cssi/SciSciGPT-SciSciNet huggingface dataset:
Gender, Sexual Experience, and the Sexual Double Standard: Evaluations of Female Contraceptive Behavior

The purpose of the present research was to compare men's and women's perceptions of female contraceptive behavior and investigate the relationship between sexual experience and these perceptions. One hundred forty-six predominantly Caucasion males (n = 76) and females (n = 70) were randomly assigned to one of three sexual scenarios in which a male provided the condom in a sexual encounter, a female provided the condom, or no condom was used. They were then asked to rate the female on several behavioral and personality measures and to complete a sexual experience scale. Results showed differences in the way men and women perceived the female target. A positive correlation was also found between sexual experience and more favorable perceptions of the sexually-prepared female.
Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection

Based on the role of tumor necrosis factor-α (TNF-α) in ischemic preconditioning (IPC) and the age-associated loss of both TNF-α-induced platelet-derived growth factor-AB (PDGF-AB)-mediated cardiop...
The Random Assignment of Students Into Elementary Classrooms Implications for Value-Added Analyses and Interpretations

>> Value-added models (VAMs) are used to measure changes in student achievement on large-scaled standardized test scores from year to year. When aggregated, VAM estimates are used to measure teacher effectiveness and hold teachers accountable for the value they purportedly add to or detract from student learning and achievement. In this study, researchers examined the extent to which purposeful (nonrandom) and random assignment of students into classrooms occurs in Arizona elementary schools (Grades 3‐6). Researchers found that overwhelmingly, students are not randomly assigned and administrators, teachers, and parents play a prodigious role in the process. Findings have current implications for value-added analyses and the extent to which nonrandom assignment practices might impact or bias teachers’ value-added scores.
Individual advantages to ecological specialization: insights on cognitive constraints from three conspecific taxa

The information-processing hypothesis (IPH) posits that specialist herbivores should make host-associated decisions more effectively than generalists and thus enjoy associated fitness advantages that may help explain the evolutionary prevalence of host-specific insects. This is because generalists must evaluate a greater diversity of host plants/cues than specialists and thus face a cognitive challenge that is predicted to constrain the efficiency and accuracy of their choices. Here, we present the first individual-level evaluation of this hypothesis. This involved experimentally quantifying the specificity, efficiency, and accuracy of host selection, as both larvae and adults, for many individuals representing each of three 'host forms' of Neochlamisus bebbianae leaf beetles. These experiments provided several significant findings: host forms differed in larval specificity, with the more specialized host forms more efficiently and accurately selecting optimal hosts as both larvae and adults. Positive correlations between larval specificity and both efficiency and accuracy across test individuals provided the most direct evidence to date for a biological association between these variables. Our results thus provide strong and consistent support for the IPH at the level of both populations and individuals. Because individual N. bebbianae make many host-associated decisions in nature, our results suggest that cognitive constraints may play a major role in the evolutionary dynamics of ongoing ecological specialization and diversification in this species.
The Effects of Sucralose on Coronal and Root-surface Caries

Sucralose is an intensely sweet, chlorinated carbohydrate structurally similar to sucrose; thus, its cariogenic potential is of great interest. Four groups of 12 Sprague-Dawley rats were infected with Streptococcus mutans (sobrinus), caged in a Konig-Hofer programmed feeding machine, and fed diet 2000 or modified diet to contain sucralose at various concentrations instead of sucrose. Rats fed sucralose diet developed significantly fewer lesions than did the rats fed regular diet 2000. Animals fed diet 2000 also harbored more S. mutans (sobrinus) than did the other groups of animals. In a concurrent study, desalivated rats were inoculated with S. mutans (sobrinus) and Actinomyces viscosus. They were fed (ad libitum) either diet 2000 (contains 56% sucrose) or diet 2000 minus sucrose plus 93 mg% sucralose. The severity of caries lesions in the sucralose-fed rats after 35 days was significantly less than those in the sucrose-fed rats. The amount of root exposure was the same in both groups. However, root-surface caries did not develop in the sucralose-fed rats. These results show that sucralose is non-cariogenic in rats.
Effective conductivity of periodic arrays of spheres with interfacial resistance

We consider the problem of analytically determining the effective thermal conductivity of a composite material consisting of periodic arrays of spheres with interfacial resistance. We applied Rayle...
Minimization of energy in quasi-static manipulation

Quasistatic mechanical systems, in which mass or acceleration is sufficiently small for the inertial term ma in F=ma to be negligible compared to dissipative forces, are discussed. It is pointed out that many instances of robotic manipulation can be well approximated as quasistatic systems, with the dissipative force being dry friction. Energetic formulations of Newton's laws have often been found useful in the solution of mechanics problems involving multiple constraints. An intuitive minimum power principle is outlined which states that a system chooses at every instant the lowest-energy, or 'easiest', motion in conformity with the constraints. Surprisingly, the principle is in general false; but it is proved that the principle is correct in the useful special case that Coulomb friction is the only dissipative or velocity-dependent force acting in the system. >
The Significance of the Small Hiatal Hernia: A Reappraisal

SUMMARY A discussion of some of the unsolved problems in our understanding of the development, symptomatology and pathophysiology of moderately sized or even large esophageal hiatal hernias has been presented. In most cases of hiatal hernia, the disturbed anatomy in the region of the esophageal hiatus of the diaphragm is the cause of distressing gastric and epigastric symptoms. If a period of conservative treatment does not alleviate these symptoms and if concurrent diseases are well controlled, operative repair of hiatal hernias should be undertaken regardless of their size.
Disagreement over the emergence of private property rights: alternative meanings, alternative explanations

This paper is an exercise in the history of thought, which compares Austrian and neoclassical theories of the emergence of private property rights, and examines, in part, the extent to which Austrians can be said to offer a commonly-agreed upon explanation that parallels Carl Menger's exemplary story of the emergence of money. We address the sources of disagreement (and apparent conflict) among emergence theorists in both schools. We try to show that some of the disagreement hinges on an unclear meaning of the term “emergence,” which is resolvable, while other sources of disagreement are fundamental at the methodological level.
Induction of chromosomal aberrations and sister chromatid exchanges by alpha particles in density-inhibited cultures of mouse 10T1/2 and 3T3 cells.

SummaryWe examined the dose—response relationships for the induction of cell killing, chromosomal aberrations and sister chromatid exchanges (SCE) by 220 kV X-rays and 5·3 MeV alpha particles from a 238Pu source. The cells were irradiated in density-inhibited, confluent cultures. The D0 values for the X-ray and alpha particle survival curves were 1·7 Gy and 0·7 Gy, and the extrapolation numbers 2·5 and 1·0, respectively, for mouse 3T3 cells. Chromosomal aberrations increased linearly with dose for alpha-radiation and roughly with the square of dose for X-rays in 3T3 cells. At 37 per cent survival, 1·0 chromosomal aberration per cell was induced by X-rays and 1·7 per cell by alpha-radiation, but the fraction of cells without aberrations was similar. In confluent holding recovery experiments there was a 50 per cent reduction in X-ray-induced aberrations during the first 4 h of confluent holding. No decline in alpha-induced aberrations was observed with holding times up to 24 h. The dose—response relationshi...
Thermally Induced Optical Distortion In High-Energy Laser Systems

High-energy laser (HEL) systems involve an optical train consisting of mirrors and windows, which may compromise the system's operation because of unavoidable irradiance-mapping aberrations resulting from the absorption of some fraction of the incident laser-beam energy. This paper describes an analytical investigation of relevant processes and discusses how laser-driven mirror/window distortions may affect the performance of HEL systems with regard to focal intensities and on-target fluences. An approximate expression for the brightness at the Gaussian focus is derived on the basis of a far-field degradation model and shown to be simple enough to allow HEL system designers to assess the capability of a contemplated optical train and to evaluate its behavior as a function of beam-power level and laser run-time. Two figures of merit are introduced for the purpose of characterizing the response of power-optics mirrors and windows in terms of thermally induced wavefront errors. For cooled mirrors, it is proposed to consider a figure of merit FoMm = K'eff/ (Am), where K'eff relates to the thermal conductivity, the heat-transfer coefficient, and the thickness of the faceplate, whereas AM measures the mirror absorptance, and E is the distortion coefficient. Similarly, the window figure of merit is FoMw = Cp/ (AW'x), where C'P represents the specific heat per unit volume, AW measures the window absorptance, and x is a distortion coefficient as defined in earlier investigations. On using these figures of merit, an important result emerges: if the window material has a positive distortion coefficient, window lensing suppresses the steady-state mirror-induced aberration at time tc = N(D/d)2FoMw/FoMm, where N is the number of relay mirrors and D/d is the telescope magnification. Under normal circumstances, the far-field irradiance exhibits strongly nonlinear features. Refocusing can eliminate the effect of mirror distortion but, ultimately, window distortion dominates and
How much testing is enough

No testing is enough, but we can maximize the test coverage by using a smart test approach. Smart testing optimizes the design verification process for maximum possible coverage, given the product cycle time, while keeping costs at or below the defined target.
Bi-Parental Cytoplasmic DNA Inheritance in Wisteria (Fabaceae): Evidence from a Natural Experiment

Cytoplasmic inheritance was investigated in interspecific hybrids of Wisteria sinensis and W. floribunda. Species-specific nuclear, mitochondrial and plastid DNA markers were identified from wild-collected plants of each species in its native range. These markers provide evidence for the bi-parental transmission of plastids in hybrid swarms of these two species in the southeastern USA. These population level molecular data corroborate previous cytological evidence of this phenomenon in Wisteria.
Ménétrier’s Disease: Its Mimickers and Pathogenesis

Menetrier’s disease is a rare protein-losing hypertrophic gastropathy. Histologically, it can be mistaken for other disorders showing hypertrophic gastropathy. The pathogenesis of Menetrier’s disease is not fully understood; however, it appears that the epidermal growth factor receptor (EGFR) ligand, transforming growth factor alpha, contributes to the pathogenesis of this disorder. In this review, we will discuss disease entities that can mimic Menetrier’s disease and the role of EGFR signaling in Menetrier’s disease.
Libertarianism vs. Objectivism: A Response to Peter Schwartz

For many years, Rand and the Randians would not mention libertarianism in print. To do so would be to give sanction to what they regarded as a mischievous and misbegotten political philosophy. Happily, this profoundly and intellectually source ended with the publication of Schwartz (1986). This was a no holds barred attack on several libertarian thinkers, including myself. It is a pleasure defending the philosophy of libertarianism in the present reply.
Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration.

We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register MRI volumes to the cryo bright field reference, we used our standard mutual information, non-rigid registration which proceeded: preprocess → affine → B-spline non-rigid 3D registration. In this report, we created two modified approaches: mask where we registered locally over a smaller rectangular solid, and sliding organ . Briefly, in sliding organ , we segmented the organ, registered the organ and body volumes separately and combined results. Though sliding organ required manual annotation, it provided the best result as a standard to measure other registration methods. Regularization parameters for standard and mask methods were optimized in a grid search. Evaluations consisted of DICE, and visual scoring of a checkerboard display. Standard had accuracy of 2 voxels in all regions except near the kidney, where there were 5 voxels sliding. After mask and sliding organ correction, kidneys sliding were within 2 voxels, and Dice overlap increased 4%–10% in mask compared to standard . Mask generated comparable results with sliding organ and allowed a semi-automatic process.
Comparative aspects of renal urate transport

Comparative aspects of renal urate transport . Urate is the major excretory end product of nitrogen metabolism in birds, most reptiles, and some amphibians and undergoes net secretion by the renal tubules. Secretion has been studied in isolated renal proximal tubules from reptiles and birds. Net secretion is influenced by passive backflux between the tubule cells that varies with perfusion rate. Transepithelial transport from bath to lumen involves uptake into the cells against an electrochemical gradient at the basolateral membrane and movement from the cells to the lumen down an electrochemical gradient. However, the apparent permeability of the basolateral membrane to urate is much higher than that of the luminal membrane. Transport into the cells at the basolateral membrane is dependent, in part, on the presence of filtrate (or an appropriate substitute) in the lumen. Because reptilian and avian nephrons filter intermittently, passive back-diffusion between the cells, high permeability of the basolateral membrane, and dependence of basolateral transport on luminal perfusion may prevent accumulation of urate in the cells or lumens of nonfiltering nephrons. In reptiles, basolateral transport is Na-independent but K-dependent and may involve countertransport for some unknown anion. In birds, this transport step, which is Na- and K-dependent, may occur by two separate systems, one involving counter-transport for an unknown anion and the other involving the general tertiary transport process for other organic anions such as PAH. It has not yet been possible to demonstrate that transport from the cells to the lumen down an electrochemical gradient is carrier-mediated in either reptiles or birds and some other process may be involved.
Probing the Fate of Lowest-Energy Near-Infrared Metal-Centered Electronic Excited States: CuCl42– and IrBr62–

Ultrafast transient absorption spectroscopy is used to investigate the radiationless relaxation dynamics of CuCl42– and IrBr62– complexes directly promoted into their lowest-energy excited metal-centered states upon near-infrared femtosecond excitation at 2000 nm. Both the excited CuCl42– 2E and IrBr62– 2Ug′(T2g) states undergo internal conversion to the ground electronic states, yet with significantly different lifetimes (55 fs and 360 ps, respectively) despite the fact that the 2E and 2Ug′(T2g) states are separated by the same energy gap (∼5000 cm–1) from the respective ground state. This difference likely arises from the predominance of the Jahn–Teller effect in a Cu2+ ion and the spin–orbit coupling effect in an Ir4+ ion. The approach documented in this work may be used for elucidating the role of low-energy metal-centered states in relaxation cascades of a number of coordination compounds, allowing for design of efficient light-triggered metal complexes.
THE ASSOCIATION OF ANTIDEPRESSANT AND STATIN USE TO FUTURE DEATH AND INCIDENT CARDIOVASCULAR DISEASE VARIES BY DEPRESSION SEVERITY

Depression has been reported to be associated with a greater risk of death and cardiovascular disease (CVD); however, the impact of antidepressants (ADM) on CVD risk remains controversial. Statin use is known to decrease CVD risk. Whether the use of these medications together affects CVD risk
Temporal and Triggered Evolution of Host–Guest Characteristics in Amphiphilic Polymer Assemblies

An amphiphilic polymer with cleavable side chain and main chain functional groups has been designed and synthesized. Specific cleavage of either of its functional groups was found to have an effect on the morphology of the assembly. Degradation of the main chain is shown to cause morphology of the supramolecular assembly to evolve with time from a micelle-like assembly to a vesicular assembly. On the other hand, stimulus-induced cleavage of the side chains causes these nanoassemblies to disassemble. These temporal (main chain) and triggered (side chain) degradation processes have implications in the design of degradable polymers as supramolecular scaffolds for biological applications.
Skinny Is Not Enough: A Content Analysis of Fitspiration on Pinterest.

Fitspiration is a relatively new social media trend nominally intended to promote health and fitness. Fitspiration messages are presented as encouraging; however, they might also engender body dissatisfaction and compulsive exercise. This study analyzed fitspiration content (n = 1050) on the image-based social media platform Pinterest. Independent raters coded the images and text present in the posts. Messages were categorized as appearance- or health-related, and coded for Social Cognitive Theory constructs: standards, behaviors, and outcome expectancies. Messages encouraged appearance-related body image standards and weight management behaviors more frequently than health-related standards and behaviors, and emphasized attractiveness as motivation to partake in such behaviors. Results also indicated that fitspiration messages include a comparable amount of fit praise (i.e., emphasis on toned/defined muscles) and thin praise (i.e., emphasis on slenderness), suggesting that women are not only supposed to be thin but also fit. Considering the negative outcomes associated with both exposure to idealized body images and exercising for appearance reasons, findings suggest that fitspiration messages are problematic, especially for viewers with high risk of eating disorders and related issues.
Dramatic Response to Carboplatin, Paclitaxel, and Radiation in a Patient With Malignant Myoepithelioma of the Breast.

Malignant myoepithelioma of the breast (MMB) is extremely rare and often presents as a diagnostic challenge. This article reports on a rare case of aggressive MMB in a 52-year-old woman who experienced a dramatic response to carboplatin, paclitaxel, and radiation.
Examiner: a system using contextual knowledge for analysis of diagnostic behavior

An approach to the use of machine generated contextual knowledge for the analysis of diagnostic behavior in medicine has been developed. The approach is illustrated by reference to EXAMINER, a system whose contextual knowledge is derived through use of the INTERNIST data base and diagnostic system[I]. EXAMINER acquires a user's characterization of a medical case in light of this contextual knowledge and analyzes it to generate commentary regarding notable aspects of the user's characterization.
The Potential Role of Glucocorticoids and the HPA Axis in Alcohol Dependence

The hypothalamic–pituitary–adrenal (HPA) axis is an important component of the stress-response system. The HPA axis carefully orchestrates a rapid hormonal stress response and subsequent return to homeostasis once the stressor has passed. However, HPA axis dysregulation that results in hypo- or hyperresponsive production of the stress hormone cortisol has been associated with hazardous alcohol use and dependence. Cortisol interacts with the brain’s reward system, may contribute to habit formation and promote habit-based learning, and may trigger important epigenetic events to potentially increase risk for, development of, and maintenance of alcohol use disorders. Further, cortisol levels during initial alcohol abstinence may indicate relapse vulnerability. Therapeutic advances currently include compounds that target brain stress systems that theoretically can reduce cortisol levels or block the effects of cortisol in the body. The implications of HPA axis dysregulation associated with alcohol use disorders are discussed.
Metallization of crystalline silicon solar cells: A review

Metallization plays both optical and electrical roles in the performance of a solar cell. Optically, the gridline width contributes to shading, which impacts the short circuit current. And electrically in the series resistance through contact and gridline resistances, which influences the fill factor. In the manufacturing of solar cell, metallization is the second most expensive step in the fabrication of a solar cell. In this paper contact formation to crystalline silicon solar cell is reviewed. It starts with the photolithography contacts, which is precise and common to other semiconductor devices but expensive and non-manufacturable, to screen-printed and the alternatives that are less expensive. The importance of less expensive contacting technologies through use of less metal is stressed with the view to decreasing the cost of photovoltaic electricity.
Biological Effects of Different Extracellular Vesicles Population on Reversal of Marrow Cells Radiation Damage

Abstract We have shown that Human or mouse mesenchymal stem cell (MSC) derived vesicles separated by differential centrifugation (300g, 10kg &100kg) can reverse radiation whole bone marrow (WBM) damage in vitro on the hematopoietic cell line FDC-P1 and in vivo on recovery of stem cells and differentiated blood cells after whole body irradiation. The vesicle separation is a classic method for preparations of exosomes. However, this separation isolates the smaller vesicles, discarding larger vesicles. Biologic healing effects of larger vesicles with or without smaller vesicles have not been investigated. Here, we investigated the healing effects of 3 different preparations of vesicles: 10k pellet (microvesicles), 100-10k pellet (exosomes) & 100k pellet (no 10k spin). Three different fractions (10k pellet, 100-10k pellet &100k pellet) of murine/human MSC or murine WBM derived vesicles were isolated by differential centrifugation. FDC-P1 cells were exposed at 500cGy irradiation and cultured with or without the addition of 3 different preparations of murine WBM or human MSC-derived vesicles for 7 days. A significant increase in cell proliferation was observed after 3 different vesicle fractions treatments. However, exosomes were clearly inferior, microvesicles and the combined exosomes and microvesicles population were superior. The capacity of human MSC-derived vesicles of different fractions on reversal of murine bone marrow damage was also evaluated in vivo. Again, the combined fractions shown a significant increase donor chimerism in bone marrow at 6 month post-transplant with 5x's the level of engraftment compared to irradiation control. The 10k and 100-10k fractions showed intermediate healing. Exposure to vesicles in irradiated FDC-P1 cells downregulated phosphorylated H2AX, the DNA damage marker and decreased apoptosis marker, PARP cleavage part. We further investigated the effect of murine marrow MSC-derived vesicles on the gene expression in peripheral blood cells from radiation damaged mice. 28 genes were altered by irradiation, 22 showed partial or complete reversal of these alterations. The characterization of three different fractions of vesicles derived from murine bone marrow cells and human MSC were evaluated by miRNA realtime PCR array (total 750 miRNA). Several MSC-EV associated miRNA responsible for the reversal of radiation damage were evaluated. Our preliminary data shown that miR-221, miR654-3p and miR210-5p could partially reverse radiation damage in FDC-P1 cells There are different biological effects in different extracellular vesicles populations. For reversal of radiation toxicity the most effective vesicle population would include both smaller (exosomes) and larger vesicles (microvesicles). Acknowedgements: This work was support by the NIH grant 5UH2TR00080 Disclosures No relevant conflicts of interest to declare.
Clinical Cardiac MRI Techniques

Cardiac magnetic resonance imaging (MRI) has many potential advantages over conventional cardiac imaging techniques. These include a lack of ionizing radiation, free choice of imaging planes, the capability for tissue characterization, qualitative and quantitative evaluation of the motion of both the blood and the myocardium, and assessment of regional perfusion. These capabilities have been realized through the implementation of many MRI techniques, which have many associated imaging options. Although this range of options to choose from when performing a cardiac MRI examination can be daunting, it provides a great deal of flexibility that can be used to tailor the examination to the patient and the particular clinical question to be addressed. Some of the current clinical indications for cardiac MRI are summarized in Table 1.
Ultrasound-Guided Peripheral Nerve Blockade

The introduction of ultrasonography into peripheral nerve blockade techniques has provided today’s anesthesiologist with a new tool for managing a myriad of perioperative situations. Due to the wide range of blocks performed, and the inability to blind observers when studying blocks, it is difficult to determine if ultrasound-guided blocks are better than other techniques [1]. The currently accepted opinion is that ultrasound-guided nerve blocks are certainly as effective, safe, and efficient as other techniques, including surface landmark base techniques and neurostimulation techniques.
When and why the topological coverage criterion works

In their seminal work on homological sensor networks, de Silva and Ghrist showed the surprising fact that it's possible to certify the coverage of a coordinate-free sensor network even with very minimal knowledge of the space to be covered. Here, coverage means that every point in the domain (except possibly those very near the boundary) has a nearby sensor. More generally, their algorithm takes a pair of nested neighborhood graphs along with a labeling of vertices as either boundary or interior and computes the relative homology of a simplicial complex induced by the graphs. This approach, called the Topological Coverage Criterion (TCC), requires some assumptions about the underlying geometric domain as well as some assumptions about the relationship of the input graphs to the domain. The goal of this paper is to generalize these assumptions and show how the TCC can be applied to both much more general domains as well as very weak assumptions on the input. We give a new, simpler proof of the de Silva-Ghrist Topological Coverage Criterion that eliminates any assumptions about the smoothness of the boundary of the underlying space, allowing the results to be applied to much more general problems. The new proof factors the geometric, topological, and combinatorial aspects, allowing us to provide a coverage condition that supports thick boundaries, k-coverage, and weighted coverage, in which sensors have varying radii.
Reflected Infrared and 3D Imaging for Object Documentation

Imaging techniques inform the conservation, research, and understanding of museum collections. Two types of imaging techniques were examined in this study: infrared (IR) and three-dimensional (3D) imaging. Reflected IR imaging is well established as an investigative tool for conservation providing information about condition, materials, and manufacture beyond visible light documentation. Reflected IR imaging results in two-dimensional images, which are limited in how they represent 3D objects. Three-dimensional imaging techniques, such as white light scanning and photogrammetry, extend the possibilities of digitization by recording the geometry and texture of an object. Reflected IR imaging, photogrammetry, and white light scanning were used to document six objects from the Freud Museum and the Smithsonian National Museum of the American Indian. The present study provides examples of reflected IR imaging for enhanced detection of features of 3D cultural heritage objects; discusses the potential of integra...
Using Cystine Knot Proteins as a Novel Approach to Retarget Oncolytic Measles Virus

Modified measles virus (MV) has effective oncolytic activity preclinically and is currently being investigated in clinical trials for various types of cancer. We investigated the use of cystine knot proteins (CKPs) to direct MV activity. CKPs are short polypeptides that bind their targets with high affinity. We used a CKP that binds αvβ3, αvβ5, and α5β1 integrins with single-digit nanomolar affinity to retarget MV to the integrins (MV-CKPint). MV-CKPint infected, replicated in, and killed human glioblastoma, medulloblastoma, diffuse intrinsic pontine glioma (DIPG), and melanoma cancer cells in vitro, all of which express the target integrins. MV-CKPint activity was competitively blocked by echistatin, an integrin binding peptide. When the CKP was cleaved from the viral H protein at an included protease site, virus activity was abrogated. When delivered intravenously (i.v.), the retargeted virus reached a subcutaneous glioblastoma tumor bed and produced cytopathic effects similar to that shown by intratumoral injection of the virus. Because these target integrins are overexpressed by tumor vascular endothelium, MV-CKPint may allow for effective therapy with i.v. injection. These results indicate for the first time that CKPs can be used to retarget MV for a receptor of choice. In addition, MV-CKPint provides proof of principle for the use of a CKP of interest to retarget any enveloped virus for both oncolytic and gene therapy purposes.
Comorbidity of alcohol abuse and depression: exploring the self-medication hypothesis

Extensive evidence exists to indicate that the comorbidity of alcohol dependence disorders and major depression occurs at a rate far exceeding that which one would expect from base rates alone. Self-medication is one theory as to why this type of comorbid combination may be over-represented. Self-medication can be defined as the conscious or unconscious tendency to drink alcohol (or use other drugs) in response to the experience of depressive symptoms. The theory holds that substance use can temporarily attenuate the negative experience of depression, and for this reason can be seen as a means of escape. Unlike successful treatment with anti-depressant prescription medication, alcohol use is not an effective means of combating depression. In fact, it is predictably counterproductive. This project was undertaken with the goal of integrating many of the research findings from the last twenty years within a study of the extent to which self-medication occurs within a college student sample, a group whose drinking behavior has been notable for it’s potential to become problematic. This was the first study to examine the self-medication hypothesis throughout the range of depressive symptomology and alcohol use, and its aim was to determine the point at which the self-medicative response becomes a serious risk as depression increases. The investigation also attempted to determine the amount of variance in alcohol use that can be explained by self-medication, specifically use motives, while controlling for the amount of self-reported depression. In general, it was expected that as depressive symptoms increase, the tendency to drink for selfmedicative reasons will increase. The results indicated strong support for the existence of self-medicative drinking even at sub-diagnosable levels of depression. A clear relation between level of depression and alcohol use was not found. However, this result was thought to be related to the collegiate sample used in this investigation and the impact of drinking in a collegiate subculture. Self-esteem was not found to have an effect on self-medication. However, changes in depression over a 4-week time period were
Comparison of the efficacy and safety of thrombectomy devices in acute stroke : a network meta-analysis of randomized trials.

Introduction Mechanical thrombectomy (MT) is increasingly used for large-vessel occlusions (LVO), but randomized clinical trial (RCT) level data with regard to differences in clinical outcomes of MT devices are limited. We conducted a network meta-analysis (NMA) that enables comparison of modern MT devices (Trevo, Solitaire, Aspiration) and strategies (stent retriever vs aspiration) across trials. Methods Relevant RCTs were identified by a systematic review. The efficacy outcome was 90-day functional independence (modified Rankin Scale (mRS) score 0–2). Safety outcomes were 90-day catastrophic outcome (mRS 5–6) and symptomatic intracranial hemorrhage (sICH). Fixed-effect Bayesian NMA was performed to calculate risk estimates and the rank probabilities. Results In a NMA of six relevant RCTs (SWIFT, TREVO2, EXTEND-IA, SWIFT-PRIME, REVASCAT, THERAPY; total of 871 patients, 472 Solitaire vs medical-only, 108 Aspiration vs medical-only, 178 Trevo vs Merci, and 113 Solitaire vs Merci) with medical-only arm as the reference, Trevo had the greatest functional independence (OR 4.14, 95% credible interval (CrI) 1.41–11.80; top rank probability 92%) followed by Solitaire (OR 2.55, 95% CrI 1.75–3.74; top rank probability 72%). Solitaire and Aspiration devices had the greatest top rank probability with respect to low sICH and catastrophic outcomes (76% and 91%, respectively), but without significant differences between each other. In a separate network of seven RCTs (MR-CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT, THERAPY, ASTER; 1737 patients), first-line stent retriever was associated with a higher top rank probability of functional independence than aspiration (95% vs 54%), with comparable safety outcomes. Conclusions These findings suggest that Trevo and Solitaire devices are associated with a greater likelihood of functional independence whereas Solitaire and Aspiration devices appear to be safer.
The Downstream Implications of Somatic Hypermutation in Multiple Sclerosis: What Are the Cellular Targets of Antibodies Produced by MS Patient CSF Derived B Cells? (P03.223)

OBJECTIVE: Expanding on our observation that B cell populations in the CSF of MS patients have unique somatic hypermutation patterns we pursued the production of recombinant antibodies from patient B cells. Our goal was to determine what antibodies, expressed by B cells from MS patients, reacted against. BACKGROUND: We have recently demonstrated that B cells from the cerebrospinal fluid of MS patients have a distinct pattern of somatic hypermutation (SHM) in their antibody genes. We call this specific SHM pattern the Antibody Gene Signature for MS (AGS-MS). The specific regions of hypermutation with the VH4 region would be expected to alter antigen binding characteristics of the antibodies. DESIGN/METHODS: We cloned and expressed antibodies that contain the AGS-MS from cerebrospinal fluid derived single B cells of patients with clinically definite MS, patients with one attack of optic neuritis and patients with one attack of transverse myelitis, and tested their capacity to bind to brain tissue. RESULTS: We found that these AGS-MS enriched antibodies from both established MS patients and patients at high risk to develop MS, bind to brain tissue with high specificity. Confocal microscopy confirms that neurons and astrocytes in the brain tissue are recognized by these antibodies. Some of these antibodies recognize both neurons and astrocytes, whereas others are specific for a single cell type. CONCLUSIONS: This study is the first to discern the antigenic targets of hypermutated B cells in patients with RRMS and CIS. The data expands upon our previous observations that B cells from MS patients have a unique pattern of somatic hypermutation. This study shows that the pattern of hypermutation leads to specific anti-neuronal and anti-astrocytic antibodies that may have pathologic significance. Supported by: National Multiple Sclerosis Society. Disclosure: Dr. Ligocki has nothing to disclose. Dr. Li has nothing to disclose. Dr. Rounds has nothing to disclose. Dr. Greenberg has received personal compensation for activities with Elan, Sanofi-Aventis, Diogenix, Biogen Idec, Accorda and MedicalLogix for consulting and from MSAA for honoraria. Dr. Greenberg hold stock and/or stock options in DioGenix, Inc., which sponsored research in which Dr. Greenberg was an investigator. Dr. Greenberg has received research support from Amplimmune, Guthy-Jackson Charitable Foundation, Accelerated Cure Project. Dr. Frohman has received personal compensation for activities with Biogen Idec, Teva Neurosciences, Acorda, Astellas, Abbott, and Novartis. Dr. Stowe has nothing to disclose. Dr. Monson has received personal compensation for activities with Genentech and MedImmune. Dr. Monson has received research support from DioGenix, Inc.
Facultative Sex Ratio Adjustment in Nonhuman Mammals

Agricultural and laboratory studies dating back to the 1800s provide abundant evidence that nonhuman mammals likely have the ability to adjust offspring sex ratios in response to environmental and social conditions. Yet, we’re not much closer to understand whether the observed patterns represent facultative manipulation of offspring sex ratios and what the underlying mechanisms are. In this chapter, I address adaptive hypotheses that have been generated to explain mammalian sex allocation and review the factors that have been linked with sex ratio variation in nonhuman mammals.
Gene therapy for repair and regeneration of bone and cartilage

Gene therapy refers to the use of viral and non-viral vectors to deliver nucleic acids to tissues of interest using direct (in vivo) or transduced cell-mediated (ex vivo) approaches. Over the past few decades, strategies have been adopted to express therapeutic transgenes at sites of injury to promote or facilitate repair of bone and cartilage. Targets of interest have typically included secreted proteins such as growth factors and anti-inflammatory mediators; however, work has also begun to focus intracellularly on signaling components, transcription factors and small, regulatory nucleic acids such as microRNAs (miRNAs). In recent years, a number of single therapeutic gene approaches (termed ‘monotherapies’) have proven effective in preclinical models of disease, and several are being evaluated in clinical trials. In particular, an ex vivo TGF-β1 gene therapy was approved in Korea in 2017 for treatment of moderate-to-severe osteoarthritis (OA). The ability to utilize viral vectors for context-specific and combinatorial gene therapy is also being investigated, and these strategies are likely to be important in more robustly addressing the complexities of tissue repair and regeneration in skeletal disease. In this review, we provide an overview of viral gene therapies being developed for treatment of bone and cartilage pathologies, with an emphasis on emerging combinatorial strategies as well as those targeting intracellular mediators such as miRNAs.
Integrated Models of Care for Individuals with Opioid Use Disorder: How Do We Prevent HIV and HCV?

To describe models of integrated and co-located care for opioid use disorder (OUD), hepatitis C (HCV), and HIV. The design and scale-up of multidisciplinary care models that engage, retain, and treat individuals with HIV, HCV, and OUD are critical to preventing continued spread of HIV and HCV. We identified 17 models within primary care (N = 3), HIV specialty care (N = 5), opioid treatment programs (N = 6), transitional clinics (N = 2), and community-based harm reduction programs (N = 1), as well as two emerging models. Key components of such models are the provision of (1) medication-assisted treatment for OUD, (2) HIV and HCV treatment, (3) HIV pre-exposure prophylaxis, and (4) behavioral health services. Research is needed to understand differences in effectiveness between co-located and fully integrated care, combat the deleterious racial and ethnic legacies of the “War on Drugs,” and inform the delivery of psychiatric care. Increased access to harm reduction services is crucial.
Self-Serving Altruistic Consumption and International Prices

Self-serving altruistic domestic consumption arises when foreign consumption contributes to the domestic utility of consumption. This is particularly the case when consumption saturated economies with excess capacities vie to increase their employment and expand their foreign trade to maintain their competitive advantage. As a result, the traditional presumption that consumption preferences are “selfish”, underlying traditional economic assumptions may be misleading. When the self-serving altruism is combined with economic reciprocity (embedded in countries’ preferences), globalization is a “win-win” economic development. Such situations have both consumption and price implications, depending on countries’ preferences, their cost structures and their trades. This paper is based on a Cournot model for two countries, each with a utility function of both countries’ consumption. An “altruism premium” is defined by the price one country pays to expand consumption in another. We assume both consumption demand and supply sides including trade between these countries and use a Nash conjecture to determine countries’ inverse demand functions (implying that consumption in one country takes for given consumption in another when deciding how much to consume as a function of price). On the supply side, optimal global supply is shown to lead to prices that are linearly related and a function of the countries preferences. We show that under certain circumstances there is no purchasing power parity (PPP), while in others, when prices are calculated net of their global marginal costs, there exists a PPP. Specific examples outlining the implications of such situations are considered.
The limiting DNA replication initiation factors Sld2 and Sld3 influence origin efficiency independent of origin firing time

Chromosome replication in Saccharomyces cerevisiae is initiated from roughly 300 origins that are regulated both by DNA sequence and by the limited abundance of four trans-acting initiation proteins (Sld2, Sld3, Dpb11 and Dbf4, collectively called "SSDD"). We set out to determine how the association of Sld2 or Sld3 at origins contributes to time of origin activation and/or origin efficiency using auxin-induced protein degradation to further decrease their abundance. Depleting cells of either factor slows growth rate, increases S-phase duration, and causes viability defects, without activating the S phase checkpoint. Chr XII is uniquely unstable with breakage occurring specifically within the rDNA locus. The efficiency of the rDNA origin is decreased while the onset of replication initiation is unchanged. We found that origin efficiency is reduced uniformly across the unique portions of the yeast genome. We conclude that the abundance of Sld2 and Sld3 contribute primarily to origin efficiency.
Complexities of genetic screening and testing in hereditary colorectal cancer

Abstract It is becoming increasingly important to identify patients at risk for hereditary colorectal cancer (CRC) given the opportunity to impact medical management and reduce morbidity and mortality among patients and their family members once inherited CRC predisposition is confirmed. Methods by which patients are identified are evolving as genetic testing costs have plummeted, resulting in many more genetic screening and testing options. Opportunities and challenges with newer approaches to genetic testing and screening for hereditary CRC are reviewed along with benefits and limitations of each approach. Regardless of how methods evolve for identifying patients with hereditary cancer risk, the need for patient education, family history taking, appropriate risk counseling, and enhancing sharing across family members will remain critical for optimal patient care.
Radiogenomics of hepatocellular carcinoma: Computed tomography biomarker to predict microvascular invasion and clinical outcome.

4089 Background: Microvascular invasion (MVI) is an independent predictor of poor outcome following surgical resection or liver transplantation (LT) in hepatocellular carcinoma (HCC); however, MVI ...
Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death

Summary Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-forming sequence kill selectively malignant cells without altering the function of normal cells. RG260 targets the hTERT G-quadruplex stem-loop folding but not tetrad DNAs, leading to downregulation of hTERT expression. To improve physicochemical and pharmacokinetic properties, we derived a small-molecule analog, RG1603, from the parent compound. RG1603 induces mitochondrial defects including PGC1α and NRF2 inhibition and increases oxidative stress, followed by DNA damage and apoptosis. RG1603 injected as a single agent has tolerable toxicity while achieving strong anticancer efficacy in a tumor xenograft mouse model. These results demonstrate a unique approach to inhibiting the hTERT that functions by impairing mitochondrial activity, inducing cell death.