cssi/SciSciGPT-SciSciNet huggingface dataset:
Development of a structured workflow for enhanced well cement integrity: Lessons learned and the way ahead

Abstract Despite the increased emphasis on enhancing short and long-term cement isolation, the oil and gas industry has not agreed upon a collective, scientifically supported blueprint to govern cement integrity standards. This is largely due to the fact that cement integrity and gas migration processes are influenced by an intricate assortment of transient elements, frequently occurring simultaneously. Ambiguity and insufficient information are an inherent component of drilling and production practices, but coordinated efforts and strategies can be instigated to minimize well integrity incidents. To aid in the assessment and mitigation of cement failure probabilities, intricate risk analysis and assessment methodologies have been established in recent years. The original monitoring and evaluation framework developed in 2004 to assess long-term radioactive waste disposal has evolved into a multifaceted evaluation process to assess the safety and enduring integrity of carbon dioxide storage facilities. This methodology has changed little over the past decade, and has failed to incorporate transient events which typically occur during the lifespan of both producing and abandoned oil and gas wells. With this in mind, a unique and systematic procedure is required to assess the array of dynamic factors which have proven to adversely affect the cement integrity of oil and gas wells. A data matrix consisting of a combination of cement, lithological, thermal, and hydraulic information must be employed to extensively evaluate cement integrity (Lavrov et al., 2014). From this input, a consequence analysis will be provided to assess the risks involved from disorganized and faulty cementing practices and techniques. This paper proposes an extensive literature review of currently published attempts to evaluate cementing integrity, and the necessity of a more expansive construct to evaluate long-term primary and secondary cementing environments.
Impact of Postdischarge Follow-Up Care on Medicare Expenditures: Does Rural Make a Difference?:

Reducing postdischarge Medicare expenditures is a key focus for hospitals. Early follow-up care is an important piece of this focus, but it is unclear whether there are rural-urban differences in the impact of follow-up care on Medicare expenditures. To assess this difference, we use the Medicare Current Beneficiary Survey, Cost and Use Files, 2000-2010. We conduct a retrospective analysis of 30-day postdischarge Medicare expenditures using two-stage residual inclusion with a quantile regression, where the receipt of 7-day follow-up care was the main independent variable. Postdischarge follow-up care increased the 25th percentile of 30-day expenditures, decreased the 75th percentile, and there were no rural-urban differences. Partial effects show postdischarge follow-up care resulted in higher 30-day expenditures among low-cost rural beneficiaries. Ensuring early follow-up care for high-cost beneficiaries may be advantageous to both rural and urban providers in helping reduce postdischarge Medicare expenditures.
Training Genotype Callers with Neural Networks

We present an open source software toolkit for training deep learning models to call genotypes in high-throughput sequencing data. The software supports SAM, BAM, CRAM and Goby alignments and the training of models for a variety of experimental assays and analysis protocols. We evaluate this software in the Illumina platinum whole genome datasets and find that a deep learning model trained on 80% of the genome achieves a 0.986% accuracy on variants (genotype concordance) when trained with 10% of the data from a genome. The software is distributed at https://github.com/CampagneLaboratory/variationanalysis. The software makes it possible to train genotype calling models on consumer hardware with CPUs or GPU(s). It will enable individual investigators and small laboratories to train and evaluate their own models and to make open source contributions. We welcome contributions to extend this early prototype or evaluate its performance on other gold standard datasets.
Potentially preventable hospitalizations in dementia: family caregiver experiences

Background Health crises in persons living with dementia challenge their caregivers to make pivotal decisions, often under pressure, and to act in new ways on behalf of their care recipient. Disruption of everyday routines and heightened stress are familiar consequences of these events. Hospitalization for acute illness or injury is a familiar health crisis in dementia. The focus of this study is to describe the lived experience of dementia family caregivers whose care recipients had a recent unplanned admission, and to identify potential opportunities for developing preventive interventions. Methods Family caregivers (n = 20) of people with dementia who experienced a recent hospitalization due to an ambulatory care sensitive condition or fall-related injury completed phone interviews. Interviews used semi-structured protocols to elicit caregivers' reactions to the hospitalization and recollections of the events leading up to it. Results Analysis of interview data identified four major themes: (1) caregiver is uncertain how to interpret and act on the change; (2) caregiver is unable to provide necessary care; (3) caregiver experiences a personal crisis in response to the patient's health event; (4) mitigating factors may prevent caregiver crises. Conclusions This study identifies a need for clinicians and family caregivers to work together to avoid health crises of both caregivers and people with dementia and to enable caregivers to manage the health of their care recipients without sacrificing their own health and wellness.
REGIONALIDADE E LITERATURA: O AUTOR SUL-RIO-GRANDENSE NA ESCOLA DE ENSINO MÉDIO

O artigo e parte integrante da dissertacao de Mestrado que analisa a presenca ou nao dos escritores do Rio Grande do Sul no ensino de literatura de duas escolas da cidade de Gramado e de duas da cidade de Canela. Pensou-se o estudo da literatura e a sua relacao com a educacao considerando-se que as duas areas estao inseridas no contexto social. Propoe-se, assim, a reflexao sobre a insercao do homem no meio em que vive sob o ponto de vista da concepcao teorica sociointeracionista, que defende um modo inovador de entender a educacao. De acordo com essa teoria, a aprendizagem e um processo continuo e progressivo, que depende das relacoes entre os individuos e a sociedade. Acredita-se que a literatura sul-riograndense dispoe de instrumentos capazes de possibilitar o crescimento intelectual do aluno nos aspectos que dependem do dominio dos meios sociais de pensamento, sempre que conhecimento adquirido tenha como ponto de partida instrumentos linguisticos e experiencias socioculturais proximas de sua realidade. Palavras-chave: Literatura. Leitura. Regionalidade. Sociedade. Ensino-aprendizagem.
Tracking and quantification of gaseous chemical plumes from anthropogenic emission sources within the Los Angeles Basin

Abstract This paper describes the sensor technology, measurement methodology and data analysis algorithms that are used to characterize gaseous emissions observed with a large-area coverage longwave-infrared (LWIR) hyperspectral imaging (HSI) sensor. In so doing the demonstrated capability is expanded well beyond the small number of gas species that have typically been reported and also sets these observations within a definitive, comprehensive framework that documents in detail the procedures used for detection, identification, and quantification of atmospheric trace gases using LWIR HSI systems, along with the methodology for determining their respective detection limits. Examples are provided for a 530 km 2 region of the Los Angeles Basin collected on July 22, 2014.
Microwave wireless coordination technologies for coherent distributed maritime radar

Developments in communications and networking have enabled separate microwave wireless systems to coordinate at increasingly detailed levels, creating a path towards distributed wireless systems. Coherent distributed arrays, where the individual wireless systems synchronize at the level of the RF carrier phase, achieve transmit power gains on the order of the number of platforms squared, and receive gains proportional to the number of platforms. For radar applications, an array with N elements yields an overall system gain of N3 in the far field of the array, providing a significant improvement in radar sensitivity. This paper analyzes improved detection capabilities for surface maritime radars operating coherently, and discusses technologies for achieving coherent gain. Recently developed microwave wireless technologies for inter-node coordination in coherent distributed arrays are presented, and future challenges for coherent arrays of maritime radars are discussed.
Non-intrusive acoustic measurement of flow velocity and temperature in a high subsonic Mach number jet

In previous studies, sonic anemometry and thermometry have generally been used to measure low subsonic Mach flow conditions. Recently, a novel configuration was proposed and used to measure unheated jet velocities up to Mach 0.83 non-intrusively. The objective of this investigation is to test the novel configuration in higher temperature conditions and explore the effects of fluid temperature on mean velocity and temperature measurement accuracy. The current work presents non-intrusive acoustic measurements of single-stream jet conditions up to Mach 0.7 and total temperatures from 299 K to 700 K. Comparison of acoustically measured velocity and static temperature with probe data indicate root mean square (RMS) velocity errors of 2.6 m s−1 (1.1% of the maximum jet centerline velocity), 4.0 m s−1 (1.2%), and 8.5 m s−1 (2.4%), respectively, for 299, 589, and 700 K total temperature flows up to Mach 0.7. RMS static temperature errors of 7.5 K (2.5% of total temperature), 8.1 K (1.3%), and 23.3 K (3.3%) were observed for the same respective total temperature conditions. To the authors' knowledge, this is the first time a non-intrusive acoustic technique has been used to simultaneously measure mean fluid velocity and static temperatures in high subsonic Mach numbers up to 0.7. Overall, the findings of this work support the use of acoustics for non-intrusive flow monitoring. The ability to measure mean flow conditions at high subsonic Mach numbers and temperatures makes this technique a viable candidate for gas turbine applications, in particular.
«Tiempos hay de acometer y tiempos de retirar»: literatura áurea y edición digital

Any state of the art on textual criticism entails a deep reflection on the digital medium. Many national traditions have already faced the transformation of the editorial model: a model that implies, above all, a different method of execution and a new presentation of the materials. We are currently at a crucial moment in which – calling to mind Sancho’s words before the imminent participation of Don Quixote in a joust – we must decide whether or not to undertake the “new” practices within the field of digital editing. In studies of Renaissance and Spanish Golden Age literature, several projects of a high philological level and digital value have been carried out. This article intends to review some of the most emblematic and committed projects to digital humanities, and to evaluate to what extent they fit with the good practices of digital scholarly edition.
Modulation of Ara-C Metabolism by Fludarabine: Therapy for Acute Myelogenous Leukemia

Despite significant progress in the treatment of acute myelogenous leukemia (AML), about 70% of patients who achieve complete remission with induction therapy relapse [1,2]. The prognosis of patients with AML who relapse is ominous. The remission rates are less than 30% in first salvage and less than 10% in subsequent salvages [3]. The incidence of long-term survivors in AML is less than 5% after relapse [3,4]. This stresses the need for new active agents and combination therapies to improve the response. The most effective therapy for AML includes arabinosylcytosine (ara-C), which must be anabolized to its active 5′-triphosphate (araCTP). A strong relationship has been demonstrated between clinical response and the pharmacokinetics and pharmacodynamics of ara-CTP in leukemia cells of patients receiving high-dose ara-C therapy for acute leukemia in relapse [5,6]. Similar trends were observed for patients with chronic myelogenous leukemia in blast crisis (CML-BC) after treatment with high-dose ara-C [7]. In patients with relapsed acute leukemia treated with high-dose ara-C, the half-life of ara-CTP elimination from cells, the trough concentration, and the total intracellular exposure to ara-CTP (the area under the accumulation and retention curve, AUC) were each correlated with the likelihood of achieving complete remission [5,6,8].
Psycholinguistic Approaches to Language and Communication in Autism

During the past decade, there has been a concerted effort to begin applying some of the basic concepts of developmental psycholinguistics to our understanding of the primary language and communication problems of autistic children. Most of these efforts have addressed two fundamental issues. First, In what ways are autistic children who acquire some functional language similar to, or different from, normal children acquiring language? And second, How can we apply psycholinguistic principles to the treatment of mute or minimally verbal autistic children? In this chapter, I will briefly review the research directed at both these issues and will then present an alternative approach to these issues demonstrating how I believe developmental psycholinguistics can make its greatest impact in furthering our understanding of the autistic child’s language and communication deficits.
Discussion of Policy Responses

Our panelists represent the views of their institutional employers. In order of presentation, we have heard the policy responses to global financial crises of the International Monetary Fund (IMF), the World Bank, the U.S. Treasury, and the Bank for International Settlements (BIS). Let me note the burden of the remarks of each of the speakers.
Promising Theoretical and Methodological Approaches and Future Directions in Health Promotion and Disease Prevention Research and Practice

The chapters in this volume outline many promising developments in theory as well as design, evaluation, and implementation methods being applied in the field of health promotion and disease prevention to address different risk behaviors and diseases in varying settings and with different populations. Despite such a heterogeneity of disciplines involved in what is currently most often such a multidisciplinary area of research that convergence of the science of health promotion and disease prevention may be hindered, advances are being made. These advances are most readily made with true interdisciplinary approaches that involve not just individuals who are contributing to a particular project or addressing a particular research question from diverse disciplines, but from active involvement of all disciplines in the research questions and efforts to integrate the disciplines into a science of health promotion and disease prevention.
Theoretical & Pragmatic Implications of a Relational Global Ethical Framework

Developing a broad ethical lens for engaging the complex ethical issues elicited by public health disasters implies that it will be applied, in part or wholly, to real life scenarios. As such, it is pertinent to systematically examine some of the possible implications and attendant social change sequelae of the proposed relational global ethical framework vis-a-vis PHDs. This chapter first presents a summary of all that has been discussed and elaborated from Chaps. 1 through 6. It then teases out the public health policy implications of the relational-based GEF. It also examines the UNESCO Declaration on Bioethics and Human Rights in relation to engaging public health disasters compared to the relational-based GEF proposed in this book.
A System of Systems Engineering Framework for Modern Power System Operation

In the literature, numerous definitions have been proposed for system of systems (SoS). The concept of system of systems has been widely used in defense applications. In addition, it has been applied to other domains, e.g., healthcare, robotics, global communication systems, transportation, space exploration, and power system operation.
IL-6 Impairs Vaccine Responses in Neonatal Mice

The inability of infants to mount proper follicular helper T (TFH) cell response renders this age group susceptible to infectious diseases. Initial instruction of T cells by antigen presenting cells and subsequent differentiation into TFH cells are controlled by T cell receptor signal strength, co-stimulatory molecules and cytokines such as IL-6 and IL-21. In immunized adults, IL-6 promotes TFH development by increasing the expression of CXCR5 and the TFH master transcription factor, B cell lymphoma 6. Underscoring the importance of IL-6 in TFH generation, we found improved antibody responses accompanied by increased TFH cells and decreased follicular regulatory helper T (TFR) cells, a Foxp3 expressing inhibitory CD4+ T cell occupying the germinal center (GC), when a tetanus toxoid conjugated pneumococcal polysaccharide type 14 vaccine was injected in adult mice together with IL-6. Paradoxically, in neonates IL-6 containing PPS14-TT vaccine suppressed the already impaired TFH development and antibody responses in addition to increasing TFR cell population. Supporting the diminished TFH development, we detected lower frequency of phospho-STAT-3+ TFH in immunized neonatal T cells after IL-6 stimulation than adult cells. Moreover, IL-6 induced more phospho-STAT-3+ TFR in neonatal cells than adult cells. We also measured lower expression of IL-6R on TFH cells and higher expression on TFR cells in neonatal cells than adult cells, a possible explanation for the difference in IL-6 induced signaling in different age groups. Supporting the flow cytometry findings, microscopic examination revealed the localization of Treg cells in the splenic interfollicular niches of immunized adult mice compared to splenic follicles in neonatal mice. In addition to the limitations in the formation of IL-21 producing TFH cells, neonatal mice GC B cells also expressed lower levels of IL-21R in comparison to the adult mice cells. These findings point to diminished IL-6 activity on neonatal TFH cells as an underlying mechanism of the increased TFR: TFH ratio in immunized neonatal mice.
Cyber Policy and Strategy Management

Strategy management is defined as a procedure to determine the relationship between the organization and its environment through the use of selected objectives and resources allocation, which allow the development of efficient and effective action programs (Schendel and Hatten 1972).
Prevention of Recurrent Bleeding: Selective Shunt Operations

In 1893, Pavlov [1] described the adverse consequences of complete portal diversion. His astute observations of dogs with patent portacaval shunts resulted in the description of the syndrome of “meat intoxication” or portasystemic encephalopathy. Pavlov also noted that sacrificed animals with patent shunts had atrophic livers, whereas dogs with occluded shunts had hepatopetal portal collaterals and normal livers. He concluded from these experiments that hepatic portal perfusion was essential for maintenance of normal hepatic physiology and structure. He also theorized that portal blood contained cerebral toxins absorbed from the intestines which resulted in the psychoneurological disturbances observed in the animals with complete diversion of portal flow.
P149 Teachers' Attitudes About Breakfast After the Bell (BATB)

Background Breakfast After the Bell (BATB) is the increasingly common approach of serving breakfast after the first school bell rings. Teachers, key stakeholders in any BATB program, can be critical to its success. Objective This study describes attitudes of teachers toward an ongoing BATB program, and examines the relationship between pre- and post-implementation approval. Study Design, Settings, Participants All K-8 teachers in an urban, low-income district were invited to complete an online survey (69% response rate). Here we report results from only the K-5 teachers (n = 249). Measurable Outcome/Analysis The survey assessed retrospective expectations of the program prior to implementation, perceived benefits and challenges of BATB, and current program satisfaction. Descriptive statistics and Pearson's correlation tests were performed. Results Among those teachers whose students were receiving BATB at the time of the survey, 64% indicated satisfaction with the program as a whole. Additionally, the majority were satisfied specifically with the food delivery system (70.9%), trash disposal and cleanup (67.5%), and the system for tracking breakfast items (67.8%). However, 43.9% of teachers indicated dissatisfaction with the variety of breakfast items served. When asked a final open-ended question about their thoughts on the program, teachers most frequently expressed their support for the program (24.1%) or discussed the healthfulness or appropriateness of breakfast (21.6%), the variety of breakfast options (12.9%), or the mess, rodents, and pests that occur because of eating breakfast in the classroom (10.3%). Additionally, 81% of teachers agreed that the program should continue and is worth the effort. There was a statistically significant, strong positive correlation between pre-program approval and current program satisfaction, r = .61, P Conclusion Overall, teachers are generally supportive of the BATB program, and those who were originally supportive were most likely to continue to support it. Addressing some of the teachers’ concerns about the healthfulness and variety of the foods offered, as well as about mess, could help to further improve perceptions of the program. Funding Rutgers University.
Customer delight and outrage in theme parks: A roller coaster of emotions

The present study explored the key drivers of customer delight and outrage in North American theme parks. Following content analysis of TripAdvisor postings, the authors revealed the most frequentl...
Rearing the Cannibalistic Larvae of Calosoma sycophanta (Coleoptera: Carabidae) in Groups

Cannibalistic immatures of the gypsy moth (Lymantria dispar L. [Lepidoptera: Lymantriidae]) predator Calosoma sycophanta L. (Coleoptera: Carabidae) must usually be reared individually. This paper d...
RNN and CNN for Way-Finding and Obstacle Avoidance for Visually Impaired

Way-finding is crucial for visually impaired as well as sighted persons. Already navigated way is useful for the visually impaired if reused. In this research, we present an assistive technology solution of reusable way-finding with obstacle avoidance for the visually impaired. We trained a recurrent neural network (RNN) model to predict the navigation activities. These activities are used as the building blocks of reusable way. A fine-tuned convolution neural network (CNN) model is used to detect obstacle. Both models are incorporated in a smart phone application to construct, share, and reuse a navigation way. The evaluation shows that using the application the visually impaired were able to navigate 95% times accurately without external help.
Social Determinants of Health: Underreported Heterogeneity in Systematic Reviews of Caregiver Interventions.

Author(s): Young, Heather M; Bell, Janice F; Whitney, Robin L; Ridberg, Ronit A; Reed, Sarah C; Vitaliano, Peter P | Abstract: BACKGROUND AND OBJECTIVES:Although most people have some experience as caregivers, the nature and context of care are highly variable. Caregiving, socioeconomic factors, and health are all interrelated. For these reasons, caregiver interventions must consider these factors. This review examines the degree to which caregiver intervention research has reported and considered social determinants of health. RESEARCH DESIGN AND METHODS:We examined published systematic reviews and meta-analyses of interventions for older adults with age-related chronic conditions using the PRISMA and AMSTAR 2 checklists. From 2,707 papers meeting search criteria, we identified 197 potentially relevant systematic reviews, and selected 33 for the final analysis. RESULTS:We found scant information on the inclusion of social determinants; the papers lacked specificity regarding race/ethnicity, gender, sexual identity, socioeconomic status, and geographic location. The majority of studies focused on dementia, with other conditions common in later life vastly underrepresented. DISCUSSION AND IMPLICATIONS:Significant gaps in evidence persist, particularly for interventions targeting diverse conditions and populations. To advance health equity and improve the effectiveness of interventions, research should address caregiver heterogeneity and improve assessment, support, and instruction for diverse populations. Research must identify aspects of heterogeneity that matter in intervention design, while recognizing opportunities for common elements and strategies.
Long Non-coding RNAs Diversity in Form and Function: From Microbes to Humans

Long non-coding (lnc) RNAs are vital regulators of a plethora of biological processes. They have been shown to play major roles as transcriptional and post-transcriptional regulators, with some being involved in imprinting genomic loci, shaping chromosome conformation and allosteric regulation of protein activities. Highly specific patterns of lncRNA expression coordinate cellular differentiation, pluripotency, and development; while the overexpression, deficiency, or mutation of lncRNA genes have been implicated in numerous disorders. Given the diversity and number of lncRNAs, it seems likely that their functions are as numerous as those of proteins, yet, only a small fraction of these transcripts have been structurally and functionally characterized. Although the vast majority of information regarding lncRNA structure and function is derived based on the studies of human lncRNAs, in recent years, these transcripts have been identified in plants, bacteria, and viruses. This chapter aims to overview the salient features, biogenesis, and biological importance of these molecules in various biological systems. We discuss a few prominent examples of lncRNAs expressed in humans, plants, bacteria, and viruses, highlighting their structural properties, physiological functions, and modes of action. There are still many questions that need to be addressed in this relatively new research area. Addressing them in the future research will enhance our knowledge of RNA plasticity as a biological control mechanism and potentially discover novel targets to control the biological outputs of cellular processes in response to different stimuli.
The History and Culture of Mormon Fundamentalism in the United States

Mormon fundamentalism has challenged the way contemporary family life is typically viewed in America. It involves people who subscribe to a brand of theology associated with The Church of Jesus Christ of Latter-day Saints (hereafter LDS Church or just Church, in appropriate contexts) founded by Joseph Smith in 1830. The most important theological points include polygamy (or plural marriage in LDS parlance), and also patriarchal authority, traditional gender roles, and religious communalism. Most fundamentalists who continue practising polygamy and communal economics (which the modern LDS Church does not) belong to schismatic, break-away movements that are strongly denounced as apostate by the LDS Church. About 75 percent of the approximately 50,000 fundamentalists residing in North America are members of the three largest movements—the Fundamentalist Church of Latter-day Saints (FLDS), the Apostolic United Brethren (AUB), and the Kingston Clan. The remainder come from the Mexican LeBaron group (The Church of the First Born) and a number of unaffiliated polygamists spread throughout the western United States (who are known as “independents.”)
Dante’s theology and contemporary thought: Recovering transcendence?:

This article outlines how Dante’s philosophy and theology turn on issues that are being debated in broader philosophical, theological, and theoretical milieus today. It emphasizes, in particular, h...
Image Reconstruction for MRI using Deep CNN Priors Trained without Groundtruth

We propose a new plug-and-play priors (PnP) based MR image reconstruction method that systematically enforces data consistency while also exploiting deep-learning priors. Our prior is specified through a convolutional neural network (CNN) trained without any artifact-free ground truth to remove under-sampling artifacts from MR images. The results on reconstructing free-breathing MRI data into ten respiratory phases show that the method can form high-quality 4D images from severely undersampled measurements corresponding to acquisitions of about 1 and 2 minutes in length. The results also highlight the competitive performance of the method compared to several popular alternatives, including the TGV regularization and traditional UNet3D.
The utility of routine head CT for hemorrhage surveillance in post-craniotomy patients undergoing anticoagulation for venous thromboembolism.

Abstract Anticoagulation for postoperative venous thromboembolism (VTE) may infer a higher risk of intracranial hemorrhage. We treat patients with VTE using slowly titrating intravenous heparin drip without bolus. When PTT is greater than 60 s, a head CT is obtained to monitor for the development of a intracranial hemorrhage before transition to oral anticoagulation. We evaluated the utility of routine surveillance head CT to monitor for intracranial hemorrhage during anticoagulation. This is a case series of neurosurgical patients in an academic quaternary hospital who developed a VTE after cranial procedures between 2007 and 2017. Over 11,000 patients were screened for the study. Patients’ demographics data, surgical indication, PTT at the time of surveillance CT head, surveillance CT head findings, and patient’s clinical course were reviewed. A total of 83 patients were included. Three patients (3.6%) developed a new subclinical hemorrhage on CT head imaging while on heparin drip. Interval CT head showed stable hemorrhage in all patients. Heparin drip was stopped in two patients and they both progressed from DVT to pulmonary embolism: one patient died due to cardiac arrest, the other patient was transitioned to oral anticoagulation. In the third patient heparin drip was continued uneventfully and transitioned to oral anticoagulation with no further clinical sequalae. Surveillance CT while on heparin drip for VTE management detected subclinical intracranial hemorrhage in a small subset of patients. Patients whose anticoagulation was stopped had progression of VTE. Undertreatment of VTE in the presence of subclinical hemorrhage may lead to significant morbidity and mortality.
A Concept Evaluation Study of a New Combination Bictegravir plus Tenofovir Alafenamide Nanoformulation with Prolonged Sustained-Drug-Release Potency for HIV-1 Preexposure Prophylaxis.

The antiretroviral treatment (ART) approach is the best-prescribed approach to date for preexposure prophylaxis (PrEP) for high-risk individuals. However, the daily combination antiretroviral (cARV) regimen has become cumbersome for healthy individuals, leading to nonadherence. Recent surveys showed high acceptance of parenteral sustained-release ART enhancing PrEP adherence. Our approach is to design a parenteral nanoparticle (NP)-based cARV sustained-release (cARV-SR) system as long-acting HIV PrEP. Here, we report a new combination of two potent ARVs (tenofovir alafenamide fumarate [TAF] and bictegravir [BIC]) loaded as a nanoformulation intended as a cARV-SR for PrEP. The BIC+TAF NPs were fabricated by using a standardized in-house methodology. In vitro intracellular kinetics, cytotoxicity, and HIV-1 protection studies demonstrated that BIC+TAF encapsulation prolonged drug retention, reduced drug-associated cytotoxicity, and enhanced HIV protection. In human peripheral blood mononuclear cells, nanoformulated BIC+TAF demonstrated significant (P < 0.05) improvement in the drug's selectivity index by 472 times compared to the BIC+TAF in solution. In vivo pharmacokinetic study of BIC, TAF, and respective drug metabolites in female BALB/c mice after single subcutaneous doses of BIC+TAF NPs demonstrated plasma drug concentrations of BIC and tenofovir above the intracellular 50% inhibitory concentration during the entire 30-day study period and prolonged persistence of both active drugs in the HIV target organs, including the vagina, colon, spleen, and lymph nodes. This report demonstrates that the encapsulation of BIC+TAF in a nanoformulation improved its therapeutic selectivity and the in vivo pharmacokinetics of free drugs. Based on these preliminary studies, we hypothesize that cARV-SR has potential as an innovative once-monthly delivery treatment for PrEP.
Conclusion: Intersectional Strategies in the Classroom

In summary, the three chapters in Part IV demonstrate that different teaching contexts call for different classroom strategies. Although all three sets of strategies rely on intersectionality as a framework for understanding and respecting the multiple identities of those involved, each set of strategies developed in response to nuanced contexts.
Abstract 15258: The Association of Genetic Polymorphism of rs2106261 in ZFHX3 and ‘Super-responder’ to Catheter Ablation Among the Patients With Long-standing Persistent Atrial Fibrillation

Introduction: The radiofrequency catheter ablation (RFCA) is challenging in patients with long-standing persistent atrial fibrillation (PeAF) and its clinical outcome is highly variable. Genome-wide association studies (GWAS) have identified that the rs2106261 polymorphism in ZFHX3 is associated with non-valuvluar AF. Hypothesis: We tested the association between the “super-responder” to the radiofrequency catheter ablation (RFCA) and the rs2106261 polymorphism among the patients with long-standing persistent AF. Methods: We included consecutive 207 patients with long-standing PeAF (79.2% male, age 58.0±9.7 years and follow-up interval 21 (16-34) months) who underwent RFCA for symptomatic long-standing PeAF. The super-responders were defined as the patients without early or clinical recurrence of AF at least for 12 months of post-procedural follow-up period without taking anti-arrhythmic drug. We looked for the characteristics of super-responders in clinical profiles, ECG in sinus rhythm, 3D-left atrial (LA) CT, or genotypes of the rs2106262. Results: 1. Fifty two patients (25.1%) were categorized as super-responders. Super-responders were younger (55.5±9.6 vs. 58.9±9.6 years old, p=0.028) and had shorter AF duration (44.9 [25.4-73.1] vs. 65.1 [34.1-113.6] month, p=0.010), shorter QTc (435.1±27.8 vs. 447.3±29.1 msec, p=0.007), lower negative P wave amplitude in lead V1 (0.07±0.03 vs. 0.08±0.04, p=0.034), and smaller LA volume index (CT) (75.2±21.0 vs. 88.2±24.1, p=0.001) than recurred patient group. 2. In additive model, the minor allele frequency of the rs2106261 was higher in super-responders (52.2%) than in recurred group (40.9%, p=0.058). 3. In multivariate analyses, LA volume index (adjusted OR=0.973, 95% CI 0.955-0.992, p=0.006) and genetic polymorphism of the rs2106261 (adjusted OR=1.808, 95% CI 1.034-3.163, p=0.038) were independently associated with super-responder to RFCA among the patients with long-standing persistent AF. Conclusion: Although the recurrence rate after catheter ablation for long-standing persistent AF is still high, pre-procedural LA volume index or the rs2106261 polymorphism may be helpful for the selection of good candidate for RFCA.
Modeling spin-dependent transport in InAs/GaSb/AISb resonant tunneling structures

The Rashba effect resonant tunneling diode is a candidate for achieving spin polarizing under zero magnetic field using only conventional non-magnetic III–V semiconductor heterostructures. We point out the challenges involved based on simple arguments, and offer strategies for overcoming these difficulties. We present modeling results that demonstrate the benefits of the InAs/GaSb/AlSb-based asymmetric resonant interband tunneling diode (a-RITD) for spin filtering applications.
“Disparate Impact” and the Establishment Clause

In Marsh v. Chambers (1983), the U.S. Supreme Court upheld the constitutionality of the practice of legislative prayer, yet in the last decade, no other Establishment Clause topic has seen as much litigation. Despite the limitations of the Court’s opinion, the question 25 years later is not so much whether Marsh was correctly decided, but how to interpret Marsh in practice today. Over the last decade, a series of fact-intensive legislative prayer decisions resulting from Establishment Clause challenges to the prayer practices or policies of deliberative bodies have provided little definitive guidance to answer this question and while a host of fresh legal scholarship has attempted to discern the direction courts are headed, both doctrinal and normative questions linger unanswered. For example, who may offer prayer? What denominations (if any) must be represented? May specific deities be mentioned, and if so, at what point is the Establishment Clause implicated? What sort of prayer policy or practice developed and/or implemented by a legislative body passes constitutional muster? Are prayer policies subject to both facial and as-applied challenges? On May 20, 2013, the U.S. Supreme Court granted a petition for a writ of certiorari to the U.S. Court of Appeals for the Second Circuit in Town of Greece v. Galloway, No. 12-696, and by June 2014 is expected to render a decision that will address the substance of the permissible boundaries of legislative prayer for only the second time in the Court’s history. This article provides a tailored capsule summary of the more nuanced issues the U.S. Supreme Court is likely to confront in Town of Greece, - issues that are akin to those the U.S. Court of Appeals for the Fourth Circuit previously confronted in 2011 in Forsyth County, North Carolina v. Joyner - a virtually indistinguishable case. Portions of this article were delivered by the author at Pepperdine University School of Law’s Religious Legal Theory Conference - “The Competing Claims of Law & Religion: Who Should Influence Whom?” in February of 2012.
Optimum Zone Plate Theory and Design

Transmission zone plates composed of materials describable by the complex index of refraction n(n = (1 − δ)+ ik) modulate both the amplitude and phase of the light passing through them. In this monograph, a general variational approach to the design of zon plate profiles which maximize system transfer functions like I(m)/IIN or I(m)/IOUT (where IIN and IOUT are the total input and output powers and I(m) is the diffracted power of the mth order) is presented in terms of the real and imaginary components of n. The variational problem, as formulated here, is shown to generate some important classical zone plate configurations as special solutions and to lead naturally to the derivation of the most general zone plate configurations possible. Some specific optimum solutions are derived for gold in the soft x-ray range and tabulated for convenient reference.
Role of complement receptors 1 and 2 (CD35 and CD21), C3, C4, and C5 in survival by mice of staphylococcus aureus bacteremia

Abstract Complement-mediated opsonization and phagocytosis of encapsulated serotype 5 Staphylococcus aureus are essential to host defense. We describe the effects of complement depletion and deficiencies of C4, C5, and complement receptors 1 and 2 on mouse survival after intravenous exposure to S aureus . Depletion of complement proteins in C57BL/6 mice with the use of cobra-venom factor decreased survival compared with that of controls after the induction of bacteremia with mucoid (90% mortality), encapsulated (73%), and unencapsulated (59%) S aureus strains. In this model complement is even more important in the control of infection with encapsulated S aureus (80% of clinical isolates) than in the control of infection by unencapsulated strains. C4-deficient mice demonstrated similar mortality from bacteremia caused by encapsulated S aureus compared with controls, suggesting that in the unimmunized animal the alternative complement pathway contributes more to control of bacteremia caused by encapsulated S aureus than the classical complement pathway or mannan-binding lectin pathway. C5-deficient mice (B10.D2- H2 d H2-T18 c Hc 0 /oSnJ) showed similar mortality when subjected to bacteremia caused by encapsulated S aureus compared with C5-sufficient (B10.D2- Hc 1 H2 d H2-T18 c / nSnJ) mice, suggesting that in this model the anaphylatoxin C5a and the late complement cascade are not critical to survival of bacteremia induced with the use of these strains. However, C5-deficient mice depleted of C3 with the use of cobra-venom factor had 60% decreased survival compared with untreated C5-deficient mice with bacteremia induced by encapsulated S aureus , suggesting that in this model C3 is more critical than C5 in controlling S aureus bacteremia. Complement receptor 1 (CD35) is the primary receptor for the opsonin C3b. Mice deficient in CD35/CD21 showed a 67% decrease in survival compared with normal mice, suggesting that CD35/CD21 is of major importance in the control of S aureus –induced bacteremia.
A note on the splitting principle

Abstract We offer a new perspective on the splitting principle. We give an easy proof that applies to all classical types of vector bundles and in fact to G -bundles for any compact connected Lie group G . The perspective gives precise calculational information and directly ties the splitting principle to the specification of characteristic classes in terms of classifying spaces.
Dopamine-derived biological reactive intermediates and protein modifications: Implications for Parkinson's disease

Dopamine (DA) undergoes monoamine oxidase catalyzed oxidative deamination to 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily to 3,4-dihydroxyphenylacetic acid (DOPAC) via aldehyde dehydrogenase (ALDH). Previous studies demonstrated DOPAL to be neurotoxic, more so than DA and other metabolites, and implicated the aldehyde intermediate as a factor in the pathogenesis of Parkinson’s disease (PD). However, the mechanism for generation of DOPAL at aberrant levels and the pathways for toxicity are not conclusively known. Various models for DA catabolism revealed the susceptibility of DOPAL biotransformation (e.g., ALDH) to products of oxidative stress, e.g., 4-hydroxy-2-nonenal, at physiologic/pathologic levels and agents that induce oxidative stress. An elevated concentration of DOPAL correlated with increased protein modification with subsequent work demonstrating significant reactivity of the DA-derived electrophile toward protein nucleophiles compared to DA and other metabolites, e.g., DOPAC. The addition of DOPAL to proteins proceeds via reaction of the aldehyde with Lys residues, yielding a Schiff base; however, post-adduction chemistry occurs for the DOPAL-modification resulting in protein cross-linking. Preliminary work indicates enzymes in DA synthesis and catabolism to be cellular targets for DOPAL. Functional consequences for elevated levels of the DA-derived aldehyde and protein modification may include adverse cellular effects. These data implicate DOPAL as a toxic and reactive intermediate potentially serving as a “chemical trigger” for some stage of PD pathogenesis.
Antibiotic therapy in cystic fibrosis: evaluation of clinical trials.

Evaluation of antibiotic efficacy for infections in previously well individuals is based on eradication of the bacterium and resolution of the signs and symptoms of inflammation. In patients with cystic fibrosis, these criteria are less applicable: systemic signs of inflammation (fever, leukocytosis, and increased erythrocyte sedimentation rate) are variably present, and bacteria are present in the lower respiratory tract after clinical improvement. Administration of a variety of antibiotics produces resolution of subjective signs and symptoms and improvement in pulmonary function tests. Because of the cost of therapy the need to evaluate new and potentially toxic antibiotics, and the desire to provide optimum care, the evaluation of therapy needs to be objective. Controlled studies evaluating efficacy in a blinded fashion and assessing lung function and resolution of local pulmonary inflammation may provide rellable data on antiblotic effectiveness in CF.
A review of musculoskeletal problems in instrumental musicians

Musculoskeletal problems are common in instrumental musicians. Most of these problems can be classified as musculotendinous overuse, nerve entrapment/thoracic outlet syndrome, or motor dysfunction. Also seen in musicians are problems related to hypermobility and degenerative arthritis. Although these problems are seen in all instrumentalists, their prevalence is highest in professional musicians, with string players most commonly affected by musculotendinous overuse. Keyboard players are the performers most commonly affected by motor dysfunction. History and physical examination performed with an understanding of the problems of musicians are usually adequate to make the correct diagnosis. Electrophysiological studies are often helpful in confirming or excluding a diagnosis of nerve entrapment. With the exception of motor dysfunction, once these problems are recognized, they can be adequately treated. Treatment should begin conservatively with rest, evaluation of technique and practice habits, and possibly nonsteroidal antiinflammatory drugs. Depending on the type and severity of the problem, physical therapy, adaptive devices, steroid injection, or surgery may be indicated. A strong partnership with music educators is important in the management and prevention of these musculoskeletal problems.
Altered frontocingulate activation during aversive interoceptive processing in young adults transitioning to problem stimulant use

Problems associated with stimulant use have been linked to frontocingulate, insular, and thalamic dysfunction during decision making and alterations in interoceptive processing. However, little is known about how interoception and decision making interact and contribute to dysfunctions that promote the transition from recreational drug use to abuse or dependence. Here, we investigate brain activation in response to reward, punishment, and uncertainty during an aversive interoceptive challenge in current and former stimulant (cocaine and amphetamine) users using functional magnetic resonance imaging (fMRI). Young adults previously identified as recreational users (n = 184) were followed up 3 years later. Of these, 18 individuals progressed to problem stimulant use (PSU), whereas 15 desisted stimulant use (DSU). PSU, DSU, and 14 healthy comparison subjects (CTL) performed a two-choice prediction task at three fixed error rates (20% = reward, 50% = uncertainty, 80% = punishment) during which they anticipated and experienced episodes of inspiratory breathing load. Although groups did not differ in insula activation or subjective breathing load ratings, PSU exhibited lower right inferior frontal gyrus (IFG) and bilateral anterior cingulate (ACC) activation than DSU and CTL during aversive interoceptive processing as well as lower right IFG in response to decision making involving uncertainty. However, PSU exhibited greater bilateral IFG activation than DSU and CTL while making choices within the context of punishing feedback, and both PSU and DSU showed lower thalamic activation during breathing load than CTL. Findings suggest that frontocingulate attenuation, reflecting reduced resources devoted to goal maintenance and action selection in the presence of uncertainty and interoceptive perturbations, may be a biomarker for susceptibility to PSU.