cssi/SciSciGPT-SciSciNet huggingface dataset:
Genetics and Mechanisms of Permethrin Resistance in the Santa Luiza Strain of Boophilus microplus (Acari: Ixodidae)

The Santa Luiza strain of the southern cattle tick, Boophilus microplus (Canestrini) (Acari: Ixodidae), is resistant to both permethrin and amitraz. A study was conducted at the USDA Cattle Fever Tick Research Laboratory in Texas to investigate the genetic basis of permethrin resistance with cross-mating experiments, and to determine the mechanisms of permethrin resistance through synergist bioassays and biochemical analysis of esterase profiles. The Munoz strain, an acaricide-susceptible reference strain, was used as the susceptible parent and the Santa Luiza strain, originating in Brazil, was used as the resistant parent. The Food and Agriculture Organization larval packet test was used to measure the levels of susceptibility of larvae of the parental strains, F1, backcross, F2, and F3 generations to permethrin. Results of reciprocal crossing experiments suggested that permethrin resistance was inherited as an incomplete recessive trait. There was no significant maternal effect on larval progeny’s susceptibility to permethrin in the F1 and subsequent generations. The values of the degree of dominance were estimated at −0.700 and −0.522 for the F1 larvae with resistant and susceptible female parents, respectively. Results of bioassays on larval progeny of the F1 backcrossed with the resistant parent strain and of the F2 generations suggested that one major gene was responsible for permethrin resistance in the Santa Luiza strain. Selection of F3 larvae with either permethrin or amitraz led to significantly increased resistance to both permethrin and amitraz, indicating a close linkage between genes responsible for permethrin and amitraz resistance. The possible involvement of metabolic enzymes in permethrin resistance in the Santa Luiza strain of B. microplus was dismissed by the lack of enhanced synergism by TPP or PBO, as observed in synergist bioassays, as well as by the lack of enhanced esterase activity in the Santa Luiza strain relative to the susceptible strain. The results of this study suggest that other mechanisms, including a possible new sodium channel mutation that is different from the one currently known, may be responsible for permethrin resistance in the Santa Luiza strain of B. microplus.
Perceptions Of Undergraduate Business Students Toward Online Courses In Higher Education Expanded And Revisited: Do Gender, Age, And/Or Past Experiences Make A Difference?

This study analyzes the perceptions and preferences of a group of undergraduate business students with respect to taking on-line or distance education courses. In this last decade, distant learning programs have become very popular , and the number of offerings continues to increase. The growing popularity of this medium for instruction is due to a combination of factors. Technological advances have made the availability both economical and practical. The economic advantages of distributing scarce resources, geographically and temporally, to students in remote locations provide a broader market for distance education. Additionally, the increasing demand from students to acquire education at times that are convenient given their busy schedules and personal commitments makes distance education attractive to working learners (Roberts 1998). The new opportunities distance learning has provided have enabled students to create an atmosphere for learning at home. The distance debate usually focuses on issues related to student learning and outcomes and student attitudes as compared to traditional classroom-based settings (Phillips, 1998; Webster & Hackley, 1997). This study attempts to address these and other topics such as what is distance learning, what are the advantages and disadvantages, and what changes can be made to improve this type of learning. This research is intended to give students a realistic expectation of what to anticipate from distance learning courses based on information we have found and studies we have done. It is important that students have a realistic perception of the distant learning experience.
A fast, universal algorithm to learn parametric nonlinear embeddings

Nonlinear embedding algorithms such as stochastic neighbor embedding do dimensionality reduction by optimizing an objective function involving similarities between pairs of input patterns. The result is a low-dimensional projection of each input pattern. A common way to define an out-of-sample mapping is to optimize the objective directly over a parametric mapping of the inputs, such as a neural net. This can be done using the chain rule and a nonlinear optimizer, but is very slow, because the objective involves a quadratic number of terms each dependent on the entire mapping's parameters. Using the method of auxiliary coordinates, we derive a training algorithm that works by alternating steps that train an auxiliary embedding with steps that train the mapping. This has two advantages: 1) The algorithm is universal in that a specific learning algorithm for any choice of embedding and mapping can be constructed by simply reusing existing algorithms for the embedding and for the mapping. A user can then try possible mappings and embeddings with less effort. 2) The algorithm is fast, and it can reuse N-body methods developed for nonlinear embeddings, yielding linear-time iterations.
Tracking Oxidatively Stressed Cardiac Stem Cells With Molecular Imaging: “Insights” Into Fate, Viability, and Function∗

Regeneration of cardiomyocytes, which have historically been thought to be terminally differentiated, appears to occur at a very slow, clinically nonsignificant rate. The left ventricle has approximately 2 to 4 billion cells (1 g of myocardium has ∼20 million cardiomyocytes), and it is estimated
Windsor's Purgatory: State Doma's Can't Stabilize Straight Marriages, But They Can Still Prevent Gay Marriage

The essay is a preview piece to a longer article on an analysis of states that enacted Defense of Marriage Acts (referred to as mini or Super DOMAs) compared with states that did not. It presents the results of an empirical analysis determining whether state DOMAs achieved the goals articulated by its enactors, namely to increase family stability by decreasing divorce rates and increasing hetereosexual marriage rates. The study reveals that DOMAs have no bearing on the marriage and divorce rates. Overall, marriage and divorce is on the decline. However, in states that enacted DOMAs, the marriage rate is declining faster, and the divorce rate is declining slower than in states that have no DOMAs. Thus, the essay raises the question of how relevant DOMAs really are in creating family stability.
Probing a panoply of curvaton-decay scenarios using CMB data

In the curvaton scenario, primordial curvature perturbations are produced by a second field that is sub-dominant during inflation. Depending on how the curvaton decays [possibly producing baryon number, lepton number, or cold dark matter (CDM)], mixtures of correlated isocurvature perturbations are produced, allowing the curvaton scenario to be tested using cosmic microwave background (CMB) data. Here, a full range of 27 curvaton-decay scenarios is compared with CMB data, placing limits on the curvaton fraction at decay, $r_D$, and the lepton asymmetry, $\xi_{\rm lep}$. If baryon number is generated by curvaton decay and CDM before (or vice-versa), these limits imply specific predictions for non-Gaussian signatures testable by future CMB experiments and upcoming large-scale-structure surveys.
The Role of Yeast in Life History Studies of the Apple Maggot, Rhagoletis Pomonella Walsh.

Rearing of the apple maggot was readily secured by feeding the adult flies a simple solution consisting of one to three per cent yeast in five per cent honey water. The flies lived for many days, readily mating and ovipositing in small cages in the field or laboratory.
Feasibility of 18F-Fluoromisonidazole Kinetic Modeling in Head and Neck Cancer Using Shortened Acquisition Times

334 Objectives PARP1 inhibitors have played an important role in pharmaceutical research and one of them, Olaparib, has been approved for treatment of advanced ovarian cancer. This study aims to utilize a recently developed 18F-labeled PARP1 inhibitor, [18F]PARPi (1), to probe the in vivo characteristics of two PARP inhibitors, Olaparib and Talazoparib in patient derived xenograft (PDX) mouse models of small cell lung cancer. The in vivo data will be compared to in vitro data from these two as well as three other PARP inhibitors currently in development. Methods The 18F-labeled PARP1 inhibitor [18F]PARPi was generated via a previously reported synthesis (1). In vivo time on target measurements were taken by first injecting the inhibitor of interest (1 mg for Olaparib, 0.01 mg for Talazoparib, corresponding to therapeutic doses for each of the compounds), then injecting [18F]PARPi (200-300 µCi) at each time point. PET/CT Imaging was performed two hours after injection of [18F]PARPi. In vitro data was obtained via FACS using the fluorescent reporter PARPi-FL (2). Results PET/CT measurements have shown that baseline uptake of [18F]PARPi in PDX mouse models of small cell lung cancer is 1.46 ± 0.14 %ID/g. After one hour, Olaparib reduces uptake to 0.21 ± 0.003 %ID/g while Talazoparib reduces uptake to 0.35 ± 0.03 %ID/g. Tumor signal increases as the time is increases between the injection of the inhibitor and that of the imaging agent until at 48 hours, Olaparib reduces uptake to 0.76 ± 0.12 %ID/g while Talazoparib reduces uptake to 0.71 ± 0.15 %ID/g. The two phase decay curve generated by the data shows a steeper decline in blocking efficiency for Olaparib than for Talazoparib, indicating that Olaparib engages the binding site for less time than the Talazoparib. The ratio of the areas under the curves for is 1.0 : 1.17, Olaparib : Talazoparib. Conclusions The in vivo time on target measurements were taken with two PARP inhibitors, Olaparib and Talazoparib, using a recently developed 18F labeled PARP imaging agent, [18F]PARPi. This study demonstrates the feasibility of using PET with [18F]PARP to non-invasively study the pharmacodynamics of PARP inhibitors in vivo. $$graphic_D8585A81-CD40-4679-8C76-094D7F44D5ED$$
Bayesian inference for a common scale parameter of several Pareto populations

ABSTRACTThis article deals with the problem of Bayesian inference concerning the common scale parameter of several Pareto distributions. Bayesian hypothesis testing of, and Bayesian interval estimation for, the common scale parameter is given. Numerical studies including a comparison study, a simulation study, and a practical application study are given in order to illustrate our procedures and to demonstrate the performance, advantages, and merits of the Bayesian procedures over the classical and generalized variable procedures.
MBE Growth and Characterization of SxGe1−x Multilayer Structures on Si (100) for Use as a Substrate for GaAs Heteroepitaxy

Investigation has continued into the use of SixGe1−x multilayer structures (MLS) as a buffer layer between a Si substrate and a GaAs epitaxial layer in order to accommodate the 4.1% lattice mismatch. SixGe1−x 4-layer and 5-layer structures terminating in pure Ge have been grown using molecular beam epitaxy. Subsequent GaAs heteroepitaxy has allowed evaluation of these various GaAs/SixGe1−xMLS/Si (100) structures. Antiphase domain boundaries have been eliminated using vicinal Si (100) substrates tilted 6° off-axis toward [011], and the etch pit density in GaAs grown on a 5-layer SixGe1−x MLS on vicinal Si (lOO) was measured to be 106 cm−2.
Second Countable and Separable Function Spaces

(1978). Second Countable and Separable Function Spaces. The American Mathematical Monthly: Vol. 85, No. 6, pp. 487-489.
Studies in the Resistance of Strawberries to Mites. IV. Effect of Season on Preference or Nonpreference of Strawberries to Tetranychus urticae

Leaf disks from field grown strawberry cultivars ‘Dixieland,’ ‘Surecrop,’ and ‘Citation’ and clones of Ky 22-61-9 and Ky 17-61-15 were utilized in laboratory studies to observe the influence of season on the acceptability of foliage to Tetranychus urticae Koch. Preference and non preference responses were measured by number of female mites active and trapped in a sticky barrier ringing the leaf disk. Fecundity also was measured to observe possible manifestation of antibiosis. Foliage was generally attractive to the mites in spring and early summer but not during July and August. Foliage was again attractive to the mites in September but reverted to a relatively unattractive condition in October and November. Cultivars Dixieland, Surecrop, and Citation were significantly preferred over Kentucky clones 22-61-9 and 17-61-15. The basis for resistance of these selections to mites apparently precluded antibiosis as a factor. A lack of tolerance was apparent in Citation; this cultivar appeared to be suffering from a deficiency of water when injured by mites. Generally, resistance was manifested as a behavioral response of the mites to some component of the leaf disk that either attracted or repelled them; the variables were strawberry selection and seasonal influcnce on the plant.
Belief about the Self: A Defense of the Property Theory of Content

Introduction 1. Mental Content and the Problem of De Se Belief 2. In Favor of the Property Theory 3. Alternatives to the Property Theory 4. Arguments against the Property Theory 5. The Property Theory and De Re Belief 6. The Property Theory, Rationality, and Kripke's Puzzle about Belief THE PROPERTY THEORY, TWIN EARTH, AND BELIEF ABOUT KINDS References Index
Structure–Activity Studies of Bis‐O‐Arylglycolamides: Inhibitors of the Integrated Stress Response

The integrated stress response comprises multiple signaling pathways for detecting and responding to cellular stress that converge at a single event-the phosphorylation of Ser51 on the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α-P) results in attenuation of global protein synthesis via the inhibitory effects of eIF2α-P on eIF2B, the guanine exchange factor (GEF) for eIF2. Herein we describe structure-activity relationship (SAR) studies of bis-O-arylglycolamides, first-in-class integrated stress response inhibitors (ISRIB). ISRIB analogues make cells insensitive to the effects of eIF2α-P by activating the GEF activity of eIF2B and allowing global protein synthesis to proceed with residual unphosphorylated eIF2α. The SAR studies described herein support the proposed pharmacology of ISRIB analogues as binding across a symmetrical protein-protein interface formed between protein subunits of the dimeric eIF2B heteropentamer.
Study on the Changes of Pulmonary Function Conducted Pre-and PostTherapeutically in Infants with Respiratory Syncytial Virus Pneumonia and Clinical Significance

Objective To discuss the changes of pulmonary function studied pre-and post-therapeutically in infants with respiratory syncytial virus pneumonia.Methods Associated measurements was taken to detect the pathogens of infants with acute pneumonia.Bacteria and virus were tested using sputum culture and direct immunofluoresence respectively.TBFVLs and relative parameters were obtained by tidal breathing analysis.Twenty-four infants admitted with RSV pneumonia,were enrolled.Results After treatment,the expiratory declined limbs became smooth and circular,and t-PTEF,tPTEF/t-E and 25/PF significantly increased while PTEF,PTEF/t-PTEF,RR as well as PTEF/Ve significantly decreased as compared with those of pre-treatmeant.But there was significant difference in t-PTEF、t-PTEF/t-E、25/PF、PTEF/t-PTEF、PTEF/Ve compared with the controls which indicated abnormality of the small airway function post-therapeutically still existed.ME/MI which related to the obstruction site and damage degree of big airways showed no significant difference.Conclusion To some degree,there exist abnormality of pulmonary function post-therapeutically in infants with RSV pneumonia.The tidal breathing analysis can provide criteria of evaluation for the severity,curative effect and prognosis.
Trends in incidences of hepatitis virus infections in Hubei province 2005-2010

Objective To characterize the epidemiological features of the viral hepatitis in Hubei and to provide scientific evidence for viral hepatitis control. Method Viral hepatitis infection cases between Jan. 2005 to Dec. 2010 from Center for Disease Control of Hubei Province were collected. Results The incidence rate of viral hepatitis was increased from 120.31/100 000 in 2005 to 145.71/100 000 in 2010,and more than 85% hepatitis cases were reported as hepatitis B. There was a decreasing tread in hepatitis A since 2005,while hepatitis B, hepatitis C and hepatitis E were all increased. The average annual change in incidence rate for hepatitis A,B,C and E was 13%,4.23%,28.78% and 11.28%, respectively. The percentage of patients under 15 years old was declined through these years. Conclusions Prevention of hepatitis B is the focus of the viral hepatitis prevention.Vaccination plays an important role in the control of viral hepatitis.A close watch on hepatitis A prevalence is still required.Hepatitis C and hepatitis E infection should be seriously taken into consideration.
Exercise training in patients with heart failure and preserved ejection fraction: findings awaiting discovery.

Since the seminal work by Coats et al. [(1)][1] that investigated the effects of exercise training in patients with heart failure with reduced ejection fraction (HFREF), a large body of clinical research has been reported that includes dozens of single-site randomized trials, numerous meta-analyses
Superdense Coding over Optical Fiber Links with Complete Bell-State Measurements.

Researchers have demonstrated the fiber transmission of quantum information in which each quantum bit carries nearly two bits of classical information.
Anxiety Management in Primary Care: Implementing the National Institute of Clinical Excellence Guidelines.

ABSTRACT More than 40 million Americans suffer from anxiety disorders, ranking them as one of the most common mental health disorders in America. The purpose of this pilot study was to educate providers on the National Institute Clinical Excellence (NICE) anxiety guidelines and monitor providers' perceived competence in managing anxiety. Results showed perceived competence increased significantly pre-intervention to immediately post-intervention (p = 0.001), and data revealed the scores did not change significantly immediately post-to six-weeks post (p = 0.170). Providers who implemented the guidelines into practice had significantly higher scores (p = 0.026) than those who did not implement the guidelines.
A Mixed-Methods Pilot Study of Student Athlete Engagement in LGBTQ Ally Actions

Reports of sexual prejudice and heterosexism in sports are still pervasive, despite growing acceptance of lesbian, gay, bisexual, transgender, and queer (LGBTQ) persons in the U.S. Yet, few studies have investigated how and why college studentathletes engage in LGBTQ-focused ally actions (e.g., standing up and speaking out against sexual prejudice; showing support at LGBTQ events). This mixed-methods pilot study describes the development and psychometric testing of the Engagement in LGBTQ Ally Actions in Sports Scale, in addition to analyses of two open-ended questions that provided supplementary insight into what it means to collegiate athletes to be an ally to the LGBTQ community. The convenience sample included 159 college student-athletes from two public universities (M age = 20.67 years, SD = 1.56). Findings indicated that the Engagement in LGBTQ Ally Actions in Sports Scale demonstrated strong internal consistency, validity, and equivalence across gender. Qualitative analyses suggested that college ...
Massachusetts Substance Use Disorder Treatment Organizations’ Perspectives on the Affordable Care Act: Changes in Payment, Services, and System Design

The Affordable Care Act (ACA) expanded insurance benefits and coverage for substance use disorder (SUD) treatment and encouraged delivery and payment reforms. Massachusetts passed a similar reform in 2006. This study aims to assess Massachusetts SUD treatment organizations' responses to the ACA. Organizational interviews addressing challenges of and responses to the ACA were conducted in person June-December 2014 with 31 leaders at 12 treatment organizations across Massachusetts. Many organizations were affiliated with medical or social services and offered a range of SUD services. Sampling was based on services offered (detoxification only, detoxification and outpatient, outpatient only). Framework analysis was used. Challenges identified were considered similar to ongoing challenges, not unique to the ACA. Organizations experienced insurance expansions in 2006 and faced new challenges, including insurance coverage, payment arrangements, expansion of services, and system design. System design efforts included care coordination/integration, workforce development, and health information technology. Differences in responses related to connections with medical and social service organizations. Many organizations engaged in efforts to respond to changing policies by expanding capacity and services. Offering a range of SUD treatment (e.g., detoxification and outpatient) and affiliating with a medical organization could enable organizations to respond to new insurance, delivery, and payment reforms.
Conclusion: The Wealth of Virtual Nations

Crowley concludes with an affirmation of the limitations of his proposed program and outlines paths for future inquiry in subsequent considerations of wealth and capital in videogame narratives. Special attention is paid to potential applications of Genette’s major theories to the videogame form as well as individual videogames. This work anticipates extended considerations of Frye’s general literary theories and their bearing on videogames, generally—as well as specific considerations of the ways in which particular economic aspirations and anxieties can be associated with videogames from select periods and nations.
Constructing large scale surrogate models from big data and artificial intelligence

Abstract EnergyPlus is the U.S. Department of Energy’s flagship whole-building energy simulation engine and provides extensive simulation capabilities. However, the computational cost of these capabilities has resulted in annual building simulations that typically requires 2–3 min of wall-clock time to complete. While EnergyPlus’s overall speed is improving (EnergyPlus 7.0 is 25–40% faster than EnergyPlus 6.0), the overall computational burden still remains and is the top user complaint. In other engineering domains, researchers substitute surrogate or approximate models for the computationally expensive simulations to improve simulation and reduce calibration time. Previous work has successfully demonstrated small-scale EnergyPlus surrogate models that use 10–16 input variables to estimate a single output variable. This work leverages feed forward neural networks and Lasso regression to construct robust large-scale EnergyPlus surrogate models based on 3 benchmark datasets that have 7–156 inputs. These models were able to predict 15-min values for most of the 80–90 simulation outputs deemed most important by domain experts within 5% (whole building energy within 0.07%) and calculate those results within 3 s, greatly reducing the required simulation runtime for relatively close results. The techniques shown here allow any software to be approximated by machine learning in a way that allows one to quantify the trade-off of accuracy for execution time.
Wake mode sidebands and instability in mode-locked lasers with slow saturable absorbers

Passively mode-locked lasers with semiconductor saturable absorption mirrors are attractive comb sources due to their simplicity, excellent self-starting properties, and their environmental robustness. These lasers, however, can have an increased noise level and wake mode instabilities. Here, we investigate the wake mode dynamics in detail using a combination of evolutionary and dynamical methods. We describe the mode-locked pulse generation from noise when a stable pulse exists and the evolution of the wake mode instability when no stable pulse exists. We then calculate the dynamical spectrum of the mode-locked pulse, and we show that it has six discrete eigenmodes, two of which correspond to wake modes. The wake modes are unstable when the wake mode eigenvalues have a positive real part. We also show that even when the laser is stable, the wake modes lead to experimentally observed sidebands.
Idiopathic Supraglottic Stenosis Refractory to Multiple Interventions Improved With Serial Office-based Steroid Injections

Summary Purpose The objective of this study was to describe a patient with idiopathic supraglottic stenosis who experienced persistent disease despite multiple office-based and operative interventions, whose disease is now better controlled with scheduled serial office-based steroid injections. Methods This is a case report and literature review. Results A 42-year-old female was referred for worsening supraglottic stenosis despite systemic steroids. She underwent awake tracheotomy. A thorough historical, histologic, and laboratory workup did not reveal an etiology to her stenosis. She later underwent endoscopic partial laryngectomy and was able to be decannulated. She underwent a second endoscopic partial laryngectomy two years later for worsening disease and then was managed over the next seven years with intermittent systemic steroids. Over the last year, she has undergone eight office-based steroid injections with improvement in her degree of stenosis and symptom burden. Conclusions There are only four prior reported cases of idiopathic supraglottic stenosis, none of which has been managed with serial office-based steroid injections. This case report adds to the small body of literature on the management of this rare disease and proposes a new office-based treatment pathway that may help induce regression of stenosis.
Coordinating Effective Field Experiences: Recommendations for Cooperating Teachers

The role of the cooperating teacher is an integral component of field-based teacher education because the cooperating teacher can bridge the gap between the knowledge developed on campus during physical education teacher education and preservice teachers' field-based learning experiences leading up to and including student teaching. In order to understand the function of the cooperating teacher, it is necessary to evaluate the relationship between cooperating teachers, preservice teachers, and physical education teacher education faculty members. Through the lens of occupational socialization theory, the purpose of this article is to explore best practices for coordinating field experiences with a focus on the role of the cooperating teacher. A conceptual model for understanding how coordinated efforts promote successful socialization is provided, and practices for effective supervision are discussed. The importance of congruence between the cooperating teacher and teacher education faculty members is str...
The Performance of Blackness and Femininity in Postfeminist Times: Visualising Serena Williams Within the Context of Corporate Globalisation

Serena Williams has been the most dominant player in the history of women’s tennis. As the Women’s Tennis Association (WTA) rapidly expands across the global marketplace, it is faced with contradictions of the deep-seated racial issues stemming from the origins of tennis and forms of the exotic Other which have heightened value in the global marketplace. The WTA’s “Strong is Beautiful” advertising campaign and the WTA’s lack of reprimanding Caroline Wozniacki when she impersonated Williams’ physical appearance during an exhibition tennis match highlight these contradictions. These contradictions are thrust upon Williams herself as she is expected to operate in both arenas: the space of corporate advertising where she is the exotic Other and in the space where she bears the brunt of the racist mocking of her body.
Biochemical and Molecular Aspects of Retinoid Action in Limb Pattern Formation

Retinoids are a class of naturally occurring compounds consisting of a hydrocarbon ring linked to an unsaturated hydrocarbon side chain with a polar terminal group. Retinoids have dramatic effects on differentiation and development. For example, retinoic acid (RA) alters positional identity in developing and regenerating systems: in the chick limb bud the anteroposterior axis is affected by locally applied RA (Tickle et al. 1982, 1985; Summerbell, 1983) and systemic and/or exogenous treatment with RA changes the rostrocaudal axis of Xenopus (Durston et al., 1989; Sive et al., 1990) and the proximodistal axis of the regenerating urodele limb (Maden, 1982; Thorns and Stocum, 1984).
Review of Spectacular Modernity: Dictatorship, Space, and Visuality in Venezuela, 1948-1958, by Lisa Blackmore

Spectacular Modernity: Dictatorship, Space, and Visuality in Venezuela, 1948-1958, by Lisa Blackmore. University of Pittsburgh Press, 2017
Discovery Process for Antibody-Based Therapeutics

Antibody-based therapeutics have entered the center stage of drug discovery as a result of a major shift in focus of many pharmaceutical companies from small molecules to a broader portfolio containing both protein and chemical therapeutic agents. The field is benefiting from both an increased understanding of the mechanistic basis of antibody-derived therapeutics and the development of sophisticated technologies to derive safe and targeted biotherapeutics. This chapter provides a general overview of the discovery process relevant for generation of antibody-based therapeutics. The discussion elaborates on target selection and validation, screening preparation, lead identification and optimization, as well as clinical candidate selection. In addition, an overview of immunogenicity, a unique challenge for protein-based therapeutics, is provided. A case study is also included to illustrate the discovery process for bapineuzumab, a humanized anti-amyloid beta (Aβ) monoclonal antibody, currently in Phase III clinical trials for the treatment of Alzheimer’s disease.
Autonomic Changes during the Acute Phase of Acute Myocardial Infarction and Ischemia

Most deaths from acute myocardial infarction occur within one hour of the onset of symptoms (1–3). There is now substantial evidence that the autonomic nervous system plays a major role in the high mortality during the acute phase of myocardial infarction (4–6). For example, sympathetic neural activation can precipitate sudden death in the early stage of myocardial infarction by decreasing the threshold for ventricular fibrillation (7,8). In addition to ventricular arrhythmias, profound changes in peripheral vascular resistance and ventricular performance can be triggered by autonomic influences during coronary occlusion (9).
Active Motion Control of High-Speed Hydrofoil Vessels by State-Space Methods

Hydrofoil ships cruising at high speeds often operate in rough weather conditions and hence experience uncomfortable or even unsafe motions without the use of some form of motion control. The research described here concerns an active motion control mechanism for high-speed hydrofoil vessels, aiming at the significant reduction of the vessel motions in regular and random waves. The seakeeping equations of motion are cast into a linear state-space form leading to a linear-quadratic optimal controller shown to attenuate the vessel motion responses significantly. The deterministic control laws designed in the present study are found to perform satisfactorily both in monochromatic and random waves for high-speed vessels supported by hydrofoils and buoyancy.
High Resolution Carbon-13 NMR Studies of Bulk Polymers

High resolution nuclear magnetic resonance (HR-NMR) spectroscopy is the apellative given to the measurement of NMR spectra under conditions that enable magnetically nonequivalent nuclei of the same spin species (e.g., protons or carbon-13) to be resolved as individual resonance lines. Such operating conditions are readily obtained for polymer melts and polymer solutions, and during the past 10–15 years, HR-NMR has evolved as a major analytical technique for the elucidation of structural features and motional characteristics of macromolecules in the liquid state. A list of the main parameters that are measured in NMR experiments is given in Table 1. The parameters have been classified as primary sources of either structural or dynamical data. Also listed are some of the specific types of information on polymeric systems that can be derived from these parameters.
Pathological correlates of brain arterial calcifications.

Abstract Background In clinical practice, calcifications seen on computed tomographic studies within the large brain arteries are often referred to as a surrogate marker for cholesterol-mediated atherosclerosis. However, limited data exist to support the association between calcification and atherosclerosis. In this study, we examined if intracranial arterial calcifications were associated with cholesterol-mediated intracranial large artery atherosclerosis (ILAA) within the arteries of the circle of Willis in an autopsy-based sample. Methods We carried out a cross-sectional analysis of histopathological characteristics of brain large arteries obtained from autopsy cases. Brain large arteries were examined for evidences of calcifications, which were rated as macroscopic (coalescent) and microscopic (scattered). In addition to calcification, we also obtained measurement of the arterial wall and the presence of ILAA and nonatherosclerotic arterial fibrosis. We built hierarchical models adjusted for demographic and vascular risk factors to assess the relationship between calcification and ILAA. Results In univariate analysis, the presence of any arterial calcifications was associated with cerebral infarcts (29% vs. 14%, P Conclusions This study demonstrates that coalescent calcifications in brain large arteries, although associated with morbidity, are not synonymous with cholesterol-driven ILAA. Understanding the precise pathological components of cerebrovascular disease, including nonatherosclerotic arterial calcifications, will help develop individualized therapies beyond amelioration of traditional risk factors such as hyperlipidemia.
Perioperative Management of Buprenorphine: Solving the Conundrum

Objective There is no consensus on the optimal perioperative management of patients on buprenorphine (BUP) for opioid use disorder (OUD). This article will review the available literature on BUP and the analgesic efficacy of BUP combined with full mu-opioid agonists and discuss the conflicting management strategies in the context of acute pain and our institution's protocol for the periprocedural management of BUP. Methods We searched published data on BUP periprocedural management from inception through March 2018 without language restrictions. Study selection included publications reporting outcomes on perioperative pain management in OUD patients maintained on BUP. Results Our search resulted in four case reports supporting periprocedural discontinuation of BUP and two case series, one secondary observational study, one prospective matched cohort study, and four retrospective cohort studies supporting periprocedural continuation of BUP. No clinical trials were identified. Conclusions Maintaining BUP perioperatively does not lead to worsened clinical outcomes. Patients can receive adequate pain control from mu-opioid agonists while maintained on BUP. Based upon available evidence, we recommend continuing BUP at a reduced dose when indicated to avoid withdrawal symptoms and to facilitate the analgesic efficacy of mu-opioid agonists administered in combination for acute postoperative pain.
Multiple exciton generation in quantum dots versus singlet fission in molecular chromophores for solar photon conversion

Both multiple exciton generation (MEG) in semiconductor nanocrystals and singlet fission (SF) in molecular chromophores have the potential to greatly increase the power conversion efficiency of solar cells for the production of solar electricity (photovoltaics) and solar fuels (artificial photosynthesis) when used in solar photoconverters. MEG creates two or more excitons per absorbed photon, and SF produces two triplet states from a single singlet state. In both cases, multiple charge carriers from a single absorbed photon can be extracted from the cell and used to create higher power conversion efficiencies for a photovoltaic cell or a cell that produces solar fuels, like hydrogen from water splitting or reduced carbon fuels from carbon dioxide and water (analogous to biological photosynthesis). The similarities and differences in the mechanisms and photoconversion cell architectures between MEG and SF are discussed.
Sampling Site Has a Critical Impact on Physiologically Based Pharmacokinetic Modeling.

It has been shown that arterial (central) and venous (peripheral) plasma drug concentrations can be very different. While pharmacokinetic studies typically measure drug concentrations from the peripheral vein such as the arm vein, physiologically based pharmacokinetic (PBPK) models generally output simulated concentrations from the central venous compartment that physiologically represents the right atrium, a merge of the superior and inferior vena cava. In this study, a physiologically based peripheral forearm sampling site model was developed and verified using nicotine, ketamine, lidocaine, and fentanyl as model drugs. This verified model allows output of simulated peripheral venous concentrations that can be meaningfully compared with observed pharmacokinetic data from the arm vein. The generalized effect of PBPK model sampling site on simulation output was investigated. Drugs and metabolites with large volumes of distribution showed considerable concentration discrepancy between the simulated central venous compartment and the peripheral arm vein after intravenous or oral administration, resulting in significant differences in values for Cmax and time taken to reach Cmax (tmax) In addition, the simulated central venous metabolite profile showed an unexpected profile that was not observed in the peripheral arm vein. Using fentanyl as a model compound, we show that using the wrong sampling site in PBPK models can lead to biased model evaluation and subsequent erroneous model parameter optimization. Such an error in model parameters along with the discrepant sampling site could dramatically mislead the pharmacokinetic prediction in unstudied clinical scenarios, affecting the assessment of drug safety and efficacy. Overall, this study shows that PBPK model publications should specify the model sampling sites and match them with those employed in clinical studies. SIGNIFICANCE STATEMENT Our study shows that sampling from the central venous compartment (right atrium) during physiologically based pharmacokinetic model development gives rise to biased model evaluation and erroneous model parameterization when observed data are collected from the peripheral arm vein. This can lead to a clinically significant error in predictions of plasma concentration-time profiles in unstudied scenarios. To address this error, we developed and verified a novel peripheral sampling site model to simulate arm vein drug concentrations that can be applied to different drug dosing scenarios.
Measurements of ultrasound attenuation in human chest wall

Knowledge of the bulk acoustic properties of human chest wall is useful in the development and study of cardiac and lung ultrasound exposimetry. However, few studies have been performed on human tissue, and there is a need for attenuation data relevant to clinical diagnostic ultrasound. In this study, we measured the bulk acoustic attenuation in unembalmed, never-frozen human chest wall samples, using a GE Vivid 7, clinical diagnostic ultrasound machine. B-mode ultrasound with frequencies from 1.6 to 5.0 MHz was transmitted through human chest wall tissue samples and compared to equivalent-source signals transmitted through normal saline. The recorded signals were analyzed to characterize the acoustic attenuation. Preliminary results based on 9 donors show that both chest wall morphology and bulk attenuation properties vary widely between individuals. Chest wall thicknesses ranged from 2 to 6 cm. The mean linear acoustic attenuation coefficients, across all samples, ranged from 1.1 dB/cm MHz at 1.6 MHz to 1.7 dB/cm MHz at 5.0 MHz, with a frequency-averaged standard deviation of 0.4 dB/cm MHz. Across all donors and frequency and power settings, linear acoustic attenuation coefficients ranged from 0.5 to 2.3 dB/cm MHz. Variation in thoracic exposure may result from variations in the chest wall composition and morphology between patients.Knowledge of the bulk acoustic properties of human chest wall is useful in the development and study of cardiac and lung ultrasound exposimetry. However, few studies have been performed on human tissue, and there is a need for attenuation data relevant to clinical diagnostic ultrasound. In this study, we measured the bulk acoustic attenuation in unembalmed, never-frozen human chest wall samples, using a GE Vivid 7, clinical diagnostic ultrasound machine. B-mode ultrasound with frequencies from 1.6 to 5.0 MHz was transmitted through human chest wall tissue samples and compared to equivalent-source signals transmitted through normal saline. The recorded signals were analyzed to characterize the acoustic attenuation. Preliminary results based on 9 donors show that both chest wall morphology and bulk attenuation properties vary widely between individuals. Chest wall thicknesses ranged from 2 to 6 cm. The mean linear acoustic attenuation coefficients, across all samples, ranged from 1.1 dB/cm MHz at 1.6 MHz to...
Increasing Pretransplant Panel Reactive Antibodies Worsens Survival in A Contemporary Heart Transplantation Cohort

Background Allosensitization as measured by presence of panel reactive antibodies (PRA) negatively impacts survival in adult heart transplant (HT) recipients. Questions remain whether these trends remain in more contemporary cohorts. We examined the interaction between long-term survival and pre-transplant PRA level in HT recipients from 2000-2018. Methods We identified adult HT recipients between 2000 and 2018 who had a pretransplant PRA in the Scientific Registry of Transplant Recipients. Study cohort was divided into groups with PRA levels; group with 0%, 1-10%, 11-24% and ≥25% PRA levels. We compared 3- and 5-year survival with the Kaplan-Meier method. We constructed Cox proportional hazards regression models to determine the risk adjusted influence of PRA category and PRA as a continuous value on survival. Results We included 24,655 HT recipients. PRA was 0% in 17,391 (70.5%) recipients, 1-10% in 3,331 (13.5%) recipients, 11-24% in 1,330 (5.4%) recipients, and ≥25% in 2,603 (10.6%) recipients. Patients with a PRA ≥25% were younger, had fewer comorbidities, and were more likely to be on ECMO or LVAD prior to HT. Unadjusted 3- and 5-year estimated survival was lower with increasing PRA category (Figure). After risk-adjustment, 5-year survival was higher for the 0% cohort compared to the 1-10% (HR 1.10, 95% CI 1.02-1.18), 11-24% (HR 1.20, 95%CI 1.08-1.34), and ≥25% (HR 1.16, 95% CI 1.07-1.26). When analyzed continuously, increasing PRA was associated with a lower survival (HR 1.003, 95% CI 1.002-1.005). Sensitivity analysis of those transplanted from 2013-2018 showed similar results. Conclusions In this contemporary cohort of HT recipients, increasing pretransplant PRA was associated with lower survival. Given the appreciable portion of HT recipients with elevated PRA, improvements in recipient selection and HT management may help improve outcomes.
Development and validation of a contouring guideline for the taste bud bearing tongue mucosa.

Abstract Purpose To introduce a contouring guideline for the taste bud bearing tongue mucosa for head and neck cancer patients receiving radiotherapy. Methods and Materials CT simulation images of oropharyngeal cancer patients were used to delineate both the whole tongue (extrinsic/intrinsic tongue muscles, floor of mouth) and the taste bud bearing tongue mucosa (method A: adaptation of the whole tongue structure; method B: axial adaptation of a mid-sagittal contour). Volumetric and dosimetric parameters of the whole tongue and the two methods of mucosal delineation, spatial overlap between methods A and B, and inter-observer variability for method B were calculated. Results The study cohort was comprised of 70 patients with T1–4 N0–1 tonsillar (83%) and base of tongue (17%) cancers. Most of the comparative parameters between the whole tongue and mucosa (method A) significantly differed (mean, minimum, and maximum dose, V5–V70, D40–D90). The mean dose calculated for the whole tongue deviated on average 3.77 Gy compared to method A. No significant differences were found between methods A and B of the taste bud bearing tongue mucosa structure, and none of the dosimetric parameters differed more than 1.03 Gy on average. The mean Dice similarity coefficient for both mucosal structures was 0.79 ± 0.05, and 0.63 ± 0.12 for the inter-observer analysis of method B. Conclusions We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.
Trends in Hospital and Surgeon Charges and Reimbursements for Revision Total Knee Arthroplasty.

Abstract Background The relationship between surgeon and hospital charges and reimbursements for revision total knee arthroplasty (TKA) has not been well examined. The objective of this study is to report trends and variations in hospital charges and payments compared to surgeons for stage 1 (S1) vs stage 2 (S2) septic revision TKA and aseptic revision (AR) TKA. Methods The 5% Medicare sample was used to capture hospital and surgeon data for revision TKA from 2005 to 2014. The charge multiplier (CM) and ratio of hospital to surgeon charges, and the payment multiplier (PM) and ratio of hospital to surgeon payments were calculated. Year-to-year variation and regional trends in-patient demographics, Charlson Comorbidity Index, length of stay (LOS), CM, and PM were evaluated. Results In total, 4570 AR, 1323 S1, and 863 S2 TKA patients were included. CM increased for all cohorts: 8.1-13.8 for AR (P Conclusion Hospital charges and payments relative to the surgeons have significantly increased for revision TKA in the setting of stable or increasing patient complexity and decreasing LOS.
Environmental effects on the strength and impact damage resistance of alumina based oxide/oxide ceramic matrix composites

Abstract In this study the effects of high temperature and moisture on the impact damage resistance and mechanical strength of Nextel 610/alumina silicate ceramic matrix composites were experimentally evaluated. Composite laminates were exposed to either a 1050°C isothermal furnace-based environment for 30 consecutive days at 6 h a day, or 95% relative humidity environment for 13 consecutive days at 67°C. Low velocity impact, tensile and short beam strength tests were performed on both ambient and environmentally conditioned laminates and damage was characterized using a combination of non-destructive and destructive techniques. High temperature and humidity environmental exposure adversely affected the impact resistance of the composite laminates. For all the environments, planar internal damage area was greater than the back side dent area, which in turn was greater than the impactor side dent area. Evidence of environmental embrittlement through a stiffer tensile response was noted for the high temperature exposed laminates while the short beam strength tests showed greater propensity for interlaminar shear failure in the moisture exposed laminates. Destructive evaluations exposed larger, more pronounced delaminations in the environmentally conditioned laminates in comparison to the ambient ones. External damage metrics of the impactor side dent depth and area directly influenced the post-impact tensile strength of the laminates while no such trend between internal damage area and residual strength could be ascertained.