cssi/SciSciGPT-SciSciNet huggingface dataset:
Ibrutinib Dose Adherence and Therapeutic Efficacy in Non-Hodgkin Lymphoma: A Single-Center Experience

Abstract Background As oral targeted agents, such as ibrutinib, become more widely used, understanding the impact of suboptimal dosing on overall survival (OS) and progression-free survival (PFS) outside of clinical trials is imperative. Patients and Methods Data on ibrutinib discontinuation, dose reductions, and treatment interruptions were collected on 170 non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL; n = 115, 64%) patients treated with ibrutinib at a single institution. Ibrutinib dose adherence was calculated as the proportion of days in which ibrutinib was administered out of the total number of days ibrutinib was prescribed in the first 8 weeks. Kaplan-Meier curves and log-rank tests were used to compare conditional survival outcomes beyond 8 weeks in patients with ≥ 80% dose adherence and patients with Results Median OS among those who discontinued therapy for progression was poor (n = 51, 1.7 months; 95% confidence interval, 0.3-3.7). Lower dose adherence ( 1 week had worse PFS (P = .047) but not OS (P = .577). Conclusion In this observational study, non-Hodgkin lymphoma and CLL patients experienced poor outcomes after discontinuing ibrutinib for disease progression. The inferior survival related to suboptimal dose adherence of ibrutinib was predominantly due to early dose reduction. These data confirm poor survival in CLL and lymphoma patients alike after ibrutinib discontinuation, and support recommendations for full dose at treatment initiation.
Diversity and Inclusion at East Tennessee State University’s Archives of Appalachia

As East Tennessee State University’s (ETSU) Archives of Appalachia approaches its fortieth anniversary, it aims to renew itself as an archive of the twenty-first century through development of a new strategic plan and mission. Diversity and inclusion are a committed part of ETSU’s mission to regional stewardship and the Archives seeks to become a more diversified cultural heritage repository and culturally competent workplace. This article applies a top-down approach to understanding diversity- and inclusion-related responses at both the university and department levels to assess current and potential diversity and inclusion initiatives. A selected analysis using the Strategic Diversity Manifesto framework juxtaposes the Archives’ diversity and inclusion responses for its local/regional communities and LGBTQ communities. Consequently, the article reports on goals and actions the Archives can take to become a more engaged member of its diverse communities.
Research on Electromechanical-electromagnetic Hybrid Simulation Algorithm for Large Scale Power System based on Boundary Nodes Grouping and Decoupling

An electromechanical-electromagnetic hybrid simulation algorithm based on boundary nodes grouping and decoupling is proposed in this paper. The UHV $AC/DC$ backbone network is described as electromagnetic transient models and the others are described as electromechanical transient models and power grids at low voltage side are decoupled at their boundary. A new partitioning method of backbone network based on heuristic rules is proposed to support electromagnetic transient parallel computing and a hybrid parallel simulation algorithm based on subnet groups is designed. The theoretical analysis and derivation of the algorithm shows that the algorithm can improve the efficiency of hybrid simulation with a large number of boundary nodes.
Distress tolerance in romantic relationships: A daily diary exploration with methodological considerations

Despite growing research interest in distress tolerance (DT), studies have routinely neglected the role that DT plays in close, interpersonal relationships and how DT fluctuates from 1 day to the next. In addition, an understanding of DT hinges on the presence of distress, yet existing studies have failed to include distress in conceptual and analytical models. To address these gaps, we conducted a 1-week, daily diary study with 65 heterosexual couples (n = 130) exploring the effects of DT on basic psychological needs satisfaction in romantic relationships—accounting for distress as a covariate and moderator. Findings indicated that DT was more variable over time than previously suggested. DT was also associated with greater relationship need satisfaction, but less so after accounting for distress. Our study provides initial data on the role of DT in the daily lives of romantic couples and the methodological consequences of accounting for distress along with DT in analytical models.
Heating Up Enzyme Kinetics: A Safe, Inexpensive & Quantitative Inquiry Activity

Enzyme kinetics is an essential process of life, but it is a concept that challenges introductory biology students. Most enzyme kinetics laboratory activities either use hazardous chemicals to visualize the enzyme product or do not afford quantitative analysis at all. We have designed an inquiry-based activity that provides insight into enzyme function and that is budget friendly, safe, and produces quantitative results. The materials required are household products, so this activity can be adapted even for online classes. Furthermore, we suggest options for a sequential, experiential experiment-design activity for students.
Neuro-Detect: A Machine Learning-Based Fast and Accurate Seizure Detection System in the IoMT

Epilepsy, which is characterized by recurrent spontaneous seizures, has a considerably negative impact on both the quality and the expectancy of life of the patient. Approximately 3.4 million individuals in the USA and up to 1% of the world population is afflicted by epilepsy. This necessitates the real-time detection of seizures which can be done by the use of an Internet of Things (IoT) framework for smart healthcare. In this paper, we propose an electroencephalogram (EEG)-based seizure detection system in the IoT framework which uses the discrete wavelet transform (DWT), Hjorth parameters (HPs), statistical features, and a machine learning classifier. Seizure detection is done in two stages. In the first stage, EEG signals are decomposed by the DWT into sub-bands and features (activity, signal complexity, and standard deviation) were extracted from each of these sub-bands. In the second stage, a deep neural network (DNN) classifier is used to classify the EEG data. A prototype of the proposed neuro-detect was implemented using the hardware-in-the-loop approach. The results demonstrate a significant difference in HP values between interictal and ictal EEG with ictal EEG being less complex than interictal EEG. In this approach, we report an accuracy of 100% for a classification of normal versus ictal EEG and 98.6% for normal and interictal versus ictal EEG.
Losartan and Vitamin D Inhibit Colonic Tumor Development in a Conditional Apc-Deleted Mouse Model of Sporadic Colon Cancer

Colorectal cancer is a leading cause of cancer deaths. The renin-angiotensin system (RAS) is upregulated in colorectal cancer, and epidemiologic studies suggest RAS inhibitors reduce cancer risk. Because vitamin D (VD) receptor negatively regulates renin, we examined anticancer efficacy of VD and losartan (L), an angiotensin receptor blocker. Control Apc+/LoxP mice and tumor-forming Apc+/LoxP Cdx2P-Cre mice were randomized to unsupplemented Western diet (UN), or diets supplemented with VD, L, or VD+L, the latter to assess additive or synergistic effects. At 6 months, mice were killed. Plasma Ca2+, 25(OH)D3, 1α, 25(OH)2D3, renin, and angiotensin II (Ang II) were quantified. Colonic transcripts were assessed by qPCR and proteins by immunostaining and blotting. Cancer incidence and tumor burden were significantly lower in Cre+ VD and Cre+ L, but not in the Cre+ VD+L group. In Apc+/LoxP mice, VD increased plasma 1,25(OH)2D3 and colonic VDR. In Apc+/LoxP-Cdx2P-Cre mice, plasma renin and Ang II, and colonic tumor AT1, AT2, and Cyp27B1 were increased and VDR downregulated. L increased, whereas VD decreased plasma renin and Ang II in Cre+ mice. VD or L inhibited tumor development, while exerting differential effects on plasma VD metabolites and RAS components. We speculate that AT1 is critical for tumor development, whereas RAS suppression plays a key role in VD chemoprevention. When combined with L, VD no longer increases active VD and colonic VDR in Cre- mice nor suppresses renin and Ang II in Cre+ mice, likely contributing to lack of chemopreventive efficacy of the combination.
Cautionary (and blessed) tales from the perils of the measurement phase

In this response to the target article, we anticipate some challenges that joy researchers will face in attempting to cultivate a research program on a revived and more robust understanding of joy....
Stressed DNA replication generates stressed DNA

Much of our understanding of eukaryotic replication dynamics, origin, and polymerase usage and replication factors has come from studies using the yeast Saccharomyces cerevisiae. From the definition of replication origins using plasmid transformation (1, 2) and two-dimensional gel electrophoresis (3), identification of replication factors using various genetic screens for cell cycle progression (4) and plasmid stability (5, 6) and genome-wide replication patterns using Okazaki fragment sequencing (7, 8) and strand-specific sequencing of incorporated ribonucleotides in DNA (9), we have learned much about DNA replication under normal and disrupted conditions. As many of the replication factors are conserved, the findings have been applicable to more complex genomes. Additionally, genome instability in yeast arising from perturbations to the normal replication program mirror those found in human cells, particularly the genome instability resulting in loss of heterozygosity (LOH), genome rearrangements, and mutagenesis found in tumor cells and other diseases with DNA repair defects (10, 11). Perturbations in the DNA replication process can result in regions of single-stranded DNA (ssDNA) accumulating near the replication fork (12, 13). A useful tool in the Saccharomyces arsenal of in vivo genetic tricks is expression of the human APOBEC3B protein to mark the location of ssDNA (14⇓–16). This protein is a member of the cytosine deaminase family and mutates cytosine residues on ssDNA to uracil, resulting in C-to-T mutations. APOBEC3B protein does not naturally occur in yeast but can be expressed from a plasmid introduced into yeast strains. The U residues that arise from C deamination are preserved by deleting the UNG1 gene … [↵][1]1Email: hannah.klein{at}nyulangone.org. [1]: #xref-corresp-1-1
Finite elements computational modeling of coupled elastic waveguides

The theoretical study of one-dimensional-infinite systems of elastically coupled parallel waveguides has established the existence of band structures with pseudo-spin characteristics. Those systems, which are named ϕ-bits, have been shown to exhibit a spinor character associated with directional degrees of freedom, which makes them potential quantum mechanical analogs. The realization of such systems is challenged by the three-dimensional and finite nature of physical elastic waveguides. We address this problem, and with it the design of ϕ-bits in general, by developing finite elements models based on COMSOL Multiphysics®. We model systems of one or more coupled finite length Al rods. The analysis of their dispersion relations, transmission spectra, and amplitudes establishes their ϕ-bit character. For three coupled finite length Al rods, the elastic field is associated with wavefunctions, tensor products of a spinor part related to the directional degrees of freedom, and an orbital angular momentum part representing the phase of the coupled waveguides. We demonstrate the possibility of creating non-separable states between these degrees of freedom.
Decoding the Language of Microbiomes: Leveraging Patterns in 16S Public Data using Word-Embedding Techniques and Applications in Inflammatory Bowel Disease

Abstract Microbiomes are complex ecological systems that play crucial roles in understanding natural phenomena from human disease to climate change. Especially in human gut microbiome studies, where collecting clinical samples can be arduous, the number of taxa considered in any one study often exceeds the number of samples ten to one hundred-fold. This discrepancy decreases the power of studies to identify meaningful differences between samples, increases the likelihood of false positive results, and subsequently limits reproducibility. Despite the vast collections of microbiome data already available, biome-specific patterns of microbial structure are not currently leveraged to inform studies. Instead, most microbiome survey studies focus on differential abundance testing per taxa in pursuit of specific biomarkers for a given phenotype. This methodology assumes differences in individual species, genera, or families can be used to distinguish between microbial communities and ignores community-level response. In this paper, we propose to leverage public microbiome databases to shift the analysis paradigm from a focus on taxonomic counts to a focus on comprehensive properties that more completely characterize microbial community members’ function and environmental relationships. We learn these properties by applying an embedding algorithm to quantify taxa co-occurrence patterns in over 18,000 samples from the American Gut Project (AGP) microbiome crowdsourcing effort. The resulting set of embeddings transforms human gut microbiome data from thousands of taxa counts to a latent variable landscape of only one hundred “properties”, or contextual relationships. We then compare the predictive power of models trained using properties, normalized taxonomic count data, and another commonly used dimensionality reduction method, Principal Component Analysis in categorizing samples from individuals with inflammatory bowel disease (IBD) and healthy controls. We show that predictive models trained using property data are the most accurate, robust, and generalizable, and that property-based models can be trained on one dataset and deployed on another with positive results. Furthermore, we find that these properties can be interpreted in the context of current knowledge; properties correlate significantly with known metabolic pathways, and distances between taxa in “property space” roughly correlate with their phylogenetic distances. Using these properties, we are able to extract known and new bacterial metabolic pathways associated with inflammatory bowel disease across two completely independent studies. More broadly, this paper explores a reframing of the microbiome analysis mindset, from taxonomic counts to comprehensive community-level properties. By providing a set of pre-trained embeddings, we allow any V4 16S amplicon study to leverage and apply the publicly informed properties presented to increase the statistical power, reproducibility, and generalizability of analysis.
PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease.

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clinical candidate PF-07059013 (23). The seminal hit molecule was discovered by virtual screening and confirmed through a series of biochemical and biophysical studies. After a significant optimization effort, we arrived at 23, a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-week multiple dose study using Townes SCD mice, 23 showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clinical trials.
Aortic size in children: Systolic measurements are different from diastolic measurements.

Background : Current guidelines recommended aortic measurements during diastole in adults and during systole in children. Recent studies in adults have demonstrated noteworthy differences in aortic measurements during systole and diastole in the same subjects. In the present study, we aimed to characterize systolic and diastolic differences in aortic measurements in healthy children. Materials and Methods : This retrospective study included 272 children who had a complete echocardiogram and no heart disease. Aortic measurements at the annulus (ANN), aortic root (AOR), sinotubular junction (STJ), and ascending aorta (AAO) were performed. Systolic and diastolic values were compared by calculating the mean systolic to diastolic (SD) percent difference for each segment; if the SD difference was >5%, it was considered clinically important. Similar measurements were conducted by another observer in 18% of the subjects. Results : Systolic measurements were larger than diastolic measurements with mean SD percent differences >5% (P Conclusions : Systolic measurements for the AOR, STJ, and AAO were larger than diastolic measurements. Normal reference values are utilized to design treatment for patients with abnormal aortic sizes, and the timing in the cardiovascular cycle used to decide the reference values should be equivalent to the timing used to make measurements in clinical practice. This is particularly imperative as patients transition their care from a pediatric to an adult cardiologist.
Peel Learning for Pathway-Related Outcome Prediction.

MOTIVATION Traditional regression models are limited in outcome prediction due to their parametric nature. Current deep learning methods allow for various effects and interactions and have shown improved performance, but they typically need to be trained on a large amount of data to obtain reliable results. Gene expression studies often have small sample sizes but high dimensional correlated predictors so that traditional deep learning methods are not readily applicable. RESULTS In this paper, we proposed peel learning, a novel neural network that incorporates the prior relationship among genes. In each layer of learning, overall structure is peeled into multiple local substructures. Within the substructure, dependency among variables is reduced through linear projections. The overall structure is gradually simplified over layers and weight parameters are optimized through a revised backpropagation. We applied PL to a small lung transplantation study to predict recipients' post-surgery primary graft dysfunction using donors' gene expressions within several immunology pathways, where PL showed improved prediction accuracy compared to conventional penalized regression, classification trees, feed-forward neural network, and a neural network assuming prior network structure. Through simulation studies, we also demonstrated the advantage of adding specific structure among predictor variables in neural network, over no or uniform group structure, which is more favorable in smaller studies. The empirical evidence is consistent with our theoretical proof of improved upper bound of PL's complexity over ordinary neural networks. AVAILABILITY AND IMPLEMENTATION PL algorithm was implemented in Python and the open-source code and instruction will be available at https://github.com/Likelyt/Peel-Learning.
Radiation-resistant binary solid solutions via vacancy trapping on solute clusters

Abstract Additions of solute that trap vacancies slow down vacancy diffusion and promote point-defect recombination in alloys subjected to irradiation. Such selective alloying can thus help to minimize the detrimental consequences resulting from point defect fluxes. The current work investigates the effect of solute additions on the recombination rate using kinetic Monte Carlo simulations for a model alloy system, which was parametrized to Cu-Ag in the dilute limit, but with an increased solubility limit, ≈ 0.86 at.% at 300K. As the solute concentration was increased above 0.1 at.%, solute clustering was observed and led to a strong increase in recombination rate. The beneficial effects of solute clustering on reducing vacancy mobility, and reducing solute drag, were analyzed by calculating relevant transport coefficients using the KineCluE code (T. Schuler et al., Computational Materials Science (2020) 172, 109191). Moreover, it was observed in the KMC simulations that large recombination rates resulted in a shift of steady-state distributions of solute cluster sizes to smaller clusters compared to equilibrium distributions in the solid solution. This shift is rationalized as resulting from the irreversible character of the interstitial-vacancy recombination reaction. These results suggest a novel irradiation effect on phase stability where a high recombination rate increases the solubility limit of a solute at steady state over its equilibrium value.
Characterizing the Dispersion of Graphene Nanoplatelets in Water with Water Reducing Admixture

This research studied the effects of surfactants on graphene nanoplatelet (GNP) dispersion in water. Samples consisted of water, GNPs, and varied amounts of water reducing admixture (WRA). The GNPs were added at a fixed 0.2 % by weight of water while the amount of WRA used served as the independent variable. Sedimentation was qualitatively characterized by observing the rate at which GNPs settled out of suspension. Scanning Electron Microscopy (SEM) was used to obtain micrographs of the dried GNPs. The time evolution of light transmission through the supernatant region was measured with ultraviolet-visible spectroscopy (UV/Vis). Improved understanding and control of GNP dispersion in water has the potential to facilitate the beneficial use of this and similar materials in composites for resulting beneficial mechanical and electrical properties.
Effect of Medical Conditions on Improvement in Self-Reported and Observed Functional Performance of Elders*

Objectives: To evaluate the effect of nine disabling medical conditions upon recovery from functional limitations by elders. Design: Retrospective analysis of prospective longitudinal cohort. Setting: Community. Participants: Persons aged 65 and older in Framingham Heart Study. Measurements: Change in function in elders from biennial Examinations 18 (1983–85; baseline) through 23 (1994–96). At each examination, subjects reported limitations in heavy household work, walking up and down stairs, walking half a mile, bathing, toileting, and continence. They were also directly observed for performance of transferring in and out of a chair, dressing, walking 50 feet, and carrying a 10-pound object 10 feet. The prevalence of functional limitations and the incidence of recovery from functional limitation by the subsequent examination for each task were calculated. The effects of congestive heart failure, cognitive impairment, diabetes mellitus, stroke, depressive symptoms, hip fracture, knee pain, claudication, and chronic obstructive pulmonary disease were evaluated. The relationship between the total number of comorbid conditions present (0, 1, 2, 3 or more), the presence of each individual condition at the start of each examination cycle, and the incidence of recovery from functional limitations were examined using generalized estimating equations. Results: One thousand eight hundred twenty-five subjects were studied at baseline; 1,026 were available 10 years later. Mean age of subjects at baseline was 73.5 (range 61–95); 60.7% were women. The prevalence of functional limitations ranged from 3.1% to 29.8% at biennial Examination 18 and increased to 15.1% to 32.4% at Examination 23. The incidence of recovery ranged from 3.2% to 78.4% depending upon the task and the examination cycle. Increasing disease burden, as measured by the number of comorbidities, was associated with a decreased likelihood of recovery from functional limitations. Diabetes mellitus, stroke, depressive symptoms, hip fracture, and knee pain had the strongest adverse effect upon recovery from functional limitations. Conclusion: In these community-dwelling elders, recovery from prevalent functional limitations was frequent. Increasing disease burden was associated with a decreased incidence of recovery. Diabetes mellitus, stroke, depressive symptoms, hip fracture, and knee pain had the strongest adverse effect on recovery from functional limitations.
A comparison of 28 natural and dredged material salt marshes in Texas with an emphasis on geomorphological variables

Fourteen dredged material marshes andfourteen natural marshes along the Texas, USA, coastare compared on the basis of 1) edge: area ratios, 2)relative exposure index values, 3) elevation profiles,4) elevation of Spartina alterniflora, 5) soilorganic carbon content, 6) soil silt-clay content, and7) belowground plant biomass. Although edge: areacomparisons cannot detect certain types of differencesin geomorphology, comparisons clearly show thatdredged material marshes, on average, have fewer pondsand flooded depressions than natural marshes. Comparisons of relative exposure index values suggestthat wave protection structures associated with somedredged material marshes may be overbuilt. Elevationprofiles illustrate the potential for structures suchas berms to lead to differences between dredgedmaterial marshes and natural marshes, but they alsoshow the high variability in elevation profiles thatexists among both dredged material and naturalmarshes. S. alternifloraelevations in dredgedmaterial marshes are not significantly different fromthose of natural marshes. Soil organic carbon andsilt-clay content of dredged material marshes are notsignificantly different from those of natural marshes. Although belowground biomass of dredged materialmarshes is significantly lower than that of naturalmarshes, regression analysis suggests that belowgroundbiomass will increase over time. Findings reportedhere suggest several points that should be consideredduring planning and design of dredged material marshesin Texas: 1) if an objective of marsh construction isto mimic natural marsh geomorphology, methods toincrease the amount of unconnected edge need to bedeveloped, 2) methods of effectively summarizinggeomorphic characteristics need further development,and 3) there is some evidence suggesting thatprotective structures may be over-built, and the needfor substantial structural protection should bebalanced against the costs of structures and risk ofsite failure during project design. Lastly, a methodfor increasing the amount of unconnected edge thatinvolves excavation of bay bottom before placement ofdredged material is suggested.
A Review of “Licensing Digital Content: A Practical Guide for Librarians”

Negotiating with content providers on licenses for electronic resources can be intimidating and challenging for librarians. Licensing Digital Content is an excellent resource for librarians who are...
Shared resource management for integrated avionics systems

Increased demand for avionics system functionality has lead to $10-15M avionics suites on recent aircraft. Support costs are high due to low avionics system reliability. When required, new functions have to be "shoe horned" onto aircraft at great expense. Integrated avionics systems are being developed to address these problems. Common module, shared resource avionics systems offer the potential for controlling the cost, size, and weight of avionics while providing a 25-fold increase in system availability and growth potential. The challenge to realizing the potential of these systems is effective utilization of the avionics resources. >
Putting aspiration back into thyroid fine‐needle biopsy—the re‐emerging role of vacuum assistance

John S. Abele, MD In the first large fine-needle aspiration (FNA) series reported by Zajicek, aspiration with the Cameco syringe holder (Belpro Medical, Anjou, Quebec, Canada; US Food and Drug Administration registration no. 3003769953), also known as the aspiration gun, was the norm. Indeed, the first 2 words of Chapter 1 in that prescient textbook are ‘‘aspiration biopsy.’’ Beginning with our first FNA experience in the late 1970s at the University of California, San Francisco, my colleagues and I used the aspirating gun on every case for many years. That changed with the 1986 publication by Zajdela et al, whose technique is referred to as the Zajdela technique, or the French technique, or simply ‘‘needle-only’’ biopsy. We soon appreciated the ability of this technique to give very good cellular yield with appreciably less blood. And, as an added bonus, this technique allowed us to approach a patient with the needle concealed in the palm of our hand as opposed to holding the intimidating aspirating gun in plain sight. Before long, we used the needle-only technique almost exclusively. Despite increasing use of the needle-only technique, FNA remains the commonly used term for these biopsies, although they lacked an ‘‘A.’’ Since coming to Sacramento in 1982, FNA has been my main focus and the most significantly growing part of our private practice group, Outpatient Pathology Associates. Knowing that the addition of ultrasound guidance (USG) to FNA greatly improves visualization of the biopsy site and the accuracy of needle placement, our FNA clinic acquired its first ultrasound machine in 2003. Although we have come to use exclusively the needle-only technique for our initial passes with the USG for ease of use, we still have identified 3 situations in which our ability to conveniently use aspiration optimizes diagnostic success: 1) cyst evacuation; 2) when initial needle-only sampling results in a dry tap or minimal material in cases of atrophic nodules secondary to chronicity, thyroid suppression, or thyroiditis or in rare cases of papillary carcinoma with a marked fibrous component; and 3) small or predominately cystic lymph nodes with papillary carcinoma. This commentary details those situations, including tips and traps, especially as they relate to USG.
Inflammation-induced endothelial-to-mesenchymal transition: a novel mechanism of intestinal fibrosis.

In addition to mesenchymal cells, endothelial cells may contribute to fibrosis through the process of endothelial-to-mesenchymal transition (EndoMT). We investigated whether human intestinal microvascular endothelial cells (HIMEC) undergo EndoMT and contribute to fibrosis in human and experimental inflammatory bowel disease (IBD). HIMEC were exposed to TGF-β1, IL-1β, and TNF-α or supernatants of lamina propria mononuclear cells (LPMC) and evaluated for morphological, phenotypic, and functional changes compatible with EndoMT. Genomic analysis was used to identify transcription factors involved in the transformation process. Evidence of in situ and in vivo EndoMT was sought in inflamed human and murine intestine. The combination of TGF-β1, IL-1β and TNF-α, or activated LPMC supernatants induced morphological and phenotypic changes consistent with EndoMT with a dominant effect by IL-1. These changes persisted after removal of the inducing agents and were accompanied by functional loss of acetylated LDL-uptake and migratory capacity, and acquisition of de novo collagen synthesis capacity. Sp1 appeared to be the main transcriptional regulator of EndoMT. EndoMT was detected in microvessels of inflammatory bowel disease (IBD) mucosa and experimental colonic fibrosis of Tie2–green fluorescent protein (GFP) reporter–expressing mice. In conclusion, chronic inflammation induces transdifferentiation of intestinal mucosal microvascular cells into mesenchymal cells, suggesting that the intestinal microvasculature contributes to IBD-associated fibrosis through the novel process of EndoMT.
Forgiveness: Truth, Memory, and Civic Reconciliation without Apology

Progress, far from consisting in change, depends on retentiveness. … Those who cannot remember the past are condemned to repeat it. Santayana Throughout this study I have argued that interpersonal forgiveness as well as political apology require that the truth be told and heard. Both are therefore committed not only to truth telling, but to the proposition that it is better to remember than to forget. I also argued that both may promote reconciliation within their respective spheres and in their respective senses of the term, which is to say that the reconciliation they afford is built on truth and memory. I did not argue that reconciliation is impossible without forgiveness or apology. In this concluding chapter, I discuss a well known and fascinating candidate for civic reconciliation that is certainly committed to remembering, but is silent on the question of apology and forgiveness, in spite of the fact that its context was that of war and bitter civic discord. I do not offer it as an example of failed apology, but as an intriguing counter-example to the theses I have advanced. What are its successes and failures? What does it teach us about the relationship between truth telling, narrative, memory, political apology, and civic reconciliation (I am not focusing here on international reconciliation)? A people's memory of itself is expressed in part through its narrative, and that narrative can be and often is presented not just discursively but also in stone, wood, and metal.
Electoral Competition, 1958-1984: Impact on State Legislative Turnover in the Indiana House:

This article addresses the widespread notion that the decline in membership turnover in American state legislatures during the last two decades was primarily due to a decline in voluntary withdrawals from office and was unrelated to electoral competition. A theory of membership turnover is presented that incorporates electoral competition as a factor in an incumbent's decision to seek reelection and his/her ability to win. Several hypotheses are tested with data on turnover in the Indiana House of Representatives. This article departs from previous efforts in that electoral competition is measured at the district level and incumbents' decisions to run for higher office are distinguished from other forms of voluntary withdrawal.
Laser velocimetry measurements of swirl and squish flows in an engine with a cylindrical piston bowl

Etude par velocimetre laser des ecoulements tangentiels et radicaux dans un moteur dont le piston est muni d'une cavite cylindrique
Electromagnetic scattering from BOR objects loaded with periodic conducting narrow strips using asymptotic boundary conditions

The asymptotic strip boundary conditions (ASBC) are used on bodies of revolution (BOR) objects loaded with periodic conducting strips with period P approaching zero. The strips are tangential to the surface and either in the circumferential direction or orthogonal to it. The ASBC method is verified by using it to obtain the scattering fields from objects and comparing them with those obtained using the exact boundary conditions.
GIS in Energy and Utilities

The past fifty years have been a fascinating period of ubiquitous evolution. Our population has exploded and centralized resulting in massive urban construction and giant multiservice utilities. We have experienced tremendous growth in the transportation industry with vehicle and plane travel becoming a day-to-day norm. Computer and mobile technology industries appeared and now dominate the Western lifestyle. Underpinning each form of our evolution is energy. Fervent growth places significant pressure on the energy system. We look for energy in more remote areas, and we produce it in harsh and sensitive locations as we work to maintain aging transmission systems. To be successful in our efforts, we need to think differently, use innovative technologies and implement them effectively. One of the leaders in the technology field is GIS. This chapter will discribe how energy organizations employ GIS technology to overcome the critical business problems of today and ensure reliable energy for the future.
Stuck in the Middle: Doctoral Education Ranking and Career Outcomes for Life Scientists:

Why do some Ph.D.'s languish in positions with little authority, and what does educational background have to do with it? Hypotheses predicted that life scientists with Ph.D.'s from elite programs would be the most likely, those from middle-ranked programs the next most likely, and those from lower ranked programs the least likely to achieve supervisory positions. A sample of 2,062 life scientists with doctorates from U.S. universities was collected from records archived from 1983 to 1995. In contrast to hypotheses, Ph.D.'s from elite and lower ranked schools did not have a significantly different chance of supervising. Within prestigious organizations, however, Ph.D.'s from top 10 programs did have a greater likelihood of leading. Ph.D.'s from middle-ranked programs were less likely to advance into supervisory positions. Qualitative interviews explored how, in a knowledgeexpanding field such as the life sciences, being stuck on the bottom rung early on can adversely affect a scientist's career.
ES cells for troubled hearts

Cardiomyocytes derived from human embryonic stem cells prove beneficial in an animal model of myocardial infarction.
Motor End-Plates

In the preparation of motor end-plates for class room work the use of sodium thiosulfate is suggested as a precaution against overstaining and as a regressive measure. Digestion of the connective tissue eliminates the tedious teasing and the possible destruction of the delicate nerve fibers. Mounting in a solution of gum arable makes the slides more durable than glycerin jelly for class use. Whole neuromuscular spindles may be obtained by this method.
Enhancement by sulfatide of Na+-independent [3H]gaba binding in mouse brain

Abstract The effect of exogenous sulfatide on [ 3 H]γ-aminobutyric acid binding to postsynaptic receptors was investigated. Sulfatide (0.1 mM) increased the high affinity binding sites by 67% when it was incubated with membrane tissue at 37°C for 20 min prior to [ 3 H]γ-aminobutyric acid binding assay. Preincubation of 0.05% Triton X-100 treated tissue with 0.1 mM sulfatide at 37°C for 20 min augmented the high and low affinity binding sites by 16.4 and 16.2%, respectively. The results of the present study indicate that sulfatide may play a significant role in contributing to the integrity of γ-aminobutyric acid receptors.
Practical liquid diets for rats: effects on growth.

Liquid diets based on the AIN-76 formula are described. The diets employ xanthan gum as a stabilizer. Information is provided on how these diets may be modified to meet the requirements of a particular experiment (e.g., variations in water content, type of protein or carbohydrate or fat, etc.). These diets are superior to widely used diets with regard to nutritional adequacy, cost, ease of preparation, versatility, stability, osmolality, and use of natural ingredients. An experiment is described which compares the effects of feeding rats a solid diet or a liquid diet prepared three different ways. The results confirm that a properly prepared liquid diet can produce overweight and obesity.
Frequency dependence of synaptic vesicle exocytosis in aortic baroreceptor neurons and the role of group III mGluRs.

Abstract Synaptic transmission between baroreceptor afferents and the nucleus tractus solitarius (NTS) is essential for reflex regulation of blood pressure. High frequency stimulation of the afferents in vivo leads to a decrease in synaptic strength and is generally attributed to reduction in presynaptic neurotransmitter release. It has been hypothesized that during high frequency stimulation glutamate a major neurotransmitter at the baroreceptor afferent terminals inhibits its own release via presynaptic group III metabotropic glutamate receptors (mGluRs). A key player in modulation of presynaptic release is vesicle exocytosis. The present study utilized cultured aortic baroreceptor neurons and the styryl dye FM2–10 to characterize (1) the dependence of exocytosis at these afferent nerve terminals on the frequency of neuronal activation, (2) the effect of duration of stimulation on the rate of exocytosis and (3) the role of mGluRs in the frequency-dependent modulation of exocytosis. Destaining in the FM2–10 loaded boutons during 3 min of stimulation, a measure of exocytosis, progressively decreased with increasing frequency (0.5, 1.0 and 10 Hz). Blockade of group III mGluRs with 300 μM (RS)-cyclopropyl-4-phosphonophenylglycine (CPPG) facilitated exocytosis evoked by 10 Hz stimulation but not at 0.5 Hz. The data suggest that aortic baroreceptor terminals exhibit frequency-dependent depression of exocytosis and support a role for group III mGluRs in the frequency-dependent modulation of exocytosis.
The Effect of Administration of Dexamethasone and Adrenocorticoids on 22Na Retention, Water Consumption and Gland Weights of Cockerels

Abstract Seventy Cobb White Rock male chicks, three weeks of age, were divided into seven equal groups. Group 1 served as control. Group 2 was injected subcutaneously daily with 2 mg. dexamethasone per kg. body weight. Groups 3 and 4 were injected daily with dexamethasone and were intramuscularly injected daily with 75 μg./kg. and 150 μg./kg. of d-aldosterone, respectively. Groups 5 and 6 were injected daily with 75 μg./kg. and 150 μg./kg. of d-aldosterone, respectively. Groups 5 and 6 were injected daily with dexamethasone and were intramuscularly injected with 2 mg./kg. and 4 mg./kg. of corticosterone. Group 7 was injected daily with the dexamethasone and a daily intramuscular injection of 75 μg./kg. d-aldosterone + 2 mg./kg. of corticosterone. The birds were dosed orally with .2 uCi. of Na and the individual radioactivity was determined by the use of a whole body counter. Counts were measured on alternate days starting at day one and ending at day thirteen. The results indicated that the dexamethasone treatment caused a significant decrease in 22Na retention for Groups 2, 5, 6 and 7. Aldosterone treatment counteracted the dexamethasone inhibition of 22Na retention. The control group had a significantly higher mean body weight than any other treatment group. Birds injected with corticosterone had a significantly lower adrenal weight.
Social support, disability and independent living of elderly persons in the United States

Abstract This article examines the effects of the availability of kin and disability on the ability of elderly persons to live alone in the United States. The first part of the article uses a sample of women aged 65 and over from the 1980 census to study the factors associated with both living in group housing and living alone. Disability and absence of a spouse or children are strongly associated with living in group housing, whereas lack of disability and lack of children are associated with living alone. In the second part, data from the Supplement on Aging to the 1984 National Health Interview Survey are used to investigate the source and amount of help received among those with difficulties in performing Activities of Daily Living (ADLs) or Instrumental Activities of Daily Living (IADLs). Those living alone or with nonrelatives are most likely to rely on paid help and this is more likely if they have few living children.
Endothelial defects and blood flow disturbance in atherogenesis.

Les observations faites sur le porc de Yorkshire montrent que certaines perturbations du flot sanguin normal se manifestent dans une zone predisposee au developpement de lesions atheromateuses et sont accompagnees de pertes de substances endotheliales. Cette destruction des cellules endotheliales permettrait au plasma riche en lipoproteines de penetrer librement dans la paroi arterielle, ce qui favorise l'atherogenese.
Abstract LB-156: A diet-derived sialic acid promotes inflammation and hepatocellular cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA N-glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid derived from the diet (primarily red meat) that can be metabolically incorporated into human tissues despite being an antigen. Since this incorporation occurs in the face of circulating anti-Neu5Gc antibodies, we hypothesized that this generates an antibody-antigen reaction and leads to inflammation termed “xenosialitis”. Although red meat consumption is prominently associated with cancer development, pathological mechanisms behind this link are yet to be conclusively proven. The purpose of our research is to investigate the relationship between “xenosialitis”, inflammation and cancer. We used a Cmah null mouse model (mimicking the human lack of Neu5Gc) to provide evidence for such inflammation and cancer promotion. Anti-Neu5Gc antibodies were generated by immunizing Cmah null mice, with chimpanzee red blood cell membranes, or with human red blood cell membranes as controls. Pooled immune or control sera were repeatedly adsorbed with human red blood cells, and the resulting polyclonal antisera passively transferred into additional Cmah null mice that were on a diet with or without Neu5Gc. Mice fed with Neu5Gc and injected with anti-Neu5Gc antibodies showed dose-dependent elevation in acute phase proteins (Serum Amyloid A and Haptoglobin) in the serum as compared to controls. Such C57BL/6 mice are prone to developing hepatic adenomas and occasional carcinomas. Cmah null but not wild-type C57BL/6 mice immunized with chimpanzee red blood cell membranes and fed with Neu5Gc developed a higher frequency of hepatocellular cancer and liver histology showed Neu5Gc accumulation and foci of inflammation. In conclusion, Neu5Gc that has metabolically incorporated into tissues from the diet interacts with anti-Neu5Gc antibodies, generating xenosialitis. Potential correlations of human anti-Neu5Gc antibody levels with red meat consumption and cancer risk are being investigated. Methods to flush out the xenogenic Neu5Gc are being pursued. Similar mechanisms may be operative in other chronic inflammatory processes in diseases epidemiologically associated with red meat consumption, such as atherosclerosis. Citation Format: Annie N. Samraj, Heinz Laubli, Oliver Pearce, Patrick Secrest, Andrea E. Garcia-Bingman, Nissi Varki, Ajit Varki. A diet-derived sialic acid promotes inflammation and hepatocellular cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-156. doi:10.1158/1538-7445.AM2014-LB-156