cssi/SciSciGPT-SciSciNet huggingface dataset:
On the Self-Referential Nature of Naive MHC Class II-Restricted T Cells

The use of mutant mice expressing a normal MHC class II molecule surface level but a severely restricted self-peptide diversity (H-2Mα −/− ) previously revealed that T cells carrying the Eα 52–68 –I-A b complex-specific 1H3.1 TCR rely on self-peptide(s) recognition for both their peripheral persistence in irradiated hosts and their intrathymic positive selection. Here, we identify Eα 52–68 structurally related self-peptide(s) as a major contributor to in vivo positive selection of 1H3.1 TCR-transgenic thymocytes in I-A b+ /I-Eα − mice. This is demonstrated by the drastic and specific reduction of the TCR high thymocyte population in 1H3.1 TCR-transgenic (Tg) mice treated with the Eα 52–68 –I-A b complex-specific Y-A e mAb. Self-peptide(s) recognition is also driving the maturation of T cells carrying a distinct MHC class II-restricted specificity (the Eα 6 αβ TCR), since positive selection was also deficient in Eα 6 TCR Tg H-2Mα −/− thymi. Such a requirement for recognition of self-determinants was mirrored in the periphery; Eα 6 TCR Tg naive T cells showed an impaired persistence in both H-2Mα −/− and I-A b β −/− irradiated hosts, whereas they persisted and slowly cycled in wild-type recipients. This moderate self-peptide(s)-dependent proliferation was associated with a surface phenotype intermediate between those of naive and activated/memory T cells; CD44 expression was up-regulated, but surface expression of other markers such as CD62L remained unaltered. Collectively, these observations indicate that maturation and maintenance of naive MHC class II-restricted T cells are self-oriented processes.
Comparison of anesthesia protocols for intravenous glucose tolerance testing in rhesus monkeys.

Background Drugs commonly used to sedate non-human primates for physiological sample collection can affect the metabolic system and alter rates of glucose metabolism. This study was designed to compare the physiological and metabolic effects of ketamine/diazepam, telazol, and ketamine/dexmedetomidine. Methods Seven female rhesus monkeys underwent intravenous glucose tolerance testing under each of three anesthesia conditions. Blood glucose, insulin, physiological parameters, and sedation characteristics were measured and recorded. Results Glucose and insulin values were both significantly impacted by ketamine/dexmedetomidine sedation while remaining consistent during ketamine and telazol sedation. Heart rate was also significantly lowered during ketamine/dexmedetomidine anesthesia. Though, ketamine/dexmedetomidine resulted in a longer time between induction of anesthesia and need for a supplemental dose of anesthesia drug. Conclusions Telazol and ketamine have minimal cardiorespiratory and metabolic effects compared to ketamine/dexmedetomidine. Although practicably interchangeable, telazol appears to be the most efficient for intravenous glucose tolerance testings with non-human primates.
Improving health behaviours of Latina mothers of youths and adults with intellectual and developmental disabilities

Background Latina mothers who care for children with intellectual and developmental disabilities (IDD) over the lifespan struggle to take care of their own health needs in the context of their caregiving experience. Services are typically aimed at the persons with IDD and not their family caregivers. Yet, attending to family caregiver needs may contribute to better long-term care of persons with IDD who remain at home. To address this unmet need, we developed a culturally sensitive health education intervention for Latina mothers who care for youth and adults with IDD. The aim of the intervention is to improve maternal health-related self-efficacy and health behaviours, and to reduce stress. Method A randomised control design was employed to determine preliminary efficacy of the intervention. Paired sample t-tests were conducted to examine within-group changes from baseline to 3-month post-test. Repeated-measures analysis of covariance was used to examine the group-by-time interaction effects. Results Intervention participants showed greater increases between pre- and post-test in health-related self-efficacy; self-care, nutrition and overall health behaviours. Both groups reported decreases in depressive symptoms and caregiver burden. Conclusions While additional research is needed to determine long-term effects and to replicate findings, our results suggest that this culturally sensitive health intervention is a promising way to increase health behaviours which may lead to overall good health for Latina mothers who care for children with IDD across the lifespan.
Synthesis of well-defined side chain fullerene polymers and study of their self-aggregation behaviors

Monoalkynyl-functionalized fullerene was precisely synthesized starting with pristine fullerene (C60) and character- ized by multiple techniques. Methyl methacrylate and 6-azido hexyl methacrylate were then randomly copolymerized via re- versible addition fragmentation chain transfer polymerization to build polymer backbones with well-controlled molecular weights and copolymer compositions. Finally, these two moi- eties were covalently assembled into a series of well-defined side chain fullerene polymers (SFPs) via the copper-mediated click reaction which was verified by Fourier transform infrared spectroscopy and 1 H NMR. The fullerene loadings of the result- ant polymers were estimated by thermogravimetric analysis and UV-vis spectroscopy, demonstrating consistent and high conversions in most of the samples. The morphology studies of the SFPs were performed both in solution and on solid sub- strates. Very intriguing self-aggregation behaviors were detected by both gel permeation chromatography and dynamic light scattering analyses. Furthermore, the scanning electron microscopic images of these polymers showed the formation of various supramolecular nanoparticle assemblies and crystal- line-like clusters depending on the fullerene contents and poly- mer chain lengths. V C 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3572-3582
Modeling Huntington׳s disease with patient-derived neurons

Huntington׳s Disease (HD) is a fatal neurodegenerative disorder caused by expanded polyglutamine repeats in the Huntingtin (HTT) gene. While the gene was identified over two decades ago, it remains poorly understood why mutant HTT (mtHTT) is initially toxic to striatal medium spiny neurons (MSNs). Models of HD using non-neuronal human patient cells and rodents exhibit some characteristic HD phenotypes. While these current models have contributed to the field, they are limited in disease manifestation and may vary in their response to treatments. As such, human HD patient MSNs for disease modeling could greatly expand the current understanding of HD and facilitate the search for a successful treatment. It is now possible to use pluripotent stem cells, which can generate any tissue type in the body, to study and potentially treat HD. This review covers disease modeling in vitro and, via chimeric animal generation, in vivo using human HD patient MSNs differentiated from embryonic stem cells or induced pluripotent stem cells. This includes an overview of the differentiation of pluripotent cells into MSNs, the established phenotypes found in cell-based models and transplantation studies using these cells. This review not only outlines the advancements in the rapidly progressing field of HD modeling using neurons derived from human pluripotent cells, but also it highlights several remaining controversial issues such as the 'ideal' series of pluripotent lines, the optimal cell types to use and the study of a primarily adult-onset disease in a developmental model. This article is part of a Special Issue entitled SI: Exploiting human neurons.
Limitations in the Use of the 340 nm Absorbance Maximum of Reduced Nicotinamide Adenine Dinucleotide Phosphate for the Determination of Oxidation Rates and Stoichiometry during Rat Hepatic Microsomal Metabolism

During rat hepatic microsomal oxidative metabolism NADPH not only is oxidized to NADP+ but is cleaved to reduced nicotinamide mononucleotide. The 340 nm absorbance maximum of NMNH interferes with the use of the 340 nm absorbance as a measure of NADPH oxidation. The pyrophosphatase responsible for NADPH cleavage can destroy 30% of the added NADPH in the absence of exogenous mixed-function oxidase substrates in microsomes from phenobarbital-treated rats. It is inhibited about 75% by 2 mM 59-AMP and 25 mM sodium pyrophosphate and about 30% by 10 mM sodium fluoride. Using pyrophosphatase inhibitors, and allowing for the turbidity enhancement of the 340 nm absorbance, the stoichiometry of NADPH oxidized to oxygen consumed approaches 1:1, especially in the presence of exogenous mixed-function oxidase substrates.
Bunyaviruses: Hantavirus and Others

The Bunyaviridae family is the largest family of RNA viruses with more than 350 named isolates. Viruses in the family are divided into five genera (Orthobunyavirus, Phlebovirus, Nairovirus, Hantavirus, and Tospovirus) on the basis of serological, molecular, antigenic, and structural characteristics. The Bunyaviridae are a unique group of viruses whose members are able to infect invertebrates, vertebrates, and plants, and they can be found worldwide. Multiple members are significant pathogens with the ability to cause severe disease in humans, such as encephalitis, hepatitis, or hemorrhagic fever. Most bunyaviruses are spread through sylvatic transmission cycles between susceptible vertebrate hosts and hematophagous arthropods, including ticks, mosquitoes, and phlebotomine flies. Unique are the members of the Hantavirus genus, in that they are not infecting insect vectors but are maintained in nature through persistent infection of rodents. Human and animal pathogenic bunyaviruses can be found in four of the five genera, with tospoviruses being plant pathogens. The large family of bunyaviruses is a pool not only for many emerging and reemerging viruses, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, and the hantaviruses, but also for recently emerged pathogens, such as the newly identified severe fever with thrombocytopenia syndrome and Heartland, Shuni, and Schmallenberg viruses. This chapter will discuss the most important human pathogens of the Orthobunyavirus, Phlebovirus, Nairovirus, and Hantavirus genera.
Microstructure Study of the Oxidation of TiN Layers During Sputtering Process

TiN provides a good template layer for the epitaxial SrTiO3 (001) growth on Si(001) single crystal substrates by RF sputtering. However, TiN template layer was oxidized into TiO2 during the subsequent sputtering process of electrodes of SrRuO3. The effect of Ru ion catalyzed oxidation and delamination of the TiN layer has been studied using transmission electron microscopy (TEM) and high-resolution transmission electron microscope (HRTEM). The epitaxial orientation relationship of the SrRuO3 and SrTiO3 was reserved to be cube on cube with respect to Si and the crystal quality of the SrRuO3/SrTiO3 film remained even when the TiN template layer was oxidized. The stress in the thin film of SrRuO3/SrTiO3/TiN structure could be determined from the buckle shape in both plan view and cross sectional TEM images.
Identification of Dorsal Ocellar Primordia in Larvae of Trichoplusia ni (Lepidoptera: Noctuidae)

The primordia for the dorsal ocelli of the moth Trichoplusia ni Hubner have been isolated and identified through a combination of ablation by cauterization and histological methods. They are located in the dorsal region of the larval head beneath and beside the invaginated larval postfrons.
Dissecting Cellulitis of the Scalp

A 25-year-old African-American male presents with an 8-month history of “a lot of bumps on my head.” He first had one painful red bump on his crown, which he believed was an ingrown hair. He then developed additional bumps over the top of his head. There was associated “cheesy” drainage and alopecia. He attempted to apply his topical acne medications to the area with mild improvement. He has not had any fevers or chills.
Editorial Commentary: Statins and acute coronary syndromes.

In this issue of the journal, the authors review the available data regarding the beneficial effects of statins on the prognosis of patients with acute coronary event syndromes and particularly of patients with myocardial infarction manifested electrocardiographically as ST segment myocardial infarction [1]. Throughout this article, the authors make the comment that transmural myocardial infarction presenting with ST segment elevation constitutes a bigger hazard than the subendocardial infarction seen in myocardial infarction patients presenting without ST segment elevation. I do not necessarily agree with that since data are available in 1 year indicating that both have a similar mortality. I do not think we should give the impression that a myocardial infarction, no matter what you call it, is good for you and that a myocardial infarction not associated with ST segment elevation on the electrocardiogram is benign. In the section on “statin administration in patients with ST elevation associated with a myocardial infarction,” the authors outline their thoughts about how statins work to alter many of the biological factors that stimulate the vascular endothelium by their pleiotropic action. In this section of the article, the authors emphasize the pleiotropic action of statins, including the reduction of platelet stimulation, and make the point that statins are plaque stabilizers. I think all agree that statins have a pleiotropic effect, and I think everything referred to is correct, but do not think there is anything new in that section, and it is difficult to remember all that was said. Although the pleiotropic effects of statins are certainly present, however, they are not measured clinically in the individual patient and thus are not very useful to the physician taking care of acute coronary syndrome patients. Only, lipid levels, and outcome are measured.
Multi-Rate Deep Learning for Temporal Recommendation

Modeling temporal behavior in recommendation systems is an important and challenging problem. Its challenges come from the fact that temporal modeling increases the cost of parameter estimation and inference, while requiring large amount of data to reliably learn the model with the additional time dimensions. Therefore, it is often difficult to model temporal behavior in large-scale real-world recommendation systems. In this work, we propose a novel deep neural network based architecture that models the combination of long-term static and short-term temporal user preferences to improve the recommendation performance. To train the model efficiently for large-scale applications, we propose a novel pre-train method to reduce the number of free parameters significantly. The resulted model is applied to a real-world data set from a commercial News recommendation system. We compare to a set of established baselines and the experimental results show that our method outperforms the state-of-the-art significantly.
Effect of Hip Reconstructive Surgery on Health-Related Quality of Life of Non-Ambulatory Children with Cerebral Palsy.

Background: The primary aim of this study was to evaluate the relationship of the migration percentage (a radiographic metric quantifying hip displacement) in children with Gross Motor Function Classification System (GMFCS) level-IV or V cerebral palsy and spastic hip dysplasia to the acetabular index and the health-related quality of life (HRQOL) as measured with the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) before and after reconstructive hip surgery. Methods: In a prospective cohort study (n = 38), the migration percentage, acetabular index, and CPCHILD scores were analyzed using the Pearson correlation analysis immediately before reconstructive hip surgery and at 6 weeks and 3, 6, 12, and 24 months after the surgery. Subgroup analysis was used to compare patients who had a preoperative migration percentage of ≥50% with those who had a preoperative migration percentage of <50% and to compare the acetabular index between patients who had a pelvic osteotomy and those who had not. Linear mixed models were used to analyze changes in the migration percentage, acetabular index, and CPCHILD scores over time. Results: The preoperative migration percentage negatively correlated with the preoperative CPCHILD score (r = −0.50; p = 0.002). This relationship continued throughout the follow-up period such that, for each additional 1% correction in migration percentage, the CPCHILD total score increased by 0.2 point (p < 0.001). There was no correlation between the acetabular index and CPCHILD total score before or after surgery (p = 0.09 to 0.71). The preoperative CPCHILD total scores differed between the migration-percentile groups (mean difference = 13 points; 95% confidence interval = 3.3 to 22.8; p = 0.01). However, after hip surgery, the CPCHILD score improved similarly for both groups. Conclusions: These data support the effectiveness of reconstructive hip surgery for the treatment of spastic hip dysplasia to improve the HRQOL of non-ambulatory children with severe cerebral palsy. Level of Evidence: Prospective Level IV. See Instructions for Authors for a complete description of levels of evidence.
A computationally efficient parallel Levenberg‐Marquardt algorithm for highly parameterized inverse model analyses

Inverse modeling seeks model parameters given a set of observations. However, for practical problems because the number of measurements is often large and the model parameters are also numerous, conventional methods for inverse modeling can be computationally expensive. We have developed a new, computationally efficient parallel Levenberg-Marquardt method for solving inverse modeling problems with a highly parameterized model space. Levenberg-Marquardt methods require the solution of a linear system of equations which can be prohibitively expensive to compute for moderate to large-scale problems. Our novel method projects the original linear problem down to a Krylov subspace such that the dimensionality of the problem can be significantly reduced. Furthermore, we store the Krylov subspace computed when using the first damping parameter and recycle the subspace for the subsequent damping parameters. The efficiency of our new inverse modeling algorithm is significantly improved using these computational techniques. We apply this new inverse modeling method to invert for random transmissivity fields in 2-D and a random hydraulic conductivity field in 3-D. Our algorithm is fast enough to solve for the distributed model parameters (transmissivity) in the model domain. The algorithm is coded in Julia and implemented in the MADS computational framework (http://mads.lanl.gov). By comparing with Levenberg-Marquardt methods using standard linear inversion techniques such as QR or SVD methods, our Levenberg-Marquardt method yields a speed-up ratio on the order of ∼101 to ∼102 in a multicore computational environment. Therefore, our new inverse modeling method is a powerful tool for characterizing subsurface heterogeneity for moderate to large-scale problems.
Selling Finite Capacity in Bulks

We consider a firm that owns a limited capacity for the delivery of services or for the production of customized products. Potential buyers specify the amount of capacity they will require for the execution of their intended services, goods or projects. Based on the size of the requirement, the firm makes a bid while being challenged in various ways: (1) it only knows the underlying probability function from which its customers’ reservation prices are drawn, (2) arrival of additional future requests is stochastic, and, (3) the firm knows in advance neither the magnitude of these potential requests nor the buyer's reservation price. The firm aims to maximize its expected profit by choosing its pricing mechanism. The fact that capacity is demanded in varying amounts distinguishes this problem from most available literature in which standard sizes are sold or partial fulfillment and displacement are permitted. Lacking such allowances presents a new challenge to the firm as in conjunction with pricing it should also address the issue of various sizes requests’ compatibility to achieve optimal utilization of its capacity in order to maximize expected profit. In this article, we consider two approaches of handling this problem: myopic and foresighted. We formulate and analyze the problem to obtain the firm's optimal bidding decisions as well as managerial insight about the optimal bid level and its important role in coordinating buyers’ requests. Furthermore, due to this role, pricing patterns in this environment are different than those in standard unit sales.
Retrotransposons – Natural and Synthetic

Transposable elements are ubiquitous among sequenced genomes. The host genomes roughly subdivide into two types: 1) streamlined, that is, small,with little space between genes and lacking large introns, or 2) bulky, with lots of space between genes and many large introns. Most microorganisms, along with selected vertebrates like the pufferfish, fall into the first class, whereas mammals and most plants fall into the second class. As can be seen from Fig. 1, transposable element abundance mirrors the genome type of the host, with mobile elements comprising half or more of many of these bulky genomes! Mobile elements are of two basic types: DNA transposons, which predominantly mobilize via a cut and paste mechanism, and retrotransposons, which move by a copy and paste mechanism involving reverse transcription of an RNA intermediate (Fig. 1 right panel; Curcio and Derbyshire 2003). Retrotransposons are found in virtually all eukaryotes, from yeast (Kim et al. 1998) to human (Lander et al. 2001). Remarkably, in a yeast cell, the number of retrotransposon copies can be changed rather dramatically without a major impact on the phenotype of the host. The change in copy number can be seen using a new tiling array technique by which it is possible to comprehensively map the unique genomic regions adjacent to all transposable element copies probed (Fig. 2; Wheelan et al. 2006). The ability of yeast strains to tolerate very high copy numbers of transposons is due in part to the fact that, in yeast, most insertions are targeted to non-essential genomic regions, even though most of the genome is protein-coding (Chalker and Sandmeyer 1990; Devine and Boeke 1996; Ji et al. 1993; Zou et al. 1996). This property and many others suggest that retrotransposons are highly coevolved with their hosts.
The Thinking Process

In this chapter, we discuss the basic mechanisms of mental functions involved in the thinking process and the universal, intellectual standards for critical thinking, as suggested by the Foundation for Critical Thinking. We will also discuss the basic structure of the parts of the brain involved in the thinking process and their interconnections (neural circuitry). Other mental functions, such as emotions, which influence thinking, are reviewed. We discuss the importance of listening in the process of collecting information to think with. We also emphasize the importance of language and semantics in thinking.
Line and Flat Processes

Stationary line processes in the plane; A non-Cox counterexample; Spanning criteria for invariance; Invariance under absolute continuity; Non-interactive particle systems; Degeneracies of flat processes; General criteria of absolute continuity.
An energy-efficient and secure hybrid algorithm for wireless sensor networks using a mobile data collector

This paper proposes a new hybrid algorithm for security, which incorporates both distributed and hierarchal approaches. It uses a mobile data collector (MDC) to collect information in order to save energy of sensor nodes in a wireless sensor network (WSN) as, in most networks, these sensor nodes have limited energy. Wireless sensor networks are prone to security problems because, among other things, it is possible to use a rogue sensor node to eavesdrop on or alter the information being transmitted. To prevent this, this paper introduces a security algorithm for MDC-based WSNs. A key use of this algorithm is to protect the confidentiality of the information sent by the sensor nodes. The sensor nodes are deployed in a random fashion and form group structures called clusters. Each cluster has a cluster head. The cluster head collects data from the other nodes using the time-division multiple access protocol. The sensor nodes send their data to the cluster head for transmission to the base station node for further processing. The MDC acts as an intermediate node between the cluster head and base station. The MDC, using its dynamic acyclic graph path, collects the data from the cluster head and sends it to base station. This approach is useful for applications including warfighting, intelligent building and medicine. To assess the proposed system, the paper presents a comparison of its performance with other approaches and algorithms that can be used for similar purposes.
State Responses to U.S. Supreme Court Campaign Finance Decisions

Recent federal court decisions have deregulated state campaign finance systems to a significant degree. These decisions are not only rooted in First Amendment jurisprudence but also raise issues of federalism. Although most studies of federal–state conflict focus on disputes between state officials and elected federal policy makers, courts are also policy-making institutions, and in the absence of policy making by other federal branches, courts have become the critical federal policy maker in this area. In response to U.S. Supreme Court rulings that deregulate campaign finance rules and are out of step with the policy preferences of many state electorates and officials, states are attempting to resist these rulings, but using different approaches than are used by states in disputes with the Congress or President. We discuss these rulings and state responses to them. We also describe the implications of these dynamics for federalism.
Contributors to the Excess Stroke Mortality in Rural Areas in the United States.

Background and Purpose—Stroke mortality is 30% higher in the rural United States. This could be because of either higher incidence or higher case fatality from stroke in rural areas. Methods—The ur...
Posterior cortical atrophy of a suspected non-Alzheimer type: a case report.

Objective: A case of Posterior Cortical Atrophy syndrome of a suspected non-Alzheimer disease pathology type is presented to illustrate prospective diagnosis and course. Method: A 54-year-old woman...
Security evaluation of cloud service providers using third party auditors

Cloud computing is a revolutionary breakthrough in computing technology. It allows businesses to supply their customers with a seemingly endless amount of resources on demand, so long as they are willing to pay for it. From a business perspective, cloud computing is revolutionizing profitability. From a security standpoint, cloud computing presents an alarming amount of risk to customer data. When customers make purchases, they transfer data to a Cloud Service Provider (CSP), but are unable to evaluate which CSP has sufficient security controls to protect their sensitive data. The Cloud Security Alliance (CSA) is an organization whose mission is to suggest best practice security controls and guidelines for CSPs to follow. The CSA provides a questionnaire or risk assessment, known as the Consensus Assessment Initiative Questionnaire (CAIQ) for CSPs to fill out in order to gauge their level of security within their organization. The CSPs access these questionnaires from the CSA's STAR (Security Trust and Assurance Registry) database. This allows for CSUs to base their level of trust in a specific organization on these assessments. However, there is no way for the CSA to validate that the CSP's responses to the questionnaire are accurate. This paper presents a framework that uses a third-party auditor (TPA) to review, audit, and validate the CAIQ responses stored in the STAR repository. Our framework provides a specific group of auditors that can be used to evaluate and validate the security controls of CSPs. Therefore, the primary objective of this research is to formulate the mechanism by which the appropriate auditor(s) can be chosen by the TPA and create a verification system in which CSUs may finally put their trust in.
Proverbs of Nonprofit Financial Management

Whereas the field of public administration has benefited from periods of critical reflection and reform aimed at reexamining the field’s traditional management paradigms, the related field of nonpr...
Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.

Abstract Objective Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model. Design Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections. Together these data were used to evaluate the effect of osteoarthritis and solute size on the rate of drug clearance from the joint. Results Clearance of 10 kDa dextran from the joint space quantified using in vivo fluorescence imaging of the knee joint region was not significantly different between naive and MMT joints. In contrast, clearance of 500 kDa dextran was significantly reduced for MMT joints when compared to naive joints by fluorescence in vivo imaging. Drug accumulation in lymph nodes and plasma were lower for the 500 kDa dextran as compared to 10 kDa dextran, and lymph node levels were further reduced with the presence of osteoarthritis. Furthermore, synovium was significantly thicker in MMT joints than in naive joints and image analysis of joint tissue sections revealed different trans-synovial distributions of 10 and 500 kDa dextran. Conclusion Large macromolecules were retained in the arthritic joint longer than in the healthy joint, while smaller molecules were cleared similarly in healthy and arthritic joints. In vivo fluorescence imaging, plasma and lymph node concentrations, and spatial distributions of drug fluorescence identified differences in higher molecular weight clearance between naive and arthritic disease states. Findings may relate to a thickening of synovium for joints with induced arthritis, and support the concept that intra-articular drug delivery effectiveness may vary with the state of joint pathology.
Design of non-equiatomic high entropy alloys with heterogeneous lamella structure towards strength-ductility synergy

Abstract A non-equiatomic FeNiCoAlCrB (NCACB) high entropy alloy (HEA) with a heterogeneous lamella (HL) structure is fabricated through conventional thermomechanical processing. In the HL microstructure, fine-grain regions result from inhibited grain growth due to Zener pinning of boundaries by NiAl (B2) precipitates, while coarse-grained regions originate from grain growth within large deformation bands in the absence of precipitates. A back-stress strengthening mechanism, unique to deformation of heterogeneous microstructures, is verified through mechanical behavior and electron backscatter diffraction enabled geometrically necessary dislocation density analysis. This mechanism gives rise to the combination of both high strength and high ductility in HL-NCACB-HEA.
Assessing the Value to Client Organizations of Student Practicum Projects

AbstractPublic policy and public administration degree programs often require students to gain real-world training by working on practicum projects with client organizations. Whereas past literatur...
Sexual violence against women living with or at risk for HIV infection.

Objectives This study investigates factors associated with sexual violence against adult women living with and at risk for HIV infection. Methods Women at least 18 years old and living in Rhode Island or southeast Massachusetts enrolled from 1987 to 1992 in a cohort study of heterosexual HIV risk. A total of 408 women provided interviews on lifetime experiences of rape and HIV-related risk exposures. Data are presented on 96 women reporting experiences with rape as adults, and 231 women who reported never experiencing rape or forced sex. Results Lifetime prevalence of sexual abuse was 43%. Over half occurred during adulthood. Thirty-five percent of women with HIV were raped as adults. Among women with HIV, adult rape experiences were associated with earlier age of first sex, more sexual partners, unprotected sex involving drugs, earlier age of injection drug use, teen pregnancy, STDs, and serious gynecologic surgery than those reporting they were never raped (prevalence odds ratios ranged from 2.8 to 11.2). Among women without HIV, adult rape was associated with similar experiences, although with some exception, the relative odds estimates were less pronounced. Women engaged in sex work were more likely to report rape. Conclusion The high prevalence of rape reported in this cohort of mostly economically poor women living with and at risk for HIV infection is consistent with other studies. Economic and social vulnerability that frames HIV risk and subsequent infection in women includes rape. Clinicians caring for women with HIV and counseling women at risk for infection need to screen routinely for sexual abuse.
Microtubule-targeted chemotherapeutic agents inhibit STAT3 signaling in breast cancer

1465 Breast cancer often arises from inappropriate activation of transcription factors involved in normal mammary development, such as the signal transducers and activators of transcription (STAT) family of transcription factors. In particular, STAT3 plays an important role during normal mammary involution and remodeling to the undifferentiated, pre-pregnancy state. We have found that STAT3 is tyrosine phosphorylated, and therefore activated, in approximately 70% of primary breast cancers, with many of these tumors being high grade and undifferentiated. Furthermore, in model systems, inhibition of STAT3 leads to a loss of tumorigenicity of breast cancer cells. Therefore, targeting STAT3 in breast cancer would be a potentially beneficial form of therapy. Given that STAT3 associates with microtubules in the cell, we considered the possibility that chemotherapeutic agents that affect microtubules may work in part by disrupting STAT3 signaling. We have found that both the microtubule stabilizing agent paclitaxel and the microtubule destabilizing agent vinorelbine, which are commonly used therapies for breast cancer, inhibit STAT3 tyrosine phosphorylation in breast cancer cell lines that contain constitutively active STAT3. This is not a feature common to all chemotherapy agents, as doxorubicin does not inhibit STAT3 tyrosine phosphorylation. In addition, pretreatment of breast cancer cells with paclitaxel or vinorelbine reduces STAT3 tyrosine phosphorylation induced by cytokines. These agents also inhibit STAT3 dependent reporter gene activity but do not inhibit STAT1 or NFkappaB dependent reporter activity, thereby demonstrating their specificity for STAT3. Moreover, these drugs inhibit the expression of endogenous STAT3 target genes, including BCL3, BCL6, Bcl-x, and SMAD7, in breast cancer cell lines containing constitutively active STAT3. Coincident with the inhibition of tyrosine phosphorylation of STAT3, treatment of breast cancer cells with either paclitaxel or vinorelbine leads to a prominent increase in phosphorylation of STAT3 on serine 727. Using a protein kinase C agonist to induce STAT3 serine phosphorylation in isolation also leads to a decrease in STAT3 tyrosine phosphorylation. This suggests that paclitaxel and vinorelbine are inducing serine phosphorylation of STAT3 which then inhibits its tyrosine phosphorylation. In breast cancer cell lines that are more resistant to these agents, STAT3 serine phosphorylation is not induced, nor is STAT3 tyrosine phosphorylation inhibited. Therefore, paclitaxel and vinorelbine may be therapeutically beneficial due in part to their ability to inhibit STAT3 signaling in breast cancer, and combinations of specific STAT3 inhibitors and these microtubule-targeted agents may be particularly effective in the treatment of breast cancer.
High-resolution Observation of Moving Magnetic Features

Moving magnetic features (MMFs) are small magnetic elements moving almost radially away from sunspots toward the boundary of moat regions. They are mostly seen during the decay phase of a sunspot. Here we present a high-resolution observation of MMFs around a sunspot in NOAA AR 12565 on 2016 July 14 using the the 1.6 m Goode Solar Telescope (GST) at Big Bear Solar Observatory. The spectropolarimetric measurements of photospheric magnetic field are obtained from GST's newly commissioned Near Infra-Red Imaging Spectropolarimeter at the Fe i 1.56 μm line. The statistical study of physical properties of identified fine-scale MMFs (i.e., size, lifetime, inclination, horizontal velocity, and flux) is presented. The origin of the minority polarity flux in the sunspot is determined. Same as the majority polarity flux, the minority polarity flux can originate from mid-penumbra with highly inclined fields. The role of MMFs in both polarities in the flux evolution of the sunspot is speculated, as they can both contribute to the sunspot evolution.
Disrupted Habituation in the Early Stage of Psychosis.

Abstract Background Learning and memory are impaired in schizophrenia. Some theories have proposed that one form of memory, habituation, is particularly impaired. Preliminary evidence suggests that memory impairment is associated with failed hippocampal habituation in patients with chronic schizophrenia. We studied how abnormal habituation of the hippocampus is related to relational memory deficits in the early stage of psychosis. Methods We measured hippocampal activity in 62 patients with early psychosis and 70 healthy individuals using functional magnetic resonance imaging. Habituation was defined as the slope of functional magnetic resonance imaging signal change to repeated presentations of faces and objects. Relational memory ability was measured as the slope of preferential viewing during a face-scene pair eye movement task outside the scanner. Results Patients with early psychosis showed impaired relational memory (p Conclusions We found evidence for disrupted hippocampal habituation in the early stage of psychosis along with an altered association between hippocampal habituation and relational memory ability. These results suggest that neural habituation may provide a novel target for early cognitive interventions in psychosis.
Stretch-induced increases in intracellular calcium of isolated vascular smooth muscle cells

Vascular smooth muscle responds to stretch with an increase in active force development. To investigate the role of Ca2+ in this response, we used the fluorescent dye fura-2 to quantitate changes in cytosolic Ca2+ in single, vascular smooth muscle cells during rapid stretch. Cells were enzymatically dispersed from pig coronary arteries, loaded with fura-2/AM, and studied using a digital-imaging microscope. Stretch of individual cells was accomplished by attachment with suction to two patch-type micropipettes to apply force to the ends of the cell. Stretch induced the release of Ca2+ from intracellular stores as well Ca2+ influx across the plasma membrane. In physiological saline solution containing 1.5 mM Ca2+, intracellular calcium increased with cell stretch in a sigmoidal fashion. This relationship was shifted upward in 10 mM Ca2+ bath solution and abolished after several minutes in Ca(2+)-free solution. The dihydropyridine Ca2+ channel blocker nifedipine, in doses sufficient to completely block inward Ca2+ current, produced only a partial block of the sustained stretch-induced intracellular Ca2+ response. It is concluded that in isolated pig coronary arterial smooth muscle cells, stretch-induced Ca2+ influx occurs in part via a nifedipine-resistant pathway, which may be a stretch-activated cation channel.
Estimating the Probability of a Phase II Project Being Discontinued

To estimate the probability of a Phase II project being discontinued, we considered the following model:
Religiosity/Spirituality and Mental Health Outcomes in Mothers of Children with Autism Spectrum Disorder: The Mediating Role of Positive Thinking

This study examines associations between dimensions of religiosity/spirituality (R/S) and anxiety symptoms in mothers of children with autism spectrum disorder (ASD). Mothers' positive ways of thinking and romantic relationship satisfaction were examined as mediators of associations. The extent to which child ASD symptom severity and maternal broad autism phenotype (BAP) behaviors predicted interactions with religious community members was also examined. Seventy-three Christian mothers of a child with ASD completed online surveys. Higher levels of spirituality were associated with viewing their child with ASD as providing a positive contribution to the family. These positive views were, in turn, associated with less anxiety symptoms. Mothers of children with more severe ASD symptoms also reported greater negative interactions with members of their congregation.
Auditory performance in bald eagles and red-tailed hawks: a comparative study of hearing in diurnal raptors

Collision with wind turbines is a conservation concern for eagles with population abundance implications. The development of acoustic alerting technologies to deter eagles from entering hazardous air spaces is a potentially significant mitigation strategy to diminish associated morbidity and mortality risks. As a prelude to the engineering of deterrence technologies, auditory function was assessed in bald eagles (Haliaeetus leucocephalus), as well as in red-tailed hawks (Buteo jamaicensis). Auditory brainstem responses (ABRs) to a comprehensive battery of clicks and tone bursts varying in level and frequency were acquired to evaluate response thresholds, as well as suprathreshold response characteristics of wave I of the ABR, which represents the compound potential of the VIII cranial nerve. Sensitivity curves exhibited an asymmetric convex shape similar to those of other avian species, response latencies decreased exponentially with increasing stimulus level and response amplitudes grew with level in an orderly manner. Both species were responsive to a frequency band at least four octaves wide, with a most sensitive frequency of 2 kHz, and a high-frequency limit of approximately 5.7 kHz in bald eagles and 8 kHz in red-tailed hawks. Findings reported here provide a framework within which acoustic alerting signals might be developed.
Pan-SHIP1/2 inhibitors promote microglia effector functions essential for CNS homeostasis.

We show here that both SHIP1 and its paralog SHIP2 are expressed at the protein level in microglia. To examine whether targeting of SHIP paralogs might influence microglial physiology and function we tested the capacity of SHIP1-selective, SHIP2-selective and pan-SHIP1/2 inhibitors for their ability to impact microglia proliferation, lysosomal compartment size and phagocytic function. We find that highly potent pan-SHIP1/2 inhibitors can significantly increase lysosomal compartment size and phagocytosis of dead neurons and Aβ1–42 by microglia in vitro. We show that one of the more potent and water-soluble pan-SHIP1/2 inhibitors, K161, can penetrate the blood-brain barrier and consistent with this K161 increases the capacity of CNS-resident microglia to phagocytose beta-amyloid and apoptotic neurons following systemic administration. These findings provide the first demonstration that small molecule modulation of microglia function in vivo is feasible and suggest the possibility that dual inhibition of the SHIP1 and 2 paralogs could provide a novel means to enhance basal microglial homeostatic functions for therapeutic purposes in Alzheimer9s Disease, and possibly other dementias where increased microglial function could be beneficial.
Heterogeneous deformation of two-dimensional materials for emerging functionalities

Atomically thin 2D materials exhibit strong intralayer covalent bonding and weak interlayer van der Waals interactions, offering unique high in-plane strength and out-of-plane flexibility. While atom-thick nature of 2D materials may cause uncontrolled intrinsic/extrinsic deformation in multiple length scales, it also provides new opportunities for exploring coupling between heterogeneous deformations and emerging functionalities in controllable and scalable ways for electronic, optical, and optoelectronic applications. In this review, we discuss (i) the mechanical characteristics of 2D materials, (ii) uncontrolled inherent deformation and extrinsic heterogeneity present in 2D materials, (iii) experimental strategies for controlled heterogeneous deformation of 2D materials, (iv) 3D structure-induced novel functionalities via crumple/wrinkle structure or kirigami structures, and (v) heterogeneous strain-induced emerging functionalities in exciton and phase engineering. Overall, heterogeneous deformation offers unique advantages for 2D materials research by enabling spatial tunability of 2D materials' interactions with photons, electrons, and molecules in a programmable and controlled manner.
Semaglutide in Cystic Fibrosis-Related Diabetes

Context and objective In spite of the evidence that inadequately controlled glycemia is associated with worse clinical outcomes, cystic fibrosis-related diabetes (CFRD) is not well controlled in a majority of patients. The objective of this report is to demonstrate the effect of the addition of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), to basal insulin to control glycemia in one such patient. Design, intervention, and the main outcome measures The replacement of rapidly acting prandial insulin with semaglutide weekly with continuation of basal insulin. Glycated hemoglobin A1c (HbA1c) was measured and continuous glucose monitoring (CGM) was conducted. Results There was a significant improvement in glycemic control, reduction in HbA1c from 9.1% to 6.7% and stable euglycemic pattern on CGM (mean glucose, 142 mg/dL; SD, 51) within 3 months of starting treatment. There was no increase in plasma pancreatic enzyme concentrations. Conclusions Semaglutide at a low dose was able to replace prandial insulin and control glycemia in combination with basal insulin.
Economic Forecasting With Autoregressive Methods and Neural Networks

Neural networks can forecast economic data with accuracy matching that of conventional autoregressive methods such as SARIMA and VAR. This study uses dense, recurrent, convolutional, and convnet/RNN hybrids to conduct time-series analysis of interest rates, consumer and producer prices, and labor market data. Training on 14 years of data, neural networks produce accurate 50-year forecasts. Gaps in these forecasts may reveal macroeconomic regime changes. Failures in otherwise accurate neural network forecasts may thus inform theoretical economic hypotheses through unsupervised machine learning.