cssi/SciSciGPT-SciSciNet huggingface dataset:
Evaluation of an Allosteric BACE Inhibitor Peptide to Identify Mimetics that Can Interact with the Loop F Region of the Enzyme and Prevent APP Cleavage

The aspartyl protease BACE1 (BACE) has emerged as an appealing target for reduction of amyloid-β in Alzheimer's disease. The clinical fate of active-site BACE inhibitors may depend on potential side effects related to enzyme and substrate selectivity. One strategy to reduce this risk is through development of allosteric inhibitors that interact with and modulate the Loop F region unique to BACE1. Previously, a BACE-inhibiting antibody (Ab) was shown by co-crystallization to bind and induce conformational changes of Loop F, resulting in backbone perturbations at the distal S6 and S7 subsites, preventing proper binding of a long APP-like substrate to BACE and inhibiting its cleavage. In an effort to discover small Loop F-interacting molecules that mimic the Ab inhibition, we evaluated a peptide series with a YPYF(I/L)P(L/Y) motif that was reported to bind a BACE exosite. Our studies show that the most potent inhibitor from this series, peptide 65007, has a similar substrate cleavage profile to the Ab and reduces sAPPβ levels in cell models and primary neurons. As our modeling indicates, it interacts with the Loop F region causing a conformational shift of the BACE protein backbone near the distal subsites. The peptide-bound enzyme adopts a conformation that closely overlays with the crystal structure (PDB: 3R1G) from Ab binding. Importantly, peptide 65007 appears to be BACE substrate and enzyme selective, showing little inhibition of NRG1, PSGL1, CHL1, or Cat D. Thus, peptide 65007 is a promising lead for discovery of Loop F-interacting small-molecule mimetics as allosteric inhibitors of BACE.
SDCworks: a formal framework for software defined control of smart manufacturing systems

Discrete manufacturing systems are complex cyber-physical systems (CPS) and their availability, performance, and quality have a big impact on the economy. Smart manufacturing promises to improve these aspects. One key approach that is being pursued in this context is the creation of centralized software-defined control (SDC) architectures and strategies that use diverse sensors and data sources to make manufacturing more adaptive, resilient, and programmable. In this paper, we present SDCWorks---a modeling and simulation framework for SDC. It consists of the semantic structures for creating models, a baseline controller, and an open source implementation of a discrete event simulator for SDCWorks models. We provide the semantics of such a manufacturing system in terms of a discrete transition system which sets up the platform for future research in a new class of problems in formal verification, synthesis, and monitoring. We illustrate the expressive power of SDCWorks by modeling the realistic SMART manufacturing testbed of University of Michigan. We show how our open source SDCWorks simulator can be used to evaluate relevant metrics (throughput, latency, and load) for example manufacturing systems.
Capillary Leak Syndrome Aggravated by Influenza Type A Infection

A 41-year-old female presented to the emergency department with nausea, vomiting, and diarrhea. Five days prior to this, she tested positive for influenza type A in an urgent care clinic and received Tamiflu. She also complained of generalized weakness in her extremities. Her initial labs were concerning for a grossly elevated hemoglobin and hematocrit despite adequate fluid resuscitation. Her condition continued to worsen as she developed distal cyanosis in all of her extremities and pulselessness. She was treated with IV hydration, bicarbonate, heparin, vasopressors, albumin replacement, Tamiflu, and phlebotomy. Her blood pressure continued to deteriorate rapidly. The arterial blood gas (ABG) depicted a case of severe metabolic acidosis that ultimately resulted in respiratory failure, and she required mechanical ventilation within 24 hours. Systemic capillary leak syndrome is a rare disease that is characterized by hypotension, hemoconcentration, and hypoalbuminemia. In this instance, influenza type A played a large role in its development.
SharP Data Constructs: Data Constructs to Enable Data-Centric Computing

Extreme-scale applications (i.e., Big-Compute) are becoming increasingly data-intensive, i.e., producing and consuming increasingly large amounts of data. The HPC systems traditionally used for these applications are now used for Big-Data applications such as data analytics, social network analysis, machine learning, and genomics. As a consequence of these trends, the system architecture should be flexible and data-centric. This can already be witnessed in the pre-exascale systems with TBs of on-node hierarchical and heterogeneous memories, PBs of system memory, low-latency, high-throughput networks, and many threaded cores. As such, the pre-exascale systems suit the needs of both Big-Compute and Big-Data applications. Though the system architecture is flexible enough to support both Big-Compute and Big-Data, we argue there is a software gap. Particularly, we need data-centric abstractions to leverage the full potential of the system, i.e., there is a need for native support for data resilience, the ability to express data locality and affinity, mechanisms to reduce data movement, the ability to share data, and abstractions to express User's data usage and data access patterns. In this paper, we (i) show the need for taking a holistic approach towards data-centric abstractions, (ii) show how these approaches were realized in the SHARed data-structure centric Programming abstraction (SharP) library, a data-structure centric programming abstraction, and (iii) apply these approaches to a variety of applications that demonstrate its usefulness. Particularly, we apply these approaches to QMCPack and the Graph500 benchmark and demonstrate the advantages of this approach on extreme-scale systems.
Artificial Structures and Shorelines: An Introduction

The coast has long been considered one of the most desirable of environments for human utilization. Rich in resources, climatically attractive, and strategically located, it enticed early peoples just as it attracts those of the present day. Although much of the evidence of early utilization is lost (mostly during the rise of sea level that accompanied the last deglaciation and subsequent coastal erosion) it is clear that occupation extended along much of the shoreline. Nonetheless, such early utilization actually had little impact on the materials, processes, and forms that were natural along the coast.
Tephrochronology at DSDP Site 502 in the Western Caribbean

A composite core consisting of four Hydraulic Piston Cores at DSDP Site 502 in the western Caribbean were analyzed for dispersed tephra. Peaks in dispersed tephra abundance were combined with megascopic ash layers to produce a tephrochronology which is based on the magnetostratigraphy and biostratigraphy for the section recovered. The frequency of tephra falls at Site 502 increased in the late Miocene and Quaternary; this may be related to subduction rates of the Cocos Plate under Central America, or to major changes in wind direction over Central America.
Waldman v. Palestine Liberation Organization (U.S. Ct. App. Second Circuit)

The 2000–2005 al Aqsa Intifada spawned a horrific wave of violence in and near Jerusalem. Numerous individuals and entities were sued in U.S. courts, by both foreign and American victims, relying on a variety of liability theories and statutes. The seminal Anti-Terrorism Act (ATA) case was filed in 2007 in the U.S. District Court for the Southern District of New York as Sokolow v. Palestine Liberation Organization. It also named the Palestinian Authority (PA) and individuals including Yasser Arafat.
Indigenous Nation Rebuilding Through Gardening: A United States Model Compatible with Indigenous Cultures

The Three Sisters, corn, beans and squash, planted together, form the foundation of sustainability for Indigenous peoples in what is now called North America as a source of balanced nutrition and nourishment for the community and for the nations' spirit. With these seeds, Indigenous peoples can engage in nation rebuilding. While Indigenous nation rebuilding literature shows numerous inherent problems and incompatibility when relying on Euro-American models, this article argues that war and victory gardens used by the United States during the two world wars to promote a sense of patriotism and national identity provides a framework harmonious with traditional Indigenous cultures. Gardening supplies the means through which Indigenous peoples reconnect with traditional lives and ways. Furthermore, as an outcome, articulating land reacquisition and use that non-Indigenous Americans recognise and have applied in their own nation rebuilding efforts could lessen misinterpretation and apprehension in land claim negotiations.
Triangular DNA Origami Tilings

DNA origami tilings provide methods for creating complex molecular patterns and shapes using flat DNA origami structures as building blocks. Square tiles have been developed to construct micrometer...
Investigating pathways linking women’s status and empowerment to skilled attendance at birth in Tanzania: A structural equation modeling approach

Maternal and newborn mortality remain unacceptably high in sub-Saharan Africa where use of a skilled birth attendant (SBA) at delivery has remained low. Despite the recognized importance of women’s empowerment as a key determinant of maternal and newborn health, evidence from sub-Saharan Africa is more limited. Using data from the 2010 Tanzania Demographic and Health Survey (n = 4,340), this study employs a robust method–structural equation modeling (SEM)–to investigate the complex and multidimensional pathways through which women’s empowerment affects SBA use. The results show that women’s education and household decision-making are positively associated with SBA use. However, not all empowerment dimensions have similar effects. Attitudes towards sex negotiation and violence as well as early marriage are not significant factors in Tanzania. Mediation analysis also confirms the indirect effect of education on SBA use only through household decision-making. The findings underscore the utility of structural equation modeling when examining complex and multidimensional constructs, such as empowerment, and demonstrate potential causal inference to better inform policy and programmatic recommendations.
Unstructured leisure in the after-school hours.

In the modern industrial world, families and schools share the responsibility for supervising children and youth. Yet there is a gap of 20 to 25 hours per week between adolescents’ school schedules and parents’ work schedules (U.S. Department of Education and Justice, 2000), leaving 25% to 31% of waking hours during the school week that may not be covered by either institution. The other chapters of this volume concern various structured activities for children and youth that may fill this time. The present chapter provides a context of comparison to those chapters by focusing on unstructured leisure during the after-school hours.
Half-Harmonic Generation: Enabling Photonic Solutions for Molecular Sensing and Non-Classical Computing

Half-harmonic generation is the inverse of second-harmonic generation. This talk overviews the concept, and how it is used for mid-IR frequency combs for molecular spectroscopy, and optical Ising machines, which can enable special-purpose nonclassical computing.
The Changing Uses of Herbarium Data in an Era of Global Change: An Overview Using Automated Content Analysis

Widespread specimen digitization has greatly enhanced the use of herbarium data in scientific research. Publications using herbarium data have increased exponentially over the last century. Here, we review changing uses of herbaria through time with a computational text analysis of 13,702 articles from 1923 to 2017 that quantitatively complements traditional review approaches. Although maintaining its core contribution to taxonomic knowledge, herbarium use has diversified from a few dominant research topics a century ago (e.g., taxonomic notes, botanical history, local observations), with many topics only recently emerging (e.g., biodiversity informatics, global change biology, DNA analyses). Specimens are now appreciated as temporally and spatially extensive sources of genotypic, phenotypic, and biogeographic data. Specimens are increasingly used in ways that influence our ability to steward future biodiversity. As we enter the Anthropocene, herbaria have likewise entered a new era with enhanced scientific, educational, and societal relevance.
Clinical Decision Supports in Electronic Health Records to Promote Childhood Obesity-Related Care: Results from a 2015 Survey of Healthcare Providers

Obesity-related clinical decision support tools in electronic health records (EHRs) can improve pediatric care, but the degree of adoption of these tools is unknown. DocStyles 2015 survey data from US pediatric healthcare providers (n = 1,156) were analyzed. Multivariable logistic regression identified provider characteristics associated with three EHR functionalities: automatically calculating body mass index (BMI) percentile (AUTO), displaying BMI trajectory (DISPLAY), and flagging abnormal BMIs (FLAG). Most providers had EHRs (88%). Of those with EHRs, 90% reporting having AUTO, 62% DISPLAY, and 54% FLAG functionalities. Only provider age was associated with all three functionalities. Compared to providers aged > 54 years, providers < 40 years had greater odds for: AUTO (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.58-5.70), DISPLAY (aOR, 2.07; 95% CI, 1.38-3.12), and FLAG (aOR, 1.67; 95% CI, 1.14-2.44). Future investigations can elucidate causes of lower adoption of EHR functions that display growth trajectories and flag abnormal BMIs.
Introduction to spatiotemporal variations of ambient air pollutants and related public health impacts

Abstract This introductory chapter first provides an overview of spatiotemporal variations of various ambient air pollutants and broad impacts of these variations on regional and global public health. Main components of ambient air pollution and their specific roles on respiratory, cardiovascular, neurological, and other relatively unknown health hazards are discussed. Next, the chapter presents challenges in epidemiological study designs and risk assessment for understanding air pollution-induced adverse health impacts. Some potential exposure measurement errors and confounding factors are discussed with an emphasis on the problems in large-scale cohort studies. Finally, the significance of air monitoring networks and models for prediction of ambient air pollutants and major recent findings on GIS applications for understanding public health impacts of air pollutants are presented.
Treatment of Congenital Ptosis in Infants With Associated Amblyopia Using a Frontalis Muscle Flap Eyelid Reanimation Technique.

PURPOSE To determine the efficacy of a frontalis muscle flap eyelid reanimation technique for correction of severe congenital ptosis and associated amblyopia in infants. METHODS The authors performed a retrospective chart review of patients 12 months of age or younger with unilateral or bilateral congenital ptosis and associated amblyopia or deemed at high risk for amblyopia due to visual deprivation. Following ptosis repair via a frontalis muscle flap technique, primary outcomes of postoperative eyelid position and amblyopia reversal were assessed. RESULTS Seventeen eyes of 12 participants were included for study. Seven of these patients had simple congenital ptosis, and the remainder had ptosis as part of a syndrome. Nine were diagnosed with amblyopia preoperatively, and the remaining 3 were too young for acuity testing but had occlusion of the visual axis by the ptotic eyelid in primary gaze. Postoperatively, the mean margin-to-reflex distance 1 was 2.4 mm (range: 0.0-4.0), and 9 patients (75%) demonstrated no evidence of amblyopia. Only 2 patients had eyelid asymmetry greater than 2 mm, which in both cases was due to lack of frontalis activation by the patient secondary to ongoing visual impairment. The most common complication was lagophthalmos in 6 eyes (35.3%), with no significant associated surface keratopathy. CONCLUSIONS The frontalis muscle flap technique may offer a new and effective approach to treating infants with severe congenital ptosis causing poor eyelid excursion and associated amblyopia while avoiding use of an implant.
Fully Bayesian Analysis of the Relevance Vector Machine Classification for Imbalanced Data.

Relevance Vector Machine (RVM) is a supervised learning algorithm extended from Support Vector Machine (SVM) based on the Bayesian sparsity model. Compared with the regression problem, RVM classification is difficult to be conducted because there is no closed-form solution for the weight parameter posterior. Original RVM classification algorithm used Newton's method in optimization to obtain the mode of weight parameter posterior then approximated it by a Gaussian distribution in Laplace's method. It would work but just applied the frequency methods in a Bayesian framework. This paper proposes a Generic Bayesian approach for the RVM classification. We conjecture that our algorithm achieves convergent estimates of the quantities of interest compared with the nonconvergent estimates of the original RVM classification algorithm. Furthermore, a Fully Bayesian approach with the hierarchical hyperprior structure for RVM classification is proposed, which improves the classification performance, especially in the imbalanced data problem. By the numeric studies, our proposed algorithms obtain high classification accuracy rates. The Fully Bayesian hierarchical hyperprior method outperforms the Generic one for the imbalanced data classification.
Systemic lupus erythematosus (SLE): emerging therapeutic targets.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a heterogeneous clinical presentation whose etiologies are multifactorial. A myriad of genetic, hormonal, immunologic, and en...
Scalable, Deployable, Flexible Phased Array Sheets

Large aperture flexible and deployable phased arrays will enable active RF fabric and deployable array structures for terrestrial and space applications. The flexible phased array design paradigm is enabled by small, multi-function radio frequency integrated circuits and low mass radiators, which avoid conventional dielectric materials. This paper presents a 256 element, 30 cm x 30 cm flexible phased array, operating at 10 GHz and focusing 0.8 W at 2 m distance. A novel beam-focusing algorithm is used to demonstrate 2-D beam-steering and deformation correction capabilities of the flexible phased array.
Heidegger’s Concept of Philosophical Method: Innovating Philosophy in the Age of Global Warming: by Vincent Blok, London, Routledge, 2020, 309 pp., £96 (Hardback), ISBN: 978-0-36741-812-0

Blok makes a compelling case for renewed consideration of philosophical method in the pressing context of environmental threats, plunging readers into the depths of Heidegger’s philosophical method...
Iatrogenic Arteriovenous Fistula Following Femoral Access Precipitating High-Output Heart Failure.

Abstract Iatrogenic complications may manifest in a variety of ways. We present the case of an 86-year-old woman who underwent a percutaneous coronary intervention with a drug-eluting stent for non...
Association between Smoking History and Tumor Mutation Burden in Advanced Non-Small Cell Lung Cancer.

Lung carcinogenesis is a complex and stepwise process involving accumulation of genetic mutations in signaling and oncogenic pathways via interactions with environmental factors and host susceptibility. Tobacco exposure is the leading cause of lung cancer, but its relationship to clinically relevant mutations and the composite tumor mutation burden (TMB) has not been fully elucidated. In this study, we investigated the dose-response relationship in a retrospective observational study of 931 patients treated for advanced-stage non-small cell lung cancer (NSCLC) between April 2013 and February 2020 at the Dana Farber Cancer Institute and Brigham and Women's Hospital. Doubling smoking pack-years was associated with increased KRASG12C and less frequent EGFRdel19 and EGFRL858R mutations, whereas doubling smoking-free months was associated with more frequent EGFRL858R . In advanced lung adenocarcinoma, doubling smoking pack-years was associated with an increase in TMB, whereas doubling smoking-free months was associated with a decrease in TMB, after controlling for age, gender, and stage. There is a significant dose-response association of smoking history with genetic alterations in cancer-related pathways and TMB in advanced lung adenocarcinoma. SIGNIFICANCE: This study clarifies the relationship between smoking history and clinically relevant mutations in non-small cell lung cancer, revealing the potential of smoking history as a surrogate for tumor mutation burden.
The RISE of a Clinical Approach to Skills Assessment

Entrepreneur development programs have many choices in terms of how they might elect to measure skills. However, any program that conceptualizes entrepreneurship as a set of skills must make this decision. In order to remain consistent with the TCOM framework and create an efficient and collaborative assessment process, we have created the Readiness Inventory for Successful Entrepreneurship (RISE).To achieve the aspirations of TCOM we have used the communimetric measurement theory. In this chapter we describe this theory and contrast it to traditional theories of measurement. We then describe the development, structure and uses of the RISE.
Multi-fidelity non-intrusive reduced-order modelling based on manifold alignment

This work presents the development of a multi-fidelity, parametric and non-intrusive reduced-order modelling method to tackle the problem of achieving an acceptable predictive accuracy under a limi...
A Patchwork of Femininities: Working-Class Women’s Fluctuating Gender Performances in a Pakistani Market:

Scholars have studied multiple femininities across different spaces by attributing variation to cultural/spatial contexts. They have studied multiple femininities in the same space by attributing v...
Sustainable changes in teacher practices: a longitudinal analysis of the classroom practices of high school mathematics teachers

This study examines the effects of professional development on various aspects of teachers’ mathematics instruction. Using data collected between 2005 and 2009, we examined the extent to which the instructional practices of 49 US high school teachers who participated in content-based, sustained professional development changed over time. We found that changes in several aspects of their instructional practices followed somewhat different patterns. Teachers made statistically significant and steady changes in mathematical discourse, instructional clarity, and the development of students’ mathematical habit of mind, but not in student interactions or in the use of multiple representations.
Quantification of the retinal vascular network structure: towards effective monitoring of vessel architecture modulation in diabetic retinopathy

Diabetic retinopathy is the most common diabetic eye disease leading to vision loss. Disturbances have been detected in many aspects of ocular circulation in diabetes. However, hemodynamic and vessel architectural modulation have not been extensively investigated in DR. Therefore, an objective test for the early diagnosis, progression and therapeutic evaluation of DR based on vascular remodeling may aid to identify the individuals at great risk for vision threatening problems. In this paper, we present a methodology to characterize the microvascular network structure in diabetic individuals. Our preliminary results may pave the path towards effective monitoring of vessel architecture modulation in diabetic retinopathy.
Mass mapping of large globin complexes by scanning transmission electron microscopy.

Abstract Scanning transmission electron microscopy (STEM) of unstained, freeze-dried biological macromolecules in the dark-field mode provides an image based on the number of electrons elastically scattered by the constituent atoms of the macromolecule. The image of each isolated particle provides information about the projected structure of the latter, and its integrated intensity is directly related to the mass of the selected particle. Particle images can be sorted by shape, providing independent histograms of mass to study assembly/disassembly intermediates. STEM is optimized for low-dose imaging and is suitable for accurate measurement of particle masses over the range from about 30 kDa to 1,000 MDa. This article describes the details of the method developed at the Brookhaven National Laboratory STEM facility and illustrates its application to the mass mapping of large globin complexes.
Congenital heart disease and acute myocardial infarction: Course and necropsy

Abstract In the fist published case of congenital ventricular septal defect and acute myocardial infarction was made on clinical data only. 1 Recently the patient died at the age of 37 years, and a post-mortem examination was made. The purpose of the present communication is to give a progress report since the original publication and to describe the necrospy findings.
The Applied Mindfulness Process Scale (AMPS): A process measure for evaluating mindfulness-based interventions☆

Abstract Objective Mindfulness-based interventions (MBIs) include the application of meditation and mind–body practices used to promote mindful awareness in daily life. Operationalizing the construct of mindfulness is important in order to determine mechanisms of therapeutic change elicited by mindfulness practice. In addition to existing state and trait measures of mindfulness, process measures are needed to assess the ways in which individuals apply mindfulness in the context of their practice. Method This report details three independent studies (qualitative interview, N = 8; scale validation, N = 134; and replication study, N = 180) and the mixed qualitative–quantitative methodology used to develop and validate the Applied Mindfulness Process Scale (AMPS), a 15-item process measure designed to quantify how mindfulness practitioners actively use mindfulness to remediate psychological suffering in their daily lives. Results In Study 1, cognitive interviewing yielded a readily comprehensible and accessible scale of 15 items. In Study 2, exploratory factor analysis derived a potential three-factor solution: decentering, positive emotion regulation, and negative emotion regulation. In Study 3, confirmatory factor analysis verified better model fit with the three-factor structure over the one-factor structure. Conclusions AMPS functions as a measure to quantify the application of mindfulness and processes of change in the context of MBIs and general mindfulness practice.
Volume relations of the nucleus in apodan spermateleosis

Seeing that this is the first attempt at a determination of the changes in the volume of the nucleus during spermateleosis, it would be hazardous to draw any far-reaching conclusions on the data available. But one striking fact that emerges from a study of the above figures is the enormous reduction in the volume of the nucleus from the spermatid to the fully formed sperm. This reduction is approximately 95% inSiphonops annulatus, 90% inIchthyophis glutinosus, Urœotyphlus narayani andGegenophis carnosus and 80% inDermophis gregorii. It is therefore clear that the chromatin of the nucleus accounts only for a small quantity of its volume. Another fact that strikes one from an examination of the Graph (Fig. 1) and Table I is that so far as the five species of Apoda are concerned, in spite of the large variation in the nuclear volumes of the different species in stages I and II, the volume in the third stage,i.e., in the fully formed sperm, is nearly the same in all the species. What significance is to be attached to this fact will not be clear till more species are examined, but the close similarity in nuclear volume of the adult sperms of these five different species of Apoda is interesting.
Crime, Punishment, and Victim Distress

The costs of crime to victims are well-known and research has described the physical, emotional, and financial injuries sustained by crime victims. To date, however, there has been little empirical work which investigates the correlates of victim distress vis-a-vis victim involvement in the criminal justice process. The present study explores the role played by the criminal justice experience in victim distress level and the relative importance of victim, offense, and system participation variables. Multivariate analysis revealed that the level of distress following the victimization is largely a function of offense type, victim perception of sentence severity, and victim demographic characteristics of sex and age. Investigation of the factors predictive of current victim distress level indicated that receiving restitution and the level of distress following the victimization are most important, in addition to the personal characteristics of race and marital status. The implications of these findings for ...
Utilizing WAIS Scores to Determine Foreign Language Pathways and Learning Assistance for Students with Learning Disabilities.

Foreign language (FL) requirements at postsecondary institutions remain a major hurdle for many students with learning disabilities (LD) as well as a significant portion of students without diagnosed LD. Many institutions have developed foreign language substitution (FLS) policies that allow students with LD to take alternate paths to meet the requirement, although the evidence to support substitutions is mixed. In a 10-year longitudinal study (presently continuing in a new phase with WAIS-IV scores), students with learning disabilities (N = 112) at a small liberal arts school who had WAIS-III scores available and self-reported foreign language difficulties were tracked for foreign language success, and then later graduation success. The purpose of this study was twofold: to develop a more generalizable substitution profile when test scores are available and to examine whether students who did not substitute an alternative to a foreign language varied significantly from those who did in terms of their suc...
Abstract 1498: Long non-coding RNAin situhybridization signal patterns correlate with breast tumor pathology

Background: Long non-coding RNAs (lncRNAs) participate in a spectrum of biological activities by diverse mechanisms. LncRNA dysregulation has been reported for many cancers. Some lncRNAs may function as oncogenes (OG) and others as tumor suppressor genes (TSG). To date, lncRNA has been investigated primarily by qRT-PCR. In this study we have examined the relationship of lncRNA expression patterns to breast tumor pathology by chromogenic in situ hybridization (CISH). Methods: Expression of six lncRNAs, HOTAIR (OG), H19 (OG), Kcnq1ot1 (OG), Meg3 (TSG), Malat1 (OG), and ZFas1 (TSG), plus HER2 and MKI67 mRNAs was examined by RNAscope® CISH using tissue microarrays (TMAs) comprising normal epithelia, ductal carcinoma in situ (DCIS), and invasive carcinoma (IC) from 45 patients. HOTAIR/H19-mediated protein EZH2 was evaluated by immunohistochemistry (IHC). CISH and IHC results were scored in terms of the percentage of stained cells ( 50%=3) and staining intensity (low=1, medium=2, high=3). Staining grade (SG) values were calculated as SG= proportion x intensity (SG value range=1-9). Results: The TMAs contained 36 normal epithelia (N), 34 DCIS (D) and 43 IC tissue punches. HOTAIR expression was common: at SG≥1, expression was detected in N:85%; D:97%; IC:100% (p>0.05). HOTAIR SG mean values (N 4.0, D 5.7, IC 6.2) were significantly higher in DCIS and IC than in normal tissues (N:D p 0.05). IC HOTAIR SGs correlated with Nottingham grade (p H19 was rarely expressed in normal epithelial or tumor cells but was strongly expressed especially in inter-lobular stromal cells around invasive growths. At SG≥1 H19 was detected in N:38%; D:55%; IC:90% (p 0.05; N:IC p Kcnq1ot1 staining was more common in DCIS and IC than in normal tissues: at SG≥1, N:77%; D:96%; IC:94% (p IC and DCIS EZH2 IHC staining correlated positively with both HOTAIR and H19 expression (p Conclusions: These data demonstrate the utility of CISH for investigating and demonstrating pathologic lncRNA expression. HOTAIR and H19 in particular and possibly Kncq1ot1 and Meg3 are potential breast cancer biomarkers. H19 may be a marker for DCIS at increased risk of progression to invasive cancer. Citation Format: Zhouwei Zhang, Zhihua Peng, Daniel Olsen, James deKay, Donald L. Weaver, Mark F. Evans. Long non-coding RNA in situ hybridization signal patterns correlate with breast tumor pathology. [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 1498. doi:10.1158/1538-7445.AM2014-1498
Increased sensitivity of the non-human primate eye to microwave radiation following ophthalmic drug pretreatment.

Previous studies in our laboratory have established that pulsed microwaves at 2.45 GHz and 10 mW/cm2 are associated with production of corneal endothelial lesions and with disruption of the blood-aqueous barrier in the non-human primate eye. In the study reported here we examined ocular damage in monkeys (M. mulatta and M. fascicularis) following topical treatment with one of two ophthalmic drugs (timolol maleate and pilocarpine) that preceded exposure to pulsed microwaves. Anesthetized monkeys were sham exposed or exposed to pulsed, 2.45 GHz microwaves (10 μs, 100 pps) at average power densities of 0.2, 1, 5, 10, or 15 mW/cm2 4 h a day for 3 consecutive days (respective SARs were 0.052, 0.26, 1.3, 2.6, and 3.9 W/kg). Immediately before microwave exposure, one or both eyes were treated topically with one drop of 0.5% timolol maleate or of 2% pilocarpine. Following administration of a drug, we observed a significant reduction in the power-density threshold (from 10 to 1 mW/cm2) for induction of corneal endothelial lesions and for increased vascular permeability of the iris. Diagnostic procedures (in vivo specular microscopy and fluorescein iris angiography) were performed following each exposure protocol. In addition, increased vascular permeability was confirmed with horseradish peroxidase tracer techniques. Although we did not measure intraocular temperatures in experimental animals, the results suggest that a mechanism other than significant heating of the eye is involved. Our data indicate that pulsed microwaves at an average SAR of 0.26 W/kg, if administered after pretreatment with ophthalmic drugs, can produce significant ocular effects in the anesthetized primate. 1992 Wiley-Liss, Inc.
Brain Plasticity and the Impact of the Electronic Environment in Law and Learning

Brain plasticity has become a hot topic in educational circles. As computers and the Internet fundamentally change how we work and how we learn, law librarians need to understand the implications of brain plasticity and learning styles. This article introduces the human brain's amazing ability to adapt and form connections that allow us to do a great number of things—including our ability to read at all.
Design for on-line coupling of supercritical fluid extraction with liquid chromatography: quantitative analysis of polynuclear aromatic hydrocarbons in a solid matrix

Supercritical fluid extraction (SFE) was directly coupled with high-performance liquid chromatography (LC) via the simplest interface--only one six-port injection valve. By using water to eliminate decompressed CO2 gas in the solid-phase octadecylsilica trap, high extraction recovery (> or = 95%) of polynuclear aromatic hydrocarbons (PAHs) from a sand matrix was achieved under optimized conditions. The volume of rinse water had little influence on the recovery, due to the very low solubility of PAHs in water and the sorption properties of the C-18 trap. Different amounts of sand matrix with a fixed mass of analytes have also been tested. No decrease in recovery was found when the matrix (sand) increased from 1 to 10 g. Methanol and acetone were used as a CO2 modifier to enhance the extraction efficiency. Finally, PAHs in naturally contaminated soil were successfully extracted and quantitatively determined by this hyphenated system. Compared to the EPA method (Soxhlet extraction following by GC/MS), on-line SFE-LC gave precise results in a much shorter time.
Trabeculectomy is associated with retrobulbar hemodynamic changes. A color Doppler analysis.

Purpose: To determine whether color Doppler hemodynamic changes occur in the retrobulbar circulation after trabeculectomy. Methods: The authors prospectively enrolled 20 patients undergoing trabeculectomy and performed color Doppler imaging of both eyes before surgery and then at approximately 2-, 5-, and 14-week intervals after surgery. The systolic maximum velocity, mean velocity, end-diastolic velocity, and vascular resistance (resistance index) of the central retinal artery, nasal and temporal short posterior ciliary arteries, and ophthalmic arteries were determined. Statistical comparison of the preoperative and postoperative measures were performed on both the operative and nonoperative eye using the paired Student's t test. Results: A statistically significant increase was observed in the mean and enddiastolic velocity and a significant decrease in the vascular resistance of the central retinal artery and both short posterior ciliary arteries at nearly all postoperative intervals (25 of 27 preoperative and postoperative comparisons; P P Conclusion: Sustained increases in mean velocity and end-diastolic velocity and decreases in resistance index were observed in the central retinal artery and the short posterior arteries with clinically attainable reductions in intraocular pressure after trabeculectomy in patients with chronic glaucoma. These findings are consistent with, but not diagnostic of, increased blood flow through these vessels.
Negative symptoms are associated with less alcohol use, craving, and "high" in alcohol dependent patients with schizophrenia.

Background Alcohol use disorders (AUDs) frequently co-occur with and exacerbate schizophrenia, yet the specific relationships between schizophrenia symptoms and alcohol use remain unclear.
The relation between sexual activity among children during preadolescence and/or early adolescence and sexual behavior and sexual adjustment in young adulthood

This study examined whether current sexual behavior and sexual adjustment in a sample of 433 college students differed as a function of having engaged in sexual activity with other children during preadolescence (prior to age 13) and/or early adolescence (ages 13–15). Four groups were compared: subjects who only had an early adolescent sexual experience; subjects who had both preadolescent and early adolescent experiences; subjects who had no sexual experience with another child during either preadolescence or early adolescence. There were no significant differences between these groups on measures of incidence of premarital intercourse, age at first intercourse, number of different intercourse partners, sexual satisfaction, sexual arousal, or sexual dysfunctions. It was concluded that in general the simple occurrence or nonoccurrence of sexual activity among children during these developmental periods has little impact, either positive or negative, on later sexual adjustment during young adulthood. Some expections, depending on the specific types of childhood sexual activity involved, were noted.
Photo-acoustic imaging of blue nanoparticle targeted brain tumor for intra-operative glioma delineation

Distinguishing the tumor from the background neo-plastic tissue is challenging for cancer surgery such as surgical resection of glioma. Attempts have been made to use visible or fluorescent markers to delineate the tumors during surgery. However, the systemic injection of the dyes requires high dose, resulting in negative side effects. A novel method to delineate rat brain tumors intra-operatively, as well as post-operatively, using a highly sensitive photoacoustic imaging technique enhanced by tumor targeting blue nanoparticle as contrast agent is demonstrated. The nanoparticles are made of polyacrylamide (PAA) matrix with covalently linked Coomassie-Blue dye. They contain 7.0% dye and the average size is 80nm. Their surface was conjugated with F3 peptide for active tumor targeting. These nanoparticles are nontoxic, chemically inert and have long plasma circulation lifetime, making them suitable as nanodevices for imaging using photoacoustics. Experiments on phantoms and rat brains tumors ex-vivo demonstrate the high sensitivity of photoacoustic imaging in delineating the tumor, containing contrast agent at concentrations too low to be visualized by eye. The control tumors without nanoparticles did not show any enhanced signal. This study shows that photoacoustic imaging facilitated with the nanoparticle contrast agent could contribute to future surgical procedures for glioma.
Axial fibrils of anaerobic spirochetes: ultrastructure and chemical characteristics.

1. Axial fibrils isolated from three species of Spirochaeta were examined by electron microscopy. Each axial fibril consisted of three main morphological components similar to those present in bacterial flagella: an insertion apparatus, a proximal hook near the insertion apparatus, and a filamentous portion. The filamentous portion appeared to be composed of a core surrounded by a non-striated sheath. The core consisted of globules arranged in a helical pattern. Striated tubular structures were observed in preparations of disrupted cells. 2. Purified axial fibril cores were dissociated by acid, alkali, urea, or guanidine-HCl, but were stable to the action of various enzymes. The proximal hooks were more resistant than the fibril cores to treatment with acid, alkali, or other chemicals. Aspartic and glutamic acids, alanine, leucine, glycine, and serine were the most abundant amino acids in axial fibril core hydrolysates. At pH 2.4 in 4 M urea, acid-dissociated axial fibril cores yielded two protein bands in polyacrylamide gel electrophoresis. Structures morphologically closely resembling the native axial fibril cores were assembled in vitro by raising the pH of acid-dissociated fibril core preparations. The data show that striking similarities exist between spirochetal axial fibrils and bacterial flagella with regard to their fine structure and physical and chemical characteristics. The results support the view that axial fibrils play a role in spirochetal motility. 3. Spirochetes from which the axial fibrils had been removed by treatment with acid maintained their coiled shape. The peptidoglycan layer purified from two species of Spirochaeta frequently retained its coiled configuration. It is concluded that, in the spirochetes studied, the axial fibrils are not responsible for maintaining the coiled shape of the cells, but that this function is served by the peptidoglycan.
Intersection of surfaces in 3-manifolds

Abstract Given a pair of incompressible surfaces F and S in an irreducible 3-manifold M, we define a directed graph T which expresses the way F may be isotoped with respect to S. We study the properties of T. We use our results about T to study properties of the intersection between F and S.
Structural Responses to Selection for Reduced Fiber Concentration in Smooth Bromegrass

Selection for reduced neutral detergent fiber (NDF) concentration has been practiced as a mechanism of increasing voluntary intake potential of forage crops. Because selection is usually conducted on the basis of whole-plant samples, there exists the potential for structural shifts in plant composition. The objective of this study was to quantify structural changes due to selection for reduced NDF concentration in smooth bromegrass (Bromus inermis Leyss). Three cycles of phenotypic selection led to reduced whole-plant NDF concentration, primarily due to reductions in NDF of stems (-5.7 to -5.8 g kg -1 1 cycle -1 ) and leaf sheaths (-3.1 to -4.9 g kg -1 cycle -1 ). Selection at both the vegetative growth stage (primarily leaf blades) or heading growth stage (all shoot components present) led to similar changes in shoot-component NDF concentrations. Selection on the basis of vegetative samples did not lead to structural changes. Conversely, selection on the basis of headed samples led to an average reduction of -7.5 % cycle -1 in stem component concentration, which was compensated largely by increases in leaf blade and sheath component concentrations. Increases in leaf:stem ratio may partially explain reductions in forage yield associated with reduced NDF concentration. Future selection efforts should attempt to avoid this response by using samples composed of a single shoot component. The NDF concentrations in various shoot components of smooth bromegrass appear to be positively correlated with each other.
STUDIES ON THE MECHANISMS OF INSULIN RESISTANCE IN CHILDHOOD OBESITY

We have shown that childhood obesity is associated with hyperinsulinemia involving the acute and chronic pools of insulin similarly. To define the mechanism(s) responsible for this, we have measured the response of plasma insulin, glucagon, growth hormone (GH) and free fatty acids (FFA) to various stimuli in 10 obese children and matched lean controls. To allow direct assessment of the uptake of glucose by peripheral tissue (impedance) we have utilized the technique of Shen (continuous infusions of glucose, insulin, epinephrine and propranolol) to suppress endogenous insulin secretion and hepatic glucose output. All patients had normal glucose tolerance. Basal insulin levels (94 vs. 10 μU/ml) and tissue impedance (247 vs. 86) were increased (p < 0.01) in obese patients. Younger obese children (3-6 yr.) had intermediate plasma insulin and tissue impedance values (30 and 168). The plasma glucagon and GH responses to arginine were blunted in obese patients. Fasting FFA and triglyceride (TG) levels and the FFA and TG responses to oral lipomul and heparin were similar in both groups. These studies demonstrate progressive impairment of glucose uptake by peripheral tissues in childhood obesity and suggest a basic tissue defect in carbohydrate metabolism.
Adsorption and characteristics of base-treated pillared clays

The effect of base treatment on the cation exchange capacity (CEC) of pillared clays and their adsorption isotherms for Cu2+, Cr3+ and Pb2+ have been investigated. Results indicate that although the CEC of pillared clays are only about 15% of that of the parent clays, a large fraction of the native clays CEC may be recovered by treatment with base. The fraction of the CEC recovered depends upon the base strength, its concentration, and the temperature. Contrary to previous suggestions the mechanism of recovery is related to the destruction of pillars which is accompanied by the loss of surface area. It is possible under conditions specified to prepare these base treated pillared clays as a new class of useful, regenerable adsorbent for heavy metal adsorption from aqueous solution.