the control group. ANALYSIS Multivariable-logistic regression to analyze the association between HCHAPS and Press Ganey scores and 30-readmission status, adjusted for patient factors. RESULTS Only 15.8% of the readmitted patients responded to the survey prior to readmission, and their scores were not significantly different from the nonreadmitted patients. The patients who responded after readmission were significantly more dissatisfied with physicians (doctors listened 73.0% vs 79.2%, aOR 0.75, P < .0001), staff responsiveness, (call button 50.0% vs 59.1%, aOR 0.71, P < .0001) pain control, discharge plan, noise, and cleanliness of the hospital. CONCLUSIONS Our findings suggest that poor patient experience may be due to being readmitted, rather than being predictive of readmission.