cssi/SciSciGPT-SciSciNet huggingface dataset:
Energy efficient VM migration revisited: SLA assurance and minimum service disruption with available hosts

We propose a VM migration approach named Energy Saving Virtual Machine Migration with Minimum Disruption (ESVM3D) that reduces SLA violations by running VMs in a data center with more available physical hosts as opposed to shutting down idle hosts to save energy. As compared to previously proposed power minimizing VM migration algorithms, simulation results show a 40% reduction in VM migrations and a 10% energy savings as a result of this approach. In summary, ESVM3D achieves a 70% reduction in the number of host shutdowns, resulting in a negligible SLA degradation (≤0.1%) as compared to the previously proposed approaches, translating to a similar SLA performance and without a degradation in energy consumption.
Slow-switching-limit loss removal in SC DC-DC converters using adiabatic charging

A novel technique to remove the slow-switching-limit (SSL) loss in switched-capacitor (SC) dc-dc converters is presented. A small series inductor is cascaded with an SC converter causing adiabatic charging of the converter's energy-transfer capacitors. In this work, the theory and necessary conditions for SSL loss elimination through an inductive output filter are derived. The new topology enables high efficiency for on-die dc-dc converters while maintaining reasonable energy density. A 2:1 SC converter is built in 65-nm CMOS process to validate the analysis methods and asses the proposed technique. The proposed adiabatic charging enhances the SC efficiency by 3.3 % with only 13 % area overhead, which otherwise requires doubling the capacitor area.
Should Trump Impose a 35% Tariff on the Importation of Chinese/Mexican Products?

This paper addresses the issue of whether Donald Trump should impose a 35% tariff on the importation of certain goods from China and Mexico, and presumably other countries. Applying utilitarian ethics leads to the conclusion that the tariff should not be imposed. The same result is obtained by applying rights theory. This paper also includes a bibliography with links to dozens of publications on various aspects of trade.
Biofunctional Hydrogels for Three-Dimensional Stem Cell Culture

Traditional two-dimensional culture systems suffer from inherent limitations that motivate the need to develop three-dimensional (3D) platforms for stem cell culture to provide greater insights into in vivo function and enable advanced applications, such as tissue-engineered constructs, biomanufacturing approaches, and platforms for drug discovery and toxicity testing. Hydrogels, which are hydrated polymer networks, share many key physical properties with native tissues and can be designed to include elements to control cell fate and function. This chapter will discuss hydrogel design criteria, including source material, degradation, topography, matrix mechanics, adhesion, and growth factor presentation, in the context of 3D stem cell culture. Additionally, approaches for the manufacture and assessment of stem cell–hydrogel constructs will provide a guide to expand the utilization of biofunctional hydrogel systems.
Renal Toxicology/Nephrotoxicity of Metals and Nanometallic Particles: Arsenic, Bismuth, Cadmium, Chromium, Indium, Lead, Platinum, Uranium, and Metallic Mixtures

Metals, metal compounds, and metal-based nanomaterials are finding increasing applications in industry, consumer products, electronics, pharmaceuticals, and medical imaging. As their applications have increased, there has been increasing concerns about the nephrotoxic potential of various metals and metal-derived products. Because of its unique physiologic functions, the kidney is often exposed to higher concentrations of metals than other organs and it is frequently a primary target of nephrotoxic injury. In this article, we review the nephrotoxic effects of various metals including arsenic, bismuth, cadmium, chromium, indium, lead, platinum, and uranium on an individual and a mixture basis. Each section includes a discussion of the mechanisms of pathophysiology as they relate to changes in the renal function and the development of renal injury. In addition, for some of the most important agents, we have included brief discussions of recent issues related to the biomonitoring of exposed populations for the early detection of metal-induced nephrotoxic injury.
A Problem with No Solution

In this chapter, we explore the reasoning of students during the second session of the intervention as they worked on a task that asked for appropriate rods that could represent particular fractions. The central task of the session asked the students to represent a particular fraction in relation to a given rod representing the unit for which there was no correct solution using the available rods.
High-grade serous carcinomas arise in the mouse oviduct via defects linked to the human disease.

Recent studies suggest that the most common and lethal type of “ovarian” cancer, high-grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium (OSE). We have developed Ovgp1-iCreERT2 mice in which the Ovgp1 promoter controls expression of tamoxifen (TAM)-regulated Cre recombinase in oviductal epithelium – the murine equivalent of human fallopian tube epithelium (FTE). We employed Ovgp1-iCreERT2 mice to show that FTE-specific inactivation of several different combinations of tumour suppressor genes recurrently mutated in human HGSCs – namely Brca1, Trp53, Rb1, and Nf1 – results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widely metastatic disease in a subset of mice. The cancer phenotype is highly penetrant and more rapid in mice carrying engineered alleles of all four tumour suppressor genes. Brca1, Trp53 and Pten inactivation in the oviduct also results in STICs and HGSCs, and is associated with diffuse epithelial hyperplasia and mucinous metaplasia not observed in mice with intact Pten. Oviductal tumours arise earlier in these mice, compared to those with Brca1, Trp53, Rb1 and Nf1 inactivation. Tumour initiation and/or progression in mice lacking conditional Pten alleles likely requires acquisition of additional defects, a notion supported by our identification of loss of the wild-type Rb1 allele in the tumours of mice carrying only one floxed Rb1 allele. Collectively, the models closely recapitulate the heterogeneity and histological, genetic, and biological features of human HGSC. These models should prove useful for studying the pathobiology and genetics of HGSC in vivo, and for testing new approaches for prevention, early detection, and treatment.
The impact of HIV infection on outcomes in patients with common non-AIDS defining malignancies: A systematic review and meta-analysis.

e13078Background: HIV infection is associated with an increased risk for several non-AIDS defining cancers (NADC). An earlier meta-analysis (Shiels et al, 2009) had shown higher incidence of certain cancers in HIV patients. However, the influence that HIV status may have on long term outcomes in these patients is unclear. Methods: A systematic search of MEDLINE and Embase was performed, utilizing individual search strategies, to identify studies which described the impact of HIV infection in patients with Hodgkin’s lymphoma, leukemia and cancers of the liver, lung, anus, head and neck, stomach and kidney. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a random effects model. Results: After applying inclusion criteria, 22 studies were selected for inclusion in the meta-analysis. In these 22 studies, outcomes were reported on HIV status for Hodgkin’s lymphoma (3 studies), leukemia (1) and cancers of the liver (7), lung (9), anus (8), head and neck (4), stomach (1) and kid...
Innexin expression in electrically coupled motor circuits

The many roles of innexins, the molecules that form gap junctions in invertebrates, have been explored in numerous species. Here, we present a summary of innexin expression and function in two small, central pattern generating circuits found in crustaceans: the stomatogastric ganglion and the cardiac ganglion. The two ganglia express multiple innexin genes, exhibit varying combinations of symmetrical and rectifying gap junctions, as well as gap junctions within and across different cell types. Past studies have revealed correlations in ion channel and innexin expression in coupled neurons, as well as intriguing functional relationships between ion channel conductances and electrical coupling. Together, these studies suggest a putative role for innexins in correlating activity between coupled neurons at the levels of gene expression and physiological activity during development and in the adult animal.
Abstract 420: Preclinical evaluation of the SF3B1 inhibitor E7107 in triple negative breast cancer

Triple-negative breast cancers (TNBC) are the most aggressive subtype of breast cancer and account for roughly 15% of human breast cancers. No effective targeted therapies are currently available against these tumors, at least in part due to their genetic and epigenetic heterogeneity. Yet, TNBCs are commonly enriched for cells arrested in a progenitor-like state. We therefore performed a genome-wide siRNA lethality screen to identify selective TNBC dependencies associated with this particular phenotype in vitro. These studies led to the identification of several spliceosome genes, including the core splicing factor SF3B1, as selectively and recurrently essential for progenitor-like (or basal-A) TNBC cell lines. On this basis, we examined the antitumor effect of E7107, a clinically tested SF3B1 inhibitor, on multiple TNBC cell lines. In vitro, treatment with E7107 for 24-48 hr selectively killed basal-A cell lines relative to differentiated luminal cell lines, decreasing viability by ≈40% or more in 5 of 6 basal-A lines tested. E7107-treated cells appeared to die of apoptosis based on immunoblotting for multiple apoptotic markers. In mice, E7107 (5 mg/kg i.v. for 4 consecutive days) suppressed the growth of preformed tumors by ≈80% and ≈50% in 2 different cell-line-derived xenograft models and was remarkably well-tolerated at this dose. Of note, tumor response in vivo closely mirrored cell sensitivity in vitro, suggesting that in vitro analysis provides a fair estimate of TNBC response to E7107 in mice. Amongst 2 additional patient-derived xenograft (PDX) models tested, E7107 inhibited tumor growth by ≈50% in one model. Thus, E7107 was therapeutically active against 3 of 4 xenograft models tested. Preliminary mechanistic studies in vitro and in vivo pointed to MCL1 inactivation as a major mechanism of action of E7107 in top responders. Together, these data suggest that the spliceosome is a druggable target in TNBC, and that E7107 or similar SF3B1 inhibitors could be effective in a TNBC subset that needs to be further defined. Citation Format: Praveen Sridhar, Stefanie Chan, Ying-Jie Lock, Fabio Petrocca. Preclinical evaluation of the SF3B1 inhibitor E7107 in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 420. doi:10.1158/1538-7445.AM2017-420
Stratifying Stroke Risk in Atrial Fibrillation: Beyond Clinical Risk Scores

See releated articles, pp 2653, 2654, 2660, 2671 Atrial fibrillation (AF) is the most common atrial arrhythmia, affecting ≈1% of the US population.1 This estimate may understate its true burden, given that a high proportion of patients have subclinical AF. The prevalence of AF increases with age,1,2 and given an aging population, the projected prevalence of AF in the United States is at least 5.6 million by the year 2050.2 AF is associated with increased risk of stroke or systemic embolism3 and death.4 The heightened thromboembolic risk seen in AF is substantially reduced by anticoagulation.5 On the contrary, long-term anticoagulation can also lead to hemorrhagic complications. The recommended approach to making decisions about anticoagulant therapy in AF is to balance the expected risks of stroke versus bleeding. In this article, we review the widely used clinical methods for predicting stroke risk in AF and augment this discussion with an overview of more recent risk predictors beyond conventional clinical scores. ### Risk Factors Several studies have reported risk factors for stroke in patients with AF. A pooled analysis of 5 trials with 5956 patient-years of follow-up found that independent risk factors for ischemic stroke were age (relative risk [RR] per 10 years, 1.4), prior stroke or transient ischemic attack (TIA; RR, 2.5), hypertension (RR, 1.8), diabetes mellitus (RR, 1.7), and congestive heart failure (RR, 1.4).6 In patients 75 years of age with one or more of these risk factors, the annual stroke rate was 8.1% (95% CI, 4.7%–13.9%).6 Another systematic review, including 7 studies with >12 000 patients, identified the …
Preconceptional antithyroid peroxidase antibodies, but not thyroid-stimulating hormone, are associated with decreased live birth rates in infertile women

Objective To study whether preconceptual thyroid-stimulating hormone (TSH) and antithyroid peroxidase (TPO) antibodies are associated with poor reproductive outcomes in infertile women. Design Secondary analysis of data from two multicenter, randomized, controlled trials conducted by the Reproductive Medicine Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Multivariable logistic regression analyses were performed to assess the association between preconceptual TSH levels and anti-TPO antibodies. Setting Not applicable. Patient(s) Serum samples from 1,468 infertile women were utilized. Intervention(s) None. Main Outcome Measure(s) Cumulative conception, clinical pregnancy, miscarriage, and live birth rates were calculated. Result(s) Conception, clinical pregnancy, miscarriage, and live birth rates did not differ between patients with TSH ≥2.5 mIU/L vs. TSH Conclusion(s) In infertile women, preconceptional TSH ≥2.5 mIU/L is not associated with adverse reproductive outcomes; however, anti-TPO antibodies are associated with increased risk of miscarriage and decreased probability of live birth. Clinical Trial Registration Number PPCOS II NCT00719186; AMIGOS NCT01044862.
Caption Placement on an Augmented Reality Head Worn Device

Head worn augmented reality devices present new opportunities for creating assistive devices. This work investigates possible locations for captions for one-on-one conversations from a visibility and usability standpoint. Even in a one-on-one conversation there are interesting design challenges. We investigate 3 main factors: 1) Reference frame for captions (viewport or world coordinates); 2) Relation to the viewer (track the viewer's view, or track the speaker); and 3) Relation to speaker's face (most desirable vertical offset for captions). In this preliminary work, we argue that world coordinates are preferable (for reference frame), and then present our work in progress on the other factors.
The Lived Experience of Being a Male Nursing Student: Implications for Student Retention and Success.

Abstract Background Despite the need to improve gender diversity in the United States nursing workforce, limited studies have explored the experience of former male nursing students and research is needed to provide guidance about teaching and mentoring strategies that can promote male student retention and success. Purpose This study was conducted to explore the lived experience of former male nursing students. Methods A descriptive phenomenological approach was used. Eleven males formerly enrolled in a pre-licensure, baccalaureate nursing program participated. Individual interviews were conducted, and themes were identified. Results Five themes emerged during data analysis: (1) gender bias exists, (2) being singled out, (3) doing manly stuff, (4) limitations in clinical settings, and (5) no male role models. Conclusions Based on study findings, recommendations to promote male nursing student retention and success include improving media portrayals of male nurses, providing faculty development to heighten self-awareness of gender bias and understanding of barriers and facilitators in nursing education for male students, addressing negative experiences in maternity clinical rotations, and implementing mentorship programs to provide male role models for male nursing students.
Comprehensive Geriatric Assessment: Interprofessional Team Recommendations for Older Adult Women With Breast Cancer

Background Geriatric oncology incorporates comprehensive geriatric assessment (CGA) and traditional oncology care. Objectives The aims are to identify limitations reflected by mean scores on the CGA instruments and describe the CGA recommendations documented in the medical record. Methods CGA was administered and consisted of the Timed Up and Go Test, the Activities of Daily Living Scale, the Instrumental Activities of Daily Living Scale, grip strength, falls, pain, the Brief Fatigue Inventory, the Pittsburgh Sleep Quality Index, the Geriatric Depression Scale, the Mini-Cog, and the Mini Nutritional Assessment. CGA recommendations were obtained from the medical record. Descriptive statistics were used to analyze the data. Findings Most recommendations were for general cancer treatment, followed by fall referral/education.
Surface Charge Characteristics of Chromium (IV) Dioxide in Tetrahydrofuran with Special Reference to Magnetic-Ink Dispersions

Electrophoretic mobilities of acicular chromium dioxide (CrO2) particles have been measured in tetrahydrofuran containing sodium perchlorate, phosphatidylcholine, and cetyl trimethyl ammonium bromide (CTAB). In sodium perchlorate solutions, CrO2 is positively charged; in phosphatidylcholine and CTAB solutions, the charge on the CrO2 particles changes from positive to negative as the solute concentration is increased. There seems to exist a good correlation between the zeta potential values and the stability of CrO2 dispersions indicating the presence of electrostatic stabilization in these systems. Application of Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory to the dispersions shows that energy barriers as high as 24 kT can exist when particles have a zeta potential of approximately 70 mV.
Dedicated Systems for Surface Electropotential Evaluation in the Detection and Diagnosis of Neoplasia

The key to effective measurement and analysis of direct current (dc) skin potentials is absolute maintenance of signal integrity from the skin surface to the signal processing components of the computer’s central processor [1]. This is critical because of the inherent low amplitude of biological dc potentials. At any point in the electronic path from skin sensor to device, potential exists for noise to intrude upon signal, thereby degrading diagnostically useful information. The central themes of this chapter are the design considerations of system components necessary for keeping noise to a minimum, and methods used to extract the critical diagnostic features from the resultant dc potentials.
Framing the Principles of Catholic Social Thought

Catholic educators received an invitation in 1998 from the National Conference of Catholic Bishops to help forge a working partnership between Catholic education and the tradition of Catholic social thought. Listed are 10 principles that condense the content of Catholic social thought and package it in a way that can be more easily and effectively communicated at all levels of Catholic education.
Chapter 3 Epigenetic Control of Complex Loci During Erythropoiesis

Epigenetic mechanisms involving dynamic changes in posttranslational histone modifications commonly control gene transcription and therefore the execution of all cellular differentiation programs. The differentiation of hematopoietic stem cells into specific progenitor cells and the diverse blood cell types represents a particularly powerful system for the study of epigenetic mechanisms. The hematopoietic system allows one to define mechanisms underlying the establishment and regulation of histone modification patterns covering entire genes and/or chromosomes at distinct stages of differentiation. This chapter reviews progress in elucidating principles underlying epigenetic control of complex loci, specifically focusing on genes differentially expressed during hematopoiesis.
Pharmaceutical significance of the cyclic imide form of recombinant human glial cell line derived neurotrophic factor.

Purpose. The purpose of this paper is to determine the significance of cyclic imide formation of an aspartic acid residue during storage on the pharmaceutical quality of a recombinant human glial cell line-derived neurotrophic factor (rhGDNF) formulation.
Predictive plasma proteomic biomarkers of immunotherapy toxicity in patients (pts) with metastatic melanoma (MM).

e21569Background: Mechanisms underlying immune checkpoint inhibition (ICI) efficacy and toxicity have yet to be fully elucidated and, to date, there are no reliable biomarkers predictive of the dev...
Bioelectronics as a Possible Therapeutic Modality Targeting Sphincteric Dysfunction in Gastrointestinal Disorders

Sphincters in the gastrointestinal tract control the movement of luminal contents in the forward direction and prevent their movement in the backward direction. Defective sphincters are responsible for many of the disorders in the gastrointestinal tract. The defects might be due to abnormally loose lower esophageal or anal sphincters, with the result being diseases such as gastroesophageal reflux disease and fecal incontinence, respectively. In some cases the lower esophageal or anal sphincter might be too tight and thus prevent the forward movement of gastrointestinal luminal contents, with the result being diseases such as achalasia or functional rectosigmoid obstruction, respectively. There are multiple causes that might lead to the disruption of the normal function of these sphincters. The probable causes include damage to the nerves supplying the sphincter or to the sphincter itself either owing to trauma or owing to infection or from congenital diseases. The majority of the causes responsible for sphincteric dysfunction are still unknown. Because the majority of the causes of sphincteric dysfunction are unknown, there are very few effective pharmacologic treatments for many of these conditions. For example, all the current treatments for gastroesophageal reflux disease are aimed at treating the symptoms by decreasing the stomach acid. These treatments do little to prevent the actual event of reflux. Bioelectronic medicine may play a major role in treating these conditions by directly manipulating either the sphincter or the nerves that supply the sphincters. Because this is a targeted approach, one can expect to have better efficiency and fewer side effects than traditional pharmacological treatments.
Plasmonic Nanofactors as Switchable Devices to Promote or Inhibit Neuronal Activity and Function

Gold nanosystems have been investigated extensively for a variety of applications, from specific cancer cell targeting to tissue regeneration. Specifically, a recent and exciting focus has been the gold nanosystems’ interface with neuronal biology. Researchers are investigating the ability to use these systems neuronal applications ranging from the enhancement of stem cell differentiation and therapy to stimulation or inhibition of neuronal activity. Most of these new areas of research are based on the integration of the plasmonic properties of such nanosystems into complex synthetic extracellular matrices (ECM) that can interact and affect positively the activity of neuronal cells. Therefore, the ability to integrate the plasmonic properties of these nanoparticles into multidimensional and morphological structures to support cellular proliferation and activity is potentially of great interest, particularly to address medical conditions that are currently not fully treatable. This review discusses some of the promising developments and unique capabilities offered by the integration of plasmonic nanosystems into morphologically complex ECM devices, designed to control and study the activity of neuronal cells.
A Nonnegative Robust Linear Model for Deconvolution of Proportions

Estimating mixing rates of a sample mixture is a popular problem in biomedical studies. Recently, it is applied to find immune cell infiltration in tumor samples. The main methodological challenge is tackling the non-Gaussian nature of gene expression data. Although a probabilistic model via Multinomial or Poisson distributions would be a solution, such a model often becomes un-identifiable. An alternative is using robust regression because non-Gaussianity is often manifested as too high or too small expression values. In this article, we propose a non-negative robust linear model (NRLM) approach that yields robust yet interpretable mixing rate estimates. In our simulation study, NRLM shows a robust performance for finding the relative abundance of specified components when a large amount of noise is present. More importantly, our approach accurately estimates the absolute level of the specified components in the presence of un-specified ones. Finally, it shows a superior performance when applied to deep deconvolution of blood samples.
Babbling elicits simplified caregiver speech: Findings from natural interaction and simulation

What is the function of babbling in language learning? Our recent findings suggest that infants' immature vocalizations may elicit simplified linguistic responses from their caregivers. The contributions of parental speech to infant development are well established; individual differences in the number of words in infants' ambient language environment predict communicative and cognitive development. It is unclear whether the number or the diversity of words in infants' environments is more critical for understanding infant language development. We present a new solution that observes the relation between the total number of words (tokens) and the diversity of words in infants' environments. Comparing speech corpora containing different numbers of tokens is challenging because the number of tokens strongly influences measures of corpus word diversity. However, here we offer a method for minimizing the effects of corpus size by deriving control samples of words and comparing them to test samples. We find that parents' speech in response to infants' babbling is simpler in that it contains fewer word types; our estimates based on sampling also suggest simplification of word diversity with larger numbers of tokens. Thus, infants, via their immature vocalizations, elicit speech from caregivers that is easier to learn.
Prognostic significance of venous invasion in node-negative head and neck squamous cell carcinoma.

Background Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. Methods A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. Results Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). Conclusion Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.
Cisplatin in Combination with MDM2 Inhibition Downregulates Rad51 Recombinase in a Bimodal Manner to Inhibit Homologous Recombination and Augment Tumor Cell Kill

Dysfunction of p53 and resistance to cancer drugs can arise through mutually exclusive overexpression of MDM2 or MDM4. Cisplatin-resistant cells, however, can demonstrate increased binding of both MDM2 and MDM4 to p53 but in absence of cellular overexpression. Whether MDM2 inhibitors alone can activate p53 in these resistant cells was investigated with the goal to establish the mechanism for potential synergy with cisplatin. Thus, growth inhibition by individual drugs and combinations was assessed by a colorimetric assay. Drug-treated parental A2780 and resistant tumor cells were also examined for protein expression using immunoblot and reverse phase protein array (RPPA) and then subjected to Ingenuity Pathway Analysis (IPA). Gene expression was assessed by real-time polymerase chain reaction, DNA damage by confocal microscopy, cell cycle by flow cytometry, and homologous recombination (HR) by a GFP reporter assay. Our results demonstrate that Nutlin-3 but not RITA (reactivation of p53 and induction of tumor cell apoptosis) effectively disrupted the p53-MDM2-MDM4 complex to activate p53, which increased robustly with cisplatin/Nutlin-3 combination and enhanced antitumor effects more than either agent alone. RPPA, IPA, and confocal microscopy provided evidence for an "apparent" increase in DNA damage resulting from HR inhibition by cisplatin/Nutlin-3. Molecularly, the specific HR protein Rad51 was severely downregulated by the combination via two mechanisms: p53-dependent transrepression and p53/MDM2-mediated proteasomal degradation. In conclusion, Nutlin-3 fully destabilizes the p53-MDM2-MDM4 complex and synergizes with cisplatin to intensify p53 function, which then downregulates Rad51 through a bimodal mechanism. As a result, HR is inhibited and antitumor activity enhanced in otherwise HR-proficient sensitive and resistant tumor cells. SIGNIFICANCE STATEMENT: Rad51 downregulation by the combination of cisplatin and Nutlin-3 inhibits homologous recombination (HR), which leads to persistence in DNA damage but not an increase. Thus, inhibition of HR enhances antitumor activity in otherwise HR-proficient sensitive and resistant tumor cells.
Chapter 4 – Machine Learning

Publisher Summary This chapter gives an account of machine learning, which is the subfield of artificial intelligence (AI) concerned with intelligent systems that can learn. This chapter adopts a view of intelligent systems as agents. Learning is often viewed as the most fundamental aspect of intelligence because it enables the agent to become independent of its creator. It is an essential component of an agent design whenever the designer has incomplete knowledge of the task environment. Therefore, learning provides autonomy in that the agent is not dependent on the designer's knowledge for its success and can free itself from the assumptions built into its initial configuration. Learning in intelligent agents is essential both as a construction process and as a way to deal with unknown environments. Learning agents can be divided conceptually into a performance element, which is responsible for selecting actions, and a learning element, which is responsible for modifying the performance element. The nature of the performance element and the kind of feedback available from the environment determine the form of the learning algorithm. The chapter develops a comprehensive theory of the complexity of induction, which analyzes the inherent difficulty of various kinds of learning problems in terms of sample complexity and computational complexity.
Compositions of liquid mixtures from near-infrared spectrum data via radial basis functions and artificial neural networks

Abstract We introduce two methods for the calculation of compositions of liquid mixtures from near infrared (NIR) absorption spectroscopy data. Radial basis function (RBF) and artificial neural network (ANN) approaches are separately applied to establish correlations between spectral data and concentrations of each component. Principal component analysis (PCA) was implemented to establish the correlations and both RBF and ANN methods were trained with the first 5 principal components (PCs) obtained from 200 absorption spectra of liquid mixture samples. The trained systems were tested with 27 laboratory measurements; both results yield very good predictions of component concentrations with root-mean-square errors (RMSE) of 2–3 %. It is shown that RBF and ANN methods yield prediction errors 33 % smaller than with traditional standard multivariate methods.
Academic makerspaces as a “design journey”: developing a learning model for how women students tap into their “toolbox of design”

An academic makerspace, home to tools and people dedicated to facilitating and inspiring a making culture, is characterized by openness, creativity, learning, design, and community. This nontraditional learning environment has found an immense increase in popularity and investment in the last decade. Further, makerspaces have been shown to be highly gendered, privileging men's and masculine understandings of making. The spike in popularity warrants deeper analysis, examining the value of these spaces for women and if learning is occurring in these spaces, specifically at higher education institutions. We implemented a phenomenologically based interviewing process to capture the making experiences of 20 women students, recruited through purposive and snowball sampling. By eliciting the narratives of women students, we captured how making, designing, and creating evolved through gendered experiences in the university makerspace. Each interview was transcribed and resulted in around 868 pages of single-spaced text transcriptions. The data were analyzed through multiple cycles of open and axial coding for common themes and patterns, where makerspaces create a culture of learning, facilitate students’ design journey, and form a laboratory for creativity. These themes forwarded the creation of a learning model that showcases how design and learning interact in the makerspace. This work demonstrates that women students are engaging learning and inspiration; developing confidence and resilience; and learning how to work with others and collaborate.
Entangled agencies: Rethinking causality and health in political-ecology:

The question of non-human agency has been particularly important and generative in political-ecology. Drawing from science studies, scholars have used actor-network theory and assemblage theory to ...
Safety and Feasibility of Transradial Access in Patients Presenting With Traumatic Injuries: A Single Urban Center Experience.

Purpose:To evaluate the efficacy, safety, and feasibility of transradial approach (TRA) for endovascular management of traumatic bleeding.Materials and Methods:A retrospective review was performed ...
Are there radio-loud and radio-quiet gamma-ray bursts?

The potential existence of two separate classes of Long-duration Gamma-Ray Bursts (LGRBs) with and without radio afterglow emission, corresponding to radio-bright/loud and radio-dark/quiet populations, has been recently argued and favored in the GRB literature. The radio-quiet LGRBs have been found to have, on average, lower total isotropic gamma-ray emissions (Eiso) and shorter intrinsic prompt gamma-ray duration (e.g., T90z). In addition, a redshift-T90z anti-correlation has been discovered among the radio-loud LGRBs, which is reportedly missing in the radio-quiet class. Here we discuss the significance of the differences between the energetics and temporal properties of the two proposed classes of radio-loud and radio-quiet LGRBs. We show that much of the proposed evidence in support of the two distinct radio populations of LGRBs can be explained away in terms of selection effects and sample incompleteness. Our arguments are based on the recent discovery of the relatively-strong highly-significant positive correlation between the total isotropic emission (Eiso) and the intrinsic prompt duration (T90z) that is present in both populations of short-hard and long-soft GRBs, predicted, quantified, and reported for the first time by Shahmoradi (2013) and Shahmoradi and Nemiroff (2015).
Development and perceived value of a master's degree in health-system pharmacy administration training.

PURPOSE To describe the development, format, and alumni and employer perceptions of a program combining a master of science (MS) degree with a residency in health-system pharmacy administration and leadership (HSPAL). SUMMARY A multisite combined MS and HSPAL residency program was developed within the University of North Carolina at Chapel Hill Eshelman School of Pharmacy to increase leadership and management education. The program balances clinical and administrative experiences with didactic courses over 2 years. The program format and perceived value of MS degree training for HSPAL residents had not been previously described in the literature. In an online survey, alumni of the program, as well as their first supervisors after completion of HSPAL training, indicated perceived attainment of the program core competencies and outcomes. Supervisors also indicated that they were more likely to hire MS degree-trained pharmacists for administrative positions. CONCLUSION Didactic training in the form of an MS degree as a part of comprehensive HSPAL residency training is perceived as beneficial by alumni and employers for promoting the development of core leadership and management skills and knowledge.
On-chip ionic current sensor

Neural implants that deliver drugs or electrical stimuli via microfluidic ports are promising in providing therapy for various disorders such as epilepsy, chronic pain, and vestibular diseases. To deliver the stimuli to a neural target, these devices incorporate two or more electrodes that apply an electric field to drive charged particles or ions along an aqueous route provided by microfluidic channels. The amount of drug/current delivered is determined by measuring the ionic current flow. When the ionic current can only travel from one electrode to another via a single route or channel, the amount of therapeutic current is stoichiometrically equal to the electronic current applied by the device and therefore can be measured with an electronic current sensor. However, some recently developed devices contain networks of branched channels. In this case, the presence of multiple parallel ionic current paths makes it so that the current through any one individual channel is no longer measurable by observing electronic current alone. Here, we present an on-chip sensor that uses two Pt/Ir electrodes to transduce the ionic current through a target channel into a measurable voltage signal. The size of the metal wires did not impact the measured voltage, the size of the channel between the two sensing electrodes determines sensitivity of the sensor, change in temperature can cause a change in readings, and input impedance of the voltage measuring equipment must be greater than 1 GΩ to maintain measurement stability. The sensor showed stability of reading in a one-week longevity test.
Pregnancy associated spontaneous coronary artery dissection: A case report and review of literature.

Background Pregnancy-associated spontaneous coronary artery dissection (PSCAD) is an important cause of chest pain and acute myocardial infarction in pregnant and postpartum women. Pregnancy is considered an isolated risk factor for spontaneous coronary artery dissection. The etiology, pathogenesis, and incidence of PSCAD are not known. Case summary We present a case of a 33-year-old postpartum female who presented with sudden onset chest pain and was diagnosed with spontaneous coronary artery dissection and needed urgent catheterization revealing left anterior descending coronary artery dissection. She underwent emergent coronary artery bypass graft surgery with good post-operative recovery. Conclusion Most patients with PSCAD can be managed conservatively with medical management and have good outcomes. Patients with high-risk presentations benefit from the invasive approach. Coronary artery bypass graft may be required in select few patients based on angiography findings. Due to the risk of recurrent spontaneous coronary artery dissection, subsequent pregnancies are discouraged.
The Mystery Dinner RCA: Using Gamification and Simulation to Teach Root Cause Analysis.

Introduction Root cause analysis (RCA) is a widely utilized tool for investigating systems issues that lead to patient safety events and near misses, yet only 38% of learners participate in an inte...
Efficient geometric nonlinear elastic analysis for design of steel structures: Benchmark studies

Abstract Most structural design codes require the consideration of geometric nonlinearities or second-order effects. Analysis of second-order forces and moments in structural members requires the solution of a nonlinear system of equilibrium equations. There are many ways to solve such a system, with varying levels of accuracy and computational expense. Numerical solution schemes for the geometric nonlinear analysis of structures have been shown to produce extremely accurate results when applying small load increments and/or implementing multiple linear analyses or iterations per increment. This paper proposes the use of an approximate solution scheme that utilizes two linear analyses within a single load increment, thereby simplifying the second-order elastic analysis to a predictor-corrector type algorithm with improved computational speed. Further contributing to its efficiency is the ability to use the analysis results from within the serviceability design process in the predictor step, thereby requiring only one linear corrector analysis per load combination investigated. The predictor-corrector scheme is proposed as a substitute for either an exact geometric nonlinear elastic analysis or the approximation of second-order results by amplifying first-order results. Twenty-two steel benchmark frames are used to assess the method's accuracy in comparison with a more exact solution scheme. Comparisons are also made, where possible, with interstory drift amplifiers applied to first-order results. The findings demonstrate the method's ability to maintain sufficient accuracy while significantly improving computational efficiency. Use of the method is demonstrated with two illustrative examples, and advantages and limitations are discussed, as well as insights regarding frame sensitivity to second-order effects.
Investigation of Displacement of Intracranial Electrode Induced by Focused Ultrasound Stimulation

Transcranial focused ultrasound (tFUS) is an emerging neuromodulation technique to modulate brain activity non-invasively with high spatial specificity and focality. Given the influence of tFUS on brain activity, combining tFUS with multi-channel intracranial electrophysiological recordings enables monitoring of the activity of large populations of neurons with high temporal resolution. However, the physical interactions between tFUS and the electrode may affect a reliable assessment of neuronal activity, which remains poorly understood. In this article, high-frequency ultrasound (HFUS) system was developed and integrated into the tFUS neuromodulation system. The performance of the HFUS-based displacement tracking and analysis was evaluated by the theoretical analysis in the literature. The effects of various pressure levels on the displacements of the silicon-based microelectrode array in ex vivo brain tissue were investigated. The developed approach was capable of tracking and measuring the motion of a solid sphere in a tissue-mimicking phantom and measured displacements were comparable to theoretical predictions. The significant changes in the averaged peak displacements of the microelectrode array in ex vivo brain were observed with a pulse duration of 200 $\mu \text{s}$ and a peak-to-peak pressure from 131 kPa at a center frequency of 500 kHz compared with the values from the negative control group. The present results demonstrate the relationship between several pressure levels and displacements of the microelectrode array in ex vivo brain through the developed approach. This approach can be used to determine a vibration-free threshold of ultrasound parameters in multi-channel intracranial recordings for a reliable assessment of electrophysiological activities of living neurons.
Preliminary Evaluation of National Campaign Scenarios for Urban Air Mobility

Urban Air Mobility and Advanced Air Mobility concepts offer a novel method for transportation of passengers and cargo. Whereas the concept may reduce congestion on roads and highways, it also introduces new complexity to the National Airspace in terms of management of such operations. NASA, in partnership with FAA and industry, approaches these complexities with research and development activities such as flight tests and simulations, in order to better understand the impacts and necessary mechanisms by which these operations could be integrated. One example of such research and development activity that NASA is conducting is the Advanced Air Mobility National Campaign effort. Flight-test scenarios were proposed as part of the National Campaign and tested in simulation for evaluation with industry partners prior to the flight test. This simulation, exercised as an engineering evaluation, provided a data collection opportunity to better understand what iterations and modifications would be needed to successfully demonstrate the flight-test scenarios in order to mature the concept of Urban Air Mobility and Advanced Air Mobility.
Materials and Devices for MEMS Piezoelectric Energy Harvesting

Piezoelectric vibration energy harvesters (PVEHs) for microelectromechanical systems (MEMS) have received considerable attention as an enabling technology for self-powered wireless sensor networks. MEMS-PVEHs are particularly attractive because of the potential to deliver power required for sensor nodes and their ability to be integrated concurrently with the microfabrication of electronic circuits such as sensor nodes. This chapter consists of four subsections, starting with Sect. 17.1, where various piezoelectric materials commonly used for MEMS-scale PVEHs are reviewed. Typical device configurations of PVEH systems are introduced in Sect. 17.2, followed by analytical modeling of different configurations in Sect. 17.3 to link material characteristics to device performance: standard capacitor type electrodes for {3–1} mode of operation and interdigitated electrodes (IDTEs) for {3–3} mode of operation. In the last section, fabrication and characterization of MEMS-scale PVEHs in both of these modes are presented with model–experiment comparisons.
Identification of Molecular and Cellular Mechanisms of Learning and Memory: The Impact of Gene Targeting

Understanding the mechanisms of learning and memory is critical for unraveling the causes of the cognitive decline. Brain regions such as the hippocampus, with an acknowledged participation in learning and memory (LM understanding the interplay among each of these physiological factors is important in defining the molecular and cellular events leading to learning. It is found that revolutionary imaging techniques and improvements in electrophysiological recordings allow unprecedented abilities to observe functioning brains during L&M. It is suggested that faster computers capable of handling large amounts of information will be able to handle increasingly more realistic models of L&M.