cssi/SciSciGPT-SciSciNet huggingface dataset:
Video-based Assessment of Peripheral Intravenous Catheter Insertion in the Resuscitation Area of a Pediatric Emergency Department

Objective The objective was to describe the frequency of and factors associated with prolonged peripheral intravenous catheter (PIV) insertion in the resuscitation area of a pediatric emergency department (PED). Methods Video-based study of a consecutive sample of nontrauma patients undergoing PIV insertion in the resuscitation area of a PED. Preexisting videos were the main data source. The primary outcome was patients with prolonged duration of PIV insertion (>90 seconds from start of first attempt to successful flush/blood draw). Logistic regression identified variables independently associated with prolonged PIV insertion. Results A total of 151 consecutive nontrauma patients underwent PIV insertion during a 2.5-month period. Sixty-nine patients (46%) had prolonged PIV insertion, including 14 for whom PED providers failed to insert PIVs. For patients with successful PIV insertion by PED providers, median duration was 48 seconds (interquartile range [IQR] = 23 to 295 seconds). Vascular access was ultimately achieved for 13 patients (93%) with initial insertion failure by the PED team (10 non-PED personnel, three intraosseous lines), with a median duration of 26.7 minutes (IQR = 19.9 to 34.2 minutes). Age ≤ 2 years (ORadj = 6.9; 95% confidence interval [CI] = 2.9 to 16.1) and musculoskeletal contractures (ORadj = 5.3; 95% CI = 1.6 to 17.2) were independently associated with prolonged PIV insertion. Conclusions Prolonged PIV insertion is common in a PED resuscitation area. When PED providers could not insert a PIV, time to insertion was very long. Young patients and those with contractures were at particular risk for prolonged and failed PIV placement. When emergent vascular access is required, alternative approaches should be considered early for these patients.
Making Sense of Future Cybersecurity Technologies: Using Ontologies for Multidisciplinary Domain Analysis

Security experts have difficulties achieving quick vulnerability mitigation because cybersecurity is a complex multi-disciplinary subject that yields itself with great difficulty to traditional methods of risk analysis. In particular, the effectiveness of mitigation strategies depends on an accurate understanding of the relationships among the components of systems that need to be protected, their functional requirements, and of the trade-off between security protection and core functionality. Mitigation strategies may have undesired ripple-effects, such as unexpectedly modifying functions that other system components rely upon. If some of the side-effects of a mitigation strategy are not clearly understood by a security expert, the consequences may be costly. Thus, vulnerability mitigation requires a deep understanding of the subtle interdependencies that exist between domains that are different in nature. This is especially difficult for new technology use models, such as Cloud-based computing and IoT, in which cyber and physical components are combined and interdependent. By their own design, ontologies and the associated inference mechanisms permit us to reason about connections between diverse domains and contexts that are pertinent for the general threat picture, and to highlight the effects and ramifications of the mitigation strategies considered. In this paper, we position ontologies as crucial tools for understanding the threat space for new technology space, for increasing security experts’ situational awareness, and, ultimately, as decision-support tools for rapid development of mitigation strategies. We follow with the discussion of the new information and insights gleaned from the ontology-based study of the root of trust in cyber-physical systems.
Primary immunodeficiency diseases due to defects in lymphocytes.

The recognition of impaired immunity in children five decades ago1,2 spurred an exponential increase in knowledge of the functions of the immune system. More than 95 inherited immunodeficiency disorders have now been identified.3,4 Genetically determined immunodeficiency can cause not only undue susceptibility to infection but also autoimmunity and an increased risk of cancer. The defects may affect one or more components of the immune system, including T cells, B cells, natural killer cells, phagocytic cells, and complement proteins. This review will focus on molecular causes of primary immunodeficiency that affect lymphocytes. Phenotypes Mutations that impair the function of . . .
Broad electrical tuning of plasmonic nanoantennas at visible frequencies

We report an experimental demonstration of electrical tuning of plasmon resonances of optical nanopatch antennas over a wide wavelength range. The antennas consist of silver nanocubes separated from a gold film by a thin 8 nm polyelectrolyte spacer layer. By using ionic liquid and indium tin oxide coated glass as a top electrode, we demonstrate dynamic and reversible tuning of the plasmon resonance over 100 nm in the visible wavelength range using low applied voltages between −3.0 V and 2.8 V. The electrical potential is applied across the nanoscale gap causing changes in the gap thickness and dielectric environment which, in turn, modifies the plasmon resonance. The observed tuning range is greater than the full-width-at-half-maximum of the plasmon resonance, resulting in a tuning figure of merit of 1.05 and a tuning contrast greater than 50%. Our results provide an avenue to create active and reconfigurable integrated nanophotonic components for applications in optoelectronics and sensing.
The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation.

Background The possibility that mu opioid agonists can influence cancer recurrence is a subject of recent interest. Epidemiologic studies suggested that there were differences in cancer recurrence in breast and prostate cancer contingent on anesthetic regimens. In this study, we identify a possible mechanism for these epidemiologic findings based on mu opioid receptor (MOR) regulation of Lewis lung carcinoma (LLC) tumorigenicity in cell and animal models.
The functional significance of morphological changes in the dentitions of early mammals

The Mesozoic marked a time of experimentation in the tooth morphology of early mammals. One particular experiment involved the movement of three points, or cusps, on the surface of a molar tooth from a line into a triangle. This transition is exemplified by two extinct insectivorous mammals, Morganucodon (cusps in a line) and Kuehneotherium (cusps in a triangle). Here we test whether this difference in cusp arrangement, alongside cusp heights and angles between cusps, is associated with differences in the ability of the teeth to fracture proxy-insect prey. We gathered measurements from molar teeth of both species and used them to create physical models. We then measured the force, time and energy at fracture and peak force, and the amount of damage inflicted by the models on hard and soft gels encased in a tough film that mimicked the material properties of insects. The Morganucodon model required less force and energy to fracture hard gels and reach peak force compared with Kuehneotherium . Kuehneotherium required a similar time, force and energy to fracture soft gels but reduced the time, force and energy to reach peak force. More importantly, Kuehneotherium also inflicted more damage to both the hard and the soft gels. These results suggest that changes in dental morphology in some early mammals was driven primarily by selection for maximizing damage, and secondarily for maximizing biomechanical efficiency for a given food material property.
Division of labor among Mycobacterium smegmatis RNase H enzymes: RNase H1 activity of RnhA or RnhC is essential for growth whereas RnhB and RnhA guard against killing by hydrogen peroxide in stationary phase

RNase H enzymes sense the presence of ribonucleotides in the genome and initiate their removal by incising the ribonucleotide-containing strand of an RNA:DNA hybrid. Mycobacterium smegmatis encodes four RNase H enzymes: RnhA, RnhB, RnhC and RnhD. Here, we interrogate the biochemical activity and nucleic acid substrate specificity of RnhA. We report that RnhA (like RnhC characterized previously) is an RNase H1-type magnesium-dependent endonuclease with stringent specificity for RNA:DNA hybrid duplexes. Whereas RnhA does not incise an embedded mono-ribonucleotide, it can efficiently cleave within tracts of four or more ribonucleotides in duplex DNA. We gained genetic insights to the division of labor among mycobacterial RNases H by deleting the rnhA, rnhB, rnhC and rnhD genes, individually and in various combinations. The salient conclusions are that: (i) RNase H1 activity is essential for mycobacterial growth and can be provided by either RnhC or RnhA; (ii) the RNase H2 enzymes RnhB and RnhD are dispensable for growth and (iii) RnhB and RnhA collaborate to protect M. smegmatis against oxidative damage in stationary phase. Our findings highlight RnhC, the sole RNase H1 in pathogenic mycobacteria, as a candidate drug discovery target for tuberculosis and leprosy.
JULiP: An efficient model for accurate intron selection from multiple RNA-seq samples

Accurate alternative splicing detection and transcript reconstruction are essential to characterize gene regulation and function and to understand development and disease. However, current methods for extracting splicing variation from RNA-seq data only analyze signals from a single sample, which limits transcript reconstruction and fails to detect a complete set of alternative splicing events. We developed a novel feature selection method, JULiP, that analyzes information across multiple samples to identify alternative splicing variation in the form of splice junctions (introns). It formulates the selection problem as a regularized program, utilizing the latent information from multiple RNA-seq samples to construct an accurate and comprehensive intron set. JULiP is highly accurate, and could detect thousands more introns in any one sample, >30% more than the most sensitive single-sample method, and over 11% more introns in the cumulative set of samples, at higher or comparable precision (>98%). Tested assemblers included Cufflinks, CLASS2, FlipFlop and StringTie, and the multi-sample assembler ISP. JULiP is multi-threaded and parallelized, taking roughly one minute to analyze up to 100 data sets on a multi-computer cluster, and can easily scale up to allow analyses of hundreds and thousands of RNA-seq samples.
Feasibility of Implementing the All Nations Breath of Life Culturally Tailored Smoking Cessation Program for American Indians in Multi-Tribal Urban Communities.

Introduction Prevalence of cigarette smoking is highest among American Indians, yet few culturally appropriate smoking cessation programs have yet been developed and tested for multi-tribal American Indian adult populations. This study examined implementation of the All Nations Breath of Life culturally tailored smoking cessation program in multi-tribal urban and suburban American Indian communities in seven locations across five states (N = 312). Methods This single-arm study used community-based participatory research to conduct a 12-week intervention whose primary purpose was to curb commercial tobacco use among American Indians. Participants were followed through month 6 in person and month 12 via telephone. The primary outcome was continuous abstinence from recreational cigarette smoking at 6 months post-baseline, verified through voluntary provision of salivary cotinine levels. Results At program completion (12 weeks post-baseline), 53.3% of program completers remained abstinent; labeling those lost to follow-up as smokers resulted in a 41.4% quit rate. At 6 months post-baseline (primary endpoint), 31.1% of retained participants quit smoking (p < .0001 compared to the highest quit rates among multi-tribal populations reported in the literature, 7%); final quit rate was 22.1% labeling those lost to follow-up as smokers (p = .002). Retention rate at endpoint was 71.2%. 12-month follow-up was attempted with all participants and had a retention rate of 49.0%. Of those participants reached, 34.0% were smoke-free. Conclusions All Nations Breath of Life shows promise as a smoking cessation program for multi-tribal urban American Indian communities. It can be successfully implemented in a variety of urban settings. Implications This is the first large feasibility study of a culturally tailored smoking cessation program for American Indians with good cessation and retention rates in a multi-tribal urban American Indian population. It shows that All Nations Breath of Life can be implemented in multiple urban settings across five states. To our knowledge, this is the first program of its kind to be implemented across multiple heterogeneous urban locations and to include salivary cotinine testing for verification of self-report data across these locations.
Management of Cavernous Sinus Involvement in Sinonasal and Ventral Skull Base Malignancies

Cavernous sinus (CS) involvement by sinonasal and ventral skull base malignancies is infrequently encountered in neurosurgical practice. Despite advancements in skull base microneurosurgery and endoscopic techniques, detailed knowledge and experience of the surgical management of these lesions are limited. This article elaborates on surgical strategies and approaches for CS involvement of malignant ventral skull base tumors. The article discusses the indications, techniques, nuances, advantages, limitations, and complications of minimally invasive CS biopsy, transcranial microscopic, and transfacial endoscopic approaches to the CS using illustrative diagrams and operative videos. The principles and nuances of a high-flow cerebral revascularization procedure are mentioned.
NMRbox: A Resource for Biomolecular NMR Computation

Advances in computation have been enabling many recent advances in biomolecular applications of NMR. Due to the wide diversity of applications of NMR, the number and variety of software packages for processing and analyzing NMR data is quite large, with labs relying on dozens, if not hundreds of software packages. Discovery, acquisition, installation, and maintenance of all these packages is a burdensome task. Because the majority of software packages originate in academic labs, persistence of the software is compromised when developers graduate, funding ceases, or investigators turn to other projects. To simplify access to and use of biomolecular NMR software, foster persistence, and enhance reproducibility of computational workflows, we have developed NMRbox, a shared resource for NMR software and computation. NMRbox employs virtualization to provide a comprehensive software environment preconfigured with hundreds of software packages, available as a downloadable virtual machine or as a Platform-as-a-Service supported by a dedicated compute cloud. Ongoing development includes a metadata harvester to regularize, annotate, and preserve workflows and facilitate and enhance data depositions to BioMagResBank, and tools for Bayesian inference to enhance the robustness and extensibility of computational analyses. In addition to facilitating use and preservation of the rich and dynamic software environment for biomolecular NMR, NMRbox fosters the development and deployment of a new class of metasoftware packages. NMRbox is freely available to not-for-profit users.
A Wearable Transcranial Doppler Ultrasound Phased Array System

Objective: Practical deficiencies related to conventional transcranial Doppler (TCD) sonography have restricted its use and applicability. This work seeks to mitigate several such constraints through the development of a wearable, electronically steered TCD velocimetry system, which enables noninvasive measurement of cerebral blood flow velocity (CBFV) for monitoring applications with limited operator interaction.
Initial Development of a High-frequency EMI Sensor for Detection of Subsurface Intermediate Electrically Conductive (IEC) Targets

The U.S. military has developed and currently uses composite material munitions. These composite munitions are typically comprised of carbon fiber and, because of their low electrical conductivity, have a much lower electromagnetic induction signature, which makes them difficult to detect using traditional metal detecting methods. The term intermediate electrically conductive (IEC) is used to describe these lower conductivity materials, with conductivity, σ , typically in the range 10 σ 5 S/m. The electromagnetic induction (EMI) relaxation response of carbon fiber munitions peaks in the low megaHertz range (
Global Trends in Board-Shareholder Engagement

There has been a rapid increase in shareholder requests for special meetings with the board. This report discusses the potential benefits and complexities of the board-shareholder engagement process, reviews global trends in engagement practices, provides insights into engagement activities at U.S. companies, and highlights developments in the use of technology to facilitate engagement. It also provides perspectives from institutional investors on the design of an effective engagement process.
William James on Democratic Individuality

William James (1842–1910) argued for a philosophy of democracy and pluralism that advocates individual and collective responsibility for our social arrangements, our morality, and our religion. In James' view, democracy resides first and foremost not in governmental institutions or in procedures such as voting, but rather in the characteristics of individuals, and in qualities of mind and conduct. It is a philosophy for social change, counselling action and hope despite the manifold challenges facing democratic politics, and these issues still resonate strongly today. In this book, Stephen S. Bush explores how these themes connect to James' philosophy of religion, his moral thought, his epistemology, his psychology, and his metaphysics. His fresh and original study highlights the relevance of James' thought to modern debates, and will appeal to scholars and students of moral and political philosophy.
Applications of the Elementary Theory

It will be important to have definite descriptions (which involve the primitive logical notion the) to facilitate the following applications. Let us stipulate that where O is any formula with one free x-variable, (ix) O (“the object x such that O”) is to be a complex object term of our language. Some examples might be: (iy)(E! y & Typ) (“the object which exists and taught Plato”) and (ix)(A!x amf; (F)(xF = F = R v F = S)) (“the object which encodes just roundness and squareness”). Semantically, we interpret descriptions like (ix) O as denoting the unique object which satisfies O, if there is one, and as not denoting anything if there is not one. To guarantee that descriptions work in our system just as we would expect them to a priori, we add a proper axiom schema which asserts that atomic formulas or defined identity formulas Ψ in which there occurs a description (ix) O are true if there is a unique object satisfying O and there is something which satisfies both O and Ψ1.
Automating Software Development for Mobile Computing Platforms

Mobile devices such as smartphones and tablets have become ubiquitous in today's modern computing landscape. The applications that run on these mobile devices (often referred to as "apps") have become a primary means of computing for millions of users and, as such, have garnered immense developer interest. These apps allow for unique, personal software experiences through touch-based UIs and a complex assortment of sensors. However designing and implementing high quality mobile apps can be a difficult process. This is primarily due to challenges unique to mobile development including change-prone APIs and platform fragmentation, just to name a few. This paper presents the motivation and an overview of a dissertation which presents new approaches for automating and improving mobile app design and development practices. Additionally, this paper discusses potential avenues for future research based upon the work conducted, as well as general lessons learned during the author's tenure as a doctoral student in the general areas of software engineering, maintenance, and evolution.
Virtual Terrain Nullification Using Phased Array Antennas for Wireless Ad Hoc Networks

Wireless communication is sensitive to ambient noise and interference due to the use of a shared medium. The link quality is affected by the surrounding terrain like buildings, hills, foliage, etc. Interference is one of the key challenges to overcome in wireless ad hoc networks. Terrain changes also pose a problem for communication and localization and in the deployment of Internet of Things (IoT). Many of these problems can be addressed through careful antenna design but can be challenging as they require complex hardware and software. We propose a novel approach called virtual terrain leveling (VTL), which acts as a trade-off between the complex antenna design approaches and simple omni-directional antennas. VTL nullifies the propagation effects of the terrain using phased array antennas to compensate for the path losses.
US Guideline Criteria for Human Immunodeficiency Virus Preexposure Prophylaxis: Clinical Considerations and Caveats

Clinical guidelines for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) developed by the US Centers for Disease Control and Prevention have been instrumental in the implementation of PrEP in medical practices throughout the country. However, the eligibility criteria contained within may inadvertently limit PrEP access for some patients. We describe the following key considerations and caveats related to these criteria: promotion of a selective vs universal approach to sexual health education involving PrEP; misalignment between criteria stated in the table and text boxes; problematic categorization and confounding of sexual orientation, gender identity, and risk behavior; underemphasis of network/community-level drivers of HIV transmission; oversimplification of serodiscordant risk; and lack of clarity surrounding the relevance of condoms to PrEP eligibility. We offer concrete recommendations to address the identified issues and strengthen future iterations of the guidelines, applying these recommendations in an alternative table of "criteria."
Treatment results of brachytherapy versus external beam radiation therapy for intermediate risk prostate cancer.

e16041 Background: The role of brachytherapy (BT) using Iodine-125 (I-125) without supplemental external beam radiation (EBRT) is usually limited to patients with low risk prostate cancer (PC). Our...
Craftec: Engaging Older Adults in Making through a Craft-Based Toolkit System

We present Craftec, an extendable toolkit system focused on engaging older adults in maker technology by supporting their use of common crafting skills. Craftec is comprised of LilyPad Arduino-based toolkits to promote easier crafting with hard and soft mediums. We describe the system's design, a pilot test with 8 students, and 2 two-hour single session workshop evaluations by 17 older adults. We found Craftec facilitated the efficient integration of circuits within crafted items, including fewer short circuits as compared to a basic LilyPad Arduino kit. We discuss insights into creating an older adult toolkit focused on building and prototyping rather than facilitating STEM education.
Nonparametric Pattern-Mixture Models for Inference with Missing Data

Pattern-mixture models provide a transparent approach for handling missing data, where the full-data distribution is factorized in a way that explicitly shows the parts that can be estimated from observed data alone, and the parts that require identifying restrictions. We introduce a nonparametric estimator of the full-data distribution based on the pattern-mixture model factorization. Our approach uses the empirical observed-data distribution and augments it with a nonparametric estimator of the missing-data distributions under a given identifying restriction. Our results apply to a large class of donor-based identifying restrictions that encompasses commonly used ones and can handle both monotone and nonmonotone missingness. We propose a Monte Carlo procedure to derive point estimates of functionals of interest, and the bootstrap to construct confidence intervals.
First-principles study of bandgap bowing in BGaN alloys

III-nitride alloys continue to drive advances in electronic and optoelectronic devices. Recently, boron-containing nitride alloys have been explored with the goal of expanding the range of applications. Using first-principles calculations with a hybrid functional, we study the electronic structure of wurtzite BGaN alloys. Strong bandgap bowing is observed, with a concentration-dependent bowing parameter. Due to the strong bandgap bowing, the fundamental bandgap in strain-free alloys is effectively unchanged for the lowest B concentrations. A crossover from a direct to an indirect bandgap occurs for B concentrations greater than 50%.
Polysemy in Elizabeth Bishop’s “The Fish”

In Remembering Elizabeth Bishop, an oral biography assembled by Gary Fountain and Peter Brazeau, the literary critic David Kalstone recalls a conversation with Bishop in which he praised her poem “...
Spiral Vein Graft for Radiation-Induced Right Common and External Iliac Artery Occlusion

A 34-year-old male underwent spiral vein graft for radiation-induced right common iliac and external iliac artery occlusion. Patient developed postoperative deep vein thrombosis. Spiral vein graft remained patent without significant dilatation 5 years following reconstruction till patient was lost to follow-up.
Protocolized Urine Sampling is Associated with Reduced Catheter-associated Urinary Tract Infections: A Pre- and Postintervention Study.

BACKGROUND Standard urine sampling and testing techniques do not mitigate against detection of colonization, resulting in false positive catheter-associated urinary tract infections (CAUTI). We aimed to evaluate whether a novel protocol for urine sampling and testing reduces rates of CAUTI. METHODS A preintervention and postintervention study with a contemporaneous control group was conducted at 2 campuses (test and control) of the same academic medical center. The test campus implemented a protocol requiring urinary catheter removal prior to urine sampling from a new catheter or sterile straight catheterization, along with urine bacteria and pyuria screening prior to culture. Primary outcomes were test campus CAUTI rates, compared between each 9-month pre- and postintervention epoch. Secondary outcomes included the percent reductions in CAUTI rates, compared between the test campus and a propensity score-matched cohort at the control campus. RESULTS A total of 7991 patients from the test campus were included in the primary analysis, and 4264 were included in the propensity score-matched secondary analysis. In the primary analysis, the number of CAUTI cases per 1000 patients was reduced by 77% (6.6 to 1.5), the number of CAUTI cases per 1000 catheter days was reduced by 63% (5.9 to 2.2), and the number of urinary catheter days per patient was reduced by 37% (1.1 to 0.69; all P values ≤ .001). In the propensity score-matched analysis, the number of CAUTI cases per 1000 patients was reduced by 82% at the test campus, versus 57% at the control campus; the number of CAUTI cases per 1000 catheter days declined by 68% versus 57%, respectively; and the number of urinary catheter days per patient decreased by 44% versus 1%, respectively (all P values < .001). CONCLUSIONS Protocolized urine sampling and testing aimed at minimizing contamination by colonization was associated with significantly reduced CAUTI infection rates and urinary catheter days.
NCLX pumps up the heat.

Abstract Mitochondrial Ca2+ signaling is a well-appreciated regulator of cell metabolism and energy production. A major function of mitochondria in brown adipose tissue (BAT) is thermogenesis. Assali et al. offer new insights into how the mitochondrial Ca2+ extrusion mediator NCLX is crucial for BAT survival and thermogenesis.
Treatment Is More Than Prevention: Perceived Personal and Social Benefits of Undetectable = Untransmittable Messaging Among Sexual Minority Men Living with HIV

Research suggests that the science of undetectable viral load (VL) status and HIV transmission—conveyed with the slogan “Undetectable = Untransmittable” or “U = U”—has gaps in acceptance despite ro...
Optimal Power Hardware-in-the-Loop Interfacing: Applying Modern Control for Design and Verification of High-Accuracy Interfaces

In this article, we develop a novel approach to design power hardware-in-the-loop (PHIL) simulation interfaces that maximize simulation bandwidth and accuracy by leveraging a modern control framework that explicitly considers objectives on accuracy and can automatically synthesize an optimal controller that meets these objectives while stabilizing the closed-loop system. The method developed improves upon common approaches to PHIL interface design that typically involve multiple design steps for manual compensation and stabilization that can result in interfaces that are stable but have suboptimal bandwidth and accuracy. The approach developed is general and can be applied to most PHIL system configurations. The modeling framework allows for the inclusion of scaling factors and hardware-under-test current injection models that are common to practical PHIL simulations and have significant impacts on stability. We also present practical methods and metrics for verifying the absolute accuracy of PHIL simulation results without relying on relative comparisons to potentially inaccurate models or previous simulation results. We demonstrate the accuracy evaluation method and show the improved performance achievable when using the optimal PHIL interface design approach in an experimental case study involving a 100-kVA battery inverter.
DDRE-22. NOVEL LonP1 INHIBITORS FOR TARGETING GLIOMA STEM CELLS

Author(s): Douglas, Christopher; Di, Kaijun; Lomeli, Naomi; Bota, Daniela | Abstract: Abstract Glioblastoma (GBM) has an exceptional high rate of reoccurrence that largely explains its l 15 months median survival. LonP1 is a serine protease that degrades misfolded proteins and regulates mitochondrial DNA replication. It drives tumor progression towards a malignant cancer phenotype in colorectal cancer, melanoma, oral cancer and cervical cancer. Dr. Daniela Bota has previously shown that LonP1 is overexpressed in human malignant gliomas and is associated with higher tumor grade and poor survival prognosis. In collaboration with Professor Bhaskar Das, we have used structure activity Relationship (SAR) analysis to generate compounds with on-target inhibition of LonP1 protease activity. Preliminary work on these novel compounds shows that these proprietary inhibitors can drastically decrease cell viability in the established D54 and U251 GBM lines. The lead compound BT317, shows on-target LonP1 and exceptional chymotrypsin-like proteasome inhibition. This has led to further testing, which has shown that BT317 has enhanced activity against glioma stem cell lines (GSC) and can cause global downregulation of hypoxia inducible factor 1 alpha (Hif1α) in a heterogenous GSC-derived organoid model. Finally, we have demonstrated that BT317 has less activity against differentiated GSC lines (e.g. through successive passages) and appears to have enhanced activity against TNFa-induced, differentiated GSC. This preliminary data highlights combinatorial, pharmacological LonP1 and proteasome inhibition as a novel strategy for targeting GSC in GBM.
The mass production of memory: travel and personal archiving in the age of Kodak: by Tammy S. Gordon, Amherst and Boston: University of Massachusetts Press, 2020, 176 pp., US$90.00 (cloth), ISBN 978-1-62534-531-8, US$27.95 (paperback) ISBN 978-1-62534-532-5

When Kodak began marketing its cameras to the American modern consumer in the late 1880s, it focused on two key themes, family pictures and the mobile modern citizen, travelling and embracing the g...
Transradial Coronary Interventions

Transradial angiography and intervention continue to become increasingly common as an access site for coronary procedures due to decreased rates of access site complications, improved patient comfort, and reduced adverse cardiac events in certain subsets. This chapter provides an overview on radial interventions.
Molecular dynamics study of wetting of alkanes on water: from high temperature to the supercooled region and the influence of second inflection points of interfacial tensions.

To explore the wetting behavior of alkanes on bulk water interfaces, molecular dynamics (MD) simulations were carried out for united-atom PYS alkane models, and for SPC/E and TIP4P/2005 water models over a wide temperature range. The MD results at each temperature were used to find (1) the surface tension of the alkanes (octane, nonane) and water, and (2) the interfacial tensions of the alkane–water systems. These quantities were then used to calculate the spreading coefficient (S) and contact angle (θc) for each alkane on water. At higher temperatures, the contact angle of octane and nonane on water is found to behave in accord with conventional expectations, i.e., it decreases with increasing temperature for both water models as each system approaches the usual high-temperature transition to perfect wetting. At lower temperatures, we found an unusual temperature dependence of S and θc for each PYS alkane on SPC/E water. In contrast to conventional expectations, θc decreases with a decrease in the temperature. For octane–SPC/E water, this unusual behavior of θc occurs due to the presence of second inflection points (SIP) in the vapor–water and the octane–water interfacial tensions, whereas the SIP effect is much less important for the nonane–water system. The unusual temperature dependence of θc observed for nonane on SPC/E water is also found for nonane on TIP4P/2005 water. On the other hand, such unusual wetting behavior has not been observed in the PYS octane–TIP4P/2005 water system, except possibly for the two lowest temperatures studied.
The Value of EphB2 Receptor and Cognate Ephrin Ligands in Prognostic and Predictive Assessments of Human Breast Cancer

Cell-cell communication proteins Eph and ephrin constitute the largest family of receptor tyrosine kinases (RTKs). They are distinguished by the fact that both receptors and ligands are membrane-bound, and both can drive intracellular signaling in their respective cells. Ever since these RTKs have been found to be involved in cancer development, strategies to target them therapeutically have been actively pursued. However, before this goal can be rationally achieved, the contributions of either Eph receptors or their ephrin ligands to cancer development and progression should be scrutinized in depth. To assess the clinical pertinence of this concern, we performed a systematic review and meta-analysis of the prognostic/predictive value of EphB2 and its multiple cognate ephrin ligands in breast cancer. We found that EphB2 has prognostic value, as indicated by the association of higher EphB2 expression levels with lower distant metastasis-free survival (DMFS), and the association of lower EphB2 expression levels with poorer relapse-free survival (RFS). We also found that higher EphB2 expression could be a prognostic factor for distant metastasis, specifically in the luminal subtypes of breast cancer. EFNB2 showed a marked correlation between higher expression levels and shorter DMFS. EFNA5 or EFNB1 overexpression is correlated with longer RFS. Increased EFNB1 expression is correlated with longer OS in lymph node (LN)-negative patients and the luminal B subtype. Higher levels of EFNB2 or EFNA5 are significantly correlated with shorter RFS, regardless of LN status. However, while this correlation with shorter RFS is true for EFNB2 in all subtypes except basal, it is also true for EFNA5 in all subtypes except HER2+. The analysis also points to possible predictive value for EphB2. In systemically treated patients who have undergone either endocrine therapy or chemotherapy, we found that higher expression of EphB2 is correlated with better rates of RFS. Bearing in mind the limitations inherent to any mRNA-based profiling method, we complemented our analysis with an immunohistochemical assessment of expression levels of both the EphB2 receptor and cognate ephrin ligands. We found that the latter are significantly more expressed in cancers than in normal tissues, and even more so in invasive and metastatic samples than in ductal carcinoma in situ (DCIS). Finally, in an in vitro cellular model of breast cancer progression, based on H-Ras-transformation of the MCF10A benign mammary cell line, we observed dramatic increases in the mRNA expression of EphB2 receptor and EFNB1 and EFNB2 ligands in transformed and invasive cells in comparison with their benign counterparts. Taken together, these data show the clinical validity of a model whereby EphB2, along with its cognate ephrin ligands, have dual anti- and pro-tumor progression effects. In so doing, they reinforce the necessity of further biological investigations into Ephs and ephrins, prior to using them in targeted therapies.
Exome sequencing of fetuses with congenital diaphragmatic hernia supports a causal role for NR2F2, PTPN11, and WT1 variants

Abstract Background To identify genes associated with congenital diaphragmatic hernia (CDH) to help understand the etiology and inform prognosis. Methods We performed exome sequencing on fetuses with CDH and their parents to identify rare genetic variants likely to mediate risk. We reviewed prenatal characteristics and neonatal outcomes. Results Data were generated for 22 parent-offspring trios. Six Likely Damaging (LD) variants were identified in five families (23 %). Three LD variants were in genes that contain variants in other CDH cohorts (NR2F2, PTPN11, WT1), while three were in genes that do not (CTR9, HDAC6, TP53). Integrating these data bolsters the evidence of association of NR2F2, PTPN11, and WT1 with CDH in humans. Of the five fetuses with a genetic diagnosis, one was terminated, two underwent perinatal demise, while two survived until repair. Conclusions Exome sequencing expands the diagnostic yield of genetic testing in CDH. Correlating CDH patients’ exomes with clinical outcomes may enable personalized counseling and therapies.
A Data-Model for a Technology and Simulation Archive

In this paper, we describe software aimed at achieving a significant reduction in the time required to develop new semiconductor technologies, by facilitating simulation sharing, and recognition and reuse of technology modules. We have created a technology and simulation archive based on the World-Wide Web (WWW) data-model. The WWW data-model is very flexible in capturing the wide variety of data formats of technology and simulation related information, and it proves to be sufficiently fast for frequent direct data retrieval by simulation tools.
Forced Random Noise Resistance Determination in Childhood Asthma

The forced random noise method for measuring respiratory resistance was studied in terms of reproducibility and correlation with spirometry and flow volumes in 30 older children (four to 17 years) with asthma and in 16 infants and children below three years of age. In the 30 older children, the mean value of individual coefficient of variations for three repeated measurements was 7.4 percent. Resistance parameters correlated well with spirometric parameters with all but three correlation coefficients greater than 0.7. In 20 older asthmatic patients, 180 μg albuterol caused a significant reduction in resistance in 11 subjects. At the same time, FEV1 increased significantly in nine subjects but showed a paradoxic decrease in five. This paradoxic response is attributed to complex reflexes caused by the maximum inspiration and forced expiration and did not occur with resistance measurements. This method requires little subject cooperation, and therefore, is well suited for infants and children.
Newborn screening for intellectual disability: Past, present, and future

Abstract Newborn screening began in the 1960s with a condition causing severe intellectual disability, phenylketonuria, a disease that could be remediated through a dietary change that prevented intellectual disability. Since then newborn screening has become a significant public health initiative offered in every birthing hospital in the United States, sometimes for more than 50 conditions. The landscape of newborn screening is changing rapidly, however, as a result of new gene discoveries, technological developments, advocacy efforts, and private market forces. Soon it will be possible to screen for many conditions causing intellectual disability, but for which there will be no immediate medical treatment, evoking issues related to the ethics of disclosing genetic information about “untreatable conditions” and the support systems that would be necessary to help families and children cope with this information. Fundamental questions have been asked about the likelihood of various costs and benefits of early identification, prompting a whole new set of demands for data on the efficacy of earlier psychosocial interventions and the timing of treatments. This chapter reviews the history and current status of newborn screening for intellectual disability, envisions a likely future of possible genetic disclosure, and identifies research questions that will need to be answered to help inform public policy.
Opinion Standards for Tax Practitioners Under U.S. Department of the Treasury Circular 230

Practitioners1 who appear before the Internal Revenue Service (IRS) are subject to the practice standards published in Treasury Department Circular 230.2 These standards cover “matters connected with a presentation to the Internal Revenue Service ... relating to a taxpayer’s rights, privileges, or liabilities under laws or regulations administered by the Internal Revenue Service.”3 The Circular 230 standards apply to a broad range of practitioner conduct, including matters such as practitioner due diligence, conflicts of interest, fees, and the provision of tax advice. Circular 230 also contains sanction provisions that apply when the practice standards are violated and procedural rules governing disciplinary proceedings. The rules set forth in Circular 230 are administered and enforced by the Director of the Office of Professional Responsibility.
Sensitive blood-retinal barrier breakdown quantitation using Evans blue.

PURPOSE. This study investigated whether a nonradioactive dye, Evans blue, can be adapted as a safe alternative to the isotope-dilution method for quantitating blood-retinal barrier breakdown. METHODS. Blood-retinal barrier breakdown was induced in rats with vascular endothelial growth factor (VEGF) or through the induction of diabetes. After allowing Evans blue to circulate in the vasculature, the dye was cleared from the bloodstream with saline, citrate, or citrate-buffered paraformaldehyde, and the efficacies of the perfusion solutions were compared. Extravasated dye was detected at 620 nm and was normalized against the time-averaged Evans blue plasma concentration, the circulation time, and also against wet and dry retina weights. RESULTS. Evans blue leakage from retinas treated with VEGF was 4.0-fold higher than that of contralateral untreated eyes (n = 6 rats, P < 0.05). Retinal Evans blue leakage of eyes from 1-week diabetic animals (n = 11 retinas) was 1.7-fold higher (P < 0.05) than that of nondiabetic controls (n = 10 retinas). Intra-animal, inter-retina weights showed significantly less variability (P < 0.05) with the use of dry weights (11.2%, n = 74 retina pairs) than with wet weights (20.5%, n = 93 retina pairs). CONCLUSIONS. The Evans blue dye technique can be modified to be as sensitive and quantitative as the isotope-dilution method for measuring blood-retinal barrier breakdown. The advantages of the Evans blue technique are its safety, relative simplicity, and economy.
Using Experiential Learning to Increase the Recognition of Everyday Sexism as Harmful: The WAGES Intervention

The harms of subtle sexism tend to be minimized despite negative cumulative effects, thus people may be less motivated to address subtle sexism. We tested the effectiveness of an experiential learning intervention, WAGES-Academic (Workshop Activity for Gender Equity Simulation-Academic), to educate about the harms of subtle sexism in the academic workplace. Across two studies, WAGES increased the recognition of everyday sexism as harmful and promoted behavioral intentions to discuss and seek information about gender inequity compared to a control condition that provided identical information as WAGES but without experiential learning. These effects were due to WAGES limiting reactance and promoting self-efficacy. Moreover, WAGES did not differ in reactance or self-efficacy compared to a control condition that provided no gender inequity information. This suggests that WAGES buffers the potential negative effects of simply presenting gender inequity information. Results suggest that WAGES, and experiential learning more broadly, has the potential to change attitudes and behaviors about everyday sexism.
Effect of organic compounds on reproductive processes: IV. Response of Japanese quail to alkylating agents

Abstract Chemosterilant chemicals were evaluated for their effects on body weight, feed consumption, egg production, reproduction, and mortality of adult Japanese quail based on a 2-week compound feeding period. Acute toxicity values to mice were also determined. Birds fed N,N′-bis(aziridinylacetyl)-1,8-octamethylenediamine at the lowest dietary level of 250 ppm lost weight associated with marked decreases in feed consumption, egg production, and high mortality. The acute LD50 value to male mice was 1070 (768–1490) mg/kg following oral intubation and 88 (60–130) mg/kg following intraperitoneal injection. Birds fed N,N′-bis(aziridinylacetyl)-1,4-trans-cyclohexylmethylamine at 125 ppm lost weight but showed no significant decrease in feed consumption or egg production; egg fertility and hatchability were markedly inhibited but returned to normal during a 4-week recovery period. At 250 ppm, body weight, feed consumption, and egg production decreased markedly but increased during the recovery period. A high mortality rate was observed at 500 ppm. The acute toxicity to mice was 71 mg/kg following oral intubation and 45 (38–53) mg/kg following intraperitoneal injection. Apholate at 125 ppm produced only marginal effects on body weight and feed consumption, but egg production was reduced; egg hatchability and fertility were completely inhibited, but increased during the recovery period. At 250 ppm, only slight decreases in body weight, feed consumption, and egg production were observed in one trial whereas marked decreases were obtained in the second trial. A few birds were found dead at 500 ppm, but the mortality rate was high at 1000 ppm
Rhetoric and rationality: A study of democratization in the Soviet Union

Can political actors use rational strategies for political conflict when established institutions are unavailable to structure political choices because the institutions are themselves among the contested issues? In Soviet politics from 1985 to 1991, cross-cutting cleavages placed in question the possibility of any stable outcome. We argue that a multi-dimensional issue space was reduced to a single dimension, along which Mikhail Gorbachev could temporarily occupy a median, by the interaction between Gorbachev's own rhetoric and rhetorical tactics used by leaders of his nomenklatura opposition, by Boris Yeltsin as the leader of the democratic opposition, and by single-issue groups called neformaly. The match between these four players' rhetorics and the four strategic options identified by a simple spatial model offers empirical evidence that rational strategies were available despite institutional flux.