cssi/SciSciGPT-SciSciNet huggingface dataset:
The TCF C-clamp DNA binding domain expands the Wnt transcriptome via alternative target recognition

LEF/TCFs direct the final step in Wnt/β-catenin signalling by recruiting β-catenin to genes for activation of transcription. Ancient, non-vertebrate TCFs contain two DNA binding domains, a High Mobility Group box for recognition of the Wnt Response Element (WRE; 5'-CTTTGWWS-3') and the C-clamp domain for recognition of the GC-rich Helper motif (5'-RCCGCC-3'). Two vertebrate TCFs (TCF-1/TCF7 and TCF-4/TCF7L2) use the C-clamp as an alternatively spliced domain to regulate cell-cycle progression, but how the C-clamp influences TCF binding and activity genome-wide is not known. Here, we used a doxycycline inducible system with ChIP-seq to assess how the C-clamp influences human TCF1 binding genome-wide. Metabolic pulse-labeling of nascent RNA with 4'Thiouridine was used with RNA-seq to connect binding to the Wnt transcriptome. We find that the C-clamp enables targeting to a greater number of gene loci for stronger occupancy and transcription regulation. The C-clamp uses Helper sites concurrently with WREs for gene targeting, but it also targets TCF1 to sites that do not have readily identifiable canonical WREs. The coupled ChIP-seq/4'Thiouridine-seq analysis identified new Wnt target genes, including additional regulators of cell proliferation. Thus, C-clamp containing isoforms of TCFs are potent transcriptional regulators with an expanded transcriptome directed by C-clamp-Helper site interactions.
Primary CD20+CD10+CD8+ T-Cell Lymphoma of the Skin With Dual IgH and TCRβ Gene Rearrangement

Most cutaneous T-cell lymphomas are derived from mature postthymic T cells of the CD4 subtype. When other less common profiles are encountered, a diagnostic challenge is posed. Accurate categorization is critical because of the specificity of therapeutic regimens, including biologics. A 65-year-old woman was seen in 2001 because of a thigh mass manifesting an unusual phenotype eventually categorized as a mature postthymic CD8+ T-cell lymphoma with CD10 and weak CD20 expression. Molecular studies revealed T-cell receptor and heavy chain immunoglobulin rearrangement. Her cutaneous disease progressed despite several cycles of chemotherapy and radiation therapy. However, a therapeutic trial with denileukin diftitox resulted in a striking response. The importance of this case lies in the novel phenotype and dual T- and B-cell rearrangements. Rather than representing an aberrant phenotype, this tumor may represent the malignant counterpart of a benign population of weakly CD20+ T cells of the CD8 subset.
Hybrid modeling of non-stationary process variations

Accurate characterization of spatial variation is essential for statistical performance analysis and modeling, post-silicon tuning, and yield analysis. Existing approaches for spatial modeling either assume that: (i) non-stationarities arise due to a smoothly varying trend component or that (ii) the process is stationary within regions associated with a predefined grid. While such assumptions may hold when profiling certain classes of variations, a number of recent modeling studies suggest that non-stationarities arise from both shifts in the process mean as well as fluctuations in the variance of the process. In order to provide a compact model for non-stationary process variations, we introduce a new hybrid spatial modeling framework that models the spatially varying random field as a union of non-overlapping rectangular regions where the process is assumed to be locally-stationary within each region. To estimate the parameters in our hybrid spatial model, we develop a host of techniques to both estimate the change-points in the random field and to find an appropriate partitioning of the chip into disjoint regions where the field is locally-stationary. We verify our models and results on measurements collected from 65nm FPGAs.
Clotting factor changes during the first cycle of oral contraceptive use

Abstract Objectives The risk of venous thromboembolism (VTE) is highest during the initial months of oral contraceptive (OC) use. We sought to evaluate the extent of hemostatic variable changes during the initial OC cycle and if such changes are related to systemic ethinyl estradiol (EE2) exposure. Study design Participants provided multiple blood samples during a 21-day OC cycle (30 mcg EE2; 150 mcg levonorgestrel) and after a single dose following a washout period. Analytes included D-dimer, factor VIII activity, protein C total antigen and the hepatic proteins corticosteroid-binding globulin (CBG) and sex-hormone-binding globulin (SHBG). EE2 pharmacokinetic analyses related to the 24 h after the first OC tablet (OC1) and at steady state (OC21). Results Seventeen women completed the study. D-dimer more than doubled by OC6 (p=.013) and remained elevated at OC21 (p=.012). D-dimer levels within women varied widely from day to day. Factor VIII increased 27% by OC2 (p Conclusions D-dimer increases during the first OC cycle were at least as great as increases seen with longer OC use. These results provide support for the increased VTE risk during initial OC use. The extreme variability in D-dimer levels may be an important component of this risk. Implications This study showed that increases in D-dimer are clearly evident in the first cycle of OC use and may be larger than are seen after a longer duration of use and thus provide biological support for the increased VTE risk during initial OC use found in epidemiological studies.
Effects of the Fed's Liquidity Programs and Quantitative Easing on Interest Rates, 2007-2010

This paper examines the effectiveness of several of the Fed’s unconventional monetary policies from 2007 to 2010 by comparing interest rate spreads with forecast estimates based on either the pure expectations hypothesis or the preferred habitat theory. We find that the effectiveness of these policies are similar to other studies in that the liquidity provided by the Fed did not have immediate or significant effects on interest rate spreads. These results are consistent with several studies that point toward counter party risk, not lack of liquidity, as the problem in financial markets at the time.
Buried or brined? Eurypterids and evaporites in the Silurian Appalachian basin

Abstract Eurypterid-bearing deposits from the late Silurian Appalachian basin are often interpreted as having been deposited under hypersaline conditions. These interpretations are based on the close association of abundant eurypterid remains with evaporite deposits and structures such as salt hoppers in the Salina and Bertie groups. To determine whether this association reflects life habitat, or is the result of taphonomic or diagenetic processes, the co-occurrence of eurypterids and salt hoppers in the upper Silurian Appalachian basin was examined at several stratigraphic scales. A survey of eurypterid remains from the prolific Ellicott Creek Breccia Member of the Fiddler's Green Formation (Bertie Group) found that 2% of the 479 specimens surveyed are crosscut by salt hoppers or incipient halite structures. In a regional survey, displacive salt hoppers occurred in the same bed as eurypterid remains in 37% (19:51) of all eurypterid-bearing units. In these units, salt hoppers were typically the only structures found intimately associated with eurypterids, sometimes crosscutting them. The disruptive nature of the hoppers in the Ellicott Creek Breccia, for example, suggests that they formed within the sediment rather than at the air-water interface, and that organic remains might have acted as nucleation points for developing halite crystals. To explain these associations, we present a depositional model in which displacive salt hoppers formed within NaCl-saturated groundwater as a result of surface evaporation in the vadose zone during regressive phases, and only after eurypterid remains were buried. In this scenario, the intimate association of eurypterids and salt hoppers in these deposits reflects early-stage diagenetic overprinting rather than conditions during life. Our model largely refutes the hypothesis that eurypterids were halotolerant organisms based on their co-occurrence with salt hoppers. We conclude that eurypterids preserved in upper Silurian carbonate ramp deposits were primarily denizens of more normal marine or hyposaline subtidal settings.
On chromatic aberration in the cornea

The effects of ocular disturbances on the chromatic aberration produced at the cornea are studied. The variation of refractive index with the wavelength of incident light arc determined for the rat cornea and aqueous humor from enucleated eyes by interference microscopy and refractometry using a monochromator light source. By computing the separation of a blue (475 nm) and a red (650 nm) fay of light simultaneously projected at either corneal surface, the effect of distorting the normal index profile is examined. Hypothetical refractive index profiles are developed for the cornea ami aqueous humor that makl; the cornea totally achromatic.
Can Open Contracts Be Profitable

This paper provides a theoretical framework in support of recent empirical findings where the use of open contracts in the form of pay-what-you-like pricing have been found to be viable compared to a fixed price. Our analysis shows that, in spite of the option to free ride, not all consumers free ride and some make positive payments. We show that for a linear demand, low marginal cost and within a specific range of demand elasticity, pay-what-you-like pricing can generate higher profits for the seller than the standard uniform pricing. The range of elasticity gets larger when no one free rides.
Lipid Control and Beyond: Current and Future Indications for Statin Therapy in Stroke.

Statins are a group of lipid-lowering agents that are competitive inhibitors of the enzyme 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase that have been used to reduce cholesterol levels and prevent cardiovascular events. Statins have been also shown to reduce the risk of stroke. In this review, we cover the role of statins in cerebrovascular disease through lipid-lowering mechanisms and other “pleiotropic” effects that provide protection against cerebrovascular events and potentially contribute to improve functional outcome after stroke.
Drugs for the prevention and treatment of acute renal failure.

SUMMARY Certain preventive measures might decrease the incidence or severity of acute renal failure, including vigorous hydration before the administration of radiocontrast agents, and use of mannitol, loop diuretics, dopamine, and calcium antagonists. However, the pharmacologic agents should be used judiciously, and clinicians should not accept blindly that they are indicated in all clinical situations involving acute renal failure until further studies are available.
Experimental studies on the second harmonic generation of broadband high-peak-power laser radiation at 527 nm using a quadrature crystal array

Ultrauniform illumination of laser fusion targets using the induced spatial incoherence (ISI) technique requires laser radiation with a short coherence time (τ ≤ 2 ps) and, therefore, a broad bandwidth (Δν > 15 cm-1).1
Using social determinants of health to link health workforce diversity, care quality and access, and health disparities to achieve health equity in nursing.

It is widely accepted that diversifying the nation’s health-care workforce is a necessary strategy to increase access to quality health care for all populations, reduce health disparities, and achieve health equity. In this article, we present a conceptual model that utilizes the social determinants of health framework to link nursing workforce diversity and care quality and access to two critical population health indicators—health disparities and health equity. Our proposed model suggests that a diverse nursing workforce can provide increased access to quality health care and health resources for all populations, and is a necessary precursor to reduce health disparities and achieve health equity. With this conceptual model as a foundation, we aim to stimulate the conceptual and analytical work—both within and outside the nursing field—that is necessary to answer these important but largely unanswered questions.
Anger and the Law

In the United States over 20,000 people are the victims of willful (nonnegligent) homicide each year. About three-quarters of these homicides are eventually “solved” with the arrest of one or more persons. The legal treatment of these defendants provides a great amount of information on the social norms related to anger and aggression.
Coverage and connectivity in three dimensional wireless sensor networks

Terrestrial wireless sensor networks are generally designed based on the assumption that sensor nodes are deployed on a two-dimensional (2D) plane. This assumption is usually invalid in an underwater sensor network, where sensor nodes may be deployed at various depths, thus creating a three-dimensional (3D) network. Other important applications of 3D networks also include future space and atmospheric networks. Consequently, new research challenges now exist in the field of wireless sensor networks, as several coverage and connectivity issues unique to 3D networks require resolution. For example, node placement strategies need to deploy the minimum number of sensor nodes and, at the same time, ensure that all points inside the network are within the sensing range of at least one sensor. All sensor nodes also need to communicate with each other, possibly over a multi-hop path. Establishment of this type of network will depend on the ratio of the communication range and the sensing range of each sensor. In this study, we use deterministic homogeneous sphere based communication and sensing range model to solve this issue, by placing a node at the center of each virtual cell created by truncated octahedron based tessellation of 3D space. This works well when the ratio of communication range and sensing range is greater than 1.7889. On the other hand, for smaller values of this ratio, the solution depends on the degree of communication redundancy needed by the network. We provide solutions for both limited and full communication redundancy requirements. We also investigate coverage and connectivity issues in 3D networks where nodes were randomly deployed. Since node location can be random, redundant nodes have to be deployed to achieve 100% sensing coverage. However, at any particular time, not all nodes are needed to achieve full sensing coverage. Consequently, a subset of sensor nodes can be dynamically chosen to remain active at a given time to achieve sensing coverage based on their location at that time. One approach to achieve that goal in a distributed and scalable way is to partition the 3D network space into virtual regions or cells, and to keep one node active in each cell. Following this approach, we achieve a fully distributed and highly scalable solution that minimizes the number of active nodes that use cells created by truncated octahedral tessellation of 3D space. By adjusting the radius of each cell, this scheme can be used to achieve k-coverage where a point inside a network has to be within the sensing of k different sensor nodes with high probability. We analyze the performance of this scheme and found that performance improves significantly where value of k is larger than 1.
Female Reproductive Parameters in Wild Geladas ( Theropithecus gelada )

Accurate data on reproductive parameters are essential for evaluating the adaptive and mechanistic bases of variation within and between species. Here, we combine fecal ovarian hormone analysis with measurements of sex skin swellings and reproductive behavior to describe female reproduction in geladas living in the Simien Mountains National Park, Ethiopia. We collected 10 years of reproductive data from 197 females across 36 units, with hormone data from a subset of these females (60 females from 16 units). First, we use these data to calculate age at maturation, age at first birth, interbirth interval, menstrual cycle length, gestation length, and duration of postpartum amenorrhea. Second, we present composite profiles of ovarian hormones, i.e., estrogens, progestogens, and sex skin measures across reproductive stages. Third, we examine whether ovarian hormones, sex skin phenotypes, and/or reproductive behaviors reliably reflect fertility or pregnancy in female geladas. The reproductive parameters calculated from our data were similar to those in previous studies on geladas and within the range of those for closely-related baboon species. We were able to reliably identify fertility and pregnancy using fecal estrogens only. The tumescent sex skin phenotypes and reproductive behaviors associated with fertility were also observed across all reproductive stages. We suggest that their presence outside of fertility may be a by-product of the flexibility needed for one or more female counterstrategies to infanticide.
Experimental study of the effects of CO2 concentration and pressure at elevated temperature on the mechanical integrity of oil and gas well cement

Abstract Oil and gas well cement reacts with carbonated brine thereby resulting in mechanical degradation after the cement is placed behind the casing. CO 2 concentration and pressure influence the rate of the reaction. This study examines the effect of these downhole parameters on the mechanical degradation of well cement. Classes G and H cements were aged in CO 2 -saturated brine. CO 2 concentration (i.e. partial pressure) was varied from 10% to 100%, total test pressure was varied from 21 MPa to 62 MPa, and temperature was kept constant at 107 °C. Compressive strength and transport properties of the specimens were measured before and after exposure to quantify the effect of CO 2 attack on cement integrity. In the analysis, these measurements are augmented by results of microstructure and mineralogy studies performed using Fourier transform infrared, X-ray diffraction, energy-dispersive X-ray, and scanning electron microscopy. Results show that the concentration of CO 2 and test pressure affect the mechanical behavior of well cement after exposure. The major governing mechanisms are carbonation reaction between cement hydrates and dissolved CO 2 , and the subsequent leaching of the product of carbonation. Although the specimens show significant physical and chemical degradation, the mechanical strength is improved. The mechanical performance is generally consistent with the evolution of transport properties and FTIR, SEM, EDX, and XRD mineralogy. Comparison of the performance of standard formulations of classes G and H cement shows that the strength of Class H cement is improved than the strength of Class G cement as CO 2 concentration and pressure increase. Investigations of the effect of CO 2 on the mechanical performance of well cement under extreme downhole conditions is limited. This study expands the understanding on how hostile and severe downhole conditions influence the degradation of well cement.
Comparative Nucleotide-Dependent Interactome Analysis Reveals Shared and Differential Properties of KRas4a and KRas4b.

The KRAS gene encodes two isoforms, KRas4a and KRas4b. Differences in the signaling functions of the two KRas proteins are poorly understood. Here we report the comparative and nucleotide-dependent interactomes of KRas4a and KRas4b. Many previously unknown interacting proteins were identified, with some interacting with both isoforms while others prefer only one. For example, v-ATPase a2 and eIF2Bδ interact with only KRas4b. Consistent with the v-ATPase interaction, KRas4b has a significant lysosomal localization. Comparing WT and constitutively active G12D mutant KRas, we examined differences in the effector proteins of the KRas4a and KRas4b. Interestingly, KRas4a binds RAF1 stronger than KRas4b. Correspondingly, KRas4a can better promote ERK phosphorylation and anchorage-independent growth than KRas4b. The interactome data represent a useful resource to understand the differences between KRas4a and KRas4b and to discover new function or regulation for them. A similar proteomic approach would be useful f...
Ion Solvation and Dynamics at Solid Electrolyte Interphases: A Long Way from Bulk?

Rechargeable lithium-ion battery technology has revolutionized energy storage for small electronic devices. However, a deeper understanding is required of the interfaces present in such devices for this technology to continue to advance. While many insights into the solid electrolyte interphase (SEI) for lithium-ion systems have been collected from decades of study, many questions also remain. In particular, this work is interested in exploring SEI composition and its impact on electrolyte structure and dynamics. By using a previously tested classical molecular dynamics approach, the impact of the crystallinity of the SEI interface as well as its content of organic and inorganic species is assessed. It is found that the presence of an amorphous SEI results in the accumulation of ions at the interface, ordering of solvent molecules, and a slowing down of solvation dynamics. These behaviors are intensified when crystal surfaces from LiF and Li2CO3 are considered. In addition to these general observations, t...
Transitioning from On-Campus to Online in a Master of Science Nursing Program: A Comparative Study of Academic Success.

This comparative study examined the academic success rates of online graduate nursing students by comparing final grades to the on-campus cohort of graduate nursing students prior to the program tr...
Characterization of children hospitalized with traumatic brain injuries after building falls

Unintentional falls cause a substantial proportion of pediatric traumatic brain injury (TBI), with building falls carrying particularly high risk for morbidity and mortality. The cohort of children sustaining building fall-related TBI has not been well-examined. We sought to characterize children hospitalized with building fall-related TBIs and evaluate if specific factors distinguished these children from children hospitalized with TBI due to other fall mechanisms. We secondarily assessed if TBI severity among children injured due to a building fall varied between children from urban versus non-urban areas. This was a secondary analysis of the Pediatric Health Information System (PHIS), an administrative database from pediatric hospitals. We identified children < 15 years old, hospitalized between 2009 and 2014, with an associated TBI-related diagnosis due to a fall as determined by International Classification of Diseases, Clinical Modification, Ninth revision (ICD9-CM) diagnosis codes. Urban versus non-urban status was determined using PHIS-assigned Rural-Urban Commuting Area codes. Injury severity (i.e. Injury Severity Score (ISS) and head Abbreviated Injury Scale (AIS) score) were calculated. Head AIS scores were dichotomized into minor/moderate (1–2) and serious/severe (3–6) for analysis. Frequencies, descriptive statistics, Chi-square analysis, and Mann-Whitney U analysis characterized populations and determined group differences. The study cohort included 23,813 children, of whom 933 (3.9%) fell from buildings. Within the building fall cohort, 707 (75.8%) resided in urban areas, 619 (66.3%) were male, 513 (55.0%) were white, and 528 (56.6%) had government insurance; the mean age was 3.8 years (SD 2.9). There was a larger proportion of children with serious/severe TBI among those injured from building falls relative to other falls (63.4% vs 53.9%, p < 0.01). Among children injured from building falls, those from non-urban areas were more likely to sustain a serious/severe TBI relative to urban children (58.9% vs 53.6%, p < 0.01). Children hospitalized following buildings falls with TBI sustained more severe injuries relative to other fall types. Although a majority of children hospitalized with building fall related-TBIs were from urban areas, those from non-urban areas frequently sustained serious head injuries. Future research should target expanding prevention efforts to include non-urban areas.
Forecasting Gang Homicides with Multi-level Multi-task Learning

Gang-related homicides account for a significant proportion of criminal activity across the world, especially in countries of Latin America. They often arise from territorial fights and, distinct from other types of homicides, are characterized by area-specific risk indicators. Current crime modeling and prediction research has largely ignored gang-related homicides owing to: (i) latent dependencies between gangs and spatial areas, (ii) area-specific crime patterns, and (iii) insufficiency of spatially fine-grained predictive signals. To address these challenges, we propose a novel context-aware multi-task multi-level learning framework to jointly learn area-specific crime prediction models and the potential operating territories of gangs. Specifically, to sufficiently learn the finer-grained area-specific tasks, the abundant knowledge from coarse-grained tasks is exploited through multi-task learning. Experimental results using online news articles from Bogota, Colombia demonstrate the effectiveness of our proposed method.
Disability and corporeal (im)mobility: how interstate variation in Medicaid impacts the cross-state plans and pursuits of personal care attendant service users

AbstractPurpose: This paper addresses how Medicaid personal care attendant (PCA) service users with physical disabilities experience barriers to cross-state movement arising from the interstate var...
Transient intermediate species in the oxidation of hydrazine.

Short lived nitrogen-hydrogen species, radical or molecular, may play a significant role in the mechanism and kinetics of chemical processes leading to the reduction of nitrogen to ammonia, in the action of nitrogen-fixing bacteria and in the chemistry of the enzyme nitrogenase. Such intermediates are common to the mechanism of hydrazine oxidation, a more convenient system for study under ambient conditions.
Privacy and regulation in a digital age

Owing to the pervasiveness of personal data collection, transmission, storage, and analysis, privacy has emerged as a central public policy concern in recent years. The chapter explains the repercussions of the digital revolution for personal privacy, and situates the current debate in proper historical context. It shows that privacy expectations vary with the social context, and derives a framework through which to understand geographic, sectoral, and temporal variation of privacy protection. Privacy regimes in Europe and the United States are not set apart by profound cultural differences, as is often argued, but instead rely on distinct sets of enforcement mechanisms. After reviewing the respective role of the public sector, the private sector, and technology in enforcing privacy standards, the chapter concludes with a look ahead to new challenges.
From Computing to Computational Thinking

Computational Thinking (CT) involves fundamental concepts and reasoning, distilled from computer science and other computational sciences, which become powerful general mental tools for solving problems, increasing efficiency, reducing complexity, designing procedures, or interacting with humans and machines. An easy-to-understand guidebook, From Computing to Computational Thinking gives you the tools for understanding and using CT. It does not assume experience or knowledge of programming or of a programming language, but explains concepts and methods for CT with clarity and depth. Successful applications in diverse disciplines have shown the power of CT in problem solving. The book uses puzzles, games, and everyday examples as starting points for discussion and for connecting abstract thinking patterns to real-life situations. It provides an interesting and thought-provoking way to gain general knowledge about modern computing and the concepts and thinking processes underlying modern digital technologies.
Three-dimensional micromechanical pavement model development for the study of block cracking

Abstract Block cracking in asphalt pavements is a primary form of surface cracking but has been the subject of very few scientific investigations. Although this deterioration mode is covered in many pavement evaluation guides and condition rating systems, the underlying mechanisms of block cracking have not been fully investigated. Therefore, understanding the mechanisms behind block cracking and tailoring preventive solutions merits rigorous investigation. In this paper, a 3D discrete element viscoelastic and inhomogeneous microstructure-based pavement model subjected to thermal straining was introduced. A typical PG 64-22, dense-graded Illinois asphalt surface mixture was adopted as the baseline material because it typically experiences block cracking later in its service life. The mechanisms of block cracking patterns were investigated as a function of the dimension of pavement segments, relaxation capacity and aging state of materials, including spatial gradients, cooling rate and pre-existing crack presence using the aforementioned discrete element models. Discrete element simulations showed that initial block cracking primarily occurred in the upper one-to-two centimeters of the surface, which agreed with field observations. In addition, it was found that block cracks formed at a warmer temperature than that associated with the onset of thermal cracking. This implied that current test criteria for thermal cracking mitigation may need to be updated or supplemented in order to control block cracking. Finally, the techniques presented herein can be extended to identify candidates for preventive maintenance, and in developing tailored maintenance techniques.
3-(3-Hydroxyphenyl)-Propionic Acid (PPA) Suppresses Osteoblastic Cell Senescence to Promote Bone Accretion in Mice.

Phenolic acids (PAs) are metabolites derived from polyphenolic compounds found in fruits and vegetables resulting from the actions of gut bacteria. Previously, we reported that the levels of seven individual PAs were found to be at least 10 times higher in the serum of rats fed a blueberry (BB)-containing diet compared to those fed a control diet. We have characterized the effects of one such BB-associated serum PA, 3-(3-hydroxyphenyl)-propionic acid (PPA), on senescence signaling and promotion of mesenchymal stem cell differentiation toward osteoblasts, while suppressing adipogenesis in the stem cells. To better understand the mechanistic actions of PPA on bone formation in vivo, we administered four doses of PPA (0.1, 0.5, 1, and 5 mg/kg/day; daily i.p.) to 1-month-old female C57BL6/J mice for 30 days. We did not observe significant effects of PPA on cortical bone; however, there were significantly higher bone volume and trabecular thickness and increased osteoblastic cell number, but decreased osteoclastic cell number in PPA-treated groups compared to controls. These morphological and cellular outcomes of bone were reflected in changes of bone formation markers in serum and bone marrow plasma. PPA treatment reduced senescence signaling as evaluated by senescence-associated β-galactosidase activity, PPARγ, p53, and p21 expression in bone. In conclusion, PPA is capable of altering the mesenchymal stem cell differentiation program and bone cell senescence. This raises the possibility that BB-rich diets promote bone growth through increasing systemic PAs, a question that merits additional investigation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model

Somatic alterations in cancer genes are being detected in normal and premalignant tissue, thus placing greater emphasis on gene-environment interactions that enable disease phenotypes. By combining early genetic alterations with disease-relevant exposures, we developed an integrative mouse model to study gastric premalignancy. Deletion of Trp53 in gastric cells confers a selective advantage and promotes the development of dysplasia in the setting of dietary carcinogens. Organoid derivation from dysplastic lesions facilitated genomic, transcriptional and functional evaluation of gastric premalignancy. Cell cycle regulators, most notably Cdkn2a, were upregulated by p53 inactivation in gastric premalignancy, serving as a barrier to disease progression. Co-deletion of Cdkn2a and Trp53 in dysplastic gastric organoids promoted cancer phenotypes but also induced replication stress, exposing a susceptibility to DNA damage response inhibitors. These findings demonstrate the utility of mouse models that integrate genomic alterations with relevant exposures and highlight the importance of gene-environment interactions in shaping the premalignant state.
From novice to expert: a qualitative study of implementation facilitation skills

It is widely reported that facilitation can aid implementation of evidence-based practices. Although scholars agree that facilitators need a diverse range of skills, only a few retrospective studies have identified some of these. During the test of a facilitation strategy within the context of a VA initiative to implement evidence-based care delivery models, we documented the skills an expert external facilitator transferred to two initially novice internal regional facilitators. Ours is the first study to explore facilitation skills as they are being applied and transferred. Facilitators applied the strategy at eight primary care clinics that lacked implementation capacity in two VA networks. We conducted monthly debriefing interviews over a 30-month period and documented these in detailed notes. External facilitator interviews focused specifically on training and mentoring internal facilitators and the skills that she transferred. We also conducted, recorded, and transcribed two qualitative interviews with each facilitator and queried them about training content and process. We conducted a content analysis of the data, using deductive and inductive methods, to identify skills the external facilitator helped internal facilitators learn. We also explored the complexity of facilitation skills and grouped them into overarching skillsets. The external facilitator helped internal facilitators learn 22 complex skills; with few exceptions, these skills were not unique but overlapped with one another. We clustered 21 of these into 5 groups of overarching skillsets: (1) building relationships and creating a supportive environment, (2) changing the system of care and the structure and processes that support it, (3) transferring knowledge and skills and creating infrastructure support for ongoing learning, (4) planning and leading change efforts, and (5) assessing people, processes, and outcomes and creating infrastructure for program monitoring. This study documented a broad range of implementation facilitation skills that are complex and overlapping. Findings suggest that studies and initiatives planning or applying facilitation as an implementation strategy should ensure that facilitators have or have the opportunity to learn the skills they need. Because facilitation skills are complex, the use of didactic methods alone may not be sufficient for transferring skills; future work should explore other methods and techniques.
The Milan system for reporting salivary gland cytopathology: A comprehensive review of the literature

Background The Milan system for Reporting Salivary Gland Cytopathology (MSRSGC) was published in 2018. Since then, many authors have published their institutional experience by retrospectively assigning salivary gland fine-needle aspiration cases to each of the MSRSGC categories and calculated their risk of malignancy (ROM) accordingly. Methods We reviewed all published articles available online in English that used the MSRSGC since or near its publication. We calculated the risk of neoplasm and ROM for each diagnostic category. In addition, the false-negative and false-positive rates from all studies were examined. Results Thirty-seven articles were identified in the English literature; 2 were published in 2017, 14 in 2018, 18 in 2019, and 3 in 2020. The total number of cases was 16 394, and 8 468 had surgical follow-up. The mean ROM was 16.9% for category I, 10.5% for category II, 39.3% for category III, 2.9% for category IVa, 39.4% for category IVb, 84.2% for category V, and 97.5% for category VI. The mean false-negative rate for MSRSGC categories II and IVa was 4.5%. Similarly, the mean false-positive rate for MSRSGC categories V and VI was 5.1%. Conclusion A tiered classification scheme of MSRSGC is helpful in effectively guiding clinical management of patients with salivary gland lesions. The reported mean ROM for each category in most studies is within the recommended range published by the MSRSGC.
Diffusion and radiation in magnetized collisionless plasmas with small-scale Whistler turbulence

Magnetized high-energy-density plasmas can often have strong electromagnetic fluctuations whose correlation scale is smaller than the electron Larmor radius. Radiation from the electrons in such plasmas – which markedly differs from both synchrotron and cyclotron radiation – is tightly related to their energy and pitch-angle diffusion. In this paper, we present a comprehensive theoretical and numerical study of particle transport in cold, ‘small-scale’ Whistler-mode turbulence and its relation to the spectra of radiation simultaneously produced by these particles. We emphasize that this relation is a superb diagnostic tool of laboratory, astrophysical, interplanetary and solar plasmas with a mean magnetic field and strong small-scale turbulence.
Conceiving Modern Sikhism: Religious Instruction, Scientism, and Comparative Religion at Khalsa College

Conceiving Modern Sikhism addresses processes of institutionalisation, standardisation, and textualisation that structured the evolution of modern Sikh tradition in colonial India. It analyses the role of Khalsa College, Amritsar, in the establishment of a distinct interpretation of Sikhism and Sikh history that is still dominant today, shaped by the scholarly work of the college’s teaching staff but also through the institution’s impact on the everyday religious life of its students. Furthermore, the chapter considers these processes as part of a broader development in global religious history. The conception of ‘religion’ as stressed among a modernist Sikh reform and education movement attempted to formulate a Sikh ‘theology’ that stood in dialogue with three elements constitutive of the modern concept of ‘religion’ as perceived through its colonial and transnational negotiation: comparatism, universalism, and scientism.
Multi-Class Detection of Laparoscopic Instruments for the Intelligent Box-Trainer System Using Faster R-CNN Architecture

Laparoscopic Surgical Box-Trainer devices have been used by surgery residents to learn specific skills not traditionally taught to surgeons. Assessment of performance, however, is crude, frequently focusing on speed alone or subjective observations. For a better, objective assessment, the residents' efficiency should be recorded and have the process be tracked and have a system in place to provide consistent automated assessment and analysis. In this paper, we propose a novel framework for the detection and recognition of multi-class laparoscopic instruments for our Intelligent Box-Trainer System. This framework is based upon the Faster R-CNN architecture and RESNet-50 for an open-source module with our custom dataset (AR-Set). Despite a relatively limited number of training examples, experimental results have proved that our approach is effective for locating regions of interest and detecting multi-class instruments. This research is a cooperation between the Department of Electrical and Computer Engineering and the Department of Surgery of the Homer Stryker M.D. School of Medicine, at WMU.
Alzheimer's Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways

Evidence suggests interplay among the three major risk factors for Alzheimer’s disease (AD): age, APOE genotype, and sex. Here, we present comprehensive datasets and analyses of brain transcriptomes and blood metabolomes from human APOE2, APOE3 and APOE4-targeted replacement mice across young, middle, and old ages with both sexes. We found that age had the greatest impact on brain transcriptomes highlighted by an immune module led by Trem2 and Tyrobp, whereas APOE4 was associated with upregulation of multiple Serpina3 genes. Importantly, these networks and gene expression changes were mostly conserved in human brains. Finally, we observed a significant interaction between age, APOE genotype, and sex on unfolded protein response pathway. In the periphery, APOE2 drove distinct blood metabolome profile highlighted by the upregulation of lipid metabolites. Our work identifies unique and interactive molecular pathways underlying AD risk factors providing valuable resources for discovery and validation research in model systems and humans.
Consumers Engagement Toward Food Brands – The Case of Dairy Products

Research background: As food markets continue to develop the role and position of food consumers evolve as well. Food producers redefine their market strategies and focus on creating loyalty, building good contacts and consumers’ engagement towards brands.
Algal-based wastewater treatment: Evaluation of nitrogenous byproducts in chlorinated effluent

Abstract Water reuse is gaining traction as a means of balancing the water portfolio in the face of rapidly growing demand for potable water in water-stressed regions. While current guidelines for restricted reuse require final disinfection of the reclaimed water and residual free chlorine, the common practice of disinfection by chlorine can potentially form carcinogenic byproducts depending on certain precursors and the disinfectant demand. This study evaluated the formation of nitrogenous byproducts of chlorination in an algal-based wastewater treatment system (AWTS) capable of yielding discharge-ready effluent with non-detectable levels of pathogenic bacteria. Impacts of chlorination of the AWTS effluent were evaluated here in terms of selected nitrosamines to determine if a comprehensive DBP assessment would be justifiable. Optimal chlorine demand of the AWTS effluent to satisfy the reuse guidelines was found as 13.0 mg Cl2/L at pH of 6. Under this condition, none of the seven nitrosamines analyzed in this study were >50 ng/L. This finding is corroborated through non-targeted screening by liquid chromatography/high resolution mass spectrometry of the unchlorinated AWTS effluent revealing negligible levels of amines, which have been reported as key precursors of nitrosamines. Results of this study indicate that the AWTS holds promise in delivering safe reuse-quality effluent, warranting further comprehensive assessments.
Pathways by Which Food Insecurity Is Associated With Atherosclerotic Cardiovascular Disease Risk.

Background Food insecurity (FI) has been associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk; however, the pathways by which FI leads to worse cardiovascular health are...
ON THE MECHANICAL RESPONSE OF A PRESSURIZED FUNCTIONALLY-GRADED CYLINDER

A pressurized functionally-graded cylinder is considered made of the material whose elastic moduli vary with the radial distance according to the power-law relation. Some peculiar features of the mechanical response are noted for an incompressible functionally-graded material with the power of radial inhomogeneity equal to two. In particular, it is shown that the maximum shear stress is constant throughout the cylinder, while the displacement changes proportional to 1/r along the radial distance. No displacement takes place at all under equal pressures applied at both boundaries.
Toll-Like Receptor Ligands Modulate Dendritic Cells to Augment Cytomegalovirus- and HIV-1-Specific T Cell Responses

Optimal Ag targeting and activation of APCs, especially dendritic cells (DCs), are important in vaccine development. In this study, we report the effects of different Toll-like receptor (TLR)-binding compounds to enhance immune responses induced by human APCs, including CD123(+) plasmacytoid DCs (PDCs), CD11c(+) myeloid DCs (MDCs), monocytes, and B cells. PDCs, which express TLR7 and TLR9, responded to imidazoquinolines (imiquimod and R-848) and to CpG oligodeoxynucleotides stimulation, resulting in enhancement in expression of costimulatory molecules and induction of IFN-alpha and IL-12p70. In contrast, MDCs, which express TLR3, TLR4, and TLR7, responded to poly(I:C), LPS, and imidazoquinolines with phenotypic maturation and high production of IL-12 p70 without producing detectable IFN-alpha. Optimally TLR ligand-stimulated PDCs or MDCs exposed to CMV or HIV-1 Ags enhanced autologous CMV- and HIV-1-specific memory T cell responses as measured by effector cytokine production compared with TLR ligand-activated monocytes and B cells or unstimulated PDCs and MDCs. Together, these data show that targeting specific DC subsets using TLR ligands can enhance their ability to activate virus-specific T cells, providing information for the rational design of TLR ligands as adjuvants for vaccines or immune modulating therapy.
R-Matrix Analysis of 232Th Neutron Transmissions and Capture Cross Sections in the Energy Range Thermal to 4 keV

Neutron resonance parameters of 232Th were obtained from the Reich-Moore SAMMY analysis of high-resolution neutron transmission measurements performed at the Oak Ridge Electron Linear Accelerator (ORELA) by Olsen in 1981, along with the high-resolution neutron capture measurements performed in 2005 at the Geel Linear Accelerator (GELINA, Belgium) by Schillebeeckx and at the n-TOF facility (CERN, Switzerland) by Aerts. The ORELA data were analyzed previously by Olsen with the Breit-Wigner multilevel code SIOB, and the results were used in the ENDF/B-VI evaluation. In the new analysis of the Olsen neutron transmissions by the modern computer code SAMMY, better accuracy is obtained for the resonance parameters by including in the experimental data base the recent experimental neutron capture data. The experimental data base and the method of analysis are described in the report. The neutron transmissions and the capture cross sections calculated with the resonance parameters are compared to the experimental values. A description is given of the statistical properties of the resonance parameters. The new evaluation results in a decrease in the capture resonance integral and improves the prediction of integral thermal benchmarks.
Strength correlation of power chips by finite element method

The ultimate tensile strength of silicon chips can be measured by the three-point bending test. During the test, the breaking load is recorded. The tensile strength of silicon chips can be calculated through the formula between stress and breaking load derived from the beam bending theory. The tests are characterized at die level, which makes it convenient to prepare for the test specimen. However, the dimension of silicon chips may not fall in the range of required geometry, and testing for bigger chip size may have more uncertainty. In this case, the calculated data may over-estimate or under-estimate the strength values. FE modeling technique is used to do correlation with the test data. The 3-D FE model of the silicon chip is created to simulate the three-point bending test. The breaking force taken from the experimental results is applied as the loading condition. The max tensile stress from the simulation results is taken as the tensile strength of the silicon chips. The study of several cases of power chips with different size and thickness is conducted by the experimental three-point bending tests and FE modeling. It is found that in some cases the test results with beam theory and FEA simulation results agree quite well, but in other cases, there is some gap, so correlation of the testing data by the beam theory and by FE modeling is necessary.