cssi/SciSciGPT-SciSciNet huggingface dataset:
A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules

Motivation: It is well known that microRNAs (miRNAs) and genes work cooperatively to form the key part of gene regulatory networks. However, the specific functional roles of most miRNAs and their combinatorial effects in cellular processes are still unclear. The availability of multiple types of functional genomic data provides unprecedented opportunities to study the miRNA–gene regulation. A major challenge is how to integrate the diverse genomic data to identify the regulatory modules of miRNAs and genes. Results: Here we propose an effective data integration framework to identify the miRNA–gene regulatory comodules. The miRNA and gene expression profiles are jointly analyzed in a multiple non-negative matrix factorization framework, and additional network data are simultaneously integrated in a regularized manner. Meanwhile, we employ the sparsity penalties to the variables to achieve modular solutions. The mathematical formulation can be effectively solved by an iterative multiplicative updating algorithm. We apply the proposed method to integrate a set of heterogeneous data sources including the expression profiles of miRNAs and genes on 385 human ovarian cancer samples, computationally predicted miRNA–gene interactions, and gene–gene interactions. We demonstrate that the miRNAs and genes in 69% of the regulatory comodules are significantly associated. Moreover, the comodules are significantly enriched in known functional sets such as miRNA clusters, GO biological processes and KEGG pathways, respectively. Furthermore, many miRNAs and genes in the comodules are related with various cancers including ovarian cancer. Finally, we show that comodules can stratify patients (samples) into groups with significant clinical characteristics. Availability: The program and supplementary materials are available at http://zhoulab.usc.edu/SNMNMF/. Contact:[email protected]; [email protected] Supplementary information:Supplementary data are available at Bioinformatics online.
A Mitochondrial DNA Primase from the Trypanosomatid Crithidia fasciculata

We have purified to near homogeneity a DNA primase from a mitochondrial fraction of the trypanosomatidCrithidia fasciculata. The enzyme is a single polypeptide chain of 28 kDa. Using a poly(dT) template and ATP as a substrate, the enzyme makes oligonucleotides of which the vast majority are about 10 nucleotides in size or smaller. With a single-stranded M13 DNA template and the four rNTPs as substrates, the enzyme makes heterogeneous oligonucleotides in the same size range. These oligonucleotides efficiently prime the synthesis of DNA by the Klenow DNA polymerase. Immunolocalization with antibodies against the purified enzyme confirms that the primase is mitochondrial. Furthermore, the enzyme localizes to specific regions of the cell's single mitochondrion, above and below the condensed kinetoplast DNA. The primase does not co-localize with the mitochondrial topoisomerase II and DNA polymerase β, both of which are associated with two protein complexes positioned on opposite sides of the kinetoplast disc. These localization studies have significant implications for the mechanism of kinetoplast DNA replication.
An automated technique to support the verification and validation of simulation models

Simulation modeling requires model validation and verification to ensure that computed results are worth being considered. While we cannot expect a magic solution to the general problem, automated techniques for particular aspects of validation and verification are feasible. In this paper, we propose a technique to deduce model properties automatically from simulation runs performed for verification and validation and to use those properties for runtime monitoring during production runs. Properties are represented as formulas in linear temporal logic and are limited to functional properties. We demonstrate the applicability of the approach with using an extended version of a stochastic Botnet model originally developed by Van Ruitenbeek and Sanders.
FairTrust: Toward secure and high performance P2P networks

Peer-to-peer (P2P) networks are becoming increasingly popular and are an exciting new class of innovative, internet-based resource sharing systems. In a P2P network, a reputation system is essential to evaluate the trustworthiness of participating peers and to combat the selfish, dishonest, and malicious peer behaviors. The system collects locally-generated peer feedbacks and aggregates them to yield the global reputation values to represent peer trustworthiness. Reputation system guides peers in choosing a server for services/resources. Most of the approaches for peers to exploit reputation metrics are to select the one with the highest reputation value as a providing server. However, it may lead to unexpectedly low efficiency for high-reputed peers, and prevents P2P networks from taking full advantage of all resources for high performance. Other approaches restrict a peer to select a server in the same or lower reputation values. However, these approaches prevent P2P networks from achieving their goal of widely resource sharing and service exchanges. In this paper, we introduce a trust-based fairness-oriented server selection policy, FairTrust, for a peer to choose another peer to interact. FairTrust takes into account both reputation and capacity factors in server selection. It helps to create a secure P2P communication environment, and meanwhile to take full advantage of system resources for high performance by fair load distribution. Simulation results show the superiority of the FairTrust policy in achieving both high security and high performance in P2P networks in comparison with other related policies.
Constructively Responding to Requests for Paraprofessionals: We Keep Asking the Wrong Questions

Paraprofessional utilization has steadily risen in an effort to meet the needs of students with disabilities in inclusion-oriented classrooms. To date, no widely accepted processes exist to assist schools in determining when the use of paraprofessional staff is warranted. Many schools have attempted to fill this void by developing local processes designed to justify paraprofessional assignment. This article describes how justification approaches to paraprofessional decision making operate from a reactive posture, include inherently problematic criteria, and perpetuate socially constructed myths that certain students need one-to-one paraprofessionals. An alternative framework for making decisions is offered through a series of school/district- and classroom/team-level concepts and corresponding actions that can be pursued in developing proactive processes and practices tailored to local contexts.
Characterization of Human UDP-glucose Dehydrogenase CYS-276 IS REQUIRED FOR THE SECOND OF TWO SUCCESSIVE OXIDATIONS

UDP-glucose dehydrogenase (UGDH) catalyzes two oxidations of UDP-glucose to yield UDP-glucuronic acid. Pathological overproduction of extracellular matrix components may be linked to the availability of UDP-glucuronic acid; therefore UGDH is an intriguing therapeutic target. Specific inhibition of human UGDH requires detailed knowledge of its catalytic mechanism, which has not been characterized. In this report, we have cloned, expressed, and affinity-purified the human enzyme and determined its steady state kinetic parameters. The human enzyme is active as a hexamer with values for Km and Vmax that agree well with those reported for a bovine homolog. We used crystal coordinates for Streptococcus pyogenes UGDH in complex with NAD+ cofactor and UDP-glucose substrate to generate a model of the enzyme active site. Based on this model, we selected Cys-276 and Lys-279 as likely catalytic residues and converted them to serine and alanine, respectively. Enzymatic activity of C276S and K279A point mutants was not measurable under normal assay conditions. Rate constants measured over several hours demonstrated that K279A continued to turn over, although 250-fold more slowly than wild type enzyme. C276S, however, performed only a single round of oxidation, indicating that it is essential for the second oxidation. This result is consistent with the postulated role of Cys-276 as a catalytic residue and supports its position in the reaction mechanism for the human enzyme. Lys-279 is likely to have a role in positioning active site residues and in maintaining the hexameric quaternary structure.
Epigenetic Alterations Are Critical for Fear Memory Consolidation and Synaptic Plasticity in the Lateral Amygdala

Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA.
Information needs in technical work settings and their implications for the design of computer tools

We interviewed information workers in multiple technical areas of a large, diverse company, and we describe some of the unsatisfied information needs we observed during our study. Two clusters of issues are described. The first covers how loosely coupled work groups use and share information. We show the need to structure information for multiple, partly unanticipated uses. We show how the construction of information compounds helps users accomplish some of this restructuring, and we explain how structuring flexibility is also required because of temperamental differences among users. The second cluster of issues revolves around collections of tightly coupled work groups. We show that information shared within such groups differs from information shared across group boundaries. We present the barriers to sharing which we saw operating both within groups and outside, and we explain the function of resource and contact broker which evolved in the settings we examined. For each of these issues we propose implications for information tool design.
Effects of intraventricular catecholamines on luteinizing hormone release in ovariectomized-steroid-primed rats.

The effects of intraventricular norepinephrine (NE) and dopamine (DA) were studied in the awake, freely behaving rat. In long-tenn ovariectomized, estrogen-progeste rone-primed (OVX E2-P) animals, blood samples were taken via indwelling intra-atrial catheters before and after intraventricular infusion of either pH-adjusted saline,NE (5 µ, 15 µg, 20 µg), or DA (4 µg, 15 µg), and plasma LH was measured by radioimmunoassay. Under urethane anesthesia, records were made of the effects of intraventricular saline and NE on the electrical activity of the arcuate nucleus in the form of multi-unit spike activity. In unanesthetized animals, intraventricular NE caused marked changes in behavior. The typical response consisted of three phases: generalized activation (5–7 min), feeding (5–15 min), and sleep (1–2 h). DA exerted similar behavioral effects but without the marked sleep phase characteristic of the NE response. The effects of the catecholamines on LH output were significant increases in plasma LH levels for ...
Calculation of Standard Atomic Volumes for RNA and Comparison with Proteins: RNA is Packed More Tightly

Traditionally, for biomolecular packing calculations research has focused on proteins. Besides proteins, RNA is the other large biomolecule that has tertiary structure interactions and complex packing. No one has yet quantitatively investigated RNA packing or compared its packing to that of proteins because, until recently, there were no large RNA structures. Here we address this question in detail, using Voronoi volume calculations on a set of high-resolution RNA crystal structures. We do a careful parameterization, taking into account many factors such as atomic radii, crystal packing, structural complexity, solvent, and associated protein to obtain a self-consistent, universal set of volumes that can be applied to both RNA and protein. We report this set of volumes, which we call the NucProt parameter set. Our measured values are consistent across the many different RNA structures and packing environments. When common atom types are compared between proteins and RNA, nine of 12 types show that RNA has a smaller volume and packs more tightly than protein, suggesting that close-packing may be as important for the folding of RNAs as it is for proteins. Moreover, calculated partial specific volumes show that RNA bases pack more densely than corresponding aromatic residues from proteins. Finally, we find that RNA bases have similar packing volumes to DNA bases, despite the absence of tertiary contacts in DNA. Programs, parameter sets and raw data are available online at.
Amygdalar activation associated with happy facial expressions in adolescents: a 3-T functional MRI study.

Objective: To study the possible role of the amygdala in the recognition of happy and sad facial expressions in adolescents aged 13 to 17 years. Method: Twelve healthy adolescents (6 females and 6 males) underwent noninvasive 3-Tesla functional magnetic resonance imaging while viewing pictures of happy, sad, and neutral facial expressions. Results: Happy faces produced signiÞcant bilateral amygdalar activation when compared with neutral faces (p < .05, corrected). Sad faces relative to neutral did not produce signiÞcant amygdalar activation. Conclusions: These results extend the role of the amygdala in adolescents to include the recognition of happy facial expressions. They demonstrate the feasibility of using happy facial expressions to noninvasively study amygdalar function in adolescents and establish a baseline against which the amygdalar response to emotional stimuli in several psychiatric conditions may be compared. J. Am. Acad.
Satiation and Stress-Induced Hypophagia: Examining the Role of Hindbrain Neurons Expressing Prolactin-Releasing Peptide or Glucagon-Like Peptide 1

Neural circuits distributed within the brainstem, hypothalamus, and limbic forebrain interact to control food intake and energy balance under normal day-to-day conditions, and in response to stressful conditions under which homeostasis is threatened. Experimental studies using rats and mice have generated a voluminous literature regarding the functional organization of circuits that inhibit food intake in response to satiety signals, and in response to stress. Although the central neural bases of satiation and stress-induced hypophagia often are studied and discussed as if they were distinct, we propose that both behavioral states are generated, at least in part, by recruitment of two separate but intermingled groups of caudal hindbrain neurons. One group comprises a subpopulation of noradrenergic (NA) neurons within the caudal nucleus of the solitary tract (cNST; A2 cell group) that is immunopositive for prolactin-releasing peptide (PrRP). The second group comprises non-adrenergic neurons within the cNST and nearby reticular formation that synthesize glucagon-like peptide 1 (GLP-1). Axonal projections from PrRP and GLP-1 neurons target distributed brainstem and forebrain regions that shape behavioral, autonomic, and endocrine responses to actual or anticipated homeostatic challenge, including the challenge of food intake. Evidence reviewed in this article supports the view that hindbrain PrRP and GLP-1 neurons contribute importantly to satiation and stress-induced hypophagia by modulating the activity of caudal brainstem circuits that control food intake. Hindbrain PrRP and GLP-1 neurons also engage hypothalamic and limbic forebrain networks that drive parallel behavioral and endocrine functions related to food intake and homeostatic challenge, and modulate conditioned and motivational aspects of food intake.
A Mathematical Modeling Framework for Analysis of Functional Clothing

In the analysis and design of functional clothing systems, it is helpful to quantify the effects of a system on a wearer’s physical performance capabilities. Toward this end, a clothing modeling framework for quantifying the mechanical interactions between a given clothing system design and a specific wearer performing defined physical tasks is proposed. The modeling framework consists of three interacting modules: (1) a macroscale fabric mechanics/dynamics model; (2) a collision detection and contact correction module; and (3) a human motion module. In the proposed framework, the macroscopic fabric model is based on a rigorous large deformation continuum-degenerated shell theory representation. Material models that capture the stress-strain behavior of different clothing fabrics are used in the continuum shell framework. The collision and contact module enforces the impenetrability constraint between the fabric and human body and computes the associated contact forces between the two. The human body is represented in the current framework as an assemblage of overlapping ellipsoids that undergo rigid body motions consistent with human motions while performing actions such as walking, running, or jumping. The transient rigid body motions of each ellipsoidal body segment in time are determined using motion capture technology. The integrated modeling framework is then exercised to quantify the resistance that the clothing exerts on the wearer during the specific activities under consideration. Current results from the framework are presented and its intended applications are discussed along with some of the key challenges remaining in clothing system modeling.
PalProtect: A Collaborative Security Approach to Comment Spam

Collaborative security is a promising solution to many types of security problems. Organizations and individuals often have a limited amount of resources to detect and respond to the threat of automated attacks. Enabling them to take advantage of the resources of their peers by sharing information related to such threats is a major step towards automating defense systems. In particular, comment spam posted on blogs as a way for attackers to do search engine optimization (SEO) is a major annoyance. Many measures have been proposed to thwart such spam, but all such measures are currently enacted and operate within one administrative domain. We propose and implement a system for cross-domain information sharing to improve the quality and speed of defense against such spam
Care at the end of life: focus on communication and race.

Objective: To profile communication and recommendations reported by adults with terminal illness and explore differences by patient and physician characteristics.Method: This pilot was a cross-sectional study sample of 90 patients (39 Caucasian, 51 African American) with advanced heart failure or cancer. Participants completed an in-person, race-matched interview.Results: Participation was high (94%). Discussion about end-of-life topics was low. For example, only 30% reported discussion of advance directives, and 22% reported their physician inquired about spiritual support. Participants with cancer were significantly more likely to be receiving pain and/or symptom management at home, aware of prognosis, and participating in hospice. African American participants who were under the care of African American physicians were less likely to report pain and/or symptom management than other racial matches.Discussion: Although additional research on factors related to communication is important, initiation of pa...
Fair representation of Transportation Research Record impacts

This paper presents results of a qualitative survey and a quantitative assessment of the relative impacts of transportation journals. The survey involved 80 research university professors, government employees, and practitioners randomly chosen to rate a list of peer-reviewed transportation journals. The quantitative assessment consisted of an extensive examination of the impact factor (IF), a widely used metric for comparing scholarly publications, of 30 major transportation journals. Although the Transportation Research Record (TRR) was ranked by far as the most “useful and important” to the work of all those surveyed in the field of transportation, the TRR’s IF is lower than those of most other transportation journals. However, compared with other transportation journals, the TRR publishes the most scholarly papers and receives the most citations annually. It is also the most widely accessed by practitioners. This paper explores key factors that affect IF calculations and identifies strategies to enhan...
The Impact of Informed Trade on Firm-Specific Return Variation

Based on the notion that private information necessarily accompanies trade and leads to return variation, this paper explores the positive relationship between informed trade and firm-specific return variation. Using the PIN as a measure of informed trade, we find that the PIN is positively related to firm-specific return variation. We also find a significant interaction effect such that the impact of informed trade on firm-specific return variation is more profound for stocks with a high trading volume than for stocks with a low trading volume. The results of various robustness checks confirm that informed trade is indeed an important determinant of firm-specific return variation.
Structure and Magnetism in Mo/Co Multilayers

The magnetic and structural properties of Co in Mo/Co multilayers are an unresolved issue. Two independent studies report different structures for thicker Co layers in multilayers of comparable dimensions as well as significant differences in both the form and the layer thickness for a loss of ferromagnetism. Both studies base their structural claims on a limited number of Bragg lines. We have used x-ray diffraction, transmission electron diffraction, and EXAFS to probe the structure of Mo/Co multilayers having Co layer thicknesses from 4 to 63A. Our structural and magnetic results for these samples are compared to those of the above studies and are contrasted with results for Mo/Fe multilayers having comparable dimensions.
Genre, methodology and feminist practice: Gladys Reichard's ethnographic voice

The rainy season is not quite over although it has nearly spent itself. I drive leisurely along five miles of roller coaster highway, down and up, up and down again as I drink in the grandeur of the sunset. I come to the 'big hill', around and over which the road twines narrowly. From its summit I see at my left a deep purple canyon, green at the bottom with irrigated fields. At my right the sun is setting across a wide valley, the shadows replaced by roseate gold interrupted by the white resplendence of chalk cliffs. As if this were not sufficient, a light female rain like that which falls constantly over the home of the Corn gods, drops between me and the sun. I gasp in my inability to comprehend the sight fully as I turn my head forty-five degrees to behold a complete rainbow and behind it the thinnest slice of a new moon. (Gladys Reichard, 1934:122)
Assessment of response bias in neurocognitive evaluations.

BACKGROUND: In clinical neuropsychological practice, assessment of response validity (e.g., effort, over-reporting, underreporting) is an essential component of the assessment process. By contrast, other health care professionals, including those in neurorehabilitation settings, often omit assessment of this topic from their evaluations or only rely on subjective impressions. OBJECTIVE: To provide the first comprehensive review of response validity assessment in the neurorehabilitation literature, including why the topic is often avoided, what methods are commonly used, and how to decrease false positives. METHODS: A literature review and documentation of personal experience and perspectives was used to review this topic. RESULTS: There is a well-established literature on the necessity and utility of assessing response validity, particularly in patients who have external incentives to embellish their presentation or to under-report symptoms. There are many reasons why nonneuropsychologists typically avoid assessment of this topic. This poses a significant problem, particularly when patients exaggerate or malinger, because it can lead to misdiagnosis and it risks increasing the cost of healthcare by performing unnecessary tests and treatments, unfair distribution of disability/compensation resources, and a reduced access to these and other health resources by patients who genuinely need them. CONCLUSIONS: There is a significant need for non-neuropsychologists to develop and incorporate symptom and performance validity assessments in clinical evaluations, including those in neurorehabilitation settings.
David Oliver: A mandate for mismanagement.

The 2015 Conservative election manifesto committed to make England “the first nation in the world to have a genuinely seven day NHS,” including “seven day a week access for everyone to a GP” and “hospitals properly staffed, so that the quality of care is the same every day of the week.”1 Conservative ministers, government communications teams, and some journalists have repeatedly argued that the outright election victory has given the party an “electoral mandate” to govern, albeit in a system where only 37% of the electorate voted for it.2 …
Sorting nexin 27 (SNX27) associates with zonula occludens-2 (ZO-2) and modulates the epithelial tight junction

Proteins of the SNX (sorting nexin) superfamily are characterized by the presence of a PX (Phox homology) domain and associate with PtdIns3P (phosphatidylinositol-3-monophosphate)-rich regions of the endosomal system. SNX27 is the only sorting nexin that contains a PDZ domain. In the present study, we used a proteomic approach to identify a novel interaction between SNX27 and ZO-2 [zonula occludens-2; also known as TJP2 (tight junction protein 2)], a component of the epithelial tight junction. The SNX27-ZO-2 interaction requires the PDZ domain of SNX27 and the C-terminal PDZ-binding motif of ZO-2. When tight junctions were perturbed by chelation of extracellular Ca2+, ZO-2 transiently localized to SNX27-positive early endosomes. Depletion of SNX27 in mpkCCD (mouse primary kidney cortical collecting duct) cell monolayers resulted in a decrease in the rate of ZO-2, but not ZO-1, mobility at cell-cell contact regions after photobleaching and an increase in junctional permeability to large solutes. The findings of the present study identify an important new SNX27-binding partner and suggest a role for endocytic pathways in the intracellular trafficking of ZO-2 and possibly other tight junction proteins. Our results also indicate a role for SNX27-ZO-2 interactions in tight junction maintenance and function.
Deformed Ears and Hearing Loss

Infants with deformed ears often do not hear well. Since this loss is conductive, both hearing aids and surgery may help. Infants with one deformed ear should have an audiologic examination at one year, but surgery should not usually be performed until the child is six. If both ears are deformed, the child should have hearing aids early so he can learn to speak properly.
The Mean Air Flow as Lagrangian Dynamics Approximation and Its Application to Moist Convection

AbstractThis paper introduces the Mean Airflow as Lagrangian Dynamics Approximation (MAFALDA), a new method designed to extract thermodynamic cycles from numerical simulations of turbulent atmospheric flows. This approach relies on two key steps. First, mean trajectories are obtained by computing the mean circulation using height and equivalent potential temperature as coordinates. Second, thermodynamic properties along these trajectories are approximated by using their conditionally averaged values at the same height and θe. This yields a complete description of the properties of air parcels that undergo a set of idealized thermodynamic cycles.MAFALDA is applied to analyze the behavior of an atmosphere in radiative–convective equilibrium. The convective overturning is decomposed into 20 thermodynamic cycles, each accounting for 5% of the total mass transport. The work done by each cycle can be expressed as the difference between the maximum work that would have been done by an equivalent Carnot cycle and...
Measuring the impact of the flipped anatomy classroom: The importance of categorizing an assessment by Bloom's taxonomy.

The flipped classroom (FC) model has emerged as an innovative solution to improve student-centered learning. However, studies measuring student performance of material in the FC relative to the lecture classroom (LC) have shown mixed results. An aim of this study was to determine if the disparity in results of prior research is due to level of cognition (low or high) needed to perform well on the outcome, or course assessment. This study tested the hypothesis that (1) students in a FC would perform better than students in a LC on an assessment requiring higher cognition and (2) there would be no difference in performance for an assessment requiring lower cognition. To test this hypothesis the performance of 28 multiple choice anatomy items that were part of a final examination were compared between two classes of first year medical students at the University of Utah School of Medicine. Items were categorized as requiring knowledge (low cognition), application, or analysis (high cognition). Thirty hours of anatomy content was delivered in LC format to 101 students in 2013 and in FC format to 104 students in 2014. Mann Whitney tests indicated FC students performed better than LC students on analysis items, U = 4243.00, P = 0.030, r = 0.19, but there were no differences in performance between FC and LC students for knowledge, U = 5002.00, P = 0.720 or application, U = 4990.00, P = 0.700, items. The FC may benefit retention when students are expected to analyze material. Anat Sci Educ 10: 170–175. © 2016 American Association of Anatomists.
Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma

Abstract Metastatic Ewing sarcoma has a very poor prognosis and therefore new investigations into the biologic drivers of metastatic progression are key to finding new therapeutic approaches. The tumor microenvironment is highly dynamic, leading to exposure of different regions of a growing solid tumor to changes in oxygen and nutrient availability. Tumor cells must adapt to such stress in order to survive and propagate. In the current study, we investigate how Ewing sarcoma cells respond to the stress of growth factor deprivation and hypoxia. Our findings reveal that serum deprivation leads to a reversible change in Ewing cell cytoskeletal phenotypes. Using an array of migration and invasion techniques, including gelatin matrix degradation invadopodia assays, we show that exposure of Ewing sarcoma cells to serum deprivation and hypoxia triggers enhanced migration, invadopodia formation, matrix degradation and invasion. Further, these functional changes are accompanied by and dependent on activation of Src kinase. Activation of Src, and the associated invasive cell phenotype, were blocked by exposing hypoxia and serum-deprived cells to the Src inhibitor dasatinib. These results indicate that Ewing sarcoma cells demonstrate significant plasticity in response to rapidly changing micro-environmental stresses that can result from rapid tumor growth and from necrosis-causing therapies. In response to these stresses, Ewing cells transition to a more migratory and invasive state and our data show that Src is an important mediator of this stress response. Our data support exploration of clinically available Src inhibitors as adjuvant agents for metastasis prevention in Ewing sarcoma.
MicroTESE and Embryo Development

Assisted reproductive technologies have dramatically advanced the opportunities for treating the most challenging cases of male infertility. In no case has this opportunity been clearer than for men with the most severe defect in spermatogenesis: nonobstructive azoospermia (NOA). In men with NOA, sperm production is so defective that no sperm reach the ejaculate. The morphology of these sperm routinely is abnormal, and our experience is that many in vitro fertilization (IVF) laboratories consider sperm obtained from these men to be unusable for assisted reproductive techniques. Sperm retrieval requires invasive techniques to identify limited foci of sperm production within the testis. Clearly, the appearance of sperm from these men is abnormal, but few data have been published on the effect of using these sperm on IVF outcomes, including embryo quality. In this chapter, we describe the outcomes of intracytoplasmic sperm injection (ICSI) using testicular sperm from men with NOA, comparing the results with those obtained with testicular sperm from men with obstructive azoospermia (controlling for testicular source) and from men with sperm in the ejaculate using donor oocytes (controlling for oocytic factors). We also present data on the use of fresh and frozen testicular sperm, as well as sperm retrieved on the day of versus the day before oocyte retrieval. The results show that use of testicular sperm from men with NOA has a substantial effect on fertilization rates (72.6 % vs. 53.3 %; P < 0.05, compared with obstructed testicular sperm) but with similar embryo development (66.2 % day 3 “good” embryos [grade 1–2] vs. 53.8 % with obstructed testicular sperm). Clinical pregnancy rates were statistically better (52.8 % vs. 41.4 %) using testicular sperm from men with obstruction versus those with NOA.
The Impact of Quality Matters Professional Development on Teaching across Delivery Formats

ABSTRACTThis study explored the impact of professional development workshops for online course design on faculty’s pedagogical practices in online, face-to-face (f2f), and blended instructional modes. It specifically focused on trainings offered by the Quality Matters (QM) organization on a rubric for assessing quality in online course development. A mixed-methods analysis of survey data collected from 2,148 participants in QM workshops over a three-year period (2012–2015) demonstrated that, across all three teaching modes, participants revised learning objectives, improved course alignment, and paid greater attention to communication with students. Additional benefits from participating in QM training related to specific modalities. Common online and blended impacts included changes in assessment practices as well as in modifying course materials to be more compliant with accessibility standards. In f2f settings, frequent changes involved redesigning learning activities to increase learner-learner intera...
The use of dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium in cardiac surgery patients over 60 years of age: a pilot study.

Background: Delirium is associated with many negative health outcomes. Postoperative sedation and opioid administration may contribute to delirium. We hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium. This pilot study aims to assess feasibility of using dexmedetomidine and IVA in cardiac surgical patients, and estimate the effect size for incidence and duration of delirium. Methods: A total of 12 adult patients >60 years of age undergoing cardiac surgery were recruited and randomized into 4 groups: Propofol only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative baseline cognition and postoperative delirium was assessed daily until discharge. The feasibility was assessed by the number of patients who completed the study. Results: All patients completed the study successfully. The total incidence of delirium in the study population was 42% (5/12): 67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in D+A group and 0%(0/3) P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean range of duration of delirium was 0-1 days. One patient expired after surgery, unrelated to the study protocol. One patient in the D group experienced hypotension (systolic blood pressure <90 mm of Hg.) Conclusions: The feasibility of performing a project is ascertained by the study. Patients receiving IVA had lower incidence of delirium compared to patients not receiving IVA which suggests that IVA may have a role in reducing the incidence of delirium. A prospective randomized, placebo-controlled trial will be the next step in investigating the role of dexmedetomidine and IVA in reducing the incidence of delirium.
pataBanana: A Web-Based Decision Support Application for Calculating the Fertilizer Amount Based on Soil Test Result

In the Philippines, the banana industry is one of best agricultural products and become a source of income for local Filipino farmers and foreign exchange earners for the country. In the Regional Research Agenda 2011-2016 issued by the National Economic Development Authority (NEDA), suitability of specific fertilizers on land/soil classes for varieties of bananas is one of the priorities. Researchers found out that agriculturists from Bureau of Soils and Water Management agency manually compute the fertilizer recommendation for a certain crop. The study aims to develop a web - based decision support application to assist agriculturists in calculating the exact amount of fertilizer by automating the computation process for fertilizer recommendation. The general formula given by the Bureau of Soils and Water Management (BSWM) serves as the algorithm for calculation. Decision Support System is used for predicting the number of banana herbs to be planted and the number of hands and fingers to be harvested. Descriptive development method using Iterative process model was utilized in the study. The application was developed using PHP Laravel 5.3, semaphore API for the SMS feature and black box for testing procedure.
Complications and Their Risk Factors in Gastrointestinal Endoscopy

More than 200,000,000 gastrointestinal procedures are performed in the United States every year. As with other therapeutic modalities, complications are inherent to gastrointestinal endoscopy. Endoscopists need to be aware of the different types and the expected frequencies of these complications, in order to use strategies to minimize their occurrence and to recognize and treat them appropriately when they occur. Furthermore, it is essential to recognize patients with a higher likelihood of developing complications. Attention must be paid to patients’ preexisting medical conditions and their ability to cope with potential complications.
Models and Instances

In this chapter we give more details on the use of MODLER with examples that came with the MODLER disk. After discussing some precepts, more examples are presented that illustrate most of the MODLER features for modeling linear programs. Then, we describe randomization to assign values to data objects.
Addressing HPV vaccine myths: practical information for healthcare providers

Human papillomavirus (HPV) vaccine uptake consistently lags behind that of other adolescent vaccines. In 2017, uptake of a single HPV vaccine dose and HPV vaccine series completion was 66% and 49%,...
UNIT 7.2 Immunoprecipitation

Selective immunoprecipitation of proteins is a useful tool for characterizing proteins and protein-protein interactions. Clear step-by-step protocols are provided for preparing lysates of cells and yeast under a variety of conditions, for binding the antibody to a solid matrix, and for performing the actual immunoprecipitation. An additional method is provided for increasing the specificity of the technique by reprecipitating the antigen with the same or a different antibody. © 2016 by John Wiley & Sons, Inc. Keywords: immunoprecipitation; immunoprecipitation-recapture; antigen; antibody; agarose bead; magnetic bead
The Supreme Court of Arizona: Its 2002-2003 Decisions

This article is the sixth annual review of the decisions of the Arizona Supreme Court, covering the period from August 1, 2002, to July 31, 2003. Extensive substantive treatment of all of the decisions is provided in this annual review by student-authored works. Preceding the analytical treatment of the court decisions, a summary statistical analysis of the past year is also provided, with comparative observations over the now six year period of these annual reviews. This combination of comprehensive analytical assessment with substantial statistical scrutiny of the Arizona Supreme Court in annual reviews is nearly unique in the country. Only the Indiana Supreme Court receives similar attention.
Neuromorphic MEMS sensor network

This work investigates the computational potential of microelectromechanical system (MEMS) networks. In these networks, each MEMS device retains the memory of past inputs through bistability and hysteresis and receives a weighted excitatory or inhibitory feedback from other devices within the network. These interactions are shown to change the dynamics of a small network of MEMS devices to produce selective switching and limit cycles through Hopf bifurcations. Furthermore, we show that interactions within large, trained MEMS networks can be used to perform computational tasks such as object classification and tracking.
Mechanical properties of hot isostatically pressed Si3N4 and Si3N4/SiC composites

The mechanical properties of hot isostatically pressed monolithic Si[sub 3]N[sub 4] and Si[sub 3]N[sub 4]--20 vol. % SiC composites have been studied by microindentation at temperatures up to 1400 [degree]C. Indentation crack patterns and microstructures have been examined by optical microscopy, scanning electron microscopy, and transmission electron microscopy. It is shown that dense Si[sub 3]N[sub 4] base materials can be synthesized by HIPing without densification aids. Both the monolithic Si[sub 3]N[sub 4] and the Si[sub 3]N[sub 4]/SiC composites exhibit high hardness values which gradually decrease with increasing temperature. Both types of material show low fracture toughness values apparently because of strong interfacial bonding. On the other hand, the fracture toughness of the composite is about 40% higher than that of the monolithic material, due to the presence of the 20 vol. % SiC whiskers. A crack deflection/debonding mechanism is likely to be responsible for the higher toughness observed in the composite. High resolution electron microscopy shows that the grain boundaries in both samples contain a thin SiO[sub 2] layer.
The relationship of loot box purchases to problem video gaming and problem gambling.

Abstract Loot boxes are virtual items in many video games that let players “gamble” on an item of chance. Loot boxes bring an element of gambling into video games, which might prime video game users to engage in online gambling activities. However, few studies have focused on this emerging issue. The present study investigated the relationships between loot box purchases and both problem video gaming and problem gambling severity. Cross-sectional, self-report data were collected from 618 adult video gamers (M = 27 years of age, SD = 8.9, 63.7% male) via an online survey. Nearly half of the sample (44.2%) spent money on loot box purchases in the past year. Loot box purchasers played video games and gambled online more frequently, reported more extended gaming and online gambling sessions, and endorsed higher levels of problem video gaming and problem gambling severity as well as greater mental distress relative to those who did not buy loot boxes. Results from a series of path analyses revealed that loot box purchasing was directly related to problem video gaming and problem gambling severity as well as indirectly through increased video gaming/online gambling engagement, which in turn is related to elevated psychological distress. The present findings provide insight into the role of loot box purchasing in the transition from recreational engagement in video gaming and online gambling to problem video gaming and/or problem gambling.
Framing a robust understanding of proportional reasoning for teachers

Proportional reasoning is foundational in school mathematics. Despite the importance of proportional reasoning, little has been written about the knowledge needed for teachers to teach proportional reasoning relative to its importance. In this paper, we present an initial definition for a robust understanding of proportional reasoning for teaching based on synthesizing past scholarship in conjunction with an empirical study of the knowledge resources practicing teachers use to make sense of proportional reasoning tasks. As a result of this effort, we present here an initial framing of operationalized knowledge resources based upon our definition for a robust understanding that could be used as an analytic tool. We also describe how such a framework of knowledge resources is useful in the context of teacher education, and we provide an example of how the framework was used to analyze the knowledge resources a teacher employed to make sense of a proportional reasoning task. We end by discussing possible implications our framework has for designing teacher education experiences and further research that is needed.
System Design Methodologies

In this chapter we will look at different design methodologies, or design flows, for multi-processor systems. Design methodologies have evolved together with manufacturing technology, design complexity, and design automation. Improvements in technology have increased design complexity to the point that designers are no longer capable of making complex designs manually. To solve this problem, design automation tools, also known as computer-aided design (CAD) tools, were introduced. In order to make CAD tools more efficient and design algorithms more manageable, design-automation researchers as well as tool developers were forced to introduce more stringent design rules, parameterize components and minimize component libraries. As design complexities continued to increase, tool developers created new design abstraction levels and tried to use the same design strategy from the circuit level, to the logic level, to the processor level, and finally to the system level.