cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular beam epitaxy growth of [CrGe/MnGe/FeGe] superlattices: toward artificial B20 skyrmion materials with tunable interactions

Abstract Skyrmions are localized magnetic spin textures whose stability has been shown theoretically to depend on material parameters including bulk Dresselhaus spin orbit coupling (SOC), interfacial Rashba SOC, and magnetic anisotropy. Here, we establish the growth of a new class of artificial skyrmion materials, namely B20 superlattices, where these parameters could be systematically tuned. Specifically, we report the successful growth of B20 superlattices comprised of single crystal thin films of FeGe, MnGe, and CrGe on Si(1 1 1) substrates. Thin films and superlattices are grown by molecular beam epitaxy and are characterized through a combination of reflection high energy electron diffraction, X-ray diffraction, and cross-sectional scanning transmission electron microscopy (STEM). X-ray energy dispersive spectroscopy (XEDS) distinguishes layers by elemental mapping and indicates good interface quality with relatively low levels of intermixing in the [CrGe/MnGe/FeGe] superlattice. This demonstration of epitaxial, single-crystalline B20 superlattices is a significant advance toward tunable skyrmion systems for fundamental scientific studies and applications in magnetic storage and logic.
TrunkDiseaseID.org: A molecular database for fast and accurate identification of fungi commonly isolated from grapevine wood

Abstract The grapevine trunk-disease complex limits vineyard longevity in all major grape-growing regions. Although trunk diseases have been distinguished based on etiologies (e.g., Botryosphaeria-, Eutypa-, and Phomopsis dieback, Esca) and causal agents, mixed infections of trunk pathogens and other wood-colonizing fungi are frequent in grapevines. These diverse fungal communities in grapevine span four classes in the Pezizomycotina (Ascomycota) and 10 genera in the Hymenochaetales (Basidiomycota). Traditional identification based on morphology is largely untenable because of overlap in colony characteristics or spore dimensions, or lack of sporulation in culture. When based on DNA sequencing, searches of uncurated, public molecular databases can lead to misidentifications. The new molecular database TrunkDiseaseID.org is populated with accurate rDNA ITS sequences from 250 + isolates (pathogens and saprobes) and secondary DNA barcodes for delineating closely related species. Currently, no such comprehensive database exists for grapevine wood-colonizing fungi. In addition to ITS and secondary barcode sequences, this database provides a scientific reference, origin, and ecological status for each isolate, to aid diagnosticians in communicating results and recommendations to growers. Outreach through the National Plant Diagnostic Network and the US Department of Agriculture's Identification Technology Program will connect diagnosticians to this new database for grape.
How block categories affect learner satisfaction with a block-based programming interface

In recent years, block-based programming languages have been employed as learning tools to help students starting out with programming. How we design the layout of the available blocks likely impacts the success of the student. In this study, we compare student performance in three conditions consisting of different layouts of block categories in a block-based language: a grouping based on computer science (CS) concepts, a grouping based on block functionality, and one with no groupings. We measured task completion time, quality of the final code product, and perceived system usability. We found that although time and quality did not differ across conditions, the students in the functionality condition reported higher usability scores than the students in the CS concepts condition. These results can inform how we design block-based interfaces to improve learner satisfaction without affecting their performance.
Hybrid Strategy for Neonates With Ductal-Dependent Systemic Circulation at High Risk for Norwood

Background Hypoplastic left heart syndrome and other cardiac lesions with ductal-dependent systemic circulation continue to be challenging to manage, especially in high-risk (HR) populations (those with prematurity, multiple congenital anomalies, moderate to severe tricuspid regurgitation, hemodynamic instability, intact atrial septum). Methods A retrospective study on our institution's experience implementing a hybrid strategy as initial palliation in HR patients with ductal-dependent systemic circulation in HR patients undergoing Norwood versus hybrid procedure. From July 2004 to May 2008, 16 HR patients underwent stage I Norwood procedure. After implementation of a hybrid strategy in 2008, 24 HR patients underwent hybrid procedure from May 2008 to November 2015. Results There was no difference in gestational age, age at procedure, or hospital length of stay. The HR Hybrid group had lower mean weight (2.6 kg vs 3.1 kg, p = 0.026). Thirty-day mortality was lower in the HR Hybrid group (4% vs 31%, p = 0.019), although there was no difference in interstage mortality (17% vs 9%, p = 0.396). Catheter-based reintervention was more prevalent in the HR Hybrid group, but did not have a negative impact on survival. One-year transplant-free survival was similar ( p = 0.416). HR Hybrid patients weighing less than 2.6 kg had higher overall survival (83% vs 25%, p = 0.013), as did patients who were premature (70% vs 0%, p = 0.003). Conclusions In high-risk patients, the hybrid procedure appears to have lower 30-day mortality and may have a survival benefit in premature patients and those less than 2.6 kg. Long-term attrition in this high-risk population is ongoing regardless of early strategy.
Drug Affinity and Efficacy

Abstract This chapter specifically discusses the concepts of affinity (expressed as a ratio of the rate of dissociation of the molecule from the protein (k2) and the rate of association to the protein (k1) in a parameter referred to as Keq, where Keq=k2/k1) and efficacy (the property of a molecule that changes the behavior of the biological target towards its cellular host when bound to that target). This latter term is general in that a given drug can have numerous “efficacies” of varying strength to yield multiple activities that are expressed either as sub-maximal (termed partial agonists) or maximal (full agonists) effects.
Significant Life Experiences and Animal-Themed Education

Significant life experiences (SLE) literature posits that people have important experiences that lead them toward certain outcomes and support a cohesive life narrative. This SLE framework has been used to identify the development of environmental values and behaviors. Our research explores how SLE influences animal-themed educators in their choice to work in this field. We find that animal-themed educators share some unifying experiences with more general environmentalist populations, but that animal-related experiences may indeed represent a somewhat unique pathway to these positions. Our work contributes to a greater understanding of environmental educators’ decisions and how SLEs influence their roles and identities as educators. The findings support pedagogical design of environmental education programs that strengthen the linkages between information, emotional connections, pro-environmental behaviors, and career opportunities.
QTL-mapping and genomic prediction for bovine respiratory disease in U.S. Holsteins using sequence imputation and feature selection.

National genetic evaluations for disease resistance do not exist, precluding the genetic improvement of cattle for these traits. We imputed BovineHD genotypes to whole genome sequence for 2703 Holsteins that were cases or controls for Bovine Respiratory Disease and sampled from either California or New Mexico to construct and compare genomic prediction models. The sequence variation reference dataset comprised variants called for 1578 animals from Run 5 of the 1000 Bull Genomes Project, including 450 Holsteins and 29 animals sequenced from this study population. Genotypes for 9,282,726 variants with minor allele frequencies ≥5% were imputed and used to obtain genomic predictions in GEMMA using a Bayesian Sparse Linear Mixed Model. Variation explained by markers increased from 13.6% using BovineHD data to 14.4% using imputed whole genome sequence data and the resolution of genomic regions detected as harbouring QTL substantially increased. Explained variation in the analysis of the combined California and New Mexico data was less than when data for each state were separately analysed and the estimated genetic correlation between risk of Bovine Respiratory Disease in California and New Mexico Holsteins was − 0.36. Consequently, genomic predictions trained using the data from one state did not accurately predict disease risk in the other state. To determine if a prediction model could be developed with utility in both states, we selected variants within genomic regions harbouring: 1) genes involved in the normal immune response to infection by pathogens responsible for Bovine Respiratory Disease detected by RNA-Seq analysis, and/or 2) QTL identified in the association analysis of the imputed sequence variants. The model based on QTL selected variants is biased but when trained in one state generated BRD risk predictions with positive accuracies in the other state. We demonstrate the utility of sequence-based and biology-driven model development for genomic selection. Disease phenotypes cannot be routinely recorded in most livestock species and the observed phenotypes may vary in their genomic architecture due to variation in the pathogen composition across environments. Elucidation of trait biology and genetic architecture may guide the development of prediction models with utility across breeds and environments.
Modeling People-AI Interaction: A Case Discussion with Using an Interaction Design Language

Artificial Intelligent (AI) system development is the current challenge for all areas related to software development practice and research, including Human-Computer Interaction (HCI). Most AI systems’ research has been focused on the performance and accuracy of Machine Learning (ML) algorithms. Recently, new research questions concerning people in the loop of AI systems development and behavior have been emerging such as bias, reasoning, and explainability. In this new people and AI systems scenario, humans and computers collaborate, using their unique and powerful capabilities in a kind of symbiosis. In this new setting, AI systems are now real social actors as they are active players in the interaction with people. Defining and understanding the behavior of an AI system and its motivation for suggestions and reasoning are definitely a complex endeavor. HCI and Software Engineering communities, with their designers and developers, use models to represent, discuss and explore different domain scenarios in different stages of the software development process. In this paper, we present and discuss a scenario represented in an interaction modeling representation and how it can enable the representation and discussion of the people-AI symbiosis.
Excised Whole Lymph Node Imaging for Cancer Staging with Angular Restriction Dual Fluorescent Optical Projection Tomography

Conventional pathology in sentinel lymph node biopsy fails to sufficiently evaluate the entire tissue volume, resulting in high rates of false negatives. To address this, a novel imaging system is proposed to augment the current protocol by providing high-resolution molecular imaging of the lymph node prior to sectioning, with the goal of guiding pathology. Optical projection tomography (OPT) offers a potential solution but spatial resolution of conventional OPT is generally quite poor in lymph node sized tissue samples. Here, we demonstrate the ability to use angular-restriction with filtered-backprojection to provide sensitive and accurate localization of clinically relevant sized micrometastases in lymph nodes (through Monte Carlo simulations and porcine lymph node metastases models).
Analysis of a Rare Earth-Free Dual Mechanical Port Machine with PM-Assisted Reluctance Rotor for Hybrid Electric Vehicles

This paper presents design and performance analysis of a novel rare-earth-free dual mechanical port machine for hybrid electric vehicle drives. A new rotor structure was proposed to enhance the reluctance torque contribution. The principle of operation, system configuration, and control issues are illustrated firstly. Design consideration of ferrite permanent magnet-assisted reluctance rotor will be discussed as well. Finally, the advanced finite element method was employed to calculate and verify the electromagnetic performance of proposed dual mechanical port machine with ferrite permanent magnet-assisted reluctance rotor.
ALIX(ir) of Life: The Pivotal Role of ALIX in Regulating Plant Responses to Abscisic Acid.

The abscisic acid (ABA) hormone can be thought of as a growth-pulse modulator, signaling to plants to temporarily halt their growth in response to environmental stressors. In particular, drought, through ABA, signals plants to reduce water loss by closing stomata in aerial organs. This is a good
Cognitive Control Moderates the Health Benefits of Trait Self-Regulation in Young Adults.

Abstract Separate lines of epidemiological research suggest that individuals with high trait self-regulation (e.g. conscientious individuals) and individuals with higher cognitive ability (e.g. executive control/intelligence) each tend to enjoy superior health and well-being outcomes. However, it remains largely unexplored whether these personological and cognitive contributions to physical health are shared, independent, or interdependent. In the current study, we examined associations between trait self-regulation, cognitive control, self-reported physical health, and subjective well-being. A domain-general model revealed little shared variance between trait self-regulation and cognitive control but revealed significant unique relationships between each predictor and physical health. Results of a latent moderation analysis suggested that cognitive control moderated the contribution of self-regulation to health but not subjective well-being. This moderation effect was characterized by a strengthened relationship between trait self-regulation and health with decreases in cognitive control. Together, our results suggest that self-regulation and cognitive control may independently contribute to health outcomes in young adults and that self-regulation may be increasingly important for individuals lower in cognitive control.
Episodic herbivory, plant density dependence, and stimulation of aboveground plant production

Herbivory is a major energy transfer within ecosystems; an open question is under what circumstances it can stimulate aboveground seasonal primary production. Despite multiple field demonstrations, past theory considered herbivory as a continuous process and found stimulation of seasonal production to be unlikely. Here, we report a new theoretical model that explores the consequences of discrete herbivory events, or episodes, separated in time. We discovered that negative density (biomass) dependence of plant growth, such as might be expected from resource limitation of plant growth, favors stimulation of seasonal production by infrequent herbivory events under a wide range of herbivory intensities and maximum plant relative growth rates. Results converge to those of previous models under repeated, short-interval herbivory, which generally reduces seasonal production. Model parameters were estimated with new and previous data from the Serengeti ecosystem. Patterns of observed frequent and large magnitude stimulated production in these data agreed generally with those predicted by the episodic herbivory model. The model thus may provide a new framework for evaluating the sustainability and impact of herbivory.
Drug Interactions and Side Effects of Co-Administration of Chloroquine/Hydroxychloroquine and Azithromycin: on the Issue of Rational Pharmacotherapy of Patients with COVID-19 with Antimalarial Drugs

This review analyzes existing approaches to the treatment of COVID-19 patients with antimalarial drugs from the standpoint of rational pharmacotherapy. Particular attention is paid to drug interactions and side effects of co-administration of chloroquine/hydroxychloroquine and azithromycin, considering the problem of cardiotoxicity and the high likelihood of cardiovascular disease in middle-aged and elderly people with COVID-19. The article discusses the prospects of using another representative from the group of antimalarial drugs - mefloquine in the treatment of COVID-19. Special attention is paid to the “proarrhythmogenic” side effects of azithromycin therapy, as well as to the problem of resistance of microorganisms to macrolides during antibiotic therapy of pneumonia, in particular to azithromycin. In conclusion, the article discusses the possibilities of alternative methods in the treatment of this disease.
Speaking dyspnea in Parkinson's disease: Preliminary findings

Abstract Purpose To determine if people with Parkinson’s disease (PD) experience dyspnea (breathing discomfort) during speaking. Method The participants were 11 adults with PD and 22 healthy adults (11 young, 11 old). Participants were asked to recall experiences of breathing discomfort across different speaking contexts and provide ratings of those experiences (Retrospective ratings); then they rated the breathing discomfort experienced while performing speaking tasks that were designed to differ in respiratory demands (immediate Post-Speaking ratings). Results Participants with PD reported experiencing breathing discomfort during speaking significantly more frequently (approximately 60 % of the time) than did healthy participants (less than 20 % of the time). Retrospective ratings did not differ significantly from Post-Speaking ratings. Breathing discomfort was experienced by the fewest number of participants with PD for Conversation (two) and Extemporaneous Speaking (three) and by the greatest number for Extended Reading (ten) and Long Counting (nine), although the magnitude of the ratings generally reflected only “Slight” discomfort. Breathing discomfort was most frequently described as air hunger and breathing work, less frequently as mental effort, and very rarely as lung tightness. A few participants with PD reported experiencing emotions associated with their breathing discomfort and most reported using strategies to avoid breathing discomfort in their daily lives. Conclusions Individuals with PD are more apt to experience speaking dyspnea than healthy individuals, especially when speaking for extended periods or when using long breath groups. Such dyspnea may contribute to a tendency to avoid speaking situations and thereby impair quality of life.
Combat helmet liner design for blunt impact absorption using multi-output Gaussian process surrogates:

A finite element based computational model simulating the standard drop tower test for military helmets was created and used in conjunction with a multi-output Gaussian process surrogate to seek di...
Nephrectomy is Associated with Increased Mortality after Renal Trauma: An Analysis of the National Trauma Data Bank from 2007-2016.

Purpose:The majority of high grade renal trauma can be managed conservatively. However, nephrectomy is still common for acute management. We hypothesized that when controlling for multiple injury s...
Binding Mode of SARS-CoV2 Fusion Peptide to Human Cellular Membrane

ABSTRACT Infection of human cells by the SARS-CoV2 relies on its binding to a specific receptor and subsequent fusion of the viral and host cell membranes. The fusion peptide (FP), a short peptide segment in the spike protein, plays a central role in the initial penetration of the virus into the host cell membrane, followed by the fusion of the two membranes. Here, we use an array of molecular dynamics (MD) simulations taking advantage of the Highly Mobile Membrane Mimetic (HMMM) model, to investigate the interaction of the SARS-CoV2 FP with a lipid bilayer representing mammalian cellular membranes at an atomic level, and to characterize the membrane-bound form of the peptide. Six independent systems were generated by changing the initial positioning and orientation of the FP with respect to the membrane, and each system was simulated in five independent replicas. In 60% of the simulations, the FP reaches a stable, membrane-bound configuration where the peptide deeply penetrated into the membrane. Clustering of the results reveals two major membrane binding modes, the helix-binding mode and the loop-binding mode. Taken into account the sequence conservation among the viral FPs and the results of mutagenesis studies establishing the role of specific residues in the helical portion of the FP in membrane association, we propose that the helix-binding mode represents more closely the biologically relevant form. In the helix-binding mode, the helix is stabilized in an oblique angle with respect to the membrane with its N-terminus tilted towards the membrane core. Analysis of the FP-lipid interactions shows the involvement of specific residues of the helix in membrane binding previously described as the fusion active core residues. Taken together, the results shed light on a key step involved in SARS-CoV2 infection with potential implications in designing novel inhibitors. SIGNIFICANCE A key step in cellular infection by the SARS-CoV2 virus is its attachment to and penetration into the plasma membrane of human cells. These processes hinge upon the membrane interaction of the viral fusion peptide, a segment exposed by the spike protein upon its conformational changes after encountering the host cell. In this study, using molecular dynamics simulations, we describe how the fusion peptide from the SARS-CoV2 virus binds human cellular membranes and characterize, at an atomic level, lipid-protein interactions important for the stability of the bound state.
Effects of Post‐Resuscitation Normoxic Therapy on Oxygen‐Sensitive Oxidative Stress in a Rat Model of Cardiac Arrest

Background Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post‐resuscitation normoxic therapy would protect organs...
Antibody responses to filovirus infections in humans: protective or not?

Summary Disease outbreaks caused by Ebola virus and other filoviruses highlight the urgent need for an in-depth understanding of the role of antibody responses in recovery. In this Personal View we aim to discuss the controversial biological role of antibodies during natural filovirus infections in humans. Survival during natural human filovirus infections correlates with the magnitude of the process of antibodies binding to the filovirus glycoprotein and neutralising the virus. Despite the severity of the disease, highly potent monoclonal antibodies have been isolated from survivors of natural filovirus infections, suggesting that the magnitude of the antibody response is insufficient for prevention of severe disease. Unlike natural infections, filovirus vaccines, which express the viral glycoprotein, do induce protective concentrations of antibodies, albeit only when administered at very high doses. Multiple mechanisms by which filoviruses can delay and reduce the antibody response have been identified in the past decade. Furthermore, subneutralising antibody concentrations have been shown to enhance filovirus infections of immune cells bearing Fc receptors. Understanding the role of antibody responses during natural filovirus infections is important for the development of safe and potent vaccines and antibody-based treatments.
Desiccation Induced Conjunctival Monocyte Recruitment and Activation - Implications for Keratoconjunctivitis.

Background Lacrimal gland secretory dysfunction in Sjogren syndrome (SS) causes ocular surface desiccation that is associated with increased cytokine expression and number of antigen-presenting cells (APCs) in the conjunctiva. This study evaluated the hypothesis that desiccating stress (DS) alters the percentage and gene expression of myeloid cell populations in the conjunctiva. Methods DS was induced by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Bone marrow chimeras and adoptive transfer of CD45.1+ bone marrow cells to CD45.2+ C-C chemokine receptor 2 knockout (CCR2-/-) mice were used to track DS-induced myeloid cell recruitment to the conjunctiva. Flow cytometry evaluated myeloid cell populations in conjunctivae obtained from non-stressed eyes and those exposed to DS for 5 days. CD11b+ myeloid lineage cells were gated on monocyte (Ly6C), macrophage (CD64, MHCII) and DC (CD11c, MHCII) lineage markers. NanoString immune arrays were performed on sorted MHCII+ and MHCII- monocyte/macrophage cell populations. Results DS significantly increased the recruitment of adoptively transferred MHCII positive and negative myeloid cells to the conjunctiva in a CCR2 dependent fashion. The percentage of resident conjunctival monocytes (Ly6C+CD64-) significantly decreased while CD64+MHCII+ macrophages increased over 5 days of DS (P<0.05 for both). Comparison of gene expression between the MHCII- monocyte and MHCII+ populations in non-stressed conjunctiva revealed a ≥ 2 log2 fold increase in 95 genes and decrease in 46 genes. Upregulated genes are associated with antigen presentation, cytokine/chemokine, M1 macrophage and NLRP3 inflammasome pathways. DS increased innate inflammatory genes in monocytes and MHCII+ cells and increased M1 macrophage (Trem1, Ido1, Il12b, Stat5b) and decreased homeostasis (Mertk) and M2 macrophage (Arg1) genes in MHCII+ cells. Conclusions There are myeloid cell populations in the conjunctiva with distinct phenotype and gene expression patterns. DS recruits myeloid cells from the blood and significantly changes their phenotype in the conjunctiva. DS also alters expression of an array of innate inflammatory genes. Immature monocytes in the unstressed conjunctiva appear to cascade to MHCII+ macrophages during DS, suggesting that DS promotes maturation of monocytes to antigen presenting cells with increased expression of inflammatory genes that may contribute to the pathogenesis of SS keratoconjunctivitis sicca.
Identifying and Mitigating Spurious Correlations for Improving Robustness in NLP Models

Recently, NLP models have achieved remarkable progress across a variety of tasks; however, they have also been criticized for being not robust. Many robustness problems can be attributed to models exploiting spurious correlations, or shortcuts between the training data and the task labels. Models may fail to generalize to out-of-distribution data or be vulnerable to adversarial attacks if spurious correlations are exploited through the training process. In this paper, we aim to automatically identify such spurious correlations in NLP models at scale. We first leverage existing interpretability methods to extract tokens that significantly affect model's decision process from the input text. We then distinguish "genuine" tokens and "spurious" tokens by analyzing model predictions across multiple corpora and further verify them through knowledge-aware perturbations. We show that our proposed method can effectively and efficiently identify a scalable set of "shortcuts", and mitigating these leads to more robust models in multiple applications.
Characterization of a Direct Sample Analysis (DSA) Ambient Ionization Source.

Water cluster ion intensity and distribution is affected by source conditions in direct sample analysis (DSA) ionization. Parameters investigated in this paper include source nozzle diameter, gas flow rate, and source positions relative to the mass spectrometer inlet. Schlieren photography was used to image the gas flow profile exiting the nozzle. Smaller nozzle diameters and higher flow rates produced clusters of the type [H + (H2O)n]+ with greater n and higher intensity than larger nozzles and lower gas flow rates. At high gas flow rates, the gas flow profile widened compared with the original nozzle diameter. At lower flow rates, the amount of expansion was reduced, which suggests that lowering the flow rate may allow for improvements in sampling spatial resolution.
A 2-Approximation for Minimum Cost {0, 1, 2} Vertex Connectivity

In survivable network design, each pair (i, j) of vertices is assigned a level of importance rij. The vertex connectivity problem is to design a minimum cost network such that between each pair of vertices with importance level r, there are r vertex disjoint paths. There is no approximation algorithm known for this general problem. In this paper, we give a 2-approximation for the problem when r ∈ {0, 1, 2}V × V, improving on a previous known 3-approximation. This matches the best known approximation for the easier problem that requires that the paths be only edge-disjoint. Our algorithm extends an iterative rounding algorithm that gives a 2-approximation for the edge-connectivity problem, for arbitrary connectivity requirements r. (K. Jain, A factor 2 approximation for the generalized Steiner network problem.) This algorithm relies on well-known uncrossing lemma for tight edge cutsets. Our extension uses a new type of uncrossing lemma for tight cutsets that may include vertices as well as edges. For r ∈ {1, k}V × V, k ≥ 3, we show that a) uncrossing tight cutsets is not possible, and b) any analysis for iterative rounding that depends directly on the largest fractional value in the linear programming solution cannot provide approximation guarantees better than the maximum connectivity requirement.
Degradation and Impurity Analysis for Pharmaceutical Drug Candidates

Abstract The objective of this chapter is to give guidance with degradation and impurity structure elucidation for pharmaceutical drug candidates. Stress testing knowledge is provided as guidance in developing and executing forced degradation experiments. Impurity and degradant structure elucidation is a collaborative effort involving the degradation chemist, analytical chemist, process chemist, and/or formulator, as well as the isolation chemist, mass spectrometry and NMR experts. Updates in this second addition include: (1) the use of quality by design (QbD) model as applied to stress testing practices, expanded oxidative experimental analysis, and expanded information on predictive programs. (2) The impact of supercritical fluid chromatography as a tool for impurity isolations, along with expanded information on process workflow. (3) Mass spectrometry: additional examples and a section on the use of accurate mass information in the role of structure elucidation. (4) Expansion on the use of NMR as applied to structure characterization and elucidation. (5) In‐depth case studies that illustrate collaborative efforts made between disciplines, as well as the impact that new technologies have on the structure elucidation process.
Affirmative Action for the Master Class: The Creation of the ProslaveryConstitution

In 1787 the Constitutional Convention made a series of compromises on slavery that led to the creation of a proslavery Constitution. This article argues that this was the nation's first form of "affirmative action" as the Constitution explicitly protected only one form of private property: slaves. The Constitution of 1787 was a proslavery document, designed to prevent any national assault on slavery, while at the same time structured to protect the interests of slave owners at the expense of African Americans and their antislavery white allies. To understand this earliest form of affirmative action, this article examines the argument that the constitution was proslavery and then explains the Convention that wrote the Constitution and the document that convention produced.
Covalent structure of collagen. Amino acid sequence of an arthritogenic cyanogen bromide peptide from type II collagen of bovine cartilage.

Bovine articular type II collagen was prepared by limited pepsin digestion, differential salt fractionation and carboxymethylcellulose chromatography. Cyanogen bromide digestion of purified type II collagen α chains yielded twelve distinct peptides designated CB1–12. The peptide α1(II)-CB11 was isolated by carboxymethylcellulose chromatography and Sephadex G-75S gel filtration. Automated Edman degradation together with chymotrypsin, thermolysin and trypsin digestion enabled identification of its complete amino acid sequence. Compared with type I and type III collagen, the data show similarity with α1(I)-CB8 and α1(III)-CB6-1-8-10-2 peptides, respectively. The peptide is located within residues 124–402 of the α1(II) collagen chain and with its identification, now extends the known amino acid sequence of bovine type II cartilage collagen to 660 amino acid residues including α1(II)-CB1-2-6-12-11-8-10 (partial). This corresponds to α1(I)-CB0-1-2-4-5-8-3-7 (partial; 1–660) and α1(III)-CB3A-3B-3C-7-6-1-8-10-2-4-5 (partial; 1–660) of bovine α1(I) and α1(III) collagen chains.
Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator

In Drosophila, signalling by the protein Hedgehog (Hh) alters the activity of the transcription factor Cubitus interruptus (Ci) by inhibiting the proteolysis of full-length Ci (Ci-155) to its shortened Ci-75 form1,2. Ci-75 is found largely in the nucleus and isthought to be a transcriptional repressor1, whereas there is evidence3,4,5 to indicate that Ci-155 may be a transcriptional activator1,2,6. However, Ci-155 is detected only in the cytoplasm, where it is associated with the protein kinase Fused (Fu), with Suppressor of Fused (Su(fu)), and with the microtubule-binding protein Costal-2 (refs 1,7,8,9). It is not clear how Ci-155 might become a nuclear activator. We show here that mutations in Su ( fu) cause an increase in the expression of Hh-target genes in a dose-dependent manner while simultaneously reducing Ci-155 concentration by some mechanism other than proteolysis to Ci-75. Conversely, eliminating Fu kinase activity reduces Hh-target gene expression while increasing Ci-155 concentration. We propose that Fu kinase activity is required for Hh to stimulate the maturation of Ci-155 into a short-lived nuclear transcriptional activator and that Su(fu) opposes this maturation step through a stoichiometric interaction with Ci-155.
Intention and Interpretation in Art: A Semiotic Analysis

KANT WAS PERHAPS the first philosopher to note the distinctive puzzle, verging on paradox, which marks our dealings with art. Works of art seem to place us under an obligation to interpret them and yet we are convinced that our interpretations will never be exhaustive. Kant attempts to account for this peculiar phenomenon by talking of "purposiveness without purpose" or of the aesthetic idea as "a representation of the imagination to which no concept is adequate." We are constrained to see some pattern or organization in a work of art and this is typically understood as a teleological or purposive organization which we may feel tempted to attribute to the intentions or experiences of some rational agent; yet we do not complete this attribution because it seems as if there is always some additional or more complex purposive pattern which escapes our comprehension. For Kant the phenomenon is to be understood in terms of the types of judgment and the need to find some link between the worlds of nature and of freedom; and it is important for his theory that he demonstrate that art is beautiful only insofar as it approximates to the beauty of nature. Others with similar metaphysical interests have introluced concepts like Schopenhauer's will or Hegel's absolute idea to cover roughly the same ground. Those who are dissatisfied
An Active Learning Approach for Jointly Estimating Worker Performance and Annotation Reliability with Crowdsourced Data

Crowdsourcing platforms offer a practical solution to the problem of affordably annotating large datasets for training supervised classifiers. Unfortunately, poor worker performance frequently threatens to compromise annotation reliability, and requesting multiple labels for every instance can lead to large cost increases without guaranteeing good results. Minimizing the required training samples using an active learning selection procedure reduces the labeling requirement but can jeopardize classifier training by focusing on erroneous annotations. This paper presents an active learning approach in which worker performance, task difficulty, and annotation reliability are jointly estimated and used to compute the risk function guiding the sample selection procedure. We demonstrate that the proposed approach, which employs active learning with Bayesian networks, significantly improves training accuracy and correctly ranks the expertise of unknown labelers in the presence of annotation noise.
Urban/Rural Differences in Prosthetic Dental Service Rates

: There have been few reports of relative rates of provision of dental health services in rural and urban settings, a comparative measure of access to care in these populations. One part of a statewide survey of active North Carolina general dentists (n=959, response rate=47%) was designed to quantify provision of prosthetic services. To determine contrasting rural and urban rates, responses were analyzed according to dentists’self-report of practice city size using analysis of covariance with percent of insured patients in the practice as the covariate. Mean per-patient-visit rates for crowns, fixed partial dentures, removable partial dentures, and extractions, as well as the distributions of treatment following tooth extraction, differed by city size, with practitioners in the smallest cities reporting treatment distributions reflecting more frequent loss of teeth and less frequent replacement. These differences in patterns of prosthetic care echo the limited existing information describing oral health status, provider supply, and receipt of care, all of which suggest that differential levels of access to care exist and lead to differences in oral health outcomes.
An algorithm for generating some inverse Laplace transforms of exponential form

A simple algorithm of finding inverse Laplace transforms of an exponential form is devised. To avoid lengthy and tedious calculations of derivatives, two functionsS andT are introduced; it is shown that derivatives ofS andT with respect to parameters are expressed by combinations ofS andT. The formulas for derivatives ofS andT can be applied repeatedly to obtain a class of inverses.
Increased (3H) Phorbol Ester Binding in Rat Cerebellar Granule Cells by Polychlorinated Biphenyl Mixtures and Congeners: Structure-Activity Relationships

Abstract Our previous reports indicate that polychlorinated biphenyl (PCB) congeners in vitro perturbed cellular Ca 2+ homeostasis and protein kinase C (PKC) translocation. We have now studied the structure-activity relationship (SAR) of 3 PCB mixtures, 24 PCB congeners, and 1 dibenzofuran for their effects on PKC translocation by measuring [ 3 H]phorbol ester ([ 3 H]PDBu) binding in cerebellar granule cells (7 days in culture). All the PCB mixtures studied increased [ 3 H]PDBu binding significantly and in a concentration-dependent manner. However, Aroclor 1016 and Aroclor 1254 were more potent than Aroclor 1260. Of the 24 congeners studied, di- ortho congeners such as 2,2′,5,5′tetrachlorobiphenyl (-TeCB), 2,2′,4,6,6′-pentachlorobiphenyl (-PeCB), 2,2′,4,6-TeCB, and 2,2′-dichlorobiphenyl (-DCB) were the most potent (E50 = 28-43 μM) while non- ortho congeners such as 3,3′,4,4′-TeCB and 3,3′,4,4′,5-PeCB were not effective. The potential contaminant of PCB mixtures, 1,2,3,7,8-pentachlorodibenzofuran had no significant effect on [ 3 H]PDBu binding. The SAR among these congeners revealed: (i) congeners with ortho -chlorine substitution such as 2,2′-DCB (E50 = 43 ± 3 μM) or ortho -lateral ( meta, para ) chlorine substitution such as 2,2′,5,5′-TeCB (E50 = 28 ± 3 μM) and 2,2′,4,6-TeCB (E50 = 41 ± 6 μM) were most potent; (ii) congeners with only para -substitution such as 4,4′-DCB or high lateral content in the absence of ortho -substitution such as 3,3′,4,4′,5,5′-HCB were not effective; and (iii) increased chlorination was not clearly related to the effectiveness of these congeners, although hexa- and heptachlorination was less effective than di- and tetrachlorination. Low lateral substitution, especially without para -substitution, or lateral content in the presence of ortho -substitution, may be the most important structural requirement for the in vitro activity of these PCB congeners in neuronal preparations.
Aneurysmectomy and endocardial resection for ventricular tachycardia: favorable hemodynamic and antiarrhythmic results in patients with global left ventricular dysfunction.

Sixty-two patients underwent aneurysmectomy and endocardial resection for control of recurrent sustained ventricular tachycardia (VT). Forty patients also had coronary artery bypass grafting (CABG) (1.5 grafts per patient). The mean preoperative left ventricular end-diastolic pressure (LVEDP) was 18 ± 8 mm Hg, cardiac index (Cl) was 2.7 ± 0.7 L/min/m2, and ejection fraction (EF) was 28 ± 10%. In a subset of 32 patients with clearly demarcated aneurysmal and contracting ventricular sections, the mean EF of the residual contracting section (CSEF) was 35 ± 13%, and 26 of these patients had a CSEF < 45%. There were five operative deaths (8%). No hemodynamic findings distinguished the patients who died during surgery. Patients with an LVEDP above the group mean or an overall EF below the group mean had an operative mortality of 10% and 7%, respectively. In the subgroup of 26 patients with a CSEF < 45%, the operative mortality was 12%. In the surgical survivors as a whole the LVEDP decreased from 17 ± 8 to 14 ± 5 mm Hg (p < 0.005) and the overall EF increased from 28 ± 9% to 39 ± 10% (p < 0.001) while the normal CI did not change. Linear regression analysis revealed that patients with the highest preoperative LVEDPs and the lowest overall EFs were most likely to have improvement in these parameters postoperatively. Patients with a preoperative CSEF < 45% had similar postoperative changes in their LVEDP (17 ± 6 to 15 ± 4 mm Hg) and overall EF (24 ± 7% to 38 ± 11%). In addition, the incidence of inducible VT postoperatively was similar in patients with a preoperative CSEF < 45% (4 of 23) and in the rest of the group (8 of 34, p = NS). We conclude that: (1) patients with ventricular aneurysms and medically refractory VT often have marked dysfunction of the residual contracting LV section; (2) aneurysmectomy and endocardial resection is an effective mode of therapy for VT and can be performed with a low operative mortality in this patient population; and (3) postoperatively the angiographic EF usually increases and the LVEDP often decreases, especially in patients with the most marked preoperative LV dysfunction.
Lensfree on-chip imaging for telemedicine applications

We discuss lensfree on-chip holography and its use in cytometry and medical diagnostics to provide a telemedicine tool for point of care applications especially in resource limited settings.
Epistatic Roles of E2 Glycoprotein Mutations in Adaption of Chikungunya Virus to Aedes Albopictus and Ae. Aegypti Mosquitoes

Between 2005 and 2007 Chikungunya virus (CHIKV) caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982) does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA) clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions prevalent in areas occupied by ECSA stains. These newly described determinants of CHIKV mosquito infectivity for Ae. albopictus and Ae. aegypti are of particular importance for studies aimed at the investigation of the detailed mechanisms of CHIKV adaptations to its vector species.
DNA hybridization-enhanced porous silicon corrosion: mechanistic investigations and prospect for optical interferometric biosensing

Abstract Hybridization of DNA oligonucleotides in neutral aqueous solutions with complementary sequences immobilized on highly doped p -type porous silicon matrix is shown to result in an unexpectedly large shift in the Fabry–Perot interference pattern to lower wavelengths implying a decrease in effective optical thickness of the porous matrix. We have determined that the observed optical effects are due to enhanced corrosion (oxidation–hydrolysis) of the porous silicon layer triggered by the formation of complementary DNA duplexes. Scanning force microscopy and reflectance spectroscopy were employed at various stages of the signal evolution process to monitor and establish the material changes induced by the DNA binding events. We postulate that the slow background corrosion process initiated at the exposed Si–H x groups is dramatically enhanced as a result of the change in carrier charge density of the porous silicon layer in response to the local increase in the electrostatic field generated by the nucleic acid hybridization. The proposed mechanism is consistent with the experimental observations that the characteristics of the porous silicon matrix and the charge density of the hybridized DNA complexes can both influence the corrosion process. Functionalized porous silicon matrices prepared from highly doped silicon wafers (resistivity 1 mΩ·cm) produce large corrosion rates and improved signal to noise ratios. Moreover, the enhanced decrease in the effective optical thickness could be prevented by either shielding the negative charges of the DNA duplex in the presence of Mg 2+ ions, or by using backbone charge neutral peptide nucleic acids (PNA) in the DNA hybridization experiments. The observed phenomenon is thus an example of an active sensor matrix in which the molecular recognition signal is transduced and amplified by a profound change in the chemical reactivity and physical property of the solid support itself. With the signal amplification mechanism described, binding of unlabeled complementary DNA oligonucleotides of approximately 0.1 amol/mm 2 has been detected suggesting the potential utility of this new approach in DNA sensing.
Marfan Syndrome: From Molecules to Medicines*

I would like to thank the American Society of Human Genetics for this great honor. To receive professional recognition is always gratifying, but to be earmarked for distinction by a group of people that I so thoroughly admire and respect is truly extraordinary.