cssi/SciSciGPT-SciSciNet huggingface dataset:
BMI and Lower Extremity Injury in U.S. Army Soldiers, 2001–2011

Introduction Little data exist regarding the long-term impact of excess weight on lower extremity musculoskeletal injury/disorder (MID) in U.S. Army Soldiers. This prospective analysis examines the association between BMI of Soldiers at accession and risk of MID. Methods A total of 736,608 Soldiers were followed from accession into the Army, 2001–2011. Data were analyzed January through March 2015. MID was categorized as any first incident lower extremity musculoskeletal injury/disorder, and secondarily, as first incident injury/disorder at a specific site (i.e., hips, upper legs/thighs, knees, lower legs/ankles, feet/toes). Multivariable-adjusted proportional hazards models estimated associations between BMI category at accession and MID risk. Results During 15,678,743 person-months of follow-up, 411,413 cases of any first MID were documented (70,578 hip, 77,050 upper leg, 162,041 knee, 338,080 lower leg, and 100,935 foot injuries in secondary analyses). The overall MID rate was 2.62 per 100 person-months. Relative to Soldiers with normal BMI (18.5 to 2 ) at accession, those who were underweight ( 2 . Conclusions Soldier BMI at accession has important implications for MID. A BMI of 21–23 kg/m 2 in newly accessing Soldiers was associated with the lowest risk of incident MID, suggesting that accession be limited to people within this range to reduce overall incidence of MID among service personnel.
Incorporating Feminism Into the Graduate Curriculum

Feminist theory and methods are vital catalysts to teaching/learning in graduate education. This article describes how feminism was integrated into a graduate course, specifically regarding nursing activism and health policy. Major themes include a learning model emphasizing the student's individual strands of life experience, reconstruction of nursing history, and small-group process. Class assignments, student responses, and the implications of feminist perspectives for advanced professional practice are discussed.
The Normativity Objection to Normative Reduction

Non-naturalists claim that the nature of normativity precludes the possibility of normative naturalism. In particular, they think that normative reduction amounts to normative elimination. This is because it always leaves out the normative. In this paper, I examine the force that the normativity objection has against Humean reductionism. I argue that the normativity objection has no argumentative force against reductionism. When it is presented as a bare intuition, it begs the question against reduction. A more interesting reading of the argument claims that the normative cannot be explained in terms of the natural because the natural is arbitrary. Yet, this version of the argument fails as well because the natural is not arbitrary in the relevant sense. The natural is contingent, so what has value is contingent. That is not an elimination of the normative though, because contingent reasons are still reasons.
Can QTAIM Topological Parameters Be a Measure of Hydrogen Bonding Strength

The block-localized wave function (BLW) method, which is the simplest variant of ab initio valence bond (VB) theory, together with the quantum theory of atoms in molecules (QTAIM) approach, have been used to probe the intramolecular hydrogen bonding interactions in a series of representative systems of resonance-assisted hydrogen bonds (RAHBs). RAHB is characteristic of the cooperativity between the π-electron delocalization and hydrogen bonding interactions and is identified in many biological systems. While the deactivation of the π resonance in these RAHB systems by the use of the BLW method is expected to considerably weaken the hydrogen bonding strength, little change on the topological properties of electron densities at hydrogen bond critical points (HBCPs) is observed. This raises a question of whether the QTAIM topological parameters can be an effective measure of hydrogen bond strength.
Halo orbit determination and control for the elliptic restricted three-body system

This paper presents further applications of an iterative numerical approach for the halo orbit determination and control problem to the elliptic restricted three-body system. The effects from both orbital eccentricity and dynamical nonlinearities are modeled as trajectory-dependent persistent disturbances, and the iterative method utilizes a disturbance accornrnodating linear state-feedback controller to determine fuelefficient, quasi-periodic or periodic orbits. The method is applied to the elliptic restricted three-body problem of the earth-moon-spacecraft system as well as the sunearthlmoon-spacecraft system.
Centrifugal and Centripetal Force Concrete Illustration to Explain Basic Principles

(1967). Centrifugal and Centripetal Force Concrete Illustration to Explain Basic Principles. Journal of Health, Physical Education, Recreation: Vol. 38, No. 8, pp. 79-80.
The Influence of the Built Environment on Graduate Student Perceptions of Graduate School Experience

AbstractIn recent years there has been an increased concern over the adequacy of educational facilities to create an environment that is conducive to learning. Many studies have investigated the influence of the built environment on undergraduate students; however, none have explicitly investigated the influence of the built environment on graduate student perceptions of their educational experience. Conclusions about the influence of the built environment on undergraduate students have previously been generalised to include graduate students, but graduate students typically have different educational motivations than undergraduates. This paper investigates the influence of the built environment on graduate student perceptions of their educational experiences. The findings challenge the generalisation of previous undergraduate research findings as being applicable to graduate students. It concludes that graduate student perceptions are not influenced by the built environment to the same degree as those of...
A Genetic Algorithm Based Approach for 3D Face Recognition

The ability to distinguish different people by using 3D facial information is an active research problem being undertaken by the face recognition community. In this paper, we propose to use a generic model to label 3D facial features. This approach relies on our realistic face modeling technique, by which the individual face model is created using a generic model and two views of a face. In the individualized model, we label face features by their principal curvatures. Among the labeled features, “good features” are selected by using a Genetic Algorithm based approach. The feature space is then formed by using these new 3D shape descriptors, and each individual face is classified according to its feature space correlation. We applied 105 individual models for the experiment. The experimental results show that the shape information obtained from the 3D individualized model can be used to classify and identify individual facial surfaces. The rank-4 recognition rate is 92%. The 3D individualized model provides consistent and sufficient details to represent individual faces while using a much more simplified representation than the range data models. To verify the accuracy and robustness of the selected feature spaces, a similar procedure is applied on the range data obtained from the 3D scanner. We used a subset of the optimal feature space derived from the Genetic Algorithm, and achieved an 87% rank-4 recognition rate. It shows that our approach provides a possible way to reduce the complexity of 3D data processing and is feasible to applications using different sources of 3D data.
Uterine myomas: clinical and pathologic aspects.

A small, asymptomatic myomatous uterus usually may be left alone but should be periodically observed. A large myomatous uterus that is subject to bleeding or produces pressure on the bowel, bladder or ureters requires surgery—usually total hysterectomy, with retention of normal ovaries if the patient is young. When a myoma in an older woman shows accelerated growth, malignant degeneration should be suspected.
Why we reason: intention-alignment and the genesis of human rationality

Why do humans reason? Many animals draw inferences, but reasoning—the tendency to produce and respond to reason-giving performances—is biologically unusual, and demands evolutionary explanation. Mercier and Sperber (Behav Brain Sci 34:57–111, 2011) advance our understanding of reason’s adaptive function with their argumentative theory of reason (ATR). On this account, the “function of reason is argumentative… to devise and evaluate arguments intended to persuade.” ATR, they argue, helps to explain several well-known cognitive biases. In this paper, I develop a neighboring hypothesis called the intention alignment model (IAM) and contrast it with ATR. I conjecture that reasoning evolved primarily because it helped social hominins more readily and fully align their intentions. We use reasons to advance various proximal ends, but in the main, we do it to overwrite the beliefs and desires of others: to get others to think like us. Reason afforded our ancestors a powerful way to build and maintain the shared outlooks necessary for a highly collaborative existence. Yes, we sometimes argue so as to gain argumentative advantage over others, or otherwise advantage ourselves at the expense of those we argue with, but more often, we reason in ways that are mutually advantageous. In fact, there are excellent reasons for thinking this must be so. IAM, I suggest, neatly explains the available evidence, while also providing a more coherent account of reason’s origins.
TUTORIAL: Silicon-Chip-Based Optical Frequency Combs

We describe recent work on the development of chip-based frequency combs based on parametric mixing that offer the promise of highly compact, robust sources for metrology, spectroscopy, and ultrafast applications. Article not available.
Creating Supersecondary Structures with BuildBeta

BuildBeta is a feature of the ProteinShop software designed to thoroughly sample a protein conformational space given the protein's sequence of amino acids and secondary structure predictions. It targets proteins with beta sheets because they are particularly challenging to predict due to the complexity of sampling long-range strand pairings. Here we discuss some of the most difficult targets in the recent 9th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP9) and show how BuildBeta can leverage some of the most successful methods in the category "template-free modeling" by augmenting their sampling capabilities. We also discuss ongoing efforts to improve the quality of the supersecondary structures it generates.
The Production of Indebted Subjects: Capitalism and Melancholia

In the essay ‘Postscript on the Societies of Control’, Deleuze discusses the differences between nineteenth-century capitalism and contemporary capitalism, characterising the former as the spaces of enclosure and the latter as the open circuits of the bank. In contemporary capitalism, ‘[m]an is no longer man enclosed, but man in debt’ (Deleuze 1992: 6). Deleuze claims that under financial capitalism, where the primary use of money is self-generation, economic relations are thought in terms of an asymmetrical power relationship between debtor and creditor, rather than an exchange between commodities. Taking up Deleuze's claim, this paper analyses how time functions in the formation of subjectivity under financial capitalism, by focusing on the temporal structure of debt. The indebted are expected to bind themselves to the past, not only in the moment they make a promise to pay back, but from that moment onwards; in this process, a subject finds himself passively subjected to the temporality determined by t...
Markov Models and Cost Effectiveness Analysis: Applications in Medical Research

This case study describes common Markov models, their specific application in medical research, health economics and cost-effectiveness analysis.
Systematicity, a missing term in historical metrics:

This essay identifies two persistent problems in the historical study of meter—nonconformant metrical patterns and metrical change—and offers a new term as a conceptual tool for understanding their interdependence. The term ‘systematic’ denotes metrical patterns that conform to synchronically operant metrical principles. The corresponding term ‘asystematic’ denotes the minority of actually occurring metrical patterns that fall outside the metrical system as such for historical reasons. All systematic patterns are necessarily metrical, but not all metrical patterns are systematic. It is argued that the systematicity/metricality distinction in historical metrics is analogous to the regularity/grammaticality distinction in historical linguistics and similarly fundamental to historical analysis. By introducing a new technical term, this essay seeks to shift the metrist’s object of study from the metrical system qua system to meter as a complex historical experience. The value of the concept of systematicity i...
Development and Phenotype Studies of a Slow Skeletal Troponin T E180 Nonsense Mutation Knock-In Mouse Line

A nonsense mutation in codon Glu180 of TNNT1 gene encoding the slow skeletal muscle isoform of troponin T (ssTnT) causes a recessively inherited severe nemaline myopathy (Amish nemaline myopathy, ANM). Muscle biopsies of ANM patients showed a total loss of ssTnT. The present study developed and characterized mice with the E180 nonsense mutation knocked-in the Tnnt1 gene (ssTnT-KI). Homozygotes of ssTnT-KI mice survived to adulthood. Histology studies revealed significant increases of centralized nuclei in the soleus muscle of ssTnT-KI when compared with age matched wild type controls. Immunohistochemistry staining showed atrophic slow type 1 fibers in ssTnT-KI mouse soleus muscle with severe inflammatory cells infiltration. Western blots confirmed the absence of full length ssTnT with no ssTnT fragments detectable, mimicking that seen in the muscle of ANM patients. Contractile properties of ssTnT-KI mouse soleus muscle measured in situ demonstrated a decreased fatigue resistance. Significant expression of cardiac TnT is detected in soleus muscle of ssTnT-KI mice, consistent with the presence of active muscle regeneration. Decrease of slow type isoforms and increase of fast type isoforms of other myofilament proteins with a significant hypertrophy of fast fibers in ssTnT-KI mouse soleus muscle indicate a potentially compensatory adaptation to the loss of slow fiber functions. The ssTnT-KI mouse line provides a model of ANM for pathogenesis, pathophysiology and therapeutic studies.
Variable region in streptococcal M-proteins provides stable binding with host fibrinogen for plasminogen-mediated bacterial invasion

Dimeric M-proteins (M-Prt) in group A Streptococcus pyogenes (GAS) are surface-expressed virulence factors implicated in processes that contribute to the pathogenicity of infection. Sequence analyses of various GAS M-Prts have shown that they contain a highly conserved sortase A-dependent cell wall-anchored C terminus, whereas the surface-exposed N terminus is highly variable, a feature used for identification and serotyping of various GAS strains. This variability also allows for strain-specific responses that suppress host defenses. Previous studies have indeed identified the N-terminal M-Prt B-domain as the site interacting with antiphagocytotic human-host fibrinogen (hFg). Herein, we show that hFg strongly interacts with M-Prts containing highly variable B-domains. We further demonstrate that specific GAS clinical isolates display high affinity for the D-domain of hFg, and this interaction allowed for subsequent surface binding of human-host plasminogen (hPg) to the E-domain of hFg. This GAS surface-bound hPg is then activated by GAS-secreted streptokinase, leading to the generation of an invasive proteolytic bacterial surface. Our results underscore the importance of the human fibrinolytic system in host-pathogen interactions in invasive GAS infections.
Business Model Mechanism

The business model mechanism constitutes the value creation and appropriation drivers that underlie the firm’s competitive advantage. Entrepreneurial incentives enhance the firm’s value creation and appropriation drivers. The entrepreneurial incentives further enhance the management logics that enable the firm to sense, seize, and act on value opportunities that provide the firm’s value creation engine the fuel to sustain competitive advantage. The business model advantage construct constitutes scalability, adaptability, and sustainability. The business model complexity, tacitness, complementaries, customer and supplier lock-in, and business model novelty and specificity enhance the business model sustainability. The business model adaptability is enhanced with activity system multiplexity, redundancy, and loose–tight coupling. The business model construct can be alternatively viewed by the four perspectives of the balanced scorecard. The strategy map links the firm’s financial performance, buyer value drivers, value activities, and core resources. Robust business models enable firms to stay ahead of the Red Queen race. The entrepreneurial incentives sustain the value creation and appropriation that enhances the business model advantage and the firm’s competitive position. A business model that has optimal complexity such that it operates at the edge of chaos provides increasing returns to scale. The management logics are the “glue” that hold a firm’s loosely coupled value activities together.
Loss of Brainstem Auditory Evoked Potentials during Microvascular Decompression For Hemifacial Spasm (P03.054)

OBJECTIVE: The primary aim of this paper is to study the pre-operative characteristics, Intraoperative monitoring (IOM) changes and post-operative outcomes in patients with complete loss of wave V of the Brainstem Auditory evoked Potential (BAEP). BACKGROUND: Intraoperative monitoring (IOM) of BAEP during microvascular decompression (MVD) prevents hearing loss (HL) in patients with hemifacial spasm (HFS). Complete loss of BAEP waveforms is uncommon event during MVD, which has significant prognostic potential. DESIGN/METHODS: We retrospectively analyzed the BAEP data of 94 patients who underwent MVD for HFS at our institute. Patients were divided into two groups those with and those without loss of wave V. The differences between two groups and outcomes were assessed using t test and χ2 (chi-square) tests. RESULTS: In our study 23 (24%) patients out of 94 had a complete loss of wave V, among these 11 (48%) patients had transient loss and 12 (52%) patients had permanent loss. There was a significantly higher incidence of HC (hearing change) and HL in patients with loss of wave V (p = .05). CONCLUSIONS: Preoperative use of botox injection was significantly higher in patients with loss of wave V during MVD. Though one fourth of the patients lost wave V more than half of them had some improvement during MVD. Some patients had no HL despite wave V loss, among them more than half had transient loss of wave V. Appropriate alarm criteria needs to be developed to warn the surgeon about an impending loss of wave V during MVD. Disclosure: Dr. Krishnaiah has nothing to disclose. Dr. Thirumala has nothing to disclose. Dr. Habeych has nothing to disclose. Dr. Crammond has nothing to disclose. Dr. Balzer has nothing to disclose.
Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium.

Background Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection. Methods We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis. Results A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded. Conclusions AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.
Facile Dehydrogenation of Ethane on the IrO2(110) Surface.

Realizing the efficient and selective conversion of ethane to ethylene is important for improving the utilization of hydrocarbon resources, yet remains a major challenge in catalysis. Herein, ethane dehydrogenation on the IrO2(110) surface is investigated using temperature-programmed reaction spectroscopy (TPRS) and density functional theory (DFT) calculations. The results show that ethane forms strongly bound σ-complexes on IrO2(110) and that a large fraction of the complexes undergo C–H bond cleavage during TPRS at temperatures below 200 K. Continued heating causes as much as 40% of the dissociated ethane to dehydrogenate and desorb as ethylene near 350 K, with the remainder oxidizing to COx species. Both TPRS and DFT show that ethylene desorption is the rate-controlling step in the conversion of ethane to ethylene on IrO2(110) during TPRS. Partial hydrogenation of the IrO2(110) surface is found to enhance ethylene production from ethane while suppressing oxidation to COx species. DFT predicts that hydr...
Structure, Policy, Services, and Performance in the Business Incubator Industry:

Business incubators are one of the newest tools on the enterprise development scene; nearly 400 are now in operation. A business incubator is a facility that provides affordable space, shared offic...
ECONOMIC FREEDOM AND INCOME LEVELS ACROSS U.S. STATES: A SPATIAL PANEL DATA ANALYSIS

There is a large literature estimating the effect of economic freedom on economic growth or income levels. Most studies examine the relationship between economic freedom and growth or income levels for countries, while a few examine the relationship for U.S. states. Absent in the state‐level literature is consideration of the presence of spatial spillovers affecting the freedom‐income relationship. Neglecting to account for spatial autocorrelation can bias estimation results and therefore inferences drawn. We find evidence of a spatial pattern in real per‐capita gross state product (GSP) that affects nonspatial estimates of the freedom‐income relationship. Taking into account the direct and indirect effects of economic freedom on real per‐capita GSP, we find a 10% increase in economic freedom is associated with a 5% increase in real per‐capita GSP. (JEL E02, O47, R11)
Nicotine in Ulcerative Colitis

Ulcerative colitis is primarily a disease of nonsmokers. The risk of developing disease after cessation of smoking is ‘dose-related’ by pack-years, and former smokers may be at higher risk than nonsmokers. Attention has been focused on nicotine as the agent responsible for this effect. Nicotine in chewing gum and transdermal patches has been shown to improve clinical symptoms and endoscopic appearance in patients with active ulcerative colitis, although no maintenance benefit has been seen.
On the Operation of Emotion in Justice Judgments: There's More Than Unfairness to Injustice

The concept of justice has been an important one for some time in the literature. The idea that fairness and unfairness drives behavior is widely held and accepted in the field. I proposed that a two-factor view of justice will mediate the relationship between an emotion and a behavior. This view contends that the emotion is the proximal outcome of an event and that the perception of justice hinges on this emotion.
In-Phase and Quadrature Analysis for Amplitude and Frequency Modulations Due to Vibrations on a Surface-Acoustic-Wave Resonator

Surface-acoustic-wave resonators (SAWRs) have found widespread usage in various modern consumer radio frequency (RF) communications electronics, such as cellular phones, wireless devices, GPS devices, frequency control, and sensing applications. External mechanical vibrations modify an SAWR relative dimensions and the substrate’s elastic properties, which alter the device’s acoustic wave propagation velocity and ultimately cause the SAWR RF response to change. Detecting vibrations are desirable for dynamic strain or vibration sensing applications, whereas external mechanical excitations can result in spurious signals which compromise SAW-based filters and oscillators used in RF communication, frequency control, and sensors targeting measurands such as temperature and pressure. Therefore, understanding and characterizing the SAWR’s response to external vibration is relevant for establishing device operation, and assisting in device design and packaging to either mitigate the impact of vibrations for RF communications and frequency control or enhance the SAWR response for sensor applications. This paper presents an in-phase and quadrature demodulation technique ( I–Q technique) to detect, quantify, and analyze the effect of externally induced mechanical vibrations on an SAWR. The I–Q technique disclosed reveals that the mechanical vibrations cause both frequency and amplitude modulations of the SAWR RF response, which can be separated by this technique. Furthermore, the procedure also allows the direct measurement of vibration frequencies and vibration magnitude. The technique, measured results, and analysis established here provide a better understanding of the impact of external mechanical vibrations on an SAWR response, which is important in contemporary communications, frequency control, and sensing applications.
Proceedings of the 31st ACM SIGPLAN Conference on Programming Language Design and Implementation

We are pleased to present the proceedings of the ACM SIGPLAN 2010 Conference on Programming Language Design and Implementation. PLDI addresses all issues relevant to the design of programming languages, the theory and practice of associated software tools, and experimentation with implementations. As always, the selected papers are a broad spectrum of the most exciting new work in the field. The pages of this volume represent only the end result of an enormous endeavor involving hundreds of people. Almost all this work is voluntary, with some individuals contributing hundreds of hours of their time to the effort. Together, the 22 members of the Program Committee (PC), the 57 members of the External Review Committee (ERC), and the 118 other individual reviewers consulted for their expertise wrote nearly 1,000 reviews. Every paper received at least four reviews and many had five or more. With the exception of submissions by the PC, each paper had at least three reviews from the PC and at least one review from an outside expert. For the second year running most of the outside reviews were done by the ERC, which was selected in advance, and additional outside reviews beyond the ERC were requested whenever appropriate or necessary. Reviewing was "first read double-blind," meaning that author identities were withheld from reviewers until they submitted a review. Revealing author names after initial reviews were written allowed reviewers to find related and previous material by the same authors, which helped greatly in many cases in understanding the context of the work, and also ensured that the author feedback and discussions at the PC meeting could be frank and direct. For the first time in many years, we allowed PC members to submit papers to the conference. Submissions co-authored by a PC member were reviewed exclusively by the ERC and other outside reviewers, and these same reviewers decided whether to accept the PC papers; no PC member reviewed a PC paper, and no PC papers were discussed at the PC meeting. After the reviewing was complete, the program committee met in Stanford, California on January 28th and 29th to select the program. Separately, the ERC decided on the PC papers in email and phone discussions. In the end, 41 of the 206 submissions (20%) were accepted for the conference. We hope you enjoy the program.
Value-added composite bioproducts reinforced with regionally significant agricultural residues

Abstract Biocomposites are potentially sustainable alternatives to traditional plastics and composites for which recycling is challenging. We assess four agricultural residue fibers (AF) in biocomposites with poly-(hydroxybutyrate-co-hydroxyvalerate) (PHBV): (i) hollow stem wheat, (ii) solid stem wheat, and (iii) barley as regionally significant food crop residues compared to (iv) hemp residue as an industrially-relevant control. AF (0 wt.%, 10 wt.%, 20 wt.%, 30 wt.%) were compounded with PHBV using two compatibilization treatments: (i) a silane coupling agent vapor deposited at room temperature and (ii) PHBV grafted to the fibers using reactive extrusion (gPHBV). Flexural modulus and ultimate strength were used to evaluate the impact of fiber fraction and treatments. Modulus increased with increasing fiber fraction, with 30% treated hemp composites having the highest modulus and strength. Hollow stem wheat was most comparable to hemp. The mechanical properties of the different AF-composites occupy a similar application space, indicating potential for robust composite processing using AF.
Pentoxifylline (trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells

Pentoxifylline (Trental), used routinely for the treatment of intermittent claudication, has been shown previously to decrease the levels of tumor necrosis factors-alpha (TNF-alpha) RNA in cancer patients and to lead to a general improvement of well being. Increased TNF-alpha levels have been observed not only in cancer patients but also in cachectic patients with the acquired immunodeficiency syndrome (AIDS), and TNF-alpha is known to increase the expression of the human immunodeficiency virus type 1 (HIV-1) via activating its long terminal repeat (LTR). Moreover, TNF-alpha decreases the therapeutic efficacy of zidovudine (AZT). Here we show a significant decrease in HIV-1 replication by pentoxifylline in infected human peripheral blood mononuclear cells. The reduction was proportional to the downregulation of expression of a reporter gene, the bacterial gene for chloramphenicol acetyl transferase, linked to the HIV-1 LTR in human monocytoid cells. We conclude that patients with AIDS may benefit from pentoxifylline treatment because of its blockage of TNF-alpha-mediated HIV-1 upregulation, from increased efficacy of AZT, and also from improvement in TNF-alpha-induced cachexia.
Creating a Defined Process to Improve the Timeliness of Serious Safety Event Determination and Root Cause Analysis

Serious Safety Events (SSEs) are defined as events in which there is a deviation from clinically accepted performance standards, causation, and significant patient harm or death. Given the nature of SSEs, it is important that the processes for declaration of SSEs, the performance of a root cause analysis (RCA), and action plan formation occur quickly, such that the window for potential recurrence of similar events is as small as possible. This manuscript describes a process put in place to improve the timeliness of SSE determination and RCA conduction and evaluates the effect of the process change on these parameters. Methods A causal analysis was performed of the baseline process to determine factors contributing to long process times. A new process was created and implemented both for the SSE determination process and the RCA completion process. We calculated the mean time for the pre-implementation phase (April 2016-December 2017) and the post-implementation phase (March 2018-January 2019) for both SSE determination and RCA completion. We evaluated differences with a two-sided t test assuming unequal variances. Results Comparing pre- versus post- implementation phases, the mean time for SSE determination for events that met the SSE criteria decreased from 38.4 to 4.8 days (P < 0.0001), determination for events that did not meet the SSE criteria decreased from 38.4 to 3.8 days (P < 0.0001), and RCA completion time dropped from 118.0 to 26.2 days (P < 0.0001). Conclusions A targeted intervention can significantly reduce SSE determination and RCA conduction times.
Application of a trabecular and cellular model of bone marrow dosimetry for targeted 223Ra therapy

139 Objectives: Absorbed dose-based treatment planning is a desirable objective for all radiopharmaceutical therapy. Ra-223, a bone-seeking radionuclide, has been used extensively as a therapeutic for bone metastases of prostate cancer. However, dosage follows a strict regimen based on mass, due to the complexity of the dosimetry including the low count rate of emissions, the disseminated and dynamic natures of the disease and organ at risk, the multiplicity of radioactive daughters as well as the short range and high LET of the alpha-particles. We propose to take an important step in Ra-223 bone marrow dosimetry by combining (a) small scale geometrical trabecular and cellular model, (b) detailed α-particle absorbed fractions from human cadaver studies, (c) high resolution autoradiography of resected mouse femurs and (d) clinical pharmacokinetics. Methods: Human pharmacokinetics, time-integrated activity (TIA) and whole organ absorbed dose values, including blood and bone were taken from the literature. The time integrated activity (number of decays) in the bone was apportioned to the bone matrix, endosteal layer and marrows cavities based on murine imaging data obtained using high resolution storage phosphor autoradiography as well as alpha-Camera images of resected mouse femurs sectioned on a cryostat. These TIAs were converted to absorbed dose to the endosteal layer, the bone matrix and the marrow as a function of marrow distance from bone surface different depths using absorbed fractions obtained from human cadaver data from a previous publication. The trabecular and cellular model was used to obtain cell dose histograms. Results: The activity and therefore TIA was primarily concentrated in the endosteal layer. Consequently, due to the short range of the α emitters, the absorbed dose was predominantly deposited near the bone surface, either in the endosteal layer or the shallow marrow. The dose cell histograms results were used to plot the percentage of marrow cells that received less than a potentially toxic dose (2 or 4 Gy) as a function of the average absorbed dose. The results show a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity, such that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity results in only a small increase in number of marrow cell with cytotoxic dose. Conclusions: Small scale modeling has been successful at interpreting localized dose in other organs, such as the kidneys and salivary glands. The dynamic and systemic nature of the bone marrow make it a more complex organ at risk, yet the use of small scale modeling offers insight into the lack of expected bone marrow toxicity as calculated from average absorbed dose and is a significant step towards reconciling dosimetry and toxicity.
Energized Oxygen in the Magnetotail: Current Sheet Bifurcation From Speiser Motion

Oxygen ions can be a major constituent of magnetospheric plasma, yet the role of oxygen in the magnetosphere is often not sufficiently understood. We examine the case of a thinning current sheet pr...
Click chemistry-based imaging to study the tissue distribution of the curcumin–protein complex in mice

Previous studies have shown that curcumin, a bioactive dietary compound with a thiol-reactive α,β-unsaturated carbonyl moiety, can covalently modify protein thiols. However, most of the previous studies were performed in cultured cells or cell-free enzyme systems, and so it remains unknown whether curcumin could covalently modify proteins after oral administration in vivo. Using click chemistry-based fluorescence imaging, here we show that oral administration of dialkyne-curcumin (Di-Cur), a “click” probe mimicking curcumin, results in covalent modifications of cellular proteins in colon and liver tissues, but not in other tissues, in mice. This result suggests that oral administration of curcumin leads to the formation of the curcumin–protein complex in a tissue-specific manner, which could contribute to the biological effects and/or pharmacokinetics of curcumin. Further studies to elucidate the identities of curcumin-binding proteins could greatly help us to better understand the molecular mechanisms of curcumin, and develop novel strategies for disease prevention.
Inherent Motor Impulsivity Associates with Specific Gene Targets in the Rat Medial Prefrontal Cortex.

Abstract High impulsivity characterizes a myriad of neuropsychiatric diseases, and identifying targets for neuropharmacological intervention to reduce impulsivity could reveal transdiagnostic treatment strategies. Motor impulsivity (impulsive action) reflects in part the failure of “top-down” executive control by the medial prefrontal cortex (mPFC). The present study profiled the complete set of mRNA molecules expressed from genes (transcriptome) in the mPFC of male, outbred rats stably expressing high (HI) or low (LI) motor impulsivity based upon premature responses in the 1-choice serial reaction time (1-CSRT) task. RNA-sequencing identified expression of 18 genes that was higher in the mPFC of HI vs. LI rats. Functional gene enrichment revealed that biological processes related to calcium homeostasis and G protein-coupled receptor (GPCR) signaling pathways, particularly glutamatergic, were overrepresented in the mPFC of HI vs. LI rats. Transcription factor enrichment identified mothers against decapentaplegic homolog 4 (SMAD4) and RE1 silencing transcription factor (REST) as overrepresented in the mPFC of HI rats relative to LI rats, while in silico analysis predicted a conserved SMAD binding site within the voltage-gated calcium channel subunit alpha1 E (CACNA1E) promoter region. qRT-PCR analyses confirmed that mRNA expression of CACNA1E, as well as expression of leucyl and cystinyl aminopeptidase (LNPEP), were higher in the mPFC of HI vs. LI rats. These outcomes establish a transcriptomic landscape in the mPFC that is related to individual differences in motor impulsivity and propose novel gene targets for future impulsivity research.
REPLICATION OF VIRUSES

Viruses are obligate intracellular parasites that replicate only within living animal, plant, or bacterial cells. Of the 71 taxonomically defined virus families, 24 contain members that infect vertebrates, and these families will be the focus of this overview. Among the smallest vertebrate viruses, the virion consists only of the viral genome and a closely associated protein coat (nucleocapsid), whereas larger viruses possess, in addition to the nucleocapsid, a variety of catalytic, regulatory and structural proteins, and in some cases a host-derived lipid membrane (envelope) containing one or more virus-encoded glycoproteins. In animal cells, virus replication is complete within several hours to at most a few days, and results in the synthesis of 103–105 virions per cell. Virus replication will be discussed in three stages: (1) early events (attachment to susceptible cells, penetration and uncoating), (2) viral biosynthetic events (replication of the viral genome, transcription and translation) and (3) virion assembly. However, because of space limitations, early events and mechanisms of virion assembly will be dealt with briefly so that viral biosynthetic strategies can be considered in greater detail.
Field dislocation mechanics and phase field crystal models

A formulation of the phase field crystal model is presented that is consistent with the necessary microscopic independence between the phase field, reflecting the broken symmetry of the phase, and both mass density and elastic distortion. Although these quantities are related in equilibrium through a macroscopic equation of state, they are independent variables in the free energy and can be independently varied in evaluating the dissipation functional that leads to some of the model governing equations. The equations obtained describe dislocation motion in an elastically stressed solid and serve as an extension of the equations of dislocation mechanics to the phase field crystal setting. Both finite and small deformation theories are considered, and the corresponding kinetic equations for the fields are derived.
Parsimonious powertrain modeling for environmental vehicle assessments: part 1—internal combustion vehicles

Environmental assessments of efforts to reduce vehicle fuel consumption require scientifically sound and robust fuel consumption models. The purpose of this paper is to introduce a novel method and model for calculating fuel consumption. This paper presents a method of powertrain modeling that is based on driving and powertrain physics, such as a net force approach to calculate force demand at the tire patch, and the use of engine maps to model engine efficiency. The presented method provides parsimonious open-source powertrain modeling to the environmental assessment community, thus an alternative to existing approaches. The modeling results are in agreement with existing values, while the modeling method is more flexible and avoids unnecessary approximations. Existing fuel consumption modeling consists of very detailed and complex powertrain simulation models, typically not available for environmental vehicle assessments, or streamlined equation-based methods that use a mix of physical laws, engineering approximations, and sometimes accounting principles. The presented modeling method and open-source model provide a valuable alternative.
‘Our family picture is a little hint of heaven’: race, religion and selective reproduction in US ‘embryo adoption’

Abstract People use selective reproductive technologies (SRT) in various family-making practices to assist with decisions about which children should be born. The practice of ‘embryo adoption', a form of embryo donation developed by white American evangelical Christians in the late 1990s, is a novel site for reconceptualizing SRT and examining how they function among users. Based on ethnographic research conducted between 2008 and 2018 on US ‘embryo adoption', this study provides an anthropological analysis of media produced by and about one white evangelical couple's race-specific preferences for embryos from donors of colour. This article shows how racializing processes and religious beliefs function as mutually reinforcing SRT for some ‘embryo adoption' participants. Evangelical convictions justify racialized preferences, and racializing processes within and beyond the church reinforce religious acts. Race-specific preferences for embryos among white evangelicals promote selective decision-making not for particular kinds of children, a current focus in studies of SRT, but for particular kinds of families. This study expands the framework of SRT to include selection for wanted family forms and technologies beyond biomedical techniques, such as social technologies like racial constructs and religious convictions. Broadly, this article encourages greater attention to religion within analyses about race and reproduction by revealing how they are deeply entwined with Christianity, especially in the USA. Wherever constructions of race and religious convictions co-exist with selective reptroductive decision-making, scholars should consider race, reproduction and religion as inextricable, rather than distinct, domains of analysis.
Automatic segmentation of the left ventricle in echocardiographic images using convolutional neural networks

Background Two-dimensional echocardiography (2D echo) is the most widely used non-invasive imaging modality due to its fast acquisition time, low cost, and high temporal resolution. Boundary identification of left ventricle (LV) in 2D echo, i.e., image segmentation, is the first step to calculate relevant clinical parameters. Currently, LV segmentation in 2D echo is primarily conducted semi-manually. A fully-automatic segmentation of the LV wall needs further development. Methods We evaluated the performance of the state-of-the-art convolutional neural networks (CNNs) for the segmentation of 2D echo images from 6 standard projections of the LV. We used two segmentation algorithms: U-net and segAN. The models were trained using an in-house dataset, which consists of 1,649 porcine images from 6 to 8 different pigs. In addition, a transfer learning approach was used for the segmentation of long-axis projections by training models with our database based on the previously trained weights obtained from Cardiac Acquisitions for Multi-structure Ultrasound Segmentation (CAMUS) dataset. The models were tested on a separate set of images from two other pigs by computing several metrics. The segmentation process was combined with a 3D reconstruction framework to quantify the physiological indices such as LV volumes and ejection fraction (EF). Results The average dice metric for the LV cavity was 0.90 and 0.91 for the U-net and segAN, respectively, which was higher than 0.82 for the level-set (P value: 3.31×10-25). The average Hausdorff distance for the LV cavity was 2.71 mm and 2.82 mm for the U-net and segAN, respectively, which was lower than 3.64 mm for the level-set (P value: 4.86×10-16). The LV shapes and volumes obtained using the CNN segmentation models were in good agreement with the results segmented by the experts. In addition, the differences of the calculated physiological parameters between two 3D reconstruction models segmented by the experts and CNNs were less than 15%. Conclusions The results showed that both CNN models achieve higher performance on LV segmentation than the level-set method. The error of the reconstruction from automatic segmentation compared to the expert segmentation is less than 15%, which is within the 20% error of echo compared to the gold standard.
Application of WNN-GNN-SVM combined algorithm to time series analysis of SF6 decomposed gas signal detected by photoacoustic spectroscopy

This paper first analyzes the principle of the photoacoustic spectroscopy detection technology, gives the absorption wavelength and the absorption line intensity of typical SF6 decomposition gas, and establishes the original database of the photoacoustic spectroscopy combined with the existing experimental platform. Furthermore, the principle of WNN-GNN-SVM combined algorithm and its construction method model are proposed, and the combined algorithm is applied to fit and predict the time series curve of sulfur hexafluoride characteristic decomposition gas with 6 peaks. The results show that the photoacoustic spectrum detection technology can effectively obtain the time series of typical sulfur hexafluoride decomposition gas, such as SO2F2, H2S, COS and CS2, and the WNN-GNN-SVM combination algorithm proposed in this paper can effectively select key points of sulfur hexafluoride decomposition gas characteristic peak for the multi spline curve quantitative fitting, and reasonably predict its change trend. In this paper, the optical detection method for typical decomposition gas of sulfur hexafluoride is effectively proposed, and the fitting and prediction post-processing method of the original data is given based on the detection results. The research results of this paper have good engineering application and theoretical research value for the detection and evaluation of the operation state of sulfur hexafluoride gas insulated power equipment.