cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B19: Role of cell-cell communication in endocrine therapy-resistant breast cancer

Endocrine therapy is the mainstay for the treatment of estrogen-receptor positive (ER+) breast cancer. However, frequent emergence of endocrine resistance is a major clinical challenge. Cell-cell cooperation in the tumor microenvironment plays a vital role in acquiring resistance, but its role is poorly understood. We studied the interactions among endocrine-resistant (R) and -sensitive (S) breast cancer cells in the presence and absence of ER-targeted endocrine therapy. We measured changes in admixed cell population remodeling by dual fluorescent labeling of LCC1 (S) with eGFP (green fluorescent protein) and their derived resistant variant (selected against the antiestrogen fulvestrant) LCC9 (R) with mCherry (red fluorescent protein), respectively. Thus, unlike most prior studies, these are genetically related cells, rather than ER+ and ER- cell lines obtained from different patients. Our results revealed that “S”cells (LCC1) acquired the phenotype of “R” cells when cultured in a mixed population. A ratio of 5:1 of S:R cells in mixed population was sufficient to confer resistance to fulvestrant to the S cells within a six-day period. Furthermore, we show that acquirement of this resistant phenotype for the S cells was partially blocked by inhibition of either gap junctions or exosome secretion, suggesting a role of cell-cell contact as well as extracellular vesicles. Global proteomic analysis of pure and admixed S and R cell populations showed that R and S can alter key molecular features of each other when present in mixed cell populations. We used a Bayesian approach to fit single culture cell populations to infer density-dependent growth parameters (growth rate, carrying capacity) and a generalized Lotka-Volterra model to understand how S and R coculture populations may be depressing or supporting growth of the other. Our results identify a net mutualistic interaction between the susceptible and resistant cancer strains, demonstrating that there are ecological dynamics to cancer resistance. In some tumors, ecological dynamics may be more mechanistically relevant than simple Darwinian-based clonal selection in driving tumor heterogeneity and determining response to treatment. Our study strongly indicates that different tumor cell types that may exist in tumors are able to influence each other, which leads to alteration of phenotype. Note: This abstract was not presented at the conference. Citation Format: Surojeet Sengupta, Rong Hu, Zachary Susswein, Adeola Fagunloye, Shweta Bansal, Robert Clarke. Role of cell-cell communication in endocrine therapy-resistant breast cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B19.
Unsupervised Ensemble-Kernel Principal Component Analysis for Hyperspectral Anomaly Detection

Unsupervised anomaly detection-which aims to identify outliers in data sets without the use of labeled training data-is critically important across a variety of domains including medicine, security, defense, finance, and imaging. In particular, detection of anomalous pixels within hyperspectral images is used for purposes ranging from the detection of military targets to the location of invasive plant species. Kernel methods have frequently been employed for this unsupervised learning task but are limited by their sensitivity to parameter choices and the absence of a validation step. Here, we use reconstruction error in the kernel Principal Component Analysis (kPCA) feature space as a metric for anomaly detection and propose, via batch gradient descent minimization of a novel loss function, to automate the selection of the Gaussian RBF kernel parameter, σ. In addition, we leverage an ensemble of learned models to reduce computational cost and improve detection performance. We describe how to select the model ensemble and show that our method yields better detection accuracy relative to competing algorithms on a pair of data sets.
Purification and partial characterization ofd-(−)-lactate dehydrogenase fromLactobacillus helveticus CNRZ 32

d-(−)-Lactate dehydrogenase (LDH) was purified to homogeneity from a cell-free extract ofLactobacillus helveticus CNRZ 32. The native enzyme was determined to have a molecular weight of 152 000 and consisted of four identical subunits of 38 000. This enzyme was NAD dependent fructose 1,6-diphosphate (FDP) and ATP independent. It was most active on pyruvate followed by β-hydroxypyruvate as substrates. TheKm values for pyruvate andd-(−)-lactate were 0.64 and 68.42 mM respectively, indicating that the enzyme has a higher affinity for pyruvate. The enzyme activity was completely inhibited byp-chloromercuribenzoate (1 mM) and partially by iodoacetate, suggesting the involvement of the sulfhydryl group (-SH) in catalysis. Optima for activity by the purified enzyme were pH 4.0 and 50–60°C. Limited inhibition ofd-(−)-LDH was observed with several divalent cations. Additionally, HgCl2 was observed to strongly inhibit enzyme activity. The purified enzyme was not affected by dithiothreitol or any of the metal chelating agents examined.
Predicting potential palliative care beneficiaries for health plans: A generalized machine learning pipeline.

Abstract Recognizing that palliative care improves the care quality and reduces the healthcare costs for individuals in their end of life, health plan providers strive to better enroll the appropriate target population for palliative care. Current research has not adequately addressed challenges related to proactively select potential palliative care beneficiaries from a population health perspective. This study presents a Generalized Machine Learning Pipeline (GMLP) to predict palliative needs in patients using administrative claims data. The GMLP has five steps: data cohort creation, feature engineering, predictive modeling, scoring beneficiaries, and model maintenance. It encapsulates principles of population health management, business domain knowledge, and machine learning (ML) process knowledge with an innovative data pull strategy. The GMLP was applied in a regional health plan using a data cohort of 17,197 patients. Multiple ML models were turned and evaluated against a custom performance metric based on the business requirement. The best model was an AdaBoost model with a precision of 71.43% and a recall of 67.98%. The post-implementation evaluation of the GMLP showed that it increased the recall of high mortality risk patients, improved their quality of life, and reduced the overall cost. The GMLP is a novel approach that can be applied agnostically to the data and specific ML algorithms. To the best of our knowledge, it is the first attempt to continuously score palliative care beneficiaries using administrative data. The GMLP and its use case example presented in the paper can serve as a methodological guide for different health plans and healthcare policymakers to apply ML in solving real-world clinical challenges, such as palliative care management and other similar risk-stratified care management workflows.
13 A learning system for safer re-opening of K-12 schools during the COVID-19 pandemic

Background School closures due to the coronavirus disease 2019 (COVID-19) pandemic are harmful to children’s education. Uncertainty in infectiousness and challenges of managing asymptomatic infection slowed school re-opening in many areas of the US. The pandemic required fast, evolving, iterative response from public health and K-12 schools. Objective Use data displays designed for improvement, coupled with expertise in learning from variation, to offer insights in a fast-paced policy environment. Provide learning support alongside data. Methods A multidisciplinary team with expertise in epidemiology, family medicine, public health, and biostatistics formed to provide support in learning methods to the second largest US K-12 school system. The team generated time series and funnel statistical process control charts, using the drill-down pathway to provide insight at multiple levels of the school system. The team identified essential capabilities in data and scientific translation to support real-time, fast-paced operational decision-making. Results Outcomes include positive COVID-19 tests identified through surveillance (figure 5), school-based secondary infection, school enrollment (figures 1 and 2), quarantine associated with being a close contact of a COVID-19 positive student or staff member, and vaccination drawing from community-level data linked with school region (figures 3 and 4). Data displays showed variation in actionable formats. Conclusions Common data displays in COVID-19 lack elements required to learn from variation, including denominators, disaggregation (granularity), and operationally relevant stratification (such as subregion and school configuration). Providing these displays offered actionable data to the school district that they employed in areas such as vaccination outreach and testing protocols. There is an ongoing need for scientific input and support of actionable data displays, for use by public health as well as school districts. Future work will include incorporating these displays into operations and generating them from developing databases.
Eminent Domain: The Solution to the Foreclosure Crisis or Overstepping Government Boundaries?

In the summer of 2012, the relatively unknown county of San Bernardino, California made national headlines when its CEO announced that he would entertain a venture fund’s proposal to use the county’s power of eminent domain to seize mortgages and sell them for restructuring in an effort to assist the county’s struggling homeowners. While many, including California Lieutenant Governor Gavin Newsom, backed the county’s resourcefulness in desperate times, others have questioned whether the county could be overstepping its constitutional bounds and causing more harm than good. Is this the long-awaited solution to America’s floundering housing market? Unfortunately, it seems a revival of the market through eminent domain is unlikely. While the San Bernardino proposal would be within the limits of the power afforded to states and municipalities by the U.S. and state constitutions, it may have a long-term cooling effect on the lending market that would greatly outweigh any short-term relief it may offer. This article will provide both an analysis of the legal concept of eminent domain and its likelihood of success in resuscitating real estate markets in towns like San Bernandino. Sections Two and Three will explore the background of the mortgage crisis and provide an indepth description of the eminent domain proposal by the Mortgage Resolution Partners (“MRP”). Section Four takes a deeper look into the state and federal precedent on a municipality’s power to use eminent domain, revealing that the definition of “legitimate public purpose” would likely apply to the seizing of mortgages. Finally, Section Five will focus on the predicted effect this proposal, if enacted, would have on lenders and borrowers, proving that San Bernardino should refrain from using eminent domain to seize private mortgages.
State of Siege and Rule of Law in Argentina: The Politics and Rhetoric of Vindication

During the Colonial period of Latin American history the conduct of officials appointed by the Spanish crown to serve in the provinces was subject to a formal review at the end of their term of office. At the public hearing, or residencia, anyone in the jurisdiction could appear before the presiding officer to present charges or to testify either for or against the incumbent. When an unfavorable judgment was rendered, the office-holder had to make restitution to the persons he had mistreated, or perhaps undergo more severe punishment. No one could leave office without first submitting to the residencia.1
Three dimensional flow at the junction between a turbine blade and end-wall

A visualization of the flow on the suction side and end-wall of a passage between two neighboring turbine blades is compared with mass (heat) transfer measurements on the same surfaces. Besides the horseshoe and passage vortices, there are several smaller vortices formed near the junction of blade and end-wall whose origins are discussed. The vortices detach from the end-wall and move up the blade's span. These vortices, sometimes in counter rotating pairs, are responsible for substantial local variations of heat transfer.
Facial expression recognition using facial features andmanifold learning

This paper explores robust facial expression recognition techniques based on the underlying low dimensional manifolds embedded in facial images of varying expression. Faces are automatically detected and facial features are extracted, normalized and mapped onto a low dimensional projection surface using Locality Preserving Projections. Alternatively, processed image pixels are used for manifold construction. Classification models robustly estimate expression from the low dimensional projections in manifold space. This method performs robustly in natural settings, enabling more engaging human computer interfaces.
Women and domestic violence: global dimensions, health consequences and intervention strategies.

Domestic violence against women is a significant health and social problem affecting virtually all societies. The sensitivities and stigma associated with domestic violence, the conceptualization of it primarily as a judicial and legal issue, and the lack of data on the dimensions of abuse have hampered understanding and the development of appropriate interventions. Secrecy, insufficient evidence, and social and legal barriers continue to make it difficult to acquire data on domestic violence against women. This paper describes the magnitude and health consequences of domestic violence. It explores factors that perpetuate violence against women, and discusses intervention strategies from around the world. Language: en
Styles of Truth in Gao Xingjian's Soul Mountain

China's Gao Xingjian, now a French citizen, was awarded the Nobel Prize for Literature in 2000. In the official announcement Gao's 'great novel' Soul Mountain was singled out for special praise. This essay draws on the work of Austrian-American political theorist Eric Voegelin's work to argue that Soul Mountain is best understood as a miniature of China's experience with and symbolic expression of various 'styles of truth' in its long and complex history of establishing and losing social and political order.
Direct Determination of Interfacial Traction-Separation Relations in Chip-Package Systems

Microelectronic devices are multilayered structures with many different interfaces. Their mechanical reliability is of utmost importance when considering the implementation of new materials. The cohesive interface modeling approach has the capability of modeling crack nucleation and growth, provided interfacial parameters such as strength and toughness of the system are available. These parameters are obtained through the extraction of traction-separation relations, through indirect either hybrid numerical/experimental methods or direct experimental methods. The direct method promises to determine the parameters in an unambiguous manner. All methods of extracting traction-separation relations require some local feature of the crack-tip region to be measured.
Pulling the Plug: Can There Be a Deal with China on Korean Unification?

North Korea is a failed state waiting to happen. It imposes horrific privations on its own citizens as well as serious security threats on its neighbors and the United States. For twenty years, Sou...
Turbulent kinetic energy budgets from a large-eddy simulation of airflow above and within a forest canopy

The output of a large-eddy simulation was used to study the terms ofthe turbulent kinetic energy (TKE) budget for the air layers above andwithin a forest. The computation created a three-dimensional,time-dependent simulation of the airflow, in which the lowest third ofthe domain was occupied by drag elements and heat sources to representthe forest. Shear production was a principal source of TKE in theupper canopy, diminishing gradually above tree-top height and moresharply with depth in the canopy. The transfer of energy to subgridscales (dissipation) was the main sink in the upper part of the domainbut diminished rapidly with depth in the canopy. Removal ofresolved-scale TKE due to canopy drag was extremely important,occurring primarily in the upper half of the forest where the foliagedensity was large. Turbulent transport showed a loss at the canopytop and a gain within the canopy. These general features have beenfound elsewhere but uncertainty remains concerning the effects ofpressure transport. In the present work, pressure was calculateddirectly, allowing us to compute the pressure diffusion term. Wellabove the canopy, pressure transport was smaller than, and opposite insign to, the turbulent transport term. Near the canopy top andbelow, pressure transport acted in concert with turbulent transport toexport TKE from the region immediately above and within the uppercrown, and to provide turbulent energy for the lower parts of theforest. In combination, the transport terms accounted for over half ofthe TKE loss near the canopy top, and in the lowest two-thirds of thecanopy the transport terms were the dominant source terms in thebudget. Moreover, the pressure transport was the largest source ofturbulent kinetic energy in the lowest levels of the canopy, beingparticularly strong under convective conditions. These resultsindicate that pressure transport is important in the plant canopyturbulent kinetic energy budget, especially in the lowest portion ofthe stand, where it acts as the major driving force for turbulentmotions.
Feeding the Premature Infant in the 20th Century

This article reviews the historical development of feeding the premature infant in the 20th century. It describes the early work determining the energy requirements of the preterm infant, the evolution of the use of human milk and its fortification for these infants, the development of special formulas for very-low-birth-weight infants and the various techniques/methods utilized including total parenteral nutrition.
Chronic Administration of the Triazolobenzodiazepine Alprazolam Produces Opposite Effects on Corticotropin-Releasing Factor and Urocortin Neuronal Systems

In view of the substantial preclinical evidence that supports a seminal role of central corticotropin-releasing factor (CRF) neuronal systems in the physiology and pathophysiology of stress and anxiety, it is reasonable to suggest that the anxiolytic properties of benzodiazepines are mediated, at least in part, via regulation of CRFergic function. To begin to test this complex hypothesis, we examined the effects of acute and chronic administration of the triazolobenzodiazepine agonist alprazolam on CRF peptide concentrations, receptor-binding density, and mRNA expression in the CNS. Additionally, we measured mRNA expression for urocortin, a recently discovered neuropeptide that is generally considered to be a second endogenous ligand for CRF receptors. Both acute and chronic alprazolam administration was found to decrease CRF concentrations within the locus coeruleus. Furthermore, chronic alprazolam decreased basal activity of the hypothalamic–pituitary–adrenal axis, CRF mRNA expression in the central nucleus of the amygdala, and CRF 1 mRNA expression and receptor binding in the basolateral amygdala. In marked contrast, urocortin mRNA expression in the Edinger-Westphal nucleus and CRF 2A receptor binding in the lateral septum and ventromedial hypothalamus were increased. Similar findings of an inverse relationship between the CRF 1 and CRF 2A receptor systems have been reported in an anxiety model based on adverse early-life experience, suggesting the intriguing possibility that CRF neuronal systems may be comprised of two separate, but interrelated, subdivisions that can be coordinately and inversely regulated by stress, anxiety, or anxiolytic drugs.
Time-Resolved X-Ray Detection Using MOS-C Detectors

To develop a fast x-ray detector with a memory, we have performed experiments with metal-oxide-semiconductor capacitor (MOS-C) devices. For timeresolved recording of the x-ray pulse, a linear array of detectors is uniformly irradiated while the elements are sequentially biased at ?t time intervals; significant positive charge trapping occurs in each element of the array only during the period ?t when the high field bias is applied across the dielectric. Detection of 10-ns resolution has been recorded. Time-resolution is presently limited by the bandwidth limitation of the bias strobing method.
Secondary ion shadow-cone enhanced desorption

The incident angle dependence of the secondary particle emission process under keV ion bombardment has been investigated. The results from the full molecular dynamics calculations indicate that the flux anisotropy of the incident beam, resulting from the non-uniform impact parameters for the surface atom of a single crystal, affects the particle desorption in a systematic fashion. The enhanced desorption at certain angles of incidence corresponds to the intensive focusing of the incident beam to the near-surface atom and the extended dissipation of momentum by large-angle scattering. This observatvon has led us to develop a new theoretical model in which the enhanced desorption is described by the distance of closest encounter along the trajectory of the incident particle to the surface atom. The computer time for the simulation of the incident-angle-dependent emission process is significantly reduced. The results from the calculation based on this model are in good agreement both with the results from the full dynamics calculation and with the experimental results. The new model also allows a complementary evaluation of the microscopic dynamics involved in the shadow-cone enhanced desorption.
High-performance liquid chromatography analysis of 1-aminocyclopropane-1-carboxylic acid using o-phthaldialdehyde precolumn derivatization

A simple, rapid, direct method for the HPLC analysis of 1-aminocyclopropane-1-carboxylic acid (ACC) as its o-phthaldialdehyde derivative is described. The method is sensitive to about 1 pmol and can be used on plant tissue extracts with no cleanup. It will prove valuable in plant extracts where the chemical conversion of ACC in the tissue extracts to ethylene is variable, or when analyzing the specific radioactivity of ACC produced from radiolabeled precursors.
Chemical-induced estrogenicity

Estrogens are critical hormones required for human health, but they have also been linked to human diseases. Inappropriate exposures to estrogens during critical developmental periods or later in life can lead to adverse health effects, and these considerations have been important for the scientific, regulatory, and public concern regarding exposures of wildlife and humans to endocrine-disrupting compounds and particularly those that exhibit estrogenic activity. An increasing number of industrial products or byproducts exhibit estrogenic activity, including organochlorine pesticides, some polychlorinated biphenyls, and phenolic compounds such as alkyl phenols and bisphenol A (BPA). Many of the estrogenic endocrine disruptors of concern, such as BPA, have multiple activities, and a detailed case study using BPA as an example has outlined some of the problems for risk assessment of these compounds. Moreover, mechanistic studies demonstrate that estrogenic endocrine disruptors are selective estrogen receptor modulators and exhibit tissue-specific estrogen receptor agonist/antagonist activities that can only be determined by extensive research and not by simple predictive receptor binding or transactivation studies in cell culture models.
The CD8 T-cell road to immunotherapy of toxoplasmosis

Toxoplasma gondii infection induces a robust CD8 T-cell immunity that is critical for keeping chronic infection under control. In studies using animal models, it has been demonstrated that the absence of this response can compromise the host ability to keep chronic infection under check. Therapeutic agents that facilitate the induction and maintenance of CD8 T-cell response against the pathogen need to be developed. In the last decade, major strides in understanding the development of effector and memory response, particularly in viral and tumor models, have been made. However, factors involved in the generation of effector or memory response against T. gondii infection have not been extensively investigated. This information will be invaluable in designing immunotherapeutic regimens needed for combating this intracellular pathogen that poses a severe risk for pregnant women and immunocompromised individuals.
Increasing the Energy of the Fermilab Booster

The Fermilab booster accelerator was originally conceived for acceleration of protons with an injection energy of 200 MeV to an extraction energy of ten GeV (to the 500 GeV main accelerator). Early booster operation has been limited to eight GeV. The booster beam will be more acceptable to the main accelerator if extraction is at ten GeV, thus we are now modifying the booster magnet system for ten GeV acceleration. Regulation of the booster magnetic field for injection at 200 MeV was a task even when operating to eight GeV. This paper outlines the approach which was adopted and how it relates to the ten GeV attempt. Further, it highlights the problems encountered in the design of any AC magnet system.
Approximation of unbounded functions via compactification

Approximants to functions f(s) that are allowed to possess infinite limits on their interval of definition, are constructed. To this end a compactification of R^nis developed which is based on the projection of R^n on a bowl-shaped subset of a parabolic surface. This compactification induces a bijection and a metric with several desirable properties that make it a useful tool for rational approximation of unbounded functions. Roughly speaking this compactification enables us to show that unbounded functions can be approximated by rational functions on a closed interval; thus we also obtain an extension to Weierstrass' celebrated theorem. An extension to a Fourier-type theorem is also obtained. Roughly speaking, our result states that unbounded periodic functions can be approximated by quotients of certain trigonometric sums. The characteristics of the main results are the following. The approximations do not require the original approximated function to possess a restricted rate of growth. Neither do they require that the approximated function possess any amount of smoothness. Moreover, the numerator and denominator, in an approximating quotient are guaranteed not to vanish simultaneously. Furthermore, some of the proposed approximations are guaranteed to be bounded at every point at which the original approximated function is bounded. Beside the tool of compactification we also employ Bernstein polynomials and Cesaro means of ''trigonometric sums''.
Preparation and properties of conducting polypyrrole doped with fluorinated imides

Abstract Doped polypyrrole is prepared electrochemically by oxidative polymerization of the monomer in aqueous solutions of the fluorinated imines, HN(SO 2 CF 3 ) 2 , HN(SO 2 CF 3 )C(O)CF 3 and HN(SO 2 F)C(O)CF 3 ; the conductivities of the free-standing films range from 3 to 22 S cm −1 . PPY +− N(SO 2 CF 3 ) 2 exhibits the expected semiconductor behaviour and is especially stable under ambient conditions in the laboratory. Polymerization of pyrrole also occurs in acetonitrile solution in the presence of the corresponding tetralkylammonium salts.
Heterogeneous survival responses of human gastric cancer clones to αDifluoromethylornithine in vitro

The effects of αDifluoromethylornithine (DFMO)2 on survival of human gastric cancer clones were studied in vitro. The responses were dose and time dependent. Treatments which lasted for less than 12 h were cytotoxic at only the highest doses used. The greatest effects on survival were observed only when cells were treated for 48 and 72 h. The effects on the clones produced by such prolonged treatment durations were heterogeneous, with survival values differing by as much as 460%. By contrast, the clonal survival responses to short DFMO treatments (12 h) were very uniform (dose differential of only 19%); however, this uniformity in response could be achieved only by using non-pharmacological doses of DFMO. The heterogeneity in survival responses in the clones might be slightly associated with their levels of intracellular spermidine. Clones with the smallest amounts of intracellular spermidine at the start of treatment were most sensitive to DFMO. However, this association may not hold up with further testing in other gastric cancer clones or when studied in other cancer lines in vitro.
The action pattern of sorghum α-amylase

Abstract The action pattern of sorghum α-amylase was examined with four substrates: amylose, soluble starch, Naegeli dextrin, and waxy maize. The products were examined by paper chromatography and by spectrophotometric measurements of their iodine-staining properties. High concentrations of maltohexaose, maltoheptaose, and maltooctaose were produced, in addition to lesser amounts of other oligosaccharides. The oligosaccharides of eight or less glucose units persisted in the digest for some time after the achroic point, but maltooctaose was hydrolyzed more rapidly than maltohexaose or maltoheptaose. The significance of the iodine-staining characteristics are discussed in terms of possible mechanisms for amylases.
Steroid Hormone Receptor Coactivation and Alternative RNA Splicing by U2AF65-Related Proteins CAPERα and CAPERβ

Abstract Increasing evidence indicates that transcription and pre-mRNA processing are functionally coupled to modulate gene expression. Here, we report that two members of the U2AF 65 family of proteins, hCC1.3, which we call CAPERα, and a related protein, CAPERβ, regulate both steroid hormone receptor-mediated transcription and alternative splicing. The CAPER proteins coactivate the progesterone receptor in luciferase transcription reporter assays and alter alternative splicing of a calcitonin/calcitonin gene-related peptide minigene in a hormone-dependent manner. The importance of CAPER coactivators in the regulation of alternative RNA splicing of an endogenous cellular gene (VEGF) was substantiated by siRNA knockdown of CAPERα. Mutational analysis of CAPERβ indicates that the transcriptional and splicing functions are located in distinct and separable domains of the protein. These results indicate that steroid hormone receptor-regulated transcription and pre-mRNA splicing can be directly linked through dual function coactivator molecules such as CAPERα and CAPERβ.
Depression-like behavior and stressor-induced neuroendocrine activation in female prairie voles exposed to chronic social isolation.

Objective—Previous evidence suggests that responses to social stressors may play a mechanistic role in the behavioral and physiological changes associated with affective disorders such as depression. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that share features of social behavior with humans, and therefore might provide a useful model for examining social regulation of behaviors and physiological responses related to depression. In the present study we hypothesized that social isolation in female prairie voles would induce depression-relevant behaviors and altered neuroendocrine responses to an acute social stressor. Methods—Twenty adult female prairie voles were exposed to either 60 days of social isolation or paired (control) housing, and tested for a depression-like behavior (anhedonia), numbers of corticotropin-releasing factor- and oxytocin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and circulating levels of hormones and peptide in response to an acute social stressor (resident-intruder test). Results—Chronic social isolation produced anhedonia, measured by a reduction in sucrose intake and sucrose preference relative to paired animals. Compared to paired animals, isolated prairie voles displayed increased plasma hormone and peptide levels (oxytocin, arginine vasopressin, and corticosterone) following a 5-minute resident-intruder test, mirrored by an increased number of oxytocin- and corticotropin-releasing factor-immunoreactive cells in the hypothalamic paraventricular nucleus. Conclusions—These findings suggest that isolation in a socially monogamous rodent model induces both behavioral and neuroendocrine changes that are relevant to depression, and may provide insight into the mechanisms that underlie the development and/or maintenance of depressive disorders in humans.
A review of designs for capture–mark–recapture studies in discrete time

Design is the most influential element in the pathway to statistical inference. Designs for capture–mark–recapture (CMR) studies have become more diverse and complex during the past 50 years. I review the history of CMR designs developed for discrete time models with a focus on the assumptions of those designs, the parameters that can be estimated, the question that can be addressed, and the interrelationship among designs. CMR designs can be used to address questions in a variety of disciplines including population dynamics, evolutionary ecology, life-history, and community ecology. Methodological advances have also enabled investigators to consider designs that include nearly all common sources of CMR data simultaneously. CMR designs have been generalized to account for many assumptions; however, more emphasis needs to placed on use of auxiliary variables to increase precision and address model assumptions. CMR designs also need to be placed in the larger context of experimentation. Finally, development of more specific designs to fully utilize data resulting from emerging technologies is needed.
Cardiac Ca2+ Channel-Blocking Effects of the Cyproheptadine Derivative AH-1058 in Isolated Guinea Pig Cardiomyocytes

Abstract The Ca2+ channel-blocking efficacy of the cyproheptadine derivative AH-1058 (4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride) was quantitatively assessed using isolated guinea pig cardiomyocytes. AH-1058 (0.001 ≫ 10 μM) and its mother compound cyproheptadine (1 ≫ 100 μM) reduced the Ca2+ currents elicited from the holding potential of -80 or -40 mV. The IC50 values for cyproheptadine at holding potentials of -80 and -40 mV were 42.44 and 7.75 μM, respectively, whereas those for AH-1058 were 4.91 and 0.32 μM, respectively, whose potency was equivalent to those of the typical Ca2+ channel blocker verapamil. These results suggest that the introduction of the cinnamil structure to cyproheptadine can generate a potent L-type Ca2+ channel-blocking compound as potent as verapamil.
Making an ethical commitment: A rhetorical case study of organizational socialization

This essay approaches formal socialization in organizations as a rhetorical process, presenting a rhetorical‐critical study of one organization's formal orientation to company objectives. The analysis reveals the orientation program as a complex act aiming to shape ethical conduct of newcomers. The study identifies a strategy of evoking identification to the organization through a series of strategically focused identifications which culminate in an attempt to shape commitment to a set of organizational values. Ethical dimensions of the discourse are analyzed from a moral rights framework, revealing a rhetorical statement about the moral role of this business in society.
STRUCTURE OF BACTERIOPHAGE T4 RNASE H, A 5' TO 3' RNA-DNA AND DNA-DNA EXONUCLEASE WITH SEQUENCE SIMILARITY TO THE RAD2 FAMILY OF EUKARYOTIC PROTEINS

Bacteriophage T4 RNase H is a 5' to 3' exonuclease that removes RNA primers from the lagging strand of the DNA replication fork and is a member of the RAD2 family of eukaryotic and prokaryotic replication and repair nucleases. The crystal structure of the full-length native form of T4 RNase H has been solved at 2.06 angstroms resolution in the presence of Mg2+ but in the absence of nucleic acids. The most conserved residues are clustered together in a large cleft with two Mg2+ in the proposed active site. This structure suggests the way in which the widely separated conserved regions in the larger nucleotide excision repair proteins, such as human XPG, could assemble into a structure like that of the smaller replication nucleases.
Abstract 1052: Dual role of MEK1/2 and MEK5 in the reversal of epithelial-to-mesenchymal transition

The mitogen-activated protein kinase (MAPK) pathway has well-established roles in cellular processes including proliferation, differentiation, and regulation of cell fate, namely survival and apoptosis. In breast cancer, constitutive activation of the MAPK/extracellular signal-regulated kinases (ERK) pathways have been linked to chemoresistance and metastatic progression through distinct mechanisms including the activation of epithelial-to-mesenchymal transition (EMT). Our previous studies have shown that overexpression of MEK5 promotes EMT markers and induces the progression to a mesenchymal phenotype. Here, we tested the effects of a novel MEK1/2 and MEK5 inhibitor, SC-1-151, and other known MAPK signaling inhibitors (PD184,352 (MEK1/2), AZD6244 (MEK1/2), BIRB796 (p38)) on a panel of mesenchymal and highly metastatic breast cancer cell lines. While the MEK1/2 and p38 inhibitors decreased cell viability across cell lines, only the dual inhibition of MEK1/2 and MEK5 though the use of SC-1-151 demonstrated a change in cell morphology indicative of mesenchymal-to-epithelial transition (MET). Furthermore, the cells exhibited a significant decrease in migration potential following SC-1-151 treatment. Further analysis of the effects of SC-1-151 in the triple-negative breast cancer cell lines revealed an alteration of the genes associated with EMT, notably a decrease in expression of Fra-1, a transcription factor downstream of MAPK. Immuno-compromised mice inoculated with the MDA-MD-231 cell line and treated with SC-1-151 demonstrated decreased tumor volumes compared to vehicle-treated animals at day 30 post cell injection, implicating the role of MEK inhibition on tumorigenesis. These data demonstrate the need for a better understanding of the dual role of MEK1/2 and MEK5 signaling in breast cancer, and suggest that inhibition of the MEK1/2 and MEK5 signaling pathways leads to a decrease in EMT and cell migration. Citation Format: Van T. Hoang, Steven Elliott, Elizabeth C. Martin, Lyndsay V. Rhodes, Henry C. Segar, Hope Burks, Suravi Chakrabarty, Darlene Monlish, Theresa B. Phamduy, Doug Chrisey, Jane E. Cavanaugh, Patrick Flaherty, Bridgette M. Collins-Burow, Matthew E. Burow. Dual role of MEK1/2 and MEK5 in the reversal of epithelial-to-mesenchymal transition. [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 1052. doi:10.1158/1538-7445.AM2014-1052
An Evolutionary Fitness Enhancement Conferred by the Circadian System in Cyanobacteria

Circadian clocks are found in a wide variety of organisms from cyanobacteria to mammals. Many believe that the circadian clock system evolved as an adaption to the daily cycles in light and temperature driven by the rotation of the earth. Studies on the cyanobacterium, Synechococcus elongatus PCC 7942, have confirmed that the circadian clock in resonance with environmental cycles confers an adaptive advantage to cyanobacterial strains with different clock properties when grown in competition under light-dark cycles. The results thus far suggest that in a cyclic environment, the cyanobacterial strains whose free running periods are closest to the environmental period are the most fit and the strains lacking a functional circadian clock are at a competitive disadvantage relative to strains with a functional clock. In contrast, the circadian system provides little or no advantage to cyanobacteria grown in competition in constant light. To explain the potential mechanism of this clock-mediated enhancement in fitness in cyanobacteria, several models have been proposed; these include the limiting resource model, the diffusible inhibitor model and the cell-to-cell communication model. None of these models have been excluded by the currently available experimental data and the mechanistic basis of clock-mediated fitness enhancement remains elusive.
The morphology of polymeric alloys

Abstract Polymeric alloys, or multicomponent polymers, comprise block copolymers, graft copolymers and polyblends. The properties of these materials are greatly affected by their morphology. In this paper we consider systematically the morphological characteristics of polymeric alloys. The discussion drawn upon the analysis of corresponding phenomena in inorganic materials, especially metals, and explores the application of quantitative stereological methods to polymers.
Coastal upwelling in the South Atlantic Bight: A revisit of the 2003 cold event using long term observations and model hindcast solutions

Abstract Long-term (2002–2008) buoy observations, satellite imagery, and regional ocean circulation hindcast solutions were used to investigate the South Atlantic Bight (SAB) cold event that occurred in summer 2003. Observations confirmed that SAB shelf water temperature during the event was significantly colder than their 7-year (2002–2008) mean states. The cold event consisted of 6 distinctive cold wakes, which were likely related with intra-seasonal oscillations in wind fields. The upwelling index analyses based on both in situ buoy wind and North American Regional Reanalysis (NARR) highlighted that the upwelling favorable winds in 2003 were the strongest and most persistent over the 7-year study period. The regional circulation model hindcast driven by the large scale data assimilative model, NARR surface meteorological forcing and coastal river runoff generally reproduced observed hydrodynamic variability during the event. Further model analyses revealed a close relationship between the cold bottom water intrusion and the Gulf Stream (GS) core intensity and its position relative to the shelf break. Being more intensive and shoreward located, the GS worked in concert with strong upwelling favorable wind field to produce abnormal upwelling in summer 2003.
Binding and cleavage studies of two proteins intercalated at the galleries of α-zirconium phosphate

Abstract Met hemoglobin (Hb) and lysozyme are intercalated in the galleries of α-Zr(IV)phosphate (α-ZrP), and the resulting bioactive materials have been characterized using scanning electron microscopy, calorimetry and chemical footprinting methods. Microscopy revealed that the inorganic material crystallizes as nanoscopic discs of 600 nm in diameter, and that the layered structure is retained when proteins are intercalated in the galleries. Isothermal titration calorimetric studies show that binding of Hb to α-ZrP at 25 °C is strongly exothermic (Δ H = −31.0 ± 2.5 kcal/mol) with a decrease in entropy (Δ S = −77 ± 8 e.u.), while a model system such as Mg(II) binding to α-ZrP was endothermic (Δ H 1 = 2.4 ± 0.03 kcal/mol, Δ H 2 = 4.3 ± 0.3 kcal/mol). These differences in the binding thermodynamics of the two guests clearly indicate that a simple electrostatic model for the binding process is not adequate to explain Hb binding to α-ZrP. The protein-solid composites are further characterized in chemical footprinting studies. PolyammineCo(III) complexes cleave Hb and lysozyme at specific sites, and these have been used as probes to examine protein-solid contact regions. Protein cleavage studies indicated that Hb bound to α-ZrP is cleaved at four specific locations, and that these sites are accessible to the Co(III) reagents. Such access strongly suggests that the Hb tetramer is oriented in the galleries with its long axis parallel to the galleries. This conclusion is consistent with the powder X-ray diffraction (XRD) and activity studies reported earlier. Most likely this is one of the significant orientations of Hb at the galleries while other orientations are also possible. Similar footprinting studies with lysozyme bound in the galleries indicated that lysozyme is cleaved predominantly at a single site, in good yield (28%). Current results support the idea that chemical footprinting methods, when coupled with powder XRD and activity studies, are useful to examine specific orientations of the proteins at solid surfaces.
Multisite comparison of mucociliary and cough clearance measures using standardized methods

Abstract Background: A standardized protocol for measuring mucociliary (MCC) and cough clearance (CC) was developed and tested at the University of North Carolina at Chapel Hill, NC (UNC), Johns Hopkins University (JHU), and the University of Pittsburgh (Pitt). Methods: A total of 50 healthy nonsmoking adults with normal lung function were studied at the three sites: 30 [21 males/9 females (21M/9F)] at UNC, 10 (6M/4F) at JHU, and 10 (4M/6F) at Pitt. Subjects inhaled an aerosol of 99mtechnetium sulfur colloid in 0.9% saline (mass median aerodynamic diameter=5.4 μm) under controlled breathing conditions (500 mL/sec, 30 breaths/min) by following a metronome and flow signal from a commercial dosimeter. Following inhalation, subjects sat in front of a gamma camera as sequential lung images were acquired for 60 min. Subjects then coughed 60 times, and images were acquired after each set of 20 coughs, i.e., at 70, 80, and 90 min. Subjects returned to the laboratory approximately 24 hr later for a final image of ...
Geochemistry of Strontium in the Scioto River Drainage Basin, Ohio

Ground water that emanates from carbonate bedrock in the Scioto River drainage basin is characterized by 87 Sr/ 86 Sr ratios in the range of 0.708 to 0.709; usually high Sr/Ca ratios in this water identify celestite lenses within the carbonate bedrock as the dominant source of strontium. Ground water from clastic bedrock, principally shale, has 87 Sr/ 86 Sr ratios that vary from about 0.710 to about 0.713 and shows low Sr/Ca ratios. Thus, there are two basic ground-water types that emanate from bedrock within the basin. They can be identified by these two parameters. Most ground water that has been in contact only with glacial till, which covers the northern two-thirds of the basin, has carbonate-type 87 Sr/ 86 Sr ratios as well as high Sr/Ca ratios. Celestite is apparently present in the till throughout much of the Scioto basin. Ground water that contains celestite-derived strontium, whether from the carbonate bedrock or the till, has so great a strontium content as to control completely the 87 Sr/ 86 Sr ratios of surface water northwest of the glacial boundary. This fact limits the usefulness of the 87 Sr/ 86 Sr parameter as a tracer in water studies within the basin.
Biofuels from crop residue can reduce soil carbon and increase CO 2 emissions

Life-cycle assessment of biofuel carbon emissions does not usually take into account the potential for soil carbon loss resulting from crop residue removal. Now estimates of CO2 emissions due to corn residue removal across the US Corn Belt indicate that the emissions from soil carbon loss could push total emissions above the US legislative mandate.