cssi/SciSciGPT-SciSciNet huggingface dataset:
Top-down connections as abstract and temporal context for self-organization and categorization

There are many bottom-up connections from inferior temporal cortex (ITC) to prefrontal cortex (PFC) and many top-down connections from PFC to ITC. It is hypothesized that neurons in PFC perform behaviorally-relevant category binding, while neurons in ITC are responsive to high-level visual features [1]. Therefore it is thought the bottom-up connections provide information about detected high-level features to PFC, which binds them together for categorization. But all the computational roles of the top-down connections are currently not known, specifically in development and learning. We seek to verify two general ideas about top-down connections via simulation: that they could act as the impetus of category-specific self-organization, e.g., seen in the fusiform face area (FFA) and parahippocampal place area (PPA), and that they can act as a “bias” (memory store) for biasing the ITC features [2]. We built networks with three interconnected neuronal layers: a sensory area (layer one), a feature representation area (layer-two: ITC), and a category-behavior area (layer-three: PFC). Each layer-two neuron receives excitatory inputs from the bottom-up, laterally, and top-down and each layer-three neuron has bottom-up inputs. Neurons compete with others on the same layer through lateral inhibition. Neurons that are not firing-inhibited learn through a Hebbian learning algorithm [3], in which the strength of synaptic learning is based on presynaptic and postsynaptic potentials. We used visual stimuli (images) of 26 classes of objects that sequentially rotate in depth, presenting them randomly, and learning in a supervised fashion. We observed two results: developed ITC neurons became more specialized to represent a particular class and grouped class areas emerged on the ITC neuronal plane. In contrast to slow feature analysis methods [4], our network’s development does not depend on slowly changing inputs, but instead the correlations between the category information from PFC and the true class of the stimulus. This might explain how PPA, which represents “places” --- a very abstract category containing members that are experienced at different times --- could develop. Networks with top-down connections showed an average error rate reduction of 63% over networks where top-down connections were disabled. The classification rate of a 40 x 40 layer-two was 95% recognition when operating in feedforward. When also utilizing top-down connections, performance reached nearly 100%, but errors were introduced during the periods when an object transitioned to another (yet the network successfully recovered). This is consistent with the idea that top-down connections can bias lower-level features based on currently detected categories.
The role of circulating tumor cells in breast cancer diagnosis and prediction of therapy response.

Background: Metastatic breast cancer (MBC) is incurable and any treatment is considered palliative. Occult dissemination of tumor cells is responsible for recurrent MBC in patients who have undergone resection of their primary tumor. The presence of circulating tumor cells (CTCs) in patients with MBC predicts progression-free and overall survival. Moreover, this prognostic value is independent of the line of therapy. Methods to detect and enumerate CTCs vary in sensitivity and specificity, and lack the standardization required for direct comparison between methods. Objective: To review the methods of detecting CTCs, the prognostic implications of CTCs, and opportunities to exploit the properties of CTCs to develop individualized therapy. Methods: The coupling of antibodies to immunomagnetic beads has facilitated the detection of low-frequency CTCs in peripheral blood of cancer patients. Results/conclusion: Standardization of methods will allow for the uniform detection of microscopic disease in the periph...
Supply Chain Responsiveness Through Modularity Based Manufacturing Practices: An Exploratory Study

Modularity based practices have long been said to improve flexibility of firms. This study extends prior research on manufacturing practices by exploring the dimension level and item level relationships between modularity based manufacturing practices and supply chain responsiveness. A large scale web-based survey yielded 294 responses from industry professionals in the manufacturing and supply chain area. The proposed relationship was first tested using structural equation modeling using AMOS, followed by regression analyses for exploring dimension and item level relationships. The study indicates that firms with high levels of modularity based manufacturing practices have high levels of supply chain responsiveness. Key modularity based manufacturing practices that improve various aspects of supply chain responsiveness are identified and discussed.
Simultaneous Water Filling in Mutually Interfering Systems

In this paper we investigate properties of simultaneous water filling for a wireless system with two mutually interfering transmitters and receivers with non-cooperative coding strategies. This is slightly different from the traditional interference channel problem which assumes that transmitters cooperate in their respective coding strategies, and that interference cancellation can be performed at the receivers. In this noncooperative setup, greedy capacity optimization by individual transmitters through various algorithms leads to simultaneous water filling fixed points where the spectrum of the transmit covariance matrix of one user water fills over the spectrum of its corresponding interference-plus-noise covariance matrix, and in our paper we study the properties of these fixed points. We show that at a simultaneous water filling point the eigenvectors of transmit covariance matrices at each receiver are aligned, and identify three regimes which correspond to simultaneous water filling that depend on the interference gains: a) complete spectral overlap, b) partial spectral overlap, and c) spectral segregation. These imply that the transmit covariance matrices will be white in regions of both overlap and segregation, but not necessarily white overall. We also consider performance as a function of interference gain and show that complete spectral overlap is a strongly suboptimal solution over a wide range of gains. Overall, our results suggest that for strong mutual interference, an effort should be made to do joint decoding over receivers since such collaboration can provide large capacity increases. For moderate interference, distributed and/or centralized conflict resolution algorithms would be most effective since more complex collaborative methods do not afford much improvement and strictly greedy methods such as water filling perform poorly, while for weak interference a laissez faire approach seems reasonable
Mass Media as a Macrolevel Source of Social Control: A New Direction in the Community Structure Model

A community structure model is grounded in the structural model of mass media originally formulated by the Minnesota team of Tichenor, Donohue, and Olien. Although recent theoretical and empirical work has led to major refinements of the community structure research, there remain substantive and promising issues that deserve to be examined by mass communication scholars. This article recasts the original structural model by integrating a community-oriented approach to social control and formulates a set of hypotheses with regard to the role of local mass media in community social control.
Evidence for electrical remodeling of the native conduction system with cardiac resynchronization therapy

Background:Cardiac resynchronization therapy (CRT) improves hemodynamics and decreases heart failure symptoms. However, the potential of CRT to bring about electrical remodeling of the heart has not been investigated. Methods and Results:We studied 25 patients, of whom 17 had a nonischemic cardiomyopathy, and 8 had an ischemic cardiomyopathy; 16 had left bundle branch block (LBBB), 1 right bundle branch block (RBBB), and 8 nonspecific intraventricular conduction delay. During routine device clinic visits, patients with chronic biventricular pacing (>6 months) were reprogrammed to VVI 40 to allow for native conduction to resume. After 5 minutes of native rhythm, a surface electrocardiogram (ECG) was recorded, and then the previous device settings were restored. This ECG was compared to the preimplant ECG. Preimplant mean ejection fraction was 19% (range, 10%–35%), and follow-up mean ejection fraction was 35% (12.5%–65%). Mean time from implant to follow-up ECG was 14 months (range, 6–31). The QRS interval prior to CRT was 155 ± 29 ms, and shortened to 144 ± 31 ms (P = 0.0006), and the QRS axis shifted from −1 ± 59 to −26 ± 53 (P = 0.03). There was no significant change in PR or QTc interval, or in heart rate. Conclusion:CRT leads to a decrease in the surface QRS duration, without affecting other surface ECG parameters. The reduced electrical activation time may reflect changes in the specialized conduction system or in intramyocardial impulse transmission.
Tsg101 Control of Human Immunodeficiency Virus Type 1 Gag Trafficking and Release

The structural precursor polyprotein of human immunodeficiency virus type 1, Pr55(gag), contains a proline-rich motif (PTAP) called the "late domain" in its C-terminal p6 region that directs release of mature virus-like particles (VLPs) from the plasma membranes of gag-transfected COS-1 cells. The motif binds Tsg101 (vacuolar protein-sorting protein 23, or Vps23), which functions in endocytic trafficking. Here, we show that accumulation of the wild-type (wt) Gag precursor in a fraction of COS-1 cytoplasm enriched in multivesicular bodies and small particulate components of the plasma membrane (P100) is p6 dependent. Cleavage intermediates and mature CA mainly partitioned with more rapidly sedimenting larger material enriched in components of lysosomes and early endosomes (P27), and this also was p6 dependent. Expression of truncated or full-length Tsg101 proteins interfered with VLP assembly and Gag accumulation in the P100 fraction. This correlated with reduced accumulation of Gag tagged with green fluorescent protein (Gag-GFP) at the plasma membrane and colocalization with the tagged Tsg101 in perinuclear early endosomes, as visualized by confocal microscopy. Fractionation analysis and confocal examination both indicated that the N-terminal region of Tsg101, which contains binding sites for PTAP and ubiquitin (Ub), was required for Gag trafficking to the plasma membrane. Expression of FLAG-tagged Tsg101 with a deletion in the Ub-binding pocket inhibited VLP release almost completely and to a significantly greater extent than expression of the wt tagged Tsg101 protein or Tsg101-FLAG containing a deletion in the PTAP-binding region. The results demonstrate that Gag associates with endosomal trafficking compartments and indicate that efficient release of virus particles from the plasma membrane requires both the PTAP- and Ub-binding functions of Tsg101 to recruit the cellular machinery required for budding.
Aflatoxin Accumulation in a Maize Diallel Cross

Aflatoxins, produced by the fungus Aspergillus flavus, occur naturally in maize. Contamination of maize grain with aflatoxin is a major food and feed safety problem and greatly reduces the value of the grain. Plant resistance is generally considered a highly desirable approach to reduction or elimination of aflatoxin in maize grain. In this investigation, a diallel cross was produced by crossing 10 inbred lines with varying degrees of resistance to aflatoxin accumulation in all possible combinations. Three lines that previously developed and released as sources of resistance to aflatoxin accumulation were included as parents. The 10 parental inbred lines and the 45 single crosses making up the diallel cross were evaluated for aflatoxin accumulation in field tests conducted in 2013 and 2014. Plants were inoculated with an A. flavus spore suspension seven days after silk emergence. Ears were harvested approximately 60 days later and concentration of aflatoxin in the grain determined. Parental inbred lines Mp717, Mp313E, and Mp719 exhibited low levels (3–12 ng/g) of aflatoxin accumulation. In the diallel analysis, both general and specific combining ability were significant sources of variation in the inheritance of resistance to aflatoxin accumulation. General combining ability effects for reduced aflatoxin accumulation were greatest for Mp494, Mp719, and Mp717. These lines should be especially useful in breeding for resistance to aflatoxin accumulation. Breeding strategies, such as reciprocal recurrent selection, would be appropriate.
Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP

Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic β-cells and increase insulin secretion and production. GLP-1R agonists are used c...
Eigenvalue Approximations for Sturm-Liouville Differential Equations with Mixed Boundary Conditions

The Sinc-Galerkin method in [1] was used to approximate the eigenvalues of Sturm-Liouville differential equations with Dirichlet boundary conditions on an interval (a,b). The discrete system of the method led to a symmetric generalized eigenvalue problem with the entries of the matrices point evaluations of known functions. The eigenvalues of this system are approximations to the eigenvalues of the differential equation (for either regular or singular differential equations) accurate to within O(exp $$( - k\sqrt N )$$ ) is a positive constant and N is related to the number of basis functions used.
What Counts as 'Speech' in the First Place?

The most fundamental problem in free speech law is not whether to protect the speech in question. Rather, it is whether ‘speech’ for First Amendment purposes is present in the first place. The Supreme Court will have another opportunity to address what counts as ‘speech’ this term in the Stevens animal cruelty video case. But the Court has historically offered inconsistent guidance in this area. This Article rejects several pessimistic approaches, but recognizes that any convincing approach to what counts as ‘speech’ for First Amendment purposes must be complex and multi-layered, with sensitive concern for broad as well as specific considerations. We begin with the constitutional text and drafter intent, but move on to the role and limitations of functionalist approaches, to the roles of symbolism and pre-symbolism in speech, to literary theory and the philosophy of vagueness and ambiguity, and then to the interaction of specific context, helpful mid-level rules, and broad theory of the purposes of protecting speech in the first place.
Chemical Synthesis and Properties of Layered Co1-yNiyO2-δOxides (0≤y≤1)

Layered Co1-yNiyO2-δ oxides with 0≤y≤1 have been synthesized by chemically extracting lithium from LiNi1-yCoyO2 with NO2PF6 at ambient temperature. The samples have been characterized by X-ray diffraction, wet-chemical analyses, infrared spectroscopy, and magnetic susceptibility measurements. While NiO2-δ retains the initial O3 (CdCl2 structure) layer structure of LiNiO2, CoO2-δ consists of a mixture of P3 and O1 (CdI2 structure) phases that are formed by a sliding of the oxide ions in the initial O3 structure. CoO2-δ and NiO2-δ have oxygen contents of, respectively, 1.67 and 1.95 and the oxygen content increases with increasing Ni content, y, in Co1-yNiyO2-δ. While CoO2-δ exhibits metallic conductivity as revealed by theabsence of absorption bands in the infrared spectrum, NiO2-δ exhibits semiconducting behavior due to a completely filled t2g band. Magnetic data reveal a transition from antiferromagnetic to ferromagnetic correlations as the Ni content in Co1-yNiyO2-δ increases.
Superficial Analysis the Design of Automotive Engine Assembly Line

If the design of assembly line is reasonable,it will bring much advantage.Firstly,it will make the engine to be assembled with high precision,high efficiency and high quality.Secondly,the line is flexible and the logistic is convenience.Thirdly,the cost is not substantive.
Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance

ABSTRACT The ability of Staphylococcus aureus to resist host innate immunity augments the severity and pervasiveness of its pathogenesis. Nitric oxide (NO˙) is an innate immune radical that is critical for the efficient clearance of a wide range of microbial pathogens. Exposure of microbes to NO˙ typically results in growth inhibition and induction of stress regulons. S. aureus, however, induces a metabolic state in response to NO˙ that allows for continued replication and precludes stress regulon induction. The regulatory factors mediating this distinctive response remain largely undefined. Here, we employ a targeted transposon screen and transcriptomics to identify and characterize five regulons essential for NO˙ resistance in S. aureus: three virulence regulons not formerly associated with NO˙ resistance, SarA, CodY, and Rot, as well as two regulons with established roles, Fur and SrrAB. We provide new insights into the contributions of Fur and SrrAB during NO˙ stress and show that the S. aureus ΔsarA mutant, the most sensitive of the newly identified mutants, exhibits metabolic dysfunction and widespread transcriptional dysregulation following NO˙ exposure. Altogether, our results broadly characterize the regulatory requirements for NO˙ resistance in S. aureus and suggest an intriguing overlap between the regulation of NO˙ resistance and virulence in this well-adapted human pathogen. IMPORTANCE The prolific human pathogen Staphylococcus aureus is uniquely capable of resisting the antimicrobial radical nitric oxide (NO˙), a crucial component of the innate immune response. However, a complete understanding of how S. aureus regulates an effective response to NO˙ is lacking. Here, we implicate three central virulence regulators, SarA, CodY, and Rot, as major players in the S. aureus NO˙ response. Additionally, we elaborate on the contribution of two regulators, SrrAB and Fur, already known to play a crucial role in S. aureus NO˙ resistance. Our study sheds light on a unique facet of S. aureus pathogenicity and demonstrates that the transcriptional response of S. aureus to NO˙ is highly pleiotropic and intrinsically tied to metabolism and virulence regulation.
Is the routine use of bevacizumab in the treatment of women with advanced or recurrent cancer of the cervix sustainable

Background New chemotherapy combinations are being tested for the treatment of women with advanced, persistent or recurrent cervical cancer. We sought to evaluate the cost effectiveness of some newer combination therapies in cervical cancer. Patients and methods A cost effectiveness decision model was used to analyze Gynecologic Oncology Group 240. All regimens were modeled for seven cycles. The regimens studied are as follows: regimen 1, cisplatin/paclitaxel (CP); regimen 2, CP with bevacizumab (CP+B); regimen 3, paclitaxel/topotecan (PT); and regimen 4, PT with bevacizumab (PT+B). Overall survival, cost, and complications were studied. Sensitivity analyses were performed. Results Mean chemotherapy costs over mean total costs for seven cycles of each follows: CP $571/$32,966; CP+B $61,671/$96,842; PT $9,211/$71,620; and PT+B $70,312/$109,211. Incremental cost-effectiveness ratio (ICER) for CP+B was $133,559/quality adjusted life year (QALY). ICER for PT+B was $124,576/QALY. To achieve an incremental ICER for CP+B:CP of 10 years for PT and 4.1 years for PT+B. Treating 1,000 women with cervical cancer with CP+B would cost almost double the cost of treating >18,000 women with ovarian cancer annually (carboplatin/paclitaxel). Conclusion CP is the most cost effective regimen. A 12-month increase in overall survival will not even make the newer combinations cost effective. Currently, the use of bevacizumab is not sustainable at today's costs.
TU‐D‐209‐04: How Useful Are Indirect Dose Metrics for Estimating Peak Skin Dose in Interventional Cardiology?

Purpose: The purpose of this study was to determine if a relationship between indirect dose metrics and PSD could be established for fluoroscopically-guided interventional cardiology procedures. Methods: PSD were measured directly using XR-RV3 radiochromic film for 94 consecutive fluoroscopically guided interventional cardiology procedures performed at two sites. Procedures were both diagnostic and therapeutic in nature. Radiation dose structured reports (RDSR) were collected for each procedure and used to calculate indirect estimates of PSD which were compared to the measured PSD. Reference air kerma (Ka,r) was also compared to the measured PSD. Pearson's correlation coefficient was calculated for each metric and metrics were compared to measured PSD using a two-tailed t-test. Data were log transformed prior to statistical analysis. Results: Both Ka,r and the calculated PSD were closely correlated with measured PSD at each sites (Ka,r: 0.92 and 0.86, indirect PSD: 0.91 and 0.88). At one site, neither Ka,r nor indirect PSD was significantly different from the measured PSD (p = 0.22 and p=0.054, respectively), while at the second site both Ka,r and indirect PSD were significantly higher than measured PSD (p<0.0001 and p<0.0001, respectively). In almost all cases, both Ka,r and indirect PSD overestimated the true PSD. Conclusions: The use of a range of gantry angles and table positions, along with variation in procedural imaging requirements, limits the utility of indirect dose metrics for predicting PSD for interventional cardiology procedures. A. Kyle Jones and Alexander S. Pasciak are owners of Fluoroscopic Safety, LLC.
The Assessment: Part I

Introduction Socrates' ad hominem challenge to Protagoras confronts this central contradiction in the sophist's thought: the egalitarianism of Protagoras' doctrine is at odds with the inegalitarian implication of his own expertise. Through this confrontation, which moves the argument toward the dialogue's central passage, Socrates shows that Protagoras' theory, his view of the character of knowledge, is instrumental to his notion of good. Protagoras expresses this notion in a particular understanding of advantage, of what's “good for” oneself. The heart of the dialogue faces the question as to whether Protagoras and his adherents, Theodorus and Theaetetus, have rightly understood human good. In particular, it explores whether advantage understood in Protagorean terms can be the good for him, or for any of us, insofar as we are beings capable of self-contradiction, beings whose heterogeneous nature generates such conflicts as that regarding equality, which are inherent in political life. The “delivery” already made evident the connection between one's view of good, on the one hand, and what knowledge is taken to be, on the other. This connection makes the adequacy of Protagoras' understanding of good bear on the explicit theme of the dialogue. Doubts about the adequacy of that understanding raise the question as to whether, like Protagoras, we should regard the knowledge we seek as the most certain means to a universally accepted good.
Hemlock Woolly Adelgid (Hemiptera: Adelgidae) Abundance and Hemlock Canopy Health Numerous Years After Imidacloprid Basal Drench Treatments: Implications for Management Programs

Hemlock woolly adelgid ( Adelges tsugae [Annand]), an invasive insect in the eastern United States, has caused widespread decline of eastern hemlock, Tsuga canadensis (L.) Carriere. Imidacloprid basal drench treatments were assessed 4–7 yr after a single treatment to determine hemlock woolly adelgid population suppression and effects on hemlock canopy health. The effects of sampling site, years post-treatment, and hemlock diameter at breast height (DBH) size classes were evaluated relative to imidacloprid treatment on hemlock woolly adelgid populations and hemlock canopy health characteristics. The influence of hemlock woolly adelgid populations on canopy health characteristics was also assessed. Imidacloprid treatments resulted in low-level hemlock woolly adelgid populations 7 yr post-treatment. Hemlock woolly adelgid was present on more hemlocks 7 yr compared with 4–6 yr post-treatment. Smaller hemlocks, dosed with 0.7 g active ingredient (AI)/2.5 cm DBH, had higher populations of hemlock woolly adelgid than the largest size class, which were treated at twice that dosage. Concentrations of imidacloprid and its olefin metabolite below the LC50 were sufficient for suppression of hemlock woolly adelgid populations, which suggests an additive effect of imidacloprid and olefin that compounds hemlock woolly adelgid mortality over many generations. Hemlock woolly adelgid populations observed in this study were too low to have an observable effect on hemlock canopy health, indicating that application intervals of up to 7 yr may be adequate to protect hemlocks.
Attitudes of Group Home Employees Towards the Sexuality of Individuals with Intellectual Disabilities

This article identifies personal factors that influence group home employees’ attitudes towards the sexuality of individuals with disabilities. Seventy-one individuals currently employed in group homes in a single state in the United States completed two surveys: a demographics survey and the Attitudes to Sexuality Questionnaire-Individuals with an Intellectual Disability. Data were analyzed using nonparametric tests due to the non-normal nature of the data. Results indicate that having an in-service training on sexuality has a positive influence on attitudes towards sexuality for individuals with an intellectual disability. In addition, personal factors (having an immediate family member with an intellectual disability, gender) also influenced attitudes towards sexuality and intellectual disability. However, data suggested no relationship between age or level of education and attitudes towards sexuality and intellectual disability. This study provides new information about factors that influence attitudes towards the sexuality of individuals with intellectual disabilities. It also provides data to support previous research on the topic.
Never events? Well, hardly ever.

Acknowledging errors and the manner in which they occur both enables doctors to hold themselves accountable and promotes understanding that can lead to error prevention.
Beyond Self-Management: Re-Membering Soul

Rogers-Vaughn addresses how to respond to the effects of neoliberalism, suggesting hope (as distinct from neoliberal optimism) as the necessary response to suffering and despair. Identifying two levels of unconsciousness endemic to third-order suffering—suffering that is not aware of itself as suffering and suffering that lacks awareness of its social origins—Rogers-Vaughn asserts that caring for souls must advance beyond self-management to the re-membering of soul. Rogers-Vaughn concludes that focused attention to suffering individuals offers a window into the dialectics of suffering as it appears under neoliberal governance. He draws from the new materialism and the notion of suffering as a form of resistance to critically reorient soul-care, using clinical material to illustrate this reorientation and suggest salient features for theorizing soul-care in the neoliberal age.
Cell Biology of Mouse Mammary Carcinogenesis in Organ Culture

Mammary carcinogenesis including human breast cancer is a major cause of premature death of women in different parts of the world. Breast cancer also is the second highest cause of mortality of women in the United States. Thus understanding of the pathgenesis of the mammary cancer has been of principal concern of the experimental oncologists
Retinal pigment epithelium and microglia express the CD5 antigen-like protein, a novel autoantigen in age-related macular degeneration.

We report on a novel autoantigen expressed in human macular tissues, identified following an initial Western blot (WB)-based screening of sera from subjects with age-related macular degeneration (AMD) for circulating auto-antibodies (AAbs) recognizing macular antigens. Immunoprecipitation, 2D-gel electrophoresis (2D-GE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), direct enzyme-linked immunosorbent assays (ELISA), WBs, immunohistochemistry (IHC), human primary and ARPE-19 immortalized cell cultures were used to characterize this novel antigen. An approximately 40-kDa autoantigen in AMD was identified as the scavenger receptor CD5 antigen-like protein (CD5L), also known as apoptosis inhibitor of macrophage (AIM). CD5L/AIM was localized to human RPE by IHC and WB methods and to retinal microglial cells by IHC. ELISAs with recombinant CD5L/AIM on a subset of AMD sera showed a nearly 2-fold higher anti-CD5L/AIM reactivity in AMD vs. Control sera (p = 0.000007). Reactivity ≥0.4 was associated with 18-fold higher odds of having AMD (χ2 = 21.42, p = 0.00063). Circulating CD5L/AIM levels were also nearly 2-fold higher in AMD sera compared to controls (p = 0.0052). The discovery of CD5L/AIM expression in the RPE and in retinal microglial cells adds to the known immunomodulatory roles of these cells in the retina. The discovery of AAbs recognizing CD5L/AIM identifies a possible novel disease biomarker and suggest a potential role for CD5L/AIM in the pathogenesis of AMD in situ. The possible mechanisms via which anti-CD5L/AIM AAbs may contribute to AMD pathogenesis are discussed. In particular, since CD5L is known to stimulate autophagy and to participate in oxidized LDL uptake in macrophages, we propose that anti-CD5L/AIM auto-antibodies may play a role in drusen biogenesis and inflammatory RPE damage in AMD.
Valve thrombosis following transcatheter aortic valve replacement: significance of blood stasis on the leaflets

OBJECTIVES Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) and valve-in-valve (ViV) procedures has been increasingly recognized. However, the factors affecting the post-TAVR/ViV thrombosis are not fully understood. This study aimed to investigate the effect of the geometric confinement of transcatheter aortic valve (TAV) on blood residence time (BRT) on the TAV leaflets and in turn on the post-TAVR valve thrombosis. METHODS Two computational models, representing a surgical bioprosthesis and a TAV, were developed to study the effect of the geometric confinement on BRT on the leaflets in ViV setting/TAVR Intra-annular positioning. 3D flow fields were obtained via a one-way fluid-solid interaction modelling approach validated by experimental testing. BRT was compared between the two models by quantification and statistical analysis of the residence time of randomly distributed particles in close proximity of the leaflets. RESULTS Significantly longer BRT on the leaflets was observed in the TAV compared to the surgical valve during different stages of the cardiac cycle. During forward flow, the mean value of BRT was found to be 39% higher in the TAV compared to the surgical bioprosthesis ( P < 0.0001). During diastole, specifically from end-systole to mid-diastole and from mid-diastole to the beginning of systole, the amount by which the mean BRT was higher for TAV compared to the surgical valve was 150% and 40%, respectively ( P < 0.0005). CONCLUSIONS The geometric confinement of TAV by the failed bioprosthesis or the calcified native valve increases the BRT on the TAV leaflets. This may act as a permissive factor in valve thrombosis.
Boundary integral equation analysis for suspension of spheres in Stokes flow

Abstract We show that the standard boundary integral operators, defined on the unit sphere, for the Stokes equations diagonalize on a specific set of vector spherical harmonics and provide formulas for their spectra. We also derive analytical expressions for evaluating the operators away from the boundary. When two particle are located close to each other, we use a truncated series expansion to compute the hydrodynamic interaction. On the other hand, we use the standard spectrally accurate quadrature scheme to evaluate smooth integrals on the far-field, and accelerate the resulting discrete sums using the fast multipole method (FMM). We employ this discretization scheme to analyze several boundary integral formulations of interest including those arising in porous media flow, active matter and magneto-hydrodynamics of rigid particles. We provide numerical results verifying the accuracy and scaling of their evaluation.
The Bishop Controversy, the Imperial Crisis, and Religious Radicalism in New England, 1763-74: By arrangement with the Colonial Society of Massachusetts the Editors of the New England Quarterly are pleased to publish the winning essay of the 2016 Walter Muir Whitehill Prize in Early American History

Abstract This essay re-examines the “bishop controversy”, a dispute between Anglicans and Dissenters in the decade preceding the American Revolution. The controversy, it argues, was part of the imperial crisis caused by the Seven Years' War and the government's toleration of French Catholics in Quebec. This perspective highlights the Church of England's limited role in the empire and the unacknowledged radicalism of loyalist Anglicans.
Diet and lifestyle intervention on chronic moderate to severe depression and anxiety and other chronic conditions

This group study explored how an intervention of diet, lifestyle and behavior modification, including a plant-based diet, daily exercise and mindfulness techniques, would affect 500 adult men and women participants diagnosed with chronic moderate to severe depression and anxiety and other conditions during a 12 week period. An analysis of the health outcomes detailed in self-reported diary entries was carried out at the conclusion of the 12 week period. These reports noted improvements in depression, anxiety and all other conditions addressed by the study, with the majority of participants reporting substantial benefits. A six month follow up indicated that these benefits persisted in most of the participants. These results demonstrate that an intervention of diet, exercise, lifestyle and behavior modification may provide considerable benefits for moderate to severe depression and anxiety as well as other conditions.
Activation of RARα, RARγ, or RXRα Increases Barrier Tightness in Human Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells.

The blood-brain barrier (BBB) is critical to central nervous system (CNS) health. Brain microvascular endothelial cells (BMECs) are often used as in vitro BBB models for studying BBB dysfunction and therapeutic screening applications. Human pluripotent stem cells (hPSCs) can be differentiated to cells having key BMEC barrier and transporter properties, offering a renewable, scalable source of human BMECs. hPSC-derived BMECs have previously been shown to respond to all-trans retinoic acid (RA), and the goal of this study was to identify the stages at which differentiating human induced pluripotent stem cells (iPSCs) respond to activation of RA receptors (RARs) to impart BBB phenotypes. Here the authors identified that RA application to iPSC-derived BMECs at days 6–8 of differentiation led to a substantial elevation in transendothelial electrical resistance and induction of VE-cadherin expression. Specific RAR agonists identified RARα, RARγ, and RXRα as receptors capable of inducing barrier phenotypes. Moreover, RAR/RXRα costimulation elevated VE-cadherin expression and improved barrier fidelity to levels that recapitulated the effects of RA. This study elucidates the roles of RA signaling in iPSC-derived BMEC differentiation, and identifies directed agonist approaches that can improve BMEC fidelity for drug screening studies while also distinguishing potential nuclear receptor targets to explore in BBB dysfunction and therapy.
Regression of Giant Calcified Thoracic Disk and Spinal Cord Compression Following Thoracic Laminectomy and Posterior Instrumented Fusion

The authors present a case report of a patient with a giant thoracic calcified disc. The patient underwent a posterior thoracic laminectomy and fusion without resection of the disc. The calcified disc regressed in size and lost its calcified component postoperatively.
Primary Systemic Amyloid Neuropathy

Primary systemic amyloidosis (PSA) is a plasma cell dyscrasia. Organ damage is caused by deposition of amyloid, derived from monoclonal light chains, in tissues including nerves. PSA damages tissues and leads to combinations of neuropathy and renal, cardiac, and liver failure. The neuropathy of PSA is relatively stereotyped with damage to small and autonomic nerve fibers and superimposed carpal tunnel syndrome. The disease is progressive and mortality is high, especially when there is early involvement of vital organs. Treatment in the past was relatively ineffective. However, with the advent of peripheral blood stem cell transplantation and chemotherapy in selected patients, prolonged survival is possible if the weight of organ damage at onset of treatment is not too high. Thus, early detection is paramount.
Synchronous DC link voltage control for microinverters with minimum DC link capacitance

This paper investigates DC link capacitor optimization for three-phase photovoltaic (PV) based microinverters. This concept minimizes the storage capacitance by allowing greater voltage ripple on the DC link. Therefore, the microinverter reliability can be significantly increased by replacing electrolytic capacitors with film capacitors. However, this intentionally increased voltage ripple can introduce harmonic distortion on the output current of the inverter stage if it is not mitigated by the DC link voltage controller. For this purpose, a robust and accurate DC link voltage control is proposed to filter this ripple while regulating the DC link voltage without using any additional circuit components. The experimental results on a 400-W three-phase half-bridge microinverter prototype validate the theoretical analysis of the DC link capacitor optimization and show that a significant reduction of the DC link capacitor requirement can be achieved. The proposed high accuracy DC link voltage controller is also implemented on this prototype to demonstrate very low harmonic distortion of the inverter output current while tightly regulating the DC link voltage even during transients.
Measuring and Evaluating Safety Maturity of Construction Contractors: Multicriteria Decision-Making Approach

AbstractEvaluating the safety maturity of construction contractors before awarding the contract is an effective strategy that many owners have started to implement. Given the importance of workplac...
Microbial Quantity Impacts Drosophila Nutrition, Development, and Lifespan

In Drosophila, microbial association can promote development or extend life. We tested the impact of microbial association during malnutrition and show that microbial quantity is a predictor of fly longevity. Although all tested microbes, when abundantly provided, can rescue lifespan on low-protein diet, the effect of a single inoculation seems linked to the ability of that microbial strain to thrive under experimental conditions. Microbes, dead or alive, phenocopy dietary protein, and the calculated dependence on microbial protein content is similar to the protein requirements determined from fly feeding studies, suggesting that microbes enhance host protein nutrition by serving as protein-rich food. Microbes that enhance larval growth are also associated with the ability to better thrive on fly culture medium. Our results suggest an unanticipated range of microbial species that promote fly development and longevity and highlight microbial quantity as an important determinant of effects on physiology and lifespan during undernutrition.
Infusion of marrow in the mouse and dog after thio-TEPA.

In mice and in dogs, the usefulness of infusions of marrow in reducing the toxicity of thio-TEPA is limited to a very narrow range of dose of drug in which prompt restoration of hematopoiesis seems critical to survival. Below this range, control animals recover spontaneously; above this range, damage to other organ systems precludes survival.
Health, Sustainable Development Goals and the New Urban Agenda

Urbanization has become one of the most important global trends of the twenty-first century, and according to OECD recent research, its impacts will be more keenly felt than climate change in the immediate future. Investing in good urbanization is a guarantee of prosperity and development, particularly in developing countries, where major urban transformations will inevitably take place. There is still a strong focus on curing the sick rather than prevention. Globally, approximately one third of diseases are the result of environmental factors, with children being some of the most vulnerable. If we consider the multiple risk factors that some communities live in (slums for example), the figures are most likely much higher. The disease burden is mainly due to non-communicable diseases (NCDs), however infectious diseases still account for a significant proportion and should not be neglected. As a priority, urgent analyses using the SDGs framework (and the UN-Habitat sample cities) of the health status in cities, disaggregated and overlaid with socio-economic profiles are needed. A city by city analysis of the problems and solutions driven by the urban authorities, together with a realization that many of the interventions that frame and support health improvements come from outside the health sector, is an important starting point. Localised plans of action for “sanitary revolutions” to reduce communicable diseases and campaigns to combat NCDs led by improved urban design and continuous monitoring need urgent attention.
Assessing the causal impact of Chinese aid on vegetative land cover in Burundi and Rwanda under conditions of spatial imprecision

Abstract There has been considerable debate regarding the efficacy of international aid in meeting the dual goals of human development and environmental sustainability. Many donors have sought to engage with this challenge by introducing environmental safeguard and monitoring initiatives; however, evidence on the success of these interventions is limited. Evaluating aid is a particular challenge in the case of donors that do not disclose information on the nature, geographic location, or extents of their interventions. In such cases, new methods that extract and geoparse data on the activities of opaque donors through the manual interpretation of thousands of news and other articles allow us to investigate the impacts of these activities. However, residual spatial uncertainty in these data remains a potential source of bias. In this article, we apply and discuss a Geographic Simulation and Extrapolation (GeoSIMEX) approach to mitigate the spatial imprecision inherent in geoparsed data. In conjunction with GeoSIMEX, we test and contrast multiple approaches to reducing the imprecision of aid, including high-assumption cases in which other covariates (i.e., nighttime lights) are leveraged to allocate aid. In our application, we find that methods which do not account for spatial imprecision find statistically significant relationships between Chinese aid and vegetation change; after accounting for spatial uncertainty, findings are similar for Rwanda and inconclusive for Burundi.
Retail Store Execution: An Empirical Study

We describe a methodology by which a retailer can identify action steps that are likely to increase sales and customer satisfaction and demonstrate the methodology using proprietary data from a large retailer with over 500 stores. We use monthly store-level data on a number of operational variables including in-stock rate, store staffing level as measured by payroll and store employee turnover, together with customer responses to satisfaction surveys. We develop a nested three-stage econometric model to analyze the marginal effects of various execution levers on sales, customer satisfaction and the percentage of customers who answer ‘yes’ to the question ‘Did you find everything you were looking for?’, which we term customer perceived in-stock. Our model explains approximately 75%, 97% and 71%, respectively, of the residual variation in sales, customer satisfaction, and customer perceived in-stock. We find that customer perceived in-stock is primarily driven by actual in-stock and customer rating of employee knowledge; overall customer satisfaction is primarily driven by customer perceived in-stock, payroll level, customer rating of employee knowledge and check-out efficiency; and sales is primarily driven by actual in-stock, overall satisfaction and payroll level. Finally, we estimate relative magnitudes of these effects, propose specific actions to improve sales and estimate the likely sales increase from those actions. Our results suggest that a modest reallocation of the payroll budget among stores could be expected to yield a 2-3% increase in sales with no increase in cost.
Factors Influencing Consumers' Purchase Intentions Towards Made-to-Order Tea Drinks in China

This article aims to identify and assess the factors influencing consumers' purchase intentions towards made-to-order (MTO) tea drinks. The made-to-order milk tea drink industry in China has generated over USD 14bn in revenue in 2018. The size of the market, the nature of the preparation and delivery to consumers, combine to create opportunities for individuals, entrepreneurs, investors, etc. Relatively little is known about the drivers of purchase intentions for MTO milk tea drink consumers. For the purposes of this research, the various options that influence purchasing of tea drinks among Chinese consumers were classified into 10 factors, and data was collected through online surveys. The results indicate the extent to which Chinese consumers' purchase intentions are influenced by consumers' age, price of the drink, pursuit of a pleasant state of mind, quest for social network interaction, search for novel experiences, and concern for health.
Prelude to Armstrong: A Mathematical Revolution That Inspired F. Ramsey, and Left Russell and Armstrong Unmoved

The story here involves F. Ramsey’s realization that the nineteenth century mathematical debate about functions had implications for the expression of statements of arithmetic in Russell and Whitehead’s Principia. We believe that it is the same flaw, – expressive inadequacy – that lies at the heart of what is wrong with D. Armstrong’s account of scientific laws.
How does exercise support dietary approaches to weight loss and better health

The rapid global rise of obesity incurs a heavy personal and healthcare burden due to obesity-associated morbidities and shortening of life. The purpose of this review is to provide evidence-based strategies for prevention, reversal, and mitigation of obesity and its sequelae. To that end, this review highlights the features of human physiology that favor fat accretion and interfere with fat loss. Strategies for prevention of obesity include understanding the basis for the strong motivating properties of palatable food, for human inability to consciously detect calories eaten or calories expended through exercise, for metabolic and hormonal adaptations to negative energy balance that drive weight regain, and for evolutionary natural selection which likely led to high human capacity for fat storage. Reversal of obesity is difficult primarily due to metabolic, hormonal, and behavioral reactions to body fat loss. Reduced resting metabolic rate presents a physiological challenge whether the weight loss is achieved through dietary restriction or energy expenditure of exercise. Increased insulin sensitivity after body fat loss drives resynthesis of storage substrates including triglycerides in the adipose tissue, muscle glycogen, and proteins, thus contributing to weight regain. Reduced basal plasma leptin concentration elicits a strong hunger drive. Mitigation of obesity-associated morbidities involves adding exercise energy expenditure to deliberate control of the quantity of food eaten, reducing postprandial hyperinsulinemia by lowering the carbohydrate load of the diet, and exercising after, rather than before, the meals to facilitate improved glucose tolerance.