cssi/SciSciGPT-SciSciNet huggingface dataset:
Discrete element modeling of deformable pinewood chips in cyclic loading test

Abstract The design of efficient lignocellulosic biomass feedstock systems is challenging, as current laboratory characterization and design methods were developed primarily for fine powders with relatively low compressibility. The discrete element method (DEM) is gaining prominence as an alternative method for modeling the bulk flow and transport of particulate materials in hoppers and feeders. However, prior DEM simulations investigating the flow of wood chips modeled the particles as simple rigid geometries such as spheres, rods or blocks, and neglected the effects of particle deformability and irregular shapes. As a consequence, those simplified DEM models may not provide enough key diagnosis to help improve the design of biomass feeding and handling equipment. This work presents a bonded-sphere DEM approach for characterizing the mechanical behavior of bulk flexible, deformable pinewood chips in a cyclic stress loading test. Clustered spheres that can bend and twist via elastic bonds are used to model irregular-shape particles in real pinewood chip samples. An axial compression tester, which contains 0.06 million bonded-sphere particles (1.35 million spheres) in a quarter cylinder, is simulated with a domain size similar to the experiments. With careful calibration, the simulations have delivered the bulk densities and the bulk moduli of elasticity that are in good agreement with those measured in the corresponding experiments. However, it is also been found challenging for the present DEM model to accurately predict the overall stress-strain behavior of bulk pinewood chips, especially the large sustained plastic deformation during unloading. Additional numerical tests have shown that the adjustment in certain contact parameters (e.g. bond stiffness) can lead to profound solution improvement, but meanwhile will induce extra challenges such as increased computing time. Future work will include an elasto-plastic particle bond model to enhance the simulation fidelity.
Simulation-based Parameter Optimization Framework for Large-Scale Hybrid Smart Grid Communications Systems Design

The design of reliable, dynamic, fault-tolerant hybrid smart grid communication networks is a challenge to achieve for autonomous power grids. Hybrid networks use different communications technologies for different area networks. A simulation-based parameter optimization framework is proposed to tune parameters of hybrid communication technologies to achieve the optimal network performance. It consists of three main components: a parallel executor used to speedup a list of simulations; a sampler running simulations using the parallel executor at each generation; and a hybrid stochastic optimization algorithm for tuning configurable parameters of hybrid designs and applications. The proposed hybrid metaheuristic optimization algorithm combines an evolutionary algorithm with a gradient method to quickly achieve an approximately global optimum solution. Three optimization test functions are employed to train the adjustable parameters of the hybrid algorithm. Results show the proposed parameter optimization framework can help the designer choose the right hybrid architecture with an optimal parameter set for a large-scale broadband PLC-WiMAX hybrid smart grid communication network.
Uncovering Profiles of Economic, Social, and Cultural Capital to Explore Depression Across Racial Groups

Research exploring the association between socio-economic status (SES) and depression is limited by conceptualizations of SES and conflicting findings across racial groups. We broaden previous research by (1) reconceptualizing SES through the lens of Bourdieusian theory to identify profiles of economic, social, and cultural capital; (2) investigating whether these profiles differ for Black and white adults; and (3) exploring whether specific profiles of capital are associated with increased depression scores. This study analyzed secondary data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative sample of US individuals. A sub-population of the sample was used, which was comprised of 4339 Black and white participants from wave IV. To address the study aims, we used the new three-step approach to conducting latent class analysis. We identified five profiles of capital, the composition of which varied by race. Compared to Blacks, whites were more likely to be in the "cultural-economic capital" (14% vs. 10%), "elevated overall capital" (35% vs. 14%), and "social-economic capital" (13% vs. 10%) profiles, whereas Blacks were more likely to be in the "limited overall capital" (35% vs. 16%) and "moderate economic capital" (32% vs 22%) profiles. Profiles differed in risk for depression; the "limited overall capital" profile had the highest depression scores, whereas the "elevated overall capital" profile had the lowest depression scores. This research has the potential to reduce health disparities, by providing policy makers and researchers with information that will allow them to target populations that are most at risk for depression.
A multi-approach peptidomic analysis of hen egg white reveals novel putative bioactive molecules

Abstract Chicken egg white is a raw material broadly used as additive for the preparation of food and cosmetoceutical products. To describe its molecular properties, various proteomic investigations were performed in the last decade characterizing highly abundant components. No peptidomic counterparts were accomplished so far; scientific literature only reports on the characterization of specific bioactive peptides or preparations from egg white and its hydrolysates, which was performed through dedicated functional assays. In this study, a broad description of the egg white peptidome at 24, 336 and 672 h after laying was achieved using three peptide extraction procedures, which were combined with MALDI-TOF-TOF-MS and nanoLC-ESI-Q-Orbitrap-MS/MS analyses. In the whole, 506 peptides were characterized; they mostly resulted from the physiological degradation of intact proteins following the activity of endoprotease ArgC-, trypsin- and plasmin-like enzymes. Eventual detection of peptide post-translational modifications also provided structural information on parental proteins. When analyzed by bioinformatics and/or compared with literature data, identified peptides allowed recognizing a number of protein fragments associated with different hypothetical biological activities. These results confirmed previous observations regarding functional characteristics of egg white unfractionated preparations or purified molecules, emphasizing the useful application of this raw material in human nutrition and cosmetics. Finally, a comparative label-free peptidomic evaluation of samples stored for different times under refrigeration identified 31 peptides showing significant quantitative changes during storage. Biological significance This study provided the largest inventory of peptides described in chicken egg while so far. In addition, it identified a number of protein fragments associated with hypothetical antihypertensive, antioxidant, antiinflammatory, antimicrobial, anticancer, antiviral, antibiofilm, calcium-binding, antidiabetic, antithrombotic, adipogenic differentiating, stimulating/immunostimulating, hormonal, lipid-binding and cell adhesion-affecting activities. These results confirmed previous observations regarding functional characteristics of egg white unfractionated preparations or purified molecules, emphasizing the useful application of this raw material in human nutrition and cosmetics.
Characterizing Trends, Variability, and Statistical Drivers of Multisectoral Water Withdrawals for Statewide Planning

AbstractSustainable water management requires understanding the factors that influence water use across multiple time scales, spatial scales, and types of use. However, existing empirical research ...
Probing the role of the conserved residue Glu166 in a class A β-lactamase using neutron and X-ray protein crystallography

The amino-acid sequence of the Toho-1 β-lactamase contains several conserved residues in the active site, including Ser70, Lys73, Ser130 and Glu166, some of which coordinate a catalytic water molecule. This catalytic water molecule is essential in the acylation and deacylation parts of the reaction mechanism through which Toho-1 inactivates specific antibiotics and provides resistance to its expressing bacterial strains. To investigate the function of Glu166 in the acylation part of the catalytic mechanism, neutron and X-ray crystallographic studies were performed on a Glu166Gln mutant. The structure of this class A β-lactamase mutant provides several insights into its previously reported reduced drug-binding kinetic rates. A joint refinement of both X-ray and neutron diffraction data was used to study the effects of the Glu166Gln mutation on the active site of Toho-1. This structure reveals that while the Glu166Gln mutation has a somewhat limited impact on the positions of the conserved amino acids within the active site, it displaces the catalytic water molecule from the active site. These subtle changes offer a structural explanation for the previously observed decreases in the binding of non-β-lactam inhibitors such as the recently developed diazobicyclooctane inhibitor avibactam.
Evaluation of BEAM As a Preparative Regimen in Patients Undergoing Autologous Stem Cell Transplantation for Lymphoma

Introduction Mainstay treatment options for patients with relapsed or refractory Hodgkin's lymphoma and Non-Hodgkin's lymphoma (NHL) include high dose chemotherapy and autologous stem cell transplantation (aSCT). Several chemotherapy regimens have been explored with various drug combinations. To date, no objective data is available to indicate that one particular regimen is better than another in regards to superiority. When selecting one regimen compared to another, the choice will depend on each institution's individual practices, guidelines, and toxicities associated with each regimen. Objective To report the safety and efficacy of the widely utilized BEAM (carmustine, etoposide, cytarabine, and melphalan) regimen in lymphoma patients at least 60 years of age who received an aSCT. Methods This was a single center, retrospective, chart review at Wake Forest Baptist Medical Center's Comprehensive Cancer Center from January 2014 to September 2019. Patients were selected via report generation if they had received BEAM as a preparative regimen during the study period. Patients received carmustine 300 mg/m2 IV on Day -6; etoposide 200 mg/m2 IV Day -5 to Day -2; cytarabine 200 mg/m2 IV Day -5 to Day -2; and melphalan 140 mg/m2 IV Day -1. The primary endpoint was the prevalence of grade 3, 4, and 5 toxicities in BEAM. Secondary endpoints included relapse-free survival (RFS), overall survival (OS), time to death, time to relapse, and days to engraftment. Descriptive statistics were utilized for demographic data. Time to event data was analyzed using the Kaplan-Meier method. Results Fifty patients were included within this analysis. All patients experienced at least one adverse event with BEAM. The most commonly reported toxicities were gastrointestinal related events including nausea/vomiting (80%) and diarrhea (94%). The most commonly reported grade 3 or 4 event was febrile neutropenia (76%). There were no grade 5 related adverse events. Three year overall survival was 70% (n=26) and no patients died within the first 60 days post-transplant. The average length of stay was 20.1 days but when patients were moved to the outpatient setting for aSCT with BEAM our average length of stay decreased to 18.1 day. The patients who were transplanted outpatient had an overall length of stay of 5 days. The time to engraftment was 11 days for neutrophils and 18 days for platelets. Conclusion BEAM was considered tolerable in the elderly lymphoma patient population with minimal grade 3 or 4 adverse events other than febrile neutropenia. The nausea and vomiting and diarrhea that occurred was such that it allowed the transition to the outpatient setting. Additionally, the administration of cytarabine and etoposide daily made administration in the outpatient setting feasible.
Desorber and rectifier geometries for ammonia-water absorption systems; Part II: Mass transfer, flooding, and component performance

Abstract An experimental investigation of two compact counter-flow vapor generation units, for use in ammonia-water absorption systems, was conducted. The vapor generation units feature integrated desorber, analyzer, and rectifier sections. The branched tray design uses pool-boiling mechanisms in the desorption process, while the vertical column uses falling-film evaporation mechanisms. Experimental mass transfer coefficients for the desorbers of both concepts were quantified and compared with correlations from the literature, generally with poor agreement. The flooding limits of these counter-flow vapor generation units were investigated and agree well with available correlations. The experimental results from Part I of this study are used in this paper, Part II, to develop revised heat and mass transfer models that accurately predict component level performance.
Development of a novel hybrid cognitive model validation framework for implementation under COVID-19 restrictions

The purpose of this study was to develop a method for validation of cognitive models consistent with the remote working situation arising from COVID-19 restrictions in place in Spring 2020 We propose a framework for structuring validation tasks and applying a scoring system to determine initial model validity We infer an objective validity level for cognitive models requiring no in-person observations, and minimal reliance on remote usability and observational studies This approach has been derived from the necessity of the COVID-19 response, however, we believe this approach can lower costs and reduce timelines to initial validation in post-Covid-19 studies, enabling faster progress in the development of cognitive engineering systems A three-stage hybrid validation framework was developed based on existing validation methods and was adapted to enable compliance with the specific limitations derived from COVID-19 response restrictions This validation method includes elements of argument-based validation combined with a cognitive walkthrough analysis, and reflexivity assessments We conducted a case study of the proposed framework on a developmental cognitive model of cardiovascular surgery to demonstrate application of a real-world validation task This framework can be easily and quickly implemented by a small research team and provides a structured validation method to increase confidence in assumptions as well as to provide evidence to support validity claims in the early stages of model development © 2021 Wiley Periodicals LLC
Abstract 1954: Identifying synthetic lethality with novel CDK2 small molecule inhibitors via integration of high-content microscopy and -omics level platforms

CDK4/6 small molecule inhibitors represent a milestone in treating hormone receptor-positive breast cancer. PALOMA (Palbociclib: Ongoing Trials in the Management of Breast Cancer) studies have confirmed prolonged progression-free survival after CDK4/6 inhibitor and anti-estrogen therapy. Notably, disease progression is observed in a subset of patients receiving Palbociclib-Fulvestrant treatment (Turner et al., NEJM 2018). Circulating tumor DNA from PALOMA-3 patients revealed genetic mutations correlating with patient response (O9Leary et al., Cancer Discov, 2018). Compensations in CDK4/6i resistance include circumvention of CDK4/6 substrate regulation, CCNE1/2 amplification (Herrera-Abreu et al., Cancer Res. 2016), and compensatory CDK2 activity. The importance of compensatory CDK2 cancer re-wiring is highlighted by recently reported, highly efficacious CDK2/4/6i (Freeman-Cook et al., in review). Thus, mechanistic understanding of cancer cell and compensatory CDK2 activity is imperative to improve patient outcome. Acute, temporal phenotypes in CDK2-signaling have been observed by live single-cell tracking microscopy in human breast epithelial and ER+ breast cancer cells (Arora & Moser et al., in review). In extending these studies, we utilize first-in-class small molecule inhibitors against CDK2 combined with high content imaging approaches to illuminate cancer cell CDK2 signaling and identify potential synthetic lethality. We report biomarkers parsed in cycling populations as quantifiable phenotypes and identify disengaged control of several processes including S- and G2/M licensing after CDK2i. Combined with internal -omics studies, CDK2i selective molecules support a positive regulatory role of CDK2 on CCNB1-PLK1 signaling before mitotic entry. We combine our high-content techniques with proximity labeling to quantify alternative CDK-Cyclin complex formation following pharmacologic perturbation. We hypothesize that dysregulated CDK-Cyclin complex formation elicits unintended CDK2 kinase activity, revealing potential synthetic lethality with inhibition of centrosome duplication pathways in ER+ breast cancers. Citation Format: Tim Sen Wang, Jon Almaden, Chen Shen, John Lapek, Sherry Niessen, Nichol Miller, Stephen Dann, Todd VanArsdale. Identifying synthetic lethality with novel CDK2 small molecule inhibitors via integration of high-content microscopy and -omics level platforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1954.
Self-efficacy in Insomnia Symptom Management after Digital CBT-I Mediates Insomnia Severity during the COVID-19 Pandemic.

Study objectives Digital cognitive behavioral therapy for insomnia (dCBT-I) can reduce acute insomnia and depressive symptoms and prevent symptom recurrence. The current study evaluated self-efficacy in managing insomnia symptoms as a potential mediator of the relationship between prior dCBT-I and subsequent insomnia and depressive symptoms assessed during the coronavirus 2019 (COVID-19) pandemic. Method Participants were 208 adults who completed a randomized controlled trial of dCBT-I versus sleep education in 2016-2017 and also completed self-report assessments of insomnia, depression, and self-efficacy in managing insomnia symptoms. Data were collected in May 2020, five weeks into state-wide COVID-19 stay-at-home orders. Regression and mediation analyses were used to evaluate the extent to which self-efficacy accounted for the relationship between treatment condition and improvement in insomnia and depressive symptoms from pre-treatment to COVID-19 follow-up. Results Prior dCBT-I predicted greater self-efficacy in managing insomnia symptoms. Self-efficacy accounted for 49% and 67% of the protective effect of dCBT-I against COVID-era insomnia and depressive symptoms, respectively. Conclusions This study affirms the importance of self-efficacy as a key intervention outcome and potential mechanism by which dCBT-I predicts future sleep and mental health. Future studies that evaluate the role of self-efficacy in treatment effectiveness and resilience can provide additional clues about how to optimize dCBT-I for maximum benefit to public health.
Intracoronary Imaging for PCI Planning and Stent Optimization

The currently available intracoronary imaging techniques in the US, including intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), play an important role in percutaneous coronary interventions (PCI). The applications of intracoronary imaging in PCI include its use for PCI planning, in which imaging is performed prior to PCI, and its use for stent optimization, in which imaging is performed after PCI. With respect to PCI planning, intracoronary imaging is useful in assessing lesions of intermediate stenosis severity, in sizing the target vessel for stent selection, and in providing risk assessment for peri-procedural myocardial infarction and angiographic no-reflow prior to PCI. With respect to stent optimization, the utilization of intracoronary imaging to assess the adequacy of the PCI result has been associated with improved clinical outcomes. Given the current litigious medical environment and the advent of public reporting of outcomes, the use of intracoronary imaging for PCI optimization is likely to gain increasing importance.
Cloud Infrastructure for Higher Education: The Sullivan Experience

The growth in data traffic within higher institutions has always been accompanied with the adoption of a more scalable IT infrastructure. With the increasing budgetary constraints, cloud computing (a disruptive technology) presents an attractive means to address the scalability challenges while realizing the potential of ubiquitous IT services. The on-demand business proposition of the cloud provides virtualized resources (software, platform, and infrastructure) with far-reaching efficiencies that have lowered the initial and operating IT costs for both small and large organizations. In migrating to the cloud environments, various organizations encounter challenges and experiences which are worthy of considerations by new entrants and established users. In this paper, we present the experiences of Sullivan University in transitioning to the complex cloud environment, in which a mixture of pilot and phased conversion steps were deployed in the migration process.
Oxygen and Evolution

Changes in atmospheric oxygen concentration may be linked to key evolutionary events during the past 550 million years.
Spatial Memory and Spatial Orientation

Navigating through a remembered space depends critically on the ability to stay oriented with respect to the remembered environment and to reorient after becoming lost. This chapter describes the roles of long-term spatial memory, sensorimotor spatial memory, and path integration in determining spatial orientation. Experiments presented here highlight the reference direction structure of long-term spatial memory and suggest that self-position and orientation during locomotion are updated with respect to those reference directions. These results indicate that a complete account of spatial orientation requires a more thorough understanding of the interaction between long-term spatial memory, sensorimotor spatial memory, and path integration.
The DOE/NREL Environmental Science Program

This paper summarizes the several of the studies in the Environmental Science Program being sponsored by DOE's Office of Heavy Vehicle Technologies (OHVT) through the National Renewable Energy Laboratory (NREL). The goal of the Environmental Science Program is to understand atmospheric impacts and potential health effects that may be caused by the use of petroleum-based fuels and alternative transportation fuels from mobile sources. The Program is regulatory-driven, and focuses on ozone, airborne particles, visibility and regional haze, air toxics, and health effects of air pollutants. Each project in the Program is designed to address policy-relevant objectives. Current projects in the Environmental Science Program have four areas of focus: improving technology for emissions measurements; vehicle emissions measurements; emission inventory development/improvement; ambient impacts, including health effects.
Comments: Gross worker and job flows in Europe by M. Burda and C. Wyplosz

Abstract The BW paper is stimulating because it addresses a difficult and important problem — how can the introduction of worker and firm heterogeneity in the processes of employment and job dynamics be used to simultaneously explain labor force flows and job creation and destruction? The paper provides one example of a tightly parameterized model that generates theoretical predictions for each of the major worker and firm flows. Although, these predictions have not been tested as thoroughly as one might have hoped, the BW framework makes clear that such tests are both feasible and economically interesting.
PCNA interacts with Prox1 and represses its transcriptional activity.

Purpose Prox1 is a transcription factor which can function either as a transcriptional activator, transcriptional repressor or a transcriptional corepressor. This paper seeks to better understand the role of protein-protein interactions in this multitude of functions. Methods We performed a yeast two-hybrid screen of an 11.5 day post coitum (dpc) mouse embryo cDNA library using the homeo-Prospero domain of Prox1 as bait. Computer modeling, cotransfection analysis and confocal immunolocalization were used to investigate the significance of one of the identified interactions. Results Proliferating cell nuclear antigen (PCNA) was identified as a Prox1 interacting protein. Prox1 interactions with PCNA require the PCNA interacting protein motif (PIP box), located in the Prospero domain of Prox1. Computer modeling of this interaction identified the apparent geometry of this interface which maintains the accessibility of Prox1 to DNA. Prox1 activated the chicken betaB1-crystallin promoter in cotransfection tests as previously reported, while PCNA squelched this transcriptional activation. Conclusions Since PCNA is expressed in the lens epithelium where Prox1 levels are low, while chicken betaB1-crystallin expression activates in lens fibers where Prox1 expression is high and PCNA levels are low, these data suggest that Prox1-PCNA interactions may in part prevent the activation of betaB1-crystallin expression in the lens epithelium.
Management of Cholecystitis in High-Risk Patients

The most common major abdominal operation in the Western Hemisphere is cholecystectomy [1]. In the United States alone, gallstone disease affects over 20 million people and is associated with $6.3 billion in direct costs annually [2, 3]. One factor that may contribute to these costs is the high rate of recurrence after initial presentation such that certain patients undergo multiple admissions and treatment regimens for the same disease process which has a nearly curative but potentially complication-fraught solution. For patients with acute cholecystitis and mild gallstone pancreatitis, evidence exists to support cholecystectomy within 48 h of presentation [4, 5] but only 40–75 % of patients with acute cholecystitis, gallstone pancreatitis, and common bile duct stones undergo cholecystectomy on initial hospitalization [6–8]. This rate of recurrence varies depending on the type of biliary disease which has been reported to be 6–50 % for acute cholecystitis [6, 9, 10], 5.3–50 % for common bile duct stones [11–13], and 16–76 % for gallstone pancreatitis [14–19].
Modeling user behavior and attention in search

In Web search, query and click log data are easy to collect but they fail to capture user behaviors that do not lead to clicks. As search engines reach the limits inherent in click data and are hungry for more data in a competitive environment, mining cursor movements, hovering, and scrolling becomes important. This dissertation investigates how remotely collecting rich user interaction data in the form of mouse cursor activity can help researchers understand fundamental human behavior and improve the design of search engines. Specifically, mining cursor activity can improve upon state-of-the-art methods for scoring and ranking search results, and estimating where users are looking without eye-tracking. Descriptive analyses of cursor movements show how users move their cursor when they search to provide signals of relevance and explain reasons for abandoning a search. User models can be used to infer visual attention on the page to identify what content users are looking at, as well as compute the relevance and attractiveness of search results to the user. This implicit feedback given to the search engine can then inform the layout and content presented on the pages, or improve the ranking of search results. This dissertation will demonstrate the following thesis: users' mouse cursor interactions can be collected efficiently on the Web, used to understand users' search behaviors, and can be useful in the design of Web search engines.
The Supply Side of the Digital Divide: Is There Redlining in the Broadband Internet Access Market?

The newest dimension of the Digital Divide is access to broadband (high-speed) Internet service. Using a comprehensive U.S. data set covering all forms of technology (chiefly DSL and cable modem), I look for evidence of redlining, where broadband carriers avoid areas with high concentrations of poor and minority households. There is little evidence of redlining based on income or on black or Hispanic concentration. There is mixed evidence concerning redlining based on Native American or Asian concentration. Other findings: market size, education, Spanish language use, commuting distance, and Bell presence increase access probability; inner city or rural location decreases access probability.
Maternal histone messenger RNA: detection by molecular hybridization

Abstract A competition-hybridization assay has been developed for the majority of sequences present in embryonically synthesized histone messenger RNA. The assay permits the first direct demonstration of specific “maternal” messengers in unfertilized sea-urchin eggs. The molecular size of histone messenger RNA stored in the egg appears to be the same as that of histone messenger RNA synthesized by the embryo. Maternal histone messenger RNA is found in the soluble phase of egg homogenates, in the form of ribonucleoprotein particles, unassociated with ribosomes.
Autoradiographic studies with 3H 1,25 dihydroxyvitamin D3 in thyroid and associated tissues of the neck region.

Rats and mice fed a vitamin D-deficient or vitamin D-complete diet were injected with 3H 1,25 (OH)2 vitamin D3. Autoradiograms prepared from cross sections through the neck region revealed nuclear concentration of radioactivity strongest in parathyroid chief cells, occasionally in thyroid follicular epithelial and interfollicular cells, in the epithelium of tubular remnants of the ultimobranchial body, in epithelium of the esophagus, in chondrocytes of tracheal cartilage, and in myoepithelial cells of tracheal glands. In the thyroid, most of the follicle epithelial cells did not show nuclear concentration of radioactivity which occurred only occasionally and predominantly in follicles located in marginal positions. Thyroglobulin in lumina of thyroid follicles contained varying amounts of radioactivity that correspond to the diameter of the follicles, with relatively high amounts in large follicles and little or no radioactivity in small follicles. Competition with excess of unlabeled 1,25 (OH)2 vitamin D3 abolished nuclear radioactivity, but not the radioactivity in the colloid, while 25 (OH) vitamin D3 did not affect either. When a combination of autoradiography and immunohistochemistry was applied, follicular and parafollicular C-cells positive for calcitonin antibodies, did not show nuclear concentration of radioactivity. Tubular remnants of ultimobranchial bodies, however, showed distinct nuclear labeling, but did not stain, or only weakly stain, with antibodies to calcitonin. When 3H 25 (OH) vitamin D3 was injected, no nuclear concentration of radioactivity was noted in any of the tissues. The results from these histochemical studies suggest the existence of nuclear receptors and direct genomic effects of 1,25 (OH)2 vitamin D3 in heterogeneous tissues of the neck region, which include parathyroid chief cells, myoepithelial cells of tracheal glands, chondrocytes of tracheal cartilage, epithelial cells of esophagus, and certain thyroid follicle epithelial cells. No evidence could be obtained for nuclear receptors in C-cells and cells of striated muscle.
Synthesis of Titanium, Zirconium, and Hafnium Complexes That Contain the [(MesitylN-o-C6H4)2O]2- Ligand

(MesitylNH-o-C6H4)2O (H2[MesNON]) has been synthesized in ∼70% yield, and several [MesNON]2- complexes of Ti, Zr, and Hf have been prepared, in particular a variety of dialkyl complexes, [MesNON]MR...
Simultaneous Single Detector Measurement of Multiple Fluorescent Sources

In many applications it is desirable to simultaneously measure the concentration of multiple fluorescent sources. In this paper, a simple robust technique for accomplishing this is realized by illuminating the fluorescent elements by excitation light modulated at different frequencies. A single microprocessor is used to drive the excitation sources (different color LEDs), and analyze the detector response at the two different frequencies. The excitation light at both colors is filtered by a single set of cross-polarized filters, and the signal from the single detector is locked-in to the different excitation light frequencies to simultaneously measure the response of different dyes. As proof-of-concept, this approach is demonstrated on two distinct systems. First, mixtures of concentrations of the fluorescent dyes trisodium 8-methoxypyrene-1, 3,6-trisulfonate and Rhodamine 6G in water are simultaneously measured in a standard fluorescence measurement. Then, the system is used for simultaneous detection of O2 and CO2 in a mixture of gases using two different gas-sensitive fluorescent films. The detection of oxygen is based on the fluorescence quenching of platinum octaethylporphine lumiphore in the presence of O2. The detection of CO2 is based on fluorescence quenching of hydroxypyrene trisulfonic acid trisodium salt in presence of CO2. The whole arrangement is a compact and low-cost simultaneous multicolor fluorescent sensor system that is suitable for many biological, chemical, and gas-monitoring applications.
Correlation Between Histone Lysine Methylation and Developmental Changes at the Chicken β-Globin Locus

Methylation of histones at specific residues plays an important role in transcriptional regulation. Chromatin immunoprecipitation of dimethylated lysine 9 on histone H3 across 53 kilobases of the chicken β-globin locus during erythropoiesis shows an almost complete anticorrelation between regions of elevated lysine 9 methylation and acetylation. Lysine 9 is methylated most over constitutive condensed chromatin and developmentally inactive globin genes. In contrast, lysine 4 methylation of histone H3 correlates with H3 acetylation. These results lead us to propose a mechanism by which the insulator in the β-globin locus can protect the globin genes from being silenced by adjacent condensed chromatin.
Systemic responses to prolonged hemorrhagic hypotension

Studies are needed to provide a rigorous examination of the relevance of monitored variables during prolonged hemorrhagic hypotension (HH). This study was designed to investigate the parameters tha...
Item and order recognition memory in subjects with hypoxic brain injury

Subjects with hypoxic brain injury resulting in significant cell loss in the hippocampus but not the parahippocampal gyrus or temporal lobes and normal control subjects were tested for memory impairments. The Denman Memory Scale was given to all subjects as a baseline memory assessment. All subjects were then tested for item and order recognition memory for lists of six words, pictures, abstract pictures, spatial locations, and motor responses. Results indicated that hypoxic subjects are impaired compared to control subjects on the Denman memory scale for verbal, non-verbal, and full-scale memory quotients. In addition, results indicated that compared to control subjects, hypoxic subjects displayed item and order recognition deficits for words, pictures, abstract pictures, and spatial locations. A recency effect for item recognition of abstract pictures, spatial locations, and hand positions was found. For motor response order recognition, both primacy and recency effects were found, with deficits in performance for the middle items of the list. It appears that subjects with hypoxic brain injury in the face of severe memory deficits for words, pictures, abstract pictures, and spatial locations display residual capacity for remembering the last items for spatial locations, abstract designs, and hand positions. Hypoxic subjects also display residual capacity for remembering motor responses using episodic or data-based memory.
Mechanism of action of β-bungarotoxin, a presynaptically acting phospholipase A2 neurotoxin: Its effect on protein phosphorylation in rat brain synaptosomes

E. Ueno and P. Rosenberg. Mechanism of action of β-bungarotoxin, a presynaptically acting phospholipase A 2 neurotoxin: its effect on protein phosphorylation in rat brain synaptosomes. Toxicon 34, 1219-1227, 1996.-The snake venom phospholipase A 2 neurotoxin, β-bungarotoxin, acts presynaptically to alter acetylcholine release in both the peripheral and central nervous systems. In investigating the mechanism of this action, we found that β-bungarotoxin inhibited phosphorylation of synapsin I, GAP-43 and MARCKS in rat brain synaptosomes. This inhibition was not due to the inhibition of ATP synthesis, action of arachidonic acid metabolites, or stimulation of phosphatase activities. Furthermore, the activities of Ca 2+ calmodulin-kinase II, cAMP-kinase and protein kinase C were not altered by β-bungarotoxin in either synaptic plasma membranes or cytosol. When synaptic plasma membranes were treated with β-bungarotoxin, MARCKS phosphorylation was inhibited, and this inhibition was overcome by the addition of exogenous protein kinase C. These results suggest that the interaction between MARCKS and endogenous protein kinase C is altered by β-bungarotoxin. In contrast, Naja naja atra phospholipase A 2 , a typical phospholipase A 2 enzyme, had effects on phosphorylation which were different from those of β-bungarotoxin: (1) inhibition of phosphorylation of synapsin I in intact synaptosomes was less potent than that by β-bungarotoxin; (2) it stimulated basal phosphorylation of GAP-43 and MARCKS; and (3) it increased the activity of protein kinase C. The inhibition of synapsin I phosphorylation by N. n. atra phospholipase A 2 in intact synaptosomes may be due to the inhibition of ATP synthesis. The stimulation of GAP-43 and MARCKS by N. n. atra phospholipase A 2 can be explained by the production of arachidonic acid, which stimulated protein kinase C activity to a similar extent as that caused by N. n. atra phospholipase A 2 . Thus, the mechanism of action of β-bungarotoxin appears to be quite different from that of a phospholipase A 2 enzyme, suggesting that phospholipase A 2 activity of β-bungarotoxin may not be essential for its action. β-Bungarotoxin may be a useful tool to study the physiological role of phosphorylation of synaptosomal proteins in neurotransmitter release.
Normal modes analyses of macromolecules

Abstract Normal modes analysis (NMA) has been a valuable tool for the study of the flexibility and the slow range of motion of proteins, and it nicely complements Molecular Dynamics techniques, where simulations are possible for only limited time spans. We demonstrate the usefulness of NMA by the example of a large globular protein, G-actin, and the filaments it forms: F-actin. We also discuss some less known aspects of NMA: (a) The density of modes of globular proteins departs from Debye’s prediction for solids, and is anomalous. (b) The use of dihedral angles, rather than Cartesian degrees of freedom, gives rise to interesting nonlinear effects, such as oscillations of certain subsets at twice the natural frequency of the mode. (c) For slow modes of macromolecules it is sufficient to use very simple-minded potentials, without the rich level of details habitual in NMA and Molecular Dynamics.
Mark A. Smith, PhD: Renegade Scientist and Visionary

FIGURE. Mark A. Smith, PhD In the recorded history of science, the prominent are often said to have died quietly, long after their important work had been completed, the specific date and circumstances of their death obscured by achievements during life, and the slow decay of time. The same cannot be said for Mark A. Smith, PhD, who died at the young age of 45 on December 19, 2010, 95 years to the day, as it would happen, after the death of Alois Alzheimer, the namesake for the condition that Mark would ultimately redefine. Mark differed from many of the other great scientists in history, however, in that his prominence was not an accident of pedigree or privilege, but rather the product of the virtues he bore witness to and developed as a working-class Brit. The proud son of a coal miner and homemaker, Mark learned to embrace hard work, self-sacrifice, and determination. Long walks to school throughout his youth-3 miles each way rain or shine-were a reality for him, in an era when such things were an anachronism on the other side of the Atlantic. It was perhaps not without reason that Mark developed an affinity for expensive English shoes later in life. Nor did it surprise anyone close to him that he would be walking a short distance toward home in his final minutes on December 19. Yet he faced his challenges from the beginning with an energy, charisma, and love of life that would never be blunted by station or hardship, and even as he gained in international prominence, Mark would never lose a sense of humility. Mark graduated from Bushloe High School in Wigston Magna, Leicester, where he was a football (soccer) standout, and would later become the first in his family to attend college after receiving …
Solid fraction measurement using equation-based cooling curve analysis

This work presents a new method of calculating the solid fraction of a solidifying alloy, using cooling curve analysis. This method, called the equation-based Newtonian method, is unique in that an equation is used to calculate the solid fraction, rather than the baseline technique of previous cooling curve analysis methods. In comparisons, the proposed method has shown good agreement with other methods of cooling curve analysis.
Proton and carbon n.m.r. spectra of butylated coal

Abstract The proton and carbon n.m.r. spectra of butylated Illinois No. 6 coal which has been fractionated by gel-permeation chromatography (GPC) are reported. The chemical shifts and spin-lattice relaxation times of model compounds provide the bases for the assignment of the spectroscopic results. The spectra of the various molecular weight fractions are clearly different. There are significant variations in the degree of aromaticity, the presence of linear alkanes, the ratio of C-butylation to O-butylation, the extent of butylation on aliphatic and aromatic carbon atoms, and the amount of carbonyl and vinyl derivatives. The results suggest that electron transfer, proton abstraction, ether cleavage, and elimination reactions are important under the conditions of the Sternberg process and that both nucleophilic and free-radical substitution reactions occur. The results also strongly suggest that the distribution of functional groups in coal is not uniform.
ADAM12 induces estrogen-independence in breast cancer cells

Antiestrogen therapy has been used successfully to prolong disease-free and overall survival of ER positive breast cancer patients. However, 50% of patients with ER+ tumors fail to respond to such therapy or eventually acquire resistance to endocrine therapy, resulting in tumor progression and mortality. It is imperative, therefore, to understand the mechanisms that lead to hormone refractory breast cancer in order to develop therapeutics that can modulate the resistance to antiestrogen therapy. The protease, ADAM12, can be detected in the urine of breast cancer patients and its levels correlate with disease status, stage, and cancer risk. Within the context of this study, the authors have investigated the role of the two distinct isoforms of ADAM12 in breast tumor cell proliferation and as potential mediators of endocrine resistance. Using stable clones of ADAM12-overexpressing MCF-7 cells, the authors analyzed proliferation rates of these ER+ breast tumor cells both in estrogen-depleted medium and in the presence of the antiestrogens, tamoxifen, and ICI 182,780. Acquired estrogen resistance in these cells was analyzed using phospho-RTK analysis. Upregulation and phosphorylation of proteins were detected via immunoprecipitation and immunoblotting. EGFR and MAPK inhibitors were used to explore the mechanism of acquired estrogen resistance in breast tumor cells. It was observed that overexpression of the two isoforms, transmembrane ADAM12-L, and secreted ADAM12-S, in breast tumor cells promoted estrogen-independent proliferation. In ADAM12-L-expressing cells, estrogen-independence was a direct result of increased EGFR expression and MAPK activation, whereas, the mechanism in ADAM12-S-expressing cells may be enhanced IGF-1R signaling. The importance of the EGFR signaling pathway in the estrogen-independent growth of ADAM12-L expressing cells was highlighted by the effect of EGFR inhibitors AG1478 and PD15035 or MAPK inhibitor U0126, each of which abolished the antiestrogen resistance in these cells. Taken together, these results demonstrate that ADAM12 isoforms confer a proliferative advantage to MCF-7 cells in the absence of estrogen stimulation, and suggest that downregulation of ADAM12 in combination with endocrine therapy may represent a useful pharmacological approach to breast cancer therapy.
HIV AND FAMILY THERAPISTS' DUTY TO WARN: A LEGAL AND ETHICAL ANALYSIS

In the absence of definitive legal precedents, family therapists must decide whether to warn sexual partners of HIV-positive clients when clients themselves refuse to do so. Deciding whether to break confidentiality reaises both legal and ethical issues. Legally, the Tarasoff ruling requires therapists to warn potential victims of illegal dangers posed by clients but does not require therapists to warn potential victims of dangers posed by their clients' legally permissible actions. unless the behavior of the seropositive client is proscribed by state law, warning the clients' partners does not fall within the scope of the Tarasoff ruling. Ethically, therapists must negotiate and adhere to a disclosure policy that balances considerations of respecting autonomy, maintaining integrity (avoiding fraud and betrayal), benefiting clients, and fostering responsibility. Some therapeutic and ethical aspects of these considerations are discussed.
A comparison of three methods for estimating substrate coarseness in rivers

Three methods were used to estimate coarseness of substrate within experimental stations in four Newfoundland rivers: (1) a categorical rating was derived by estimating proportions of types of all the substrate within an area; (2) a similar type of rating was derived, but from substrate types within 30 cm sections delineated on a lead rope stretched across the station; and (3) an index of coarseness of the substrate was measured from a depth sampler constructed of 11 sliding rods supported within a 1 m long frame. The rod, or depth, sampler was considered to provide the least subjective method and could therefore provide an index to validate the other methods. Compared with the standard deviations of depths for the rod sampler, the categorical ratings from the general estimate had an rs= 0.85, and the 30 cm sampler an rs= 0.86. It was deduced that the two methods of visually estimating substrate types in shallow clear rivers are reasonably adequate methods for describing coarseness, but that the depth sampler would be the more precise under certain conditions.
Incorporating electronic products into the acquisitions workflow in a small college library

Electronic products have changed the number of options available for individualizing the acquisitions workflow. Individual preferences and cost-effectiveness determine the mix of print with electronic products for each selector, with some advantages of the electronic medium being desktop availability at each workstation, the ease of electronic transfer of bibliographic information for ordering, access to the latest ordering information available, electronic searching capability, and e-mail alerts. Some of the electronic products choices used at Saint Mary’s College, a small, liberal arts oriented college, are discussed briefly.