cssi/SciSciGPT-SciSciNet huggingface dataset:
MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis

Hypersensitivity pneumonitis is an interstitial lung disease that is characterized by alveolitis, granuloma formation, and in some patients, fibrosis. Using the Saccharopolyspora rectivirgula animal model of Farmer's lung disease, our laboratory has demonstrated that neutrophils play a critical role in IFN-gamma production during the acute phase of the disease. As IFN-gamma is necessary for granuloma formation, it is important to identify the factors that lead to neutrophil recruitment during disease. To begin to identify the pattern recognition receptors (PRRs) that initiate chemokine production, leading to neutrophil recruitment following S. rectivirgula exposure, we examined the role of MyD88 and TLR2. Our results demonstrate that neutrophil recruitment, as measured by flow cytometry and the myeloperoxidase assay, was abolished in the absence of MyD88 following S. rectivirgula exposure. The decrease in neutrophil recruitment was likely a result of a significant decrease in production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine. These results suggest that S. rectivirgula interacts with PRRs that are upstream of the MyD88 pathway to initiate cytokine and chemokine production. In vitro studies suggest that S. rectivirgula can interact with TLR2, and stimulation of adherent cells from TLR2 knockout (KO) mice with S. rectivirgula resulted in a significant decrease in MIP-2 production. However, TLR2 KO mice did not have a reduction in neutrophil recruitment compared with wild-type mice following S. rectivirgula exposure. The results from our studies suggest that one or more PRR(s) upstream of MyD88 are necessary for neutrophil recruitment following S. rectivirgula exposure.
Finding a catalog: generating analytical catalog records from well-structured digital texts

One of the criticisms library users often make of catalogs is that they rarely include information below the bibliographic level. It is generally impossible to search a catalog for the titles and subjects of particular chapters or volumes. There has been no way to add this information to catalog records without exponentially increasing the workload of catalogers. At the same time, well-structured full-text XML transcriptions of printed works are becoming increasingly available. This paper describes how existing investments in full text digitization and structural markup combined with current named-entity extraction technology can efficiently generate the detailed level of catalog data that users want, at no significant additional cost. This system is demonstrated on an existing digital collection within the Perseus Digital Library.
A fully implicit parallel algorithm for simulating the non‐linear electrical activity of the heart

In this paper, we study a fully implicit parallel Newton–Krylov–Schwarz method (NKS) for solving the bidomain equations describing the electrical excitation process of the heart. NKS has been used successfully for many non-linear problems, but this is the first attempt to use this method for the bidomain model which consists of a system of time dependent partial differential equations of mixed type. Our experiments on parallel computers show that the method is scalable and robust with respect to many of the parameters in the bidomain model. In the outer layer of the algorithm, we use a non-linearly implicit backward Euler method to discretize the time derivative, and the resulting systems of large sparse non-linear equations are solved using an inexact Newton method. The Jacobian system required to solve in each Newton iteration is solved with a GMRES method preconditioned by a new component-wise restricted additive Schwarz preconditioner. The efficiency and robustness of the overall method depend heavily on what preconditioner we use. By comparing several preconditioners, we found our new restricted additive Schwarz method offers the best performance. Our parallel software is developed using the PETSc package of Argonne National Laboratory. Numerical results obtained on an IBM SP will be reported. Copyright © 2004 John Wiley & Sons, Ltd.
Field versus laboratory turbulent boundary layers

The universal logarithmic profile that describes the mean streamwise velocity in the inner layer of any wall-bounded flow is the best known example of the stated classical idea. In the present research, data from numerous numerical and physical experiments have been carefully analyzed, and it is shown that boundary layers, in fact, never achieve true self-preservation and that neither inner nor outer scaling is strictly valid. We present an informative summary of value.
What's Inside That Seed We Brew? A New Approach To Mining the Coffee Microbiome

Coffee is a critically important agricultural commodity for many tropical states and is a beverage enjoyed by millions of people worldwide. Recent concerns over the sustainability of coffee production have prompted investigations of the coffee microbiome as a tool to improve crop health and bean quality. This review synthesizes literature informing our knowledge of the coffee microbiome, with an emphasis on applications of fruit- and seed-associated microbes in coffee production and processing. A comprehensive inventory of microbial species cited in association with coffee fruits and seeds is presented as reference tool for researchers investigating coffee-microbe associations. It concludes with a discussion of the approaches and techniques that provide a path forward to improve our understanding of the coffee microbiome and its utility, as a whole and as individual components, to help ensure the future sustainability of coffee production.
The State of Work (and Workers) in America

Informed discussions of many important topics in the sociology of work and occupations—such as earnings and wealth inequality, employment and unemployment, gender and race differences in earnings a...
Asian and Pacific American Early Education: Research Needs.

An analysis of literature on the education of young Asian and Pacific American children points to research needs in three areas. First, objective information concerning values, attitudes, and learning styles of previously neglected cultural groups is required for appropriate educational planning. Second, investigation methods could be broadened to include more observational approaches and examinations of within-group differences. Finally, a need exists for research on which to base decisions regarding policy issues and instructional methods.
On the Economics of Adulteration in Food Imports: Application to US Fish and Seafood Imports

This essay shows the role of economics in the adulteration of food imports.The mechanism of impact in the model is the choice of input quality by exporting firms. One implication of the model is that conomic variables can be used to predict adulteration in food imports. The essay offers an application to US fish and seafood imports following the closing of fisheries in the Gulf of Mexico because of the Deepwater Horizon platform oil spill. Simulations show an increase in adulteration in fish and seafood imports after the Deepwater Horizon incident. Empirical evidence supports simulations' findings.
Comparison of Microfacet BRDF Model to Modified Beckmann-Kirchhoff BRDF Model for Rough and Smooth Surfaces

A popular class of BRDF models is the microfacet models, where geometric optics is assumed. In contrast, more complex physical optics models may more accurately predict the BRDF, but the calculation is more resource intensive. These seemingly disparate approaches are compared in detail for the rough and smooth surface approximations of the modified Beckmann-Kirchhoff BRDF model, assuming Gaussian surface statistics. An approximation relating standard Fresnel reflection with the semi-rough surface polarization term, Q, is presented for unpolarized light. For rough surfaces, the angular dependence of direction cosine space is shown to be identical to the angular dependence in the microfacet distribution function. For polished surfaces, the same comparison shows a breakdown in the microfacet models. Similarities and differences between microfacet BRDF models and the modified Beckmann-Kirchhoff model are identified. The rationale for the original Beckmann-Kirchhoff F(bk)(2) geometric term relative to both microfacet models and generalized Harvey-Shack model is presented. A modification to the geometric F(bk)(2) term in original Beckmann-Kirchhoff BRDF theory is proposed.
O11.5 Incorporating spatial variability to generate sub-national estimates of hiv prevalence

Introduction The design and evaluation of national HIV programs often relies on aggregated national level data. However, there is often substantial geographical heterogeneity in the HIV epidemic within countries, which could be used to tailor programmatic responses to the specific local needs. Given this background, the study attempts to answer the question: Could environmental and socio-behavioural factors be used to generate sub-national estimates of HIV prevalence in sub-Saharan Africa? Methods Data were obtained from Demographic and Health Surveys (DHS) conducted in Tanzania, Malawi, and Kenya. Associations between covariates and HIV prevalence were assessed using non-spatial logistic regression models. Covariates included life time number of sexual partners, percentage of condom use, wealth index, percentage of male circumcision (MC), distance to urban settings, distance to roads, and normalised difference vegetation index (NDVI). The prediction formula generated from the covariate analysis along with kriging interpolation techniques were used to produce high resolution continuous surface maps of HIV prevalence. Results Condom use, MC, distance to main roads, NDVI, poverty and wealth index were associated with HIV prevalence in Tanzania and Malawi, and were included to generate HIV prevalence maps in these countries. Conversely, only NDVI, poverty life time number of sexual partners and MC were associated with HIV prevalence in Kenya. All three maps illustrated substantial geographical variation of HIV prevalence within the country, and localised areas where HIV prevalence is concentrated. Conclusion The HIV prevalence maps generated highlight the stark spatial disparities in the epidemic within a country, and localise areas where both the burden and drivers of the HIV epidemic are concentrated. These maps present an opportunity to apply differential local approaches to maximise impact by informing both planning and delivery of defined packages of services. Additional work is needed for routine incorporation of such strategies into existing national HIV estimation processes. Disclosure of interest statement Nothing to declare.
Fighting for the Forgotten: Risk and Resilience of Children and Families Involved with the Foster Care System

Children and youth in foster care are some of the most underserved and holistically unhealthy people in our country today. Toxic stress, mental illness, environmental instability, and unrecognized or under diagnosed chronic disease are just a few issues that plague this special population of children that then grow into ill or maladapted adults with higher rates of morbidity and mortality than their “nonfoster” counterparts. Their story is not complete however. We can increase the resilience of our foster children and rewrite the outcomes of their futures through the responsible and intentional interventions of our health care professionals, child welfare workers, and communities.
An organizing model for recent cognitive science work on the self

An organizing model of 'the self' emerges from applying various kinds of brain injury to recent cognitive science and philosophical work on 'the self'. This model unifies various contents and mechanisms central to current notions of the self. The article then highlights several criteria and aspects of this notion of self. Qualities of the right type and level of psychological significance delineate 'the self' as an organizing concept useful for recent philosophical work and cognitive science research.
Parent & Child Perceptions of Child Health after Sibling Death.

Background: Understanding children’s health after a sibling’s death and what factors may affect it is important for treatment and clinical care. This study compared children’s and their parents’ perceptions of children’s health and identified relationships of children’s age, gender, race/ethnicity, anxiety, and depression and sibling’s cause of death to these perceptions at 2 and 4 months after sibling death. Methods: 64 children and 48 parents rated the child’s health “now” and “now vs before” the sibling’s death in an ICU or ER or at home shortly after withdrawal of life-prolonging technology. Children completed the Child Depression Inventory and Spence Children’s Anxiety Scale. Sibling cause of death was collected from hospital records. Results: At 2 and 4 months, 45% to 54% of mothers’ and 53% to 84% of fathers’ ratings of their child’s health “now” were higher than their children’s ratings. Child health ratings were lower for: children with greater depression; fathers whose children reported greater anxiety; mothers whose child died of a chronic condition. Children’s ratings of their health “now vs before” their sibling’s death did not differ significantly from mothers’ or fathers’ ratings at 2 or 4 months. Black fathers were more likely to rate the child’s health better “now vs before” the death; there were no significant differences by child gender and cause of death in child’s health “now vs before” the death.
The transient shear rheology of a thermotropic liquid crystalline polymer in the super-cooled state

Abstract To determine the processing temperature of a representative thermotropic liquid crystalline polymer (TLCP) in the super-cooled state, small amplitude oscillatory shear (SAOS), the startup of shear flow and differential scanning calorimetry (DSC) measurements were performed. Good agreement on the onset crystallization temperature was obtained from the SAOS and the startup of shear flow. Compared with DSC, the rheological measurements were more sensitive for detecting crystallization in the super-cooled state. The rheological study suggested that crystallization did not occur unless the TLCP was cooled 30 °C below its melting point, and its viscosity was significantly increased as the material was super cooled. Additionally, super cooling the TLCP did not significantly affect the relaxation of shear stress after preshearing. However, the recovery of transient shear stress in the interrupted shear measurements was suppressed to a great extent in the super-cooled state.
The dynamic model and hybrid phase-shift control of a dual-active-bridge converter

This paper presents an averaged model and a small-signal model of a bidirectional dual active bridge (DAB) DC-DC converter. Based on the proposed model, the stability and transient power flow in the system can be analyzed. A novel hybrid controller is proposed for the phase-shift based feed-back and feed-forward control of a 600V/10kW prototype. The hybrid controller can ease the difficulties of the parameter selection of a traditional PI. The effectiveness of the models and proposed hybrid controller are validated by simulations and experiments in both transient and steady state operations.
A Novel Application of the Host-Guest Paradigm: Design of Organic Optoelectronic Materials

A ferroelectric polarization P (permanent, spontaneous electric dipole moment) is predicted for certain non-racemic liquid crystals based upon simple symmetry arguments. The magnitude of this polarization is a major factor in determining the electro-optic response times achievable in ferroelectric liquid crystal (FLC) light valves and spatial light modulators — devices with excellent potential utility in devices for optoelectronic computing and large-area, high resolution flat panel displays.
Dissociative electron attachment to halogen molecules: Angular distributions and nonlocal effects

We study dissociative electron attachment (DEA) to the ClF and ${\mathrm{F}}_{2}$ molecules. We formulate a method for calculation of partial resonance widths and calculate the angular distributions of the products in the ClF case using the local and nonlocal versions of the complex potential theory of DEA. They show the dominance of the $p$ wave except in a narrow energy region close to zero energy. Comparison of the local and nonlocal DEA cross sections show that the former are smaller than the latter by a factor of 2 in the energy region important for calculation of thermal rate coefficients. This result is confirmed by comparison of the local and nonlocal calculations for ${\mathrm{F}}_{2}$. Only at low energies below 30 meV the local cross sections exceed nonlocal due to the $1/E$ divergence of the local results. On the other hand, the thermal rate coefficients generated from the local cross sections agree better with experiment than those calculated from the nonlocal cross sections. The most likely reason for this disagreement is the overestimated resonance width in the region of internuclear distances close to the point of crossing between the neutral and anion potential-energy curves.
Addressing a question answering challenge by combining statistical methods with inductive rule learning and reasoning

A group of researchers from Facebook has recently proposed a set of 20 question-answering tasks (Facebook's bAbl dataset) as a challenge for the natural language understanding ability of an intelligent agent. These tasks are designed to measure various skills of an agent, such as: fact based question-answering, simple induction, the ability to find paths, co-reference resolution and many more. Their goal is to aid in the development of systems that can learn to solve such tasks and to allow a proper evaluation of such systems. They show existing systems cannot fully solve many of those toy tasks. In this work, we present a system that excels at all the tasks except one. The proposed model of the agent uses the Answer Set Programming (ASP) language as the primary knowledge representation and reasoning language along with the standard statistical Natural Language Processing (NLP) models. Given a training dataset containing a set of narrations, questions and their answers, the agent jointly uses a translation system, an Inductive Logic Programming algorithm and Statistical NLP methods to learn the knowledge needed to answer similar questions. Our results demonstrate that the introduction of a reasoning module significantly improves the performance of an intelligent agent.
Cell cycle: Division enzyme regulates metabolism

Cell division requires the action of key regulator proteins called cyclins and CDKs. It emerges that a cyclin–CDK complex can regulate cell metabolism, and targeting this metabolic regulation causes tumour regression in mice. See Letter p.426 Cyclin–CDK complexes are commonly amplified in cancer and promote cell cycle progression. Inhibitors for CDK4/6 are being tested in clinical trials and are thought to work in patients that retain expression of the CDK substrate RB1. Here, the authors describe an additional pro-survival role of one cyclin–CDK complex, D3–CDK6, which controls cellular metabolism. When hyperactivated in cancer cells, the complex phosphorylates and inactivates two glycolysis enzymes. This redirects glycolytic intermediates to the pentose phosphate and serine pathways, providing enhanced antioxidant capacity. CDK4/6 inhibitors can induce apoptosis by increasing the oxidative stress in tumour cells expressing high levels of D3–CDK6 complexes. The findings suggest that, in addition to RB1, markers such as levels of D3–CDK6 complexes could be useful for identifying patients likely to respond to CDK4/6 inhibitors.
Red/near infrared light stimulates release of an endothelium dependent vasodilator and rescues vascular dysfunction in a diabetes model.

Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) increased NO from nitrosyl-heme stores, therefore we hypothesized R/NIR can stimulate vasodilation in healthy and diabetic blood vessels. Vasodilation was tested by ex vivo pressure myography in wild type C57Bl/6, endothelial nitric oxide synthase (eNOS) knockout, and db/db mice (10mW/cm2 for 5min with 10min dark period). NOS inhibition with N-Nitroarginine methyl ester (L-NAME) or the NO scavenger Carboxy-PTIO (c-PTIO) tested the specificity of NO production. 4,5-Diaminofluorescein diacetate (DAF-2) measured NO in human dermal microvascular endothelial cells (HMVEC-d). R/NIR significantly increased vasodilation in wild type and NOS inhibited groups, however R/NIR dilation was totally abolished with c-PTIO and blood vessel denudation. Interestingly, the bath solution from intact R/NIR stimulated vessels could dilate light naive vessels in a NO dependent manner. Characterization of the bath identified a NO generating substance suggestive of S-nitrosothiols or non heme iron nitrosyl complexes. Consistent with the finding of an endothelial source of NO, intracellular NO increased with R/NIR in HMVEC-d treated with and without L-NAME (1mM), yet c-PTIO (100µm) reduced NO production. R/NIR significantly dilated db/db blood vessels. In conclusion, R/NIR stimulates vasodilation by release of NO bound substances from the endothelium. In a diabetes model of endothelial dysfunction, R/NIR restores vasodilation, which lends the potential for new treatments for diabetic vascular disease.
Sex Differences in the Prevalence and Correlates of Handgun Carrying Among Adolescents in the United States

Handgun carrying is associated with a wide range of delinquent behaviors, but very little is known about sex differences in this behavior and current trends in handgun carrying in the United States...
A mHealth randomized controlled trial to reduce sugar-sweetened beverage intake in preschool-aged children.

BACKGROUND Sugar-sweetened beverages and maternal weight are strong drivers of child obesity, but few studies have targeted these risk factors as an obesity prevention strategy in children. OBJECTIVE The objective of this study was to test the efficacy of a smartphone-delivered intervention to reduce parent-provided sugar-sweetened beverage and juice (SSB/juice) consumption among children ages 3-5 and maternal weight. METHODS Mothers with overweight or obesity, who had a child ages 3-5 that consumed at least 12 fl. oz./day of SSB/juice (N = 51 dyads) were randomized to the Smart Moms group that received one group session, lessons on a mobile website, and text messages, or to a waitlist control group. Mothers self-monitored their children's beverages in addition to their own beverages, high-calorie foods, and weight. Assessments at baseline, 3, and 6 months included dietary recalls to measure SSB/juice intake and objectively measured maternal weight. RESULTS Using linear mixed models controlling for baseline values, child age and race, there was a greater reduction in child SSB/juice in Smart Moms compared with control at 6 months (-9.7 oz./day vs. 1.7 oz./day, p < .01). Mothers in Smart Moms lost 2.4 kg at 6 months compared with a 0.9-kg gain in the control group (p < .01). CONCLUSIONS An intervention delivered using mHealth technologies can target mothers to change child dietary behaviours and improve maternal weight, which suggests a novel approach to family-based obesity prevention.
Transfer capability improvement through market-based operation of series FACTS devices

Traditionally, electric system operators have dispatched generation to minimize total production costs, ignoring the flexibility of the transmission system. Implementation of smart-grid systems could allow operators to co-optimize flexible transmission alongside generation dispatch; the technologies that would enable such co-optimization are still regulated as part of the monopoly transmission system. One particular flexible transmission asset is variable impedance flexible AC transmission system (FACTS). This paper 1) points out the positive externality problem existing in a recent market design proposal with active transmission participation, and 2) proposes a sensitivity-based method to estimate the marginal market value of FACTS adjustments to overcome this positive externality problem. The marginal value would suggest efficient impedance adjustments to the operator and provide the right financial incentives for the FACTS owners to operate their assets in a socially optimal way. Revenue adequacy is demonstrated under specific conditions and more broadly investigated through simulation studies. An analytical example on a two-bus system as well as a numerical study on the IEEE 118-bus system are presented. The results suggest that inclusion of a price signal for FACTS devices would lead to significant social welfare improvements in competitive power markets.
Targeted, Multifunctional Hydrogel Nanoparticles for Imaging and Treatment of Cancer

Use of nanoparticles as a platform for carrying drugs, image contrast agents, or both has been considered to be a revolutionary approach for cancer diagnosis and therapy. Especially, hydrogel nanoparticles have drawn considerable interest as a very promising platform because of their favorable characteristics, based on the conceptual combination of nanoparticle and hydrogel. Nanoparticles can carry high payloads and target selectively to tumors because of their nanosize and engineering capability. The hydrogel characteristics, including hydrophilicity and reversible, stimuli-responsive swelling/deswelling, enable long plasma circulation times and controlled drug release. Hydrogel nanoparticles made of natural, synthetic, or combinations of both polymers have been designed, prepared, and applied for treatment and imaging of cancer with various therapeutic and imaging modalities. This chapter describes various types of hydrogel nanoparticles developed for cancer applications and their preparation methods and analyzes their characteristics which make them suitable for cancer therapy and imaging. It also presents selected applications of hydrogel nanoparticles for imaging (for diagnosis and surgical delineation) and therapeutic modalities as well as for integrated therapy and imaging.
Treatment of postoperative high-volume lymphatic complications using isosulfan blue.

Abstract Background Lymphocele (LC) and lymphocutaneous fistula (LF) are infrequent but serious complications that occur when lymphatics are disrupted during a vascular procedure. Conservative management with bed rest, extremity elevation, aspiration, and pressure dressing is often ineffective. This study evaluated the effectiveness of isosulfan blue (ISB) to identify disrupted lymphatics for ligation. Methods Between 1998 and 2016, there were 33 lymphatic complications treated with ISB-directed ligation in 32 patients. The patients' records were retrospectively reviewed, recording demographics, comorbid conditions, index vascular operation causing the lymphatic complication, details of the procedure done to treat the lymphatic complication, and outcomes. In each patient, between 1 and 3 mL of ISB was injected in the subcutaneous tissue of the interdigital web space. The wound associated with the lymphatic complication was opened. The appearance of dye within the wound identified disrupted lymphatic ducts for suture ligation. Results The lymphatic complications were either LC (11 [33%]) or LF (22 [66%]) and were associated with femoral vein harvest (9), great saphenous vein harvest (8), exposure of femoral arteries (13), creation of an upper extremity fistula (1), repeated femoral access for coronary angiography, or excision of an LC (1). Most patients were male (66%), and the mean age was 56.8 ± 13.1 years. In comparing patients with LF and LC, the diagnosis of LF was made earlier (13.8 ± 7.0 days vs 23.4 ± 14.1 days; P = .02), and treatment occurred sooner for LF than for LC (22.1 ± 8.1 days vs 48.8 ± 51.2 days; P = .02). In all patients, ISB identified one or more disrupted lymphatics. The appearance of the ISB dye within the wound after injection was rapid, often within 5 to 10 minutes. After ligation of the lymphatics, most wounds were closed primarily (26 [79%]), but a muscle flap (5 [15%]), negative pressure dressing (1 [3%]), and dressing changes (1 [3%]) were also used. Wound healing was achieved in all patients on average 32.5 ± 21.5 days after lymphatic ligation. Conclusions The current series is one of the largest reported experiences using ISB to identify injured lymphatics responsible for LC or LF. Lymphatic complications after a vascular procedure usually occur within 3 weeks of the index vascular procedure, with LF being identified and treated earlier than LC. ISB injection rapidly identifies disrupted extremity lymphatics. Ligation of these lymphatics results in reliable resolution of the lymphatic complication.
Textual Analysis: Frequencies and Stop Words in Dirty Text

The third of the six Digital Humanities assignments, Textual Analysis, is presented in this chapter, beginning with a brief introduction to textual analysis as an analytical method of great interest to humanities programmers. The assignment description (written in a form and with a point-of-view suitable to be copied and pasted into materials given directly to students), required support files and resources, skills utilized in the assignment (which include file I/O, string methods and indexing, and an introduction to algorithm design), assignment management techniques and issues (mostly involved with helping students learn to build mental models to deal with abstract structures, like parallel lists), atomic code for the assignment (a solar system planet exercise), expected output from student submitted work in this assignment, and variations for a number of student skill levels are provided.
A likelihood approach to testing hypotheses on the co-evolution of epigenome and genome

Central questions to epigenome evolution include whether interspecies changes of histone modifications are independent of evolutionary changes of DNA, and if there is dependence whether they depend on any specific types of DNA sequence changes. Here, we present a likelihood approach for testing hypotheses on the co-evolution of genome and histone modifications. The gist of this approach is to convert evolutionary biology hypotheses into probabilistic forms, by explicitly expressing the joint probability of multispecies DNA sequences and histone modifications, which we refer to as a class of Joint Evolutionary Model for the Genome and the Epigenome (JEMGE). JEMGE can be summarized as a mixture model of four components representing four evolutionary hypotheses, namely dependence and independence of interspecies epigenomic variations to underlying sequence substitutions and to underlying sequence insertions and deletions (indels). We implemented a maximum likelihood method to fit the models to the data. Based on comparison of likelihoods, we inferred whether interspecies epigenomic variations depended on substitution or indels in local genomic sequences based on DNase hypersensitivity and spermatid H3K4me3 ChIP-seq data from human and rhesus macaque. Approximately 5.5% of homologous regions in the genomes exhibited H3K4me3 modification in either species, among which approximately 67% homologous regions exhibited local-sequence-dependent interspecies H3K4me3 variations. Substitutions accounted for less local-sequence-dependent H3K4me3 variations than indels. Among transposon-mediated indels, ERV1 insertions and L1 insertions were most strongly associated with H3K4me3 gains and losses, respectively. By initiating probabilistic formulation on the co-evolution of genomes and epigenomes, JEMGE helps to bring evolutionary biology principles to comparative epigenomic studies.
SECTION 9.9 – Hydrogen Transport and Interaction with Material Deformation: Implications for Fracture

This chapter presents two models: non-hydride-forming systems and hydride-forming systems. It discusses; the validity, background, description of the model, identification of model, and how to use this model. The non-hydride-forming systems applies to a variety of systems, such as fcc, bcc, hcp, pure metals, solid solutions, precipitation-strengthened systems, and intermetallics. It is used to calculate the local hydrogen concentration qualified by hydrostatic stress and trapping induced by plastic straining. Then by using information on whether the fracture is strain or stress-controlled, one can predict the location of the first microcracking event in a specimen. The hydride-forming system applies to systems that fail predominantly by hydride formation and cleavage. These are systems in which hydrides are either stable or can be stabilized by the application of a stress field. Examples are the IVb and Vb metals and their alloys, as well as a number of other metals such as Mg and A1. This hydride mechanism is supported by microscopic observations and thermodynamic calculations.
Autism, spectrum or clusters? An EEG coherence study

Autism prevalence continues to grow, yet a universally agreed upon etiology is lacking despite manifold evidence of abnormalities especially in terms of genetics and epigenetics. The authors postulate that the broad definition of an omnibus ‘spectrum disorder’ may inhibit delineation of meaningful clinical correlations. This paper presents evidence that an objectively defined, EEG based brain measure may be helpful in illuminating the autism spectrum versus subgroups (clusters) question. Forty objectively defined EEG coherence factors created in prior studies demonstrated reliable separation of neuro-typical controls from subjects with autism, and reliable separation of subjects with Asperger’s syndrome from all other subjects within the autism spectrum and from neurotypical controls. In the current study, these forty previously defined EEG coherence factors were used prospectively within a large (N = 430) population of subjects with autism in order to determine quantitatively the potential existence of separate clusters within this population. By use of a recently published software package, NbClust, the current investigation determined that the 40 EEG coherence factors reliably identified two distinct clusters within the larger population of subjects with autism. These two clusters demonstrated highly significant differences. Of interest, many more subjects with Asperger’s syndrome fell into one rather than the other cluster. EEG coherence factors provide evidence of two highly significant separate clusters within the subject population with autism. The establishment of a unitary “Autism Spectrum Disorder” does a disservice to patients and clinicians, hinders much needed scientific exploration, and likely leads to less than optimal educational and/or interventional efforts.
Multi-scale Mechanics of Collagen Networks: Biomechanical Basis of Matrix Remodeling in Cancer

The study of fiber network structure and mechanics is key to understanding extracellular matrix (ECM) remodeling in a variety of diseases, including cancer. The tumor microenvironment, which consists of stromal cells and ECM constituents, is altered by tumor cells via biochemical and biomechanical signals in order to support cancer progression. In particular, the tumor ECM displays consistent remodeling phenotypes that have been shown to aid cancer invasion both in vivo and in vitro. In this chapter, we focus on collagen—the most abundant protein in the body that endows the ECM with its structural and mechanical properties. Hydrogels made of reconstituted collagen fibers are commonly used as ECM models to study cell-matrix interactions and cancer cell migration in vitro. Due to their hierarchical organization, collagen networks reveal complex mechanical properties at different length scales. We present a comprehensive review of the experimental and modeling techniques available to investigate the structure and multi-scale mechanics of collagen. We emphasize the nonlinear mechanical properties of collagen from monomers to fiber networks and highlight the different aspects of collagen mechanics investigated using different loading conditions. Improved methods for quantitative imaging and biomechanical modeling are continuously needed to provide a holistic understanding of collagen remodeling in response to cell-generated traction forces and to elucidate the mechanobiological pathways underlying cellular responses to biophysical cues.
The contours of purpose beyond the self in midlife and later life.

AbstractPurpose has been shown in adolescence and young adulthood to be an important component of positive development; however, little is known about its prevalence and function in later life. Sur...
Integrating mindfulness and connection practices into preservice teacher education improves classroom practices

Abstract Teachers vary in their ability to enact effective teaching practices. We randomly assigned 88 early education preservice teachers to standard teacher education or teacher education plus a 9-week mindfulness-based intervention. Using the Classroom Assessment Scoring System (CLASS) as our primary outcome, we assessed effective teaching practices at baseline and at a 6-month follow-up that occurred during full-time student teaching. Mindfulness, negative affect, and well-being were assessed at baseline, post-test, and follow-up. At follow-up, we observed significant GROUP × time interactions on all major CLASS domains: Instructional supports, Emotional supports, and Classroom organization favoring the intervention group (Cohen's d's 0.53–0.65). Daily mindfulness practice was significantly associated with intervention group improvements on Instructional supports (r = .39) and Classroom organization (r = .38). No group differences were observed on negative affect or well-being. Implications for teacher education are discussed.
Exploring Targeted Degradation Strategy for Oncogenic KRASG12C.

Summary KRAS is the most frequently mutated oncogene found in pancreatic, colorectal, and lung cancers. Although it has been challenging to identify targeted therapies for cancers harboring KRAS mutations, KRASG12C can be targeted by small-molecule inhibitors that form covalent bonds with cysteine 12 (C12). Here, we designed a library of C12-directed covalent degrader molecules (PROTACs) and subjected them to a rigorous evaluation process to rapidly identify a lead compound. Our lead degrader successfully engaged CRBN in cells, bound KRASG12C in vitro, induced CRBN/KRASG12C dimerization, and degraded GFP-KRASG12C in reporter cells in a CRBN-dependent manner. However, it failed to degrade endogenous KRASG12C in pancreatic and lung cancer cells. Our data suggest that inability of the lead degrader to effectively poly-ubiquitinate endogenous KRASG12C underlies the lack of activity. We discuss challenges for achieving targeted KRASG12C degradation and proposed several possible solutions which may lead to efficient degradation of endogenous KRASG12C.
Discovery of a cryptic allosteric site in Ebola’s ‘undruggable’ VP35 protein using simulations and experiments

Abstract Many proteins are classified as ‘undruggable,’ especially those that engage in protein-protein and protein-nucleic acid interactions. Discovering ‘cryptic’ pockets that are absent in available structures but open due to protein dynamics could provide new druggable sites. Here, we integrate atomically-detailed simulations and biophysical experiments to search for cryptic pockets in viral protein 35 (VP35) from the highly lethal Ebola virus. VP35 plays multiple essential roles in Ebola’s replication cycle, including binding the viral RNA genome to block a host’s innate immunity. However, VP35 has so far proved undruggable. Using adaptive sampling simulations and allosteric network detection algorithms, we uncover a cryptic pocket that is allosterically coupled to VP35’s key RNA-binding interface. Experimental tests corroborate the predicted pocket and confirm that stabilizing the open form allosterically disrupts RNA binding. These results demonstrate simulations’ power to characterize hidden conformations and dynamics, uncovering cryptic pockets and allostery that present new therapeutic opportunities.
Advanced High-Content-Screening Applications of Clonogenicity in Cancer:

Since its first report in 1956 by Puck and Marcus, the clonogenic assay has not been completely adapted into high-content-screening (HCS) workflows despite the numerous automated systems available. Initially, clonogenic assays were used to observe the effects of radiation on cell survival, particularly with cancer cells. The clonogenic assay has since been well characterized as a measure of cancer stem cell (CSC) stemness, demonstrating that a single CSC can generate clonogenic colonies. CSCs are highly tumorigenic with an unlimited proliferation potential and capacity to generate malignant tumors. Furthermore, CSCs are also known to resist conventional chemotherapy as well as more contemporary targeted therapies alike. Therefore, given the complexity of CSCs and their clinical relevance, new methods must follow to more effectively study and characterize CSC mechanisms that allow them to proliferate and persist, and to develop drugs and other therapies that can more effectively target these populations. Herein, we present a HCS method to quantify the number and size of colonies in 2D and 3D culture models and to distinguish colonies based on fluorescent markers using an Opera Phenix high-content-screening system. In addition, we present a method to scan at low magnification and rescan at a higher magnification to capture in greater detail colonies or even single cells of interest. These methods can be adapted to numerous applications or other imaging systems to study CSC biology using high-content analysis and for high-throughput drug discovery.
Devaluation-sensitive responding to preconditioned cues requires orbitofrontal cortex during initial cue-cue learning

The orbitofrontal cortex (OFC) is necessary for value inference in tests of model-based reasoning. This ability could be accounted for by either representation of value or by representation of broader associative structure. Our lab recently reported correlates of both value and of valueless associative structure in OFC using single-unit recording (Sadacca et al., 2018). This incidental stimulus-stimulus representation was surprising since OFC was thought to be involved only when items of biological significance were driving responses. However, we did not assess whether this activity was necessary for encoding the associative information that would contribute to value inference during probe testing. Here, we used optogenetic OFC inhibition during sensory preconditioning to test this. We found that OFC inhibition during preconditioning impaired value inference during the probe test, demonstrating that the correlates we previously observed are not simply downstream readouts of sensory processing and instead contribute to encoding valueless sensory associative information.
Fuelwood collection as daily practice: a wood charcoal study for the colonial period North Carolina Piedmont

European colonization brought innumerable changes and choices to Native groups across the Southeast. Scholars continue to examine the various ways communities navigated these disruptions. Studying ...
Crowding-induced interactions of ring polymers

Macromolecular crowding and the presence of surfaces can significantly impact the spatial organization of biopolymers. While the importance of crowding-induced depletion interactions in biology has been recognized, much remains to be understood about the effect of crowding on biopolymers such as DNA plasmids. A fundamental problem highlighted by recent experiments is to characterize the impact of crowding on polymer-polymer and polymer-surface interactions. Motivated by the need for quantitative insight, we studied flexible ring polymers in crowded environments using Langevin dynamics simulations. The simulations demonstrated that crowding can lead to compaction of isolated ring polymers and enhanced interactions between two otherwise repulsive polymers. Using umbrella sampling, we determined the potential of mean force (PMF) between two ring polymers as a function of their separation distance at different volume fractions of crowding particles, φ. An effective attraction emerged at φ≈ 0.4, which is similar to the degree of crowding in cells. Analogous simulations showed that crowding can lead to strong adsorption of a ring polymer to a wall, with an effective attraction to the wall emerging at a smaller volume fraction of crowders (φ≈ 0.2). Our results reveal the magnitude of depletion interactions in a biologically-inspired model and highlight how crowding can be used to tune interactions in both cellular and cell-free systems.
Editorial Commentary: Fluoroscopy Is Seldom Required During Knee Posterolateral Reconstruction

Abstract Identifying the structures of the lateral knee is critical during knee posterolateral corner reconstruction. Several methods exist that can help estimate the femoral insertions of these structures on lateral radiographs. However, it is important to recognize the limitations of these methods and that anatomic visualization is often more practical and more accurate. Until percutaneous or more minimally invasive techniques become standardized, intraoperative fluoroscopy is seldom needed or used for posterolateral corner reconstruction, whereas radiographic analysis of lateral knee structures could be of benefit in cases of failed reconstruction to assess tunnel placement.
Microservice Architecture for Cognitive Networks

This paper develops the concept of a cognitive network and describes a microservice based architecture which could be used to implement such a system. Delay tolerant networking (DTN) influences the design of the architecture as well as the networking scenarios that the system attempts to address. A cognitive storage and fragmentation service is developed based on existing artificial intelligence techniques such as Advantage Actor Critic (A2C) and Deep Q-Networks. The system is simulated using OpenAI Gym in a custom developed DTN environment.
Air superiority and battlefield victory

Air superiority enhances military firepower and maneuverability and is critical to battlefield success. We offer the first quantitative test of the relationship between air superiority and battlefi...
The Optimal Denomination of Currency: A Conjecture

Telser (1995) and Sumner (1993) argue that the optimal system of denominations of currency would consist of a sequence of denominations that differed from each other by a factor of three. The fact is that today no currency follows the powers-of-three principle. I argue that existing currency systems are the result of an evolution over time that is subject to historical influences and social factors, especially the counting systems that societies use.
Fatigue and the Need for Recovery among Latino/a Immigrant Cattle Feedyard Workers.

Cattle feedyards are animal feeding operations where beef cattle are finished to market weight on grain. Cattle feeding can be dirty, demanding, and dangerous work. This study sought to assess the ...