cssi/SciSciGPT-SciSciNet huggingface dataset:
Fused Thoracic Vertebrae in Birds

The notarium, a group of fused thoracic vertebrae, is characteristic of birds of five orders and is found in one or more families of five more orders of non-passerine birds. Sixteen patterns of variation in the number of vertebrae in the notarium and of unfused vertebrae between it and the synsacrum were found. The occurrence of these patterns in the groups having a notarium is tabulated. Selective factors favoring the evolution of fusion of these vertebrae may have included the shock induced by landing on hard substrates or of striking prey and the prevention of downward bending of the ends of the thoracic portion of vertebral column while the birds are in flight. Phylogenetic implications of the presence of a notarium in several groups are discussed.
The Brethren pastor : differential conceptions of an emerging role /

Several years ago Russell Dynes in an article' on the sociology of religion pointed to the need for research studies which would lead to systematic analysis of religious authority and leadership; he concluded the article by stating that the "study of the priest, the prophet, the saint, the preacher, the seer, the leader of new sects, and the intricacies of the religious hierarchy will require an intensive role analysis."2 The research which is reported in this paper grew out of an interest in the characteristics of religious leadership, focusing particularly upon the analysis of the conceptions of the pastoral role held by a sample of lay officeholders and pastors from the Church ofthe Brethren. The analysis was directed generally toward the discovery of the degree of professionalism expected in the pastoral role and particularly the discovery of the degree of similarity between the role expectations of laymen and pastors. From the founding of the Church of the Brethren in Germany in 1708 to the
Effects of a mechanical engineering design course on students’ motivational features:

Diverse learning opportunities and deep engagement are needed to support development of engineering competencies and expertise. Deep engagement evolves from productive and high-quality motivation t...
What is a hologram? And why should you care?

Debating definitions is usually foolish. But the word “holography” is more abused than most and has come to stand for nonsense. Brilliant cosmologists, TV editors, and “New Age” devotees all believe that holograms are magic.
Analysis of Antigen-Specific T Cell-Mediated Suppression at the Clonal Level

For the purpose of investigating inhibition of T cell activation at a molecular level, we have assembled a panel of T cell hybridomas whose members respond to antigen and Class II molecules by production of the cytokine, IL-2, and have established bulk cultured Ts cells which inactivate certain T hybridomas. Several important observations concerning the interaction between T hybridomas and Ts cells have contributed to our understanding of inhibitory cellular interactions. These findings are 1) antigen-induced cytokine production by HEL/I-Ab specific T hybridomas is specifically and completely inhibited by HEL-induced Ts cells, 2) T cell hybridomas of other specificities (e.g. HEL/I-Ad) are not inhibited by HEL-Ts cells, 3) bulk cultured Ts cells are functionally superior to primary Ts cells following their short term culture in lymphokine supplemented media. This experimental system now provides an excellent opportunity to learn how helper T cells become inactivated by Ts and to describe the mechanism of inactivation in molecular terms.
Persian Gulf illnesses : preliminary neurological impressions

We review the initial impressions of the first 65 patients evaluated neurologically at Madigan Army Medical Center as mandated by the Comprehensive Clinical Evaluation Program of the Department of Defense for Persian Gulf veterans. No consistent patterns of neurologic disease or new neurologic syndromes emerged. Our experience suggests that full neurological evaluation of such patients without a clear history of neurological symptoms is not cost effective. Headaches and sleep difficulties were the two most frequent complaints. We suggest that sleep disorders may be underdiagnosed in active duty populations.
Measurement of changes in cell volume based on fluorescence quenching

The intracellular fluorescence of 6-methoxy-N-(3-sulfopropyl)-quinolinium (SPQ), a Cl(-) -sensitive fluorescent dye, is quenched by intracellular organic anions and proteins of unknown identity. The concentration of these intracellular quenchers (ICQs), however, is dependent on cell volume. In the absence of Cl-, changes in the observed SPQ fluorescence may therefore reflect changes in cell volume. This concept has been applied to determine relative changes in cell volume of cultured corneal endothelium in response to anisosmotic shocks, using NO3- as the Cl- substituent. SPQ fluorescence increased with decreasing osmolarity and vice versa. A 20 mosM hypertonic shock was needed to detect a change in SPQ fluorescence with a signal-to-noise ratio of >25. Assuming dynamic quenching by ICQs, we applied an extension of the Stern-Volmer equation to develop a simple relationship between the measured SPQ fluorescence and relative changes in cell volume. For large hyposmotic shocks, regulatory volume decrease (RVD) was observed. The rate of RVD could be enhanced by exposure to 0.5 microM gramicidin in low-Na+ Ringer solution (i.e., K+-NO3- efflux), indicating that K+ conductance is rate limiting for RVD. These results demonstrate the principle of using fluorescence quenching to measure changes in cell volume in real time. Because SPQ is sensitive to Cl-, its usefulness as a quenching probe is limited. However, a structure-activity study can be expected to yield useful Cl(-)-insensitive analogs.
Packaged heteroclite subgenomic RNAs of PRRSV.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a member of the Arteriviridae family of the Nidovirales (Meulenberg et al, 1993b; Nelsen et al., 1999). While the complete genomes of three PRRSV strains are known (Allende et al., 1999; Meulenberg et al., 1993; Nelsen et al., 1999), main questions remains to be elucidated concerning viral replication and transcription processes.
Obesity Prevalence and Dietary Intake of Antioxidants in Native American Adolescents

Antioxidants are well known for possessing anti-inflammatory properties, which can reduce the risk of chronic disease and obesity. However, very little research has been done to examine antioxidant intake among adolescent minority populations such as Native American adolescents. Our study examined the significance of antioxidant intake among Native American adolescents at an urban residential high school in Southern California. Our study population consisted of 183 male and female Native American adolescents, 14-18 years of age, representing 43 tribes from across the United States. Students’ primary source of meals was provided by the school food service. Based on the BMI calculations, the rate of obesity within our population was 38% for males and 40% for females, more than two-fold the national rate indicated by NHANESIII data. We used the Harvard School of Public Health Youth/Adolescent Questionnaire (HSPH YAQ), a semi-quantitative food frequency questionnaire, to examine antioxidant nutrient intake and evaluate the differences in the intake between normal and obese weight students. Statistical analysis of the results showed that intakes of vitamins C, E, and lycopene were the antioxidant nutrients found to be significantly different between normal and obese weight students and intakes of these nutrients were found to be higher among normal weight students (p-values = 0.02451, 0.00847, and 0.04928, respectively). These results suggest that dietary intake of antioxidants could be increased among Native American adolescents. Further research is needed to confirm our findings and identify effective ways for school food service to incorporate antioxidant rich foods into school menus.
Prenatal Cocaine Exposure Upregulates BDNF-TrkB Signaling.

Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters BDNF-TrkB signaling during brain development. Here we show prenatal cocaine exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX) of 21-day-old rats without affecting the expression levels of TrkB, P75NTR, signaling molecules, NMDA receptor—NR1 subunit as well as proBDNF and BDNF. Prenatal cocaine exposure reduces activity-dependent proBDNF and BDNF release and elevates BDNF affinity for TrkB leading to increased tyrosine-phosphorylated TrkB, heightened Phospholipase C-γ1 and N-Shc/Shc recruitment and higher downstream PI3K and ERK activation in response to ex vivo BDNF. The augmented BDNF-TrkB signaling is accompanied by increases in association between activated TrkB and NMDARs. These data suggest that cocaine exposure during gestation upregulates BDNF-TrkB signaling and its interaction with NMDARs by increasing BDNF affinity, perhaps in an attempt to restore the diminished excitatory neurotransmission.
Der Einfluß von Steroidhormonen auf die Low-Density-Lipoprotein (LDL)-Rezeptoraktivität in Hautfibroblasten

In Zellkultur genommene Hautfibroblasten besitzen, wie auch glatte arterielle Muskelzellen und andere extrahepatische Zellen, spezifische, in der Zellmembran lokalisierte, Rezeptoren fur Low-Density-Lipoproteine (LDL), der cholesterinreichen Lipoproteine niedriger Dichte [1]. Die physiologische Bedeutung dieser Rezeptoren besteht wahrscheinlich darin, das sie die Zelle mit exogenem Cholesterin beliefern [1] und dadurch zum Katabolismus der LDL aus der Blutbahn wesentlich beitragen [2]. In Patienten mit familiarer Hypercholesterinamie, in denen die LDL-Rezeptoren fehlen oder in verminderter Zahl vorliegen, ist die katabole Abbaurate von LDL aus der Blutzirkulation vermindert [3]. Diese genetisch determinierte Erkrankung geht daher mit hohen Serum-LDL-Konzentrationen und fruhzeitig einsetzender Atherosklerose einher.
Rumen Fluid Metabolomics Analysis Associated with Feed Efficiency on Crossbred Steers

The rumen has a central role in the efficiency of digestion in ruminants. To identify potential differences in rumen function that lead to differences in average daily gain (ADG), rumen fluid metabolomic analysis by LC-MS and multivariate/univariate statistical analysis were used to identify differences in rumen metabolites. Individual feed intake and body-weight was measured on 144 steers during 105 d on a high concentrate ration. Eight steers with the greatest ADG and 8 steers with the least-ADG with dry matter intake near the population average were selected. Blood and rumen fluid was collected from the 16 steers 26 d before slaughter and at slaughter, respectively. As a result of the metabolomics analysis of rumen fluid, 33 metabolites differed between the ADG groups based on t-test, fold changes and partial least square discriminant analysis. These metabolites were primarily involved in linoleic and alpha-linolenic metabolism (impact-value 1.0 and 0.75, respectively; P < 0.05); both pathways were down-regulated in the greatest-ADG compared with least-ADG group. Ruminal biohydrogenation might be associated with the overall animal production. The fatty acids were quantified in rumen and plasma using targeted MS to validate and evaluate the simple combination of metabolites that effectively predict ADG.
Museo de la Memoria y los Derechos Humanos de Santiago de Chile: crisis de memoriales y lógicas urbanísticas de mercado

El presente articulo discute el impacto producido por la inauguracion en 2010 del Museo de la Memoria y los Derechos Humanos en Santiago de Chile, en el marco de la celebracion del Bicentenario de la Independencia. La lectura que se propone entiende el Museo como respuesta al deseo del gobierno de la Concentracion por controlar el significado del resto de memoriales de Chile, que se habian vuelto demasiado ambiguos e independientes. El Museo se concibe, por tanto, como archi-memorial para controlar el sentido de los demas memoriales de Chile. Reestructura el mapa de la memoria de Santiago y, en ultima instancia, de todo el pais, a la vez que reincide en el centralismo politico. Tambien se propone un analisis de la exposicion permanente del Museo con respecto a lo excluido, tanto de la historia de otras memorias, desde el allendismo hasta el conflicto mapuche, como de la relacion jerarquica entre la exposicion permanente y las muestras temporales. Finalmente, se aboga por la necesidad de interpretar el Museo dentro de las logicas del mercado urbanistico, la gentrificacion y la espectacularizacion de la arquitectura, a partir de las politicas oficiales de reconstruccion nacional, marca-ciudad y terciarizacion economica de la modernidad neoliberal.
Optimization of Through Crackstop via using finite element modeling

The ability of Through Crackstop Via (TCV) to prevent cracks from propagation is compared to conventional crackstop using a novel systematic simulation methodology. The design of TCV is, then, optimized by varying the angle between the metal layers as well as the TCV width. The larger angle and width result in a better TCV. The improvement in the TCV saturates at a specific TCV width.
Phosphorylated Mechanistic Target of Rapamycin (p-mTOR) and Noncoding RNA Expression in Follicular and Hürthle Cell Thyroid Neoplasm

Oncocytic (Hurthle cell) and follicular neoplasms are related thyroid tumors with distinct molecular profiles. Diagnostic criteria separating adenomas and carcinomas for these two types of neoplasms are similar, but there may be some differences in the biological behavior of Hurthle cell and follicular carcinomas. Recent studies have shown that noncoding RNAs may have diagnostic and prognostic utility in separating benign and malignant Hurthle cell and follicular neoplasms. In this study, we examined expression of various noncoding RNAs including metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and miR-RNA-885-5p (miR-885) in distinguishing between benign and malignant neoplasms. In addition, the expression of phosphorylated mechanistic receptor of rapamycin (p-mTOR) was also analyzed in these two groups of tumors. Tissue microarrays (TMAs) with archived tissue samples were analyzed using in situ hybridization (ISH) for MALAT1 and miR-885 and immunohistochemistry (IHC) for p-mTOR. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was also performed on a subset of the cases.MALAT1 and miR-885 were increased in all neoplastic groups compared to the normal thyroid tissues (p < 0.05). MALAT1 was more highly expressed in HCCs compared to FTCs, although the differences were not statistically significant (p = 0.06). MiR-885 was expressed at similar levels in FTCs and HCCs. P-mTOR protein was more highly expressed in FTCs than in HCCs (p<0.001). qRT-PCR analysis of noncoding RNAs supported the ISH findings. These results indicate that the noncoding RNAs MALAT1 and miR-885 show increased expression in neoplastic follicular and Hurthle cell thyroid neoplasms compared to normal thyroid tissues. P-mTOR was most highly expressed in FTC but was also increased in HCC, suggesting that drugs targeting this pathway may be useful for treatment of tumors unresponsive to conventional therapies.
Monoclonal Antibody Therapy For Malignant Glioma

Monoclonal antibody (mAb) therapy is a rapidly evolving treatment immunotherapy modality for malignant gliomas. Many studies have provided evidence that the blood brain barrier—both at baseline and in the context of malignancy—is permissive for mAbs, thus providing a rationale for their use in treating intracranial malignancy. Furthermore, techniques such as convection enhanced delivery (CED) are being implemented to maximize exposure of tumor cells to mAb therapy. The mechanisms and designs of mAbs are widely varying, including unarmed immunoglobulins as well as immunoglobulins conjugated to radioisotopes, biological toxins, boronated dendrimers and immunoliposomes. The very structure of the immunoglobulin molecule has also been manipulated to generate a diverse armamentarium including single-chain Fv, bispecific T-cell engagers and chimeric antigen receptors. The targeted neutralization capacity of mAbs has been employed to modulate the immunologic milieu in hopes of optimizing other immunotherapy platforms. Many clinical trials have evaluated these mAb strategies to treat malignant gliomas, and the implementation of mAb therapy seems imminent and optimistic.
Specificity versus Processivity in the Sequential Modification of DNA: A Study of DNA Adenine Methyltransferase

A detailed analysis is carried out on both published experimental results and new experiments for the methylation kinetics of two-site DNA substrates (with site separations between 100 and 800 bp) catalyzed by bacterial DNA adenine methyltransferase (Dam). A previously reported rate enhancement for the second methylation event (relative to that of the first methylation) is shown to result from elevated substrate specificity for singly methylated DNA over that of unmethylated DNA and not processive turnover of both sites by the same copy of Dam. An elementary model is suggested that cleanly fits the experimental data over a broad range of intersite separations. The model hypothesizes a looping mediated interference between competing unmethylated Dam sites on the same DNA strand.
Identifying Symptoms Using Technology

The widespread usage of technology and personal devices can help track the state of well-being and mental illnesses in the general population. This chapter provides an overview of the technology used in mental health to identify symptoms with a particular focus on depression. Detection of physiological and behavioral signals such as facial expressions, vocal prosody, sleep patterns, and social behavior change that reveal symptoms of depression is discussed.
Developmental Constraints in Evolutionary Processes

Epigenetic interactions during development drastically constrain processes of morphological change during evolution. Development does not only define the apportionment of phenotypic variation upon which selection operates, but it can result in discontinuities and directionality in morphological transformations. It is argued that these properties of development in evolution are simply the result of the dynamic nature of developmental programs. Considerations of developmental mechanisms in evolution are essential to understand phyletic trends since developmental interactions basically define the universe of possible morphologies and impose limits on the directional action of natural selection.
Materials and Processes for Emerging Memories

Resistive memories such as STT-MRAM, RERAM and PCRAM use many elements, alloys and compounds that are not used in traditional semiconductor memory and even logic devices. Even newer FERAM materials based on doped HfOx, require optimizing crystal structure to get ferro-electric properties, that are not typically preferred for logic devices. For all these materials, requirements such as precise thickness in sub Angstrom values, precise composition control, surface smoothness and texture control become very critical. In addition, etching of these materials provide new challenges because halogens used in traditional RIE are in many cases too aggressive for some of these materials. The focus of this paper is on status of deposition (PVD and ALD) and etching approaches used for resistive memories. Blanket film data as well as some typical electrical behavior obtained from metalinsulator-metal (MIM) pillar structures is presented.
Spectra of Condensed, Chemisorbed, and Polymeric Molecules: An Overview

Here we show how the K-shell excitation spectra of simple free molecules, discussed in Chap. 4, evolve under the influence of extramolecular interactions in the form of van-der-Waals or chemical bonds at surfaces, and develop a molecular-orbital-based understanding of the systematic changes of the spectra with increasing molecular size.
Bromocriptine and Lergotrile in Parkinson Disease

Bromocriptine and lergotrile were compared in 24 patients with advanced Parkinson disease (PD) no longer satisfactorily responding to levodopa. For the group there was a significant decrease in rigidity, bradykinesia and total score on either drug. Thirteen of 24 patients improved at least one-stage on bromocriptine and 14 improved at least one-stage on lergotrile. Involuntary movements (IM) were more frequent on bromocriptine, while hepatoxicity was more frequent on lergotrile. Both drugs are useful in patients with advanced PD.
Constitutive Transport Element-Mediated Nuclear Export

The molecular biology of retrovirus replication and gene regulation has been intensely analyzed for many years. These studies have made it clear that retroviral expression is controlled not only at the transcriptional level, but also by posttranscriptional mechanisms that regulate the export of RNA from the host cell nucleus to the cytoplasm. This involves the action of proteins that actively shuttle between the nucleus and cytoplasm using specific nuclear import and export signals. Thus retroviruses have become important model systems for nucleo-cytoplasmic trafficking (for previous reviews, see Hammarskjold 1997; Gullen 1998; Pollard and Malim 1998)
Background Removal and Vessel Filtering of Noncontrast Ultrasound Images of Microvasculature

Objective: Recent advances in ultrasound Doppler imaging have made it possible to visualize small vessels with diameters near the imaging resolution limits using spatiotemporal singular value thresholding of long ensembles of ultrasound data. However, vessel images derived based on this method present severe intensity variations and additional background noise that limits visibility and subsequent processing such as centerline extraction and morphological analysis. The goal of this paper is to devise a method to enhance vessel-background separation directly on the power Doppler images by exploiting blood echo-noise independence. Method: We present a two-step algorithm to mitigate these adverse effects when using singular value thresholding for obtaining gross vasculature images. Our method comprises a morphological-based filtering for removing global and local background signals and a multiscale Hessian-based vessel enhancement filtering to further improve the vascular structures. We applied our method for in vivo imaging of the microvasculature of kidney in one healthy subject, liver in five healthy subjects, thyroid nodules in five patients, and breast tumors in five patients. Results: Singular value thresholding, top-hat filtering, and Hessian-based vessel enhancement filtering each provided an average peak-to-side level gain of 1.11, 18.55, and 2.26 dB, respectively, resulting in an overall gain of 21.92 dB when compared to the conventional power Doppler imaging using infinite impulse response filtering. Conclusion: Singular value thresholding combined with morphological and Hessian-based vessel enhancement filtering provides a powerful tool for visualization of the deep-seated small vessels using long ultrasound echo ensembles without requiring any type of contrast enhancing agents. Significance: This method provides a fast and cost-effective modality for in vivo assessment of the microvasculature suitable for both clinical and preclinical applications.
Why Privatize: The Reasons Rulers Today Buy, Rent, or Create Private Militaries

The era in which most wars were fought by armies created and controlled by states lasted merely a few hundred years from the seventeenth to the end of the twentieth century. That era coincided with the rise and fall of conscription. This chapter identifies the reasons why private armies coexisted with, and for centuries successfully fought against, state armies in medieval and Renaissance Europe, and why they eventually were overwhelmed by state-controlled conscript armies. I then turn to the recent revival of two sorts of private armies: those hired by nation states instead of or alongside states’ own armed forces and the dominance of private militaries in zones of weak state control. I conclude by identifying forces that are likely to increase the role of private armies in the world and factors that might reverse the recent move toward private armies.
The impact of acute central hypovolemia on cerebral hemodynamics: does sex matter?

Tolerance and cerebral blood velocity responses to simulated hemorrhage (elicited by lower body negative pressure) were similar between male and female subjects. Interestingly, the change in etCO2 ...
Counter-narratives as resistance: Creating critical social studies spaces with communities

Abstract Social studies’ explanations of race can marginalize educators of color, due to a lack of focus in the curriculum or conversations in the classroom. This article addresses the problem through composite counter-narratives, created from collaborations between the author and current social studies teachers of color. Two teachers, Charlie Smith and Rosita Hernandez, describe their experiences learning and teaching social studies through the lens of community. Current research positions counter-narratives as a pedagogical tool for pre-service teachers resisting majoritarian narratives or as a curricular tool for elementary social studies teachers challenging mainstream historical texts. However, a gap exists on in-service social studies teachers using community to create counter-narratives. Composite counter-narratives serve as a starting point in addressing this gap. This article aims to provide scholarship space for the voices of teachers of color while situating the community as a significant influence in teaching social studies.
Schottky-Barrier Photodiode Internal Quantum Efficiency Dependence on Nickel Silicide Film Thickness

In this paper we show that the internal quantum efficiency of NiSi Schottky-barrier photodetectors can be significantly improved as the silicide film thickness is reduced close to its percolation threshold. We fabricated photodetectors in two optical configurations (front-side and back-side illuminated) at four different film thicknesses between 1-4 nm as well as a thick (100 nm) reference device. We simultaneously fit the reflection and transmission data for each silicide film on silicon as well as for front and backside illuminations to extract the refractive index dispersion of each film. Using this technique, we can accurately determine the absorption of each constituent layer and extract the wavelength-dependent internal quantum efficiency from the external quantum efficiency. We show that the internal quantum efficiency is highly dependent on the silicide film thickness while the dark current is not. The internal quantum efficiency of our thinnest detector is the highest reported of any silicide Schottky-barrier photodetector of comparable barrier height to date with a 57× improvement over the thick (reference) device. Using an approximation to Vickers' model, we were able to fit the IQE spectra to extract the hot carrier mean-free path of electrons in NiSi.
The effects of arts-integrated instruction on memory for science content

Strong correlational evidence suggests that involvement in the arts improves students' academic outcomes and memory of learning events [1-3]. It is unclear whether the improved outcomes are the result of general exposure to the arts, the integration of arts into content instruction, the use of effective instructional practices, or a combination of these factors. Moreover, as a growing number of studies suggest that arts-integrated pedagogy enhances learning, few empirical studies have explicitly examined the direct effect of an arts-integrated curriculum on learning and specifically on students' memory for non-arts academic content. Thus, this study sought to determine the effects of arts-integrated lessons on long-term memory for science content. We hypothesized that embedding arts-based activities into conventionally taught lessons would produce learning outcomes as good as or better than traditional instruction. This paper describes the results of a randomized control trial that measured retention of science content using arts-integrated science units and matched units employing convention science instruction. The study was conducted in 16 fifth-grade classrooms in an urban mid-Atlantic school district.
Chemoproteomic Profiling Uncovers CDK4-Mediated Phosphorylation of the Translational Suppressor 4E-BP1.

Summary Recent estimates of the human proteome suggest there are ∼20,000 protein-coding genes, the protein products of which contain >145,000 phosphosites. Unfortunately, in-depth examination of the human phosphoproteome has outpaced the ability to annotate the kinases that mediate these post-translational modifications. To obtain actionable information about phosphorylation-driven signaling cascades, it is essential to identify the kinases responsible for phosphorylating sites that differ across disease states. To fill in these gaps we have developed an unbiased, chemoproteomic approach for identifying high-confidence kinase-substrate interactions with phosphosite specificity. Using this assay, we uncovered the role of cyclin-dependent kinase 4 (CDK4), a clinically validated kinase important for cell-cycle progression, in regulating cap-dependent translation via phosphorylation of the tumor suppressor 4E-BP1. The discovery of this signaling axis sheds light on the mechanisms by which CDK4/6 inhibitors control cell proliferation and constitutes a successful example of kinase discovery using an activity-based, kinase-directed probe.
Abstract P5-05-06: Progesterone receptor (PR) isoform-specific expansion of breast cancer stem-like cells occurs through a phospho-PR/FOXO1 driven signaling axis

Luminal breast cancers account for ˜75% of cases and are positive for progesterone receptor (PR) and estrogen receptor (ER) expression. PR is a classical ER-target gene and is used as a biomarker of ER activity; however, a growing body of evidence supports the role of PR as an important modifier of ER actions and a key driver of luminal breast cancer progression. Progesterone signaling is mediated by two PR isoforms: full-length PR-B and truncated PR-A, which lacks the N-terminal 164 amino acids. Little is known about PR isoform-specific actions in PR-expressing breast tumors, given that total PR expression is measured clinically. Herein, we sought to identify phenotypic differences in luminal breast cancer cells (T47D) overexpressing PR-A (T47D-YA) or PR-B (T47D-YB). We demonstrate that PR-B expression is required for anchorage-independent colony formation, while PR-A expressing cells fail to proliferate in soft agar. PR-B driven proliferation has been mapped to PR phosphorylation events, which include MAPK or CDK consensus sites such as Ser294. We demonstrate that in contrast to previous reports, PR-A is well phosphorylated at Ser294 in response to progestins (e.g. R5020) using our custom phospho-PR (Ser294) polyclonal antibody. Interestingly, Ser294 phosphorylation of PR-A occurs more rapidly and robustly following hormone treatment compared to PR-B expressing cells. Our findings indicate that PR-A is a dominant driver of stem-like expansion in breast cancer cells. PR-A tumorspheres exhibited enriched ALDH+ and CD44+/CD24- populations compared to PR-B and promoted heightened gene expression of stem-like genes (e.g. FOXO1). We demonstrate that the PR target gene and co-activator FOXO1 promotes both PR-A and PR-B phosphorylation at Ser294 and augments tumorsphere formation. Direct inhibition of FOXO1 levels abrogates phospho-PR (Ser294) levels and tumorsphere formation in PR expressing cells. Finally, we show that Ser294 is required for PR-A induced expression of stem-like genes (e.g. FOXO1) and stem-like behavior as measured by ALDH+/CD44+ tumorspheres. Taken together, our data reveal unique functions of PR isoforms as modulators of distinct and opposing pathways (i.e. proliferation versus stem-like expansion) in luminal breast cancer models. A clear understanding of PR isoform-specific actions, phosphorylation events, and the role of co-factors such as FOXO1 may lead to novel biomarkers of advanced tumor behavior and reveal new approaches to pharmacologically target PR isoforms in luminal breast cancers. Citation Format: Truong TH, Dwyer AR, Diep CH, Lange CA. Progesterone receptor (PR) isoform-specific expansion of breast cancer stem-like cells occurs through a phospho-PR/FOXO1 driven signaling axis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-05-06.
A phase I study of the safety and immunogenicity of a multi-peptide personalized genomic vaccine in the adjuvant treatment of solid tumors and hematological malignancies.

e14307Background: Mutation-derived tumor antigens (MTAs) arise as a direct result of somatic variations that occur during carcinogenesis and can be characterized via genetic sequencing and used to ...
Real-Time Interaction and Cost Estimating within Immersive Virtual Environments

AbstractThe architecture, engineering, and construction industry has increased the adoption of virtual reality (VR) tools and applications in recent years. VR is an extremely versatile tool for cre...
Achieving Health Equity in Preventive Services: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

This systematic review examines the effects of provider and population barriers on adoption and implementation of 10 preventive services, as well as the effectiveness of interventions (provider–pat...
A Generalized Dynamic Planning Framework for Green UAV-Assisted Intelligent Transportation System Infrastructure

Roadside unit (RSU) planning is vital for the operation of an intelligent transportation system (ITS). RSUs provide ground coverage limited by obstacles. Unmanned aerial vehicles (UAVs) can complement RSU coverage by providing flexible connectivity capable of adapting coverage for traffic fluctuations, energy consumption, and budgetary constraints that all have effects on ITS operations. This article proposes a general RSU/UAV joint planning solution, where complex dynamic parameters are investigated. The objective is to maximize the effective coverage of placed RSUs and UAV docks given: a budget comprised of periodic operating expenses and capital expenditures, limitations of the ground transceivers and UAVs, and use of renewable energy to offset the on-grid electricity cost. We formulate a mixed-integer quadratically constrained problem that can determine the optimal placement of RSUs and UAV stations, RSU activation schedules, if solar panels are attached, and their coverage during each time period. Due to NP-hard complexity of such a planning problem, we design a heuristic algorithm that produces suboptimal solutions in less time. Afterward, we perform a sensitivity analysis and show that changes to the parameters lead to logical shifts in infrastructure coverage. Additionally, we visualize the algorithm's performance on a large setting—Manhattan Island.
A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging

Summary Mammalian tissues engage in specialized physiology that is regulated through reversible modification of protein cysteine residues by reactive oxygen species (ROS). ROS regulate a myriad of biological processes, but the protein targets of ROS modification that drive tissue-specific physiology in vivo are largely unknown. Here, we develop Oximouse, a comprehensive and quantitative mapping of the mouse cysteine redox proteome in vivo. We use Oximouse to establish several paradigms of physiological redox signaling. We define and validate cysteine redox networks within each tissue that are tissue selective and underlie tissue-specific biology. We describe a common mechanism for encoding cysteine redox sensitivity by electrostatic gating. Moreover, we comprehensively identify redox-modified disease networks that remodel in aged mice, establishing a systemic molecular basis for the long-standing proposed links between redox dysregulation and tissue aging. We provide the Oximouse compendium as a framework for understanding mechanisms of redox regulation in physiology and aging.
The Association between Hypertension and Race/Ethnicity among Breast Cancer Survivors.

Hypertension is a significant, modifiable risk factor for cardiovascular disease (CVD). African American women who are diagnosed with early-stage breast cancer have a significantly higher risk of premature death due to CVD. The purpose of this study was to examine the association between hypertension and race/ethnicity among breast cancer survivors using data from the National Health and Nutrition Examination Surveys 1999–2014. Non-Hispanic African American and non-Hispanic White women who were diagnosed with breast cancer were identified. Hypertension was defined as taking medication to treat hypertension, having a systolic blood pressure ≥ 140, or a diastolic blood pressure ≥ 90. Modified Poisson regression was performed to estimate the prevalence ratios (PR) and corresponding 95% confidence intervals (CI) for race/ethnicity, as it relates to hypertension controlling for potential confounders. Of the 524 breast cancer survivors included in our study, 107 (20.4%) were African American and 417 (80.0%) were White. After adjusting for age, marital status, education, annual household income, health insurance, smoking and drinking status, physical inactivity, obesity, and diabetes, African American breast cancer survivors had a 30% higher prevalence of hypertension (PR = 1.30 [95% CI, 1.11–1.52]) than White breast cancer survivors. These results indicate that African American breast cancer survivors have a significantly higher risk of CVD due to hypertension even after controlling for other comorbid conditions such as diabetes and obesity.
Reconstruction of Temperature, Accumulation Rate, and Layer Thinning From an Ice Core at South Pole, Using a Statistical Inverse Method

Data from the South Pole ice core (SPC14) are used to constrain climate conditions and ice-flow-induced layer thinning for the last 54,000 years. Empirical constraints are obtained from the SPC14 i...
ON THE DISTINCTION BETWEEN FRACTAL AND SEASONAL DEPENDENCIES IN TIME SERIES DATA

Many techniques are currently available to test time series data for fractal patterns, but concerns have been raised about the fact that they do not always yield consistent results. Furthermore, fr...
Understanding spiritual assessment and intervention in China: A roadmap for addressing client spirituality in an ethical and professional manner

Spirituality is an important factor in the lives of many people in China. Yet, little information exits on how to address Chinese clients’ spiritual beliefs appropriately. This paper addresses this...
Assessing the Impact of ARF Excitation Beam Width and Tracking Beam Concurrency on DoPIo Imaging Performance in a Calibrated Phantom

Double-profile intersection (DoPIo) ultrasound combines two displacement profiles capturing identical tissue motion following an acoustic radiation force (ARF) push to estimate shear elastic modulus via an empirically derived model. However, the displacement-tracking scheme may be impacted by differences in focal configurations for both the push and track beams. A wider push beam imparts a more uniform displacement gradient than narrow ARF pushes for on-axis tracking beams, while the simultaneous formation of two displacement profiles from a single, wide transmit pulse enables the tracking of identical scatterer distributions at the cost of diminished differences between the two displacement profiles. In silico experiments suggested that DoPIo acquisitions performed using a wide ARF push beam and simultaneous tracking provided the most accurate and precise elasticity estimates. While all four combinations of parameters enabled the differentiation of a soft inclusion within a stiff background in vitro, elasticity estimates on a commercially calibrated phantom were consistently overestimated.
The Nonprofit Service Provider’S Strategic Response to Anticipated Changes in Government Funding for Hiv/Aids Programs: the California Experience

This study investigates nonprofit HIV/AIDS service providers’ strategic responses to anticipated changes in their future funding environments. The findings suggest that the service providers are willing to consider a broad range of strategic responses. Four underlying strategic dimensions are presented: Cost Management, Imagery, Revenue Producing, and Donative. Three dimensions were found to be influenced by the type of service provider. Specific strategies were identified to be significant given the type of service provider. Managerial and future research implications are addressed.
Epileptic Apnea in a Neonate

ABSTRACT.We describe an infant who had epileptic apnea in the newborn period. Response to pain was decreased during the event. The corresponding electrographic phenomena were most marked over the left central and midtemporal regions. A CT scan showed findings compatible with a hemorrhagic infarction in the left temporoparietal region. The seizures responded to phenobar-bitone. The patient has remained seizure free and was neurode-velopmentally normal when assessed at 41 months of age.
Accretion onto Intermediate-mass Seed Black Holes in Primordial Galaxies

The origin of the supermassive black holes that power the most distant quasars observed is largely unknown. One hypothesis is that they grew rapidly from intermediate-mass seeds (~100 M_sun) left by the first stars. However, some previous studies argued that accretion onto these black holes was too low to build up the mass due to strong suppression by radiative feedback. Here, we re-exam the accretion process of such a black hole embedded in a primordial gas cloud, by considering a wide range of physical and numerical parameters not explored before. We find that, while radiative heating and pressure indeed suppress accretion effectively, self-gravity of the gas eventually overcomes the feedback effects and boosts the accretion to the Eddington rate after one free-fall timescale of the cloud. Moreover, for a given black hole mass, there exists a critical density above which the accretion can reach Eddington limit. Furthermore, we find a universal correlation between black hole accretion rate and ambient gas density, which may serve as a realistic recipe for black hole growth in simulations.
Quantifying the value of constructive induction, knowledge, and noise filtering on inductive learning

Abstract Machine learning research, as one of its central goals, tries to measure, model, and understand how learning-problem properties effect average-case learning performance. For example, we would like to quantify the value of constructive induction, noise filtering, and background knowledge. This paper works toward this goal by combining psychology's mathematical learning theory with computational learning theory. The paper defines the effective dimension, a new learning measure that empirically links problem properties to learning performance. Like the Vapnik-Chervonenkis (VC) dimension, the effective dimension is often in a simple linear relation with problem properties. Also, it can be used to make verifiable predictions about learning performance. Unlike the VC dimension, the effective dimension is estimated empirically; its predictions are average case. It is therefore more widely applicable to machine-and human-learning research. The measure has been applied to several learning systems including Backpropagation. It has also been used to precisely predict the benefit of using FRINGE, a feature construction system. (The benefit was found to decrease as the complexity of the target concept increases.)
A kinetic study of the oxidation and reduction of praseodymium oxides: (17) Pr7O12 + (17 −x2)O2 ⇄ PrO2−x

Abstract Kinetic and thermodynamic studies between the ordered ι ( n = 7 in Pr n O 2 n −2 ) and the disordered α (PrO 2− x ) phases have been carried out as a function of oxygen pressure at 655, 675, 695, and 715°C using a sample of small single crystals. The existence of a reproducible hysteresis loop, which depends on the temperature and pressure, having an inflection point around a composition PrO 1.75 is shown. The inflection point is interpreted as a phase of n = 8 in Pr n O 2 n −2 (η) coherently intergrown with n = 7, 9, and 10, giving an average composition of PrO 1.75 . In order to interpret the kinetic data, various theoretical models were examined, for example, oxygen diffusion, a phase-boundary reaction control, or nucleation and growth. None of these models, however, is capable of correlating the experimental data. It was found that a plot of the reaction rate versus the ambient oxygen pressure extrapolates linearly to a finite pressure at zero rate, as was previously observed in the oxidation reaction between the ι and ζ phases of the same system. The model developed for the oxidation reaction between the ι and ζ phases has been modified by taking into account the intermediate phases around PrO 1.75 , through which the reaction passes. The modified rate law has two reaction constants: the rate constant from the reactant transforming to the intermediate phase ( k 1 ) and for the transformation from the intermediate to the product phase ( k 2 ). The fit to the experimental curve is satisfactory for both the oxidation and reduction reaction. From the temperature dependence of the observed rate constants, the activation energy for the oxidation and reduction was determined to be 75.0 and 60.9 kcal/mole, respectively.
Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming.
Some mysterious sequences associated with LDPC codes

One of the most important research areas in coding theory is weight enumeration. This is a large subject, but the basic problem is easily stated: determine or estimate the weight enumerator (B 0, ..., B n ) for an (n,k) binary linear code, specified by a (n − k) ×n parity-check matrix \(\mathcal{H}\) with entries from GF(2). Here