cssi/SciSciGPT-SciSciNet huggingface dataset:
A New Multilayer Hierarchy Model for Classifying Weighted Data Point: SNP Genotype Calls

Most of the current studies on the association of Single Nucleotide Polymorphism (SNP) with disease are statistically based on the results of SNP genotype. The accuracy of genotype calls on 2-D plots is the key element in making the data analysis successful in SNP microarray technology. Ambiguous or incorrect cluster classification will cause wrong genotype calls and mislead the associated statistical results. The SNP spots on the plot could be weighted data points because they could have the same coordinates with the same reaction results. Cluster classification and outlier detection are the essential processes for determining the genotype calls with the consideration of these weighted points. Most of the current clustering algorithms are based on rules or statistical methods without taking into the consideration of weights. They have limitations or are only suitable for certain types of data, which might not work for classifying weighted data. In addition, the new microarray systems produce huge volume of data points through the interactions of millions of SNPs with hundreds of samples in a short period. Therefore, the question of how to automatically and accurately classify SNP clusters and to fail the outliers in high throughput mode is the ultimate goal. In this paper, a new hierarchical model with two phases is presented to robustly classify unsupervised SNP data into clusters and to fail the outliers successfully.
A system-design methodology: executable-specification refinement

As methodologies and tools for chip-level design mature, design effort becomes focused on increasingly higher levels of abstraction. We present a methodology and tool for system-level specification, design and refinement that result in an executable specification for each system component. The specification for each component can then be synthesized into hardware or compiled to software. We highlight advantages of the proposed methodology compared to current practice. >
The Effect of Hurricane ike on Personal Network tie Activation as Response and Recovery Unfolded

Most social network research on disaster preparedness and response emphasizes networks as independent variables rather than as outcomes themselves. Here, we evaluate the effect that Hurricane Ike had on the number and types of relationships people of Mexican origin enumerated on a social network questionnaire conducted prior to, during, and after the 2008 disaster struck the Greater Houston area. We also compare the extent of perceived reciprocity in the exchange of favors between network members in the predisaster, response, and recovery phases. Our findings from this natural experiment suggest that individuals in this population activate ties to their extended kin, deactivate friendship ties, and perceive imbalance in the extent to which the favors they send to members in their networks are reciprocated during the long-term disaster recovery.
Randomized Controlled Trial to Determine the Efficacy of Early Switch From Vancomycin to Vancomycin Alternatives as a Strategy to Prevent Nephrotoxicity in Patients With Multiple Risk Factors for Adverse Renal Outcomes (STOP-NT)

Background: Use of alternative antimicrobials to vancomycin is a potential strategy to reduce acute kidney injury (AKI) in high-risk patients, but current data do not support widespread adoption of...
A total synthesis of (−)-hortonone C

A total synthesis of the cytotoxic terpenoid hortonone C was accomplished and its absolute stereochemistry confirmed. Intermediate (+)-4 was synthesized using either an asymmetric conjugate addition strategy, or by elaboration of the Hajos-Parrish ketone. Reduction of (+)-4 under dissolving-metal conditions and trapping the enolate intermediate served to control the cis-stereochemistry at the ring fusion and provide a silyl enol ether necessary for ring expansion. Comparison of optical rotation data confirmed that the absolute configuration of natural hortonone C is (6S,7S,10S).
Mechanical properties of canine osteosarcoma-affected antebrachia

Objective To determine the influence of neoplasia on the biomechanical properties of canine antebrachia. Study design Ex vivo biomechanical study. Sample population: Osteosarcoma (OSA)-affected canine antebrachia (n = 12) and unaffected canine antebrachia (n = 9). Methods Antebrachia were compressed in axial loading until failure. A load-deformation curve was used to acquire the structural mechanical properties of neoplastic and unaffected specimens. Structural properties and properties normalized by body weight (BW) and radius length were compared using analysis of variance (ANOVA). Modes of failure were compared descriptively. Results Neoplastic antebrachia fractured at, or adjacent to, the OSA in the distal radial diaphysis. Unaffected antebrachia failed via mid-diaphyseal radial fractures with a transverse cranial component and an oblique caudal component. Structural mechanical properties were more variable in neoplastic antebrachia than unaffected antebrachia, which was partially attributable to differences in bone geometry related to dog size. When normalized by dog BW and radial length, strength, stiffness, and energy to yield and failure, were lower in neoplastic antebrachia than in unaffected antebrachia. Conclusions OSA of the distal radial metaphysis in dogs presented for limb amputation markedly compromises the structural integrity of affected antebrachia. However, biomechanical properties of affected bones was sufficient for weight-bearing, as none of the neoplastic antebrachia fractured before amputation. The behavior of tumor invaded bone under cyclic loading warrants further investigations to evaluate the viability of in situ therapies for bone tumors in dogs.
Cardiomyocyte Proliferation: Teaching an Old Dogma New Tricks.

The inability of the adult heart to repair or regenerate is manifested in prevalent morbidity and mortality related to myocardial infarction and heart failure. Cardiomyocyte proliferation, especially after myocardial infarction or in the context of heart failure, has been an area of intense research by many investigators for decades. As a researcher working in this area for the past 25 years, this has been an exciting time, requiring an open mind in leaving old accepted ideas behind and moving forward towards exploiting this new knowledge of cardiomyocyte plasticity.
Proteomics Analysis Identifies Orthologs of Human Chitinase-Like Proteins as Inducers of Tube Morphogenesis Defects in Drosophila melanogaster

Elevated levels of human chitinase-like proteins (CLPs) are associated with numerous chronic inflammatory diseases and several cancers, often correlating with poor prognosis. Nevertheless, there is scant knowledge of their function. The CLPs normally mediate immune responses and wound healing and, when upregulated, they can promote disease progression by remodeling tissue, activating signaling cascades, stimulating proliferation and migration, and by regulating adhesion. We identified Imaginal disc growth factors (Idgfs), orthologs of human CLPs CHI3L1, CHI3L2, and OVGP1, in a proteomics analysis designed to discover factors that regulate tube morphogenesis in a Drosophila melanogaster model of tube formation. We implemented a novel approach that uses magnetic beads to isolate a small population of specialized ovarian cells, cells that nonautonomously regulate morphogenesis of epithelial tubes that form and secrete eggshell structures called dorsal appendages (DAs). Differential mass spectrometry analysis of these cells detected elevated levels of four of the six Idgf family members (Idgf1, Idgf2, Idgf4, and Idgf6) in flies mutant for bullwinkle (bwk), which encodes a transcription factor and is a known regulator of DA-tube morphogenesis. We show that, during oogenesis, dysregulation of Idgfs (either gain or loss of function) disrupts the formation of the DA tubes. Previous studies demonstrate roles for Drosophila Idgfs in innate immunity, wound healing, and cell proliferation and motility in cell culture. Here, we identify a novel role for Idgfs in both normal and aberrant tubulogenesis processes.
Knightian Uncertainty, Sytemic Risk Regulation and the Limits of Judicial Review

In MetLife, Inc. v. Financial Stability Oversight Council, Civil Action No. 15-0045 (RMC) (D.D.C. March 30, 2016), the U.S. District Court for the District of Columbia overturned the designation of MetLife, Inc., as a systemically important financial institution regulated by the Federal Reserve Board. It reversed on two grounds. First, it held that the Financial Stability Oversight Council ignored its published guidance by not calculating the statistical probability of MetLife experiencing material financial distress or the magnitude of ensuing losses to MetLife’s counterparties. In addition, it determined that FSOC failed to but should have considered the costs of designation to MetLife. In doing so, the District Court ignored the fact that much of systemic risk oversight operates on the frontiers of what the economist Frank H. Knight termed the unknowable. It is impossible to quantify the likelihood of material financial distress (in its systemic sense) at any given nonbank financial services provider through multivariate statistical analysis. For that reason, in the Dodd-Frank Act, Congress permitted FSOC to evaluate systemic risk at nonbank firms based on qualitative factors and descriptive statistics without the need for multivariate statistical regressions or multivariate similar techniques. By requiring FSOC to make statistical projections that are impossible to make with confidence, the District Court not only vacated MetLife’s designation but undermined major aspects of the broader scheme for regulating systemic risk that Congress mandated in Dodd-Frank.
Using deep learning to bridge the gap between perception and intelligence

We propose a method to for robot planning using deep learning to integrate object detection and natural language understanding. This is different from other techniques, such the RCTA World Model,1 which explicitly defines the interfaces between each module. These boundaries simplify the design and testing of complex robotic systems, but also introduce constraints that may reduce overall system performance. For example, perception tasks generate large amounts of data, but much of it is discarded to simplify interpretation by higher level tasks, e.g., a 3D object becomes a point in space, or a distribution over classifications is reduced to its mode. Further, errors in the robot’s overal task are not back-propagated to lower level tasks, and therefore, these tasks never adapt themselves to improve robot performance. We intend to address this by using a deep learning framework to replace these interfaces with learned interfaces that select what data is shared between modules and allow for error back-propagation that could adapt each module to the robot’s task. We will do this in a simplified system that accepts aerial orthographic images and simple commands and generates paths to achieve the command. Paths are learned from expert example via inverse optimal control. In time, we hope to evolve this simplified architecture towards something more complex and practical.
The role of radiology in preclinical anatomy: a critical review of the past, present, and future.

Rationale and Objectives Radiology has been an increasingly important component of preclinical anatomy instruction since the 1960s. The global status of medical imaging pedagogies and radiologists' roles in medical anatomy education is not well established but is important in determining the specialty's contribution to undergraduate medical education. Materials and Methods PubMed was searched with various combinations of MeSH terms including “radiology,” “undergraduate medical education,” and “anatomy.” Articles were reviewed for relevance, and referenced articles of possible relevance were hand-traced to ensure a wide capture of articles. Results Although more medical schools around the world are using medical imaging to teach anatomy, some regions, such as the United States, show a decline in the proportion of imaging taught by radiologists. Lectures, small group discussions, and self-instruction remain the mainstay of current pedagogies and have witnessed dramatic changes over the past few decades with respect to the types of imaging used. Newer pedagogies use contextual and hands-on experiences to improve spatial and application principles. Qualitative and quantitative studies report somewhat mixed results of pedagogical efficacies but demonstrate generally high acceptance by students and instructors and often significant exam score improvement. Radiology as a specialty must overcome several challenges for it to become more involved in anatomy education, including teaching incentives and protected academic time. Conclusions As anatomy instruction and clinical medicine grow increasingly digital, it is ever more important that radiologists continue to develop new anatomy pedagogies and contribute to anatomy education in greater roles.
Roles of 5-lipoxygenase activating protein in cell proliferation and apoptosis

5-Lipoxygenase activating protein (FLAP) functions as a facilitator of 5-lipoxygenase (5-LOX) activity. However, on the basis of the induction of apoptosis by the FLAP inhibitor MK886 in cells lacking 5-LOX, it is possible that this fatty acid-binding protein has other activities. This study was designed to examine potential roles of FLAP in apoptosis and cell proliferation. Overexpression of FLAP protein (2.2-fold) was achieved by stable transfection of IL-3-dependent murine prolymphoid progenitor cells (FL5.12) with a construct expressing the cDNA under a CMV promoter. The overexpressed protein was localized to nuclear membranes as with endogenous FLAP. The initial growth rate of FLAP-transfected cells was greater than that of control cells. After 48 h, when cell density had increased, the growth rate of FLAP-transfected cells declined substantially and there and there was a decrease in viability relative to control transfected cells. The FLAP-transfected cells were also more susceptible to withdrawal of IL-3 than were control cells. There was, however, no difference between FLAP and control cells in their susceptibility to MK886, NDGA, or etoposide during the log growth phase. Overexpression of FLAP did not alter Bcl-xL protein expression, but did decrease Bax protein and somewhat increased COX-1 and COX-2 mRNA levels. The failure of increased FLAP to alter susceptibility to MK886 provides further support to the concept that this agent induces apoptosis by mechanisms unrelated to FLAP. The data also suggest that FLAP can affect cell proliferation.
Z-Plasty technique using a large C-flap to maximize symmetry of Cupid´s bow and minimize scar in unilateral cleft lip repair

Purpose: Gaining symmetry of Cupid's bow can be challenging in cleft lip repair. We describe a technique that utilizes a modified rotation-advancement type repair to gain maximum length and to minimize scar. Methods: A retrospective chart review of unilateral cleft lip repairs performed by a single surgeon between 2010 and 2014, with at least 6 months of postoperative follow-up, Pre-, intra-, and post-operative photographs were reviewed. Patients included were those who had undergone unilateral cleft lip repair using a Z-plasty type rotation of the C-flap. Postoperative photographs were analyzed for overall symmetry of Cupid's bow and scar appearance using a 5-point visual analog scale (VAS) performed by five independent evaluators. Results: Twenty-three patients were analyzed. On VAS assessment by five independent observers, 22 out of 23 patients (96%) had good, very good, or excellent symmetry of Cupid's bow. All patients (100%) had good, very good, or excellent scar appearance. Twenty-two out of 23 patients (96%) had good, very good, or excellent overall appearance of the repaired lip. Conclusion: Z-Plasty with a very large C-flap as the method for the rotation flap in unilateral cleft lip repair is a useful technique for leveling Cupid's bow and for attaining scars that are nearly imperceptible. Further work will include longer-term follow-up, will look at the severity of the preoperative cleft, and will compare this to postoperative appearance of the lip (symmetry of Cupid's bow and scar).
Complicating marginalisation: the case of Mormon and nonreligious college students in a predominantly Mormon context

There is now compelling evidence that both nonreligious individuals and members of minority religions report feeling marginalised in the United States. However, to date, no one has explored whether...
Permanent Interstitial Brachytherapy for Previously Irradiated Head and Neck Cancer.

Objective To evaluate our institutional experience using brachytherapy for the re-irradiation of the head and neck. Study design/methods We reviewed the records of patients who received brachytherapy for head and neck cancer in a previously irradiated field between 2007 and 2016. Results Sixty-nine patients received brachytherapy-based re-irradiation. Forty-nine patients (71%) were treated for recurrent cancers, 15 patients (22%) had second primary cancers, and five patients (7%) were treated for persistent tumors. The median dose was 90 Gy (range 30-180). Median follow-up was 3.0 years for surviving patients and 0.6 years for all patients. Overall survival at one, three, and five years was 58%, 19%, and 12%, respectively. Local control at one, three, and five years was 55%, 38%, and 28%, respectively. A disease-free interval of less than one year was associated with significantly worse local control (p=.04). Patients who received brachytherapy for a neck disease had significantly worse locoregional control than those who received brachytherapy for mucosal disease (heart rate (HR) 2.14, 95% CI 1.00-4.56, p=.05). Patients who had an extranodal extension had significantly worse overall survival than those without an extranodal extension (HR 2.57, 95% CI 1.28-5.37, p=.008). Seventy-four percent of patients who had pain before brachytherapy (with or without surgery) had an improvement of symptoms. Acute and chronic toxicity of at least Common Terminology Criteria for Adverse Events Grade 3 was seen in 27% and 19% of the patients, respectively. Conclusions Brachytherapy-based re-irradiation is an effective approach for patients undergoing re-irradiation for head and neck cancer. Brachytherapy may be more effective for mucosal recurrences than neck recurrences.
Chaff Allocation and Performance for Network Traffic Obfuscation

This work considers performance analysis of chaff-based traffic obfuscation against a passive adversary aiming to obtain contextual information, e.g. such as the protocol being used. The obfuscation could be either in terms of chaff bytes which are dummy bytes appended to packets of the intended traffic stream, or chaff packets which are dummy packets again inserted in specific intervals of the original packet stream. Despite consisting of dummy bytes, chaff deployment still results in additional resource consumption and potential drawbacks, and hence has to be deployed in a controlled manner. We first define notions of vulnerability of traffic patterns in terms of contextual privacy. Next, we fix the adversary and focus on optimal allocation of the chaff resources among the traffic to be obfuscated. For adversaries which perform statistical characterization based on packet sizes and interarrival times, we derive chaff placement algorithms based on the waterfilling algorithm commonly used in the field of information theory. We apply our derived algorithms to representative real-world scenarios to obfuscate certain applications vulnerable to contextual privacy leakage.
ELECTRON-CAPTURE AND $beta$$sup -$ DECAY OF $sup 122$Sb ORIENTED IN IRON.

Angular distributions have been measured of $\ensuremath{\gamma}$ radiations emitted in the decay of $^{122}\mathrm{Sb}$ nuclei oriented at low temperatures in an iron lattice. Angular momentum admixtures in the (first forbidden) $\ensuremath{\beta}$ radiation fields have been deduced; results indicate that the component of the radiation field carrying away two units of angular momentum contributes to the electron-capture decay to $^{122}\mathrm{Sn}$ with at least twice the magnitude as to the ${\ensuremath{\beta}}^{\ensuremath{-}}$ decay to $^{122}\mathrm{Te}$. These results are interpreted in terms of particle-hole correlations in the nuclear shell model. In addition, the $\frac{E2}{M1}$ mixing ratio of the 691-keV $\ensuremath{\gamma}$ transition in $^{122}\mathrm{Te}$ is deduced to be -2.90 \ifmmode\pm\else\textpm\fi{} 0.25.
Age, Sociology of

The sociology of age is a multifaceted approach to (a) people as they grow older and as cohorts (born at the same time) succeed one another; and (b) the surrounding age-related social structures (or institutions). The central focus is on (c) the continuing interplay between people and structures as each influences and is influenced by the other. This special field, which reflects and also contributes to sociology as a whole, has been emerging since the 1970s and promises to continue into the future. It involves researchers from several countries and encompasses old age, childhood and adolescence, and the life course, as well as relevant aspects of psychology and life sciences. Intertwined working principles and research findings have been identified such as: (a) neither lives nor structures are entirely fixed or immutable; (b) because society changes, members of different cohorts age in different ways; (c) imbalances or ‘lags’ between changes in lives and in structures arise because of their differences in timing (or asynchrony), which exert pressures for change on both people and structures. Currently a lag of structures behind the unprecedented length and capacities of lives forecasts the breakdown of age barriers, thereby bringing together people of all ages (‘age integration’). Thus the emerging sociology of age is freeing the meaning of age from its early biological determinants and proposing new social meanings in a society undergoing fundamental change.
The effect of UV stars on the intergalactic medium

We have investigated the effect of ionizing radiation from the UV stars (hot prewhite dwarfs) on the intergalactic medium (IGM). If the UV stars are powered only by gravitational contraction they radiate most of their energy at a typical surface temperature of 1.5×105 K which produces a very highly ionized IGM in which the elements carbon, nitrogen and oxygen are left with only one or two electrons. This results in these elements being very inefficient coolants. The gas is cooled principally by free-free emission and the collisional ionization of hydrogen and helium. For a typical UV star temperature ofT=1.5×105 K, the temperature of the ionized gas in the IGM isT g =1.2×105 K for a Hubble constantH o=75 km s−1 Mpc−1 and a hydrogen densityn H =10−6 cm−3. Heating by cosmic rays and X-rays is insignificant in the IGM except perhaps inHi clouds because when a hydrogen atom recombines in the IGM it is far more likely to be re-ionized by a UV-star photon than by of the other two types of particles due to the greater space density of UV-star photons and their appreciably larger ionization cross-sections. If the UV stars radiate a substantial fraction of their energy in a helium-burning stage in which they have surface temperatures of about 5×104 K, the temperature of the IGM could be lowered to about 5×104 K.
Sensitivity Analysis of Growth Rate

A central question in demography is: how do vital rates interact to determine growth rate and population structure? The answer is a bit complicated even in the deterministic case, because there is no analytical formula giving r in terms of vital rates. Ecologists and demographers have resorted to studying how r changes when vital rates change (Lewontin 1965, Keyfitz 1968, 1977, Caswell 1978, Arthur 1980). This amounts to studying the derivatives of r, and is called sensitivity analysis (Caswell 1978). The stochastic analog is the sensitivity analysis of the long-run growth rate a. In this chapter I begin with a quick summary of sensitivity analysis for r, and then set out the sensitivity analysis for a.
Normal Heart and Great Vessels

The radiological appearance of the heart and great vessels has a wide variation. The configuration of the cardiovascular silhouette varies according to the body build (chest shape) or habitus, respiratory cycle, the age and sex of the individual, and position (effects of gravity) at the time of examination (supine, erect), changes in intrathoracic pressure (Valsalva and Mueller maneuvers), and the like.
A New Approach to Glaciochemical Time Series Analysis

Time series obtained from glacier ice cores present special difficulties to the scientist and time series analyst. These series generally represent multivariate non-stationary and non-linear processes sampled non-uniformly in time. As a consequence, few of the traditional methods of time series analysis are immediately applicable in their usual formulation. Here we discuss the analytical problems presented by glaciochemical time series and review some of the procedures available or under development to explore the paleoclimatological information they contain.
Hot Pressing: Technology and Theory

Publisher Summary This chapter describes the technology and theory of hot pressing method. Hot pressing is the densification of a loosely packed powder or a compacted preform by the simultaneous application of heat and pressure. The specific benefits of hot pressing are seen in terms of the achievement of high final density and microstructural improvement such as fine grain size. Hot pressing procedures include simple linear hot pressing, continuous pressing, and hot isostatic pressing. The main disadvantages of the process are its high cost and its limited capacity to fabricate a variety of shapes at mass-production rates. The most successful approach to the modeling of hot pressing has been to use creep models suitably modified to account for the effects of porosity and external pressure. The ideal powder for hot pressing should contain no agglomerates, have a narrow particle size distribution, and a fine particle size for promoting rapid densification. It is found that the actual pressing conditions are determined largely by the powder sinterability and the desire to form a particular microstructure.
Forest Preservation Under REDD+ Schemes With Incentives Distortions

Abstract This analysis is based on a model of REDD+ implementation where a sponsor, assumed to be either “benevolent” (altruistic) a toward farmers, or completely selfish, compensates a farmer for the protection of a patch of rainforest under the latter's control. This model is applied to cases with less effective (“diluted”) incentives, in two ways: the sponsor must compensate all farmers in a group instead of only the single farmer targeted (“group incentives”); and a fraction of REDD+ payments is captured by an elite not directly involved in forest protection, and not worthy of support by a benevolent sponsor (“elite capture”). I extend the traditional REDD+ literature by including “benevolent” sponsors who are fully concerned with the welfare of the target (farmer) group. Payments are then increased, perhaps dramatically; but reduced by a selfish sponsor. An efficient solution can then be attained by a benevolent sponsor, albeit only for a high PES payment. With elite capture, payments are reduced for all sponsors, and full efficiency never attained. With selfish sponsors no viable PES scheme may exist. When the group incentive scheme rewards only farmers who save their forests, incentives are not eroded by the scheme.
The Effects of a Structured Classroom Management System in Secondary Resource Classrooms

Comprehensive classroom management that promotes positive student behavior is necessary in secondary school. Techniques must be easy for teachers to manage across multiple class periods and be deve...
Disorders of Consciousness: Ethical Issues of Diagnosis, Treatment, and Prognostication

Consciousness defines our humanity more than any other biologic phenomena that a clinician might be called upon to examine, diagnose, or treat. When family comes to the bedside of a patient, they hope to find them talking, thinking, and feeling. The complexity of consciousness allows an expansive gradation of dysfunction such that we must consider numerous potential insults, possible interventions, and often an unknown likelihood of recovery. As value-laden questions are more often in the hands of surrogate decision makers, the neurologist is given the herculean task of not only diagnosing and treating alterations of consciousness but also predicting the likely course of the disease to empower surrogates to make a choice most consistent with the preferences of the patient. The degree of uncertainty in the diagnosis and prognosis demands that the clinician consider the ethics of the diagnosis, treatment, and prognostication of disorders of consciousness. Expectations of acute and chronic care, the extent of the formal neurological investigation, the potential of therapeutic trials, the self-fulfilling prophecy that can occur with prognostication, and the challenges of shared decision making are all subjects that we explore.
Forbidden Desire: Shades of Racinian Fatality in Marie Laberge’s Juillet

Marie Laberge is widely recognized as a celebrated dramatist but has also written numerous novels that have been well received by readers and critics. Her first novel, Juillet (1989), highlights he...
9R phase enabled superior radiation stability of nanotwinned Cu alloys via in situ radiation at elevated temperature

Abstract Nanotwinned metals exhibit outstanding radiation tolerance as twin boundaries effectively engage, transport and eliminate radiation-induced defects. However, radiation-induced detwinning may reduce the radiation tolerance associated with twin boundaries, especially at elevated temperatures. Here we show, via in-situ Kr ion irradiation inside a transmission electron microscope, that 3 at. % Fe in epitaxial nanotwinned Cu (Cu97Fe3) significantly improves the thermal and radiation stability of nanotwins during radiation up to 5 displacements-per-atom at 200 °C. Such enhanced stability of nanotwins is attributed to a diffuse 9R phase resulted from the dissociation of incoherent twin boundaries in nanotwinned Cu97Fe3. The mechanisms for the enhanced stability of twin boundaries in irradiated nanotwinned alloys are discussed. The stabilization of nano-twins opens up opportunity for the application of nanotwinned alloys for aggressive radiation environments.
Psychological Maltreatment and Medical Neglect of Transgender Adolescents: The Need for Recognition and Individualized Assessment.

Maura Priest (2019) asserts that psychological harms have historically been ignored and have only recently begun to receive appropriate attention, and that “transgender adolescents have a fundament...
The DTA Mouse Model for Oligodendrocyte Ablation and CNS Demyelination

Genetic mouse models facilitate investigation of mechanisms underpinning human diseases and aid the development of novel therapeutic treatments. To better understand the demyelination and remyelination processes in adult-onset demyelinating diseases like multiple sclerosis (MS), we have developed the DTA mouse model system that allows for the widespread ablation of the mature oligodendrocytes, resulting in demyelination throughout the central nervous system (CNS). Induction of oligodendrocyte death in young adult DTA mice causes extensive CNS demyelination that leads to a severe neurological disease, followed by a full recovery that is associated with extensive replenishment of oligodendrocytes and remyelination. Thus, the DTA mouse enables investigation of the mechanisms that promote remyelination in MS and other adult-onset demyelinating diseases. Approximately 30 weeks later, the recovered DTA mice develop a fatal secondary demyelinating disease that is mediated by autoimmune T cells. Therefore, the DTA mouse model is also ideal for elucidating the role of oligodendrocyte death in eliciting autoimmunity in MS. In this chapter we describe the methods we used to generate the DTA mouse model and to analyze both the primary and secondary demyelinating diseases in DTA mice.
Autocrine production of reproductive axis neuropeptides affects proliferation of canine osteosarcoma in vitro

Osteosarcoma strikes hundreds of people each year, of both advanced and younger ages, and is often terminal. Like many tumor types, these bone tumors will frequently undergo a neuroendocrine transition, utilizing autocrine and/or paracrine hormones as growth factors and/or promoters of angiogenesis to facilitate progression and metastasis. While many of these factors and their actions on tumor growth are characterized, some tumor-derived neuropeptides remain unexplored. Using validated canine osteosarcoma cell lines in vitro, as well as cells derived from spontaneous tumors in dogs, we explored the autocrine production of two neuropeptides typically found in the hypothalamus, and most closely associated with reproduction: gonadotropin-releasing hormone (GnRH) and kisspeptin (Kiss-1). We evaluated gene expression and protein secretion of these hormones using quantitative RT-PCR and a sensitive radioimmunoassay, and explored changes in cell proliferation determined by MTS cell viability assays. Our current studies reveal that several canine osteosarcoma cell lines (COS, POS, HMPOS, D17, C4) synthesize and secrete GnRH and express the GnRH receptor, while COS and POS also express kiss1 and its cognate receptor. We have further found that GnRH and kisspeptin, exogenously applied to these tumor cells, exert significant effects on both gene expression and proliferation. Of particular interest, kisspeptin exposure stimulated GnRH secretion from COS, similarly to the functional relationship observed within the neuroendocrine reproductive axis. Additionally, GnRH and kisspeptin treatment both increased COS proliferation, which additionally manifested in increased expression of the bone remodeling ligand rankl within these cells. These effects were blocked by treatment with a specific GnRH receptor inhibitor. Both neuropeptides were found to increase expression of the specific serotonin (5HT) receptor htr2a, the activation of which has previously been associated with cellular proliferation, suggesting that production of these factors by osteosarcoma cells may act to sensitize tumors to circulating 5HT of local and/or enteric origin. Here we report that kisspeptin and GnRH act as autocrine growth factors in canine osteosarcoma cells in vitro, modulating RANKL and serotonin receptor expression in a manner consistent with pro-proliferative effects. Pharmacological targeting of these hormones may represent new avenues of osteosarcoma treatment.
Framework for Conducting and Analyzing Crystal Simulations of Nucleic Acids to Aid in Modern Force Field Evaluation.

Crystal simulations provide useful tools, along with solution simulations, to test nucleic acid force fields, but should be interpreted with care owing to the difficulty of establishing the environmental conditions needed to reproduce experimental crystal packing. These challenges underscore the need to construct proper protocols for carrying out crystal simulations and analyzing results to identify the origin of deviations from crystallographic data. Toward this end, we introduce a novel framework for B-factor decomposition into additive intramolecular, rotational, and translational atomic fluctuation components and partitioning of each of these components into individual asymmetric unit and lattice contributions. We apply the framework to a benchmark set of A-DNA, Z-DNA, and B-DNA double helix systems of various chain lengths. Overall, the intramolecular deviations from the crystal were quite small (≤1.0 A), suggesting high accuracy of the force field, whereas crystal packing was not well reproduced. The present work establishes a framework to conduct and analyze crystal simulations that ultimately take on issues of crystal packing and can provide insight into nucleic acid force fields.
Biology of Rotator Cuff Healing

Rotator cuff tears are the most common source of shoulder pain and dysfunction in adults worldwide. It is estimated that 30–40% of the current population over the age of 60 will suffer a full-thickness rotator cuff tear [1]. Due to the enormity of this population, significant research efforts have been undertaken to identify strategies for prevention, treatment, and rehabilitation of rotator cuff tears. The rate of recurrence of rotator cuff tears, estimated to range from 5% to 85%, is also a significant factor to consider when assessing the overall burden that these injuries impart upon healthcare systems. The majority of recurrent tears occur in the first 3 months following primary repair, and this high rate of recurrence is primarily attributed to poor healing [2]. Despite ever-improving biomechanics of fixation, biological failure following rotator cuff repair remains a significant burden on healthcare systems worldwide.
Exosomal miR-16-5p as a target for malignant mesothelioma

Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.
Development of ReproKnow, a reproductive knowledge assessment for women with rheumatic diseases.

The objective of this study was to develop an assessment tool, ReproKnow, to evaluate the reproductive health knowledge of women with a wide range of rheumatic diseases. The 10-item multiple-choice questionnaire was developed with feedback from a panel of content experts and female patients with rheumatic diseases. Construct validity using known-groups analysis was evaluated through comparison of median total ReproKnow scores between rheumatology fellows and nurses. Female patients aged 18–50 years were recruited to take ReproKnow and demographic questionnaires in two outpatient clinics. Associations between patients’ mean total knowledge scores and demographic characteristics were assessed using independent-sample t-tests. Questions were also categorized by topical area, and the percentages were calculated. The completion rate of questions in ReproKnow was 100% across all users. Median ReproKnow scores were significantly higher among rheumatology fellows than among nurses (p = 0.045). The 153 patients recruited to the study had at least one of 15 rheumatic diseases. Patients’ mean knowledge score was 5.05 (SD 2.24) out of a possible high score of 10. Patients who were younger, White, and more educated had significantly higher scores than did other patients (p’s < 0.05). Patients who bore children after their disease diagnosis had higher knowledge scores than did women whose children were born prior to their diagnosis; in contrast, women with histories of surgical sterilization or hysterectomy had lower knowledge scores than other women. Knowledge scores of women who used potentially fetotoxic medications did not vary from the remainder of the sample. Patients demonstrated gaps in knowledge about birth outcomes, contraceptive efficacy, and breastfeeding safety. Initial testing of ReproKnow suggests that it may be a promising tool to assess the reproductive health knowledge of women with diverse rheumatic diseases. Specific knowledge deficits elicited from ReproKnow may be important targets for future educational interventions.
Realization of an Asymmetric Non-Aqueous Redox Flow Battery through Molecular Design to Minimize Active Species Crossover and Decomposition

This communication presents a mechanism-based approach to identify organic electrolytes for non-aqueous redox flow batteries (RFBs). Symmetrical flow cell cycling of a pyridinium anolyte and a cyclopropenium catholyte resulted in extensive capacity fade due to competing decomposition of the pyridinium species. Characterization of this decomposition pathway enabled the rational design of next-generation anolyte/catholyte pairs with dramatically enhanced cycling performance. Three factors were identified as critical for slowing capacity fade: (1) separating the anolyte-catholyte in an asymmetric flow cell using an anion exchange membrane (AEM); (2) moving from monomeric to oligomeric electrolytes to limit crossover through the AEM; and (3) removing the basic carbonyl moiety from the anolyte to slow the protonation-induced decomposition pathway. Ultimately, these modifications led to a novel anolyte-catholyte pair that can be cycled in an AEM-separated asymmetric RFB for 96 h with >95 % capacity retention at an open circuit voltage of 1.57 V.
Clarifying the Standards for Personal Jurisdiction in Light of Growing Transactions on the Internet: The Zippo Test and Pleading of Personal Jurisdiction

Currently, despite the vast and attractive Internet market, the Supreme Court has not ruled definitively on which test should govern personal jurisdiction in cases involving transactions on the Internet. As a result, different tests and diverging results have developed concerning the constitutionality of specific jurisdiction on the Internet, and cases range from those finding that advertising on a website is sufficient for personal jurisdiction to those requiring that a defendant must have specifically directed activities towards the forum state with the manifested intent to do business in the state. Rules for jurisdictional discovery are similarly unclear — one reason being the lack of consideration about how personal jurisdiction, jurisdictional discovery, and pleading standards are related. The lack of clarity in the rules for personal jurisdiction and jurisdictional discovery creates problems for businesses and sellers who are uncertain about the kinds of activities that might subject them to jurisdiction in a particular state. This uncertainty discourages businesses that are worried about the costs of litigation from using the Internet to share information and engage in business transactions, thus inhibiting their growth and ability to compete. This Note argues that courts should use the Zippo test for analyzing specific jurisdiction in cases involving commercial transactions on the Internet and should interpret the pleading standard for personal jurisdiction in accordance with the approach of the Eighth Circuit. The Zippo test, described in Zippo Manufacturing Co. v. Zippo Dot Com, Inc., supports analyzing personal jurisdiction on the Internet by considering the level of interactivity of the website and the nature and quality of commercial activity that occurs on the Internet. This Note first introduces the history of personal jurisdiction and the relationship among personal jurisdiction, jurisdictional discovery, and pleading standards. Second, this Note discusses how the uncertainty caused by the lack of clear rules for personal jurisdiction and jurisdictional discovery restricts the sharing of information on the Internet, commerce, and competition. Finally, this Note supports use of the Zippo test by explaining the benefits of the Zippo test, which includes its focus on objective factors and objective manifestations of intent in analyzing personal jurisdiction, and why the Zippo test is better than alternative tests. This Note also proposes extending the plausibility standard that applies to Federal Rule of Civil Procedure Rule 8(a)(2) to cover pleading of personal jurisdiction in Rule 8(a)(1), consistent with the Eighth Circuit’s approach and in harmony with the use of the Zippo test. This would require the plaintiff to state in the complaint facts sufficient to support a reasonable inference that the defendant may be subject to personal jurisdiction. The solutions suggested in this Note aim to promote business transactions and the sharing of information on the Internet.
Changes In Left Atrial Appendage Orifice Following Percutaneous Left Atrial Appendage Closure Using Three-Dimensional Echocardiography

Percutaneous left atrial appendage occlusion (LAAO) with the Watchman device is increasingly performed in patients with atrial fibrillation and long-term contraindications for anticoagulation. Changes of LAA orifice size following LAAO and its impact on left upper pulmonary venous (LUPV) velocities
Aging-Resilient SRAM-based True Random Number Generator for Lightweight Devices

A random number generator (RNG) is an important building block for cryptographic operations primarily to generate random nonces and secret keys. The power-up value of an SRAM array has been widely accepted as an entropy source for generating random numbers. However, only a few cells of the SRAM are truly random upon repeated power-ups; the vast majority of cells display a distinct bias from manufacturing process variations. Consequently, a relatively large SRAM array is required to obtain sufficient entropy for generating random numbers. Earlier research has proposed the use of controlled device aging at pre-deployment stage to enhance the initial entropy of an SRAM array. However, aging in the field can adversely affect the entropy and degrade randomness; we show here that any initial aging to increase SRAM entropy can even be counterproductive. Instead, we propose an SRAM-based random number generation approach, which continually manipulates device aging during operation to constantly maximize entropy for the entire deployment period. The key idea is to continually stress the SRAM cells in their power-up states at regular intervals. This helps counteract the aging caused by the random memory states that occur during operation. Silicon results are presented to validate our proposed approach.